U.S. patent application number 10/775038 was filed with the patent office on 2004-10-14 for enhanced bioavailability of nutrients, pharmaceutical agents, and other bioactive substances through laser resonant homogenization or modification of molecular shape or crystalline form.
Invention is credited to Ovokaitys, Todd F., Strachan, John Scott.
Application Number | 20040204746 10/775038 |
Document ID | / |
Family ID | 10859948 |
Filed Date | 2004-10-14 |
United States Patent
Application |
20040204746 |
Kind Code |
A1 |
Ovokaitys, Todd F. ; et
al. |
October 14, 2004 |
Enhanced bioavailability of nutrients, pharmaceutical agents, and
other bioactive substances through laser resonant homogenization or
modification of molecular shape or crystalline form
Abstract
A method for improving the bioavailability of a bioactive
substance includes subjecting the bioactive substance to laser
radiation. The laser radiation modifies the bioactive substance to
thereby modify reactions relating thereto in the body. The method
enables reductions in inflammation associated with autoimmune
diseases, modification of reaction by-products in the body,
increased homogenization and flattening of molecular shape and
improved methylation. The improved methylation can be utilized to
reduce homocysteine blood levels, and to reduce anxiety,
depression, paranoia, hostility, somatization (perception of bodily
distress) and obsessive-compulsive symptoms. Enhanced nitric oxide
generation from modified L-arginine can be used to reduce systolic
and diastolic blood pressure, lower total and LDL cholesterol
levels, and improve the ratio of total to HDL cholesterol.
Increased depth of penetration of sparse constructive nodes of
laser radiation may increase the range of photodynamic therapy
applications and a wide range of in vitro and in vivo modifications
of molecular shape and activity. Laser acoustic resonance can be
utilized to increase the homogeneity of crystals, or favor the
generation of novel or preferred crystalline forms.
Inventors: |
Ovokaitys, Todd F.;
(Carlsbad, CA) ; Strachan, John Scott; (Edinburgh,
GB) |
Correspondence
Address: |
RANDALL B. BATEMAN
BATEMAN IP LAW GROUP
4 TRIAD CENTER, SUITE 825
PO BOX 1319
SALT LAKE CITY
UT
84110
US
|
Family ID: |
10859948 |
Appl. No.: |
10/775038 |
Filed: |
February 9, 2004 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10775038 |
Feb 9, 2004 |
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10069052 |
Feb 21, 2002 |
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10069052 |
Feb 21, 2002 |
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PCT/GB00/03280 |
Aug 29, 2000 |
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60446146 |
Feb 10, 2003 |
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60505910 |
Sep 25, 2003 |
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Current U.S.
Class: |
607/89 ;
128/898 |
Current CPC
Class: |
A61N 5/067 20210801;
A61N 5/00 20130101 |
Class at
Publication: |
607/089 ;
128/898 |
International
Class: |
A61N 005/06; A61B
019/00 |
Foreign Application Data
Date |
Code |
Application Number |
Aug 28, 1999 |
GB |
UK 9920351.5 |
Claims
What is claimed is:
1. A method for modifying bioavailability of a bioactive substance,
the method comprising subjecting said bioactive substance to a
laser to modify the structure thereof.
2. The method according to claim 1, wherein said method comprises
subjecting said bioactive substance to a laser prior to
ingestion.
3. The method according to claim 1, wherein the method comprises
subjecting the bioactive substance to the laser while said
bioactive substance is in powder form.
4. The method according to claim 1, wherein the method comprises
subjecting the bioactive substance to the laser while said
bioactive substance is in crystalline form.
5. The method according to claim 1, wherein the method comprises
subjecting the bioactive substance to the laser while said
bioactive substance is in a solution.
6. The method according to claim 1, wherein said bioactive
substance is an amino acid.
7. The method according to claim 1, wherein said method comprises
providing a fractional frequency shift to said laser to traverse
sparse constructive nodes through said bio-active substance.
8. The method according to claim 1, wherein the method comprises
altering said bioactive substance to modify nitric oxide production
following ingestion of said modified bioactive substance.
9. The method according to claim 1, wherein said method comprises
modifying the structure of said bioactive substance to homogenize
and flatten chemical bonds within said bioactive substance.
10. The method according to claim 9, wherein said bioactive
substance is betaine hydrochloride.
11. The method according to claim 1, wherein said method comprises
modifying said bioactive substance to enhance methylation after
ingestion.
12. The method according to claim 11, wherein said bioactive
substance is trimethylglycine plus metabolic cofactors.
13. A method for modifying production of nitric oxide within a
mammal, said method comprising: selecting an amino acid; modifying
said amino acid with a laser; and ingesting said modified amino
acid.
14. The method according to claim 13, wherein said amino acid is
arginine.
15. The method according to claim 13, wherein said amino acid is
modified by exposure to laser radiation with an amplitude
modulation at a resonance frequency of or more acoustic vibration
frequencies of said amino acid and said laser radiation is
structured in polarization and wave patterns.
16. A method for increasing homogeneity and flattening in a
bioactive substance, said method comprising: selecting a bioactive
substance to modify; and exposing said bioactive substance to laser
radiation with an amplitude modulation at a resonance of one or
more acoustic vibration frequencies of said bioactive substance and
said laser radiation is structured in polarization and wave
patterns.
17. A method for reducing blood levels of homocysteine comprising:
modifying trimethylglycine and cofactors through exposure to laser
radiation; and ingesting an effective amount of said modified
trimethylglycine and cofactors.
18. The method for reducing blood levels of homocysteine according
to claim 17, wherein said method comprises consuming at least 2
grams of modified trimethylglycine and cofactors daily.
19. The method for reducing blood levels of homocysteine according
to claim 17, wherein said method comprises consuming at least 4
grams of modified trimethylglycine and cofactors daily.
20. The method for reducing blood levels of homocysteine according
to claim 17, wherein said method comprises consuming at least 6
grams of modified trimethylglycine and cofactors daily.
21. The method for reducing blood levels of homocysteine according
to claim 17, wherein the method comprises forming said modified
trimethylglycine and cofactors by exposure to laser radiation with
an amplitude modulation at a resonance frequency of one or more
acoustic vibration frequencies of said trimethylglycine and
cofactors and said laser radiation is structured in polarization
and wave patterns.
22. A method for treating anxiety comprising: preparing modified
trimethylglycine and cofactors by subjecting said trimethylglycine
and cofactors to laser radiation; and ingesting an effective amount
of said modified trimethylglycine and cofactors.
23. The method for treating anxiety according to claim 22, wherein
said method comprises consuming at least 2 grams of modified
trimethylglycine and cofactors daily.
24. The method for treating anxiety according to claim 22, wherein
said method comprises consuming at least 4 grams of modified
trimethylglycine and cofactors daily.
25. The method for treating anxiety according to claim 22, wherein
said method comprises consuming at least 6 grams of modified
trimethylglycine and cofactors daily.
26. The method for treating anxiety according to claim 22, wherein
the method comprises forming said modified trimethylglycine and
cofactors by exposure to laser radiation with an amplitude
modulation at a resonance frequency of one or more acoustic
vibration frequencies of said trimethylglycine and cofactors and
said laser radiation is structured in polarization and wave
patterns.
27. A method for treating depression comprising: preparing modified
trimethylglycine and cofactors by subjecting said trimethylglycine
and cofactors to laser radiation; and ingesting an effective amount
of said modified trimethylglycine and cofactors.
28. The method for treating depression according to claim 27,
wherein said method comprises consuming at least 2 grams of
modified trimethylglycine and cofactors daily.
29. The method treating depression according to claim 27, wherein
said method comprises consuming at least 4 grams of modified
trimethylglycine and cofactors daily.
30. The method for treating depression according to claim 27,
wherein said method comprises consuming at least 6 grams of
modified trimethylglycine and cofactors daily.
31. The method for treating depression according to claim 27,
wherein the method comprises forming said modified trimethylglycine
and cofactors by exposure to laser radiation with an amplitude
modulation at a resonance frequency of one or more acoustic
vibration frequencies of said trimethylglycine and cofactors and
said laser radiation is structured in polarization and wave
patterns.
32. A method for treating obsessive-compulsive symptoms comprising:
preparing modified trimethylglycine and cofactors by subjecting
said trimethylglycine and cofactors to laser radiation; and
ingesting an effective amount of said modified trimethylglycine and
cofactors.
33. The method for treating obsessive-compulsive symptoms according
to claim 32, wherein said method comprises consuming at least 2
grams of modified trimethylglycine and cofactors daily.
34. The method for treating obsessive-compulsive symptoms according
to claim 32, wherein said method comprises consuming at least 4
grams of modified trimethylglycine and cofactors daily.
35. The method for treating obsessive-compulsive symptoms according
to claim 32, wherein said method comprises consuming at least 6
grams of modified trimethylglycine and cofactors daily.
36. The method for treating obsessive-compulsive symptoms according
to claim 32, wherein the method comprises forming said modified
trimethylglycine and cofactors by exposure to laser radiation with
an amplitude modulation at resonance frequency of one or more
acoustic vibration frequencies of said trimethylglycine and
cofactors and said laser radiation is structured in polarization
and wave patterns.
37. A method for treating paranoia comprising: preparing modified
trimethylglycine and cofactors by subjecting said trimethylglycine
and cofactors to laser radiation; and ingesting an effective amount
of said modified trimethylglycine.
38. The method for treating paranoia according to claim 37, wherein
said method comprises consuming at least 2 grams of modified
trimethylglycine and cofactors daily.
39. The method for treating paranoia according to claim 37, wherein
said method comprises consuming at least 4 grams of modified
trimethylglycine and cofactors daily.
40. The method for treating paranoia according to claim 37, wherein
said method comprises consuming at least 6 grams of modified
trimethylglycine and cofactors daily.
41. The method for treating paranoia according to claim 37, wherein
the method comprises forming said modified trimethylglycine and
cofactors by exposure to laser radiation with an amplitude
modulation at a resonance frequency of one or more acoustic
vibration frequencies of said trimethylglycine and cofactors and
said laser radiation is structured in polarization and wave
patterns.
42. A method for treating hostility comprising: preparing modified
trimethylglycine and cofactors by subjecting said trimethylglycine
and cofactors to laser radiation; and ingesting an effective amount
of said modified trimethylglycine and cofactors.
43. The method for treating hostility according to claim 42,
wherein said method comprises consuming at least 2 grams of
modified trimethylglycine and cofactors daily.
44. The method for treating hostility according to claim 42,
wherein said method comprises consuming at least 4 grams of
modified trimethylglycine and cofactors daily.
45. The method for treating hostility according to claim 42,
wherein said method comprises consuming at least 6 grams of
modified trimethylglycine and cofactors daily.
46. The method for treating hostility according to claim 42,
wherein the method comprises forming said modified trimethylglycine
and cofactors by exposure to laser radiation with an amplitude
modulation at a resonance frequency of one or more acoustic
vibration frequencies of said trimethylglycine and cofactors and
said laser radiation is structured in polarization and wave
patterns.
47. A method for treating perceptions of bodily distress, aches,
and pains comprising: preparing modified trimethylglycine and
cofactors by subjecting said trimethylglycine and cofactors to
laser radiation; and ingesting an effective amount of said modified
trimethylglycine and cofactors.
48. The method for treating perceptions of bodily distress, aches,
and pains according to claim 47, wherein said method comprises
consuming at least 2 grams of modified trimethylglycine and
cofactors daily.
49. The method for treating perceptions of bodily distress, aches,
and pains according to claim 47, wherein said method comprises
consuming at least 4 grams of modified trimethylglycine and
cofactors daily.
50. The method for treating perceptions of bodily distress, aches,
and pains according to claim 47, wherein said method comprises
consuming at least 6 grams of modified trimethylglycine and
cofactors daily.
51. The method for treating perceptions of bodily distress, aches,
and pains according to claim 47, wherein the method comprises
forming said modified trimethylglycine and cofactors by exposure to
laser radiation with an amplitude modulation at resonance frequency
of one or more acoustic vibration frequencies of said
trimethylglycine and cofactors and said laser radiation is
structured in polarization and wave patterns.
52. A method for increasing systemic DNA methylation and SAMe
levels, the method comprising: preparing modified trimethylglycine
and cofactors by subjecting said trimethylglycine and cofactors to
laser radiation; and ingesting an effective amount of said modified
trimethylglycine and cofactors.
53. The method for increasing systemic DNA methylation and SAMe
levels according to claim 52, wherein said method comprises
consuming at least 2 grams of modified trimethylglycine and
cofactors daily.
54. The method for increasing systemic DNA methylation and SAMe
levels according to claim 52, wherein said method comprises
consuming at least 4 grams of modified trimethylglycine and
cofactors daily.
55. The method for increasing systemic DNA methylation and SAMe
levels according to claim 52, wherein said method comprises
consuming at least 6 grams of modified trimethylglycine and
cofactors daily.
56. The method for increasing systemic DNA methylation and SAMe
levels according to claim 52, wherein the method comprises forming
said modified trimethylglycine and cofactors by exposure to laser
radiation with an amplitude modulation at resonance frequency of
one or more acoustic vibration frequencies of said trimethylglycine
and cofactors and said laser radiation is structured in
polarization and wave patterns.
57. A method for treating autoimmune disorders comprising:
preparing modified betaine and cofactors by subjecting said betaine
and cofactors to laser radiation; and ingesting an effective amount
of said modified betaine and cofactors.
58. A method for treating autoimmune disorders according to claim
57, wherein said method comprises consuming at least 6 grams of
laser treated betaine plus cofactors daily for an induction period
of 2-3 months, followed by a maintenance dose of 1-2 grams of said
laser treated betaine plus cofactors daily to be maintained or
adjusted based on clinical or biochemical response.
59. The method for treating autoimmune disorders according to claim
57, wherein the method comprises forming said modified betaine plus
cofactors by exposure to laser radiation with an amplitude
modulation at a resonance frequency of one or more acoustic
vibration frequencies of said betaine plus cofactors and said laser
radiation is structured in polarization and wave pattern.
60. A method for treating elevated serum total cholesterol levels
comprising: preparing modified L-arginine and cofactors by
subjecting said L-arginine and cofactors to laser radiation; and
ingesting an effective amount of said modified L-arginine and
cofactors.
61. The method for treating elevated serum total cholesterol levels
according to claim 60, wherein said method comprises consuming at
least 3.5 grams of modified L-arginine and cofactors daily.
62. The method for treating elevated serum total cholesterol levels
according to claim 60, wherein said method comprises consuming at
least 6.5 grams of modified L-arginine and cofactors daily.
63. The method for treating elevated serum total cholesterol levels
according to claim 60, wherein said method comprises consuming at
least 7.3 grams of modified L-arginine and cofactors daily.
64. The method for treating elevated serum total cholesterol levels
according to claim 60, wherein said modified L-arginine and
cofactors are formed by exposure to laser radiation with an
amplitude modulation at a resonance frequency of one or more
acoustic vibration frequencies of said L-arginine and cofactors and
said laser radiation is structured in polarization and wave
patterns.
65. A method for treating elevated serum LDL cholesterol levels
comprising: preparing modified L-arginine and cofactors by
subjecting said L-arginine and cofactors to laser radiation; and
ingesting an effective amount of said modified L-arginine and
cofactors.
66. The method for treating elevated serum LDL cholesterol levels
according to claim 65, wherein said method comprises consuming at
least 3.5 grams of modified L-arginine and cofactors daily.
67. The method for treating elevated serum LDL cholesterol levels
according to claim 65, wherein said method comprises consuming at
least 6.5 grams of modified L-arginine and cofactors daily.
68. The method for treating elevated serum LDL cholesterol levels
according to claim 65, wherein said method comprises consuming at
least 7.3 grams of modified L-arginine and cofactors daily.
69. The method for treating elevated serum LDL cholesterol levels
according to claim 65, wherein said modified L-arginine and
cofactors are formed by exposure to laser radiation with an
amplitude modulation at a resonance frequency of one or more
acoustic vibration frequencies of said L-arginine and cofactors and
said laser radiation is structured in polarization and wave
patterns.
70. A method for treating elevated serum total-to-HDL cholesterol
ratios comprising: preparing modified L-arginine and cofactors by
subjecting said L-arginine and cofactors to laser radiation; and
ingesting an effective amount of said modified L-arginine and
cofactors.
71. The method for treating elevated serum total-to-HDL cholesterol
ratios according to claim 70, wherein said method comprises
consuming at least 3.5 grams of modified L-arginine and cofactors
daily.
72. The method for treating elevated serum total-to-HDL cholesterol
ratios according to claim 70, wherein said method comprises
consuming at least 6.5 grams of modified L-arginine and cofactors
daily.
73. The method for treating elevated serum total-to-HDL cholesterol
ratios according to claim 70, wherein said method comprises
consuming at least 7.3 grams of modified L-arginine and cofactors
daily.
74. The method for treating elevated serum total-to-HDL cholesterol
ratios according to claim 70, wherein the method comprises forming
said modified L-arginine and cofactors by exposure to laser
radiation with an amplitude modulation at a resonance frequency of
one or more acoustic vibration frequencies of said L-arginine and
cofactors and said laser radiation is structured in polarization
and wave patterns.
75. A method for treating elevated systolic blood pressure
comprising: preparing modified L-arginine and cofactors by
subjecting said L-arginine and cofactors to laser radiation; and
ingesting an effective amount of said modified L-arginine and
cofactors.
76. The method for treating elevated systolic blood pressure
according to claim 75, wherein said method comprises consuming at
least 3.5 grams of modified L-arginine and cofactors daily.
77. The method for treating elevated systolic blood pressure
according to claim 75, wherein said method comprises consuming at
least 6.5 grams of modified L-arginine and cofactors daily.
78. The method for treating elevated systolic blood pressure
according to claim 75, wherein said method comprises consuming at
least 7.3 grams of modified L-arginine and cofactors daily.
79. The method for treating elevated systolic blood pressure
according to claim 75, wherein said modified L-arginine and
cofactors are formed by exposure to laser radiation with an
amplitude modulation at a resonance frequency of one or more
acoustic vibration frequencies of said L-arginine and cofactors and
said laser radiation is structured in polarization and wave
patterns.
80. A method for treating elevated diastolic blood pressure
comprising: preparing modified L-arginine and cofactors by
subjecting said L-arginine and cofactors to laser radiation; and
ingesting an effective amount of said modified L-arginine and
cofactors.
81. The method for treating elevated diastolic blood pressure
according to claim 80, wherein said method comprises consuming at
least 3.5 grams of modified L-arginine and cofactors daily.
82. The method for treating elevated diastolic blood pressure
according to claim 80, wherein said method comprises consuming at
least 6.5 grams of modified L-arginine and cofactors daily.
83. The method for treating elevated diastolic blood pressure
according to claim 80, wherein said method comprises consuming at
least 7.3 grams of modified L-arginine and cofactors daily.
84. The method for treating elevated diastolic blood pressure
according to claim 80, wherein said modified L-arginine and
cofactors are formed by exposure to laser radiation with an
amplitude modulation at a resonance of one or more acoustic
vibration frequencies of said L-arginine and cofactors and said
laser radiation is structured in polarization and wave
patterns.
85. A method for treating erectile dysfunction comprising:
`preparing modified L-arginine and cofactors by subjecting said
L-arginine and cofactors to laser radiation; and ingesting an
effective amount of said modified L-arginine and cofactors.
86. The method for treating erectile dysfunction according to claim
85, wherein said method comprises consuming at least 3.5 grams of
modified L-arginine and cofactors daily.
87. The method for treating erectile dysfunction according to claim
85, wherein said method comprises consuming at least 6.5 grams of
modified L-arginine and cofactors daily.
88. The method for treating erectile dysfunction according to claim
85, wherein said method comprises consuming at least 7.3 grams of
modified L-arginine and cofactors daily.
89. The method for treating erectile dysfunction according to claim
85, wherein said modified L-arginine and cofactors are formed by
exposure to laser radiation with an amplitude modulation at a
resonance frequency of one or more acoustic vibration frequencies
of said L-arginine and cofactors and said laser radiation is
structured in polarization and wave patterns.
90. A method for improving immunologic function comprising:
preparing modified L-arginine and cofactors by subjecting said
L-arginine and cofactors to laser radiation; and ingesting an
effective amount of said modified L-arginine and cofactors.
91. The method for improving immunologic function according to
claim 90, wherein said modified L-arginine and cofactors are formed
by exposure to laser radiation with an amplitude modulation at a
resonance frequency of one or more acoustic vibration frequencies
of said L-arginine and cofactors and said laser radiation is
structured in polarization and wave patterns.
92. A method for modifying amino acids to reduce the immune
reaction to said amino acids, as would be beneficial to provide
systemic and tissue amino acids in inflammatory, autoimmune, and
allergic conditions, comprising: preparing modified amino acids by
subjecting said amino acids to laser radiation; and ingesting an
effective amount of said modified amino acids.
93. The method for modifying amino acids to reduce the immune
reaction to said amino acids according to claim 92, wherein the
method comprises forming said modified amino acids by exposure to
laser radiation with an amplified modulation at a resonance
frequency of one or more acoustic vibration frequencies of said
amino acids and said laser radiation is structured in polarization
and wave pattern.
94. A method for modifying amino acids to reduce inflammation,
through reducing inflammatory cytokine production in response to
said amino acids comprising: preparing modified amino acids by
subjecting said amino acids to laser radiation; and ingesting an
effective amount of said modified amino acids.
95. The method for modifying amino acids to reduce inflammation,
through reducing inflammatory cytokine production, according to
claim 94, wherein the method comprises forming said modified amino
acids by exposure to laser radiation with an amplitude modification
at a resonance frequency of one or more acoustic vibration
frequencies of said amino acids and said laser radiation is
structured in polarization and wave pattern.
96. A method for increasing the voltage potential of the brain
comprising: preparing modified amino acids by subjecting said amino
acids to laser radiation; and ingesting an effective amount of said
modified amino acids.
97. The method for increasing the voltage potential of the brain
according to claim 96, wherein said method comprises consuming at
least 1.5 grams of said modified amino acids.
98. The method for increasing the voltage potential of the brain
according to claim 96, wherein said method comprises forming said
modified amino acids by exposure to laser radiation with an
amplitude modulation at a resonance frequency of one or more
acoustic vibration frequencies of said amino acids and said laser
radiation is structured in polarization and wave patterns.
99. A method for improving the coherence of brain wave patterns
comprising: preparing modified amino acids by subjecting said amino
acids to laser radiation; and ingesting an effective amount of said
modified amino acids.
100. The method for improving the coherence of brain wave patterns
according to claim 99, wherein said method comprises consuming at
least 1.5 grams of said modified amino acids.
101. The method for improving the coherence of brain wave patterns
according to claim 99, wherein said method comprises forming said
modified amino acids by exposure to laser radiation with an
amplitude modulation at a resonance frequency of one or more
acoustic vibration frequencies of said amino acids, and said laser
radiation is structured in polarization and wave patterns.
102. A method for improving the quality of crystal formation
through increased homogeneity of unit cell elements or reduced
defects in the crystal lattice, or both, comprising: selecting the
molecular species to be crystallized; and subjecting said molecular
species to laser radiation during the process of
crystallization.
103. The method for improving the quality of crystal formation
through increased homogeneity of unit cell elements or reduced
crystal defects or both according to claim 102, wherein the method
comprises subjecting the selected molecular species, during the
crystallization process, to laser radiation with an amplitude
modulation at a resonance frequency of one or more acoustic
vibration frequencies of said molecular species, and said laser
radiation is structured in polarization and wave patterns.
104. A method for improving the quality of crystals that have
already solidified through homogenizing unit cell elements and/or
liberating trapped water in the crystal lattice comprising:
selecting the crystal form to be homogenized and/or dried; and
subjecting said crystal form to laser radiation.
105. The method for improving the quality of crystals that have
already solidified through homogenizing unit cell elements and/or
drying according to claim 104, wherein the method comprises
subjecting said selected crystal form to laser radiation with an
amplitude modulation at a resonance frequency of one or more
acoustic vibration frequencies of the molecular species of said
selected crystal form, and said laser radiation is structured in
polarization and wave patterns.
