U.S. patent application number 17/534667 was filed with the patent office on 2022-03-17 for method of treating or ameliorating skin conditions with a magnetic dipole stabilized solution.
This patent application is currently assigned to REVEN PHARMACEUTICALS, INC.. The applicant listed for this patent is REVEN PHARMACEUTICALS, INC.. Invention is credited to Brian Denomme, Zishan Haroon, Tracy L. Krebs, Peter Lange, Sezgin Ozgur, Henk Van Wyk, Mariette Van Wyk.
Application Number | 20220079978 17/534667 |
Document ID | / |
Family ID | 1000005996860 |
Filed Date | 2022-03-17 |
United States Patent
Application |
20220079978 |
Kind Code |
A1 |
Lange; Peter ; et
al. |
March 17, 2022 |
METHOD OF TREATING OR AMELIORATING SKIN CONDITIONS WITH A MAGNETIC
DIPOLE STABILIZED SOLUTION
Abstract
The present invention is directed to methods for treating or
ameliorating skin conditions, diabetic conditions, cardiovascular
conditions, cancer, infections or metal poisoning, enhancing
performance, or providing nutritional support, comprising
administering to a subject in need thereof compositions comprising
a magnetic dipole stabilized solution (MDSS). The MDSS solution may
include additional components and can be provided in a kit.
Inventors: |
Lange; Peter; (Denver,
CO) ; Denomme; Brian; (Northville, MI) ; Van
Wyk; Henk; (Glendale, CO) ; Van Wyk; Mariette;
(Glendale, CO) ; Krebs; Tracy L.; (Sarasota,
FL) ; Ozgur; Sezgin; (Cary, NC) ; Haroon;
Zishan; (Durham, NC) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
REVEN PHARMACEUTICALS, INC. |
Westminster |
CO |
US |
|
|
Assignee: |
REVEN PHARMACEUTICALS, INC.
Golden
CO
|
Family ID: |
1000005996860 |
Appl. No.: |
17/534667 |
Filed: |
November 24, 2021 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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15848853 |
Dec 20, 2017 |
11202798 |
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17534667 |
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15398233 |
Jan 4, 2017 |
9867849 |
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15848853 |
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14017811 |
Sep 4, 2013 |
9572810 |
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15398233 |
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13811547 |
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PCT/US2011/044947 |
Jul 22, 2011 |
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14017811 |
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61366844 |
Jul 22, 2010 |
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61366845 |
Jul 22, 2010 |
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61366852 |
Jul 22, 2010 |
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61366853 |
Jul 22, 2010 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61K 47/40 20130101;
A61K 31/7036 20130101; A23L 33/15 20160801; A61Q 19/00 20130101;
A61K 47/14 20130101; A61Q 19/007 20130101; A61K 31/465 20130101;
A61K 8/676 20130101; A61K 31/455 20130101; A23L 33/10 20160801;
A61K 31/65 20130101; A61K 8/41 20130101; A61K 31/197 20130101; A61K
2800/78 20130101; A61K 31/51 20130101; A61K 31/4415 20130101; A61K
31/122 20130101; A61K 33/20 20130101; A61K 31/167 20130101; A61K
33/12 20130101; A61K 9/08 20130101; A61K 31/375 20130101; A61K
47/02 20130101; A61K 8/19 20130101; A61K 31/513 20130101; A61K
31/519 20130101; A61K 8/67 20130101; A61K 9/0019 20130101; A61K
8/20 20130101; A61K 8/675 20130101; A61K 33/40 20130101; A61K 8/42
20130101; A61K 31/714 20130101; A61K 31/7048 20130101; A61K 31/525
20130101; A61K 8/73 20130101; A61K 2800/805 20130101; A61Q 19/08
20130101; A61K 2800/5922 20130101; A61K 31/133 20130101; A61K
