U.S. patent application number 10/347284 was filed with the patent office on 2003-09-25 for aqueous metal bicarbonate solution and method of use.
Invention is credited to Beckett, Russell John.
Application Number | 20030180386 10/347284 |
Document ID | / |
Family ID | 25645376 |
Filed Date | 2003-09-25 |
United States Patent
Application |
20030180386 |
Kind Code |
A1 |
Beckett, Russell John |
September 25, 2003 |
Aqueous metal bicarbonate solution and method of use
Abstract
An aqueous neutral to mildly alkaline metal bicarbonate solution
is disclosed. The solution comprises metal bicarbonate dissolved in
the solution, the metal bicarbonate comprising bicarbonate anions
and metal cations. In addition there is a pH adjusting agent in the
solution in an amount whereby the solution is at a neutral to
mildly alkaline pH. Also disclosed is a process of preparing an
aqueous neutral to mildly alkaline metal bicarbonate solution
comprising bicarbonate anions and metal cations. The process
comprises reacting a compound selected from the group consisting of
metal carbonate, metal carbonate hydroxide, metal oxide, metal
hydroxide and any mixture thereof with an effective concentration
of a pH adjusting agent to produce the aqueous neutral to mildly
alkaline metal bicarbonate solution, wherein the pH adjusting agent
is present in an amount whereby the solution is at a neutral to
mildly alkaline pH. Further disclosed are a method of preventing
and/or treating certain inflammatory diseases and/or degenerative
diseases in a mammal, a method of preventing and/or treating
certain viral diseases in a mammal, a method of decreasing and/or
treating senescence and/or of increasing longevity in a mammal, a
method of scavenging protons in a mammal, a method of decreasing
proton concentrations in a mammal by altering carbonic anhydrase
enzyme reactions in said mammal, a method of decreasing
inflammation and/or inflammatory conditions in a mammal and a
method of increasing motor activity and/or decreasing fatigue in a
mammal.
Inventors: |
Beckett, Russell John; (Red
Hill, AU) |
Correspondence
Address: |
JONES, TULLAR & COOPER, P.C.
P.O. BOX 2266 EADS STATION
ARLINGTON
VA
22202
|
Family ID: |
25645376 |
Appl. No.: |
10/347284 |
Filed: |
January 21, 2003 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10347284 |
Jan 21, 2003 |
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09962163 |
Sep 26, 2001 |
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6544561 |
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09962163 |
Sep 26, 2001 |
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09422645 |
Oct 22, 1999 |
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6328997 |
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09422645 |
Oct 22, 1999 |
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09041787 |
Mar 13, 1998 |
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6048553 |
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Current U.S.
Class: |
424/686 |
Current CPC
Class: |
A61P 19/10 20180101;
A61K 33/00 20130101; A61P 29/00 20180101; A61P 43/00 20180101; A61K
33/10 20130101; A61K 47/02 20130101; A61P 31/12 20180101; A61K
2300/00 20130101; A61K 33/00 20130101; A61K 33/10 20130101; A61K
2300/00 20130101; A61K 9/0019 20130101 |
Class at
Publication: |
424/686 |
International
Class: |
A61K 033/10 |
Foreign Application Data
Date |
Code |
Application Number |
Mar 17, 1997 |
AU |
PO5677 |
Nov 28, 1997 |
AU |
PP0608 |
Claims
1. An aqueous neutral to mildly alkaline metal bicarbonate
solution, comprising metal bicarbonate dissolved in the solution,
said metal bicarbonate comprising bicarbonate anions and metal
cations, and a pH adjusting agent in the solution in an amount
whereby the solution is at a neutral to mildly alkaline pH.
2. The aqueous neutral to mildly alkaline metal bicarbonate
solution of claim 1, wherein the metal bicarbonate is selected from
the group consisting of magnesium bicarbonate, sodium bicarbonate,
a mixture of sodium bicarbonate and magnesium bicarbonate,
potassium bicarbonate, a mixture of potassium bicarbonate and
magnesium bicarbonate, calcium bicarbonate, a mixture of calcium
bicarbonate and magnesium bicarbonate, lithium bicarbonate, and a
mixture of lithium bicarbonate and magnesium bicarbonate.
3. The aqueous neutral to mildly alkaline metal bicarbonate
solution of claim 1, wherein the bicarbonate anions are 150 mg to
3500 mg per litre of the solution.
4. The aqueous neutral to mildly alkaline metal bicarbonate
solution of claim 1, wherein the metal cations are 30 mg to 500 mg
per litre of the solution.
5. The aqueous neutral to mildly alkaline metal bicarbonate
solution of claim 1, wherein a stoichiometric concentration of
metal cations is in association with the bicarbonate anions.
6. The aqueous neutral to mildly alkaline metal bicarbonate
solution of claim 1, wherein the pH adjusting agent is selected
from the group consisting of carbon dioxide, hydrated carbon
dioxide, carbonic acid and any mixture thereof.
7. The aqueous neutral to mildly alkaline metal bicarbonate
solution of claim 1, wherein the aqueous metal bicarbonate solution
has a pH 7 to 8.6.
8. The aqueous metal bicarbonate solution of claim 1, wherein the
aqueous neutral to mildly alkaline metal bicarbonate solution has a
pH of 8.0 to 8.6.
9. The aqueous metal bicarbonate solution of claim 1, wherein the
aqueous neutral to mildly alkaline metal bicarbonate solution has a
temperature in the range selected from the group consisting of 0 to
25.degree. C., 0 to 20.degree. C., 0.5 to 25.degree. C., 0.5 to
20.degree. C., 0.5 to 15.degree. C., 0.5 to 10.degree. C., 0.5 to
9.degree. C., 0.5 to 8.degree. C., 0.5 to 7.degree. C., 1 to
20.degree. C., 1 to 15.degree. C., 1 to 10.degree. C., 1.5 to
20.degree. C., 1.5 to 15.degree. C., 1.5 to 10.degree. C., 2 to
20.degree. C., 2 to 15.degree. C., 2 to 10.degree. C., 3 to
20.degree. C., 3 to 15.degree. C., 4 to 20.degree. C., 4 to
15.degree. C., 4 to 10.degree. C., 5 to 20.degree. C., 5 to
15.degree. C., 6 to 20.degree. C., 6 to 15.degree. C., 6 to
10.degree. C., 7 to 20.degree. C., 7 to 15.degree. C., 7 to
10.degree. C., 8 to 20.degree. C., 8 to 15.degree. C., 8 to
10.degree. C., 9 to 20.degree. C., 9 to 15.degree. C., 9 to
10.degree. C., 10 to 15.degree. C., 0 to 15.degree. C., 0 to
10.degree. C., 3.degree. C. to 10.degree. C. and 5.degree. C. to
10.degree. C.
10. The aqueous neutral to mildly alkaline metal bicarbonate
solution of claim 1, wherein the metal bicarbonate comprises a
mixture of sodium bicarbonate and magnesium bicarbonate.
11. A solution for preventing and/or treating certain inflammatory
diseases and/or degenerative diseases and/or certain viral diseases
in a mammal, comprising the aqueous neutral to mildly alkaline
metal bicarbonate solution of claim 1 wherein the metal bicarbonate
is in an amount effective to prevent and/or treat said
diseases.
12. A solution for decreasing and/or treating senescence and/or
increasing longevity in a mammal, comprising the aqueous neutral to
mildly alkaline metal bicarbonate solution of claim 1 wherein the
metal bicarbonate is in an amount effective to decrease and/or
treat senescence and/or increase longevity.
13. A solution for scavenging protons in a mammal, comprising the
aqueous neutral to mildly alkaline metal bicarbonate solution of
claim 1 wherein the metal bicarbonate is in an amount effective to
scavenge protons.
14. A solution for decreasing proton concentrations in a mammal,
comprising the aqueous neutral to mildly alkaline metal bicarbonate
solution of claim 1 wherein the metal bicarbonate is in an amount
effective to decrease proton concentrations.
15. A solution for decreasing inflammation and inflammatory
conditions in a mammal comprising the aqueous neutral to mildly
alkaline metal bicarbonate solution of claim 1 in an amount
effective to decrease inflammation and/or inflammatory
conditions.
16. A solution for increasing motor activity and/or decrease
fatigue in a mammal, comprising the aqueous neutral to mildly
alkaline metal bicarbonate solution of claim 1 in an amount
effective to increase motor activity.
17. A process of preparing an aqueous neutral to mildly alkaline
metal bicarbonate solution comprising bicarbonate anions and metal
cations, which process comprises reacting a compound selected from
the group consisting of metal carbonate, metal carbonate hydroxide,
metal oxide, metal hydroxide and any mixture thereof with an
effective concentration of a pH adjusting agent to produce the
aqueous neutral to mildly alkaline metal bicarbonate solution,
wherein the pH adjusting agent is present in an amount whereby the
solution is at a neutral to mildly alkaline pH.
18. The process of preparing an aqueous neutral to mildly alkaline
metal bicarbonate solution of claim 17, wherein the pH adjusting
agent is selected from the group consisting of carbon dioxide,
hydrated carbon dioxide, carbonic acid and any mixture thereof.
19. The process of preparing an aqueous neutral to mildly alkaline
metal bicarbonate solution of claim 17, wherein the metal
bicarbonate is selected from the group consisting of magnesium
bicarbonate, sodium bicarbonate, a mixture of sodium bicarbonate
and magnesium bicarbonate, potassium bicarbonate, a mixture of
potassium bicarbonate and magnesium bicarbonate, calcium
bicarbonate, a mixture of calcium bicarbonate and magnesium
bicarbonate, lithium bicarbonate, and a mixture of lithium
bicarbonate and magnesium bicarbonate.
20. The process of preparing an aqueous neutral to mildly alkaline
metal bicarbonate solution of claim 17, wherein the bicarbonate
anions are 150 mg to 3500 mg per litre of aqueous neutral to mildly
alkaline metal bicarbonate solution.
21. The process of preparing an aqueous neutral to mildly alkaline
metal bicarbonate solution of claim 17, wherein the metal cations
are 30 mg to 500 mg per litre of aqueous neutral to mildly alkaline
metal bicarbonate solution
22. The process of preparing an aqueous neutral to mildly alkaline
metal bicarbonate solution of claim 17, wherein the aqueous neutral
to mildly alkaline metal bicarbonate solution has a pH of 7 to
8.6.
23. The process of preparing an aqueous neutral to mildly alkaline
metal bicarbonate solution of claim 17, wherein the aqueous metal
bicarbonate solution has a pH of 8.0 to 8.6.
24. The process of preparing an aqueous neutral to mildly alkaline
metal bicarbonate solution of claim 17, wherein the aqueous metal
bicarbonate solution has a temperature in the range selected from
the group consisting of 0 to 25.degree. C., 0 to 20.degree. C., 0.5
to 25.degree. C., 0.5 to 20.degree. C., 0.5 to 15.degree. C., 0.5
to 10.degree. C., 0.5 to 9.degree. C., 0.5 to 8.degree. C., 0.5 to
7.degree. C., 1 to 20.degree. C., 1 to 15.degree. C., 1 to
10.degree. C., 1.5 to 20.degree. C., 1.5 to 15.degree. C., 1.5 to
10.degree. C., 2 to 20.degree. C., 2 to 15.degree. C., 2 to
10.degree. C., 3 to 20.degree. C., 3 to 15.degree. C., 4 to
20.degree. C., 4 to 15.degree. C., 4 to 10.degree. C., 5 to
20.degree. C., 5 to 15.degree. C., 6 to 20.degree. C., 6 to
15.degree. C., 6 to 10.degree. C., 7 to 20.degree. C., 7 to
15.degree. C., 7 to 10.degree. C., 8 to 20.degree. C., 8 to
15.degree. C., 8 to 10.degree. C., 9 to 20.degree. C., 9 to
15.degree. C., 9 to 10.degree. C., 10 to 15.degree. C., 0 to
15.degree. C., 0 to 10.degree. C., 3.degree. C. to 10.degree. C.
and 5.degree. C. to 10.degree. C.
25. An aqueous neutral to mildly alkaline metal bicarbonate
solution whenever prepared by the process of claim 17.
26. A method of preventing and/or treating certain inflammatory
diseases and/or degenerative diseases in a mammal in need of such
prevention and/or treatment comprising administering to said mammal
an effective amount of an aqueous neutral to mildly alkaline metal
bicarbonate solution of claim 1.
27. A method of preventing and/or treating certain viral diseases
in a mammal in need of such prevention and/or treatment comprising
administering to said mammal an effective amount of an aqueous
neutral to mildly alkaline metal bicarbonate solution of claim
1.
28. A method of decreasing and/or treating senescence and/or of
increasing longevity in a mammal comprising administering to said
mammal an effective amount of an aqueous neutral to mildly alkaline
metal bicarbonate solution of claim 1.
29. A method of scavenging protons in a mammal comprising
administering to said mammal an effective amount of a proton
scavenger.
30. The method of claim 29, wherein said proton scavenger comprises
the aqueous neutral to mildly alkaline metal bicarbonate solution
of claim 1.
31. The method of claim 29, wherein said proton scavenger is a
metal bicarbonate.
32. A method of decreasing proton concentrations in a mammal by
altering carbonic anhydrase enzyme reactions in said mammal
comprising administering to said mammal an effective amount of an
aqueous neutral to mildly alkaline metal bicarbonate solution of
claim 1.
33. A method of decreasing inflammation and/or inflammatory
conditions in a mammal comprising administering to said mammal an
effective amount of an aqueous neutral to mildly alkaline metal
bicarbonate solution of claim 1.
34. A method of increasing motor activity and/or decreasing fatigue
in a mammal comprising administering to said mammal an effective
amount of an aqueous neutral to mildly alkaline metal bicarbonate
solution of claim 1.
35. The method of any one of claims 26, 27, 30, 31, 32, 33 or 34,
wherein said mammal is human and said aqueous neutral to mildly
alkaline metal bicarbonate solution is administered to said human
on an empty stomach.
36. The method of any one of claims 26, 27, 30, 31, 32, 33 or 34,
wherein said mammal is human, said aqueous neutral to mildly
alkaline metal bicarbonate solution is administered to said human
on an empty stomach and the metal bicarbonate comprises a mixture
of sodium bicarbonate and magnesium bicarbonate.
37. A combination comprising a substantially stable aqueous neutral
to mildly alkaline metal bicarbonate solution, comprising metal
bicarbonate dissolved in the solution, said metal bicarbonate
comprising bicarbonate anions and metal cations, and a pH adjusting
agent in the solution in an amount whereby the solution is at a
neutral to mildly alkaline pH, in combination with a stabilising
agent in an amount effective to maintain and stabilise the
bicarbonate anions in the neutral to mildly alkaline solution.
Description
TECHNICAL FIELD
[0001] This invention relates to an aqueous metal bicarbonate
solution, a process of preparing the aqueous metal bicarbonate
solution and a method of preventing and treating certain
inflammatory diseases, degenerative diseases and viral diseases in
mammals. Generally the certain inflammatory diseases, degenerative
diseases and viral diseases in mammals are those that require
extracellular or intracellular acidic conditions or extracellular
or intracellular proton concentrations at some point in disease
process or disease pathogenesis.
[0002] Typically the certain inflammatory diseases, degenerative
diseases and viral diseases in mammals are those that require the
activities of carbonic anhydrase enzymes and/or the activities of
acid (aspartic) protease enzymes and/or the activities of endosomal
or lysosomal acid-requiring-enzymes and/or the activities of V-type
ATPase proton pumps at some point in disease process or disease
pathogenesis. Typically the certain inflammatory diseases,
degenerative diseases and viral diseases in mammals are represented
by the diseases of arthritis and influenza.
[0003] This invention relates to a method of using an aqueous metal
bicarbonate solution to decrease senescence and to increase
longevity in mammals. Generally senescence is decreased and
longevity is increased in mammals by improving the buffering
capacity of the extracellular and intracellular fluids of the body.
Generally senescence is decreased and longevity is increased in
mammals by the improved buffering capacity causing a decrease in
proton concentrations in the extracellular and intracellular fluids
of the body. Typically senescence is decreased and longevity is
increased in mammals by improving the buffering capacity of the
extracellular and intracellular bicarbonate buffers. Typically
senescence is decreased and longevity is increased in mammals by
the improved extracellular and intracellular bicarbonate buffers
causing a decrease in proton concentrations.
BACKGROUND ART
[0004] Certain inflammatory diseases, degenerative diseases and
viral diseases are major causes of morbidity and mortality in
mammals. Typically these diseases are represented by the diseases
of arthritis and influenza.
[0005] Arthritis is any inflammatory condition of the joints,
characterised by pain and swelling. Osteoarthritis is the most
common form of arthritis in which one or many joints undergo
degenerative changes. Treatment includes rest of the involved
joints, heat, and antiinflammatory drugs. Intraarticular injections
of corticosteroids may give relief. Surgical treatment is sometimes
necessary and may reduce pain and greatly improve the function of
the joint. However these treatments, apart from surgical treatment,
only provide temporary relief and some may have severe side
reactions
[0006] Influenza is a highly contagious infection of the
respiratory tract caused by a myxovirus and transmitted by airborne
droplet infection. It occurs in isolated cases, epidemics and
pandemics. Treatment is symptomatic and usually involves bed rest,
antipyretics such as aspirin and drinking of fluids. New strains of
the virus emerge at regular intervals so it is difficult to take
preventative measures to avoid the infection. There is a need for a
method to prevent and to treat certain inflammatory diseases,
degenerative diseases and viral diseases in mammals. There is a
need for a method to prevent and to treat arthritis and influenza
in mammals.
[0007] Senescence in mammals is characterised by progressive
oxidations of the structural and functional molecules that
constitute body cells and tissues. Oxidations of the structural and
functional molecules in body cells and tissues are increased in
rate by acidic conditions. Oxidations of structural and functional
molecules are increased in rate by the presence of excess proton
concentrations. There is a need for a method to prevent and treat
excess proton concentrations in body cells so that oxidations of
structural and functional molecules are decreased in rate. There is
a need for a method to decrease and treat senescence in
mammals.
OBJECTS OF INVENTION
[0008] It is an object of this invention to provide an aqueous
metal bicarbonate solution to prevent and to treat certain
inflammatory diseases, degenerative diseases and viral diseases in
mammals. It is a further object of this invention to provide a
process of preparing the aqueous metal bicarbonate solution. It is
also an object of this invention to provide methods for the
prevention and treatment of certain inflammatory diseases,
degenerative diseases and viral diseases in mammals using the
aqueous metal bicarbonate solution. Generally the certain
inflammatory diseases, degenerative diseases and viral diseases in
mammals are those that require extracellular or intracellular
acidic conditions or extracellular or intracellular proton
concentrations at some point in disease process or disease
pathogenesis. Typically the certain inflammatory diseases,
degenerative diseases and viral diseases in mammals are those that
require the activities of carbonic anhydrase enzymes and/or the
activities of acid (aspartic) protease enzymes and/or the
activities of endosomal or lysosomal acid-requiring-enzymes and/or
the activities of V-type ATPase proton pumps at some point in
disease process or disease pathogenesis. Typically the certain
inflammatory diseases, degenerative diseases and viral diseases in
mammals are represented by the diseases of arthritis and
influenza.
[0009] It is an object of tins invention to provide an aqueous
metal bicarbonate solution to decrease senescence and to treat
senescence and to increase longevity in manuals. It is a further
object of this invention to provide a process of preparing the
aqueous metal bicarbonate solution. It is also an object of this
invention to provide methods for the decrease of senescence and the
treatment of senescence and the increase in longevity in mammals
using the aqueous metal bicarbonate solution. Generally senescence
is decreased and longevity is increased in mammals by improving the
buffering capacity of the extracellular and intracellular fluids of
the body. Generally senescence is decreased and longevity is
increased in mammals by the improved buffering capacity causing a
decrease in proton concentrations in the extracellular and
intracellular fluids of the body. Typically senescence is decreased
and longevity is increased in mammals by improving the buffering
capacity of the extracellular and intracellular bicarbonate
buffers. Typically senescence is decreased and longevity is
increased in mammals by the improved extracellular and
intracellular bicarbonate buffers causing a decrease in proton
concentrations.
DISCLOSURE OF INVENTION
[0010] According to a first embodiment of the present invention
there is provided an aqueous metal bicarbonate solution comprising
a stoichiometric concentration of bicarbonate anions and a
corresponding substantially stoichiometric concentration of metal
cations in association with the bicarbonate anions, the metal
bicarbonate being present in a therapeutically effective amount and
an acceptable carbon dioxide-containing-aqueous diluent to maintain
the metal bicarbonate in the aqueous diluent.
[0011] Typically the solution is acceptable for oral
administration.
[0012] In one embodiment there is provided a combination comprising
the solution of the first embodiment in combination with a
stabilising agent in an amount effective to maintain and stabilise
the bicarbonate anions in the neutral to mildly alkaline solution.