106. The method for generating highly crystalline and homogeneous
simvastatin comprising: dissolving simvastatin in a solvent and
subjecting said simvastatin to laser radiation during the
crystallization process.
107. The method for generating highly crystalline and homogeneous
simvastatin according to claim 106, wherein the method comprises
dissolving said simvastatin in a solvent and subjecting said
simvastatin to laser radiation with an amplitude modulation at a
resonance frequency of one or more acoustic vibration frequencies
of said simvastatin, and said laser radiation is structured in
polarization and wave patterns.
108. The method for generating amorphous simvastatin comprising:
dissolving simvastatin in a solvent and subjecting said simvastatin
to laser radiation during the crystallization process.
109. The method for generating amorphous simvastatin according to
claim 108, wherein the method comprises dissolving said simvastatin
in ethanol or another solvent and subjecting said simvastatin to
laser radiation with an amplitude modulation at a resonance
frequency of one or more acoustic vibration frequencies of said
simvastatin, and said laser radiation is structured in polarization
and wave patterns.
110. The method for generating amorphous crystals comprising:
dissolving the subject compound in a solvent and subjecting said
compound to laser radiation during the crystallization process.
111. The method for generating amorphous crystals according to
claim 110, wherein the method comprises dissolving the subject
compound in a solvent and subjecting said compound to laser
radiation with an amplitude modulation at a resonance frequency of
one or more acoustic vibration frequencies of said compound, and
said laser radiation is structured in polarization and wave
patterns.
112. A method for generating novel or desired crystal structures
comprising: selecting the molecular species to be crystallized; and
subjecting said molecular species to be crystallized to laser
radiation during the crystallization process.
113. The method for generating novel or desired crystal structures
according to claim 112, wherein the method comprises subjecting
said molecular species during crystallization to laser radiation
with an amplitude modulation at a resonance frequency of one or
more acoustic vibration frequencies of said molecular species, most
ideally a higher acoustic vibration frequency than that of the
backbone of said molecular species, and said laser radiation is
structured in polarization and wave patterns.
113. A method for modifying hydrogen bonding in a crystal
comprising: selecting a crystal in which hydrogen bonding is to be
modified; and subjecting said crystal to laser radiation.
114. The method for modifying hydrogen bonding in a crystal
according to claim 113, wherein the method comprises subjecting
said crystal to laser radiation with an amplitude modulation at a
resonance frequency of one or more acoustic vibration frequencies
of said crystal, and said laser radiation is structured in
polarization and wave patterns.
115. A method for modifying the activity or function of two or more
molecules at the same time comprising: selecting two or more
molecules to modify; and subjecting said molecules to laser
irradiation.
116. The method of modifying 2 or more molecules at the same time
according to claim 115, wherein the method comprises selecting 2 or
more molecules to modify; and subjecting each selected molecule to
laser radiation with an amplitude modulation at a resonant
frequency of one or more acoustic vibration frequencies of each
selected molecule, and said laser radiation is structured in
polarization and wave patterns.
117. The method of modifying 2 or more molecules at the same time
or 2 or more regions of the same molecule according to claim 116,
wherein the method comprises applying laser radiation with 2 or
more lasers of the same or different primary wavelengths; and each
laser may have one or more modulation frequencies; and each laser
may be individually tuned with respect to power level and
characteristics of the optical elements used; and the lasers may be
focused as a matrix of rows and columns, or may be focused along a
row or column, or may be parabolically arranged to focus on a
single point.
118. A method for modifying the activity of an enzyme, substrate,
or ligand, the method comprising: selecting an enzyme, substrate,
or ligand to be modified; and subjecting said enzyme, substrate, or
ligand to laser irradiation to modify the structure thereof.
119. The method for modifying the activity of an enzyme, substrate,
or ligand according to claim 118, wherein the method comprises
selecting an enzyme, substrate, or ligand to be modified; and
subjecting said enzyme, substrate or ligand to laser radiation with
an amplitude modulation at a resonance frequency of one or more
acoustic vibration frequencies of said enzyme, substrate or ligand
to modify the structure thereof, and said laser radiation is
structured in polarization and wave patterns.
120. A method of increasing the depth of penetration of laser
electromagnetic signals and energy through tissue to enhance the
depth and range of therapeutic efficiency of photodynamic therapy,
this method comprising: identifying a condition in tissue that may
be responsive to photodynamic therapy; and determining a suitable
photodynamic compound, photoactivating laser wavelength, and laser
radiation dose to use for treatment of said condition; and
administering said photodynamic compound and allowing sufficient
time for accumulation of said compound in said tissue to be
treated; and applying a sufficient dose of sparse constructive
nodes of laser radiation to the tissue to be treated via external
beam, endoscopically, endarterially or other route as appropriate,
with said laser radiation having an amplitude modulation at a
resonant frequency of one or more acoustic vibration frequencies of
said photodynamic compound, and said laser radiation is structured
in polarization and wave pattern.
121. A method of homogenizing, flattening, and reducing the
distortion of backbone twist of aromatic amino acids and L-dopa,
and any other dopaminergic, catecholaminergic, or serotonergic
precursor, compound, or pharmaceutical agent to enhance the
bioavailability of the modified molecular structure, the method
comprising: selecting the dopaminergic, catecholaminergic, or
serotonergic precursor, compound, or pharmaceutical agent to be
modified; and treating said dopaminergic, catecholaminergic, or
serotonergic precursor, compound, or pharmaceutical agent with
laser radiation.
122. The method of homogenizing, flattening, and reducing the
distortion of backbone twist distortion of aromatic amino acids and
any other dopaminergic, catecholaminergic, or serotonergic
precursor, compound, or pharmaceutical agent to enhance the
bioavailability of the modified molecular structure according to
claim 121, wherein said method comprises selecting a doparninergic,
catecholaminergic, or serotonergic precursor, compound or
pharmaceutical agent to be modified; and treating said
dopaminergic, catecholaminergic, or serotonergic precursor,
compound or pharmaceutical agent with laser radiation, with an
amplitude modulation at a resonance frequency of one or more
acoustic vibration frequencies of said precursor, compound or
pharmaceutical agent, and said laser radiation is structured in
polarization and wave pattern.
123. A method of homogenizing, flattening, and reducing the
distortion of backbone twist of a nutrient, pharmaceutical agent,
or other bioactive substance to enhance the bioavailability of the
modified substance, the method comprising: selecting a nutrient,
pharmaceutical agent, or other bioactive substance to modify; and
treating said nutrient, pharmaceutical agent, or other bioactive
substance with laser radiation.
124. The method of homogenizing, flattening, and reducing the
distortion of backbone twist of a nutrient, pharmaceutical agent,
or other bioactive substance to enhance the bioavailability of the
modified substance according to claim 123, wherein said method
comprises selecting a nutrient, pharmaceutical agent, or other
bioactive substance to modify; and treating said nutrient,
pharmaceutical agent, or other bioactive substance with laser
radiation with an amplitude modulation at a resonant frequency at
one or more acoustic vibration frequencies of said nutrient,
pharmaceutical agent, or other bioactive substance, and said laser
radiation is structured in polarization and wave patterns.
125. A method for increasing the bioavailability of nucleic acid
bases, nucleosides or deoxynucleosides, or nucleotide or
deoxynucleotide monophosphates, diphosphates, or triphosphates, the
method comprising: selecting a nucleic acid base, nucleoside or
deoxynucleoside, or nucleotide or deoxynucleotide monophosphate,
diphosphate, or triphosphate; and subjecting said selected
substance to laser radiation to modify the structure thereof.
126. A method for increasing the bioavailability of nucleic acid
bases, nucleosides or deoxynucleosides, or nucleotide or
deoxynucleotide monophosphates, diphosphates, or triphosphates
according to claim 125, wherein the method comprises selecting a
nucleic acid base, nucleoside or deoxynucleoside, or nucleotide or
deoxynucleotide monophosphate, diphosphate, or triphosphate to
modify; and subjecting said nucleic acid base, nucleoside or
deoxynucleoside, or nucleotide or deoxynucleotide monophosphate,
diphosphate, or triphosphate to laser radiation with an amplitude
modulation at a resonance frequency of one or more acoustic
vibration frequencies of said nucleic acid base, nucleoside or
deoxynucleoside, or nucleotide or deoxynucleotide monophosphate,
diphosphate, or triphosphate, and said laser radiation is
structured in polarization and wave patterns.
127. A method of increasing the bioactivity of high energy
phosphates of nucleotides or deoxynucleotides, the method
comprising: selecting a nucleotide or deoxynucleotide to modify;
and subjecting said nucleotide or deoxynucleotide to laser
radiation.
128. The method of increasing the bioactivity of high energy
phosphates of nucleotides or deoxynucleotides according to claim
127, wherein the method comprises selecting a nucleotide or
deoxynucleotide to modify; and subjecting said nucleotide or
deoxynucleotide to laser radiation with an amplitude modulation at
a resonance frequency of one or more acoustic vibration frequencies
of high energy phosphates of said nucleotide or deoxynucleotide,
and said laser radiation is structured in polarization and wave
pattern.
129. A method of increasing the bioavailability of a nucleic acid
base, nucleoside or deoxynucleoside, or nucleotide or
deoxynucleotide monophosphate, diphosphate, or triphosphate whether
or not it has been modified with laser treatment according to claim
128, the method comprising: making a solution of said nucleic acid
base, nucleoside, or nucleotide monophosphate, diphosphate, or
triphosphate with a concentration at least 10 times that of blood
plasma; and applying said solution for at least 30 seconds to oral
or other nonintestinal mucosa for direct transmucosal absorption to
overcome the extensive degradation of nucleic acid elements as
occurs in intestinal mucosa.
130. A method for amplifying or modifying the production or
purification of a selected stereoisomer or epimer of a bioactive
substance, the method comprising: selecting the stereoisomer to
amplify or modify; and subjecting said stereoisomer or epimer to
rotationally polarized laser light, with an amplitude modulation at
a resonance frequency at one or more acoustic vibration frequencies
of said stereoisomer or epimer, and said laser radiation is
structured in polarization and wave pattern.
131. A method of reshaping prions or other pathogenic proteins to
reduce their pathogenicity, said method comprising: selecting a
prion or other pathogenic protein to reshape; and subjecting said
prion or other pathogenic protein to laser radiation.
132. The method of reshaping prions or other pathogenic proteins to
reduce their pathogenicity according to claim 131, wherein said
method comprises selecting a prion or other pathogenic protein to
reshape; and subjecting said prion or other pathogenic protein to
laser radiation with an amplitude modulation at a resonance
frequency of one or more acoustic vibration frequencies of said
prion or other pathogenic protein, and said laser radiation is
structured in polarization and wave pattern.
133. The method of reshaping prions or other pathogenic proteins to
reduce their pathogenicity according to claim 132, wherein said
method comprises selecting a prion or other pathogenic protein to
reshape; and determining the peak absorption frequencies of said
prions or other pathogenic proteins and their nonpathogenic
counterparts using sonoluminescence with CO2 nucleation absorption
spectrum analysis or other spectroscopic method or mathematical
modeling; and subjecting said prions or other pathogenic proteins
to laser radiation with an amplitude modulation of one or more peak
absorption frequencies of normal protein, the pathogenic protein,
or the differential absorption pattern between the normal and
pathogenic counterpart protein to reshape said prions or other
pathogenic proteins to reduce their pathogenicity, and said laser
radiation is structured in polarization and wave patterns.
134. A method of reshaping pathogenic substances or components of
infectious pathogens to reduce their pathogenicity, said method
comprising: selecting a pathogenic substance or one or more
components of an infectious pathogen to reshape; and subjecting
said pathogenic substance or one or more components of said
infectious pathogen to laser radiation.
135. The method of reshaping pathogenic substances or components of
infectious pathogens to reduce their pathogenicity according to
claim 134, wherein said method comprises selecting a pathogenic
substance or one or more components of an infectious pathogen to
reshape; and subjecting said pathogenic substance or one or more
components of said infectious pathogen to laser radiation, with an
amplitude modulation at a resonance frequency of one or more
acoustic vibration frequencies of said pathogenic substance or of
one or more components of said infectious pathogen, and said laser
radiation is structured in polarization and wave pattern.
136. The method of reshaping pathogenic substances or components of
infectious pathogens to reduce their pathogenicity according to
claim 135, wherein said method comprises selecting a pathogenic
substance or one or more components of an infectious pathogen to
reshape; and determining the peak absorption frequencies of said
pathogenic substance or one or more components of said infectious
pathogen using sonoluminescence with CO2 nucleation absorption
spectrum analysis or other spectroscopic method or mathematical
modeling; and subjecting said pathogenic substance or one or more
components of said infectious pathogen to laser radiation, with an
amplitude modulation of one or more peak absorption frequencies of
said pathogenic substance or of one or more components of said
infectious pathogen, and said laser radiation is structured in
polarization and wave pattern.
137. A method of selectively activating specific regions of
selected molecules to increase the production of desired products
in a chemical reaction, to generate novel reaction sequences for
products, or to generate the production of novel products with
specific molecular shapes, properties, and activities, said method
comprising: selecting one or more molecular species to modify; and
subjecting said molecular species to laser radiation.
138. The method of selectively activating specific regions of
selected molecules to increase the production of desired products
in a chemical reaction, to generate novel reaction sequences for
products, or to generate the production of novel products with
specific molecular shapes, properties, and activities according to
claim 137, wherein said method comprises selecting one or more
molecular species to modify; and subjecting said molecular species
to laser radiation with an amplitude modulation at a resonance
frequency of one or more acoustic vibration frequencies of said
molecular species, and said laser radiation is structured in
polarization and wave pattern.
139. The method of selectively activating specific regions of
selected molecules to increase the production of desired products
in a chemical reaction, to generate novel reaction sequences for
products, or to generate the production of novel products with
specific molecular shapes, properties, and activities according to
claim 136, wherein said method comprises selecting one or more
molecular species to modify; and determining the peak absorption
frequencies of said specific regions of selected molecular species
to be modified using sonoluminescence with CO2 nucleation
absorption spectrum analysis, other spectrographic method, or
through mathematical molecular modeling; and subjecting said
molecular species to laser radiation with an amplitude modulation
of one or more peak absorption frequencies of said molecular
species, and said laser radiation is structured on polarization and
wave pattern.
140. The method of selectively activating molecular species or
specific regions of molecular species to generate a signal for
qualitative or quantitative detection or analysis, said method
comprising: selecting a specific molecular species or region of a
molecular species to activate through resonance; and subjecting
said molecular species to laser radiation with an amplitude
modulation at a resonance frequency of one or more acoustic
vibration frequencies of said molecular species, and said laser
radiation is structured in polarization and wave pattern.
141. The method of selectively activating molecular species or
specific regions of molecular species to generate a signal for
qualitative or quantitative detection or analysis according to
claim 140, wherein said method comprises selecting a specific
molecular species or region of a molecular species to activate
through resonance; and determining the peak absorption frequencies
of said specific molecular species or region of a molecular species
using sonoluminescence with CO2 nucleation absorption spectrum
analysis, other spectrographic method, or through mathematical
molecular modeling; and subjecting said molecular species to laser
radiation with an amplitude modulation of one or more peak
absorption frequencies of said molecular species, and said laser
radiation is structured in polarization and wave pattern.
142. A method for creating sub-picosecond laser pulses comprising:
passing a laser beam through a first diffractive grating, a
refractive element, and a second diffractive grating.
143. A method for creating a tightly coherent string of
sub-picosecond duration laser pulses comprising: passing a laser
beam through a first diffractive grating, a refractive element, and
a second diffractive grating.
144. A method for creating a structured electro magnetic field
comprising: passing a laser beam through a first diffractive
grating, a refractive element, and a second diffractive grating.
Description
RELATED APPLICATIONS
[0001] The present application is a continuation-in-part of U.S.
application Ser. No. 10/069,052, which is the U.S. Nationalization
of International Application No. PCT/GB00/03280, filed Aug. 29,
2000 which claims priority to GB 9920351.5, filed Aug. 28, 1999,
and claims the benefit of U.S. Provisional Application No.
60/446,146, filed on Feb. 10, 2003, and U.S. Provisional
Application No. 60/505,910, filed on Sep. 25, 2003.
BACKGROUND
[0002] 1. Field of the Invention
[0003] The present invention relates to novel dietary amino acid
and nutrient products, as well as enhanced pharmaceutical products,
and method for producing the same. More particularly, the present
invention relates to such products and a method wherein the
products have advantageously modified bioactivity reaction profiles
and method for producing said products by means of exposure to
specific amplitude modulated and structured laser light processes.
These processes alter the bond structure and shape of molecules in
the compound and thus alter the reaction characteristics such that
certain preferred biological reactions can be enhanced and in other
cases less preferred reactions can be suppressed at least over an
initial period after ingestion or administration so the product can
be more accurately tailored to deliver a desired therapeutic or
nutrient effect. Accordingly, the present invention also relates to
the molecular resonance of molecules, in particular to molecular
resonance generated by laser radiation.
[0004] 2. State of the Art
[0005] The concept of introducing high Q molecules that may be
stimulated by laser light to deliver toxic or therapeutic effects
is known from Dunlavy U.S. Pat. No. 5,313,315. However, the direct
stimulation of natural biological processes by means of molecular
resonance using modulated or selective wavelength lasers has
hitherto proved to be impossible. This is because of the scattering
nature of the medium, the close proximity of many resonances in
natural molecules and the difficulty of differentially raising the
temperature and thereby the reactivity of individual desired
molecules.
[0006] The present invention defines an apparatus and method which
overcomes some of these problems and covers the nature and type of
molecule susceptible to differential stimulation. [0005] Many
critical chemical reactions in the body are functions of the Cell
Surface Cell Adhesion Molecules that are in turn moderated by
various integrins. The geometric structure of many Cell Adhesion
Molecules and particular integrins is such that they are capable of
supporting a resonance at relatively low frequencies and
surprisingly high frequencies. Unlike most protein structures which
are heavily damped or inherently rigid in structure, these
molecules generally take the form of a pair of relatively rigid
structures separated by space often bridged by a singled strand.
This structure is especially sensitive to periodic stimulation by a
laser source especially when the molecule surface is neutral or
slightly negatively charged. The polar and hydrophobic regions of
the molecule also differentially absorb energy from laser light.
This causes brief alterations in both the structural bond energy
and consequently tends to amplify the vibration of the molecule.
The effect of this is to slightly increase the chemical reactivity
of particular molecules on a cell surface relative to the
surrounding molecules of a more generally damped structure or other
high Q molecules of a different resonant frequency.
[0007] In vivo the scattering of light at suitable excitation
wavelengths is extreme and as a result even quite low frequency
modulation signals tend to be corrupted by the multiple scatter
path lengths and by the delay in absorption and release of photons
in those atoms at low energy states.
[0008] Also if continuous laser radiation is delivered to a mass of
cells the high damping factor of the structure means that in
general the overall temperature of the cell mass rises. This occurs
even if modulated at the resonant frequency of a particular
molecule. The use of laser radiation in this way produces an
increase in the reactivity of the entire cell surface which means
that no actual change in the reaction products occur because the
cells are in general, at equilibrium.
[0009] Conversely if very low energy is delivered at the resonance
frequency of the cell adhesion molecules or if energy can be
delivered as an intermittent pulse of extremely short duration, the
cell adhesion molecules and the integrins with their inherently
high Q structure tend to maintain a slightly higher temperature
than the surrounding molecules. Thus the cell adhesion molecules
can be stimulated to a greater reactivity than the surrounding
surface molecules.
[0010] Many biological processes can be disturbed into a cascade of
increasing reactivity if an initial response is initiated. The
immune response is a powerful example of this but the nature of
biological reactions on the cell surface means that similar cascade
reactions occur for a wide variety of initial conditions disturbed
from equilibrium. Thus a very small change in the reactivity of a
surface molecule for a short time can result in a dramatic change
in the chemistry of the cell surface for a considerable period
after the stimulation.
[0011] This effect depends on the cell chemistry being
substantially in equilibrium at the commencement of the delivery of
the radiation, otherwise the resonance effect will tend to be
swamped by the current dominant reaction. Thus the target cells
must be in a relatively neutral pH environment and obviously not
engaged in a vigorous metabolic process. Ideally also the cell
surface molecule would be neutral or slightly negative as this
increases the absorption of photons and so increases the transfer
of energy from the laser to the molecule.
[0012] Although this limits the use of this method, it has one
beneficial effect with respect to therapeutic use in carcinomas.
The undifferentiated cells of a carcinoma are generally at
equilibrium on the surface as most of the chemical energy of the
cell is expended internally in the cell duplication process. This
means that the undifferentiated cells of a carcinoma are
particularly susceptible to the effect of the method on the surface
chemistry since by their nature they conform to the ideal
requirements for low energy disturbance of the equilibrium.
[0013] It is a critical requirement of this effect that the initial
stimulation is periodic and of very low overall energy, as higher
energy stimulation would merely raise the temperature of the entire
cell by conduction and would not change the reaction equilibrium.
To achieve such a change, individual molecules on the cell surface
must be at different temperatures. Ideally it would consist of
small, directed bursts of light modulated at the frequency of the
desired molecule. Unfortunately it is clearly impossible to direct
such a beam in the highly scattering medium of a living human
body.
[0014] If a conventional laser or simple light beam is directed at
a highly scattering medium, the modulation is eliminated at any
substantial frequency because the light paths to any given point
are so numerous and of such differing lengths that any modulation
is reduced to noise after a few millimeters of the scattering
medium. Even at lower frequencies the general level of overall
energy delivered to the cells means that conduction and convection
tend to raise the overall temperature of the cell surface rather
than allow isolated temperature differences to exist for any useful
length of time. Further it is impractical to generate a light pulse
which is of sufficiently short duration and with a sufficiently
high pulse repetition frequency to be of practical use in the
stimulation of any resonance of a Q likely to occur in a living
cell surface molecule.
[0015] This invention provides a means of differentially
stimulating at least those molecules susceptible by their structure
to resonant stimulus.
[0016] The body or specific organs in the body make use of
nutrients in a variety of complex ways. These biological processes
often occur in reactions that are moderated by enzymes. The
efficiency of a given nutrient or compound depends on the relative
ease with which it can be incorporated by the body in the desired
form. This ease of incorporation is termed "bioavailability" for
the purposes of the present disclosure. Thus, it will be understood
that references to increased bioavailability may relate to the
amount of a compound that is utilized by the body, or the speed or
efficiency with which the compound is utilized depending on the
context discussed.
[0017] Furthermore, improved bioavailability can also refer to
improvements in the manner in which a compound is absorbed. In
other words, absorption of a nutrient or pharmacologic agent with
decreased irritation or reduced adverse effects is improved
bioavailability, even though the actual amount of the compound
absorbed may not increase.
[0018] It is known from Strachan PCT/GB00/03280 that sparse nodes
of constructive interference of electromagnetic (EM) waves
generated as rapidly as sub-femtosecond duration can be configured
to overcome much of the limitations of scatter pathways through
organic and other molecular media to selectively stimulate specific
molecular resonances far more efficiently than ordinary laser EM
stimulation.
[0019] Ordinarily, laser EM stimulation tends to rapidly degenerate
to nonspecific thermal effects through the scattering medium. In
contrast, the polarization and field structure of the EM radiation
in a sparse constructive node beam can be maintained sufficiently
stable such that the polar and hydrophobic regions of a molecule
differentially absorb laser energy from these sparse constructive
nodes to influence structural bond energy due to primarily acoustic
resonance of the molecule altering molecular shape, and consequent
chemical reactivity.
[0020] Sparse constructive nodes are generated and modulated
through an optical device as described in Strachan EP865618A1.
Specifically, a laser beam is passed through a first diffraction
grating, a refractive element, and a second diffraction grating
such that the beam is substantially canceled.
[0021] A refractive element allows the cancellation to occur over a
small percentage of the wavelength variance of the laser source
rather than at a single critical wavelength. This means that a
complex Fresnel/Fraunhoffer zone will be generated, defined by the
beat frequency of the high and low frequencies as a function of the
aperture.