31/727 20130101; A61K 33/00 20130101; A61K 8/673 20130101 |
International
Class: |
A61K 33/00 20060101
A61K033/00; A23L 33/10 20060101 A23L033/10; A23L 33/15 20060101
A23L033/15; A61K 9/00 20060101 A61K009/00; A61K 9/08 20060101
A61K009/08; A61K 31/375 20060101 A61K031/375; A61K 31/4415 20060101
A61K031/4415; A61K 31/519 20060101 A61K031/519; A61K 31/7036
20060101 A61K031/7036; A61K 31/7048 20060101 A61K031/7048; A61K
47/02 20060101 A61K047/02; A61K 47/40 20060101 A61K047/40; A61K
33/40 20060101 A61K033/40; A61K 31/197 20060101 A61K031/197; A61K
31/455 20060101 A61K031/455; A61K 31/51 20060101 A61K031/51; A61K
31/525 20060101 A61K031/525; A61K 31/714 20060101 A61K031/714; A61K
33/20 20060101 A61K033/20; A61K 8/19 20060101 A61K008/19; A61K 8/20
20060101 A61K008/20; A61K 8/41 20060101 A61K008/41; A61K 8/42
20060101 A61K008/42; A61K 8/67 20060101 A61K008/67; A61K 8/73
20060101 A61K008/73; A61K 31/122 20060101 A61K031/122; A61K 31/133
20060101 A61K031/133; A61K 31/167 20060101 A61K031/167; A61K 31/465
20060101 A61K031/465; A61K 31/513 20060101 A61K031/513; A61K 31/65
20060101 A61K031/65; A61K 31/727 20060101 A61K031/727; A61K 33/12
20060101 A61K033/12; A61K 47/14 20060101 A61K047/14; A61Q 19/00
20060101 A61Q019/00; A61Q 19/08 20060101 A61Q019/08 |
Claims
1. A method of treating wounds comprising administering to a
patient in need thereof a composition comprising substances
dissolved in water, the substances comprising ascorbic acid,
thiamine HCl, magnesium sulfate, cyanobalamin, a B-vitamin,
pyridoxine HCl, riboflavin 5'-phosphate, calcium D-pantothenate,
sodium bicarbonate, and sodium chloride.
2. The method of claim 1, wherein the ascorbic acid is at a
concentration from about 100 mg to about 500 mg, the thiamine is at
a concentration from about 1 mg to about 100 mg, the magnesium
sulfate is at a concentration from about 100 mg to about 500 mg,
the cyanobalamin is at a concentration from about 100 .mu.g to
about 500 .mu.g, the B-vitamin is at a concentration from about 1
mg to about 300 mg, the pyridoxine HCl is at a concentration from
about 1 mg to about 100 mg, the riboflavin 5'-phosphate is at a
concentration from about 1 mg to about 100 mg, and the calcium
D-pantothenate is at a concentration from about 1 mg to about 100
mg.
3. The method of claim 1, wherein the composition further comprises
at least one of trace metals, 2 di-methyl amino ethanol HCl, lipoic
acid, folic acid, an antibiotic, vitamins, vitamers, salts, acids,
amino acids, an anesthetic, trace metals, and heparin.
4. The method of claim 3, wherein the composition comprises the
antibiotic.
5. The method of claim 4, wherein the antibiotic is selected from
the group consisting of erythromycin and gentamicin.
6. The method of claim 1, wherein the composition further comprises
vitamin K2.
7. The method of claim 1, wherein the composition further comprises
arginine.
8. The method of claim 1, wherein the water is electroactivated
water having an electrical potential of -200 to +800 with the
substances dissolved therein.
9. The method of claim 8, wherein the B-vitamin is niacinamide.
10. The method of claim 9, wherein concentrations of the substances
are 4.047% to 4.947% by weight ascorbic acid, 0.285% to 0.349% by
weight thiamine HCl, 3.636% to 4.444% by weight magnesium sulfate,
0.0085% to 0.011% by weight cyanocobalamin, 0.5345% to 0.6535% by
weight of niacinamide, 0.5345% to 0.6535% by weight pyridoxine HCl,
0.012% to 0.014% by weight riboflavin-5'-phosphate, 0.013% to
0.016% by weight calcium D-pantothenate, 2.10% to 6.30% by weight
sodium bicarbonate, and 0.0009% to 0.0011% by weight sodium
chloride.