Generally the combination is kept in a sealed or closed container
at 0.8 to 5 atmospheres, more typically 1 atmosphere at
0-25.degree. C., more typically 0.1-10.degree. C. In one particular
embodiment the stabilising agent may be present in the solution in
an amount effective to maintain and stabilise the bicarbonate
anions in the neutral to mildly alkaline solution. In another
particular embodiment the stabilising agent may consist of or
comprise a gas above the solution in an amount effective to
maintain and stabilise the bicarbonate anions in the neutral to
mildly alkaline solution. In a further particular embodiment the
stabilising agent may be present in the solution and also may
consist of or comprise a gas above the solution, the total amount
of stabilising agent in the solution and in the gas above the
solution being in an amount effective to maintain and stabilise the
bicarbonate anions in the neutral to mildly alkaline solution. The
stabilising agent which consists of a gas above the solution may be
carbon dioxide. The stabilising agent which comprises a gas above
the solution may be carbon dioxide in an an inert gas such as
nitrogen, air, oxygen, argon and/or helium, for example. The
stabilising agent in the solution may be carbon dioxide dissolved
in the solution, hydrated carbon dioxide, carbonic acid, and/or
other suitable source of carbon dioxide.
[0013] According to a second embodiment of the present invention
there is provided a process of preparing an aqueous metal
bicarbonate solution comprising a stoichiometric concentration of
bicarbonate anions and a corresponding substantially stoichiometric
concentration of metal cations in association with the bicarbonate
anions, which process comprises reacting a concentration of a metal
carbonate or metal carbonate hydroxide or metal oxide or metal
hydroxide with a concentration of carbonic acid or hydrated carbon
dioxide to produce the metal bicarbonate aqueous solution, wherein
said metal bicarbonate being present in a therapeutically effective
amount.
[0014] Typically the aqueous metal bicarbonate solution has a
neutral to mildly alkaline pH. Typically the pH is in the range 7
to 9. Typically the temperature of the aqueous metal bicarbonate
solution is maintained at a level to maintain the metal bicarbonate
in the aqueous diluent.
[0015] According to a third embodiment of the present invention
there is provided an aqueous metal bicarbonate solution whenever
prepared by the process of the second embodiment.
[0016] According to a fourth embodiment of the present invention
there is provided a method of preventing and treating certain
inflammatory diseases and degenerative diseases in a mammal in need
of such prevention or treatment comprising administering to said
mammal an effective at amount of an aqueous metal bicarbonate
solution of the first or third embodiment or a metal
bicarbonate.
[0017] Generally the certain inflammatory diseases and degenerative
diseases in a mammal are those that require extracellular or
intracellular acidic conditions or extracellular or intracellular
proton concentrations at some point in disease process or disease
pathogenesis.
[0018] Typically the certain inflammatory diseases and degenerative
diseases in a mammal are those that require the activities of
carbonic anhydrase enzymes and/or the activities of acid (aspartic)
protease enzymes and/or the activities of endosomal or lysosomal
acid-requiring-enzymes and/or the activities of V-type ATPase
proton pumps at some point in disease process or diseases
pathogenesis.
[0019] Typically the certain inflammatory diseases or degenerative
diseases may present as arthritis. Typically the arthritis may
present as osteoarthritis.
[0020] According to a fifth embodiment of the present invention
there is provided a method of preventing and treating certain viral
diseases in a mammal in need of such prevention or treatment
comprising administering to said mammal an effective amount of an
aqueous metal bicarbonate solution of the first or third embodiment
or a metal bicarbonate.
[0021] Typically the certain viral diseases require intracellular
acidic conditions or intracellular proton concentrations for either
removal of viral protein coats or assembly of viral protein coats.
Typically the viral diseases may present as influenza.
[0022] According to a sixth embodiment of the present invention
there is provided a method of decreasing and treating senescence
and of increasing longevity in a mammal comprising administering to
said mammal an effective amount of an aqueous metal bicarbonate
solution of the first or third embodiment or a metal
bicarbonate.
[0023] Typically senescence is decreased and longevity is increased
by maintaining or increasing normal extracellular and/or
intracellular alkaline conditions. Typically senescence is
decreased and longevity is increased by improving the buffering
capacity of the extracellular and intracellular fluids of the body
Typically longevity is increased by maintaining or increasing
normal mitochondrial alkaline conditions. Typically longevity is
increased by decreasing extracellular and intracellular acidic
conditions or by decreasing extracellular and intracellular proton
concentrations.
[0024] Typically senescence is decreased and longevity is increased
in mammals by improving the buffering capacity of the extracellular
and intracellular bicarbonate buffers. Typically senescence is
decreased and longevity is increased in mammals by the improved
extracellular and intracellular bicarbonate buffers causing a
decrease in proton concentrations. Typically senescence is
decreased and longevity is increased by preventing or treating
certain inflammatory diseases, degenerative diseases and viral
diseases in mammals. Typically longevity is increased by decreasing
the morbidity and mortality associated with these diseases.
[0025] According to a seventh embodiment of the present invention
there is provided a method of scavenging protons in a mammal
comprising administering to said mammal an effective amount of a
proton scavenger.
[0026] Typically the proton scavenger comprises a metal
bicarbonate. Typically the metal bicarbonate is in the form of the
aqueous metal bicarbonate solution of the first or third
embodiment.
[0027] According to an eighth embodiment of the present invention
there is provided a method of decreasing proton concentrations in a
mammal by altering carbonic anhydrase enzyme reactions in said
mammal comprising administering to said mammal an effective amount
of an aqueous metal bicarbonate solution of the first or third
embodiment or a metal bicarbonate.
[0028] According to a ninth embodiment of the present invention
there is provided a method of decreasing inflammation and
inflammatory conditions in a mammal comprising administering to
said mammal an effective amount of an aqueous metal bicarbonate
solution of the first or third embodiment or a metal
bicarbonate.
[0029] Generally inflammation and inflammatory conditions are
decreased by decreasing the extracellular and intracellular acidic
conditions that are required for inflammatory processes. Generally
inflammation and inflammatory conditions are decreased by
decreasing the extracellular and intracellular proton
concentrations that are required for inflammatory processes.
Typically inflammation is decreased by altering carbonic anhydrase
enzyme reactions and/or decreasing the activities of acid
(aspartic) protease enzymes and/or decreasing the activities of
endosomal or lysosomal acid-requiring-enzymes and/or decreasing the
activities of V-type ATPase proton pumps.
[0030] According to a tenth embodiment of the present invention
there is provided a method of increasing motor activity in a mammal
comprising administering to said mammal an effective amount of an
aqueous metal bicarbonate solution of the first or third embodiment
or a metal bicarbonate.
[0031] Typically motor activity is increased by decreasing
extracellular and intracellular acidic conditions or by decreasing
extracellular and intracellular proton concentrations. Typically
motor activity is increased by improving the buffering capacity of
extracellular and intracellular fluids. Typically motor activity is
increased by improving the buffering capacity of the extracellular
and intracellular bicarbonate buffers. Typically motor activity is
increased by increasing extracellular and intracellular alkaline
conditions.
[0032] Typically motor activity is increased by scavenging protons
produced by ATP hydrolysis, lactic acid production, lipid
metabolism and other metabolic processes.
[0033] According to an eleventh embodiment of the present invention
there is provided an aqueous neutral to mildly alkaline metal
bicarbonate solution, comprising metal bicarbonate dissolved in the
solution, said metal bicarbonate comprising bicarbonate anions and
metal cations, and a pH adjusting agent in the solution in an
amount whereby the solution is at a neutral to mildly alkaline
pH.
[0034] Typically a corresponding substantially stoichiometric
concentration of metal cations are in association with the
bicarbonate anions. Typically the solution is acceptable for oral
administration.
[0035] In one embodiment there is provided a combination comprising
a substantially stable aqueous neutral to mildly alkaline metal
bicarbonate solution, comprising metal bicarbonate dissolved in the
solution, said metal bicarbonate comprising bicarbonate anions and
metal cations, and a pH adjusting agent in the solution in an
amount whereby the solution is at a neutral to mildly alkaline pH,
in combination with a stabilising agent in an amount effective to
maintain and stabilise the bicarbonate anions in the neutral to
mildly alkaline solution. In another embodiment there is provided a
combination comprising a substantially stable aqueous neutral to
mildly alkaline metal bicarbonate solution, comprising metal
bicarbonate dissolved in the solution, said metal bicarbonate
comprising bicarbonate anions and metal cations, in combination
with a stabilising agent in an amount effective to maintain and
stabilise the bicarbonate anions in the solution whereby the
solution is at a neutral to mildly alkaline pH.
[0036] The pH adjusting agent and the stabilising agent may be the
same or different. Generally the combination is kept in a sealed or
closed container at 0.8 to 5 atmospheres, more typically 1
atmosphere at 0-25.degree. C., more typically 0.1-10.degree. C.
[0037] In one particular embodiment the stabilising agent may be
present in the solution in an amount effective to maintain and
stabilise the bicarbonate anions in the neutral to mildly alkaline
solution. In another particular embodiment the stabilising agent
may consist of or comprise a gas above the solution in an amount
effective to maintain and stabilise the bicarbonate anions in the
neutral to mildly alkaline solution. In a further particular
embodiment the stabilising agent may be present in the solution and
may consist of or comprise a gas above the solution, the total
amount of stabilising agent in the solution and in the gas above
the solution being in an amount effective to maintain and stabilise
the bicarbonate anions in the neutral to mildly alkaline solution.
The stabilising agent which consists of a gas above the solution
may be carbon dioxide. The stabilising agent which comprises a gas
above the solution may be carbon dioxide in an an inert gas such as
nitrogen, air, oxygen, argon and/or helium, for example. The
stabilising agent in the solution may be carbon dioxide dissolved
in the solution, hydrated carbon dioxide, carbonic acid, and/or
other suitable source of carbon dioxide.
[0038] According to a twelfth embodiment of the present invention
there is provided a solution for preventing and/or treating certain
inflammatory diseases and/or degenerative diseases and/or certain
viral diseases in a mammal, comprising the aqueous neutral to
mildly alkaline metal bicarbonate solution of the eleventh
embodiment whereby the metal bicarbonate is present in an amount
effective to prevent and/or treat said diseases.
[0039] According to a thirteenth embodiment of the present
invention there is provided a solution for decreasing and/or
treating senescence and/or increasing longevity in a mammal,
comprising the aqueous neutral to mildly alkaline metal bicarbonate
solution of the eleventh embodiment whereby the metal bicarbonate
is present in an amount effective to decrease and/or treat
senescence and/or increase longevity.
[0040] According to a fourteenth embodiment of the present
invention there is provided a solution for scavenging protons in a
mammal, comprising the aqueous neutral to mildly alkaline metal
bicarbonate solution of the eleventh embodiment whereby the metal
bicarbonate is present in an amount effective to scavenge
protons.
[0041] According to a fifteenth embodiment of the present invention
there is provided a solution for decreasing proton concentrations
in a mammal, comprising the aqueous neutral to mildly alkaline
metal bicarbonate solution of the eleventh embodiment whereby the
metal bicarbonate is present in an amount effective to decrease
proton concentrations.
[0042] According to a sixteenth embodiment of the present invention
there is provided a solution for decreasing inflammation and
inflammatory conditions in a mammal, comprising the aqueous neutral
to mildly alkaline metal bicarbonate solution of the eleventh
embodiment whereby the metal bicarbonate is present in an amount
effective to decrease inflammation and/or inflammatory
conditions.
[0043] According to a seventeenth embodiment of the present
invention there is provided a solution for increasing motor
activity and/or decrease fatigue in a mammal, comprising the
aqueous neutral to mildly alkaline metal bicarbonate solution of
the eleventh embodiment whereby the metal bicarbonate is present in
an amount effective to increase motor activity.
[0044] According to an eighteenth embodiment of the present
invention there is provided a process of preparing an aqueous
neutral to mildly alkaline metal bicarbonate solution comprising
bicarbonate anions and metal cations, which process comprises
reacting a compound selected from the group consisting of metal
carbonate, metal carbonate hydroxide, metal oxide, metal hydroxide
and any mixture thereof with an effective concentration of a pH
adjusting agent to produce the aqueous neutral to mildly alkaline
metal bicarbonate solution, wherein the pH adjusting agent is
present in an amount whereby the solution is at a neutral to mildly
alkaline pH.
[0045] Typically a corresponding substantially stoichiometric
concentration of metal cations are in association with the
bicarbonate anions. Generally the solution is stored in a sealed or
closed container at 0.8 to 5 atmospheres, more typically 1
atmosphere at 0-25.degree. C., more typically 0.1-10.degree. C. In
one embodiment the process further comprises combining the solution
with a stabilising agent in an amount effective to maintain and
stabilise the bicarbonate anions in the neutral to mildly alkaline
solution. In one particular embodiment the process comprises
conducting the process under gaseous atmosphere comprising a
stabilising agent in an amount effective to maintain and stabilise
the bicarbonate anions in the neutral to mildly alkaline solution.
The stabilising agent may be carbon dioxide or comprise carbon
dioxide in an inert gas such as nitrogen, air, oxygen, argon and/or
helium, for example. Generally the combination is stored in a
sealed or closed container at 0.8 to 5 atmospheres, more typically
1 atmosphere at 0-25.degree. C., more typically 0.1-10.degree.
C.
[0046] One particular embodiment may comprise adding the
stabilising agent to the solution in the solution in an amount
effective to maintain and stabilise the bicarbonate anions in the
neutral to mildly alkaline solution. Another particular embodiment
may comprise blanketing the solution with a gas consisting of or
comprising the stabilising agent in an amount effective to maintain
and stabilise the bicarbonate anions in the neutral to mildly
alkaline solution. A further particular embodiment may comprise
adding the stabilising agent to the solution in the solution and
blanketing the solution with a gas consisting of or comprising the
stabilising agent, the total amount of stabilising agent in the
solution and in the gas above the solution being in an amount
effective to maintain and stabilise the bicarbonate anions in the
neutral to mildly alkaline solution. The stabilising agent which
consists of a gas above the solution may be carbon dioxide. The
stabilising agent which comprises a gas above the solution may be
carbon dioxide in an inert gas such as nitrogen, air, oxygen, argon
and/or helium, for example. The stabilising agent in the solution
may be carbon dioxide dissolved in the solution, hydrated carbon
dioxide, carbonic acid, and/or other suitable source of carbon
dioxide.
[0047] According to a nineteenth embodiment of the present
invention there is provided a aqueous neutral to mildly alkaline
metal bicarbonate solution whenever prepared by the process of the
eighteenth embodiment.
[0048] According to a twentieth embodiment of the present invention
there is provided a method of preventing and/or treating certain
inflammatory diseases and/or degenerative diseases in a mammal in
need of such prevention and/or treatment comprising administering
to said mammal an effective amount of an aqueous neutral to mildly
alkaline metal bicarbonate solution of the eleventh or a metal
bicarbonate.
[0049] Generally the certain inflammatory diseases and degenerative
diseases in a mammal are those that require extracellular or
intracellular acidic conditions or extracellular or intracellular
proton concentrations at some point in disease process or disease
pathogenesis.
[0050] Typically the certain inflammatory diseases and degenerative
diseases in a mammal are those that require the activities of
carbonic anhydrase enzymes and/or the activities of acid (aspartic)
protease enzymes and/or the activities of endosomal or lysosomal
acid-requiring-enzymes and/or the activities of V-type ATPase
proton pumps at some point in disease process or disease
pathogenesis.
[0051] Typically the certain inflammatory diseases or degenerative
diseases may present as arthritis. Typically the arthritis may
present as osteoarthritis.
[0052] According to a twenty-first embodiment of the present
invention there is provided a method of preventing and/or treating
certain viral diseases in a mammal in need of such prevention
and/or treatment comprising administering to said mammal an
effective amount of an aqueous neutral to mildly alkaline metal
bicarbonate solution of the eleventh embodiment or a metal
bicarbonate.
[0053] Typically the certain viral diseases require intracellular
acidic conditions or intracellular proton concentrations for either
removal of viral protein coats or assembly of viral protein coats.
Typically the viral diseases may present as influenza.
[0054] According to a twenty-second embodiment of the present
invention there is provided a method of decreasing and/or treating
senescence and/or of increasing longevity in a mammal comprising
administering to said mammal an effective amount of an aqueous
neutral to mildly alkaline metal bicarbonate solution of the
eleventh embodiment or a metal bicarbonate.
[0055] Typically senescence is decreased and longevity is increased
by maintaining or increasing normal extracellular and/or
intracellular alkaline conditions. Typically senescence is
decreased and longevity is increased by improving the buffering
capacity of the extracellular and intracellular fluids of the body.
Typically longevity is increased by maintaining or increasing
normal mitochondrial alkaline conditions. Typically longevity is
increased by decreasing extracellular and intracellular acidic
conditions or by decreasing extracellular and intracellular proton
concentrations. Typically senescence is decreased and longevity is
increased in mammals by improving the buffering capacity of the
extracellular and intracellular bicarbonate buffers. Typically
senescence is decreased and longevity is increased in mammals by
the improved extracellular and intracellular bicarbonate buffers
causing a decrease in proton concentrations.
[0056] Typically senescence is decreased and longevity is increased
by preventing or treating certain inflammatory diseases,
degenerative diseases and viral diseases in mammals.
[0057] Typically longevity is increased by decreasing the morbidity
and mortality associated with these diseases.
[0058] According to a twenty-third embodiment of the present
invention there is provided a method of scavenging protons in a
mammal comprising administering to said mammal an effective amount
of a proton scavenger.
[0059] Typically the proton scavenger comprises a metal
bicarbonate. Typically the metal bicarbonate is in the form of the
aqueous neutral to mildly alkaline metal bicarbonate solution of
the eleventh embodiment.
[0060] According to a twenty-fourth embodiment of the present
invention there is provided a method of decreasing proton
concentrations in a mammal by altering carbonic anhydrase enzyme
reactions in said mammal comprising administering to said mammal an
effective amount of an aqueous neutral to mildly alkaline metal
bicarbonate solution of the eleventh embodiment or a metal
bicarbonate.
[0061] According to a twenty-fifth embodiment of the present
invention there is provided a method of decreasing inflammation
and/or inflammatory conditions in a mammal comprising administering
to said mammal an effective amount of an aqueous neutral to mildly
alkaline metal bicarbonate solution of the eleventh embodiment or a
metal bicarbonate.
[0062] Generally inflammation and inflammatory conditions are
decreased by decreasing the extracellular and intracellular acidic
conditions that are required for inflammatory processes. Generally
inflammation and inflammatory conditions are decreased by
decreasing the extracellular and intracellular proton
concentrations that are required for inflammatory processes.
Typically inflammation is decreased by altering carbonic anhydrase
enzyme reactions and/or decreasing the activities of acid
(aspartic) protease enzymes and/or decreasing the activities of
endosomal or lysosomal acid-requiring-enzymes and/or decreasing the
activities of V-type ATPase proton pumps.
[0063] According to a twenty-sixth embodiment of the present
invention there is provided a method of increasing motor activity
and/or decreasing fatigue in a mammal comprising administering to
said mammal an effective amount of an aqueous neutral to mildly
alkaline metal bicarbonate solution of the eleventh embodiment or a
metal bicarbonate.
[0064] The methods of the invention typically involve orally
administering to the mammal, the mammal being typically human.
Further the methods of the invention typically involve orally
administering to a mammal in need of treatment for the specified
condition of the particular embodiment, the mammal being typically
human. Typically motor activity is increased by decreasing
extracellular and intracellular acidic conditions or by decreasing
extracellular and intracellular proton concentrations. Typically
motor activity is increased by improving the buffering capacity of
extracellular and intracellular fluids. Typically motor activity is
increased by improving the buffering capacity of the extracellular
and intracellular bicarbonate buffers. Typically motor activity is
increased by increasing extracellular and intracellular alkaline
conditions. Typically motor activity is increased by scavenging
protons produced by ATP hydrolysis, lactic acid production, lipid
metabolism and other metabolic processes.
[0065] The term mammal as used herein includes vertebrate. Examples
of mammals and vertebrates to which the methods of the invention
apply include a bovine, human (male or female), ovine, equine,
caprine, Leporine, feline or canine mammal or vertebrate. Specific
examples of animals include sheep, cattle, horses, rabbits, cats,
goats, alpacas, cats, dogs, pigs, rabbits, fowls, deer, buffaloes
and other livestock and domestic animals.
[0066] Metal Bicarbonate Generally
[0067] Generally the pH of the aqueous metal bicarbonate solution
is neutral to mildly alkaline, typically mildly alkaline and more
typically in the range of 7 to 9 even more typically 8 to 8.6 and
the temperature of the aqueous neutral to mildly alkaline metal
bicarbonate solution is maintained at such a level so as to
maintain the metal bicarbonate in the aqueous diluent. The aqueous
neutral to mildly alkaline metal bicarbonate solution may be kept
under an atmosphere comprising carbon dioxide of from about 0.8 to
5 or 1 to 5 atmospheres, more typically 1 to 3 atmospheres and even
more typically slightly above atmospheric pressure such as the
sorts of pressures that soft drinks are currently under in cans or
bottles, for example, so as to maintain the metal bicarbonate in
the aqueous diluent.
[0068] Generally the metal cation is an alkaline earth metal cation
or an alkali metal cation.