[0022] Thus, relatively sparse zones of constructive interference
will occur between the high and low frequency passes of the
cancellation element in selected directions from the aperture.
Fractional changes in wavelength of the laser or relative
amplitudes of wavelengths in the laser cause rapid translation in
the location of these nodes. In effect the continuous beam is
transformed into a string of extremely short duration pulses,
typically of sub-femtosecond duration by the simple means of
relatively small low frequency amplitude modulation.
[0023] Strachan (PCT/GB00/03280) also describes the use of an array
of constructive node beams to sequence and promote the folding
steps of a protein much as a chaperonin-like effect. In addition,
amino acid structures that may have heterogeneous forms in the dry
state may be homogenized into a more self-consistent form to
selectively alter the biological reactivity of the structure.
[0024] In particular, the homogenization can make metabolic
utilization significantly more efficient, due to the consequently
simpler enzyme moderated reactions resulting from the reduced range
of crystalline forms. This is especially so when the resulting
forms are generally more polar, increasing the production of
desired products relatively more rapidly than usual, and thereby
reducing nonspecific degradation of the substrate.
[0025] Strachan further describes the ability to favor the
production of structures of desired "handedness" in chiral
compounds (as well as epimers through logical extension) through
modulating the beam at the resonance of the structure, either to
enhance the production of the desired rotation, or reduce the
production of the less desired rotation. This last effect can be
further promoted by the application of a rotational component to
the polarization state of the beam.
SUMMARY OF INVENTION
[0026] While Strachan teaches that it is possible to modify the
structure of various compositions, it focuses principally on cell
adhesion, integrins and apoptosis. The present invention, however,
has found that the method discussed in Strachan is highly
advantageous for the modification of amino acids, phytonutrients,
nutrient and food substances, pharmacologic agents, and other
bioactive substances regardless of the method of administration, to
modify the bioavailability of the substance and/or to modify the
manner in which the body reacts to that substance.
[0027] On a fundamental level, the present invention involves a
method utilizing the technology taught in Strachan regarding
molecular stimulation. In particular, a beam of light is passed
through a bioactive substance in such a manner that resonance
causes the modifications in the molecular structure of the
molecule. This may be the folding of the molecule, the promotion or
inhibition of a certain "handed-ness" of a stereoisomeric molecule,
or simply a modification in the molecular dimensions of the
molecule. By selectively controlling the molecules, however,
significant changes can be made in bioavailability, and/or
physiologic reaction to the molecule.
[0028] The intrinsic line variation of the gas laser in the absence
of an etalon or other line narrowing apparatus is adequate to
provide the fractional frequency shift needed to traverse the
sparse constructive nodes through the mixture. The polarization
plane of the laser will define the primary axis of crystalline
formation or distortion in the case of a dry state application.
Note that a circularly polarized laser will tend to favor the
crystallization of one stereoisomer over the other. Further control
of the final molecular form can be provided by modulating the laser
amplitude at a frequency resonant with a given bond or bond group
in the molecule or crystal.
[0029] In the absence of a specific amplitude modulation, the
modulation caused by the constructive node traverse resulting from
laser line instability will tend to thermally energize and spread
the carbon-hydrogen and carbon-oxygen and hydrogen-oxygen bonds
while leaving planar and cyclic carbon bonds at a low energy. This
will have a tendency to "dry" the crystalline form in that it will
tend to reduce the water content in the molecule.
[0030] There will be a tendency for stray hydrogen bonds to
proliferate in the molecule at least temporarily, largely as a
result of this effect. The dry state of the molecule (even in
solution) will, of course, result in the crystal form being less
constrained by the hydrophobic nodes and in the absence of this
force the laser stimulation and thermal vibration of the outer
bonds will tend to favor a flatter form of the molecule. Thus,
whereas amino acid compounds and isomers typically tend to
crystallize more or less randomly from various seed crystals in a
solution depending on the bonded water distribution, under laser
stimulation, the vast majority of the crystal formation will be of
the flattest form the molecule will allow. Thus the entire
"mixture" of random molecular configurations will tend to become
highly homogeneous.
[0031] While it would seem that this process might best be applied
during initial crystallization, in practice, this is not necessary
as the laser stimulates the water bonds directly and thus can
effectively "evaporate" the bonded water in a the dry state as well
as alter the bond formation in a solution form. In addition to the
water bond effect the asymmetric heating of the molecule combined
with the field forces from the EM wave itself will induce the
flatter state in any case where the modulation frequency is below 3
MHz and above 100 KHz.
[0032] Specific molecular forms can be induced by the use of
specific modulation frequencies and node traverse speeds; however,
this patent deals primarily with the bulk effects of laser acoustic
resonance and its application to the manipulation of the
physiological effects of nutritional supplements and pharmacologic
agents.
[0033] In this respect one skilled in the art of physiological and
pharmacological effects desired may consider which of a group of
amino acids or bioactive substances he wishes to be metabolized
preferentially or temporally in advance of other components of a
mixture and adjust the metabolic absorption of the compound
accordingly by means of the disclosed method.
[0034] The present invention relates to specific compounds that are
treated according to the method disclosed with the simple intent of
increasing or modifying the metabolization rate of the entire
mixture. This produces the measured crystallographic effects
described. The resulting physiological effect may be inferred from
the bioassay results and from the clinical trials below.
[0035] Efficiency of the laser stimulation is improved if the
compound is maintained at a neutral pH and is exposed at a
background temperature of 25-35 degrees C. It is critically
important that the laser stimulation average power is extremely
low, less than would raise the bulk substrate temperature by more
than a degree per mole per second, as otherwise purely random
thermal effects will dominate the resonance and field effects of
the laser.
[0036] The sparse constructive nodes in the optical device taught
by Strachan occur as rapidly translating islands of constructive
interference in a background of photons that are highly
self-cancelled through destructive interference of photons in the
center frequencies of the laser wavelength band. The beat frequency
generated as the difference between the highest and lowest
frequencies in the laser wavelength band produces constructive
nodes that are very precisely placed in space. The next photon
packet arrives at the same space in resonance with the traverse of
the preceding photon packet. The resulting train of resonant
constructive nodes behaves as though it is a series of ultrashort
pulses separated spatially and temporally by an intervening medium
of highly self-interfered waves. The duration of these effective
pulse nodes can be as brief as subfemtosecond in their translation
across molecular structure.
[0037] The impulse or "bang" on each molecule from the sparse
constructive node is defined by photon absorption from the node or
retransmission from the molecule that has been stimulated to ring
due to acoustic resonance. Photon absorption or retransmission is
described in mathematical terms as a Dirac, an impulse that
functions as a spike essentially of infinite height and infinite
narrowness. In order to make any structure ring at a resonant
frequency, it must be stimulated with a frequency equal to or
higher than its natural frequency, which condition is thus
satisfied by any photon absorption or emission.
[0038] The passage of the molecule from the constructive node with
a high probability of photon absorption into the much larger
intervening space of the destructive nodes with a very low
probability of photon absorption means that the molecule will have
a high probability of releasing the photon, i.e., dropping the
electron orbit of one or more of its atoms in the intervening time.
Since the molecule will react to both the absorption and release of
photons with an acoustic vibration on the backbone of the molecule,
ideally the constructive nodes would be provided exactly at this
frequency.
[0039] However, while that is the ideal, any presentation of
constructive nodes substantially lower in frequency than the
primary backbone resonance, but still faster than the damping time
of the molecular resonance will be preferable to continuous wave
laser stimulation in terms of delivering a flattening or stretching
effect on the molecule. Delivering the ideal frequency is best, but
just above this frequency there is likely to be interference
between the constructive nodes and substrate coupled acoustic
energy that would reduce the stimulation to the continuous wave
laser effect, or basic thermal heating.
[0040] As an alternative to delivering the exact resonant frequency
of the backbone of a given molecule, in many cases it may be better
to deliver the pulse train "bang and ring" effect of a low
modulation frequency sufficient to cause a rapid node translation
and avoid the potential frequency overshoot of attempting to
deliver a perfectly tuned wave that may degrade to a purely random
thermal effect.
[0041] In the case of a general homogenization process it is
possible that the inhomogeneity of the reagent would be sufficient
to make a pure wave high Q delivery counterproductive, so that
delivery of a pulse train frequency below the resonant frequency of
the molecular backbone, yet faster than the damping time of the
molecule, may in many cases give a preferable result than
attempting to match the resonant frequency of the molecular
backbone.
[0042] In selected cases in which more specific molecular effects
are desired, the first step may be a general molecular
homogenization followed by tuning the constructive node frequency
to that of the backbone resonance or other specific intramolecular
resonances.
[0043] The sparse constructive node frequencies may be tuned by
using a wider or narrower band Strachan optical interference plate,
using a primary laser with a wider or narrower emission line,
adjusting the aperture or angle of the interference plate, using a
higher or lower frequency laser, or modulating the primary laser
beam by electronic amplitude modulation or passing the beam through
an acoustical-optical crystal modulation system.
[0044] Higher frequency modulation can be achieved through a wider
band interference plate, use of a laser with a wider wavelength
emission line, use of a higher frequency laser, or a higher
frequency of primary beam modulation before it traverses the
Strachan optical interference device.
[0045] The transition of a sparse constructive node past a given
point is defined by the complex interaction of the various phase
additions of the beat frequency and the modulations of the beat
frequency by changes in both the center frequency of the laser and
the relative amplitudes and positions of the upper and lower limits
of the laser emission line which straddle the interference band of
the Strachan optical device.
[0046] The modulation of the laser can be quite slow even when the
constructive interference nodes are translating past a fixed point
in space at very high speed. Even if there were no modulation of
the laser, the beat frequency of the upper and lower limits can
still cause a moving rather than a standing constructive wave
pattern. If the constructive node transition frequency can be
anything other than zero when the modulation frequency is zero, it
follows that in general the node transition frequency will be
higher than the modulation frequency.
[0047] The are always several frequencies involved: the laser
frequency that is uncancelled above the interference canceling
frequency and the frequency that is below the cancelled frequency,
the beat frequency of those as the sum and as the difference, and
the spatial separation of the constructive nodes versus the speed
of the phase traverse, the last depending on the aperture and the
frequencies involved.
[0048] Also there is the absorption "pulse" of the transition of
the electron shell as an atom absorbs or releases a photon, which
can be considered infinite relative to the other frequencies.
[0049] The sparse constructive node beam differs significantly from
conventional continuous wave lasers in its interactions with
molecular structure. When a molecule absorbs a photon from a
conventional continuous wave laser, the stimulated atom tends to
remain excited with the electrons in the excited shell, because in
the absence of the destructive nodes the atom is always bombarded
by photons. The atom in an excited state becomes reflective of
further photons. Since the atom cannot absorb more photons from a
continuous beam, it is neither excited more, nor is it capable of
effectively emitting photons because as soon as the electron shell
tries to drop to a lower energy, another photon impinges from the
beam so that the molecular structure is not excited
acoustically.
[0050] In the case of a sparse constructive node beam, however, the
atom absorbs a photon and the molecule rings a little as it
redistributes the kinetic energy of the absorption. Photon
absorption sends a pulse wave to the other end of the molecule
along the backbone, that in turn reflects to the origin, so the
process of absorption, travel down the backbone to the opposite
end, and reflection to the origin intrinsically tends to occur at
the natural frequency of the backbone, determined by the shape,
size, and composition of the molecule. If the subsequent
destructive node lasts long enough, then as the kinetic energy
acoustic signal reflects down the backbone, it will release the
photon. Once again the kinetic energy of the release will
distribute along the backbone.
[0051] In the case of an ideally tuned sparse constructive node
beam, as the kinetic acoustic wave hits the end of the molecule and
reflects to the origin, a new constructive node will arrive at the
molecule and once again excite ground state atoms to higher shells.
In this resonant case with the described tuned sparse constructive
node, the "shock" of the arriving photon is in phase with the
ringing of the shock of the previous photon absorption and release.
Hence the increase in overall kinetic energy of the molecule is now
twice what it would be if stimulated by an ordinary continuous wave
laser.
[0052] The process repeats as above and depending on the damping
loss of the molecule, which depends on the bond structure, the
kinetic energy will rise from this factor of two to a factor of
many thousands. The kinetic energy or temperature of the molecule
is thus raised substantially with respect to its local
environment.
[0053] If the constructive nodes are too close, then the resonant
buildup as described will be inhibited through lack of sufficient
relaxation time for photon re-emission. Likewise the coupling of
acoustic energy molecule to molecule through the medium in which
the molecule exists (water if in solution and the solid if the
molecule is in powder form) will tend to interfere with the above
described pure resonance. Too much or too close acoustic coupling
tends to have the same effect as the sparse nodes being too close
and the result can be the inability of the molecule to absorb and
release photons at the ideal resonant frequency reducing the
ability to amplify the net kinetic energy of the molecule.
[0054] There are critical differences between the sparse
constructive node effect and conventional continuous wave lasers in
terms of energy transmitted to the molecule being stimulated. If
the molecule is bathed in continuous wave light of the given
wavelength, all of the atoms that can, will absorb photons and will
have excited electrons. The hydrogen bonds will be destroyed
temporarily; once that happens, the thermal effects will cause
molecules in bulk to oscillate at greater amplitude but there will
only be random forces on individual molecules.
[0055] Conversely in the case of sparse constructive node
irradiation, the individual molecules rarely saturate with
absorption of all possible photons, but rather will have time to
absorb and release photons and will tend to do so at the resonant
frequency of the backbone. Thus the energy exchanged with the
backbone is higher in the sparse constructive node mode than in
continuous wave laser mode and in addition the molecule is excited
in a high polarization EM field state impossible in a highly
scattered continuous wave mode.
[0056] Excitation of the molecule by sparse constructive node laser
stimulation is caused by the absorption and release of photons,
which absorptions and releases can be considered as infinite
frequency impulses, much as the impact of a clapper hitting a bell
is infinite with respect to the frequency of the bell's ring. At
the same time the molecule is excited by these absorptions and
releases, it is also under stress from the electric and magnetic
field of the electromagnetic wave that is generally very large with
respect to the stimulated molecule.
[0057] For example, L-arginine and betaine molecules are only a few
nanometers long, while the laser wavelength in stimulation
experiments has been 670 nanometers long. The effect can be
considered similar to tapping a sheet of iron filings on top of a
magnet. If you don't tap the sheet the iron filings stick to the
sheet. As the sheet is tapped the filings are briefly free to move.
In the absence of the magnetic field, they would simply disperse
randomly, but in the presence of the field they line up with the
lines of force.
[0058] Similarly with sparse constructive node irradiation, the
tapping of the sheet is represented by the absorption and release
of photons, while the EM field of the wavelength of the laser
frequency represents the overall magnetic lines of force.
[0059] Through this process the molecule is subjected to the very
long wavelength field effect of the EM wave at a given polarization
that tends to pull the molecule in line with the field at the same
time as one or more atoms in the molecule absorb individual photons
from the node. This ensures that the molecule will ring at its
natural frequency and will tend to orient with the field.
[0060] When more specific effects are desired than the simple "bang
and ring" of the low frequency flatten and stretch effect, a
specific bond resonance frequency for a given molecule would be
applied. This would be at a much higher frequency and would cause
very specific alterations in the molecule rather than the general
homogenization effect caused by lower frequencies and sparser
nodes. These alterations range from breaking specific molecular
bonds, perhaps with a view to immediate incorporation of the
cleavage fragment into another molecule, to causing a particular
end of a molecule to preferentially bond in a polymerization
process.
[0061] The estimated dosage of laser irradiation to achieve the
general molecular homogenization effect has been estimated for the
betaine molecule to be as rapid as 3 seconds per mole per milliwatt
of applied laser energy under ideal conditions of particle
exposure. Smaller particle size and dispersion or air suspension of
particles will tend to make the process more efficient. Using the
molar ratio of treatment for betaine gives an approximate fastest
rate of homogenization effect at a dosage of 30 seconds per
kilogram per milliwatt.
[0062] For larger molecules the duration of treatment per mole per
milliwatt will be greater, but this will roughly increase in
proportion to molecular weight so that the fastest effective
treatment duration per kilogram will remain roughly the same.
Treatment duration longer than required will not tend to further
increase the effect nor will it likely degrade to purely thermal
effects as long as the radiation applied is generally below or much
below that which would raise the bulk temperature of the treated
species by more than one degree Celsius per mole per second.
[0063] For practical purposes, to increase the tendency to maximum
homogenization effect, treatment dosage has usually ranged from
0.03 to 0.05 kilograms per minute per milliwatt of sparse
constructive node laser irradiation.
[0064] Comparing and contrasting the sparse constructive node laser
EM irradiation to routinely configured continuous wave lasers,
several essential differences appear. As noted in Strachan
PCT/GB00/03280, the depth of penetration of visible wavelengths of
conventional laser EM through an intensely scattering medium such
as human skin is typically less than 5 mm even at the most
penetrating wavelengths. In contrast, the pulse train of sparse
constructive nodes, by virtue of much decreased scattering, may
have effective coherent penetration of 60 mm through skin and even
greater penetration through other tissues.
[0065] For combined modality treatments such as photodynamic
therapy (PDT) which combines the effects of photosensitizing
compounds such as benzoporphyrin derivative with the application of
photons to cause photo-oxidation reactions resulting in elimination
of pathologic tissue, application of sparse constructive node laser
irradiation could greatly extend the current reach of this
treatment modality.
[0066] For practical purposes, for example in the treatment of
malignancy, photodynamic therapy is limited to application to
endoscopically visible lesions in the respiratory or digestive
tracts, or to other areas topical to the skin or directly
accessible with a fiberoptically transmitted laser EM signal.
Greater depth of effective coherent signal penetration could make a
wider range of malignant lesions and other PDT sensitive conditions
accessible to treatment with this generally effective and well
tolerated modality.
[0067] Conventional lasers usually produce equal ratios of
constructive and destructive nodes, representing a small ratio of
overall output energy, generally much less than 1% of output
energy. Even a modulated beam of conventional laser EM will not
have a sufficient duration of relaxation time before the entry of
the next photon to permit efficient per cycle release of absorbed
photons. In contrast, in a sparse constructive node beam,
destructive nodes are highly dominant and highly structured in the
emission from the optical device.
[0068] When an atom absorbs a photon from a conventional laser
beam, the atom becomes highly reflective of additional photons,
until the absorbed photon is emitted. Because of the absence of
sufficient destructive nodes to permit enough conduction of energy
away from the atom before the next packet arrives for absorption,
the atom tends to remain in an excited and reflective state.
[0069] In contrast, with sparse constructive node laser EM
irradiation, each atom is excited at resonance with the molecular
backbone. The intervening traverse of the destructive node permits
the collapse to ground state with photon emission. The atom is then
ready to absorb the next photon from the constructive node when it
arrives, to sustain and magnify the resonance effects.
[0070] The high level of surface reflectance due to molecular
absorption of photons from conventional laser irradiation causes
intense photon scattering at the surface irradiated. All light
scatters and plumes at the beginning of the entry of the beam
through the absorptive medium. There is a flare at the surface
only, with scattering thereafter, preventing potential resonance
effects.
[0071] In contrast, in a sparse constructive node beam, the
constructive nodes are rare and destructive nodes dominate. The
space between the constructive nodes allows intramolecular
resonance and intermolecular tuning. Unlike a bright continuous
wave beam, the sparse constructive node effect is spread through
the medium, so the effect is less scattering, permitting deeper
penetration and greater degrees of molecular resonant
stimulation.
[0072] Although a pulsed conventional laser with a short pulse
duration time may overcome some of the limitations of continuous
wave lasers for resonant stimulation, the absence of predominant
destructive nodes in the pulse waves will still tend to result in
high degrees of surface scattering. The ultrashort constructive
nodes with the relaxation phase of the destructive nodes will tend
to enhance the performance of a sparse constructive node beam over
an ordinary pulsed laser beam for acoustic resonance and coherent
depth of penetration.
[0073] The performance of a conventional pulsed laser in
stimulating molecular resonance would be expected to improve if the
pulses themselves were configured into sparse constructive nodes by
passing the pulsed beam through a Strachan interference optical
device.
[0074] Conventional continuous wave laser irradiation has a high
probability of hitting a molecule more than once per resonant cycle
of the irradiated molecule. In contrast, with sparse constructive
node laser irradiation, the probability of an atom being hit by
another photon in a period of excitation is low, but once per cycle
is high.
[0075] By analogy, consider several bells lined up in a row. The
deluge of scattering photons in a continuous wave laser beam
squashes the resonance of the first bell. In comparison, sparse
constructive node irradiation stimulates resonant ringing of the
first bell that then stimulates the other bells to begin to ring,
translating the resonant signal deeper into the irradiated medium.
In this manner the sparse constructive node can stimulate
intramolecular and intermolecular resonance. In the sparse
constructive node, the probability of photon arrival at the
intended molecule is adjusted to permit building cycles of
molecular resonance that increase molecular kinetic energy.
[0076] Continuous wave laser irradiation causes an abrupt increase
of thermal energy at the absorptive surface that is conducted
randomly from the locus of stimulation. In contrast, sparse
constructive nodes deliver lower total energy, but deliver this
energy through resonance to very specific locations. The structured
energy retained per molecule can be many times greater than that
delivered through conventional continuous wave laser stimulation,
increasing the reactivity of the treated molecules.
[0077] Continuous wave laser irradiation excites molecules at the
time there should be a trough. This is akin to kicking a swing
continuously, which will deliver impulses out of phase with the
natural frequency of the swing cycle. Sparse constructive nodes
deliver less energy, but provide it in phase with the natural
frequency of the molecule stimulated. The kinetic energy that
builds in the backbone structure of the molecule will tend to
stretch and flatten the molecule.
[0078] In addition, this will tend to remove bonded water from the
molecule, resulting in a dryer structure, even in a molecule
already in dry powder form. Hydrogen bonds may be rearranged,
altering solubility factors and potentially modifying the free
energy of chemical bonds thus restructured.
[0079] In general, the stretched and flattened shape stimulated by
sparse constructive node laser irradiation will tend to be highly
homogeneous from molecule to molecule. The molecules thus
homogenized will tend to have a lower overall energy configuration
with a higher electric and magnetic field moment than molecules not
homogenized with this process.
[0080] Homogeneity, flattened and stretched shape, and high
electric and magnetic field moments favor efficient binding of
substrates to enzymes or ligands to receptor sites, especially the
binding of the next reactant molecule to an enzyme if it is highly
similar in shape to the reactant that has just been released from
the enzyme.
[0081] Conventional continuous wave laser irradiation has a low
probability of maintaining resonance, exciting everything and
delivering photons at the wrong time. It is therefore inefficient
at changing the shape of molecules in a consistent fashion. In
contrast, sparse constructive node laser stimulation is
intrinsically efficient at stimulating the natural frequencies of
molecules and homogenizing their shape.
[0082] Chemical and especially enzymatically catalyzed reactions
are highly shape dependent. The relatively random effects on
molecular shape caused by conventional laser irradiation may do
little to increase efficiency of chemical reactions other than rate
acceleration due to thermal heating alone (with the exception of
wavelength specific photochemical reactions). In contrast, sparse
constructive node laser irradiation can provide vastly greater
control over chemical reactions. This can be through homogenization
of substrate or specifically heating a bond that is desired to be
more active in the reaction process.
[0083] Sparse constructive node stimulation is especially
advantageous in a reaction in which heating would damage one
reagent while leaving the other unharmed. Sparse constructive node
irradiation can be used to heat the temperature resistant substrate
while leaving the temperature sensitive reactant unharmed.
[0084] For a chemical reaction, especially an enzyme moderated one,
the homogenization process can increase the chemical potential, or
potential difference, that drives it. The chemical potential
depends on the intrinsic properties of the substrate and product
molecules, and their concentrations. If a reaction process A+B=C+D
is reversible, the direction and rate of the reaction depends on
the properties of A, B, C, and D and the effective quantities of
each. The more A and B one adds, the more C and D are formed, and
vice versa; also, if C or D is removed as fast as it is made, the
reaction is driven to the right.