11. The method of claim 10, wherein concentrations of the
substances are 4.4967% by weight ascorbic acid, 0.3167% by weight
thiamine HCl, 4.040% by weight magnesium sulfate, 0.00965% by
weight cyanocobalamin, 0.5940% by weight of niacinamide, 0.5940% by
weight pyridoxine HCl, 0.0127% by weight riboflavin-5'-phosphate,
0.0147% by weight calcium D-pantothenate, 4.20% by weight sodium
bicarbonate, and 0.001% by weight sodium chloride.
12. The method of claim 11, wherein the water is water for
injection (WFI) and the substances conform to USP quality
standards.
13. The method of claim 1, wherein the administering is by
injection, oral administration, topical administration,
transmucosal administration, or transdermal administration.
14. A method of treating wounds comprising administering to a
patient in need thereof a composition comprising the product of
mixing contents of a first vial with contents of a second vial in a
1:1 ratio, the first vial containing an aqueous solution comprising
ascorbic acid, thiamine HCl, magnesium sulfate, cyanocobalamin, a
B-vitamin, pyridoxine HCl, riboflavin-5'-phosphate, calcium
D-pantothenate, and sodium chloride; the second vial containing an
aqueous solution comprising sodium bicarbonate, and sodium
chloride, wherein the aqueous solution in the first vial has an
electrical potential of +1000 to +1300 prior to mixing, and the
aqueous solution in the second vial has an electrical potential of
+5 to +700 prior to mixing, wherein the composition has an
electrical potential of -1 to -200 after mixing.
15. The method of claim 14, wherein the B-vitamin is a form of
vitamin B3.
16. The method of claim 15, wherein the form of vitamin B3 is
niacinamide.
17. The method of claim 16, wherein concentrations in the first
vial are 8.094% to 9.893% by weight ascorbic acid, 0.570% to 0.697%
by weight thiamine HCl, 7.272% to 8.888% by weight magnesium
sulfate, 0.017% to 0.021% by weight cyanocobalamin, 1.069% to
1.307% by weight of niacinamide, 1.069% to 1.307% by weight
pyridoxine HCl, 0.023% to 0.028% by weight riboflavin-5'-phosphate,
0.026% to 0.032% by weight calcium D-pantothenate, and 0.0009% to
0.0011% sodium chloride, and concentrations in the second vial are
4.20% to 12.60% by weight sodium bicarbonate, and 0.0009% to
0.0011% by weight sodium chloride.
18. The method of claim 17, wherein concentrations in the first
vial are 8.9933% by weight ascorbic acid, 0.6333% by weight
thiamine HCl, 8.080% by weight magnesium sulfate, 0.0193% by weight
cyanocobalamin, 1.188% by weight of niacinamide, 1.188% by weight
pyridoxine HCl, 0.0253% by weight riboflavin-5'-phosphate, 0.0293%
by weight calcium D-pantothenate, and 0.001% sodium chloride, and
concentrations in the second are 8.40% by weight sodium
bicarbonate, and 0.001% by weight sodium chloride.
19. The method of claim 14, wherein the administering is by
injection, oral administration, topical administration,
transmucosal administration, or transdermal administration.
20. The method of claim 19, wherein the administering is the
topical administration.
Description
CROSS REFERENCE TO RELATED APPLICATION
[0001] This application is a continuation of U.S. patent
application Ser. No. 15/848,853, which was filed Dec. 20, 2017 as a
continuation of Ser. No. 15/398,233, which was filed Jan. 4, 2017,
issued Apr. 27, 2017 as U.S. Pat. No. 9,867,849, and was a
continuation of U.S. patent application Ser. No. 14/017,811, which
was filed Sep. 4, 2013, issued as U.S. Pat. No. 9,572,810, and was
a continuation of U.S. patent application Ser. No. 13/811,547,
which is now abandoned and was a 371 of PCT/US2011/044947, which
was filed Jul. 22, 2011 and claimed the benefit of U.S. Provisional
Patent Application No. 61/366,853, filed Jul. 22, 2010, U.S.