[0069] Generally a metal cation is chosen which is capable of
acting as a bicarbonate transporter into mammalian cells. More
particularly the metal cation may be cations of magnesium, sodium,
potassium, calcium, lithium or any mixture thereof. Where a mixture
of alkaline earth metal cations or alkali metal cations are used:
(1) two different alkaline earth metal cations or alkali metal
cations or mixtures thereof, the molar ratio of the first metal
cation to the second may be in the range 0.5:99.5 to 99.5:0.5,
typically 75:25 to 25:75, more typically 0.7:1 to 1:0.7; (2) three
different alkaline earth metal cations or alkali metal cations or
mixtures thereof, the molar ratio of the first metal cation to the
second to the third may be in the range 99.5:0.5:0.5 to
0.5:99.5:99.5, typically 75:25:25 to 25:75:75, more typically
0.5:1:1 to 1:0.5:0.5; (3) four different alkaline earth metal
cations or alkali metal cations or mixtures thereof, the molar
ratio of the first metal cation to the second to the third to the
fourth may be in the range 99.5:0.5:0.5:0.5 to 0.5:99.5:99.5:99.5,
typically 75:25:25:25 to 25:75:75:75, more typically 0.5:1:1:1 to
0.5:1:1:1. Generally the metal cation is magnesium or a mixture of
magnesium and sodium metal cations. Typically the aqueous neutral
to mildly alkaline metal bicarbonate solution has a high metal
cation concentration in association with bicarbonate anions.
[0070] Typically the metal bicarbonate is used at a concentration
of 10-100 mole % or weight % of its saturation solubility (which
will depend on the actual metal bicarbonate(s) used), more
typically 10-90%, 10-80%, 10-70%, 10-60%, 10-50%, 10-40%, 10-30%,
10-20%, more typically 15-95%, 15-85%, 15-75%, 15-65%, 15-55%,
15-45%, 15-35%, 15-25%, more typically 15-90%, 15-80%, 15-70%,
15-60%, 15-50%, 15-40%, 15-30%, 15-20%, more typically 10-95%,
10-85%, 10-75%, 10-65%, 10-55%, 10-45%, 10-35%, 10-25%, more
typically 20-90%, 20-80%, 20-70%, 20-60%, 20-50%, 20-40%, 20-30%,
more typically 25-95%, 25-85%, 25-75%, 25-65%, 25-55%, 25-45%,
25-35%, more typically 25-90%, 25-80%, 25-70%, 25-60%, 25-50%,
25-40%, 25-30%, more typically 20-95%, 20-85%, 20-75%, 20-65%,
20-55%, 20-45%, 20-35%, more typically 30-90%, 30-80%, 30-70%,
30-60%, 30-50%, 30-40%, more typically 35-95%, 35-85%, 35-75%,
35-65%, 35-55%, 35-45%, more typically 35-90%, 35-80%, 35-70%,
35-60%, 35-50%, 35-40%, more typically 30-95%, 30-85%, 30-75%,
30-65%, 30-55%, 30-45%, more typically 40-90%, 40-80%, 40-70%,
40-60%, 40-50%, more typically 45-95%, 45-85%, 45-75%, 45-65%,
45-55%, more typically 45-90%, 45-80%, 45-70%, 45-60%, 45-50%, more
typically 40-95%, 40-85%, 40-75%, 40-65%, 40-55%, more typically
50-90%, 50-80%, 50-70%, 50-60%, more typically 55-95%, 55-85%,
55-75%, 55-65%, more typically 55-90%, 55-80%, 55-70%, 55-60%, more
typically 50-95%, 50-85%, 50-75%, 50-65%, more typically 60-90%,
60-80%, 60-70%, more typically 65-95%, 65-85%, 65-75%, more
typically 65-90%, 65-80%, 65-70%, more typically 60-95%, 60-85%,
60-75%, more typically 70-90%, 70-80%, more typically 75-95%,
75-85%, more typically 75-90%, 75-80%, more typically 70-95%,
70-85%, more typically 80-90%, more typically 85-95%, more
typically 85-90%, more typically 80-95%, more typically 20-100%,
30-100%, 40-100%, 50-100%, 60-100%, 70-100%, 80-100% or 90-100%.
Depending on the solubility of the metal bicarbonate, the amount of
metal cation may range from 20 mg to 1250 mg or 25 mg to 1250 mg
per litre of aqueous neutral to mildly alkaline metal bicarbonate
solution, typically 20 mg to 1000 mg or 50 mg to 1000 mg per litre
of aqueous neutral to mildly alkaline metal bicarbonate solution,
more typically 20 mg to 750 mg or 50 mg to 750 mg or 20 mg to 600
mg or 50 mg to 600 mg per litre of aqueous neutral to mildly
alkaline metal bicarbonate solution, even more typically 20 mg to
500 mg or 30 mg to 500 mg or 50 mg to 500 mg per litre of aqueous
neutral to mildly alkaline metal bicarbonate solution, even more
typically 20 mg to 250 mg or 50 mg to 250 mg per litre of aqueous
neutral to mildly alkaline metal bicarbonate solution, most
typically 100 mg to 500 mg or 100 mg to 400 mg or 100 mg to 300 mg
or 100 mg to 250 mg per litre of aqueous neutral to mildly alkaline
metal bicarbonate solution, even most typically 20 mg to 200 mg or
20 to 150 mg or 20 mg to 120 mg or 120 mg to 300 mg or 120 mg to
200 mg. Typically when the metal cation is magnesium, the amount of
magnesium may range from 30 mg to 140 mg per litre of aqueous
neutral to mildly alkaline metal bicarbonate solution, typically 30
mg to 130 mg, 30 mg to 120 mg, 30 mg to 110 mg, 30 mg to 100 mg, 30
mg to 90 mg, 30 mg to 80 mg, 30 mg to 70 mg, 30 mg to 60 mg, 30 mg
to 50 mg, 30 mg to 40 mg, 50 mg to 120 mg, 60 mg to 120 mg, 70 mg
to 120 mg, 80 mg to 120 mg, 90 mg to 120 mg or 75 mg to 120 mg or
100 mg to 120 mg per litre of aqueous neutral to mildly alkaline
metal bicarbonate solution. Typically when the metal cation is
sodium and/or potassium, the amount of sodium and/or potassium may
range from greater than 30 mg to 1250 mg per litre of aqueous
neutral to mildly alkaline metal bicarbonate solution, typically 50
mg to 1000 mg or 50 mg to 750 mg or 50 mg to 500 mg or 75 mg to
1250 mg or 75 mg to 1000 mg or 75 mg to 500 mg or 100 mg to 1000 mg
or 100 mg to 500 mg or 250 mg to 1000 mg or 250 mg to 500 mg per
litre of aqueous neutral to mildly alkaline metal bicarbonate
solution. Typically when the metal cation is calcium, the amount of
calcium may range from greater than 20 mg to 1250 mg per litre of
aqueous neutral to mildly alkaline metal bicarbonate solution,
typically 20 mg to 1000 mg or 20 mg to 750 mg or 20 mg to 500 mg or
20 mg to 250 mg or 20 mg to 200 mg or 20 mg to 150 mg or 20 mg to
100 mg per litre of aqueous neutral to mildly alkaline metal
bicarbonate solution. Typically the amount of bicarbonate anion
present will be stoichiometric with the amount of metal cation in
solution so as to form the metal bicarbonate. Alternatively, the
concentration of the metal bicarbonate can be based on the
bicarbonate anion concentrations in which case the amount of
bicarbonate anion (which will depend on the saturation solubility
of the actual metal bicarbonate anion(s) used). The concentration
of bicarbonate typically ranges from 120 mg or 150 mg to 3500 mg
per litre of aqueous neutral to mildly alkaline metal bicarbonate
solution, typically 120 mg or 150 mg to 3000 mg or 200 mg to 3000
mg per litre of aqueous neutral to mildly alkaline metal
bicarbonate solution, more typically 250 mg to 2100 mg or 300 mg to
2000 mg or 200 mg to 1500 mg or 300 mg to 1500 mg or 400 mg to 1500
mg or 500 mg to 1500 mg or 600 mg to 1500 mg or 700 mg to 1500 mg
or 800 mg to 1500 mg or 900 mg to 1500 mg or 1000 mg to 1500 mg or
200 mg to 1000 mg or 300 mg to 1000 mg or 400 mg to 1000 mg or 500
mg to 1000 mg or 600 mg to 1000 mg or 700 mg to 1000 mg or 800 mg
to 1000 mg or 900 mg to 1000 mg or 1000 mg to 1500 mg or 1200 mg to
1500 mg per litre of aqueous neutral to mildly alkaline metal
bicarbonate solution, even more typically 600 mg to 1000 mg or 500
mg to 1500 mg per litre of aqueous neutral to mildly alkaline metal
bicarbonate solution, most typically 950 mg or 200 mg to 2000 mg or
200 mg to 1750 mg or 200 mg to 1250 mg or 200 mg to 100 mg per
litre of aqueous neutral to mildly alkaline metal bicarbonate
solution. Typically at least 600 mg of bicarbonate anions per litre
of solution is present, more typically 600-1800 mg/l, 600-1500
mg/l, 600-1350 mg/l, 600-1200 mg,/l 600-1100 mg/l, 600-1000 mg/l,
600-950 mg/l, 600-900 mg/l, 600-850 mg/l, 600-800 mg/l, 600-750
mg/l, 600-700 mg/l or 600-650 mg/l. Typically a mildly alkaline
saturated magnesium bicarbonate solution is used or a mildly
alkaline solution comprising a mixture of sodium and/or potassium
and magnesium bicarbonate, more typically sodium and magnesium
bicarbonate. Typically the range for a mixture of sodium and/or
potassium and magnesium bicarbonate, more typically sodium and
magnesium bicarbonate varies from 20 mg to 1250 mg or 25 mg to 1250
mg per litre of aqueous neutral to mildly alkaline metal
bicarbonate solution, typically 20 mg to 1000 mg or 50 mg to 1000
mg per litre of aqueous neutral to mildly alkaline metal
bicarbonate solution, more typically 20 mg to 750 mg or 50 mg to
750 mg or 20 mg to 600 mg or 50 mg to 600 mg per litre of aqueous
neutral to mildly alkaline metal bicarbonate solution, even more
typically 20 mg to 500 mg or 30 mg to 500 mg or 50 mg to 500 mg per
litre of aqueous neutral to mildly alkaline metal bicarbonate
solution, even more typically 20 mg to 250 mg or 50 mg to 250 mg or
even more typically 20 mg to 300 mg or 50 mg to 300 mg per litre of
aqueous neutral to mildly alkaline metal bicarbonate solution, most
typically 75 mg to 1000 mg or 75 mg to 500 mg or 100 mg to 1000 mg
or 100 mg to 500 mg or 100 mg to 400 mg or 100 mg to 300 mg or 100
mg to 250 mg per litre of aqueous neutral to mildly alkaline metal
bicarbonate solution, even most typically 20 mg to 200 mg or 20 to
150 mg or 200 mg to 120 mg or 120 mg to 300 mg or 120 mg to 200 mg.
Usually the ratio (weight to weight) of magnesium to sodium is in
the range 25:1 to 1:4, typically 1:1.125.
[0071] Generally the aqueous diluent is water or comprises water.
Generally the carbon dioxide-containing-aqueous diluent may be
carbonic acid in water, hydrated carbon dioxide in water, carbon
dioxide gas dissolved in water, carbonated soft drinks, carbonated
mineral water, soda water or other carbon
dioxide-containing-aqueous diluents. If carbon dioxide gas is used,
the carbon dioxide may be either bubbled into aqueous solutions
containing metal carbonate or metal carbonate hydroxide or metal
oxide or mixture thereof or the carbon dioxide may be introduced in
the form of a blanket over aqueous solutions containing metal
carbonate or metal carbonate hydroxide or metal oxide or mixture
thereof. Typically the carbon dioxide-containing-aqueous diluent is
pharmaceutically acceptable. Typically carbonated mineral water,
carbonic acid, hydrated carbon dioxide in water or carbonated water
is used. The amounts of carbon dioxide-containing-aqueous diluent
and metal carbonate or metal carbonate hydroxide or metal oxide or
mixture thereof used are sufficient to obtain a clear solution at a
neutral to mildly alkaline pH, typically pH 7 to 9 or pH 7 to 8.6,
more typically pH 7.5 to 8.8 or pH 7.5 to 8.5 or pH 7.8 to 8.6, pH
7.8 to 8.5, pH 7.8 to 8.4, pH 7.8 to 8.3, pH 7.8 to 8.2, pH 7.8 to
8.1, pH 7.8 to 8.0, pH 7.8 to 7.9, pH 7.9 to 8.6, pH 7.9 to 8.5, pH
7.9 to 8.4, pH 7.9 to 8.3, pH 7.9 to 8.2, pH 7.9 to 8.1, pH 7.9 to
8.0, pH 8.0 to 8.6, pH 8.0 to 8.5, pH 8.0 to 8.4, pH 8.0 to 8.3, pH
8.0 to 8.2, pH 8.0 to 8.1, pH 8.1 to 8.6, pH 8.1 to 8.5, pH 8.1 to
8.4, pH 8.1 to 8.3, pH 8.1 to 8.2, pH 8.2 to 8.6, pH 8.2 to 8.5, pH
8.2 to 8.4, pH 8.2 to 8.3, pH 8.3 to 8.6, pH 8.3 to 8.5, pH 8.3 to
8.4, pH 8.4 to 8.6, pH 8.4 to 8.5, pH 8.5 to 8.6, even more
typically pH 8 to 8.5 or pH 8.2 to 8.6, most typically pH 8.3.
Usually 10 to 60 mL, typically 25 to 55 mL, more typically 40 to 50
mL, most typically approximately 45 mL of chilled carbonated
mineral water per litre of water is used. Usually the chilled
carbonated mineral water is at a temperature of 0 to 25.degree. C.,
0 to 20.degree. C., 0.5 to 25.degree. C., 0.5 to 20.degree. C., 0.5
to 15.degree. C., 0.5 to 10.degree. C., 0.5 to 9.degree. C., 0.5 to
8.degree. C., 0.5 to 7.degree. C., 1 to 20.degree. C., 1 to
15.degree. C., 1 to 10.degree. C., 1.5 to 20.degree. C., 1.5 to
15.degree. C., 1.5 to 10.degree. C., 2 to 20.degree. C., 2 to
15.degree. C., 2 to 10.degree. C., 3 to 20.degree. C., 3 to
15.degree. C., 4 to 20.degree. C., 4 to 15.degree. C., 4 to
10.degree. C., 5 to 20.degree. C., 5 to 15.degree. C., 6 to
20.degree. C., 6 to 15.degree. C., 6 to 10.degree. C., 7 to
20.degree. C., 7 to 15.degree. C., 7 to 10.degree. C., 8 to
20.degree. C., 8 to 15.degree. C., 8 to 10.degree. C., 9 to
20.degree. C., 9 to 15.degree. C., 9 to 10.degree. C., 10 to
15.degree. C., typically 0 to 15.degree. C., more typically 0 to
10.degree. C., even more typically 3.degree. C. to 10.degree. C.,
most typically 5.degree. C. to 10.degree. C. and even most
typically 5.degree. C. Alternatively the metal carbonate or metal
carbonate hydroxide or metal oxide or mixture thereof can be added
after the carbon dioxide has been added.
[0072] Generally the metal bicarbonate in aqueous solution may be
derived from a metal carbonate or metal carbonate hydroxide or
metal oxide or metal bicarbonate or metal, hydroxide or other
appropriate metal compound or any mixture thereof. Examples include
magnesium, sodium, potassium, calcium, lithium carbonate or
carbonate hydroxide or oxide or bicarbonate or a mixture of any two
or more thereof. For example magnesium carbonate hydroxide
pentahydrate, the calcite series or dolomite series of minerals
(Mg, Ca)CO.sub.3 or limestone or dolomite rocks is used. Generally
magnesium carbonate hydroxide pentahydrate or a mixture of
magnesium carbonate hydroxide pentahydrate and sodium bicarbonate
is used.
[0073] Generally the pH of the aqueous metal bicarbonate solution
for oral administration is neutral to mildly alkaline, typically in
the range pH 7 to 9 or pH 7 to 8.6, more typically pH 7.5 to 8.8 or
pH 7.5 to 8.5 or pH 7.8 to 8.6, pH 7.8 to 8.5, pH 7.8 to 8.4, pH
7.8 to 8.3, pH 7.8 to 8.2, pH 7.8 to 8.1, pH 7.8 to 8.0, pH 7.8 to
7.9, pH 7.9 to 8.6, pH 7.9 to 8.5, pH 7.9 to 8.4, pH 7.9 to 8.3, pH
7.9 to 8.2, pH 7.9 to 8.1, pH 7.9 to 8.0, pH 8.0 to 8.6, pH 8.0 to
8.5, pH 8.0 to 8.4, pH 8.0 to 8.3, pH 8.0 to 8.2, pH 8.0 to 8.1, pH
8.1 to 8.6, pH 8.1 to 8.5, pH 8.1 to 8.4, pH 8.1 to 8.3, pH 8.1 to
8.2, pH 8.2 to 8.6, pH 8.2 to 8.5, pH 8.2 to 8.4, pH 8.2 to 8.3, pH
8.3 to 8.6, pH 8.3 to 8.5, pH 8.3 to 8.4, pH 8.4 to 8.6, pH 8.4 to
8.5, pH 8.5 to 8.6, even more typically pH 8 to 8.5 or pH 8.2 to
8.6, most typically pH 8.3. Generally the pH of the aqueous metal
bicarbonate solution for parenteral administration is neutral to
very mildly alkaline, typically in the range pH 7 to 7.6, or pH 7.0
to 7.5, or pH 7.1 to 7.5, more typically pH 7.2 to 7.5 or pH 7.3 to
7.5 or pH 7.4 to 7.5. Generally the aqueous neutral to mildly
alkaline metal bicarbonate solution is prepared and stored at a
temperature ranging from 0 to 25.degree. C., 0 to 20.degree. C.,
0.5 to 25.degree. C., 0.5 to 20.degree. C., 0.5 to 15.degree. C.,
0.5 to 10.degree. C., 0.5 to 9.degree. C., 0.5 to 8.degree. C., 0.5
to 7.degree. C., 1 to 20.degree. C., 1 to 15.degree. C., 1 to
10.degree. C., 1.5 to 20.degree. C., 1.5 to 15.degree. C., 1.5 to
10.degree. C., 2 to 20.degree. C., 2 to 15.degree. C., 2 to
10.degree. C., 3 to 20.degree. C., 3 to 15.degree. C., 4 to
20.degree. C., 4 to 15.degree. C., 4 to 10.degree. C.,, 5 to
20.degree. C., 5 to 15.degree. C., 6 to 20.degree. C., 6 to
15.degree. C., 6 to 10.degree. C., 7 to 20.degree. C., 7 to
1.5.degree. C., 7 to 10.degree. C., 8 to 20.degree. C., 8 to
15.degree. C., 8 to 10.degree. C., 9 to 20.degree. C., 9 to
15.degree. C., 9 to 10.degree. C., 10 to 15.degree. C., typically 0
to 15.degree. C., more typically 0 to 10.degree. C., even more
typically 3.degree. C. to 10.degree. C., most typically 5.degree.
C. to 10.degree. C. and even most typically 5.degree. C.
[0074] Generally the pH adjusting agent is carbon dioxide gas,
carbonic acid in water, hydrated carbon dioxide in water, carbon
dioxide gas in water, carbonated soft drinks, carbonated mineral
water, soda water or other carbon dioxide-containing-aqueous
diluents or an alkali or any mixture thereof. Examples of alkalis
are water soluble drinkable alkalis such as sodium hydroxide,
sodium carbonate, potassium carbonate or potassium hydroxide or any
mixture thereof.
[0075] Typically additions may be added during the process of the
invention or to the aqueous neutral to mildly alkaline metal
bicarbonate solution. The additives may be 0 mg or 0.5 mg to 1000
mg sodium) bicarbonate per litre of aqueous neutral to mildly
alkaline metal bicarbonate solution, typically 25 mg to 900 mg per
litre of aqueous neutral to mildly alkaline metal bicarbonate
solution, typically 50 mg to 800 mg or 50 mg to 500 mg per litre of
aqueous neutral to mildly alkaline metal bicarbonate solution, more
typically 100 mg to 700 mg per litre of aqueous neutral to mildly
alkaline metal bicarbonate solution, even more typically 200 mg to
600 mg per litre of aqueous neutral to mildly alkaline metal
bicarbonate solution, most typically 300 mg to 500 mg per litre of
aqueous neutral to mildly alkaline metal bicarbonate solution, even
most typically 500 mg per litre of aqueous neutral to mildly
alkaline metal bicarbonate solution. The additives may also be
chlorides and other appropriate salts of magnesium sodium,
potassium, calcium and lithium, such as carbonates or hydroxides or
sulfates, with or without the addition of sodium bicarbonate. For
example, magnesium sulfate, magnesium chloride or other soluble
salts of magnesium. Further additives may include potassium
bicarbonate, calcium bicarbonate or lithium bicarbonate. Generally
calcium bicarbonate is prepared by adding carbonic acid or
carbonated water or hydrated carbon dioxide or carbon dioxide gas
to a mixture of calcium carbonate in water. Generally lithium
bicarbonate is prepared by adding carbonic acid and/or carbonated
water and/or hydrated carbon dioxide and/or carbon dioxide gas
and/or solid carbon dioxide to a mixture of lithium carbonate in
water.