[0085] Homogeneity in the reactants is equivalent to increased
concentration because the reaction surface of the cell can be more
regular and thus more compact, and because enzymes will bond
considerably faster to a molecule identical to that just released
than to one even slightly dimensionally different.
[0086] Considering the chemical potential as defined above with
respect to enzyme moderated reactions, it can be seen that
increasing the homogeneity of one or more of the reactants is
equivalent to both increasing the effective concentration of the
reactant and lowering the first stage energy of binding the
reactant to the enzyme, because the enzyme that fits one molecule
needs virtually no energy to fit the next if the substrate shapes
are identical, let alone requiring, as in the case of highly
inhomogeneously crystallized reactants, the manufacture of a wider
range of enzymes to moderate a given reaction. The energy potential
of the reactions rise because of the increase in effective
concentration of the reactants.
[0087] Some molecules will have a change in the free energy of
certain bonds due to the overall shape change of the molecule.
Depending on the product desired, this may help or hinder the
production of a given product, whereas increasing the similarity
molecule to molecule of bond energy and dimension will always
facilitate the production of a product in an enzyme moderated
reaction. The effect on each interaction may be tiny but the
overall effect can be substantial.
[0088] The rate at which a reactant can be supplied to an enzyme or
receptor is directly proportional to the self-similarity of the
molecules of the reactant or the receptor ligand. Thus a given
quantity of reactant or receptor ligand can generate more product
or stimulate more potent receptor effects the greater the
self-similarity of the reactant molecules to each other. Molecules
irradiated with sparse constructive nodes will in general be highly
similar to one another in terms of shape and dimensions,
distribution and location of water, and the presence of relatively
high electric and magnetic field moments for that molecular
species.
[0089] One particular advantage of this invention is that the
homogenizing action on a dry powder of L-arginine can be translated
into differential effects in vitro after dissolving the dry powder
into solution. Thus, the treatment of the dry power causes a
structural change in the molecules that changes the bioavailability
and/or the physiologic reaction to the substance. This, in turn,
materially alters the utilization of the substance by a body--and
in particular, a mammalian body. The substance is sufficiently
stable to maintain the effects of molecular stimulation that
creates an enhanced biological effect even after the substance is
dissolved in solution. In addition, the use of the method on a
solution containing the substance can produce similar
enhancements.
[0090] In accordance with another aspect of the present invention,
the method is used to modify the physiologic production of nitric
oxide from the amino acid L-arginine. For a given molar
concentration of L-arginine, depending on the laser resonance
applied, the production of nitric oxide from macrophages in vitro
may be statistically significantly increased or decreased. Thus, by
utilizing the present invention, one can increase desirable
byproducts or decrease undesirable byproducts associated with a
nutrient, pharmacological agent, or other bioactive substance in
the body.
[0091] In accordance with another aspect of the present invention,
the method involves increasing the potency of L-arginine to amplify
a wide range of reported physiologic benefits of arginine-derived
nitric oxide (ADNO). These include, but are not limited to, the
effects of ADNO to lower blood pressure with a minimum of
physiologic side effects; to dilate bronchial tubes and improve
pulmonary function test results; to mediate long-term potentiation
in neural tissue and thereby promote memory function; to improve
oxygen delivery in tissues through hemoglobin-related mechanisms;
to reduce LDL and total cholesterol levels and LDL oxidation; to
promote the release of growth hormone and its wide range of
anti-aging benefits; to improve microvascular blood flow and tissue
perfusion; to increase the immunologic actions of ADNO that include
generation of nitric oxide "bullets" for direct anti-microbial and
anti-tumor effects, increased natural killer cell activity, and
enhanced cytokine production, e.g., tumor necrosis
factor-alpha.
[0092] In addition, the ADNO effects mediated through increased
cyclic guanosine monophosphate (cyclic-GMP) generation can also be
enhanced; these include the effects of ADNO via cyclic GMP to
enhance male sexual potency, and probably female vaginal
lubrication, as well as increased genital sensitivity in both men
and women.
[0093] In accordance with still yet another aspect of the
invention, it has been found that reducing the potency of
L-arginine for ADNO production may preserve nutritive benefits of
L-arginine while reducing the risk of adverse effects of L-arginine
supplementation that can occur in selected circumstances in
susceptible individuals. These situations include but are not
limited to persons with Herpes simplex viral infection that may
have an increased risk of outbreaks with L-arginine supplementation
and persons with inflammatory conditions for whom supplemental
L-arginine may aggravate nonspecific inflammatory symptoms. In
particular, reduced risks of Herpes simplex outbreaks may result
from the use of reduced potency L-arginine in conjunction to the
addition of at least one gram daily of the amino acid L-lysine.
[0094] An additional aspect of the present invention involves the
ability to modify hydrophobic and hydrophilic interactions through
laser resonance, as observed through X-ray crystallography. In
particular, the method can be used to develop new forms of
L-arginine hydrochloride and other molecular structures in both dry
states and in solution.
[0095] For example, the disclosed method was used to compare the
crystal structures of L-arginine hydrochloride grown without versus
with laser resonant stimulation. L-arginine hydrochloride was
dissolved in de-ionized water and then crystallized without and
with laser stimulation by slow evaporation at room temperature. The
control L-arginine hydrochloride upon crystal structure solution
was found to have the typical features of L-arginine hydrochloride
monohydrate reported in the literature, with one molecule of water
per molecule of L-arginine hydrochloride in the crystal lattice.
The laser treated L-arginine hydrochloride demonstrated a
significantly different crystal structure, an L-arginine
hydrochloride without water in the crystal lattice with different
unit cell characteristics, and a very high level of uniformity of
elongation of the nitrogenous side chain.
[0096] The sparse constructive node laser treated L-arginine
hydrochloride showed the predicted effects of high levels of
homogenization and reduction of the bonded water in the molecular
structure. This result suggests the ability to modify a wide range
of molecular structures in intended ways, both in the dry state and
in solution.
[0097] In accordance with one aspect of the present invention, the
method of Strachan (or other molecular modification methods) can be
used to modify the immunologic effects of a blend of a complete
spectrum of amino acids.
[0098] In accordance with this aspect of the invention, a highly
immunostimulant amino acid or blend of amino acids is laser
treated. The laser modifies the structure of the amino acid(s) to
reduce the immune stimulation to the baseline level without the
amino acids. In other words, modifying the amino acid structure
reduces negative immune reactions to the amino acids. Such a
modified form of nutrition may be highly desirable for persons with
poor nitrogen balance and immune overactivity, e.g., autoimmune
diseases, food allergies, and other inflammatory conditions such as
inflammatory bowel disease. Thus, in accordance with this aspect of
the invention a route of elemental, readily absorbed and
assimilated nutrition is provided that will not further aggravate
an underlying inflammatory condition.
[0099] In accordance with still yet another aspect of the present
invention, there is disclosed an improved method of administration
of dietary nucleic acid elements and dietary nucleotide precursors.
In a presently preferred embodiment of one aspect of the invention,
a method is disclosed that does not require parenteral
administration, yet provides better delivery of nucleic acid
elements to tissues than oral ingestion.
[0100] Metabolic incorporation studies indicate that orally
administered purines and pyrimidines undergo significant metabolic
degradation both by intestinal bacteria and the intestinal
epithelium. Orally administered pyrimidines show an incorporation
level of approximately 5% in the intestinal lining and only 3% in
the liver. Orally ingested purines are even more extensively
oxidized such that less than 1% of purine nucleosides are
incorporated into hepatic nucleic acid pools.
[0101] Studies with radiolabeled purines show that intravenous
injection compared to oral ingestion results in vastly higher
incorporation levels in certain metabolically active tissues, with
IV:oral incorporation levels as high as 29-59:1 in pituitary,
thymus, salivary, thyroid, adrenal, and lymphoid tissues.
[0102] Recent evidence indicates that although the body can
manufacture nucleic acid bases from amino acids and other
precursors, some tissues have a synthetic capacity below that
required for optimum tissue maintenance, repair, and regeneration.
This may be particularly true of lymphoid tissues, especially under
conditions of stress. Numerous studies have shown marked
immunologic benefits of supplemental nucleic acid elements
especially on improved cellular immunity. Animal studies have shown
significant improvements in outcomes for systemic bacterial and
fungal infections, as well as malignancies. Human studies show
marked improvement in cellular immunity as well as enhanced
intestinal growth, maturation, and repair.
[0103] To overcome the limits of oral ingestion, this disclosure
presents, as a preferred embodiment of one aspect of the invention,
the delivery of nucleic acid elements via an intra-oral spray
formula or by rectal or vaginal suppository. Absorption studies
suggest that nutrients applied to the oral mucosa may achieve up to
90% direct systemic absorption while also overcoming the
limitations of hepatic first pass metabolism. These elements may
include one or more of the following forms: laser treated DNA and
RNA nucleobases, nucleosides and deoxynucleosides, and nucleotide
and deoxynucleotide monophosphates, diphosphates, and
triphosphates. It is possible that laser treatment of nucleotides
and deoxynucleotides may at least temporarily generate higher
energy more highly bioactive high energy phosphate groups.
[0104] This formula may also contain one or more laser homogenized
amino acids, in particular those amino acids known to be precursors
of endogenous nucleobase synthesis: glycine, L-glutamine, L-serine,
and L-aspartic acid. This formula may also contain one or more
laser treated vitamins, minerals, trace elements, and other
nutrient cofactors that support nucleotide metabolism. This laser
irradiated formulation for enhanced nucleic acid metabolism may
also be provided intravenously or through other parenteral
injection routes, such as subcutaneously or intramuscularly.
Although improved absorption through oral ingestion of laser
treated versus untreated nucleic acid elements is anticipated,
significant intestinal mucosal degradation remains likely.
[0105] In accordance with yet another aspect of the present
invention, the method is used to create a homogenized form of
trimethylglycine (TMG). TMG, also known as betaine, is a methyl
group donor that participates in many fundamental chemical pathways
in the body.
[0106] TMG is derived from the simplest of the amino acids,
glycine, that has 3 methyl groups replacing the 3 hydrogen atoms of
the amino group. X-ray crystallography comparing the control versus
laser treated hydrochloride of betaine shows the predicted effects
of molecular homogenization and the flattening and stretching of
molecular shape.
[0107] Homogenization, creating greater self-similarity of
molecular shape, is shown by a significant reduction of crystal
defects in the laser treated sample compared to the control sample,
despite both samples being crystallized by slow evaporation at room
temperature. Increased defects in the control crystal would be
predicted from the greater range of shapes of the untreated
compound having difficulty fitting uniformly in the crystal
lattice.
[0108] In contrast, consistent flattening and stretching of shape
from molecule to molecule permits more rapid incorporation into a
uniform crystal lattice. The X-ray crystallographic analysis shows
the explicit 3-dimensional shapes for the control and treated
hydrochlorides of betaine, and is consistent with the predicted
changes in shape.
[0109] The laser treated sample in particular shows flattening and
stretching of the carbon-nitrogen bonds of the amino methyl groups,
and to a lesser degree also suggests flattening and stretching of
the carbon-hydrogen bonds of the methyl groups, as well as the
carbon-oxygen bonds of the carboxyl group. This flattened shape
will tend to have higher field energy with reduced bond energy,
favoring lower energy of enzymatic binding and higher enzymatic
reactivity.
[0110] It is understood from the current evidence, that this
activated state creates a reactive methyl group that facilitates a
variety of biological processes in the body, and provides numerous
benefits to the body.
[0111] For example, it has been found that betaine can reduce blood
levels of homocysteine, a substance that has been linked to
numerous negative physiological conditions, through the enzyme
betaine-homocysteine methyltransferase that transfers a methyl
group from betaine to homocysteine to convert it to the amino acid
methionine.
[0112] By providing the activated betaine combined with nutrients
that serve as cofactors in the methyl group transfer pathways in
the body, significant homocysteine reductions can be achieved,
thereby limiting the risk of heart attack, strokes, dementia,
pre-eclampsia, and certain malignancies, especially of epithelial
origin, such as cervical, colon, and possibly bronchogenic
neoplasms.
[0113] The activated betaine and cofactors can also be used to
reduce anxiety, depression, hostility, paranoia, somatization (body
aches and pains), and obsessive-compulsive symptom scales.
[0114] In light of the present disclosure, it will be appreciated
that a variety of chemicals can be modified in accordance with the
principles of the present invention. In particular, any organic
molecule whose shape may be twisted or deformed through the
processes of chemical synthesis, purification, or drying may be
homogenized to a more self-similar and more bioavailable shape
configuration.
[0115] This process will tend to be relatively less efficient for
small molecules with few degrees of rotational freedom or planar
cyclic molecules; whereas molecules with long unsaturated mobile
side chains, such as L-arginine, that may take numerous ground
state configurations, are well suited to homogenization and
reshaping through this process.
[0116] The enhanced amino acids and other substances described in
this invention may be provided as dry powders or as solutions
through several routes of administration. These include oral spray,
mucosal, oral ingestion, enteral feeding tube, parenterally through
various routes, and topically.
BRIEF DESCRIPTION OF THE DRAWINGS
[0117] The above and other objects, features and advantages of the
invention will become apparent from a consideration of the
following detailed description presented in connection with the
accompanying drawings in which:
[0118] FIG. 1 is a block diagram of an apparatus embodying the
invention;
[0119] FIG. 2 illustrates an interference pattern produced by the
apparatus of FIG. 1;
[0120] FIG. 3 shows the same interference in a scattering
medium;
[0121] FIG. 4 shows a typical cell adhesion molecule;
[0122] FIG. 5 shows a typical cell adhesion molecule;
[0123] FIG. 6 shows a human integrin molecule with a single
substantial high Q resonance;
[0124] FIG. 7 shows the zinc structure of the GAG protein in the
HIV virus;
[0125] FIG. 8 shows a typical laser diode spectrum;
[0126] FIG. 9A shows the X-ray powder diffraction (XRPD) pattern of
control simvastatin sample Sim 1A;
[0127] FIG. 9B shows the XRPD pattern of laser treated simvastatin
sample Sim 1B demonstrating increased crystallinity;
[0128] FIG. 10A shows the XRPD pattern of laser treated simvastatin
sample Sim 2A demonstrating lower intensity reflections indicative
of amorphous content;
[0129] FIG. 10B shows the XRPD pattern of laser treated simvastatin
sample Sim 2B demonstrating very low intensity reflections
indicative of an even higher amorphous content;
[0130] FIG. 11A shows frontal and lateral photomicrographs of
crystals of control untreated L-arginine hydrochloride
monohydrate;
[0131] FIG. 11B shows frontal and lateral photomicrographs of
crystals of laser treated anhydrous L-arginine hydrochloride;
[0132] FIG. 11C shows X-ray crystallographic results of laser
treated or modified L-arginine hydrochloride;
[0133] FIG. 12A shows a quantitative EEG (QEEG) study of baseline
alpha brainwave coherence;
[0134] FIG. 12B shows a QEEG study of alpha brainwave coherence one
hour after ingestion of untreated amino acids;
[0135] FIG. 12C shows a QEEG study of alpha brainwave coherence one
hour after ingestion of laser treated or modified amino acids;
[0136] FIG. 13A shows lateral photomicrographs of crystals of
control betaine hydrochloride and laser treated or modified betaine
hydrochloride;
[0137] FIG. 13B shows frontal photomicrographs of crystals of
control betaine hydrochloride and laser treated or modified betaine
hydrochloride;
[0138] FIG. 13C shows x-ray crystallographic results of
intermolecular hydrogen bonding for control betaine
hydrochloride;
[0139] FIG. 13D shows x-ray crystallographic results of
intermolecular hydrogen bonding for laser treated or modified
betaine hydrochloride;
[0140] FIG. 13E shows x-ray crystallographic results for the
molecular structure of control betaine hydrochloride as dashed
lines and for laser treated or modified betaine hydrochloride as
solid lines, showing backbone models in the upper diagram and ball
and stick models in the lower diagram;
[0141] FIG. 14A shows a diagram of the methyl group transfer
metabolic pathways;
[0142] FIG. 14B shows a graph demonstrating reduced homocysteine
levels after treatment with modified betaine;
[0143] FIG. 14C shows a graph demonstrating a control group;
[0144] FIG. 14D shows a graph demonstrating reduced homocysteine as
a function of treatment quantity in a subgroup of subjects with
moderately elevated baseline homocysteine levels (.gtoreq.10);
[0145] FIG. 14E shows a graph demonstrating reduced anxiety as
function of treatment quantity;
[0146] FIG. 14F shows a graph demonstrating reduced somatization as
a function of treatment quantity;
[0147] FIG. 14G shows a graph demonstrating reduced obsessive
compulsive symptoms as a function of treatment quantity; and
[0148] FIG. 14H shows a graph demonstrating reduced depression as a
function of treatment quantity;
[0149] FIG. 14I shows a graph demonstrating reduced paranoia as a
function of treatment quantity;
[0150] FIG. 14J shows a graph demonstrating reduced hostility as a
function of treatment quantity;
[0151] FIG. 14K shows a graph demonstrating reduced global severity
index as a function of treatment quantity.
DETAILED DESCRIPTION OF THE INVENTION
[0152] Referring to FIG. 1, the apparatus comprises a laser diode 2
that is controlled by an amplitude modulator 1. The laser diode 2
is selected to have a reasonably linear relationship between
current and wavelength with minimum mode hopping. The amplitude
modulator 1 modulates the current to the laser diode 2 that in turn
results in a very small wavelength modulation of the laser, for
purposes discussed below.
[0153] The output of the laser diode 2 is collimated by a lens 3
and passed to an optical element 4. The optical element 4 consists
of a first diffraction grating, a refractive element, and a second
diffraction grating such that the beam is substantially cancelled.
A preferred form of the optical element 4 is as disclosed in
WO97/22022 (now EP-AL-086561 8A and U.S. Pat. No. 6,064,500). This
allows the cancellation to occur over a small percentage of the
wavelength variance of the laser source, rather than at a single
critical wavelength. Wavelengths beyond the acceptance bandwidth of
the canceling optic 4 above and below the center frequency pass
without being cancelled. This means that a complex
Fresnel/Fraunhoffer zone will be generated, defined by the beat
frequency of the high and low frequencies as a function of the
aperture. This means that relatively sparse zones of constructive
interference will occur between the high and low frequency passes
of the cancellation element in selected directions from the
aperture, as shown in FIG. 2.
[0154] As seen in FIG. 1, the optical element can be adjusted
angularly between position 4A and 4B. This varies the ratio of
constructive to destructive interference.
[0155] In effect the continuous beam is transformed into a string
of extremely short duration pulses typically of sub-femtosecond
duration. The small wavelength modulation of the laser diode 2
causes the constructive and destructive nodes to move rapidly
through the volume of the Fresnel zone of the collimator lens
aperture. This has the effect of simulating very short
(sub-picosecond) pulse behavior at any point in the Fresnel zone
through which the nodes pass at a pulse repetition frequency
defined by the amplitude modulator frequency.
[0156] The wavelength of the cancellation and constructive
interference zones for a theoretical single path would be the
difference between the two frequencies. If the bandwidth of the
canceling element is narrow this difference is very small and the
effective wavelength of the cancelled/non-cancelled cycle would be
very long, of the order of picoseconds. Therefore, the system would
behave substantially similarly to a system with no cancellation
because it requires an aperture much larger than the primary light
wavelength to generate a useful Fresnel/Fraunhoffer zone. Such an
aperture would greatly multiply the available Feynman diagram paths
eliminating any useful effect, even if it were possible to generate
a sufficiently coherent source of such an aperture.
[0157] If the beat frequency can be made high enough the wavelength
of the cancelled to non-cancelled cycle can be a fraction of a
practical aperture. This will make this wavelength sufficiently
small to limit the Feynman paths to within a cycle or two in free
space allowing the Fresnel/Fraunhoffer effect to be apparent. Since
the center frequency and spectrum spread of a laser diode is easily
modulated by adjusting the current and or temperature of the
junction, the pattern of the Fresnel/Fraunhoffer zones can be
varied dramatically by very small variations in the wavelength of
one or both pass frequencies. Such modulation is produced in the
apparatus of FIG. 1 by the amplitude modulator 1.
[0158] Ideally the diode is modulated only slightly so that the
frequencies of the laser spectra move by an amount smaller than
that which would cause a second lobe to spill outside the bandpass
of the cancellation element. As described above the aperture of the
apparatus has a dimension some substantial multiple of the
wavelength of the laser and some significantly smaller multiple of
the cancellation cycle. Thus the number of different Feynman
diagram path lengths will be substantially less than infinite for
any given cycle length. Thus as different rays from the laser take
slightly different paths through the optical element and thereafter
cause the complex Fraunhoffer zone with the beam the pattern
generated is the inverse of a typical narrow spectrum Fraunhoffer
zone.
[0159] Therefore, instead of the center frequencies of the beam
being in general uncanceled, the center frequencies are totally
cancelled. Thus instead of a general constant level of light in the
beam, the beat frequency beam is characterized by isolated
relatively sparse "islands" of constructive interference occurring
in the generally cancelled beam. Small variations in the center
frequency of the laser as a result of modulation of the current or
temperature of the diode cause these islands of constructive
interference to move rapidly within the beam.
[0160] Thus at any given point within the beam path, a constructive
interference node can be made to modulate with respect to the
modulation frequency of the laser, irrespective of the scattering
of the path to that point. This is because few areas of
constructive interference exist in the initial beam and while a
constructive node can occur at any point that happens to have
suitable path lengths through the scattering medium to the source,
the initially cancelled portion of the beam cannot be reconstructed
to become a constructive node at any point. Since the modulation of
the laser changes the locations of the constructive nodes at the
modulation frequency of the laser the result is that for any point
(or more accurately for the substantial majority of points) within
the beam a modulation occurs irrespective of the scattering nature
of the medium. This is because the probability of a scatter from
one sparse node to a region where another sparse node has existed
within frequency of the modulation is extremely low.
[0161] In a typical coherent beam, the presence of constructive or
destructive interference is of equal likelihood and the modulation
of the beam will generally shift one constructive node only to be
replaced by another causing any initial modulation of the beam to
be swamped by the noise of the multiple paths. In contrast, the
limiting factor for the modulation frequency of a sparse
constructive interference beam is simply the overall maximum path
length of any substantial probability in the Feynman diagram. Path
length is substantially shorter than the wavelength of the
modulation.
[0162] For a depth of five or six centimeters in human tissue this
allows frequencies in excess of 10 MHz to be successfully modulated
and in many human tissues such as bone or neural tissue the depth
would be substantially greater or the limiting frequency
higher.
[0163] A conventional coherent or incoherent beam would have high
probability paths in the Feynman diagram. These paths would overlap
at very low frequencies (kHz) and be of little practical use in the
stimulation of molecular resonance. It should be noted however that
the phenomena described above may be used as a means to multiply
the modulation frequency, up to the point where the beam
effectively becomes continuous. Thus by careful selection of the
aperture, the region of he beam selected for transmission through
the medium and the modulation frequency it is possible to cause the
constructive nodes to pass across any given point in the beam at
frequencies many times higher than the modulation frequency. In
ideal conditions the duration of exposure to a constructive node of
any point would be for a period equivalent to a quarter of the
duration of a wavelength of the molecular frequency repeated once
per cycle.
[0164] If the wavelength of the laser is chosen to be one easily
absorbed by the atomic structures it is desired to induce to
resonance, then the beam will efficiently deliver the desired
modulation frequency to the desired molecules. The energy of the
beam is extremely low but sufficiently high to differentially raise
the temperature of those molecules of sufficient Q. Higher energy
intensity would tend to cause sufficient scatter even from the
isolated island nodes to swamp the modulation. Again the result
would be a general temperature increase rather than the
differential temperature increase of the desired molecules.
[0165] Higher intensity cannot significantly increase the energy
delivered to the desired molecules. Once the probability of a
single photon absorption at any point on the molecule in a given
resonant frequency cycle is exceeded, there is little advantage in
increasing the intensity since a second photon will scatter without
delivering more energy to the given atom structure. The maximum
temperature difference that can be induced will be a function of
the damping factor and the Q of the resonant component of the
molecule. Therefore, increasing the time of stimulation is
pointless beyond some reasonable multiple of the known time
required to initiate the reaction desired because the maximum
possible temperature variance will occur within a few seconds.