Provisional Patent Application No. 61/366,852, filed Jul. 22, 2010,
U.S. Provisional Patent Application No. 61/366,845, filed Jul. 22,
2010, and U.S. Provisional Patent Application No. 61/366,844, filed
Jul. 22, 2010, all of which are incorporated herein by reference as
if fully set forth herein.
FIELD OF THE INVENTION
[0002] The present invention is directed to methods involving the
administration of a composition comprising a magnetic dipole
stabilized solution to a subject in need thereof for treating or
ameliorating skin conditions, diabetic conditions, cardiovascular
conditions, cancer and infections, chelating, reducing the amount
of metal in a subject or increasing the amount of excretion of
metal from a subject, providing nutritional support or enhancing
performance.
BACKGROUND
[0003] A magnetic dipole stabilized solution which can be an
electro-activated water is sterile and non-pyrogenic and is
produced by exposing the water to a strong electrical (magnetic)
field force in a tightly isolated and fully enclosed reactor space.
It is capable of producing both a negative (cathodic) and a
positive (anodic) stream of activated water.
[0004] Electrolysis of water, including saline solutions, is known
for antimicrobial properties and for use on hard surfaces (U.S.
Pat. Nos. 4,236,992 and 4,316,787). Electrolyzed water has been
administered for therapeutic use through ingestion or topical
administration. Published U.S. Patent Application No. 20060008908
discloses a beverage containing electrolyzed water and a cesium or
rubidium salt for promoting longevity. The application notes that
there may be an electro-physiological imbalance that is the origin
of disease and that electrolyzed water can restore optimal pH. The
electrolyzed water is disclosed as an alkaline water. Published
U.S. Patent Application No. 20050074421 discloses an acidic
electrolyzed water composition. It is for external use and is
purported to be a cosmetic and a hair growing tonic. An
electrolyzed water composition is disclosed in U.S. Pat. No.
6,544,502. An antibiotic can be admixed in the water and used
topically to treat acne. An electrolyzed saline solution containing
regulated amounts of ozone and active chlorine species is described
in U.S. Pat. No. 5,622,848. The solution can be given
intravenously.
[0005] Cardiovascular diseases, which include coronary heart
disease (heart attacks), cerebrovascular disease, raised blood
pressure (hypertension), peripheral artery disease, rheumatic heart
disease, congenital heart disease and heart failure, derive from
dysfunctional conditions of the heart, arteries, and veins that
supply oxygen to vital life-sustaining organs, including the brain
and the heart itself. Major causes of cardiovascular disease are
tobacco use, physical inactivity and an unhealthy diet.
[0006] Heart attacks and strokes are mainly caused by a blockage in
the inner walls of the blood vessels that prevents blood from
flowing to the heart or the brain. Arteriosclerosis and
atherosclerosis are excess buildup of fat or plaque deposits,
respectively, that cause narrowing of the veins that supply
oxygenated blood to the heart and may lead to ischemic heart
disease, an obstruction of blood flow to the heart. Excess fat or
plaque buildup may also cause high blood pressure (hypertension), a
disease known as "The Silent Killer" because the first warning sign
is an angina attack, a deadly heart attack or a stroke. Kidney
disorders, obesity, diabetes, smoking, excess alcohol, stress, and
thyroid and adrenal gland problems can also exacerbate a high blood
pressure condition.