[0076] The aqueous neutral to mildly alkaline metal bicarbonate
solution may further include a stabilising agent. The stabilising
agent may also be a pH adjusting agent. Typically the stabilising
agent is a gaseous phase, for example carbon dioxide gas, which
maintains and/or stabilises the solution at a pH of 7 to 9 and at a
temperature of 0 to 55.degree. C. more typically 0 to 25.degree.
C.
[0077] Generally once the solution is prepared, the solution may be
stored under a blanket of carbon dioxide gas or a mixture of carbon
dioxide gas and a nondeleterious inert gas, for example, argon,
helium, air, oxygen and/or nitrogen wherein the amount of carbon
dioxide present in the inert gas is sufficient to maintain the
solution at a pH of 7 to 9 and at a temperature of 0 to 25.degree.
C. and to prevent the metal bicarbonate from forming insoluble
compounds which can precipitate out of solution. Typically the
carbon dioxide gas above the solution prevents loss of carbon
dioxide from the solution. The amount of carbon dioxide in the
gaseous mixture provides partial pressure on the liquid which is
substantially equal to the partial pressure which is produced from
equilibrium of bicarbonate in the solution at the mixing
temperature.
[0078] Magnesium Bicarbonate Particularly
[0079] Typically the production of magnesium bicarbonate utilises
the dissolution of magnesium carbonate by carbonic acid or hydrated
carbon dioxide solutions. Ideally, the dissolution is produced
within a defined range of conditions--a defined range of pH values,
a defined range of temperature values and a defined minimum time.
For optimal biological and medical activities, and for therapeutic
safety, the concentrations of the component ions are defined
also.
[0080] Typically to prepare the aqueous neutral to mildly alkaline
metal bicarbonate solution, crushed or powdered metal carbonate, or
metal carbonate hydroxide or metal oxide, such as magnesium
carbonate MgCO.sub.3, or commercial magnesium carbonate hydroxide
pentahydrate (MgCO.sub.3).sub.4.Mg(OH).sub.2.5H.sub.2O, or other
commercial magnesium carbonate hydroxides, or hydrated magnesium
oxides, or magnesium oxides heated with carbon dioxide, or the
calcite series or dolomite series of minerals (Mg, Ca)CO.sub.3, or
limestone or dolomite rocks is mixed with water. A cloudy
suspension is obtained. Sufficient carbonic acid and/or hydrated
carbon dioxide and/or carbon dioxide gas and/or solid carbon
dioxide is added to obtain a solution having a pH 7 to 9 or pH 7 to
8.6, more typically pH 7.5 to 8.8 or pH 7.5 to 8.5 or pH 7.8 to
8.6, pH 7.8 to 8.5, pH 7.8 to 8.4, pH 7.8 to 8.3, pH 7.8 to 8.2, pH
7.8 to 8.1, pH 7.8 to 8.0, pH 7.8 to 7.9, pH 7.9 to 8.6, pH 7.9 to
8.5, pH 7.9 to 8.4, pH 7.9 to 8.3, pH 7.9 to 8.2, pH 7.0 to 8.1, pH
7.9 to 8.0, pH 8.0 to 8.6, pH 8.0 to 8.5, pH 8.0 to 8.4, pH 8.0 to
8.3, pH 8.1 to 8.2, pH 8.0 to 8.1, pH 8.1. to 8.6, pH 8.1 to 8.5,
pH 8.1 to 8.4, pH 8.1 to 8.3, pH 8.1 to 8.2, pH 8.2 to 8.6, pH 8.2
to 8.5, pH 8.2 to 8.4, pH 8.2 to 8.3, pH 8.3 to 8.6, pH 8.3 to 8.5,
pH 8.3 to 8.4, pH 8.4 to 8.6, pH 8.4 to 8.5, pH 8.5 to 8.6, even
more typically pH 8 to 8.6 or pH 8.2 to 8.6, most typically pH 8.3.
The solution is then typically placed in a closed or sealed
container at 0 to 20.degree. C. or 0 to 15.degree. C. with
occasional mixing until a clear solution develops. The amount of
carbonic acid and/or hydrated carbon dioxide and/or carbon dioxide
gas bubbled through the solution and dissolved therein and/or solid
carbon dioxide is sufficient to prevent precipitation of water
insoluble metal compounds (such as magnesium or calcium carbonate).
A clear solution is generally obtained in about 6 hours to 7 days,
typically 12 hours to 5 days, more typically 24 hours to 5 days,
most typically 24 hours to 3 days. Generally the aqueous neutral to
mildly alkaline metal bicarbonate solution is prepared and stored
at a temperature ranging from 0 to 55.degree. C., 0 to 25.degree.
C., 0 to 20.degree. C., 0.5 to 25.degree. C., 0.5 to 20.degree. C.,
0.5 to 15.degree. C., 0.5 to 10.degree. C., 0.5 to 9.degree. C.,
0.5 to 8.degree. C., 0.5 to 7.degree. C., 1 to 20.degree. C., 1 to
15.degree. C., 1 to 10.degree. C., 1.5 to 20.degree. C., 1.5 to
15.degree. C., 1.5 to 10.degree. C., 2 to 20.degree. C., 2 to
15.degree. C., 2 to 10.degree. C., 3 to 20.degree. C., 3 to
15.degree. C., 4 to 20.degree. C., 4 to 15.degree. C., 4 to
10.degree. C.,, 5 to 20.degree. C., 5 to 15.degree. C., 6 to
20.degree. C., 6 to 15.degree. C., 6 to 10.degree. C., 7 to
20.degree. C., 7 to 15.degree. C., 7 to 10.degree. C., 8 to
20.degree. C., 8 to 15.degree. C., 8 to 10.degree. C., 9 to
20.degree. C., 9 to 15.degree. C., 9 to 10.degree. C., 10 to
15.degree. C., typically 0 to 15.degree. C., more typically 0 to
10.degree. C., even more typically 3.degree. C. to 10.degree. C.,
most typically 5.degree. C. to 10.degree. C. and even most
typically 5.degree. C. Alternatively the crushed or powdered metal
carbonate, or metal carbonate hydroxide or metal oxide or mixture
thereof is added to an aqueous solution of the carbonic acid and/or
hydrated carbon dioxide and/or to an aqueous solution through which
carbon dioxide gas is bubbled and/or solid carbon dioxide has been
added. The amount of carbonic acid and/or hydrated carbon dioxide
and/or carbon dioxide gas bubbled through the solution and
dissolved therein and/or solid carbon dioxide is sufficient to
prevent precipitation of water insoluble metal compounds (such as
magnesium or calcium carbonate).
[0081] Typically one litre of water is placed in a container and
sufficient carbonic acid and/or carbonated water and/or hydrated
carbon dioxide and/or carbon dioxide gas and/or solid carbon
dioxide is added to produce a pH value of approximately pH 5.2. (In
practice, approximately 40 to 45 mL of chilled (5.degree. C.)
carbonated mineral water is used depending on the initial pH of the
water). The container is sealed and the contents are mixed. 485 mg
magnesium carbonate hydroxide pentahydrate powder
(MgCO.sub.3).sub.4.Mg(OH).sub.2.5H.sub.2O, molecular weight 485 is
added. The container is again sealed and the contents are mixed.
The container is stored at a temperature of 0 to 10.degree. C. and
the contents mixed regularly. Sufficient time is allowed for a
clear solution of magnesium bicarbonate to develop at a range of pH
8.0 to pH 8.6, preferably pH 8.3. This takes approximately 24 to 72
hours. Alternatively the carbonic acid and/or carbonated water
and/or hydrated carbon dioxide and/or carbon dioxide gas and/or
solid carbon dioxide is added to the magnesium carbonate hydroxide
pentahydrate powder in water. Alternatively one litre of water is
placed in a container and sufficient carbonic acid and/or
carbonated water and/or hydrated carbon dioxide and/or solid carbon
dioxide is added to produce a pH value less than pH 5.2. (In
practice, approximately 30 mL to 40 mL of chilled water is used
depending on the initial pH of the water). The container is sealed
and the contents are mixed. 485 mg magnesium carbonate hydroxide
pentahydrate powder (MgCO.sub.3).sub.4.Mg(OH).sub.2.5H.sub.2O,
molecular weight 485 is added. The container is again sealed and
the contents are mixed. The container is stored at a temperature of
0 to 10.degree. C. and the contents mixed regularly. The pH of the
water is then adjusted with an alkali such as sodium hydroxide or
potassium hydroxide to a pH of 8 to 8.6, typically pH 8.3.
Alternatively the carbonic acid or carbonated water and/or hydrated
carbon dioxide and/or carbon dioxide gas and/or solid carbon
dioxide is added to the magnesium carbonate hydroxide pentahydrate
powder in water.
[0082] The above processes may optionally be conducted under an
atmosphere of carbon dioxide or a gas comprising carbon
dioxide.
[0083] Generally once the solution is prepared, it may be stored
under a blanket of carbon dioxide gas to maintain the solution at a
pH of 7 to 9 and at a temperature of 0 to 25.degree. C. Usually one
litre of the magnesium bicarbonate solution prepared above contains
approximately 120 mg of magnesium per litre of aqueous neutral to
mildly alkaline metal bicarbonate solution and approximately 600 mg
of bicarbonate. 500 mg sodium bicarbonate (or potassium
bicarbonate) is added to the magnesium bicarbonate solution and
mixed. The mixture is stored in a sealed container in a
refrigerator. The mixture contains approximately 120 mg magnesium
per litre of aqueous neutral to mildly alkaline metal bicarbonate
solution, 135 mg sodium per litre of aqueous neutral to mildly
alkaline metal bicarbonate solution and 950 mg bicarbonate per
litre of aqueous neutral to mildly alkaline metal bicarbonate
solution.
[0084] Generally the aqueous neutral to mildly alkaline metal
bicarbonate solution of the invention is administered or consumed
orally. Typically the solution is an orally drinkable solution.
Typically the solution is a therapeutic orally drinkable solution.
Alternatively a gelling agent may added to the solution and the
solution subjected to gelling conditions to gel the solution and
the resultant gel may be consumed orally. For example, the aqueous
neutral to mildly alkaline metal bicarbonate solution may be
prepared as a solution or an iced confectionary, such as an ice
block or iced dessert, which is ingested orally. Alternatively the
aqueous neutral to mildly alkaline metal bicarbonate solution may
be prepared in the form of a tablet, lozenge or lolly which is
ingested orally. For example, the aqueous neutral to mildly
alkaline metal bicarbonate solution may be administered for
metabolic acidosis or renal failure. Optionally the solution may be
sterilised. Typically the aqueous neutral to mildly alkaline metal
bicarbonate solution is prepared as a solution which is ingested on
a regular basis hourly, daily, monthly or yearly. The amount and
frequency of aqueous neutral to mildly alkaline metal bicarbonate
solution administered/consumed in a day is generally sufficient so
as to maintain a steady bicarbonate level in the bicarbonate
concentration of a taker's body fluids. It is preferable to avoid a
rapid increase in the bicarbonate level in the bicarbonate
concentration of a taker's body fluids. The amount of aqueous
neutral to mildly alkaline metal bicarbonate solution administered
in a day ranges from 250 mL to 6 litres, typically 250 mL to 5.5
litres, 250 mL to 5 litres, 250 mL to 4.5 litres, 250 mL to 4
litres, 250 mL to 3.5 litres, 250 mL to 3 litres, 500 mL to 6
litres, 500 mL to 5.5 litres, 500 mL to 5 litres, 500 mL to 4.5
litres, 500 mL to 4 litres, 500 mL to 3.5 litres, 500 mL to 3
litres, more typically 1 litre to 6 litres, 1 litre to 5.5 litres,
1 litre to 5 litres, 1 litre to 4.5 litres, 1 litre to 4 litres, 1
litre to 3.5 litres, even more typically 1 litre to 3 litres, 1.5
litres to 6 litres, 1.5 litres to 5.5 litres, 1.5 litres to 5
litres, 1.5 litres to 4.5 litres, 1.5 litres to 4 litres, 1.5
litres to 3.5 litres, 1.8 litres to 3.3 litres, 1.8 to 2.8 litres,
1.8 to 2.5 litres, 1.8 to 2.3 litres, 1.8 to 2.0 litres, most
typically 2 to 3 litres, typically 2.3 to 2.8 litres, more
typically 2.3 to 2.6 litres, usually 2.1 to 3 litres. The aqueous
neutral to mildly alkaline metal bicarbonate solution may be
administered on a full or empty stomach, typically the aqueous
neutral to mildly alkaline metal bicarbonate solution is
administered on an empty stomach. Usually 1.5 to 3.5 litres,
typically 1.8 to 3 litres, more typically 1.5 to 2.4 litres, even
more typically 1.8 to 2.1 litres and usually between 1.8 and 2.7
litres of aqueous neutral to mildly alkaline metal bicarbonate
solution is ingested, administered or consumed on an empty stomach
by a mammal (typically a human) in equal or non equal volume
amounts (100 mL-1000 mL, 200-800 mL, 250-750 mL, 275-700 mL,
300-650 mL, 350-600 mL, 400-550 mL, 450-500 mL, typically about
300-400 mL, more typically about 375 mL volume amounts a number of
times (typically at set times) each day for the required number of
times per day to drink the desired daily amount of the solution).
For example if 1800 mL per day is to be consumed then a user may
drink six 300 mL amounts of the solution every 2 to 2.5 hours
throughout the day. The oral consumption of the solution three or
more times at roughly equally spaced apart intervals throughout the
day is more desirable than consuming the solution in one or two
lots throughout the day. The idea of taking the solution is to take
it regularly throughout the day so that a simulated continuous oral
intake or a close to continuous regular oral intake of the solution
occurs. Thus depending on the condition and the subject one
suitable administration/consumption regime could be nine by 200 mL
amounts of the solution, each 200 mL amount being orally
administered/consumed about every 1.5-1.75 hours to provide a total
daily intake of 1800 mL. Alternatively, once again depending on the
condition and the subject one suitable administration/consumption
regime could be nine by 300 mL amounts of the solution, each 300 mL
amount being orally administered/consumed about every 1.5-1.75
hours to provide a total daily intake of 2700 mL. Alternatively,
once again depending on the condition and the subject one suitable
administration/consumption regime could be nine by 350 mL amounts
of the solution, each 350 mL amount being orally
administered/consumed about every 1.5-1.75 hours to provide a total
daily intake of 3150 mL. Typically the solution is
administered/consumed 3 to 30, 3-25, 3-20, 3-15, 3-12, 3-10, 3-9,
3-8, 3-7, 3-6, 3-5, 3-4, 4-30, 4-25, 4-20, 4-15, 4-12, 4-10, 4-9,
4-8, 4-7, 4-6, 4-5, 5-30, 5-25, 5-20, 5-15, 5-12, 5-11, 5-10, 5-9,
5-8, 5-7, 5-6, 6-30, 6-25, 6-20, 6-15, 6-12, 6-11, 6-10, 6-9, 6-8,
6-7, 7-30, 7-25, 7-20, 7-15, 7-12, 7-11, 7-10, 7-9, 7-8, 8-30,
8-25, 8-20, 8-15, 8-12, 8-11, 8-10, 8-9 times per day at regular or
irregular intervals or a mixture of both regular and irregular
intervals, throughout each day. Typically the solution is
administered/consumed every 0.3-10, 0.3-8, 0.3-7, 0.3-6, 0.3-5,
0.3-4.5, 0.3-4, 0.3-3.5, 0.3-3, 0.3-2.5, 0.3-2, 0.3-1.5, 0.3-1,
0.3-0.75, 0.3-0.5 hours/day when the subject is awake. More
typically the solution is administered/consumed every 0.5-8, 0.5-7,
0.5-6, 0.5-5, 0.5-4.5, 0.5-4, 0.5-3.5, 0.5-3, 0.5-2.5, 0.5-2,
0.5-1.5, 0.5-1, 0.5-0.8, 0.5-0.75 hours/day when the subject is
awake. Where possible the solution is consumed/administered on an
empty (e.g. before eating). The solution may be administered
according to these latter dosages over short (for example 1 to 60
days, 10 t days, 3 months to 6 months, 1 day to 6 months) or long
(for example 6 months to 10 years or more, 9 months to 18 months, 1
year to 3 years, 1 year to 5 years, 2 to 6 years) period required.
Usually the amount of aqueous neutral to mildly alkaline metal
bicarbonate administered to a mammal is 5 to 100 mL per Kg, more
usual 10 to 50 mL per Kg, usual 14 to 29 mL per Kg or 25 to 43 mL
per Kg.
[0085] The solution may include other additives such as sweeteners,
preservatives, flavourings and other suitable additives. Examples
of suitable sweetners include sucrose, lactose, glucose, aspartame
or saccharine. Examples of suitable flavouring agents include
peppermint oil, oil of wintergreen, cherry, orange or raspberry
flavouring. Examples of suitable preservatives include sodium
benzoate, vitamin E, alpha-tocopherol, ascorbic acid, methyl
paraben, propyl paraben or sodium bisulphite.
[0086] Typically the aqueous neutral to mildly alkaline metal
bicarbonate solution is orally administered/consumed on an empty
stomach. Usually consumption in this manner avoids the mixing of
bicarbonate anions with stomach acid which may result in the loss
of bicarbonate. Usually the aqueous neutral to mildly alkaline
metal bicarbonate solution is consumed in small amounts a number of
times through a day typically at set times each day to avoid a
rapid increase in the bicarbonate concentration of body fluids.
Usually the amount of aqueous neutral to mildly alkaline metal
bicarbonate solution consumed at commencement is 500 mL per day and
is increased by increments over a period of one month to the
maximum consumption. This start-up schedule generally avoids any
gastrointestinal side effects due to the smooth muscle relaxation
properties of magnesium.
[0087] The aqueous neutral to very mildly alkaline metal
bicarbonate solution of the invention may be administered
intraveniously (e.g. by discrete injection, semi continuous
injection or drip feed or continuous injection or drip feed) or by
other parenteral routes. Another embodiment of the invention is
directed to a pharmaceutical composition comprising the solution of
the first or eleventh embodiments together with one or more
pharmaceutically acceptable carriers, diluents, adjuvants and/or
excipients. Typically the pharmaceutical composition is suitable
for oral or parenteral administration. Another embodiment of the
invention is directed to a veterinary composition comprising the
solution of the first or eleventh embodiments together with one or
more veterinarily acceptable carriers, diluents, adjuvants and/or
excipients. Typically the veterinary composition is suitable for
oral or parenteral administration. The amount and frequency of
aqueous neutral to mildly alkaline metal bicarbonate solution
administered/consumed in a day is generally sufficient so as to
maintain a steady bicarbonate level in the bicarbonate
concentration of a taker's body fluids. It is preferable to avoid a
rapid increase in the bicarbonate level in the bicarbonate
concentration of a taker's body fluids. For parenteral
administration, the solution is generally sterile. Suitable
mono-toxic parenterally acceptable diluents or solvents include
water, Ringer's solution, isotonic salt solution, 1,3-butanediol,
ethanol, propylene glycol or polyethylene glycols in mixtures with
water. Aqueous solutions or suspensions may further comprise one or
more buffering agents. Suitable buffering agents include sodium
borate, sodium acetate, sodium citrate, or sodium tartrate, for
example. Typically the solution is administered on a regular basis
throughout a day to a patient requiring treatment. For example a
patient may be parenterally administered the solution by way of a
continuous drip feed or alternatively by way of a number of
injections of the solution throughout a day (e.g. every 0.5-8
hours, more typically every 1-4 hours). The treatment is generally
continued as long as required to alleviate the patient's symptoms
to a satisfactory level. For concentration of metal bicarbonate in
the compositions, frequency of administration and amount
administered see discussion under oral administration.
BRIEF DESCRIPTION OF DRAWINGS
[0088] FIG. 1 are plots of the survival curves for a control group
of sheep and a treatment group of sheep;
[0089] FIG. 2 is a photograph showing osteoarthritis in the joints
of the fingers and thumb. Osteoarthritis before the consumption of
aqueous metal bicarbonate solution. Note the swelling and
`claw-like` hand resulting from joint flexion and joint
displacement. (The patient was pushing down with her hand `as hard
as possible` in an attempt to place her hand flat on the underlying
surface.); and
[0090] FIG. 3 is a photograph showing osteoarthritis in the joints
of the fingers and thumb. Osteoarthritis twelve months after
commencement of the consumption of aqueous metal bicarbonate
solution. Note that the fingers can be extended and the joints are
`straighter` than twelve months previously. (The patient bad placed
her hand flat on the underlying surface without exerting any
force.)
BEST MODE AND OTHER MODE(S) FOR CARRYING OUT THE INVENTION
[0091] Magnesium bicarbonate is a natural hydrated salt which
exists only in an aqueous solution. It may be formed in spring
water by an ion exchange process between the protons in carbonic
acid (formed from the hydration of carbon dioxide located in the
atmosphere, organic material, soils and rocks) and the magnesium in
the constituent minerals of rocks (particularly the ferromagnesian
minerals known as pyroxene and olivine that constitute basalt
rocks).