[0166] The effect is therefore, only of merit in systems where a
small temperature variance can disturb the equilibrium. Naturally
this limits the range of molecules that can be stimulated by this
method. It is fortunate however that many of the most usefully
stimulated molecules have exactly the characteristics required.
Most particularly the cell adhesion molecules and integrins
mentioned above. It should be noted of course that all biological
reactions occur within a narrow temperature range and the progress
of most reactions can be varied quite significantly by small
temperature differences. It is of course a natural consequence of
light stimulation of a molecular resonance that the molecular node
temperature of the resonant structure will coincide with the
maximum valence state of the atoms since they are in the process of
absorbing and emitting photons and so the electrons are in general
at a relatively high energy state. Naturally specific photochemical
reactions will be favored and this may either help or hinder the
ability of the method to stimulate a specific desired reaction
depending on the proximity of unwanted photochemical reaction sites
to the resonant stimulated sites. In designing a specific stimulus
these factors should be taken into account along with the
equilibrium state and the pH.
[0167] As stated above cell adhesion molecules and human integrins
such as Alpha 4 Beta 1 are ideally suited for excitation to
chemical activity by this method.
[0168] The stimulation of cell adhesion molecules and integrins
moderates a number of extremely useful biological processes. Not
least of these is cell adhesion itself. It is obviously beneficial
to stimulate the adhesion molecules of a carcinoma as the cell
adhesion of carcinomas is relatively depressed and enhancing the
adhesion serves to reduce the probability of metastasis. Such an
effect would be especially beneficial prior to the excision of a
tumor, reducing the likelihood of surgically shedding carcinoma
dells into the blood or lymph system. The cell adhesion process and
the integrins especially Alpha 4 Beta 1 and Alpha 4 Beta 2 are
responsible not only for adhesion but also cell recognition.
[0169] Bissel and Weaver have shown that by chemical inhibition of
adhesion sites of Alpha 4 Beta1, the cell recognition can be
moderated. It is therefore possible to reduce an undifferentiated
carcinoma cell to its nonmalignant phenotype by correctly
moderating the adhesion reaction. The method used by Bessel and
Weaver is practical for in vitro application and can be used as
described in their patent for the measurement of response to
chemotherapy but it cannot practically be used in vivo. Conversely
the laser radiation method can be used in vivo and because of the
extremely low energies it is inherently safe at least in terms of
the radiation used. Care must of course by taken to ensure that the
stimulation delivered will have a desirable consequence and much
work is needed to determine both the chemical responses that are
most easily stimulated and which of those are desirable in a given
case.
[0170] Gradually a library of reaction responses susceptible to the
stimulation will be developed from theory and experiment and this
library will be used to define a range of reactions that are both
of clinical use and practical to stimulate. To date we have
demonstrated the stimulation of adhesion in leukocytes and neural
carcinomas. We have demonstrated substantial moderation of cell
surface chemistry in the prostate gland.
[0171] This shows promise in the treatment of various carcinomas.
Stimulation of cell adhesion and recognition alters the metabolism
of the carcinoma and causes induced, spontaneous apoptosis as a
result of undifferentiated cells communicating sufficiently. This
in turn causes the natural apoptosis of undifferentiated cells in
an undifferentiated environment. We have substantial evidence that
like Bissel and Weaver we have observed the reduction to phenotype
of undifferentiated cells and leukocytes.
[0172] Wayner U.S. Pat. No. 5730978 has shown an integrin-moderated
process which suggests that the method may have application in the
treatment of autoimmune diseases and in the manipulation of the
immune response in general.
[0173] In vitro, the method can be used to alter the chemistry of a
variety of proteins and simple amino acid structures in a manner
that may be useful in the production of pharmaceutical compounds
and nutrition products. Since the polar and hydrophobic components
of molecules have substantially different electron populations,
Quantum Electrodynamics (QED) shows that these components
differentially absorb energy from photons. Coupled with a
modulation frequency close to one of the major axes of a given
molecule, modulated laser stimulation can be used to increase the
homogeneity of a population of proteins or simple amino acid
structures. This can be highly advantageous since the metabolic
absorption of amino acid structures is moderated in vivo by shape
specific enzymes.
[0174] If a simple amino acid nutrient is made homogeneous the
number of enzymes required to metabolize the nutrient is reduced.
Again the cascade effect of cell chemistry means that such a
reduction in the complexity of a particular chemical process can
dramatically increase the speed of absorption sometimes by several
orders of magnitude since the required enzyme population is far
more rapidly manufactured. This is of critical importance in many
simple amino acid nutrients since they have a limited life before
they are broken down by incidental chemical effects before they can
deliver the required effect to the target cells.
[0175] Under ideal conditions it will be possible to order the
folding of a protein to the desired biological form by successive
stimulation of suitable resonant frequencies and the differential
polar and hydrophobic absorption of photons. Again the application
of a suitable modulated beam to a sufficient volume of protein by
conventional means would be impossible as result of the scattering
of the light. The sparse constructive node beam disclosed in the
present application makes the delivery of the required modulation a
practical possibility. A suitable array of the disclosed sparse
constructive node beams could be arranged on a conveyor passing the
proteins or simple amino structures sequentially under the various
modulation frequencies designed to favor each of the desired
folding steps.
[0176] Clearly much research would be required to determine what
modulations would be required to produce a desired protein shape
and it may be that in practice very few proteins can be usefully
manipulated in this way. Such research is not within the scope of
this application; rather this application discloses a method and
apparatus capable of moderating aspects of the folding process of
proteins in a manner that can be applied to a bulk mass for the
first time. It is extremely likely that a range of practical
protein structures can be generated by this method and it has been
shown by experiment that a population of proteins or simple amino
structures can be at least made homogeneous which as mentioned
above is useful in itself.
[0177] In this regard it should be noted that the rotational
polarization of the light source would cause differential
absorption of energy depending on the "handedness" of a given
molecular structure. In addition, if the beam is modulated at the
resonance of a given structure, it is possible to either enhance
the production of one rotation of a molecule versus the other. At
slightly higher energy it is possible to cause the destruction by a
separate chemical process of one or other rotation by
differentiating the temperature and therefore the reactivity of one
rotation versus the other. This is a particularly useful
application of the method as many drugs and nutrients depend on
only one form of the molecule being present.
[0178] In this case of course the maximum Feynman path must be very
much shorter and so the maximum depth that rotational polarization
effects would occur would be no greater than a few millimeters in a
typically scattering medium. Hitherto no simple practical method
has existed to purify a population of molecules to one or other
rotation. The method disclosed here provides a means of operating
on bulk media to generate a homogeneous single rotation population
or to allow a chemical process to preferentially destroy one
rotation relative to the other in a mixed population of
molecules.
[0179] The chemical consequences discussed herein of molecular
stimulation by sparse constructive node techniques result primarily
from the repeated acceptance and release of photons by atoms at the
resonant frequency of the local atomic bonds or local structure.
There is a secondary effect on certain molecular forms such as
tetrahedral which can be induced to spin provided the effective
pulse length is sufficiently short.
[0180] While the sparse constructive interference beam is the
primary thrust of the present application, it is worth noting that
the Hamiltonian solution to Maxwell's equations suggest that
cancelled light, although carrying no energy in the conventional
sense in that it can not interact by conventional Quantum
Electrodynamics (QED) processes may have an effect on the
permitivity of free space and some theorists suggest an effect on
the strong nuclear force. However since it can not scatter by QED
effects this has no detrimental affect on the efficiency of the
sparse constructive interference modulation and it could be argued
that the permitivity and nuclear absorption effect, should it
exist, would tend to enhance the efficiency of the modulated
frequency coupling to the molecule. It should be noted that the
presence of the Hamiltonian effect has never been satisfactorily
proven and many theorists discount its existence as a mere
mathematical oddity, however we note it here simply to point out
that the effect would tend to enhance rather than degrade the
benefit of the sparse constructive in interference effect. The
apparatus by its nature can therefore be used as a means of
delivering such a theoretical modulated Hamiltonian "scalar"
wave.
[0181] FIGS. 2 to 8 illustrate elements of the foregoing in more
detail.
[0182] FIG. 2 shows the sparse constructive interference effect
from a 1 percent bandwidth cancellation plate of 5 mm aperture.
Black represents constructive nodes.
[0183] FIG. 3 shows the same sparse constructive interference in a
scattering medium showing minimal degradation of the effect and an
increased path width of majority destructive interference.
[0184] FIGS. 4 and 5 show typical Cell Adhesion Molecules. Both
would have two primary resonances a high Q resonance between the
main elements at a relatively low frequency and a higher frequency
lower Q resonance between the lobes of each element. The molecule
in FIG. 4 has a higher frequency resonance between the main
elements as it has some backbone structure between the main
elements.
[0185] FIG. 6 shows a human integrin molecule that will have a
single substantial high Q resonance defined by the mass of the two
main elements and the compliance of the single backbone structure
between the elements. This molecule is extremely easy to resonate
sufficiently to moderate reactions and was the first molecule to be
successfully manipulated by the method disclosed. This allowed an
in vitro demonstration of cell adhesion stimulated by laser
stimulation through a sparse constructive node cancellation optical
device. "Tracks" of adhered cell chains could be generated in the
beam path of the device in a population of cells with substantially
reduced expression of the integrin and generally little adhesion in
the absence of the beam.
[0186] FIG. 7 shows the zinc "finger like" structure of the GAG
protein in the HIV virus. Again the molecule shows the easily
resonated dual element with compliant single backbone bridge. This
molecule is much smaller and requires a higher energy and resonant
frequency. It was successfully resonated with 470 nm light using
the method disclosed. It should be noted that the chemical
conditions around a small viral particle are far harder to control
or predict and variable results are to be expected. Even so
substantial alterations in the processes of the viral coat were
observed and the viral penetration of a cell population could be
substantially altered.
[0187] FIG. 8 shows a typical laser diode spectrum, with a typical
cancelled portion of the spectrum and the depth of the modulation
that can be induced without causing the nodes to spill outside the
cancellation zone and complicate the beat frequency pattern.
[0188] Different laser designs have different resonant modes and
these can be selected to obtain the most useful range for a given
application. Bragg gratings can be used to stabilize the laser
emission line and expand the modulation amplitude that can be used
while keeping the overall frequency shift within the required
boundary. Lasers can be pulsed with short duration pulses, which
will produce an isolated traverse though the frequency mode of the
laser and this can be determined to a high degree of repeatability.
If a Bragg grating is used with a pulse laser the resulting
frequency modulated pulse will have a very high degree of control.
The combination of the short laser pulse and the rapid resulting
traverse of the sparse constructive nodes means that a given point
in the volume in front of the laser will be exposed to extremely
short (sub picosecond) duration pulses. There are several
applications for such short pulses and conventional methods for
short pulse generation are relatively costly.
[0189] The various aspects of the present invention will now be
discussed so as to enable one skilled in the art to make and use
the invention. It is to be understood that the following
descriptions are only exemplary of the principles of the various
aspects of the present invention, and should not be viewed as
narrowing the pending claims. It is also to be understood that each
embodiment may not accomplish each object of the invention, but
provides one or more advantages over the prior art.
EXAMPLE 1
Production of Highly Homogeneous Simvastatin with Increased
Crystallinity through Applying Laser Acoustic Resonance
[0190] Two Samples of United States Pharmacopeia (USP) reference
standard simvastatin of 21 mg each were used for this study. Each
sample was dissolved in 200 mg of 100% ethanol and placed in a
10.times.35 mm polystyrene Petri dish. Sim 1A was prepared as the
untreated control and Sim 1B was prepared for treatment with
modulated sparse constructive node laser acoustic resonance to
assess for differences in crystallinity using X-ray powder
diffraction.
[0191] Both samples were crystallized by slow evaporation at room
temperature. Sim 1A served as the control and had no additional
treatment modalities applied to it. Sim 1B was treated with a 670
nm diode laser of 4.7 mW primary power phase conjugated through the
optical elements to a power level of 2.35 mW. The beam was
modulated at 10 MHz and passed through the middle of the fluid
meniscus of the solution until Sample 2 was fully crystallized.
Both samples were then sent to a reference lab for X-ray powder
diffraction (XRPD) studies.
[0192] FIG. 9A shows the XRPD pattern for Sim 1A, the control
reference standard of simvastatin. FIG. 9B shows the XRPD pattern
for laser acoustic resonance treated Sim 1B. The corresponding
peaks in FIG. 9B are .about.70% greater in amplitude than FIG. 9A.
The sharper resolution and significantly increased amplitude of the
reflections for Sim 1B indicate a higher degree of crystallinity
for Sim 1B.
[0193] Based on thermodynamic considerations, increased
crystallinity is associated with increased stability of the crystal
form. For storage purposes of a pharmaceutical or other compound, a
more highly crystalline form is more likely to maintain its form
and characteristics for a longer period of time, and thus will tend
to have a significantly longer shelf life.
[0194] Perhaps more importantly, the risk of converting to a
different crystal form during storage may be decreased, as such
conversions can greatly alter the effects of the compound in the
body. Particularly for metastable crystal forms that are not
already in the lowest free energy form, increasing the
crystallinity of the metastable form may reduce the risk of the
very undesirable conversion to the more stable form that has
usually been avoided because of poor solubility and low
bioavailability. Increasing the probability of maintaining the
metastable form in a predictable way can provide a great advantage
for those compounds that must be provided in this form to be
sufficiently soluble and bioavailable to be of clinical
benefit.
EXAMPLE 2
Production of Partially Amorphous Simvastatin through Application
of Laser Acoustic Resonance
[0195] Two Samples of United States Pharmacopeia (USP) reference
standard simvastatin of 21 mg each were used as an extension of the
study described in Example 1. Each sample was dissolved in 200 mg
of 100% ethanol and placed in a 10.times.35 mm polystyrene Petri
dish. Sim 2A and Sim 2B were prepared for treatment with modulated
sparse constructive node laser acoustic resonance to assess for
differences in crystallinity using X-ray powder diffraction.
[0196] Both samples were crystallized by slow evaporation at room
temperature. Sim 2A was treated with a 458 nm pumped argon gas
laser of 2.1 mW primary power phase conjugated through the optical
elements to a power level of 1.05 mW. The beam was modulated at 6.4
MHz and passed through the middle of the fluid meniscus of the
solution until Sample 2A was fully crystallized. Sim 2B was treated
with a Quantel Nd-YAG pulsed laser at 467 nm with an average pulse
amplitude of 2-5 mJ/pulse over 5 nanoseconds, 12 pulses per second.
The optics were adjusted to maximum cancellation and the beam was
passed through the middle of the fluid meniscus of the solution
until Sample 2B was fully crystallized. Both samples were then sent
to a reference lab for X-ray powder diffraction (XRPD) studies.
[0197] FIG. 10A shows the XRPD pattern for Sim 2A and FIG. 10B
shows the XRPD pattern for Sim 2B. The XRPD pattern for Sim 2A
shows relatively low intensity reflections and the XRPD pattern for
Sim 2B displays very low intensity reflections. The low intensity
reflections may be attributed to amorphous content, with the
pattern of Sim 2B suggesting an even higher degree of amorphous
content than Sim 2A.
[0198] Sim 2A and Sim 2B solidified in a glassy appearance with
only slight crystalline development compared to the modestly
developed crystal formations of Sim 1A and the highly developed
crystal formations of Sim 1B. The degree of glassy appearance
observed in Sim 2A and Sim 2B was consistent with the degree of
amorphous content suggested by XRPD.
[0199] Amorphous materials generally have significantly higher free
energy than crystalline materials of the same substance. Due to
their greater energetic states, they tend to have higher
solubilities and faster rates of dissolution than their less
energetic crystalline counterparts. In many cases, the amorphous
form of a pharmaceutical compound is chosen for clinical use
because the lower solubility and bioavailability of the crystalline
form limits the clinical value. Even in the case of simvastatin, it
is possible that adding significant amorphous content to the
composition may increase the rate of absorption and
bioavailability, resulting in greater efficacy at a lower dose. If
a lower dose proves sufficient for the desired clinical results,
the likelihood of adverse effects may also decrease.
[0200] In contrast to the extreme conditions far from equilibrium
that are often required to produce amorphous forms, laser acoustic
resonance can achieve this formation at room temperature and
pressure without drastic changes in pH. Avoidance of extreme
conditions may reduce the degree of degradation of the compound
that may occur under more aggressive conditions to improve product
yield and perhaps result in a more stable amorphous form.
[0201] The application of laser acoustic resonance through
modulated sparse constructive nodes may provide a means of reliably
producing amorphous forms of compounds that are otherwise difficult
to produce in an amorphous form. This may salvage compounds that
would be likely to be clinically useful but do not otherwise
achieve sufficient solubility to be effective. For other compounds,
producing a stable amorphous content may increase bioavailability
to the degree of increasing clinical efficacy, reducing dosage
requirements, or decreasing the risk of adverse effects.
EXAMPLE 3
Increased Arginine-Derived Nitric Oxide Production through Laser
Treatment
[0202] The use of laser modification of compounds enhances the
ability to modify not only the compound itself, but also
by-products created by the body's use of the modified compound.
[0203] For example, four Samples of L-arginine (Arg) of 20 grams
each, 3 for laser treatment and 1 an untreated control, were
measured. Arg #1 was treated with a Quantel Nd-YAG pulsed laser at
532 nm with an average pulse amplitude of 2-5 mJ/pulse over 5
nanoseconds, 12 pulses per second. The optics were adjusted to
maximum cancellation and the sample was treated for 30 seconds. Arg
#2 was treated with a 458 nm pumped argon gas laser with a primary
power of 16.5 mW adjusted through the optics to a power level of
5.06 mW. Arg #3 was treated with a 670 nm diode laser of 4.85 mW
primary power adjusted through the optical elements to a power
level of 2.94 mW. Arg #4 was the untreated control sample.
[0204] Paracelsian in Ithaca, N.Y., an outside independent lab,
performed the following bioassays. Each arginine sample was added
to 12 wells of murine macrophages to achieve a concentration of 120
mcg/ml. This is the estimated serum concentration for a 70 Kg
person after ingesting a 6-gram serving of arginine, a level
observed in numerous clinical studies to be associated with a wide
range of physiologic benefits. LPS at 1 ng/ml was added to each
well and the cells were incubated for 24 hours. The nitrite
concentration in each well's supernatant was determined 24 hours
after initiation of treatment as a relative measure of nitric oxide
production.
[0205] The results are listed in order of relative nitrite
production, from greatest to least. The first column is the Arg #,
the second the mean plus or minus the standard deviation of the
optical density measurement at 540 nm, a measure of nitrite
concentration, and the third column the relative production of
nitrites expressed in micrograms per ml as determined from optical
density. The final column shows the results of a Students 1-Tailed
T-Test comparing the highest producing Arg #3 to the other
samples.
1 Sample ID Mean O.D. .+-. S.D. Nitrites P Value Arg #3 .232 .+-.
.010 12.0 -- Arg #4 .224 .+-. .006 11.4 .0216 Arg #2 .219 .+-. .008
10.8 .0016 Arg #1 .215 .+-. .007 10.6 .0001
[0206] The laser modulation applied to Arg #3 resulted in this
sample producing statistically significantly more nitric oxide
byproducts than the control untreated Arg #4. The laser modulations
applied to Arg #1 and Arg #2 resulted in their producing
statistically significantly less nitric oxide byproducts than the
control untreated Arg #4 and highly statistically significantly
less than the laser activated Arg #3.
[0207] It is very important to note that the greatest effect of
providing L-arginine on nitric oxide production in vitro and in
vivo is probably within the first 30-60 minutes of delivery, so
that a 24 hour equilibration survey may substantially underestimate
the full magnitude of differential nitric oxide production of the
laser treated versus control forms of L-arginine.
[0208] This example shows the ability to modify the production of
the intended metabolic byproduct significantly upward or downward
depending on the laser stimulus applied. The experiment was
performed at an energy level too low to cause ionization or
significant thermal degradation. It is most likely that changes in
molecular shape that persist in effects even after material in the
dry state goes into solution are moderating enzyme-substrate fit
and reaction rates in the intended directions.
EXAMPLE 4
Homogenization, Elongation, and Dehydration of L-arginine
Hydrochloride through Laser Resonant Stimulation
[0209] In each of two 10.times.35 mm polystyrene Petri dishes 135
mg of L-arginine Hydrochloride were measured. Each sample was
dissolved in 0.50 grams of deionized water. The control sample was
crystallized by slow evaporation at room temperature over 24 hours.
The average room temperature was approximately 26 degrees
Centigrade. The average ambient humidity was approximately 33%.
[0210] The treated sample was crystallized under the same
conditions with the addition of pulsed modulated energy at 532 nm
as described for Arg #1 in Example 2 above. The beam was passed
through the center of the meniscus of solution in the
container.
[0211] Crystals from the control and treated samples were selected
for further study. Selected crystals all had dimensions of
approximately 0.5 mm on a side or less as per the latest standards
in the art. The crystal structures were solved using a SMART X-ray
diffraction analytical device.
[0212] Highly significant differences were seen between the control
and laser treated crystals. FIG. 11A shows the somewhat blocky and
irregular habit of anterior and lateral views of the control
sample; whereas FIG. 11B shows a more uniform cylindrical habit on
comparable views for the laser treated L-arginine hydrochloride.
The control L-arginine hydrochloride was found to have the typical
unit cell characteristics of the monohydrated crystal reported in
the literature. In contrast, the laser treated crystal was found to
have a significantly different unit cell that was free of water in
the crystal lattice, demonstrating the conversion of a monohydrate
to an anhydrous crystal. This is particularly significant since the
crystallization was done from water at room temperature. As shown
in FIG. 11C, and consistent with the predicted effects of
stimulating backbone resonances with sparse constructive nodes,
there is a high level of homogenization of elongated L-arginine
structures in the lattice.
[0213] The process described in this invention has the potential to
be applied to a wide range of molecular forms to modify the
relative intensities of hydrophilic and hydrophobic interactions.
Material in the dry state can be pre-treated to upregulate or
downregulate specific reaction processes in the directions
intended. Crystals grown from solution using this process may have
novel and desirable properties. This process may also be applied in
solution to modify reaction rates and product ratios. Greater depth
of penetration through media of sparse constructive nodes of laser
EM waves can extend this process to a broad range of industrial, in
vitro, and in vivo applications.
EXAMPLE 5
Reduced Production of Inflammatory Cytokines through Laser
Treatment of a Complete Spectrum Blend of Amino Acids
[0214] A mixture of amino acids was prepared as follows: Dry
powders of the following free form amino acids were measured and
mixed in the following proportions: L-cysteine 3.4 grams, L-taurine
6.8grams, L-threonine 27.0 grams, glycine 368.4 grams, L-glutamic
acid base 67.6 grams, L-glutamine 67.6 grams, L-lysine
monohydrochloride 67.6 grams, L-arginine 60.8 grams, L-aspartic
acid 13.6 grams, L-ornithine monohydrochloride 12.2 grams,
L-histidine 13.6 grams, L-leucine 60.8 grams, L-valine 33.8 grams,
L-methionine 33.8 grams, DL-phenylalanine 129.0 grams, L-isoleucine
40.6 grams, L-alanine 16.8 grams, L-proline 13.6 grams, L-serine
33.8 grams, and L-citrulline 10.2 grams.
[0215] Twenty (20) grams each of this mixture were used for control
and laser treated samples. Sample 1 was the control, Sample 2 was
treated with a 670 nm diode laser of 4.85 mW primary power adjusted
through the optical elements to a power level of 2.94 mW, and
Sample 3 was treated with a 458 nm pumped argon gas laser with a
primary power of 16.5 mW adjusted through the optics to a power
level of 5.06 mW. Durations of laser treatments for Samples 2 and 3
were 30 seconds each.
[0216] An independent outside lab, Paracelsian in Ithaca, N.Y.,
performed the following bioassays. A standardized Echinacea sample
alone or with 20 mg/ml of Samples 1, 2, or 3 were incubated in the
tissue culture media of triplicate wells of murine macrophages for
24 hours after Echinacea stimulation and then assayed for tumor
necrosis factor-alpha (TNF-alpha) production in triplicate ELISA
wells. Positive controls with lipopolysaccharide (LPS) at 1 ng/ml
and negative controls were also assayed in the same manner.
[0217] Those skilled in the art will appreciate that the use of
murine macrophages simulates the body's immune response. Adding the
herb Echinacea provides a similar response to that of an immune
system that is being irritated. A TNF-alpha reading is a good
marker for the extent of inflammation. Thus a substance that causes
a significant increase in TNF-alpha in the macrophages can be
expected to create substantial inflammation in a human
body--especially a body suffering from an autoimmune disease such
as inflammatory bowel disease, as well as other physiological
problems such as systemic lupus erythematosus, rheumatoid arthritis
and food allergies.
[0218] The results were as follows:
2 Sample ID TNF-alpha .+-. S.D. Negative Control 215 .+-. 13.7
Echinacea Positive Control 683 .+-. 27.1 LPS 1 ng/ml Control 2863
.+-. 185.7 Echinacea + Sample 1 1568 .+-. 45.8 Echinacea + Sample 2
850 .+-. 57.6 Echinacea + Sample 3 761 .+-. 100.3
[0219] Using a Students 2-Tailed T-Test, the Echinacea positive
control was compared to the results of Echinacea plus Samples 1, 2,
or 3. The addition of Sample 1 resulted in a highly significant
increase in TNF-alpha at p<0.0001. The relative increase in
TNF-alpha production was not as great after the addition of Sample
2, but was still statistically significant at p<0.03. The
addition of Sample 3 did not significantly increase TNF-alpha
production, with p=0.31. Thus the laser treatment of Sample 3
reduced the robust increased production of TNF-alpha observed with
control Sample 1 back to the baseline level of Echinacea alone.
[0220] In other words, the negative control is indicative of the
immune system of a normal person. Adding the Echinacea heightened
the immune response. The addition of lipopolysaccharide (LPS)
simulates a maximum immune stimulus, as a point of reference.
[0221] The addition of Sample 1, the unmodified amino acids, showed
a marked increase in TNF-alpha production. Thus, a person with an
autoimmune disease, or other inflammatory processes, would expect
to have substantial inflammation as a result of ingesting the amino
acids.
[0222] In contrast to Sample 1, Sample 2 and Sample 3 were modified
as set forth above. Not only did the Samples not create a strong
likelihood of inflammation, as did Sample 1, the increase in
TNF-alpha was very minor. In fact, Sample 3 showed virtually no
increase in inflammation of the Echinacea positive control.
[0223] Those familiar with nutrition will appreciate that many
people have difficulty tolerating certain nutrients that are
required for good health. The amino acids discussed above are a
prime example. By subjecting a wide variety of amino acids to laser
treatment, the bioavailability of the amino acids can be greatly
increased. Obviously, if a person with an autoimmune disorder or
other inflammatory condition does not react negatively to the amino
acids, considerably more can be incorporated into the person's diet
without risk of unwanted side effects.
[0224] Those skilled in the art will appreciate that inflammation
is not always a bad thing. There are many times when a heightened
immunological response may be desired. For example, increased
inflammation/immunologic activity may be used to fight tumors, or
other undesirable conditions. By modifying the laser treatment of
chemicals, the chemicals can be altered so that they increase
immunologic response, rather than minimize the same, as already
demonstrated through increased nitric oxide production of
macrophages from laser treated versus untreated control
L-arginine.
EXAMPLE 6
Improved Brain Coherence Using Laser Homogenized Versus Untreated
Amino Acids
[0225] An electroencephalogram (EEG) is a diagnostic study that
places recording electrodes over the brain to measure the pattern
of electrical activity in the brain. A quantitative EEG, or brain
map, is a detailed study that measures the power of brainwaves in
the frequency bands delta, theta, alpha, and beta, with power
expressed in microvolts. In addition, a brain map also measures
coherence, which refers to whether the phases of the brainwaves
from one region to another are in a relationship consistent with
healthy versus disordered brain function.
[0226] The standard conditions for a quantitative EEG are in the
morning after a good night's sleep, with avoidance of caffeine and
other stimulants. A cap with conductive electrodes is placed over
the scalp such that the electrodes localize over specific regional
brain areas. Measurements are taken with the eyes closed and the
subject resting supine for a period of 20-30 minutes. If baseline
and post intervention measures are done, the same protocol is
followed with the cap left in place to insure reliability of
localization from measurement to measurement. Resting with closed
eyes tends to cause significant augmentation of the alpha wave band
at 8-12 cycles per second, making this wave band of particular
significance for study interpretation. The quantitative EEG
equipment used for the following studies measured power output and
coherence data over 19 different locations over the brain.
[0227] The study test formula consisted of a blend of amino acids
intended to increase mental energy, concentration, and alertness.
The two most important amino acids for increased brain energy and
alertness are L-phenylalanine and L-tyrosine, as these are the
precursors to the catecholamine neurotransmitters dopamine,
norepinephrine, and epinephrine. In the standard chemical pathway,
L-phenylalanine is hydroxylated to L-tyrosine, which is then itself
hydroxylated to form L-dopa. The enzyme L-dopa decarboxylase then
converts L-dopa to dopamine; differential hydroxylation of dopamine
can then yield either norepinephrine or epinephrine, the other
major catecholamine neurotransmitters that can have profoundly
stimulant effects in the central nervous system and
systemically.
[0228] The study formula was composed of the following ingredients
as percentages by weight: L-tyrosine 6.6%, L-phenylalanine 3.3%,
DL-phenylalanine 2.2%, glycine 4.4%, L-arginine 7.7%, L-omithine
7.7%, L-lysine 3.3%, L-taurine 6.6%, L-glutathione 9.9%, L-glutamic
acid 5.5%, L-glutamine 4.4%, L-methionine 4.4%, L-cystine 7.7%,
L-cysteine 3.3%, L-alanine 5.5%, L-threonine 2.2%, L-valine 6.6%,
L-isoleucine 4.4%, L-leucine 1.1% L-histidine 2.2%, and L-aspartic
acid 1.1%. Into clear gelatin capsules, 750 mg of the study formula
were placed per capsule. The control untreated capsules received no
further modification. The laser treated capsules were irradiated
with pumped argon laser light at 458 nm, as in Example 1 for
Arginine #3. The treated capsules were slowly rotated through the
beam for one minute per capsule.
[0229] The subjects were two young adult white females with no
known medical problems and no history of brain injuries or
neurologic illness. They were chosen as subjects to represent the
brain physiologic responses of young healthy persons. As
anticipated the baseline quantitative EEGs showed a preponderance
of alpha waves as expected for the resting state with eyes closed.
After taking the baseline readings the subjects were each given 2
capsules of the untreated study formula, 1.5 grams total per
subject. After 30 minutes to permit absorption and assimilation of
the formula, quantitative EEG measurements were repeated. Following
the measurements of the untreated study formula, the subjects then
ingested two capsules of the laser treated formula, 1.5 grams total
per subject. After 30 minutes to permit absorption and assimilation
of the treated formula, quantitative EEG measurements were again
repeated.
[0230] The following table shows the mean and standard deviation
(SD) values for the power output in the alpha band for baseline,
post untreated amino acids, and post treated amino acids.
3 Mean (Microvolts) Standard Deviation Baseline 8.339 4.876
Untreated Amino Acids 11.2842 6.7014 Treated Amino Acids 11.9842
8.2596
[0231] A General Linear Model repeated measures analysis of
variance was used to analyze the effect of a laser energized amino
acid formula on enhancing brain power, comparing baseline,
ingestion of the untreated formula, and ingestion of the laser
treated formula. Multivariate testing indicated a significant
increase in brain power over baseline with Wilks' Lambda=0.219, F
(2,36)=64.128, p.ltoreq.0.0001. Paired two-tailed t-test analysis
indicated significant increases in brain power were found over
baseline after ingesting both the untreated and laser treated amino
acids, both comparisons statistically significant at p<0.0001.
Further, the laser treated amino acid formula significantly
increased brain power over the untreated formula, with t
(37)=-2.349, p=0.024.
[0232] In addition, use of the laser treated formula also showed a
significantly better coherence result than the use of the untreated
amino acid formula. One of the two subjects showed the adverse
effect of a significant degradation of her brainwave coherence in
alpha after the ingestion of the untreated amino acids that
improved to better than baseline after ingesting the laser treated
amino acids. FIG. 12A shows the baseline coherence study for this
subject that demonstrates a single brainwave coherence abnormality
in the left posterior region of the brain. Following the ingestion
of the untreated amino acid formula, FIG. 12B shows the development
of extensive coherence abnormalities. From a single defect at
baseline, 11 regions of abnormality have developed that show
intense front to back coherence defects bilaterally, with a region
of interhemispheric coherence defect as well. Following the
ingestion of the laser treated amino acids, FIG. 12C shows the
complete resolution of all coherence defects. Use of the laser
treated amino acids not only showed the ability to increase the
power output of the brain significantly over the untreated amino
acids, but also showed the ability to reverse the adverse effect of
abnormal brainwave coherence that occurred with the use of the
untreated amino acids. It is possible that inhomogeneities in shape
and backbone twist, particularly of the precursors to the phenolic
neurotransmitters, may predispose to inconsistent receptor effects
and suboptimal neurophysiologic responses.
[0233] In the commercial production of L-tyrosine, the heating and
dehydration processes to which the molecules are subjected,
particularly pulling water molecules from the structure, may result
in twisting the phenol ring on the backbone chain or other
distortions of the molecular shape. For the untreated L-tyrosine,
those shapes that failed to provide optimum receptor fit for its
catecholamine neurotransmitter metabolites may be a factor in the
development of coherence abnormalities. The homogenization of the
configuration of the laser treated L-phenylalanine and L-tyrosine
could be a key factor promoting the restoring of normal brain
coherence that may occur through improved receptor fit of
neurotransmitters, while also sustaining increased brain
energy.
[0234] Likewise, L-dopa is subjected to thermal and dehydration
stresses during its commercial manufacture. These stresses may also
result in molecular distortions of the phenolic ring alignment on
the backbone. Widely used as a pharmaceutical agent to treat
Parkinson's disease, L-dopa provides the substrate to increase
dopamine levels deficient in specific brain regions (especially the
substantia nigra and other striatal nuclei) in that condition.
L-dopa is usually given with carbidopa, an inhibitor of dopa
decarboxylase outside of the brain so that higher concentrations of
L-dopa cross the blood-brain barrier. Although L-dopa may help to
relieve the movement disorders of Parkinson's disease, its use is
frequently complicated by side effects such as nausea and
agitation. Because of diminishing efficacy, escalating doses are
often required, which also tends to further increase side effects,
which may become dose limiting. The use of laser resonance to
homogenize L-dopa may yield a shape that more consistently promotes
the intended clinical effects, while reducing the side effect
profile. It may be possible that a given dose of laser treated
L-dopa will provide equivalent or greater clinical benefits, may
reduce the tendency of adverse effects, and delay the requirement
of dosage escalation. The initial protocol to use for the laser
treatment of L-dopa would follow the practice used for treating the
amino acid formula as above, scaled up for higher volume powder
delivery as suited to commercial production levels.
EXAMPLE 7
Increased Quality of Crystal Formation with Flattened and Stretched
Carbon-Nitrogen, Carbon-Hydrogen, and Carbon-Oxygen Bonds in Laser
Treated Versus Untreated Betaine Hydrochloride
[0235] In accordance with the present invention sparse constructive
node laser irradiation has been used to resonate betaine
hydrochloride molecules to a homogeneous flattened and stretched
shape. The homogenization effect is observed at the level of much
improved crystal formation of the laser treated betaine
hydrochloride versus the untreated control. X-ray crystallography
of the laser treated betaine hydrochloride shows the predicted
flattening and stretching of the bonds in the treated molecules
compared to the control untreated molecules.
[0236] The control and treated betaine hydrochloride samples shown
in FIGS. 13A, 13B, 13C, 13D, and 13E were prepared by dissolving
0.6 grams of betaine hydrochloride in 3.0 grams of deionized water
and placing the solutions thus prepared in 10.times.35 mm Petri
dishes. Crystallization was done in open containers by slow
evaporation at room temperature, a procedure often used in the art
of crystallography. Ambient humidity was maintained at or below 30
percent with laboratory dehumidifiers. The treated betaine
hydrochloride was irradiated with a 670 nm continuous wave diode
laser modulated at 10 MHz with a primary beam power of 2.7
milliwatts that was phase conjugated to 1.35 milliwatts. The 5 mm
diameter beam was passed through the middle of fluid meniscus of
the treated solution during the entire crystallization process. The
control untreated betaine hydrochloride was prepared under the same
conditions, except that it was not irradiated with the sparse
constructive node generating laser system.
[0237] The quality of crystal formation in control versus laser
treated betaine hydrochloride is shown in FIGS. 13A and 13B. The
crystallographic term for the overall geometric shape of the
crystal that has formed is the crystal habit. In FIGS. 13A and 13B
the control crystals on the left have a markedly different habit
from the treated crystals on the right.
[0238] The magnified lateral view photographs of FIG. 1 3A show a
significant difference between the control and laser treated
betaine hydrochloride. The control crystal has numerous inclusion
defects, surface irregularities and much shallower depth. In
contrast, the treated crystal shows a high level of uniformity,
free of defects, with a smooth surface, and a greater front to back
depth. The frontal views of FIG. 13B show a wavy, irregular surface
of the control crystal with a coarse outline of the edges. In
comparison, the laser treated crystal on the right shows a much
smoother surface with smoother contours of the edges.
[0239] These figures demonstrate the process of homogenization.
Betaine hydrochloride tends to have a backbone twist, resulting in
a range of shapes in solution. Even with a slow evaporation over
several hours, the differential of shapes prohibited an orderly
arrangement in the crystal lattice, leaving gaps and irregularities
in the crystal. As slightly different shapes were added to the
growth zone of the crystal, the growth planes were distorted
resulting in crystal irregularities.
[0240] In contrast, the betaine hydrochloride grown under the
influence of laser homogenization achieved such self-similarity
that a highly organized crystal free of gross defects was formed.
The slight heating of the medium that may have resulted from low
power laser application would, if anything, have tended to cause
less organization, which was overridden by the sparse constructive
node effects.
[0241] It is important to note that the production of the control
crystal by slow evaporation is a very gentle process compared to
the usual modes of industrial drying of bulk quantities of product.
Typically much higher temperatures are used, up to the threshold of
thermal degradation of the compound.
[0242] Such aggressive conditions will substantially increase the
tendency for more widespread and extreme distortion of molecular
structure through random thermal motion and greater intensity of
dehydration. Sparse constructive node laser irradiation can be
applied to dried powders (as in Examples 1, 3 and 4) or during the
dehydration process to homogenize molecular shapes and thereby
improve bioavailability.
[0243] X-ray crystallography was performed using a SMART device
made by Siemens. FIGS. 13C and 13D show the intermolecular hydrogen
bonding of control versus laser treated betaine hydrochloride,
respectively. FIG. 13C shows 4 intermolecular hydrogen bonds per
molecule of untreated betaine hydrochloride. In comparison, FIG.
13D shows only 3 intermolecular hydrogen bonds for each molecule of
treated betaine hydrochloride. Although this is a soft feature of
the crystallography, reducing the number of hydrogen bonds can
increase solubility; faster dissolving of substrate into solution
could promote more rapid absorption of the molecule.
[0244] FIG. 13E shows the crystal solution for control and laser
treated betaine hydrochloride through x-ray crystallography. The
crystallographic solution refers to the process of using the x-ray
diffraction pattern to determine the precise localization of all of
the atoms in the molecule being analyzed.
[0245] In the two diagrams, the dashed lines show the structure of
control untreated betaine hydrochloride, whereas the solid lines
show the structure of the laser treated betaine hydrochloride. The
upper diagram shows backbone model representations and the lower
diagram shows ball and stick model representations. In both
diagrams, the treated betaine hydrochloride shows the predicted
effects of flattening and stretching of the molecule. In
particular, there is flattening and stretching of carbon-nitrogen
bonds (of the methyl groups), carbon-oxygen bonds, and to a lesser
degree carbon-hydrogen bonds.
[0246] Homogenization and molecular flattening and stretching can
increase the efficiency of enzyme moderated reactions through at
least three basic mechanisms, thereby enhancing bioavailability.
Increasing the homogenization of the substrate is analogous to
increasing the concentration of the substrate for the isoform of
the enzyme preferred for that substrate. In any enzyme moderated
reaction increased substrate concentration will proportionately
increase reaction rates and product generation.
[0247] Secondly the flattest shape will tend to be the lowest
energy state that is homogeneous. In this configuration bond
strength is lowest, while field strength is highest. This is a very
reactive state as the substrates behave as whole molecules.
[0248] In addition, the high self-similarity from molecule to
molecule facilitates enzyme binding, because enzymes will bond
considerably faster to a molecule identical to that just released
than to one even slightly dimensionally different. This means that
the rate at which the reactant can be supplied is directly
proportional (times a constant) to the self-similarity of the
molecules in the reactant. Thus cells will make more product the
more similar the molecules of the reactant are to each other with
respect to dimensional shape and water distribution. Molecules
exposed to sparse node irradiation will in general be highly
similar in terms of water distribution and location, will tend to
have the flattest low energy shape possible with a high electrical
and magnetic moment, and will be extremely self-similar in all
dimensions.
[0249] The betaine hydrochloride crystals made from exposed and
unexposed betaine hydrochloride showed this effect to a marked
degree because small individual differences add up to larger
macroscopic differences visible in a grown crystal. Self-similarity
also reduces the need for a cell to manufacture a wider range of
enzymes to moderate a given reaction than is the case if the cell
is presented with a highly inhomogeneously crystallized reactant
with widely varying shapes. Increasing the similarity of bond
energy and dimension molecule to molecule will generally tend to
favor the production of any product in an enzyme moderated
reaction, and thereby increase bioavailability.
[0250] The process of cells making a product can be viewed as a
manufacturing process where the cells take in raw materials at one
end with the aim of producing a specific product at the other. The
concept of a nutritional supplement at the fundamental level is to
make available raw materials for a given product that would
otherwise require prior reactions to extract from available
foodstuffs. Thus the principle of a nutritional supplement is to
reduce the reaction complexity of a given product and hence the
energy and time required to produce it.
[0251] Increasing the homogeneity of the nutritional supplement is
simply an enhancement of that same principle further reducing the
complexity of the reaction and increasing the speed and efficiency
of producing the desired product, thus enhancing bioavailability
over unhomogenized nutrients. Likewise a pharmaceutical agent
intended to increase a desired product in the body through enzyme
moderated reactions, such as producing dopamine from L-dopa, may
also show enhanced bioavailability and potentially fewer side
effects if laser homogenized rather than if untreated
pharmaceutical agents are used.
[0252] In addition, pharmaceutical agents that are designed to
increase receptor activity (such as the beta-blocker propranolol)
may show similar shape moderated effects of bioactivity. It is well
known that receptor--ligand fit is highly shape dependent.
Homogenization to a highly self-similar flattened shape with a high
electric and magnetic field moment may similarly function as though
increasing ligand concentration for the desired receptor-ligand
effect. This may permit both lower dosing for similar clinical
benefits as well as reduced adverse effects at similar dosing
levels.
EXAMPLE 8
Clinical Effects of Laser Treated Betaine to Reduce Homocysteine
and Improve Clinical Symptoms
[0253] A randomized prospective placebo controlled double blind
study was performed to determine the effects of laser treated
betaine plus metabolic cofactors on methylation metabolism and
clinical symptoms. Methylation metabolism refers to the transfer of
methyl groups, the simple organic chemical group consisting of a
carbon atom bonded to three hydrogen atoms (CH.sub.3).
[0254] Also known as single carbon transfers, methyl group
transfers are among the most fundamental and important chemical
transfers in cell biology. Methyl group transfers are involved in
the manufacture of DNA, the repair and maintenance of cell
membranes, synthesis and balance of neurotransmitters in the
central nervous system, and numerous other processes that modify
proteins, lipids, and sugars into their biologically useful
configurations.
[0255] Methylation metabolism is also intimately involved in DNA
regulation and biological timing mechanisms. Given the widespread
importance of methyl group transfer metabolism, therapeutic agents
that enhance methyl metabolism would be expected to have
significant potential for improving overall metabolic balance and
related clinical conditions.
[0256] A key indication of the integrity of methyl metabolism in
the body is the homocysteine level. Elevation of serum homocysteine
indicates impairment of one or more of the main methyl metabolism
pathways. Elevated homocysteine is also clinically relevant.
Published epidemiologic data indicates an exponential rise in the
relative risk of cardiovascular disease for homocysteine levels
above 6.3, as shown in the following chart:
4 Homocysteine Level <6.3 6.3 10 15 20 Relative Cardiac Risk
<1 1 2 4 9
[0257] In addition, elevated homocysteine has been associated with
an increased risk of stroke, Alzheimer's disease, pre-eclampsia,
neural tube birth defects, fetal loss, human hostility, and the
development of malignancies. In homocystinuria, a metabolic
disorder in which homocysteine can rise into the hundreds,
accelerated aging, neurologic disease, and atherosclerosis can be
highly aggressive even at early ages.
[0258] Homocysteine is produced in the body as a byproduct of
metabolism of the amino acid methionine. There are three main
pathways the body uses to clear homocysteine that when effective
can prevent its rise to hazardous levels.
[0259] The first pathway is the transsulfuration pathway that uses
vitamin B6 (pyridoxine) and zinc to detoxify homocysteine to the
amino acid cysteine. Methionine and cysteine are the main sulfur
containing amino acids, and methionine can be converted to cysteine
via homocysteine if their pathways are intact. Some persons are
unable to phosphorylate pyridoxine to its activated state; in these
persons, pyridoxal-5'-phosphate must be given to overcome the
metabolic block.
[0260] The second homocysteine detoxification pathway uses vitamin
B12 and folic acid to remethylate homocysteine back to methionine.
Deficiencies of B12 and folic acid are well known to result in
neurologic, psychiatric, and hematologic defects. Disturbed methyl
group transfer metabolism impairs the synthesis of DNA,
neurotransmitters, and myelin that can result in anemia, dementia,
psychiatric disease, and peripheral neuropathies. Deficiencies of
folic acid in particular have been associated with an increased
risk of colon and cervical cancer, as well as birth defects of the
central nervous system. Genetic defects of this pathway are common
in certain populations, e.g., 38% of French Canadians are
heterozygous for defective activity of the enzyme
methyltetrahydrofolate reductase. Aggressive support of the
complete methyl metabolic pathways may significantly reduce the
health hazards of such inborn metabolic defects.
[0261] The third pathway for clearing homocysteine, and perhaps the
most powerful clinically, uses betaine as a methyl group donor.
Through betaine-homocysteine methyltransferase, an enzyme found in
the liver and kidneys, a methyl group from betaine is transferred
to homocysteine to convert it into the essential amino acid
methionine. Betaine itself is a derivative of the amino acid
glycine that has had its three amino hydrogen atoms replaced with
three methyl groups; thus betaine is a methyl group rich methyl
group donor also known as N,N,N-trimethylglycine, or simply as
TMG.
[0262] A double blind clinical study conducted by Morrison et al.
in 1953 looked at the effects of administering methyl group
transfer factors on subjects that had just survived a first
myocardial infarction. Treated subjects received high-dose betaine
of 9 grams daily plus vitamin B12, a liver extract, and a creatine
precursor. After one year, subjects given the placebo had 25%
mortality versus no mortality in the treatment group, which was a
highly significant reduction of mortality in the treatment
group.