[0092] The ion exchange process can be represented by the following
equations: 1
[0093] The term magnesium bicarbonate is used universally to
describe the mixture of magnesium cations and bicarbonate anions
found in spring waters and mineral waters. Most spring waters and
mineral waters have acidic pH values (about pH 6.0). If the pH
value of the water rises (due to contact with hydroxides), the
magnesium cations and bicarbonate anions "attract" each other
(reversibly) to form the true salt. The chemical formula of
magnesium bicarbonate may be written as Mg(HCO.sub.3).sub.2, or
(more accurately) Mg(H.sub.2O).sub.4(HCO.sub.3).sub.2. This latter
formula takes into account the hexahydrated magnesium cation
Mg(H.sub.2O).sub.6.sup.2+.
[0094] In essence, magnesium bicarbonate exists in aqueous solution
probably as an hydrated salt of indeterminate hydration size due to
the hydrogen bonds between linked water dipoles centred around the
hydrated magnesium cation.
[0095] The chemical processes occurring in magnesium bicarbonate
solutions are complex and depend on the concentrations of magnesium
cations and other ions. The following reactions are considered to
occur: 2
[0096] There exists also a range of possible acid-base equilibria
involving HCO.sub.3.sup.-, H.sub.3O.sup.+, CO.sub.3.sup.2- and
OH.sup.- ions and CO.sub.2 and H.sub.2CO.sub.3. Usually the pH
adjusting agent (and/or stabilising agent) maintains the acid-base
equilibria.
[0097] Typically to prepare the aqueous neutral to mildly alkaline
metal bicarbonate solution, crushed or powdered metal carbonate, or
metal carbonate hydroxide or metal oxide, such as magnesium
carbonate MgCO.sub.3, or commercial magnesium carbonate hydroxide
pentahydrate (MgCO.sub.3).sub.4.Mg(OH).sub.2.5H.sub.2O, or other
commercial magnesium carbonate hydroxides, or hydrated magnesium
oxides, or magnesium oxides heated with carbon dioxide, or the
calcite series or dolonite series of minerals (Mg, Ca)CO.sub.3, or
limestone or dolomite rocks is mixed with water. A cloudy
suspension is obtained. Sufficient carbonic acid or hydrated carbon
dioxide or carbon dioxide gas is added to obtain a solution having
a pH 7 to 9 or pH 7 to 8.6, more typically pH 7.5 to 8.8 or pH 7.5
to 8.5 or pH 7.8 to 8.6, pH 7.8 to 8.5, pH 7.8 to 8.4, pH 7.8 to
8.3, pH 7.8 to 8.2, pH 7.8 to 8.1, pH 7.8 to 8.0, pH 7.8 to 7.9, pH
7.9 to 8.6, pH 7.9 to 8.5, pH 7.9 to 8.4, pH 7.9 to 8.3, pH 7.9 to
8.2, pH 7.9 to 8.1, pH 7.9 to 8.0, pH 8.0 to 8.6, pH 8.0 to 8.5, pH
8.0 to 8.4, pH 8.0 to 8.3, pH 8.0 to 8.2, pH 8.0 to 8.1, pH 8.1 to
8.6, pH 8.1 to 8.5, pH 8.1 to 8.4, pH 8.1 to 8.3, pH 8.1 to 8.2, pH
8.2 to 8.6, pH 8.2 to 8.5, pH 8.2 to 8.4, pH 8.2 to 8.3, pH 8.3 to
8.6, pH 8.3 to 8.5, pH 8.3 to 8.4, pH 8.4 to 8.6, pH 8.4 to 8.5, pH
8.5 to 8.6, even more typically pH 8 to 8.5 or pH 8.2 to 8.6, most
typically pH 8.3. The solution is then typically placed in a sealed
container at 0 to 20.degree. C. with occasional mixing until a
clear solution develops. A clear solution is generally obtained in
about 6 hours to 7 days, typically 12 hours to 5 days, more
typically 24 hours to 5 days, most typically 24 hours to 3 days.
Generally the aqueous neutral to mildly alkaline metal bicarbonate
solution is prepared and stored at a temperature ranging from 0 to
25.degree. C., 0 to 20.degree. C., 0.5 to 25.degree. C., 0.5 to
20.degree. C., 0.5 to 15.degree. C., 0.5 to 10.degree. C., 0.5 to
9.degree. C., 0.5 to 8.degree. C., 0.5 to 7.degree. C., 1 to
20.degree. C., 1 to 15.degree. C., 1 to 10.degree. C., 1.5 to
20.degree. C., 1.5 to 15.degree. C., 1.5 to 10.degree. C., 2 to
20.degree. C., 2 to 15.degree. C., 2 to 10.degree. C., 3 to
20.degree. C., 3 to 15.degree. C., 4 to 20.degree. C., 4 to
15.degree. C., 4 to 10.degree. C., 5 to 20.degree. C., 5 to
15.degree. C., 6 to 20.degree. C., 6 to 15.degree. C., 6 to
10.degree. C., 7 to 20.degree. C., 7 to 15.degree. C., 7 to
10.degree. C., 8 to 20.degree. C., 8 to 15.degree. C., 8 to
10.degree. C., 9 to 20.degree. C., 9 to 15.degree. C., 9 to
10.degree. C., 0 to 15.degree. C., typically 0 to 15.degree. C.,
more typically 0 to 10.degree. C., even more typically 3.degree. C.
to 10.degree. C., most typically 5.degree. C. to 10.degree. C. and
even most typically 5.degree. C. Alternatively the crushed or
powdered metal carbonate, or metal carbonate hydroxide or metal
oxide or mixture thereof is added to an aqueous solution of the
carbonic acid or hydrated carbon dioxide or carbon dioxide gas.
[0098] Typically one litre of water is placed in a container and
sufficient carbonic acid or carbonated water or hydrated carbon
dioxide or carbon dioxide gas is added to produce a pH value of
approximately pH 5.2. (In practice, approximately 40 to 45 mL of
chilled (5.degree. C.) carbonated mineral water is used depending
on the initial pH of the water). The container is sealed and the
contents are mixed. 485 mg magnesium carbonate hydroxide
pentahydrate powder (MgCO.sub.3).sub.4.Mg(O- H).sub.2.5H.sub.2O,
molecular weight 485 is added. The container is again sealed and
the contents are mixed. The container is stored at a temperature of
0 to 10.degree. C. and the contents mixed regularly. Sufficient
time is allowed for a clear solution of magnesium bicarbonate to
develop at a range of pH 8.0 to pH 8.5, typically pH 8.3. This
takes approximately 24 to 72 hours. Alternatively the carbonic acid
or carbonated water or hydrated carbon dioxide or carbon dioxide
gas is added to the magnesium carbonate hydroxide pentahydrate
powder in water.
[0099] Alternatively one litre of water is placed in a container
and sufficient carbonic acid or carbonated water or hydrated carbon
dioxide gas is added to produce a pH value less than pH 5.2. (In
practice, approximately 30 mL to 40 mL of chilled water is used
depending on the initial pH of the water). The container is sealed
and the contents are mixed. 485 mg magnesium carbonate hydroxide
pentahydrate powder (MgCO.sub.3).sub.4.Mg(OH).sub.2.5H.sub.2O,
molecular weight 485 is added. The container is again sealed and
the contents are mixed. The container is stored at a temperature of
0 to 10.degree. C. and the contents mixed regularly. The pH of the
water is then adjusted with an alkali such as sodium hydroxide or
potassium hydroxide to a pH of 8 to 8.5, typically pH 8.3.
Alternatively the carbonic acid or carbonated water or hydrated
carbon dioxide or carbon dioxide gas is added to the magnesium
carbonate hydroxide pentahydrate powder in water.
[0100] Generally once the solution is prepared, the solution may be
stored in a closed container under a blanket of carbon dioxide gas
or a mixture of carbon dioxide gas and usually a nondeleterious
inert gas, for example, argon, helium and/or nitrogen to maintain
the solution at a pH of 7 to 9 and at a temperature of 0 to
25.degree. C. and at 0.8 to 5 atm. The carbon dioxide gas blanket
prevents loss of carbon dioxide from the solution. The amount of
carbon dioxide in the gaseous mixture provides partial pressure on
the liquid which is substantially equal to the partial pressure of
carbon dioxide from carbon dioxide from the solution which is
produced from equilibrium of bicarbonate in the solution at the
particular temperature. In this way the solution is stabilised. If
the solution were left in an open container for any substantial
length of time precipitation of metal carbonate from the solution
would occur as a result of decomposition of the bicarbonate in the
solution as carbon dioxide is liberated from the solution. By using
a stabilising agent in and/or above the solution such decomposition
is substantially minimised or prevented. Alternatively the solution
may be stored in a closed or sealed container (generally airtight)
which is substantially filled with the solution whereby there is
substantially no gas in the container or little gas compared to the
amount of liquid in the container.
[0101] The relevant chemical reactions may be represented by the
following equations: 3
[0102] Usually one litre of the magnesium bicarbonate solution
prepared above contains approximately 120 mg of magnesium per litre
of aqueous neutral to mildly alkaline metal bicarbonate solution
and approximately 600 mg of bicarbonate. 500 mg sodium bicarbonate
(or potassium bicarbonate) is added to the magnesium bicarbonate
solution and mixed. The mixture is stored in a sealed container in
a refrigerator. The mixture contains approximately 120 mg magnesium
per litre of aqueous neutral to mildly alkaline metal bicarbonate
solution, 135 mg sodium per litre of aqueous neutral to mildly
alkaline metal bicarbonate solution and 950 mg bicarbonate per
litre of aqueous neutral to mildly alkaline metal bicarbonate
solution.
[0103] In the body, normal intracellular pH value is pH 7.2. Under
acidic conditions, such as adenosine triphosphate (ATP) hydrolysis,
intracellular pH value may decrease to pH 6.5. In practice, a pH
value is chosen for bicarbonate solutions that exceeds normal blood
plasma pH value (pH>7.38).
[0104] A low temperature, between 0 and 10.degree. C., typically 5
to 10.degree. C., ensures that carbon dioxide stays dissolved in
solution to maximise carbon dioxide hydration Above 15 to
20.degree. C., the solubility of carbon dioxide is low, the carbon
dioxide leaves the solution, and particles and sediments may occur
in the solution. Above 15 to 20.degree. C., the solution may be
cloudy in appearance.
[0105] At high magnesium concentrations, a minimum time, at least
24 to 72 hours at 5.degree. C., is required for completion of the
kinetic processes that produce a clear solution of magnesium
bicarbonate. (The kinetic processes include the hydration of carbon
dioxide, the dissolution of magnesium carbonate and the dissolution
of magnesium hydroxide.)
[0106] The concentration of magnesium cations (in association with
bicarbonate anions) is generally in the range 25 mg to 250 mg per
litre aqueous neutral to mildly alkaline metal bicarbonate solution
(depending on the pH value of the metal bicarbonate solution).
Usually the maximum magnesium concentration that can be maintained
in solution as magnesium bicarbonate may be approximately 120 mg
per litre aqueous neutral to mildly alkaline metal bicarbonate
solution at pH 8.3. As the pH value decreases, the concentration of
magnesium that can be maintained in solution increases. Because
magnesium chloride is soluble, higher concentrations of magnesium
can be maintained in solution if chlorides (such as sodium
chloride) are added to the aqueous neutral to mildly alkaline metal
bicarbonate solution.
[0107] The solubility product constant for magnesium carbonate is
reported to be approximately 3.5.times.10.sup.-8. The solubility
product constant for magnesium hydroxide is reported to be
approximately 1.1.times.10.sup.-11. Calculated from these values,
the maximum concentrations of magnesium cations that can exist in
solution as carbonates or hydroxides are approximately 20 mg per
litre aqueous metal bicarbonate solution and 10 mg per litre
aqueous neutral to mildly alkaline metal bicarbonate solution
respectively.
[0108] Generally the aqueous neutral to mildly alkaline metal
bicarbonate solution of the invention is administered or consumed
orally. Typically the solution is an orally drinkable solution.
Typically the solution is a therapeutic orally drinkable solution.
For example, the aqueous neutral to mildly alkaline metal
bicarbonate solution may be prepared as a solution or an iced
confectionary, such as an ice block or iced dessert, which is
ingested orally. Alternatively the aqueous neutral to mildly
alkaline metal bicarbonate solution may be prepared in the form of
a tablet, lozenge or lolly which is ingested orally. For example,
the aqueous neutral to mildly alkaline metal bicarbonate solution
may be administered for metabolic acidosis or renal failure.
Optionally the solution may be sterilised. Typically the aqueous
neutral to mildly alkaline metal bicarbonate solution is prepared
as a solution which is ingested hourly, daily, monthly or yearly.
The amount of aqueous neutral to mildly alkaline metal bicarbonate
solution administered in a day ranges from 250 mL to 6 litres,
typically 250 mL to 5.5 litres, 250 mL to 5 litres, 250 mL, to 4.5
litres, 250 mL to 4 litres, 250 mL to 3.5 litres, 250 mL to 3
litres, 500 mL to 6 litres, 500 mL to 5.5 litres, 500 mL to 5
litres, 500 mL to 4.5 litres, 500 mL to 4 litres, 500 mL to 3.5
litres, 500 mL to 3 litres, more typically 1 litre to 6 litres, 1
litre to 5.5 litres, 1 litre to 5 litres, 1 litre to 4.5 litres, 1
litre to 4 litres, 1 litre to 3.5 litres, even more typically 1
litre to 3 litres, 1.5 litres to 6 litres, 1.5 litres to 5.5
litres, 1.5 litres to 5 litres, 1.5 litres to 4.5 litres, 1.5
litres to 4 litres, 1.5 litres to 3.5 litres, most typically 2 to 3
litres, usually 2.1 to 3 litres. The aqueous neutral to mildly
alkaline metal bicarbonate solution may be administered on a full
or empty stomach, typically the aqueous neutral to mildly alkaline
metal bicarbonate solution is administered on an empty stomach.
Usually 1.5 to 3 litres, more typically 1.5 to 2.4 litres, even
more typically 1.8 to 2.1 litres and usually between 1.8 and 2.7
litres of aqueous neutral to mildly alkaline metal bicarbonate
solution is ingested on an empty stomach in approximately 300 mL
volumes at set times each day. The solution may be administered
according to these latter dosages over short (for example 1 to 10
days) or long (for example 6 months to 10 years or more) periods as
required. Usually the amount of aqueous neutral to mildly alkaline
metal bicarbonate solution administered to a mammal is 5 to 100 mL
per Kg, more usual 10 to 50 mL per Kg, most usual 14 to 29 mL per
Kg or 25 to 43 mL per Kg.
[0109] Typically the aqueous neutral to mildly alkaline metal
bicarbonate solution is consumed on an empty stomach. Usually
consumption in this manner avoids the mixing of bicarbonate anions
with stomach acid which may result in the loss of bicarbonate.
Usually the aqueous neutral to mildly alkaline metal bicarbonate
solution is consumed in small amounts at set times each day to
avoid a rapid increase in the bicarbonate concentration of body
fluids. Usually the amount of aqueous neutral to mildly alkaline
metal bicarbonate solution consumed at commencement is 500 mL per
day and is increased by increments over a period of one month to
the maximum consumption. This start-up schedule generally avoids
any gastrointestinal side effects due to the smooth muscle
relaxation properties of magnesium.
[0110] The advantages of the aqueous neutral to mildly alkaline
metal bicarbonate solution of the invention are that the magnesium
cations function as bicarbonate transporters into body cells.
Magnesium bicarbonate enters body cells and the bicarbonate anions
function to displace from equilibrium the dissociation reaction of
intracellular carbonic acid. Magnesium bicarbonate enters body
cells and the bicarbonate anions function as an intracellular
proton sink (or proton scavenger). These reactions can be
represented by the one equation 4
[0111] Magnesium bicarbonate enters body cells and the bicarbonate
anions function to displace from equilibrium the hydration reaction
of carbon dioxide which is catalysed by the enzyme carbonic
anhydrase. This reaction can be represented by the equation 5
[0112] Usually appropriate salts of magnesium, sodium, potassium,
calcium and lithium should not exceed the concentrations of the
component elements recommended by health authorities. The
concentrations of component elements cannot exceed concentrations
restricted by the solubility product constants of respective
hydroxides and carbonates.
EXAMPLE 1
An Experiment to Decrease Intracellular Proton Concentrations and
to Increase Intracellular Bicarbonate Concentrations in Mammalian
Cells In Vitro
[0113] Aqueous bicarbonate anions act as proton sinks in the
presence of excess proton concentrations in solution. This reaction
can be represented by the chemical equation 6
[0114] In the presence of sufficient concentrations of bicarbonate
anions, the reaction is essentially complete and proton
concentrations decrease. The pH value of the solution increases.
When plasma bicarbonate anions are present outside mammalian body
cells in sufficient concentrations, they are translocated into the
cytoplasm of the cells across the cell plasma membranes. Indeed
bicarbonate anions equilibrate rapidly across mammalian cell
membranes. Bicarbonate translocation into cells takes place via
several processes. These processes include a chloride-bicarbonate
anion exchange and a sodium dependent chloride-bicarbonate anion
exchange and potassium co-transport and magnesium co-transport.
[0115] An experiment was conducted to decrease intracellular proton
concentrations and to increase intracellular bicarbonate
concentrations in mammalian body cells in vitro. Throughout the
experiment, extracellular pH determinations were made using a pH
electrode and intracellular pH determinations were made using a
trapped fluorescein derivative. An increase in intracellular proton
concentrations (intracellular acidification) was achieved by
applying 10 mmol ammonium chloride (NH.sub.4Cl) solution to a
suspension of cells and then removing the NH.sub.4Cl. An increase
in intracellular bicarbonate concentrations was achieved by
applying an aqueous metal bicarbonate solution to a suspension of
cells. The aqueous metal bicarbonate solution contained
approximately Mg.sup.2+ 120 mg per litre, Na.sup.+ 135 mg per litre
and HCO.sub.3.sup.- 950 mg per litre at pH 8.3. This aqueous metal
bicarbonate solution was equivalent to 15 mmol bicarbonate
approximately. Blood was collected in sodium heparin from a range
of mammals and the leucocytes removed. The leucocytes were washed
and re-suspended in isotonic saline. Intracellular pH
determinations were made by loading leucocytes for 15 minutes with
(10 micromol in saline)
2,7-bis(carboxyethyl)-5,6-carboxyfluorescein (BCECF). Cells were
illuminated at 440 nm and 490 nm and fluorescence was measured at
530 nm.
[0116] The experiment utilising sheep leucocytes is given stepwise
below:
[0117] Step 1. Increase in intracellular proton concentrations
(cytoplasmic acidification)
[0118] A. Leucocytes suspended in normal saline after pretreatment
with fluorescein.
[0119] Extracellular pH 7.2
[0120] Intracellular pH 7.1
[0121] B. 10 mmol ammonium chloride (NH.sub.4Cl) solution pH 7.5
applied to suspension of leucocytes for 10 minutes.
[0122] C. Leucocytes washed and re-suspended in normal saline.
[0123] Extracellular pH 7.3
[0124] Intracellular pH 6.1
[0125] Result: Cells have increased intracellular proton
concentrations. Cytoplasm is acidified.
[0126] Step 2. Decrease in intracellular proton concentrations
[0127] A. Acidified leucocytes (from Step 1.) divided into two
groups; Control group and Treatment group.
[0128] B. Treatment group of leucocytes exposed to aqueous metal
bicarbonate solution.
[0129] After 3 minutes:
[0130] Extracellular pH 7.5
[0131] Intracellular pH 7.0
[0132] C. Control group of leucocytes not exposed to aqueous metal
bicarbonate solution.
[0133] After 5 minutes:
[0134] Extracellular pH 7.2
[0135] Intracellular pH 6.6
[0136] Result: Cells treated with aqueous metal bicarbonate
solution rapidly decrease intracellular proton concentrations.
Cytoplasm shows rapid recovery from acidification relative to
non-treated cells.
[0137] Step 3. Increase in intracellular bicarbonate
concentrations
[0138] A. Leucocytes suspended in normal saline after pretreatment
with fluorescein.
[0139] Extracellular pH 7.2
[0140] Intracellular pH 7.1
[0141] B. Aqueous metal bicarbonate solution applied to suspension
of leucocytes for 20 minutes.
[0142] Extracellular pH 7.9
[0143] Intracellular pH 7.4
[0144] Result: Cells treated with aqueous metal bicarbonate
solution have increased intracellular bicarbonate concentrations
which are manifested by an increase in pH value of cytoplasm.
[0145] The experiment was repeated with leucocytes from mice, rats,
guinea pigs, cattle, horses, dogs, cats and humans. In all cases,
acidified cells treated with aqueous metal bicarbonate solution had
decreased intracellular proton concentrations. In all cases, cells
treated with aqueous metal bicarbonate solution had increased
intracellular bicarbonate concentrations which were manifested by
increased pH values of cytoplasm.
[0146] The experiment was repeated with aqueous metal bicarbonate
solutions that contained a range of concentrations of Mg.sup.2+,
Na.sup.+, HCO.sub.3.sup.- and K.sup.+ and Ca.sup.2+ ions.
Significant results were obtained for the following range of
concentrations:
1 Range of concentrations to achieve Ion significant results
Mg.sup.2+ 20 to 120 mg/litre Na.sup.+ 50 to 500 mg/litre K.sup.+ 50
to 500 mg/litre Ca.sup.2+ 20 to 150 mg/litre HCO.sub.3.sup.- 250 to
2,100 mg/litre (HCO.sub.3.sup.-) (4 mmol to 35 mmol)
[0147] Significant results were obtained for pH range pH 7.5 to
9.5. (pH 9.5 was achieved by the addition of NaOH).