[0263] Persons with homocystinuria, the most extreme scenario of
disturbed methyl metabolism, may also show a reduction of
homocysteine level with vitamins B6, B12, and folic acid, but often
do not have a significant improvement in clinical condition. In
contrast, adding high dose betaine (typically 6-9 grams daily) has
been associated with reversal of graying hair, improved
cardiovascular status and even reversal of neurological defects.
Women with homocystinuria have been able to conceive and have
normal gestation and term deliveries when betaine has been added to
their regimen.
[0264] Ingestion of betaine has also been associated with reduced
body fat, increased muscle mass, and enhanced athletic performance.
Betaine also plays a role in intracellular osmotic regulation,
especially in the kidney.
[0265] The generation of methionine, particularly in the liver,
sets the stage for one of the most important processes of methyl
metabolism. A molecule of methionine combines with the energy
molecule ATP (adenosine triphosphate) to form the molecule
S-adenosyl-methionine (SAMe), through the action of the enzyme SAMe
synthetase. The SAMe thus formed is the predominant methyl group
donor in cellular metabolism, involved in several dozen methyl
group transfer reactions.
[0266] In particular, all of the DNA methyltransferases, the
enzymes that regulate DNA transcription, aging, and repair through
DNA methylation, exclusively use SAMe as the DNA methyl group
donor. In addition, SAMe donates methyl groups to proteins, lipids,
and carbohydrates to modify them into their biologically active
configuration. Membrane lipids in particular require methylation
for optimum fluidity and receptor function.
[0267] From the neurologic standpoint, SAMe provides methyl groups
for neurotransmitter synthesis and balance, particularly the
synthesis of serotonin, as well as for production of the insulating
myelin sheaths of nerves.
[0268] Double blind clinical studies using ingested SAMe have
documented several therapeutic benefits. At doses of 1600 mg per
day, anti-depressant effects comparable to tricyclic
anti-depressant drugs have been seen. In contrast to tricyclic
pharmaceutical agents, the anti-depressant effects of SAMe were
seen within one week as opposed to the usual 4-6 weeks required to
achieve clinical benefits with tricyclic medications. In addition,
the use of SAMe was essentially free of side effects, as opposed to
the frequent anti-cholinergic and cardiovascular adverse effects
observed with tricyclic pharmaceutical agents.
[0269] Other reported clinical benefits of SAMe include reduced
pain and increased function in osteoarthritis, reduced symptoms of
fibromyalgia, and improved cardiovascular health. SAMe use has also
been reported to protect the liver from toxins and promote liver
repair, even of cirrhosis. The latter effects are likely related to
SAMe enhancing methylation in the liver, an important pathway of
detoxification.
[0270] Once SAMe donates its methyl group, it then becomes
S-adenosyl-homocysteine (SAH). Upon release of the adenosyl group,
homocysteine is the resultant byproduct. FIG. 14A shows the general
outline of the methyl group transfer pathways. Although
administration of SAMe has been associated with clinical benefits,
it has the potential drawback of increasing the homocysteine
load.
[0271] A more ideal method of optimizing methyl metabolism would be
to increase endogenous SAMe production while reducing homocysteine
levels, as long as SAMe can be sufficiently boosted. Betaine
administration is a strong candidate for raising SAMe while
reducing homocysteine, as animal studies have shown that giving
betaine may raise liver SAMe levels up to fourfold. Consistent with
the betaine results on raising liver SAMe levels, giving betaine
has also been shown to protect the liver from the adverse effect of
toxins, in particular protecting the liver from alcohol induced
toxicity.
[0272] Supportive of this role for betaine, a case study of a young
woman with severe homocystinuria and major neurologic defects
showed marked resolution of neurologic deficits when betaine was
added, but not with vitamin administration alone; in addition her
cerebrospinal fluid SAMe levels rose from nearly undetectable to
normal levels, in conjunction with clinical improvement upon
addition of betaine to her regimen.
[0273] As a pilot test, a female subject with osteoarthritis had
blood SAMe levels measured while taking SAMe and then while taking
a betaine formulation. The subject was taking 800 mg of SAMe daily,
which provided a moderate degree of relief from knee pain. On this
level of SAMe ingestion for three months, her blood SAMe level was
4.9 (the normal range for this lab is 4.2-8.2). At this time, SAMe
was discontinued and she started a methylation formula with one
gram of laser treated betaine plus laser treated metabolic
cofactors. The betaine and metabolic co-factors were in the same
ratios as in the double blind clinical study formula to be
described below.
[0274] After one month, her blood SAMe level had risen to 6.2 and
her right knee pain had nearly fully resolved. Thus giving the
precursor of SAMe rather than SAMe itself resulted in a
significantly higher blood level of SAMe and a greater clinical
response. In particular, the dual effect of raising SAMe while
reducing homocysteine would be expected to preserve and improve the
condition of DNA methylation, as SAMe is the exclusive methyl group
donor for DNA methylation.
[0275] Elevation of homocysteine has been found to be the most
reliable marker of impaired DNA methylation, other than the direct
measurement of DNA methylation status. Elevated homocysteine has
also been associated with accelerated shortening of the telomeres
in vascular endothelial cells. Telomeres are the ends of
chromosomes that tend to shorten with each cellular division. When
telomeres shorten excessively, the cells tend to lose the ability
to replicate. Homocysteine elevation is thus associated with two
fundamental DNA aging mechanisms; reducing homocysteine would
therefore be expected to have significant effects supporting life
extension.
[0276] The pattern of DNA methylation at birth is vitally important
to the integrity of function of each type of cell. Methyl groups
are placed on specific cytosine residues to differentiate the DNA
expression of each cell type, through blocking the transcription of
genes not appropriate to be produced in that cell line. The methyl
groups on specific cytosine residues thus serve as regulatory
blocks to prevent expression of genes inappropriate for that cell
type. This mechanism, for example, prevents brain cells from making
muscle proteins and muscle cells from making proteins that would be
the exclusive province of brain cells. Every cell line therefore
has a particular pattern of which residues in the genome undergo
cytosine methylation.
[0277] This methylation pattern thus serves as a type of
fingerprint that differentiates one cell line from another through
blockade of transcribing gene products not suitable to that cell
line. Cytosine methylation is a central regulatory process that
determines which of the approximately 100,000 genes in the human
genome will be expressed in a particular cell line.
[0278] The gradual loss of methyl groups from DNA is one of the
most important timing mechanisms for aging and DNA degradation in
the cell. At birth, depending on the type of cell, the cytosine
methylation level ranges from 2-6% of the cytosine residues. The
highest level of DNA methylation in humans and other mammals is
typically seen in the thymus gland, with a cytosine methylation
level of 6%. As methyl groups are gradually lost from DNA,
integrity of transcription and DNA regulation is reduced. The DNA
may begin to transcribe inappropriate genes for that particular
cell line. Oncogenes may lose the suppressive effect of methylation
and be at risk for activation, a change that may increase the
likelihood of tumor formation. The cell chemistry associated with
impaired methylation then increases the risk of DNA strand breaks
and mutations.
[0279] At least in part due to the DNA changes associated with
demethylation, a 20% loss of methyl groups from birth is associated
with a significant increase in the risk of certain malignancies,
particularly colon and cervical. Looking at the single variable of
folic acid, persons with high versus low folic acid levels have
been shown to have an approximately 50% lower risk of colon or
cervical cancer.
[0280] At a 40% DNA demethylation level, for humans and other
mammalian species, degenerative death tends to occur. At this level
of DNA demethylation, if generalized throughout the tissues,
information integrity is so impaired, that survival of the organism
is no longer supported. Thus any factor that slows, stops or
reverses the loss of methyl groups from DNA will tend to slow, stop
and even reverse the aging process at the DNA level.
[0281] Although a 50% DNA demethylation level throughout the body
would generally not support survival, a loss at this level can
occur in selective tissues in certain conditions. In particular,
50% DNA demethylation has been reported selectively in lymphocyte
populations in the autoimmune diseases systemic lupus erythematosis
and rheumatoid arthritis.
[0282] The extreme loss of DNA information integrity in these
immunity regulating cells may be at the core of dysfunction that
results in the immune system identifying self antigens as foreign
antigens and initiating a destructive inflammatory process against
the self. Various anti-inflammatory agents work primarily to reduce
the end inflammatory effects rather than address the core
information and DNA regulatory defects. In contrast, correcting the
methylation defects in affected immune cells may help correct
autoimmune conditions at the level of information
dysregulation.
[0283] Homocysteine elevation, associated with both accelerated DNA
demethylation and telomere shortening, is a marker for accelerated
aging processes at the DNA level. Any program that intends to
achieve life extension effects must address DNA methylation, SAMe
generation, and homocysteine levels to be complete.
[0284] The pathologic effects of homocysteine extend beyond
accelerated DNA demethylation. Homocysteine is also a significant
factor in increasing the pathogenicity of cholesterol in the
etiology of vascular disease. Homocysteine and thiolactone combine
with LDL cholesterol to promote LDL oxidation.
[0285] Animal studies have shown that administration of high doses
of unoxidized cholesterol has little effect on blood vessels, but
the addition of even a trace of oxidized cholesterol results in
rampaging atherosclerosis. The action of homocysteine to induce LDL
cholesterol oxidation can greatly increase the atherogenicity of
LDL cholesterol, even at levels considered to be in the normal
range.
[0286] In addition, elevated homocysteine increases the binding of
lipoprotein(a) to fibrin. Elevated homocysteine also tends to
increase the propensity of the soluble clotting factors to form
blood clots. Both of these factors increase the likelihood that a
blood clot will form and obstruct a vessel, especially in a region
of vulnerable vascular plaque, that may result in a heart attack,
stroke, or peripheral tissue gangrene.
[0287] Studies of blood vessel tone show that the higher the
homocysteine level above a physiologic normal, the greater the
inhibition of nitric oxide production from the vascular
endothelium. As nitric oxide dilates blood vessels, inhibiting
nitric oxide impairs the ability of the affected vessel to dilate
in response to a need for greater blood flow. Antagonism of nitric
oxide production may predispose to vascular spasm, increasing the
likelihood that a tissue will undergo ischemia, or reduced blood
flow and oxygenation below that needed to support viability of the
tissue.
[0288] Through these multiple mechanisms, elevated homocysteine may
accelerate atherosclerosis, impair blood vessel dilation required
for adequate blood flow, or increase the likelihood of blood clot
formation. For these reasons, homocysteine can be a much greater
risk factor for premature heart attack (below age 55) then elevated
cholesterol, as well as for stroke and peripheral vascular disease.
Elevated homocysteine has been shown to increase the relative risk
of a premature heart attack by up to 40 fold, whereas the relative
risk for increased cholesterol is only about 4 fold.
[0289] From the standpoint of malignancy, homocysteine has been
found to accumulate in malignant cells and interfere with DNA and
protein chemistry. Administrating methylation enhancing nutrients
to smokers with premalignant bronchial cytology showed a
significant regression of lesions toward normal, whereas there was
no improvement in bronchial cytology of the placebo control group.
In addition, administering methylation enhancing factors has also
appeared to improve the clinical course of lymphoma.
[0290] Reducing homocysteine levels and improving methyl metabolism
may have wide ranging benefits, including anti-aging effects,
reducing cardiovascular risks, and reducing the risk of and
mitigating the course of malignancy. Elevating SAMe has also been
associated with relieving depression and osteoarthritis symptoms,
improved symptom profiles in fibromyalgia, and enhancement of
cardiac and liver health and function.
[0291] A randomized placebo controlled double blind prospective
clinical study was performed to assess the effects of laser treated
betaine plus laser treated cofactors on homocysteine levels and
other clinical and metabolic profiles. A comprehensive protocol for
human clinical study was submitted to the Western Institutional
Review Board (WIRB) in Olympia, Wash., which protocol was approved
for following accepted guidelines for human clinical studies.
[0292] Study subjects were recruited from the Seattle and Olympia,
Wash. areas through notification in a local newspaper. Forty
subjects over the age of forty were selected for participation. The
minimum age of forty was selected as homocysteine levels tend to
rise with age, to choose a study group expected to have at least a
moderate level of homocysteine elevation to see the effects of the
study formula on reducing homocysteine levels.
[0293] The study formula, designed and laser treated for
enhancement of methylation metabolism, consisted of the following
ingredients in the stated proportions: betaine (trimethylglycine)
2000 mg, choline bitartrate 750 mg, inositol 500 mg, inositol
hexanicotinate 375 mg (a nonflushing form of niacin, vitamin B3,
that provides 80% niacin by weight, or 300 mg of niacin), magnesium
amino acid chelate 18.42% 162.9 mg (providing 30 mg magnesium),
cyanocobalamin 1% 100 mg (providing lmg of vitamin B12), pyridoxine
hydrochloride 25 mg (vitamin B6), zinc chelate 20.17% 24.8 mg
(providing 5 mg zinc as amino acid chelate), calcium chloride 37
mg, magnesium stearate 27 mg, pyridoxal-5-phosphate 5 mg (vitamin
B6 in phosphorylated form), and folic acid 1.6 mg. These
ingredients were measured by weight and mixed to a uniform
consistency and distribution in a commercial mixing device. The
total weight of the formula, balanced to 2 grams of betaine is
4.008 grams, filling 6 gelatin caps of 00 size with 668 mg
each.
[0294] The study methylation enhancement formula was treated with
sparse constructive node laser illumination at a primary laser
wavelength of 670 nm. Two GaAs diode lasers were used with primary
powers of 4.6 mW and 3.0 mW phase cancelled to 2.3 mW and 1.5 mW,
respectively. These lasers were further electronically modulated at
10 MHz. The study formula was placed in a clear plastic container
with 2 kg of formula per container. Each container was treated with
dual laser irradiation with the container rotating in a gyroscopic
device for 12 minutes per container. The average laser irradiation
dose was 0.044 kg/min/mW.
[0295] Study subjects were randomized into treatment or placebo
groups after entry into the study. Baseline homocysteine levels
were stratified by level from high to low, and for each range two
thirds of subjects were randomized to receive active treatment with
the laser treated methylation formula and one third to receive a
placebo.
[0296] All subjects received, reviewed and signed informed consent
forms for the study protocol before starting the study. All
subjects ingested 18 cobalt blue opaque gelatin capsules that
obscured for the subjects whether they were receiving placebo or
active formula. During the first month of the study, the treatment
group received 2 grams of laser homogenized betaine plus a
proportionate level of laser treated cofactors daily; the balance
of the weight of their capsules was filled with maltodextrin 580, a
low glycemic carbohydrate polymer of glucose that would not be
expected to have a significant impact on methyl metabolism.
[0297] During the second month of the study the treatment group
received 4 grams of laser homogenized betaine plus a proportionate
level of laser treated cofactors daily; the balance of the weight
of their capsules was filled with maltodextrin. During the third
month of the study the treatment group received 6 grams of laser
homogenized betaine plus a proportionate level of laser treated
cofactors daily; this quantity of formula completely filled the
capsules and no additional maltodextrin was required. For the
entire duration of the study, all of the capsules ingested in the
placebo group were filled only with maltodextrin.
[0298] All subjects filled out daily questionnaires that indicated
the number of capsules they ingested on each day. On the daily
questionnaires subjects also recorded food and beverages ingested,
amount of exercise, whether they smoked and how much, as well as
their general mood, energy, and quality and duration of sleep. In
addition, space was provided to record any symptomatic benefits,
side effects or general comments.
[0299] Intake and study completion surveys were also done just
before starting and upon concluding the study. In addition to the
general dieting, exercise, well being, and smoking questions asked
above, these surveys also inquired about the presence of any known
medical problems, medication use, nutritional supplement ingestion,
and any alcohol or caffeine intake.
[0300] At baseline, and after each week of the study, all subjects
completed a clinical assessment questionnaire known as the
SCL-90-R. Produced by National Computer Systems, Inc (NCS),
SCL-90-R stands for Symptom Checklist 90-Revised. The SCL-90-R is
an extensively used highly statistically validated survey of 90
questions used in "clinical trials to help measure the change in
symptoms such as depression and anxiety." It is a brief
multidimensional self-report inventory that screens for symptoms of
psychopathology and provides global distress indices. NCS provides
a scoring template that gives a percentile rank for the study
subject for each of the symptom scales tested, for the study
subject compared to the general population. Test scales measured
included anxiety, depression, paranoid ideation,
obsessive-compulsive, somatization (perceptions of bodily
dysfunction), and hostility scales, and a global severity index,
the latter an index for all symptoms measured together as a
composite.
[0301] At baseline, and at the end of each month of the study,
subjects reported to the clinical laboratory of St. Peters Hospital
in Olympia, Wash. for phlebotomy. Blood tests measured serially
were complete blood counts with differential white blood cell
counts and platelets, chemistry panels including glucose,
electrolytes, blood urea nitrogen (BUN), creatinine, liver enzymes,
and lipid panels that included triglycerides, total cholesterol,
LDL cholesterol, and HDL cholesterol. Homocysteine levels were also
drawn. In addition, blood samples were centrifuged and fractionated
for red cells, white cells, and plasma components and then frozen
for specialized studies to be conducted at an independent research
laboratory, to include red blood cell SAMe and DNA methylation
levels. Samples were collected and shipped as per the established
lab protocol.
[0302] For all areas measured, not more than ten subjects dropped
out of any measure. The main reasons for dropping a subject from
data analysis were failure to do one or more blood tests or
complete forms, a medical or metabolic condition interfering with
analysis, or other administrative reasons.
[0303] As this study achieved baseline and three different dosage
measures, the statistical analysis method of autoregression with
multiple measures was employed. As this method uses each subject as
their own control, a formal control group is not required for
statistical analysis. The placebo control group was used in this
study primarily to exclude significant random fluctuations in the
metabolic measures tested in the absence of the study formula.
[0304] The reduction of homocysteine level was statistically
significant at every dosage given, with p<0.00001 even at the
lowest dose. The average homocysteine level in the treatment group
dropped from 9.1 at baseline to 7.1 after the first month of the
study formula, using 2 grams of laser homogenized betaine plus
laser treated cofactors. Reductions in the treatment group at the
second and third dosage levels of 4 grams and 6 grams of
homogenized betaine plus proportionately increased levels of laser
treated cofactors yielded average homocysteine values of 6.8 and
6.1, respectively. At 6.1, this placed the treatment group as a
whole at the lowest cardiovascular risk level for homocysteine,
below that of the general population.
[0305] FIG. 14B shows the dose response curve graphically with the
statistical significance values for each dosing level.
[0306] The placebo control group started at homocysteine levels not
statistically significantly different from the treatment group.
Over the 3 month course of the study there was no significant
reduction in homocysteine levels; if anything there was a minor
statistically insignificant increase in homocysteine levels. The
average homocysteine values for the placebo control group over the
three months of the study are shown graphically in FIG. 14C.
[0307] As greater degrees of homocysteine elevation are associated
with commensurately higher cardiovascular and other risks, the
subgroup of the treated subjects who started with the highest
homocysteine levels was separately analyzed for dose response
effects.
[0308] FIG. 14D shows the dose response curve to the laser treated
study formula for those subjects whose baseline homocysteine values
were at least 10. The average reduction was statistically
significant at every dosage level, with a 30% reduction from 13.2
to 9.3 even at the lowest dose of the study formula. Higher doses
further reduced the homocysteine levels on average to 8.3 and 7.3,
after the second and third months, respectively. The highest
proportionate drop was a subject whose baseline homocysteine of 15
dropped to 5 after the second month of the study formula, or a
nearly 70% reduction of homocysteine. These results indicate that
the laser homogenized methylation formula may be especially helpful
for regulating and lowering the highest risk elevations of
homocysteine.
[0309] The use of the study formula was also associated with a
statistically significant reduction of the anxiety scale. FIG. 14E
shows the linear dose response curve for greater reduction of
anxiety with higher doses of the study formula. In contrast, there
was no significant reduction of anxiety scale in the placebo
group.
[0310] FIG. 14F shows a highly significant reduction of the
somatization scale (perceptions of bodily distress, aches and
pains) with an especially steep reduction at the lowest dosage
level.
[0311] FIG. 14G shows statistically significant reduction of
depression, increased at higher dosage levels. As the study formula
is expected to increase SAMe levels, the results shown in FIGS. 14F
and 14G are consistent with the reported effects of the use of SAMe
directly--namely reductions of aches and pains, whether due to
osteoarthritis or fibromyalgia, as well as relief of
depression.
[0312] FIG. 14H shows the highly statistically significant
reduction of obsessive-compulsive symptoms at every dosage
level.
[0313] FIG. 14I shows a significant and linear reduction of
paranoia symptoms with increasing doses of the study formula.
[0314] FIG. 14J shows a statistically significant reduction of
hostility with use of the laser homogenized study formula. Recent
research has shown a correlation with elevated homocysteine and
increased human hostility. This is one of the first interventions
to show not only a reduction in homocysteine, but also a
corresponding reduction in measured hostility.
[0315] FIG. 14K shows the dose response curve for the global
severity index, an overall measure of all the symptom and severity
scales assessed collectively. This index shows highly statistically
significant reductions of the global symptom profile at all dosage
levels, increasing at every dose, with an especially marked
relative response at the lowest dose.
[0316] Improving fundamental methyl group transfer biochemistry,
especially at the level of cell membrane fluidity and function,
neurotransmitter production and balance (particularly of
serotonin), post-transcriptional modification of proteins, DNA
synthesis and repair, endothelial vascular protection, and numerous
other facilitated pathways may be expected to have widespread
benefits on cellular metabolism and function.
[0317] The optimum use of the laser homogenized methylation formula
can be adjusted based on the response to treatment of homocysteine
levels, SAMe levels, DNA methylation assays, inflammatory markers,
or changes in clinical condition. In persons who are clinically
well, it would be advised to adjust the dosage of the formula to
sustain the homocysteine levels associated with the lowest
cardiovascular risk, at or below the cutoff value of 6.3.
EXAMPLE 9
Case Report of Improved Lupus with Laser Treated Methylation
Formula as a Model for Relief of Autoimmune Disease Pathology
[0318] Autoimmune disease is a condition in which the immune system
recognizes self-antigens as foreign and initiates an immune
inflammatory attack on self-tissues. Central to the disease process
is an information defect in the ability of the immune system to
distinguish components of host tissue from foreign or invading
antigens.
[0319] A phenomenon repeatedly observed in two of the most common
autoimmune diseases, lupus and rheumatoid arthritis, is extensive
DNA demethylation of T cell lymphocytes. Although lymphocytic DNA
demethylation could be a phenomenon secondary to the inflammatory
response, it is also possible that the DNA demethylation process
has a primary role in disease etiology through impaired regulation
of DNA control mechanisms. Recent research showing that clinical
improvement in rheumatoid arthritis with methotrexate treatment is
associated with increased DNA methylation supports the hypothesis
of DNA demethylation as an etiologic factor in disease.
[0320] If the tissues of the body suffer a generalized 40% DNA
demethylation, degenerative death usually occurs. In rheumatoid
arthritis and lupus, up to 50% DNA demethylation of T cell
lymphocytes is observed, suggesting an accelerated degenerative
process selective to these immune regulatory and effector cells.
Aggressive treatment to remethylate DNA may do more than merely
suppress the inflammatory response secondary to immune
dysregulation, but may help to relieve and correct the underlying
information defect at the DNA level.
[0321] The exemplary patient, a 59-year-old white female, had
suffered with relapsing lupus for several years. At the time of
entry into the methylation formula studies of EXAMPLE 6, she had
experienced a relapse of severe disease for several months.
[0322] Her disease was characterized by exquisitely tender
blistering and ulcerating lesions on her hands and feet that made
it difficult to walk or open a cabinet door without severe pain.
Her skin was pallid, she was extremely fatigued with a chronic low
energy state, and had suffered extensive hair loss. Her
sedimentation rate, a marker for systemic inflammation, was highly
elevated at 99, whereas a normal level would be 0-30. She was
treated only with Plaquenil that did little to relieve her
symptoms. She declined the use of corticosteroids due to severe
treatment side effects during a prior relapse.
[0323] The subject was randomized to the placebo control group and
for 3 months had no improvement in condition. In the second phase
of the study, she was placed on a high dose of the methylation
formula of 6 grams of laser treated betaine plus cofactors daily.