[0148] Aqueous metal bicarbonate solutions, containing a range of
cation and bicarbonate anion concentrations, decrease intracellular
proton concentrations and increase intracellular bicarbonate
concentrations in mammalian cells in vitro.
EXAMPLE 2
An Experiment to Demonstrate Bicarbonate Anion Translocation From
Aqueous Metal Bicarbonate Solution Into the Mammalian Body Against
a Bicarbonate Anion Concentration Gradient
[0149] Mammalian plasma contains bicarbonate anions at a
concentration about 25 mmol (HCO.sub.3.sup.- 1,500 mg per litre).
When ingested, aqueous metal bicarbonate solution produces
biochemical, physiological and medical effects at bicarbonate anion
concentrations about 16 mmol (HCO.sub.3.sup.- 950 mg per litre).
Aqueous metal bicarbonate solution, at bicarbonate anion
concentration about 16 mmol, contains two thirds the bicarbonate
anion concentration of plasma, so bicarbonate anions must be
translocated into the mammalian body against a bicarbonate anion
concentration gradient.
[0150] Mammalian plasma contains cations at concentrations around
Mg.sup.2.sup.+ 24 mg per litre, Na.sup.+ 3,300 mg per litre,
K.sup.+ 175 mg per litre and Ca.sup.2+ 100 mg per litre. Aqueous
metal bicarbonate solution commonly contains cations at
concentrations around Mg.sup.2+ 120 mg per litre, Na.sup.+ 13.5 mg
per litre, K.sup.+ 100 mg per litre and Ca.sup.2+ 20 mg per litre.
Aqueous metal bicarbonate solution commonly contains 5 times the
magnesium cation concentration of plasma. Other cations are present
commonly in aqueous metal bicarbonate solution in concentrations
lower than plasma.
[0151] The concentrations in cations and anions in plasma can be
compared with concentrations of cations and anions in aqueous metal
bicarbonate solution by examination of the following table:
2 Concentrations of cations and anions Aqueous metal Ion Plasma
bicarbonate solution Cl.sup.- 3,600 mg/litre 0 mg/litre Na.sup.+
3,300 mg/litre 135 mg/litre HCO.sub.3.sup.- 1,500 mg/litre 950
mg/litre K.sup.+ 175 mg/litre 100 mg/litre Ca.sup.2+ 100 mg/litre
20 mg/litre Mg.sup.2+ 24 mg/litre 120 mg/litre
[0152] It is suggested that sodium cations and chloride anions
leave plasma along their respective concentration gradients and
magnesium and bicarbonate ions enter plasma along a magnesium
cation concentration gradient. Magnesium functions as a bicarbonate
transporter. In addition, it is suggested that bicarbonate anions
enter plasma by chloride-bicarbonate exchange processes along a
chloride anion concentration gradient (chloride `out`, bicarbonate
`in`).
[0153] In mammals, any large increases in plasma bicarbonate
concentrations can be decreased normally by a number of biochemical
and physiological homeostatic control processes. These processes
occur in time frames that range from minutes to hours and longer.
One of the main control processes that occurs as a result of
increased plasma bicarbonate concentration is an alteration in
bicarbonate chemistry in the kidneys. This is manifested by a
decrease in proton concentration in urine and by a pH value of
urine that is less acidic. In the presence of increased plasma
bicarbonate, kidney tubule cells decrease their excretion of
protons. Kidney control of bicarbonate concentration is not
instantaneous and occurs within a time frame of several hours to
several days. Unless a mammal has physiological or clinical
acidosis, it is difficult to detect small increases in plasma
bicarbonate concentration. Any increases in plasma bicarbonate
concentration are taken up by body cells. Indeed, plasma
bicarbonate equilibrates with intracellular bicarbonate rapidly In
a normal mammal, a measurable increase in plasma bicarbonate
concentration occurs only during an artificially induced alkalosis
and is detectable either when the consumption of bicarbonate anions
(as NaHCO.sub.3) greatly exceeds the concentration of bicarbonate
in normal plasma or when bicarbonate anions (as NaHCO.sub.3) are
administered intravenously.
[0154] An experiment was conducted to determine if bicarbonate
anions in aqueous metal bicarbonate solutions are translocated
against a bicarbonate concentration gradient into the body.
Bicarbonate translocation against a concentration gradient could
occur either via energy (ATP) dependent processes or via anion
(chloride-bicarbonate) exchange or via co-transport with cations
along cation concentration gradients. There are also complex
thermodynamic processes involving intracellular and extracellular
concentrations of bicarbonate anions, hydroxide anions, protons and
carbon dioxide that may assist in the overall translocation of
bicarbonate anions. These processes often involve the production of
bicarbonate anions by carbonic anhydrase enzymes. In the
experiment, entry of bicarbonate anions into the body was assessed
by determinations of proton concentration in urine; that is, the pH
value of urine.
[0155] Ten people had urine pH value ssed once per week for 3
months. Urine pH values were assessed once per week for a further 3
months after commencement of consumption of aqueous metal
bicarbonate solution. The aqueous metal bicarbonate solution
contained approximately Mg.sup.2+ 120 mg per litre, Na.sup.+ 135 mg
per litre and HCO.sub.3.sup.- 950 mg per litre. The major component
of the solution was magnesium bicarbonate Mg(HCO.sub.3).sub.2 720
mg per litre approximately. Results are given below:
3 Mean pH value of urine (Early morning sample) Prior to
consumption of aqueous pH 5.9 metal bicarbonate solution: After
commencement of consumption pH 6.7 of aqueous metal bicarbonate
solution:
[0156] The consumption of aqueous metal bicarbonate solution
decreases proton excretion by the kidneys. The pH value of urine
increases.
[0157] These results demonstrate that bicarbonate anions from
aqueous metal bicarbonate solution are translocated against a
bicarbonate anion concentration gradient into the body. This may
occur either via co-transport with cations along a cation
concentration gradient or via chloride-bicarbonate exchange
processes along a chloride anion concentration gradient (chloride
`out`, bicarbonate `in`). In the case of aqueous metal bicarbonate
solution, the only cation concentration gradient possible is that
involving magnesium cation concentrations.
[0158] The consumption of aqueous metal bicarbonate solution leads
to an increase in bicarbonate anion concentration in the body which
is manifested by a decrease in proton concentration in urine; an
increase in pH value of urine.
EXAMPLE 3
An Experiment to Improve the Buffering Capacities of the
Extracellular and Intracellular Bicarbonate Buffers and to Decrease
Senescence and to Increase Longevity in a Representative Mammal
[0159] Mammalian body cells produce continuously concentrations of
carbon dioxide. Upon hydration, carbon dioxide increases proton
concentrations in the cytoplasm of body cells. The pH values of the
cytoplasm of body cells are lowered. The production of protons in
cytoplasm by the hydration of carbon dioxide can be represented by
the following chemical equations:
CO.sub.2+H.sub.2OH.sub.2CO.sub.3
H.sub.2CO.sub.3+H.sub.2OH.sub.3O.sup.++HCO.sub.3.sup.-
[0160] The protons produced the cytoplasm of body cells by the
hydration of carbon dioxide, and other intracellular reactions, are
buffered normally by intracellular bicarbonate buffers. The
bicarbonate anions in intracellular buffers derive manly from the
extracellular bicarbonate of blood plasma. The bicarbonate anions
in blood plasma originate from erythrocytes as products of
erythrocyte carbonic anhydrase enzyme reactions.
[0161] When plasma bicarbonate anions are present outside mammalian
body cells in sufficient concentrations, they are translocated into
the cytoplasm of the cells across the cell plasma membranes.
Indeed, plasma bicarbonate equilibrates with cytoplasmic
bicarbonate rapidly. Bicarbonate translocation into cells takes
place via several processes. These processes include a
chloride-bicarbonate anion exchange and a sodium dependent
chloride-bicarbonate anion exchange and potassium co-transport and
magnesium co-transport. There are also complex thermodynamic
processes involving intracellular and extracellular concentrations
of bicarbonate anions, hydroxide ions, protons and carbon dioxide
that may assist in the overall translocation of bicarbonate anions.
These processes often involve the production of bicarbonate anions
by carbonic anhydrase enzymes.
[0162] Concentrations of bicarbonate anions that are translocated
into mammalian body cells improve the buffering capacity of the
cytoplasm of the cells. Concentrations of bicarbonate anions and
concentrations of carbon dioxide form a buffer system described by
the Henderson-Hasselbalch equation:
pH=pK+log ([HCO.sub.3.sup.-]/[H.sub.2CO.sub.3])
[0163] (Where pK is the pK of hydrated carbon dioxide
H.sub.2CO.sub.3 and has an approximate numerical value of 6.35)
[0164] For a classical (closed system) buffer to be effective, the
ratio of the conjugate base to the acid (in the above case
[HCO.sub.3.sup.-]/[H.sub.2CO.sub.3]) must be between 0.1 and 10.
This ratio applies also to buffers in biological (open) systems. In
mammalian body cells, the continuous and open production of carbon
dioxide means that continuous supplies of bicarbonate anions are
required to maintain effective and optimal buffering capacities.
Under conditions of excess proton concentrations, from carbon
dioxide production and ATP hydrolysis and other metabolic
processes, the supply of bicarbonate fails and the effective and
optimal buffering capacities of mammalian body cells falter.
[0165] The vitality of mammalian body cells is linked critically to
the buffering capacities of the extracellular fluids and the
cytoplasm of the cells. Processes of cellular degeneration occur
when buffering capacities falter in the presence of excess proton
concentrations. Cellular degenerations are manifested in the
mammalian body by degenerative diseases and senescence. Examples of
degenerative diseases in mammals that are linked casually to
extracellular and intracellular proton concentrations include
osteoporosis, osteoarthritis, the diseases associated with chronic
inflammation, the diseases associated with lysosomal enzyme
activities, the diseases associated with oxidations of cell nucleic
acids, cell protein amino acids and cell membrane lipids, and the
diseases associated with aberrations of mitochondrial
respiration.
[0166] An experiment was conducted to improve the buffering
capacities of the extracellular and intracellular bicarbonate
buffers and to consequently decrease senescence and increase
longevity in a representative mammal. One hundred and ten Merino
ewe lambs were divided randomly at weaning into a control group and
a treatment group. The groups were of equal size and were
maintained under similar conditions except for the pH values and
aqueous metal bicarbonate concentrations of drinking water
supplies. Sheep were selected as the representative mammal because
their life span and body weight are more representative of typical
mammals than laboratory rodents, their life span is not excessively
long, their body size permits multiple blood and tissue sample
collections, they are easy to handle and their husbandry is suited
to experimental conditions. The control group was maintained, for
the full life span of the sheep, in small experimental paddocks
with slightly acidic (less than pH 6.5) drinking water supplies
that contained bicarbonate concentrations less than 30 mg per
litre. The treatment group was maintained, for the full life span
of the sheep, in small experimental paddocks with slightly alkaline
(pH 7.8 to 9.0) drinking water supplies that contained bicarbonate
concentrations between 300 mg per litre and 800 mg per litre. The
drinking water supplies for the treatment group were loaded with
the appropriate concentrations of bicarbonate anions by the
addition of crushed and powdered magnesite MgCO.sub.3 to the water.
The magnesite frequently contained calcite CaCO.sub.3 and dolomite
(Ca,Mg)CO.sub.3. The magnesite was dissolved in the drinking water
either with the assistance of commercial supplies of carbon dioxide
gas or carbonic acid or with local supplies of hydrated carbon
dioxide. This dissolution process can be represented by the
following chemical equations:
CO.sub.2+H.sub.2OH.sub.2CO.sub.3
H.sub.2CO.sub.3+H.sub.2OH.sub.3O.sup.++HCO.sub.3.sup.-
MgCO.sub.3+H.sub.3O.sup.++HCO.sub.3.sup.-Mg(HCO.sub.3).sub.2+H.sub.2O
[0167] The treatment group of sheep consumed slightly alkaline (pH
7.8 to 9.0) drinking water that contained bicarbonate
concentrations between 300 mg per litre and 800 mg per litre. At
this pH value, and this bicarbonate concentration, bicarbonate was
mostly in the form of magnesium bicarbonate Mg(HCO.sub.3).sub.2:
7
[0168] In addition, some sediments of carbonate (Ca,Mg)CO.sub.3
were present in the drinking water during summer months: 8
[0169] The mean pH values and the mean magnesium, calcium and
bicarbonate concentrations in the drinking water supplies are given
below (the concentrations of cations and bicarbonate anions were
not stoichiometric in the drinking water--particularly the drinking
water of the control group--because of the presence of some
concentrations of sulphate, chloride and sodium ions):
4 Means of parameters in drinking water Control Group Treatment
Group pH 6.1 8.4 Mg.sup.2+ mg/litre 13 110 Ca.sup.2+ mg/litre 20 30
HCO.sub.3.sup.- mg/litre 25 660
[0170] In the late stages of pregnancy, there is a tendency for
pregnant mammals to become hypoglycaemic and hyperketonaemic.
Hyperketonaemia subjects the pregnant mammal to an acid load
(increase in proton concentrations). This acid load may result in
clinical acidosis. Like all mammals, pregnant ewes tend to be
hypoglycaemic and hyperketonaemic late in pregnancy. In ewes
affected clinically with acidosis, bicarbonate concentrations range
between 14 to 20 mmol per litre plasma.
[0171] Over several years, plasma bicarbonate concentrations were
determined for the control group and the treatment group one week
prior to lambing. Determination of plasma bicarbonate
concentrations prior to lambing is a direct measure of
extracellular and intracellular bicarbonate buffering capacity. In
ewes with effective extracellular and intracellular bicarbonate
buffers, bicarbonate concentrations are maintained in a range
between 24 to 27 mmol per litre plasma. Plasma bicarbonate
concentrations are given below:
5 Mean plasma bicarbonate concentrations one week prior to lambing
(mmol per litre) Age (years) Control Group Treatment Group 4 24.9
26.1 6 22.8 25.9 8 22.2 26.4 10 21.9 25.8 The treatment group had
larger plasma bicarbonate concentrations than the control
group.
[0172] The consumption of aqueous metal bicarbonate solution,
principally magnesium bicarbonate solution, improves the buffering
capacities of extracellular and intracellular bicarbonate buffers
in mammals.
[0173] In mammalian demography, there are two measurements utilised
commonly in the experimental study of degenerative diseases and
senescence. The first measurement is called fifty percent survival.
Fifty percent survival describes the chronological age at which
half an original population bas died. The second measurement is
called maximum life span. Maximum life span describes the age of
the longest lived survivors of a population. The fifty percent
survival measurement is considered to reflect susceptibility to
accidents and infectious and degenerative diseases in mammals. The
maximum life span measurement is considered to reflect the innate
processes of senescence in mammals. The fifty percent survival
measurement and the maximum life span measurement for the control
group and the treatment group are given below:
6 Fifty percent survival Control group 8 years Treatment group 11
years Maximum life span Control group 13 years Treatment group 17
years
[0174] The treatment group had a larger fifty percent survival
measurement and a larger maximum life span measurement than the
control group.
[0175] The death of each member of a population of mammals can be
plotted graphically. The continuous function representing mortality
in a population is known as a survival curve. Survival curves for
the control group and treatment group are represented in FIG.
1.
[0176] The survival curves show that more mature sheep were alive
in the treatment group than the control group at any time. This
occurred with the consumption of normal physiological volumes of
water (as aqueous metal bicarbonate solution).
[0177] The consumption of aqueous metal bicarbonate solution,
extends the maximum life span of mammals by at least twenty percent
and increases the number of mature mammals alive at any time.
[0178] Senescence in mammals is characterised by progressive
oxidations of the structural and function molecules that constitute
body cells and tissues. These oxidations occur particularly in
nucleic acids, protein amino acids and cell membrane lipids.
[0179] Because protons often participate in biological redox
reactions, oxidations of many structural and functional molecules
in body cells and tissues are increased in rate by the presence of
excess proton concentrations. Oxidations of structural and
functional molecules are increased in rate by acidic
conditions.
[0180] In general, oxidations of molecules are linked to proton
concentrations described by a formulation of the Gibbs energy
equation
E.sub.pH=E.sub.m+2.3 RT/F log ([oxidised]/[reduced])
[0181] where E.sub.pH is a measure of oxidising power at a
particular pH value and E.sub.m is the mid-point potential. In
practice, E.sub.pH is decreased by between -30 mV and -60 mV for
each decrease in proton concentration by a factor of 10. That is,
oxidising power is decreased by between -30 mV and -60 mV for each
increase in pH value by 1 pH unit.
[0182] Oxidations of nucleic acids and protein amino acids lead to
nucleic acid and protein degradation respectively. These
degradations lead to senescence in mammals. Nucleic acid
degradation is manifested by either cell death or cell
transformation to the cancerous state. Protein degradation is
manifested by increased urea concentrations in the body which can
be detected in the plasma.
[0183] Determination of plasma urea concentrations in elderly
mammals is a direct measure of amino acid oxidation, protein
degradation and overall nitrogen (anabolic/catabolic) balance.
Determination of plasma urea concentrations in elderly mammals is a
direct measure of cellular degenerations and senescence.
[0184] Over several years, plasma urea concentrations were
determined for the control group and the treatment group. Plasma
urea concentrations are given below:
7 Mean plasma urea concentrations in elderly sheep (mmol per litre)
Age (years) Control Group Treatment Group 8 11 5 10 13 3 12 13 7
The treatment group had smaller plasma urea concentrations than the
control group.
[0185] The consumption of aqueous metal bicarbonate solution,
principally magnesium bicarbonate solution, decreases amino acid
oxidations, decreases protein degradation and improves overall
nitrogen (anabolic/catabolic) balance in mammals. The consumption
of aqueous metal bicarbonate solution, principally magnesium
bicarbonate solution, delays cellular degenerations and senescence
in mammals.
[0186] Autopsies were performed on sheep, when conditions
permitted, within 24 hours of death. Macroscopic signs of
significant degenerative diseases and other diseases were recorded.
Significant pathology is given below:
8 Prevalence of pathology at autopsy (%) Macroscopic Significant
Pathology Control Group Treatment Group (* most significant) (42
autopsies) (38 autopsies) Lungs 24% 21% *Heart 29% 11% Liver 43%
21% Kidney 24% 16% Other Genito-urinary 17% 16% Lymph nodes 40% 37%
Intestinal tract 10% 8% *Joints 43% 5% *Bone 24% 3% Teeth 71% 40%
*Skin-wool 48% 21% Cancer 12% 3% The treatment group had a lower
overall prevalence of pathology than the control group. In general,
pathology in the treatment group was delayed (sheep were older at
autopsy) and progression was less advanced.
[0187] The consumption of aqueous metal bicarbonate solution,
principally magnesium bicarbonate solution, decreases the
prevalence of joint pathology (arthritis) and bone pathology
(osteoporosis) and cardiac pathology and skin pathology most
significantly and decreases the overall prevalence of the pathology
of most organs.
EXAMPLE 4
An Experiment to Distinguish Between the Consumption of Magnesium
Bicarbonate and the Consumption of Magnesium Cations Per Se in
Increasing Longevity in a Mammal
[0188] An experiment was conducted to assess if the consumption of
magnesium bicarbonate increased longevity in a mammal compared to
the consumption of magnesium cations per se. A short-lived
mammalian species was chosen. Short-lived mammals possess high
levels of proton leak across inner mitochondrial membranes, high
levels of carbonic anhydrase enzyme activities (for acid
production) and high levels of spontaneous cancer development and
spontaneous death. Any increase in longevity in a short-lived
species is indicative of an improvement in fundamental cell
biochemistry. Two hundred outbred (Swiss) female mice were divided
randomly at weaning into two groups of 100 mice and were maintained
under identical management and environmental conditions.
[0189] One group of mice was supplied with drinking water that
consisted of aqueous metal bicarbonate solution with a pH value
between pH 8.1 and pH 8.5. The aqueous metal bicarbonate solution
contained approximately Mg.sup.2+ 120 mg per litre, Na.sup.+ 135 mg
per litre and HCO.sub.3.sup.- 950 mg per litre. The major component
of the solution was magnesium bicarbonate Mg(HCO.sub.3).sub.2 720
mg per litre approximately. The second group of mice was supplied
with drinking water that contained magnesium sulphate (Epsom salts)
1 gram per litre with a pH value between pH 6.5 and pH 7.0. This
drinking water contained approximately Mg.sup.2+ 120 mg per litre.
Bicarbonate anions were absent.
[0190] Both groups of mice were fed commercial laboratory food that
contained 1 grain of magnesium per kilogram of food. Both groups of
mice were fed on alternate days with no food available on the other
days. Group-specific drinking water (as described above) was
available at all times. Feeding on alternate days decreased the
possible loss of bicarbonate anions by stomach acid and food
ingesta.
[0191] Results of the experiment are given below:
9 Fifty Percent Survival Group consuming magnesium bicarbonate 790
days Group consuming magnesium sulphate 736 days Maximum Life Span
Group consuming magnesium bicarbonate 1152 days Group consuming
magnesium sulphate 1040 days
[0192] The group of mice consuming aqueous metal bicarbonate
solution had longevity increased by ten percent compared to the
group of mice consuming magnesium cations per se.
[0193] The consumption of aqueous metal bicarbonate solution,
principally magnesium bicarbonate solution, extends the maximum
life span of mammals by ten percent more than the consumption of
magnesium cations per se
EXAMPLE 5
An Experiment to Decrease the Clinical Signs of Osteoarthritis
[0194] Osteoarthritis is a disease of degeneration. There is
degradation and inflammation of the joints of the body.
Osteoarthritis is defined as a disease process involving a
disturbance of the normal balance of degradation and repair in the
articular cartilage and subchondral bone of joints. This
disturbance of balance causes areas of morphological damage and
results in clinical problems such as pain and disability.
Osteoarthritis is manifested as a slowly progressive degeneration
of the joints of the hands and large weight-bearing joints (hips
and knees). It is common in post menopausal women. Osteoarthritis
is characterised by pain, enlargement of joints and limitation of
joint movements. The linings of osteoarthritic joints show a
moderate to marked degree of inflammation. The principle
pathological changes associated with osteoarthritis are destruction
of joint cartilage and neoformations of bone at joint margins
(osteophytes). In osteoarthritis, destruction of joint cartilage is
caused by acid protease enzymes (and other enzymes) derived often
from the lysosomes of cartilage cells (chondrocytes), inflammatory
cells and other cells.
[0195] Acid protease enzymes possess optimal activity in an acidic
environment; that is, an environment with high proton
concentrations. Proton concentrations involved in the pathogenesis
of osteoarthritis derive from the hydration of carbon dioxide
catalysed by intracellular carbonic anhydrase enzymes. The
production of protons by carbonic anhydrase enzymes call be
represented by the equation 9
[0196] Protons formed by carbonic anhydrase enzymes are
concentrated by intracellular V-type proton pumps and stored in the
endosomes and lysosomes of body cells.
[0197] Functional endosomes and lysosomes maintain internal
concentrations of protons which give them internal pH values
between pH 3.0 and pH 6.0. Many degenerative diseases, including
osteoarthritis, involve intracellular and extracellular release of
lysosomal enzymes. In osteoarthritis, chemical fluxes through the
reactions catalysed by lysosomal enzymes result in the breakdown of
cartilage and bone.
[0198] An experiment was conducted to assess if the clinical signs
of osteoarthritis could be decreased by the consumption of aqueous
metal bicarbonate solution. The clinical signs of osteoarthritis
include pain, swelling, inflammation, skill discoloration, joint
deformities and decrease in joint function. An increase in
extracellular and intracellular bicarbonate anion concentrations
would decrease the production of protons from reactions catalysed
by carbonic anhydrase enzymes, decrease the pumping of protons by
V-type proton pumps, decrease the activities of acid protease
enzymes and decrease other activities of lysosomes. The clinical
signs of osteoarthritis would be alleviated. A group of ten people
were chosen who had been diagnosed with having osteoarthritis. Each
person in the group had been suffering from (clinical)
osteoarthritis for between 2 and 5 years. Five of the group were
post menopausal women who had clinical signs of osteoarthritis in
the joints of their hands. The osteoarthritic joints included the
distal and proximal interphalangeal joints of the fingers and the
carpometacarpal joint of the thumbs. In all 5 cases, loss of joint
function was moderate to severe.
[0199] In all 5 cases, the women suffered pain, swelling of the
fingers and loss of joint movement. Mucous cysts were associated
with distal joint osteoarthritis. Lateral deformities occurred in
some proximal joints with severe loss of joint function. Women with
affected thumbs had considerable loss of function and considerable
pain. Many hands were "claw-like" in appearance (FIG. 2). The
remainder of the group had osteoarthritis in the hips and knees.
These people suffered pain and moderate loss of joint
functions.
[0200] The people consumed aqueous metal bicarbonate solution with
a pH value between pH 8.1 and 8.5. The aqueous metal bicarbonate
solution contained approximately Mg.sup.2+ 120 mg per litre,
Na.sup.+ 135 mg per litre and HCO.sub.3.sup.- 950 mg per litre. The
major component of the solution was magnesium bicarbonate
Mg(HCO.sub.3).sub.2 720 mg per litre approximately.
[0201] Consumption of the aqueous metal bicarbonate solution was
commenced at half a litre per day and increased by increments over
a period of one month to between 2 to 3 litres per day. Consumption
occurred on an empty stomach to avoid the loss of bicarbonate by
stomach acid (HCl). Consumption occurred in small amounts (300 ml)
at set times each day to avoid rapid increases in bicarbonate
concentrations of body fluids and to avoid over hydration.
[0202] The results of the experiment were unequivocal. Within 3 to
6 months, all participants in the experiment demonstrated
substantial decreases in the clinical signs of osteoarthritis.
[0203] In all cases, there were remissions in the clinical signs of
osteoarthritis which were quantifiable by standard tests of
movement, flexibility and strength. The participants showed
considerable increases in joint functions and decreases in acute
and chronic joint swellings. The "stabbing" pain or osteoarthritis
was alleviated. Some participants had remissions of inflammation
and arthritis to the stage where many chronic swellings were no
longer observable and joint mobilities and functions were restored
(FIG. 3).
[0204] People in the experiment consumed aqueous metal bicarbonate
solution continuously for at least 2 years. During this period,
there was evidence of progressive improvement in healing processes.
Mucous cysts associated with distal joint osteoarthritis were no
longer visible.
[0205] Remissions in the clinical signs of osteoarthritis were
maintained only with the continual consumption of aqueous metal
bicarbonate solution. Once the consumption of aqueous metal
bicarbonate solution was halted, clinical signs of pain and
swelling began to reappear within 10 days. Clinical signs again
went into remission upon continuation of consumption of aqueous
metal bicarbonate solution.
[0206] The consumption of aqueous metal bicarbonate solution,
principally magnesium bicarbonate solution, results in remissions
in the clinical signs of osteoarthritis.
EXAMPLE 6
An Experiment to Maintain and Improve Motor Activity in Mammals. An
Experiment to Decrease Fatigue and Lethargy and Improve Motor
Activity. An Experiment to Decrease the Fatigue and Lethargy of
Chronic Disease and Improve Motor Activity
[0207] Mammals convert food energy into chemical energy that can be
used by body cells to maintain essential cell processes and cell
functions. The main chemical energy in mammalian body cells is the
chemical ATP (adenosine triphosphate). ATP is synthesised mainly in
the mitochondria of body cells. Mitochondrial ATP production is
linked intimately to the respiration rates of mitochondria. The
respiration rates of mitochondria are dependent on many factors
including the proton concentrations (pH values) of the cytoplasm of
body cells. If the intracellular bicarbonate buffer of mammalian
body cells is not maintained, and is not functional, proton
concentrations increase in the cytoplasm and the pH value of the
cytoplasm decreases. When proton concentrations increase in the
cytoplasm sufficiently (pH value decreases sufficiently) the
respiration rates of mitochondria are diminished. When the
respiration rates of mitochondria are diminished, the production of
ATP is diminished. When the production of ATP is diminished, ATP
concentrations in the cell decrease and the main chemical energy
source for mammalian body cells becomes depleted. Under these
conditions, body cells cannot maintain essential cell processes and
cell functions. The body becomes fatigued and lethargic.
[0208] In addition to the hydration of carbon dioxide per se, one
of the sources of increased proton concentrations in the cytoplasm
of body cells is the hydrolysis of ATP. The hydrolysis of ATP can
be represented by the chemical equation
ATP+H.sub.2OADP+P.sub.i+H.sup.+
[0209] Increased proton concentrations from the hydrolysis of ATP
occur particularly in the cytoplasm of muscle cells during muscular
(motor) activity. This is referred to often as an increase in
`lactic acid` (the lactic acid is, in fact, lactate derived from
glycolysis and the `acid` is the protons derived from ATP
hydrolysis).
[0210] An experiment was conducted to assess if motor activity
could be maintained and improved in mammals by improving the
buffering capacity of the extracellular and intracellular
bicarbonate buffers.
[0211] Two hundred inbred (Balb c) female mice were divided
randomly at weaning into two groups of 100 mice and maintained
under identical conditions for 3 years. Control groups of mice were
given drinking water that was deionised and slightly acidic (pH
5.0). Treatment groups of mice were given drinking water that
consisted of aqueous metal bicarbonate solution with a pH value
between pH 8.1 and 8.5. The aqueous metal bicarbonate solution
contained approximately Mg.sup.2+ 120 mg per litre, Na.sup.+ 135 mg
per litre and HCO.sub.3.sup.- 950 mg per litre. The major component
of the solution was magnesium bicarbonate Mg(HCO.sub.3).sub.2 720
mg per litre approximately.
[0212] Motor activity in mice was assessed at regular intervals for
a 12 month period between 1 year and 2 years of age. Results of the
experiment are given below:
10 Mean motor activity in mice Control Group Treatment Group Mean
number of mice per hour 26 95 climbing to lid of cage Mean number
of mice per hour 48 82 engaged in exploratory activity Mean time to
exhaustion during 5 minutes 9 minutes enforced motor activity The
treatment group had improved motor activity relative to the control
group.
[0213] The consumption of aqueous metal bicarbonate solution,
principally magnesium bicarbonate solution, maintains and improves
motor activity in mammals.
[0214] Mitochondria are described as `efficient` if they maintain
sufficient production of ATP for maintenance of essential cell
processes and cell functions. Efficient mitochondria are the
mitochondria of young mammals.
[0215] In mammals, there are declines in the efficiencies of
mitochondria which are correlated to chronological age. The
capacities of cells to maintain their particular energy
requirements are diminished progressively with chronological age.
Cells that are unable to meet their particular energy requirements
undergo senescence, become non-functional and decline progressively
towards cell death. This is manifested by body senescence and
ageing. Mitochondria are described as `inefficient` if they cannot
maintain the necessary production of ATP for maintenance of
essential cell processes and cell functions. Mitochondrial
inefficiency arises from oxidative damage to mitochondrial nucleic
acids, mitochondrial enzymes and mitochondrial membrane proteins
and lipids. Inefficient mitochondria gradually and progressively
dominate in body cells through middle age to old age. Middle aged
and elderly mammals are fatigued and lethargic relative to the
young. Normal body cells attempt to produce buffers that maintain a
cytoplasmic pH value of about pH 7.2. In vitro, if mitochondria are
placed for a period in a medium either with an improved buffer at
pH 7.2 or with a pH value buffered slightly higher than pH 7.2,
there occurs an increase in mitochondrial respiration rate and an
increase in the production of ATP.
[0216] An experiment was conducted to assess if fatigue and
lethargy could be decreased and motor activity improved by
improving the buffering capacity of the cytoplasmic bicarbonate
buffer in a group of middle aged and elderly people.
[0217] Improving the buffering capacity of the cytoplasmic
bicarbonate buffer would increase mitochondrial respiration rate
and increase the production of ATP. Mitochondria would become more
`efficient`. More chemical energy would be available for
maintenance of essential cell processes and cell functions. Fatigue
and lethargy would decrease and motor activity would improve.
[0218] A group of nineteen people were chosen, with a mean age of
61 years, who had a history of fatigue and lethargy. In the context
of this experiment, fatigue and lethargy were determined as
subjective feelings of general exhaustion which were manifested by
mild to moderate lack of function. The people consumed aqueous
metal bicarbonate solution with a pH value between pH 8.1 and 8.5.
The aqueous metal bicarbonate solution contained approximately
Mg.sup.2+ 120 mg per litre, Na.sup.+ 135 mg per litre and
HCO.sub.3.sup.- 950 mg per litre. The major component of the
solution was magnesium bicarbonate Mg(HCO.sub.3).sub.2 720 mg per
litre approximately.
[0219] Consumption of the aqueous metal bicarbonate solution was
commenced at half a litre per day and increased by increments over
a period of one month to between 2 to 3 litres per day. Consumption
occurred on an empty stomach to avoid the loss of bicarbonate by
stomach acid (HCl). Consumption occurred in small amounts (300 ml)
at set times each day to avoid rapid increases in bicarbonate
concentrations of body fluids and to avoid over hydration.
[0220] The results of the experiment were unequivocal. Within 3
months, all participants in the experiment demonstrated substantial
decreases in fatigue and lethargy. All participants described a
feeling of well-being (mild euphoria). All participants
demonstrated an increased capacity for mild physical activity; an
improvement in motor activity. Function was restored.
[0221] The consumption of aqueous metal bicarbonate solution,
principally magnesium bicarbonate solution, decreases fatigue and
lethargy and improves motor activity in middle aged and elderly
people.
[0222] Chronic disease (including degenerative disease) is
manifested often by chronic fatigue and lethargy and chronic pain.
This is the particularly for chronic inflammatory diseases and
autoimmune diseases.
[0223] The fatigue, lethargy and pain of chronic disease are
correlated often to the high proton concentrations involved in the
pathogenesis of chronic disease. In addition to the hydration of
carbon dioxide per se, proton concentrations involved in the
pathogenesis of chronic disease derive from the hydration of carbon
dioxide catalysed by intracellular carbonic anhydrase enzymes. The
production of protons by carbonic anhydrase enzymes can be
represented by the equation 10
[0224] Protons formed by carbonic anhydrase enzymes are
concentrated often by V-type proton pumps and stored in endosomes
and lysosomes in the cell. The breakdown of endosomes and lysosomes
creates concentrations of protons in the cell cytoplasm. This
lowers the pH value of the cytoplasm and decreases the production
of ATP in mitochondria. Cells become energy deficient. Cells are
unable to maintain essential cell processes and cell functions, the
body becomes fatigued and lethargic.
[0225] Functional endosomes and lysosomes maintain internal
concentrations of protons which give them internal pH values
between pH 3.0 and pH 6.0. Many of the chronic and degenerative
diseases of the body involve intracellular lysosomal activities and
intracellular and extracellular release of lysosomal enzymes.
Chemical fluxes through the reactions catalysed by lysosomal
enzymes result in the breakdown of cells and tissues. Many
lysosomal enzymes require low pH values for optimal activity. Some
of these enzymes are known as acid protease enzymes.
[0226] Lysosomes located in cells known as macrophages, and in some
other cells, are involved in antigen processing and antigen
presentation. Antigen processing and presentation leads to cell to
cell interactions within the immune system which triggers release
of a set of chemicals called cytokines. Cytokine concentrations in
the body are correlated often to many of the clinical signs of
inflammation and disease. These clinical signs include heat,
swelling, pain, fatigue and lethargy.
[0227] An experiment was conducted to assess if fatigue and
lethargy could be decreased and motor activity improved by
improving the buffering capacity of the cytoplasmic bicarbonate
buffer in a group of people diagnosed and suffering with chronic
disease.
[0228] Improving the buffering capacity of the cytoplasmic
bicarbonic buffer would decrease the hydration of carbon dioxide
per se, would decrease the production of protons from reactions
catalysed by carbonic anhydrase enzymes, decrease the pumping of
protons by V-type proton pumps, decrease the activities of acid
protease enzymes, decrease the activities of lysosomes, decrease
antigen processing and presentation, and increase the production of
ATP. Fatigue and lethargy would decrease and motor activity would
improve. Some of the clinical signs of chronic disease would be
alleviated.
[0229] A group of twenty three people were chosen who had been
diagnosed with having chronic disease. Each person had been
suffering from chronic disease for between 3 and 8 years. The
diseases consisted of chronic viral diseases, chronic inflammatory
diseases and autoimmune diseases and included rheumatoid arthritis
and dermatitis. All people had a history of fatigue and lethargy In
the context of this experiment, fatigue and lethargy were
determined as subjective feelings of general exhaustion which were
manifested by moderate to severe lack of function. The people
consumed aqueous metal bicarbonate solution with a pH value between
pH 8.1 and 8.5. The aqueous metal bicarbonate solution contained
approximately Mg.sup.2+ 120 mg per litre, Na.sup.+ 135 mg per
litre, K.sup.+ 100 mg per litre and HCO.sub.3.sup.- 1,100 mg per
litre. The major component of the solution was magnesium
bicarbonate Mg(HCO.sub.3).sub.2 720 mg per litre approximately.
Potassium bicarbonate 250 mg per litre was a component of the
aqueous metal bicarbonate solution to improve the co-transport of
bicarbonate anions into body cells. Consumption of the aqueous
metal bicarbonate solution was commenced at half a litre per day
and increased by increments over a period of one month to between 2
to 3 litres per day. Consumption occurred on an empty stomach to
avoid the loss of bicarbonate by stomach acid (HCl). Consumption
occurred in small amounts (300 ml) at set times each day to avoid
rapid increases in bicarbonate concentrations of body fluids and to
avoid over hydration.
[0230] The results of the experiment were delayed but unequivocal.
Within 3 to 9 months, all participants in the experiment
demonstrated substantial decreases in fatigue and lethargy. All
participants demonstrated an increased capacity for mild physical
activity; an improvement in motor activity. Function was improved.
Those participants with chronic rheumatoid disease (rheumatoid
arthritis) demonstrated some decreases in inflammation and some
decreases in pain. Those participants with chronic skin disease
(dermatitis) demonstrated decreases in inflammation. Those
participants with tissue calcification demonstrated decreases in
calcium deposits.
[0231] The consumption of aqueous metal bicarbonate solution,
principally magnesium bicarbonate solution, decreases fatigue and
lethargy and improves motor activity in people suffering with
chronic disease.
[0232] The consumption of aqueous metal bicarbonate solution,
principally magnesium bicarbonate solution, decreases clinical
signs of inflammation and pain and calcification in people
suffering with chronic disease.
EXAMPLE 7
An Experiment to Prevent and to Treat the Clinical Signs of
Diseases Caused by Viruses that Require Proton Concentrations for
Infectivity
[0233] Many viruses become infective by utilising high
intracellular proton concentrations in host cells. Proton
concentrations involved in the infectivity of viruses, and the
pathogenesis of viral diseases, derive from the hydration of carbon
dioxide catalysed by intracellular carbonic anhydrase enzymes. The
production of protons by carbonic anhydrase enzymes can be
represented by the equation 11
[0234] Protons formed by carbonic anhydrase enzymes are
concentrated by intracellular V-type proton pumps and stored in the
endosomes and lysosomes of body cells. Functional endosomes and
lysosomes maintain internal concentrations of protons which give
them internal pH values between pH 3.0 and pH 6.0.
[0235] Virus infectivity often requires the activities of acid
protease enzymes. Acid protease enzymes are enzymes that function
optimally at acidic pH levels. Acid protease enzymes are located in
endosomes and lysosomes of body cells.
[0236] Influenza viruses require acid protease enzyme activities
for their replication and infectivity. The acid proteases of
lysosomes and endosomes in body cells act to liberate the nucleic
acid (RNA) of the influenza virus from the outer viral
membrane.
[0237] Many viruses contain their own acid-dependent enzymes which
utilise proton concentrations in host cells. For example, the acid
proteases of lentiviruses are required for virus protein assembly
and viral infectivity.
[0238] An experiment was instigated with the aim of preventing and
treating the clinical signs of diseases caused by viruses that
require proton concentrations for infectivity. Natural infections
with influenza viruses and flu-like respiratory viruses were taken
as the model infections. Influenza is an acute febrile infectious
respiratory disease manifested by inflammation of the bronchial
mucosa. It is complicated often by bacterial pneumonia. Clinical
signs of influenza include initially fever, malaise, headache and
muscle pain followed by coughing, sneezing and respiratory tract
effusions. Flu-like respiratory viruses cause respiratory diseases
manifested generally by clinical signs of less intensity than
influenza.
[0239] Twenty people were chosen and divided into two equal groups.
The control group did not consume aqueous metal bicarbonate
solution. The treatment group consumed aqueous metal bicarbonate
solution with a pH value between 8.1 and 8.5. The aqueous metal
bicarbonate solution contained approximately Mg.sup.2+ 120 mg per
litre, Na.sup.+ 135 mg per litre and HCO.sub.3.sup.- 950 mg per
litre. The major component of the solution was magnesium
bicarbonate Mg(HCO.sub.3).sub.2 720 mg per litre approximately.
Consumption of the aqueous metal bicarbonate solution was commenced
at half a litre per day and increased by increments over a period
of one month to between 2 to 3 litres per day. Consumption occurred
on an empty stomach to avoid the loss of bicarbonate by stomach
acid (HCl). Consumption occurred in small amounts (300 ml) at set
times each day to avoid rapid increases in bicarbonate
concentrations of body fluids and to avoid over hydration.
[0240] Aqueous metal bicarbonate solution was consumed by people in
the treatment group for 2 years.
[0241] People in both groups worked either in child care centres or
in homes for the elderly and were exposed to influenza and other
respiratory infections over a 2 year period. Clinical signs of
influenza and flu-like virus infections were observed and recorded
over the 2 years. Results are given below:
11 Record of influenza and flu-like virus infections over a 2 year
period Control Group Treatment Group Influenza Number of infections
8 2 Duration of symptoms 5 to 10 days 2 to 3 days Severity of
symptoms (0 to 4) 4 1 to 2 Flu-like viruses Number of infections 15
3 Duration of symptoms 3 to 7 days 2 to 3 days Severity of symptoms
(0 to 4) 2 to 4 1 to 2
[0242] People consuming aqueous metal bicarbonate solution had a
lower prevalence of the clinical signs of influenza and flu-like
virus infections than people not consuming aqueous metal
bicarbonate solution. People consuming aqueous metal bicarbonate
solution had less severe symptoms and shorter duration of symptoms
than people not consuming aqueous metal bicarbonate solution.