Within 1-2 weeks of starting the active formula she began to notice
clinical improvement.
[0324] At the conclusion of the 3 months of the second phase, she
reported clearance of 90% of the lesions on her hands and feet with
a marked improvement of her malaise and fatigue. At this time her
sedimentation rate had dropped to 58. She remained on the same dose
of Plaquenil for the course of the study, her only change in
treatment being the addition of the active methylation formula in
the second 3-month phase of the study.
[0325] The subject continued on a lower dose of the laser treated
methylation formula for 5 more months, reduced to 1-2 grams of the
laser treated betaine plus cofactors. During this period she had
complete remission of all clinical symptoms. At the end of fifth
month of lower dose treatment, her sedimentation rate had dropped
to the very low normal value of 1, the lowest level ever recorded
for her.
[0326] Other clinical markers indicated significant improvement in
her underlying lupus. Pretreatment C-reactive protein was elevated
at 3.4 (normal 0-1.5) that decreased to normal at 1.1 at the end of
the treatment course.
[0327] Pretreatment complement levels of C3 and C4 were reduced to
84 (normal 94-192) and 11.5 (13.0-52.0), respectively, indicating
an active inflammatory process consuming complement factors. By the
third month of the high dose methylation formula, her levels had
returned to normal with a C3 and C4 of 98 and 13.2, respectively,
demonstrating a reduction in the autoimmune inflammation.
Anti-double stranded DNA antibodies are a specific marker for SLE.
Pretreatment titers elevated at 1:40 dilution (normal <1:10
dilution) were reduced essentially to normal at 1:10 dilution by
the end of the first month of use of the high dose formula.
[0328] She had complete clearance of the lesions on her hands and
feet and complete resolution of all other clinical features. Her
energy returned to a high level for the first time in several
years. Her pallor resolved and her hair regrew luxuriously.
[0329] She discontinued the use of the methylation formula at this
time and felt clinically well for 7 months. However, a repeat
sedimentation rate after 7 months off the formula showed an
increase of her level to 103. Within a few weeks of the noted
sedimentation rate elevation she began to have aching in her
fingers and the early onset of skin lesions in her hands. Within a
few weeks of resuming the high dose laser treated methylation
formula, her early recurrence symptoms resolved fully. With
continued use of the formulation her sedimentation rate again
returned to normal.
[0330] Her experience is consistent with numerous studies in
methylation chemistry that indicate a prompt tendency of the
biochemical markers to return to pretreatment levels after stopping
delivery of methylation enhancing factors. In general, long-term
consistent use is recommended for the best results.
[0331] Systemic lupus erythematosus is a prime example of a wide
range of autoimmune conditions with immunologic attack on
self-antigens. Aggressive remethylation with the laser treated
methylation formula is an appropriate treatment to consider for any
form of autoimmune disease, especially those known to be
characterized by reduced lymphocyte methylation, such as rheumatoid
arthritis and lupus. Such treatment has a very high therapeutic
index and may help remedy underlying DNA regulatory defects rather
than merely suppress symptoms due to the inflammatory process.
EXAMPLE 10
Potential Prion Inactivation and other Protein Reshaping Effects
Using Laser Acoustic Resonance
[0332] Prions are a unique class of proteinaceous infectious agents
particularly noted for causing slowly progressive neurodegenerative
disease. Prions are distinct from other classes of transmissible
agents in that they do not require DNA or RNA effector mechanisms
to cause pathological changes. Prions have been observed to pass
through microfilters too small in pore size to admit even the
smallest viruses or bacterial agents. They are also resistant to
sterilization at temperatures usually effective for clearing
microbial pathogens. With a deceptive biologic strategy independent
of nucleic acids, no treatment has yet been developed for these
devastating disease conditions.
[0333] The human syndrome most closely associated with prion
transmission is Creutzfeld-Jacob disease. Although rare,
Creutzfeld-Jacob disease is the most common spongiform
encephalopathy in humans, characterized by typical vacuolar changes
in brain tissue and astrocyte proliferation. Disease transmission
has been reported through injection of growth hormone prepared from
pooled human pituitary extracts, corneal transplantation, and
implantation of contaminated stereotactic electrodes to treat
epilepsy. Incubation periods have typically ranged from 15-31
months. The average duration of illness is approximately 6 months
to demise from progressive dementia, myoclonus, and motor
dysfunction.
[0334] As defined by Prusiner, prions are "small proteinaceous
infectious particles which resist inactivation by procedures that
modify nucleic acids" . Perhaps the most extraordinary feature of
this class of diseases is that the pathological protein appears to
be encoded by the host cell genome. The gene for the human prion
protein (PrP) has been mapped to chromosome 20. The normal gene
product, PrP.sup.c, appears to have the same amino acid sequence as
the pathological protein, PrP.sup.sc. Differences in the
3-dimensional folding convert the normal variant of the membrane
sialoglycoprotein to an abnormal isoform that aggregates into nodes
of pathological proteins visible with electron microscopy. Prion
aggregates may be responsible for the amyloid plaques and fibrils
seen in brain tissue in this group of diseases.
[0335] Chaperonins are a class of effector proteins that help to
shape peptide sequences into their biologically active
3-dimensional conformation. A dysfunction of chaperonin activity in
the prion diseases may be responsible for the abnormal folding and
aggregation of the otherwise normal peptide sequences.
[0336] Applying the `bang and ring` of sparse constructive nodes,
while orienting and shaping molecules with their relatively large
EM field waves compared to molecular size may provide
chaperonin-like effects. The sparse constructive node and EM field
patterns may help guide the 3-dimensional folding of peptide
sequences, mimicking the process of shaping in the chaperonin
pocket. The ability of sparse constructive node irradiation to
modify the shape of individual amino acids may thus be potentially
extended to chains of amino acids to favor desirable polypeptide
folding patterns.
[0337] To determine whether laser acoustic resonance may be able to
favor the normal as opposed to the pathological conformation of
PrP, we would do acoustic spectrum analysis of both forms. If the
acoustic spectra of the preferred to non-preferred form are
different, then in principle there would be the possibility of
favoring the formation of the desired form by applying sparse
constructive node laser irradiation modulated with the spectral
frequencies of the preferred form. Even then, it is possible that
the total energy required to switch from one form to the other may
be well above that achievable by resonance before other damping
losses dominate.
[0338] A cost effective method for determining acoustic resonance
spectra for application to complex molecules would use
sonoluminescence with supersaturated carbon dioxide bubble
nucleation to create a single point acoustic emitter in a solution.
The main example of sonoluminescence is the use of ultrasound to
compress small bubbles to infinitesimal size, resulting in a sudden
dramatic increase in temperatures sometimes by many thousands of
degrees in a tiny space.
[0339] In some systems this temperature spike (often with light)
can be used to drive chemical reactions directly; however, in this
context the bubble nucleation is used to create a single point
acoustic emitter that can be used to measure acoustic absorption
spectra of molecules in solution.
[0340] For example if carbon dioxide is dissolved in water using a
`soda stream`, and you place in the water a wide band hydrophone
made of PVDF (polyvinyledene fluoride), the acoustic spectrum of
pure water will be measured. Dissolving a test molecule of choice
in the water will change the absorption spectrum. The differential
absorption spectrum will show the frequencies of the main modes of
oscillation of the molecules tested. In addition, the narrowness of
the absorption lines will show the homogeneity of the compound in
solution.
[0341] In the general case of use, we would choose the largest
absorption line and tune the laser modulation to that frequency.
Such primary resonant frequencies can be delivered highly
efficiently to the molecules. This will provide an additional level
of control of molecular shapes over and above the general "bang and
ring" effect of using the dirac-like acoustic spikes of photon
absorption and re-emission.
[0342] In a simple lab experiment of homogenization, a dry powder
(or solution) of a compound could be divided into two batches. One
batch would be irradiated with a modulation frequency chosen from a
previous CO.sub.2 nucleation absorption spectrum analysis. This
powder is then added to a CO.sub.2 solution and the control powder
is added to a different CO.sub.2 solution. The absorption spectrum
of each of the two solutions is then to be measured. To the degree
homogenization has occurred, the irradiated sample will show a
narrower absorption spectrum than the control sample.
[0343] A simple compound like betaine will show a relatively small
number of absorption lines, while a compound like fibronectin or
glucoamylase will have hundreds. Each line chosen for irradiation
is expected to narrow after irradiation.
[0344] For the prion example, the normal and pathological prion
configurations would be dissolved in separate CO.sub.2 solutions
and the absorption spectrum of these solutions would be measured.
Absorption peaks seen in the normal versus pathological prions
could then be replayed into the pathological prion solution to
favor the resonances and configurations of the normal form. The
frequencies would be applied as modulations of a beam of sparse
constructive nodes of laser acoustic resonance.
[0345] Conversely, absorption peaks of pathological prions could be
replayed into the solution of the pathological forms to heat the
local resonances sufficiently to disrupt the overall structure.
Such intense local heating may simply denature the 3-dimensional
conformation or, if targeted to susceptible bonds, may cause
disruption of covalent bonds. The primary laser wavelength, if
intended for resonant denaturation, would be shifted toward the
violet-ultraviolet end of the electromagnetic spectrum, whereas the
infrared-red end of the spectrum is more suited to the
reconfiguration strategy.
[0346] The ability to convert pathological prions to a normal
configuration or to denature the structure would have a potential
role as a rapid low energy sterilization procedure for tissues or
instruments for transplantation. Because of the increased depth of
penetration of sparse constructive nodes through tissue compared to
ordinary conventional laser EM irradiation, this energy could also
be applied as a direct in vivo treatment. The clearance of
pathological prions from clinical samples, tissues, and instruments
for greater lab and clinical safety could also be accomplished.
[0347] If further developed, there are also potential veterinary
and animal husbandry applications. Prion disease in animals causing
spongiform encephalopathy is especially well recognized in sheep
and goats as scrapie and in cows as mad cow disease. Applications
could include treatment or prevention of this otherwise untreatable
disease or to sterilize potentially infected or infectious tissues
or contaminated instruments.
[0348] From a general applications standpoint, the process of using
sonoluminescent CO.sub.2 nucleation absorption spectral analysis
can provide resonant modulation frequencies to further enhance the
intended homogenization effects. Other spectrographic methods may
be used, but the advantage of this suggested preferred mode is its
ease and cost effectiveness.
[0349] Modulating sparse constructive nodes of laser irradiation
with resonant spectral peaks may cause further specific structural
changes over and above the general homogenization and flattening
effects. This may be especially important for enhancing desirable
effects of pharmaceuticals, especially agents targeted to receptor
effects. This may further improve receptor shape fit, increase
desirable therapeutic action at a given dose, and reduce
non-specific dose related and dose-independent adverse effects.
[0350] Such further specific targeting of a wide range of
nutraceutical and pharmaceutical effects would require further in
vitro, animal and clinical testing as appropriate to the desired
effect. A prime candidate for such effects would be modifying the
action of agents that function in the receptor pathways of the
phenolic neurotransmitters dopamine, epinephrine, and
norepinephrine. The ability to modify the backbone twist and
overall flattening and shape of molecules with phenol (hydroxylated
benzene) rings may enhance desired function and reduce the often
significant side effects.
[0351] Virtually all receptor-ligand and enzyme-substrate mediated
systems are highly shape dependent. The ability to modify and
homogenize ligand or substrate shape will concentrate the effect of
the shape modification either to increase or decrease reactivity of
the system as desired. Thus, a wide range of nutrients,
pharmaceuticals, and other bioactive agents may be modified to
enhance the intended biological or physiological effects.
[0352] Specific resonances using higher frequency blue-violet to
ultraviolet primary laser systems may be found that denature
specific pathological agents. Using modulation of sparse
constructive laser irradiation may potentially inactivate a wide
range of pathogens.
[0353] Specific resonance systems may greatly raise the temperature
of selected chemical bonds, making them more reactive. Some
covalent bonds may be susceptible to breakage, resulting in a
reactive fragment of specific shape and structure. This may be used
to create reaction sequences that would otherwise be
thermodynamically unfavorable to increase yield of structures
difficult to produce or to create novel beneficial compounds.
[0354] Potential development of the use of sparse constructive node
resonant laser irradiation thus includes the possibility of
reshaping prions to render them no longer pathogenic; enhancing or
even mimicking intrinsic enzyme, receptor, and signal transduction
systems; and modifying components of a wide range of infectious
agents or toxins to reduce their pathogenicity or toxicity.
EXAMPLE 11
Clinical Effects of Laser Treated L-Arginine to Reduce Blood
Pressure and Cholesterol Levels
[0355] Subjects in the double-blind study of EXAMPLE 6, upon
completion of the first phase of the study, were invited to
participate in the Western IRB approved second phase of the study.
Subjects that had been in the placebo group were invited to enter a
dose-response study of a laser treated L-arginine formula. Subjects
that had been in the active treatment group were invited to
continue with the high dose methylation formula while adding a
dose-response study of a laser treated L-arginine formula.
[0356] Each size 00 capsule of the laser treated L-arginine formula
was compounded to provide 500 mg of homogenized L-arginine. In
addition, each capsule contained the following composition of laser
treated ingredients: inositol hexanicotinate 25 mg (80% molar ratio
of niacin, or 20 mg of niacin), pyridoxine (vitamin B6) 2.5 mg,
magnesium amino acid chelate 18.42% 54.3 mg (providing 10 mg of
magnesium), zinc amino acid chelate 20.17% 4.1 mg (providing 0.833
mg of zinc), and selenomethionine 0.5% 2.33 mg (providing 11.67
micrograms of selenium chelated to methionine), and calcium
pantothenate (vitamin B5) 11 mg.
[0357] Laser homogenization of the arginine plus supportive
vitamins and mineral cofactors was performed as follows. Dry powder
of this formula weighing 2 kg per clear plastic container was
placed on a gyroscopic device rotating the product through three
axes. Two diode lasers of 670 nm with primary powers of 4.6 mW and
3.0 mW were conjugated into sparse constructive node laser
irradiation at 2.3 mW and 1.5 mW, respectively. The beams were also
further amplitude modulated at 10 MHz electronically. Average laser
dose was 0.044 kg/min/mW for a treatment duration of 12 minutes per
container.
[0358] Subjects that had been in the treatment group in the first
phase of the study were continued at the dose of 6 grams of laser
treated betaine plus laser homogenized cofactors, the highest daily
dose of the treated methylation formula from the first phase. For
the first month, the subjects took 9 capsules daily of the laser
treated arginine formula, providing 4.5 grams of activated arginine
plus a proportionate ratio of treated cofactors. For the second
month, the daily dose was increased to 18 capsules, or a base of 9
grams of laser treated arginine. During the third month, the daily
dose was increased to 27 capsules daily, or 13.5 grams, as
tolerated by the GI tract.
[0359] The placebo group from the first phase of the study was
switched to taking the laser treated arginine formula only. For
months 1, 2 and 3 of the second phase, the arginine base doses were
4.5grams, 9 grams, and 13.5 grams daily, respectively, with the
same proportion of laser treated cofactors as the comparison group
also taking the treated methylation formula.
[0360] Three subjects declined taking the activated arginine
complex either because of the known tendency of arginine to
predispose to recurrences of Herpes simplex viral outbreaks, or due
to research suggesting it be used with caution in persons with
autoimmune disease. One of these participants was the subject with
active lupus whose course is described in EXAMPLE 7. All subjects
in this group were given the highest dose of the laser treated
methylation formula studied, 6 grams of treated betaine plus
proportionate cofactors.
[0361] Subjects continued to complete daily questionnaires as
described in EXAMPLE 6, in. particular to document daily capsule
ingestion of the respective capsules, as well as for reporting
subjective benefits or side effects. Weekly SCL-90 questionnaires
were also done. At the end of the study subjects completed exit
questionnaires and study summaries.
[0362] At baseline and monthly, patients had the following blood
work drawn and analyzed: triglycerides and total, LDL, and HDL
cholesterol levels, and red cells, white cells, and plasma for
advanced studies at an independent research lab. In addition,
baseline and monthly, the subjects had their blood pressure
measured at the time of the blood draws. An approved informed
consent form was provided by Western IRB for the second phase of
the study. After review and signature of these informed consent
forms, the subjects began the second three-month phase of the
study. Over the course of the second phase, subjects taking the
laser homogenized L-arginine formula showed statistically
significant reductions in total cholesterol, LDL cholesterol, and
the ratio of total to HDL cholesterol, with significant reduction
in these measures requiring 2-3 months of use. In addition systolic
and diastolic blood pressure also showed statistically significant
reduction, again requiring 2-3 months of use to achieve significant
levels. Triglyceride levels also dropped from an average of 140 to
118, but this reduction did not achieve statistical
significance.
[0363] In contrast to the first phase of the study in which the
recommended intake of capsules was consistently ingested, intake
was quite variable in the second phase of the study. Instead of a
dose response curve, the results are more indicative of cumulative
effects over time of bulk dosage intake for the entire group.
[0364] Based on summation of capsule intake from the daily reports,
the range of ingestion of the laser treated L-arginine formula for
the first month was 105-410 capsules. The average intake was 210
capsules, or approximately 7.0 capsules per day. During the second
month, the range of ingestion was 126-513 capsules, with an average
intake of 386 capsules, or approximately 12.9 capsules per day. For
the third month, the range of ingestion was 27-756 capsules, with
an average intake of 436 capsules, or approximately 14.5 capsules
per day. The average daily intake of the laser homogenized
L-arginine for the first, second, and third months was thus 3.5
grams, 6.5 grams, and 7.3 grams, respectively.
[0365] A one-way repeated measures analysis of variance was used to
analyze the effect of the laser homogenized L-arginine formula on
total cholesterol levels over time, with the analysis limited to
the 29 subjects whose baseline total cholesterol exceeded 180. The
multivariate tests indicate a significant cholesterol reduction
effect, Wilks' Lambda=0.77, F (2,26)=3.813, p=0.035. This effect
required 2 months to be evident.
[0366] From baseline to the end of the second month, 18 of 29, or
62% of treated subjects showed a reduction in total cholesterol. Of
those who showed a reduced total cholesterol, 61% had a reduction
of 10% or more, and 18% showed a reduction of 20% or more. The
greatest individual total cholesterol reduction of 32% was from a
baseline of 213 to a treated level of 146.
[0367] A one-way repeated analysis of variance was used to test the
effect of the laser homogenized L-arginine formula on LDL
cholesterol over time. The multivariate tests indicate a
significant LDL cholesterol reduction effect, Wilk's Lambda=0.655,
F(3,20), p=0.034. Further paired t-test analysis revealed that the
most significant drop in LDL cholesterol occurred after the third
month of treatment. The average baseline level was elevated at 140
and dropped after the third month of treatment to 128, a clinically
important level of reduction.
[0368] Of 26 subjects with a baseline cholesterol over 180 , 61%
showed a reduction in LDL cholesterol after 3 months of treatment
with laser homogenized L-arginine. Of those that showed a
reduction, 75% had a lowering of 10% or more, and 25% had a
lowering of 20% or more. The greatest single reduction was 66%,
from a highly elevated level of 223 to a normal level of 75.
[0369] To assess the relative effect on HDL cholesterol, a one way
repeated measures analysis of variance was computed for the
dependent variable of the total to HDL cholesterol ratio. The
multivariate analysis of variance indicates a significant effect in
reducing this ratio over time, Wilk's Lambda=0.691, F(3,21),
p=0.048. The average baseline ratio of 4.1 decreased after three
months of treatment to 3.8, a 7% reduction, with 63% of subjects
showing a reduction in this ratio.
[0370] A one-way repeated measures analysis of variance was
computed for the dependent variable systolic blood pressure over
time with the independent variable being the treatment formula. A
statistically significant reduction in systolic blood pressure was
found over time, Wilks' Lambda=0.715, F(3,26)=3.447, p=0.03; a
significant linear effect was also found, F(1,28)=6.522,
p=0.016.
[0371] The average systolic blood pressure of 131 for the entire
group dropped to 126 after three months of treatment with the laser
homogenized L-arginine formula, the paired t-test comparing
baseline to three months of treatment statistically significant at
p=0.004. In the subgroup of subjects with systolic hypertensive
blood pressure of 140 mmHg or higher, 9 of 10, or 90% demonstrated
a reduction in systolic blood pressure after three months of study
formula treatment, which reduction was statistically significant at
p=0.033; pretreatment values in this group ranged from 140-208 mmHg
which dropped post treatment to 123-160 mmHg. The range of
reduction of systolic blood pressure in those subjects showing a
drop was 2-48 mmHg, with an average reduction of 19.4 mmHg.
[0372] A one-way repeated measures of variance was computed on the
dependent variable of diastolic blood pressure with the independent
variable the ingestion of the laser homogenized L-arginine formula
taken over a period of three months. A univariate analysis of
variance indicated a significant reduction in diastolic blood
pressure, F(3,26)=4.014, p=0.01. A significant linear effect in the
reduction of diastolic blood pressure was observed, F(1,28)=7.236,
p=0.012. Using paired t-tests, statistically significant reductions
in diastolic blood pressure were seen from baseline to two months
of treatment, p=0.043, and from baseline to three months of
treatment, p=0.019.
[0373] Average diastolic blood pressure at baseline of 82 dropped
progressively at one, two, and three months to 81, 78, and 76,
respectively. Although only 5 subjects had diastolic hypertension
of 90 mmHg or greater, 80% showed a reduction in diastolic blood
pressure, the pretreatment range of 90-128 mmHg dropping after
three months of treatment to 60-99 mmHg. In those subjects with
diastolic hypertension showing a drop in diastolic blood pressure,
the range of reduction was 9-40 mmHg with an average reduction of
25.8 mmHg diastolic.
[0374] No subject with low normal systolic or diastolic blood
pressure had a reduction in blood pressure to hypotensive levels. A
common and potentially serious side effect of other
antihypertensive remedies, the laser homogenized formulation of
L-arginine was found to be entirely free of this problem.
[0375] At higher doses of the laser treated L-arginine, some
subjects developed gastrointestinal side effects, in particular
diarrhea. The literature indicates that up to 15 grams of untreated
L-arginine may typically be ingested daily before the development
of loose stools. Although some subjects were able to tolerate 13.5
grams of laser treated L-arginine if taken in divided doses,
occasional subjects developed loose stools on as little as 4.5
grams, suggesting generally increased potency of the L-arginine; in
all cases, reducing the intake below the individual threshold level
for GI symptoms resulted in resolution of symptoms.
[0376] In addition, male subjects reported improved rather than
impaired erectile function when taking the laser treated L-arginine
formula. In contrast to many hypertensive agents that may cause
impotence, L-arginine supplementation can often increase sexual
function, even reversing impotence in a significant fraction of men
studied. This is through the effect of L-arginine derived nitric
oxide production stimulating increased cyclic-GMP in the genital
tissues, the specific signal resulting in the vasodilation that
produces the erectile response.
[0377] The use of laser homogenized L-arginine may thus effectively
reduce total and LDL cholesterol, while improving the total to HDL
cholesterol ratio. It may also safely and effectively reduce
systolic and diastolic blood pressure. Side effects are relatively
few and minor, and usually readily reversed with dose
reduction.
[0378] Thus, the present invention is able to improve the
bioavailability of nutrients, pharmaceutical agents and other
bioactive compounds in a mammalian body by treating the compounds
with a laser to modify the compound's average structure. The
improved bioavailability may be achieved by increasing the
absorption of the compound, by decreasing inflammation or other
negative reactions to the compound, or by increasing the
availability of functional groups to be used in biological
processes within the body. Furthermore, because the treatment can
be done to the compound in either dry or solution forms, it will be
relatively easy for those of skill in the art to modify a wide
range of nutrients, pharmaceuticals and other compounds to enhance
bioavailability in humans and other mammals.
[0379] Thus there is disclosed an improved method for administering
dietary amino acids, pharmaceutical agents, and other bioactive
substances. While the present disclosure discloses a variety of
substances, those skilled in the art will appreciate numerous other
substances can be modified within the teachings of the present
invention without departing from the scope and spirit thereof. The
appended claims are intended to cover such modifications.
* * * * *