[0243] The consumption of aqueous metal bicarbonate solution,
principally magnesium bicarbonate solution, decreases the
prevalence of the clinical signs of diseases caused by viruses that
require proton concentrations for infectivity.
[0244] The consumption of aqueous metal bicarbonate solution,
principally magnesium, bicarbonate solution, decreases the severity
and the duration of the clinical signs of diseases caused by
viruses that require proton concentrations for infectivity.
EXAMPLE 8
Suitable Formulation and Range of Parameters and Range of
Administration Volumes for the Aqueous Metal Bicarbonate
Solution
[0245] A suitable formulation for the aqueous metal bicarbonate
solution contains Mg(HCO.sub.3).sub.2 720 mg per litre
approximately (Mg.sup.2+ 120 mg per litre and HCO.sub.3.sup.- 600
mg per litre approximately). The formulation usually contains also
NaHCO.sub.3 485 mg per litre approximately (Na.sup.+ 135 mg per
litre and HCO.sub.3.sup.- 350 mg per litre approximately). The pH
of the formulation is pH 8.3. The formulation is stored either at
5.degree. C. to 10.degree. C. at 1 atmosphere in a sealed container
or at higher temperatures at higher pressures. The formulation is
administered or consumed by a mammalian (typically human) user in
300 ml doses approximately 6 to 10 times per day usually on an
empty stomach at approximately equal time intervals throughout the
day. Usually the total amount of formulation usually administered
is 1.8 to 3 litres per day.
[0246] The parameters of a suitable formulation for the aqueous
metal bicarbonate solution may be conveniently represented as
follows:
12 Typical parameter range Specific parameters Mg(HCO.sub.3).sub.2
150 mg/litre to saturation Mg(HCO.sub.3).sub.2 720 mg/litre
solubility per litre (Mg.sup.2+ 120 mg/litre and HCO.sub.3.sup.-
600 mg/litre) NaHCO.sub.3 0 to 1,000 mg/litre NaHCO.sub.3 485
mg/litre (Na.sup.+ 135 mg/litre and HCO.sub.3.sup.- 350 mg/litre pH
8.0 to 8.5 pH 8.3 0.degree. C. to 10.degree. C. at 1 atmosphere
5.degree. C. to 10.degree. C. at 1 atmosphere 300 ml dose
approximately 1 to 15 300 ml dose approximately times per day 6 to
10 times per day
[0247] There exists a range of combinations and concentrations of
metal cations that may be included in the suitable formulation of
the aqueous metal bicarbonate solution. There exists a range of
anions (other than bicarbonate) that may be included in
stoichiometric amounts with metal cations in the suitable
formulation of the aqueous metal bicarbonate solution. There exists
a range of concentrations of bicarbonate anions that may be
included in stoichiometric amounts with metal cations in the
suitable formulation of the aqueous metal bicarbonate solution.
[0248] A typical range of parameters that may be combined and
included in the suitable formulation of the aqueous metal
bicarbonate solution may be conveniently represented as
follows:
13 Final Concentration in Solution Typical parameter range Specific
parameters Mg.sup.2+ 50 to 500 mg/litre 120 to 300 mg/litre
Na.sup.+ 50 to 1,000 mg/litre 120 to 300 mg/litre K.sup.+ 50 to 500
mg/litre 120 to 300 mg/litre Ca.sup.2+ 50 to 500 mg/litre 120 to
300 mg/litre HCO.sub.3.sup.- 200 to 3,000 mg/litre 600 to 2,000
mg/litre Anions other than Stoichiometric with metal cation
concentrations HCO.sub.3.sup.-(eg. Cl.sup.-, SO.sub.4.sup.2-)
[0249] There exists a range of pH values for the suitable
formulation of aqueous metal bicarbonate solution (that includes
cation and anion parameter ranges above). The pH values may be
conveniently represented as follows:
14 Typical pH range Specific pH range pH 7.5 to 8.8 pH 8.0 to
8.5
[0250] Above pH 8.5, the solution tends to become cloudy due to the
formulation of metals carbonates (CO.sub.3.sup.2-).
[0251] There exists a range of physical parameters for the suitable
formulation of aqueous metal bicarbonate solution (that includes
cation and anion parameter ranges above). The physical parameters
may be conveniently represented as follows:
15 Typical parameter range Specific parameter range 0.degree. C. to
30.degree. C. 5.degree. C. to 10.degree. C. 1 to 3 atmospheres 1
atmosphere
[0252] Above 10.degree. C., carbon dioxide leaves solution and the
solution tends to become cloudy (with time) due to the formation of
metal carbonates (CO.sub.3.sup.2-). This may be controlled by
increasing the pressure on the solution.
[0253] There exists a range of volumes of administration for the
suitable formulation of metal bicarbonate solution (that includes
cation and anion parameter ranges above). The volume of aqueous
metal Bicarbonate solution administered depends on the purpose for
the administration.
[0254] The administered volumes of aqueous metal bicarbonate
solution may be conveniently represented as follows:
16 Purpose for administration Typical volume of aqueous metal range
administered bicarbonate solution to 70 kg human Increased
longevity 1 to 2 litres per day (normal and delay in senescence
physiological volume requirement for water intake) Prevention of 1
to 2 litres per day (normal degenerative diseases physiological
volume requirement for water intake) Treatment of osteoarthritis
1.8 to 3.0 litres per day Treatment of chronic disease 1.8 to 3.0
litres per day Maintain and improve 1.8 to 3.0 litres per day motor
activity Decrease fatigue and lethargy 1.8 to 3.0 litres per day
Prevention and treatment of 1.8 to 3.0 litres per day influenza and
other acid-dependent viral diseases
[0255] Aqueous metal bicarbonate solution is administered typically
in 300 ml doses approximately 6 to 10 times per day at equal time
intervals throughout the day. Typically, the solution is allowed to
stand prior to consumption until the solution reaches 15.degree. C.
to 20.degree. C. (cool room temperature).
[0256] A suitable formulation for the aqueous metal bicarbonate
solution contains Mg(HCO.sub.3).sub.2 720 mg per litre at pH 8.3.
The formulation usually contains also NaHCO.sub.3 485 mg per litre.
The aqueous metal bicarbonate solution may contain a range of
cations and anions within a pH range pH 7.5 to 8.8. The aqueous
metal bicarbonate solution is administered in volumes ranging from
1 to 3 litres per day.
EXAMPLE 9
[0257] Osteoarthritis is a slowly progressive degeneration of the
joints of the hands and large weight-bearing joints (hips and
knees). Osteoarthritis is common in post menopausal women.
Osteoarthritis is characterised by pain, enlargement of joints and
limitation of joint movements. The linings of osteoarthritic joints
show a moderate to marked degree of inflammation. The principle
pathological changes associated with osteoarthritis are destruction
of joint cartilage and neoformations of bone at joint margins
(osteophytes). In osteoarthritis, destruction of joint cartilage is
caused by acid protease enzymes (and other enzymes) derived often
from the lysosomes of cartilage cells (chondrocytes), inflammatory
cells and other cells.
[0258] For an experimental trial, a group of post menopausal women
were chosen who had clinical signs of osteoarthritis in the joints
of their hands. The osteoarthritic joints included the distal and
proximal interphalangeal joints of the fingers and the
carpometacarpal joint of the thumbs. In all cases, loss of joint
function was moderate to severe.
[0259] In all cases, the women suffered pain, swelling of the
fingers and loss of joint movement. Mucous cysts were associated
with distal joint osteoarthritis. Lateral deformities occurred in
some proximal joints with severe loss of joint function. Women with
affected thumbs had considerable loss of function and considerable
pain. Many hands were "claw-like" in appearance. Women consumed
magnesium bicarbonate solution, with added sodium bicarbonate. The
women consumed between 2 to 3 litres of bicarbonate solution per
day. In this solution, the magnesium concentration was
approximately 120 mg per litre, sodium concentration was
approximately 135 mg per litre and bicarbonate concentration was
approximately 950 mg per litre. Consumption was commenced at half a
litre per day and increased by increments over a period of one
month to 2 to 3 litres per day. Consumption occurred on an empty
stomach to a void the loss of bicarbonate by stomach acid.
Consumption occurred in small amounts (300 mL) at set times each
day to avoid rapid increases in bicarbonate concentrations of body
fluids.
[0260] In all cases, there were remissions in the clinical signs of
osteoarthritis which were quantifiable by standard tests of
movement, flexibility and strength. The participants showed
considerable increases in joint functions and decreases in acute
and chronic joint swellings. The "stabbing" pain of osteoarthritis
was alleviated. Some participants had remissions of inflammation
and arthritis to the stage where many chronic swellings were no
longer observable and joint mobilities and functions were restored.
However, these improvements were maintained only with the continued
consumption of bicarbonate anions. Once the consumption of
bicarbonate anions ceased, clinical signs of inflammation began to
reappear often within a week.
[0261] The participants commented on an absence of lethargy and the
presence of a feeling of well-being. Magnesium bicarbonate
alleviated the pain and swelling associated with
osteoarthritis.
[0262] None of the participants demonstrated any clinical signs of
influenza or other respiratory viral infections over the two year
period of the trial. This occurred despite several of the
participants working in situations where exposure to viral
infections was high (nursing homes and child care centres).
EXAMPLES 10
[0263] Influenza is an acute febrile infectious respiratory disease
manifested by inflammation of the bronchial mucosa. Influenza is
complicated often by bacterial pneumonia which may be fatal.
[0264] For an experimental trial, a group of men and women were
chosen who worked in situations where exposure to the influenza
virus was likely to occur (nursing homes and child care centres).
Each person in the experimental group consumed magnesium
bicarbonate solution, with added sodium bicarbonate. Each person
consumed between 2 to 3 litres of bicarbonate solution per day. In
this solution, the magnesium concentration was approximately 120 mg
per litre, sodium concentration was approximately 135 mg per litre
and bicarbonate concentration was approximately 950 mg per
litre.
[0265] Consumption was commenced at half a litre per day and
increased by increments over a period of one month to 2 to 3 litres
per day. Consumption occurred on an empty stomach to avoid the loss
of bicarbonate by stomach acid. Consumption occurred in small
amounts (300 mL) at set times each day to avoid rapid increases in
bicarbonate concentrations of body fluids.
[0266] Over the two year period of the experimental trial, no
person in the experimental group showed any clinical signs of
influenza.
EXAMPLE 11
[0267] A suitable formulation for the aqueous metal bicarbonate
solution contains 720 mg Mg(HCO.sub.3).sub.2 per litre (120 mg
Mg.sup.2+ per litre and 600 mg HCO.sub.3.sup.- per litre
approximately) and 485 mg NaHCO.sub.3 per litre (135 mg Na.sup.+
per litre and 350 mg HCO.sub.3.sup.- per litre approximately). The
pH of this formulation is pH 8.3. This formulation is stored at 5
to 10.degree. C. at 1 atmosphere or it can be stored at higher
temperatures at higher pressures. This formulation is administered
in 300 mL doses approximately 6 to 10 times per day. That is the
amount of formulation usually administered per day is 1.9 to 3
litres per day.
[0268] The parameters of the formulation may be conveniently
represented as follows:
17 Typical Parameter Range Specific Parameters 100 mg - saturation
solubility 720 mg Mg(HCO.sub.3).sub.2 per litre (120 mg
Mg(HCO.sub.3).sub.2 per litre Mg.sup.2+ and 600 mg HCO.sub.3.sup.-
per litre) 0-1000 mg NaHCO.sub.3 per litre 485 mg NaHCO.sub.3 per
litre (135 mg Na.sup.+ and 350 mg HCO.sub.3.sup.- per litre) pH
8-8.6, typically 8-8.5 pH 8.3 0-10.degree. C. @ 1 atmosphere
5-10.degree. C. @ 1 atmosphere 300 mL dose approximately 1 to 300
mL dose approximately 6 to 10 20 times per day times per day
EXAMPLE 12
[0269] Mitochondria are inefficient if they cannot maintain the
necessary production of ATP for maintenance of essential cell
processes and cell functions. This inefficiency is due often to
functional damage to the mitochondrial inner membrane and other
mitochondrial molecules. Inefficient mitochondria are not able to
maintain normal carbon, electron and proton fluxes.
[0270] However, in middle age, carbon and electron fluxes may be
maintained by the synthesis of fatty acids in the cytoplasm of body
cells. In body cells of the middle aged, fatty acids can be
regarded as carbon and electron sinks necessary for the maintenance
of essential fluxes; that is, for the maintenance of essential life
processes. The synthesis of fatty acids utilises ATP. However, the
fluxes for production of ATP in mitochondria are decreased in
middle age. There is a consequent `energy` deficit. The middle aged
are flat and lethargic relative to the young, though they can be
regarded as fat by necessity; the necessity of staying alive. In
addition to utilisation of cell ATP, the synthesis of fatty acids
in body cells adds to the carbon dioxide load of the cells and adds
to concentrations of intracellular protons. This occurs because the
series of chemical reactions that synthesise fatty acids results in
a net utilisation of bicarbonate anions and a net production of
carbon dioxide and protons. For example, each molecule of the fatty
acid palmitate that is synthesised by cells utilises seven
molecules of ATP and seven bicarbonate anions and produces seven
molecules of carbon dioxide and seven protons. Of course, fatty
acids are oxidised continuously from fat stores in the body which
produces even more carbon dioxide. When excess calories are
consumed at any chronological age (and converted to fatty acids)
the overall carbon dioxide load is considerable. Caloric restricted
rodents avoid this extra carbon dioxide load and, as a consequence,
they live longer lives with delays in the onset of degenerative
diseases.
[0271] A trial involving people consuming bicarbonate anions in
water was conducted. These people were middle aged and overweight
and complained of tiredness and lethargy. No control group was
maintained for the duration of the trial (people in an initial
control group were unable to consume the volumes of soft water
required). People involved in the trial were given a series of
lectures on the biochemistry of mitochondrial processes. They were
requested to decrease their food (calorie) intake considerably and
to avoid dietary fats. Excessive aerobic exercise was not
recommended due to the consequent increase in hunger it produces,
the large increase in carbon dioxide concentrations that occur with
increased aerobic muscle activity and the damage excess activity
does to inefficient mitochondria. Indeed, active muscle cells
contain mitochondria with most nucleic acid damage relative to
other body cells.
[0272] The trial consisted of each person consuming between two to
three litres per day of a mixture of magnesium bicarbonate and
sodium bicarbonate in water. Bicarbonate concentration was
established at a maximum of one gram per litre. (This concentration
of bicarbonate is well within the concentrations in several water
sources utilised for human consumption in Europe. In these waters
however, the bicarbonate is in the form of calcium and sodium
bicarbonate and pH values often are not very alkaline.) Consumption
was commenced at half a litre per day and increased by increments
over a period of one month to the maximum consumption. This
start-up schedule avoided any gastrointestinal side effects due to
the smooth muscle relaxation properties of magnesium. Capillary
dilation in the face was apparent in several people (which was
interpreted by those affected as rosy, healthy cheeks). The
capillary dilation may have been due to magnesium or may have been
due to a decrease in activity of renin which is an acid protease
enzyme from the kidney that is central to the control of blood
pressure. (Renin exerts its effects ultimately by constriction of
small blood vessels.)
[0273] Each participant in the trial was advised to consume the
bicarbonate solution `on an empty stomach`. Consumption in this
manner avoided the mixing of bicarbonate anions with stomach acid
which would have resulted in the loss of bicarbonate. Advice was
given also to consume the solution in small amounts at set times
each day. Consumption in this manner avoided a rapid increase in
the bicarbonate concentrations of body fluids.
[0274] The results were unequivocal. Body weight was lost at about
one half of a kilogram per week after the initial start-up period
was completed. Other beneficial effects (more important than weight
loss to the participants in the trial) included the absence of
lethargy, the presence of a feeling of well-being (mild euphoria)
and the increased capacity for mild physical activity. The
participants all commented that their `energy levels` had improved
and that their outlook on life had consequently become more
positive.
EXAMPLE 13
[0275] A heart muscle cell contains mitochondria that occupy one
quarter of the cell volume. It is natural to expect the heart to be
rich in mitochondria when one considers the workload of the heart
and its subsequent requirement for `energy`. The consumption of
magnesium bicarbonate may assist in maintaining efficient
mitochondria in heart muscle cells. In the presence of bicarbonate
anions, mitochondrial efficiency in heart muscle cells is
maintained by processes which include decreases in proton leaks
across inner mitochondrial membranes, establishment of proton
circuits independent of proton leaks and maintenance of alkaline pH
values in mitochondrial matrixes. In the presence of bicarbonate
anions, mitochondrial damage and mitochondrial failure are
decreased. Efficient mitochondria in heart muscle cells maintain
ATP production so that the heart remains functional as a vital
organ.
[0276] There are further beneficial effects to the cardiovascular
system resulting from the consumption of magnesium bicarbonate.
First, decreased fatty acid synthesis in body cells results in
lowered body weight with subsequent reduction in high blood
pressure to a normal value. Indeed, these effects were observed in
people participating in the trial reported in Example 5. Second,
lysosomal enzyme damage to ischaemic heart muscle may be prevented
or decreased.
[0277] There is unequivocal evidence of correlation that heart
disease, senescence, degenerative diseases and death are caused by
inefficient mitochondria. Though inefficient mitochondria may not
be the only cause of these conditions. There is sufficient evidence
however that senescence and general degeneration in all species
studied, from fungi to humans, are correlated to the damage to the
complex molecules of the mitochondria. For example, the
mitochondria of aged people carry nucleic acid and protein defects
not observed in the mitochondria of young people. This is true
particularly of the mitochondria in muscle, heart and brain cells.
Accordingly, it has been proposed that several chronic diseases
common in old age may be related to mitochondrial failure,
including heart disease, late-onset diabetes and Parkinson's and
Alzheimer's diseases. That is, the gradual loss of efficiency of
cell mitochondria results in a diminution of the functional
capacity of body cells with pathological consequences.
[0278] A progressive decline in organ function is characteristic of
old age. Some of the changes that occur as people grow older
are:
[0279] 1. The ability to focus the eyes decreases and response time
to stimuli becomes slower.
[0280] 2. Cancers in epithelial tissues (skin, lung, colon, mammary
gland) become more common.
[0281] 3. Heart disease and widely disseminated atherosclerosis
occur.
[0282] 4. Osteoporosis and bone and joint pathology occur.
[0283] 5. Thermoregulation becomes inpaired.
[0284] 6. There is a decline in the ability of body organs such as
the reproductive organs, lungs, glandular tissues and kidneys to
maintain their specialised life processes.
[0285] 7. There is a reduced capacity for surviving
haemorrhage.
[0286] 8. There is an increase in autoimmune diseases and chronic
inflammatory diseases.
[0287] Relative to their life span of around three years, mice
develop heart disease, kidney disease, arthritis and cancer at
similar stages in life to humans. In other words, both senescence
and the similar degenerative diseases of mice and humans are
correlated to the chronological age of each species but cannot be
linked causally to chronological age per se. It has been observed
in many experiments that rodents fed caloric restricted diets
suffer less from the above diseases than control animals. It has
been observed also that careful necropsies on diet-restricted
rodents often do not reveal any gross or microscopic pathology.
[0288] Mitochondrial proton leak is a contributing cause of
mitochondrial inefficiency and hence a source of senescence and
degenerative diseases in short-lived rodents. Mitochondrial proton
leak may be a source of senescence and degenerative diseases in
humans. Because the proton leak in humans is only a fraction of the
leak in rodents, humans develop senescence and degenerative
diseases at a later chronological age than rodents.
[0289] It may be possible to prevent inefficient processes in
mitochondria in order to extend longevity and to delay degenerative
diseases. Exogenous sources of appropriate bicarbonate anions can
be absorbed by body cells to maintain intracellular alkaline pH
values and that alkaline pH values maintain mitochondrial
respiration rates and maintain effective proton concentration
gradients across inner mitochondrial membranes.
[0290] Intracellular alkaline pH values appear necessary for
optimum activities of many enzymes in body cells. These enzymes
include polymerases, phosphofructokinase and carbonic anhydrase.
Enzymes permit life processes to be perpetuated. Therefore,
maintenance of enzyme activities by maintenance of intracellular
alkaline pH values may assist in the perpetuation of longevity.
[0291] The long-term provision of appropriate bicarbonate anions to
body cells maintains efficient mitochondrial function, maintains
the DNA polymerase activity of mitochondria and therefore maintains
the integrity of mitochondrial DNA. This latter effect results in
accurate syntheses of the complex functional molecules that are
involved in electron fluxes in mitochondria. Of course, bicarbonate
anions will decrease the proton load per se in body cells with a
subsequent decrease in proton damage to other cell molecules and a
decrease in the tendency of oxidation reactions to occur. Decreased
oxidations result in decreased DNA mutation and decreased amino
acid oxidations. Degenerative diseases are delayed.
Industrial Applicability
[0292] An aqueous metal bicarbonate solution of the invention can
be readily utilised in medicine to prevent and to treat certain
inflammatory diseases, degenerative diseases and viral diseases in
mammals.
* * * * *