[0007] Damage to the heart tissues from cardiovascular diseases or
heart surgery disrupts the natural electrical impulses of the heart
and results in cardiac arrhythmia. Sudden fluctuations in heart
rate can cause cardiac irregularities and insufficiencies,
including palpitations, supraventricular tachycardia, fibrillation
faintness or dizziness, and even initiate a heart attack. Mismatch
of cardiac output during strenuous exercise may lead to muscle
damage, induce fatigue and affect athletic performance. Arteries
spasm and irregular contraction and expansion of blood vessels in
the brain may reduce flow of blood from the occipital lobe and
trigger migraines. Levels of total blood cholesterol above 250
mg/dL, LDL cholesterol above 130 mg/dL (3.0 mmol/L), HDL
cholesterol below 35 mg/dL and lipoprotein(a) level greater than 30
mg/dL may also lead to a heart attack or stroke.
[0008] Infections of the heart, known as carditis and endocarditis,
may occur as a result of a weak immune system, liver problems,
heart surgery, or from an autoimmune disorder like rheumatic
fever.
[0009] Heavy smoking may cause Buerger's disease, also known as
thrombophlebitis obliterans, an acute inflammation and thrombosis
(clotting) of arteries and veins of the hands and feet, which is
often associated with intense pain in the extremities, claudication
in the feet and/or hands, numbness and/or tingling in the limbs,
skin ulcerations, gangrene and Raynaud's phenomenon, a condition in
which the distal extremities turn white upon exposure to cold.
[0010] Peripheral arterial occlusive disease may cause diabetic
ulcers, which are the most common foot injuries leading to lower
extremity amputation in diabetic patients.
[0011] Research indicates the course of events which leads to the
loss of function, deterioration, destruction and death of the human
cell and to a large extent research relates to the issue of human
cellular reliance on oxygen metabolism, which occurs
intracellularly. Oxygen uptake intracellularly is governed by the
metabolic need for energy and takes place within the mitochondria
to produce ATP, the cell's energy source. Such chemical reactions
are not 100% efficient and the resultant release of highly reactive
oxygen species cytoplasm is responsible for cellular damage. The
relative amount of such oxygen by-products is less than the amount
produced in many other mammal species, however, such by-products
are highly toxic. Such examples include superoxide and hydroxyl
radicals, which can cause oxidative damage to cells and tissues.
Superoxide and water produce concentrated hydrogen peroxide and is
capable of intense skin damage within a few seconds, when applied
to human skin. The same reaction occurs intracellularly within the
cytoplasm and causes severe damage. The cells are protected by
means of enzymes to destroy peroxide radicals continually, however,
such defenses are not 100% efficient with the result that chemical
destruction of cells occurs.
[0012] Free oxygen radicals, also known as reactive oxygen species
(ROS), cause much damage to macromolecules, including lipids,
proteins and nucleic acids. One major toxic effect of oxygen
radicals is damage to cellular membranes, including the plasma,
mitochondrial and endo-membrane systems, which is initiated by
lipid peroxidation and is accompanied by increased membrane
rigidity, decreased activity of membrane-bound enzymes, altered
activity of membrane receptors and altered membrane permeability.
Furthermore, oxygen radicals can also directly attack membrane
proteins and induce lipid-lipid, lipid-protein and protein-protein
crosslinking, which in turn affects membrane function.
[0013] Because of their reactivity, free oxygen radicals may react
with DNA, resulting in mutations that can adversely affect the cell
cycle and potentially lead to cancer and malignancies. Moreover,
oxygen free radicals are involved in cardiovascular diseases, the
aging process, neurodegenerative diseases, including ALS,
Parkinson's disease and Alzheimer's disease, cataractogenesis,
atherosclerosis, diabetes mellitus, ischemia-reperfusion injury,
kwashiorkor, senile- and drug-induced deafness, schizophrenia,
atherosclerosis and alcohol-induced liver damage.
[0014] There is strong evidence in the literature that free oxygen
radicals oxidize low density lipoprotein (LDL), which is then
engulfed by phagocytes to form foam cells and plaques in the
cardiovascular wall. These plaques harden and narrow the blood
vessels and impair blood flow, thus depriving the heart of oxygen
and nutrients. In addition, ischemia is often followed by
reperfusion injury, which is caused by inadequate supplies of
intracellular antioxidants. Ischemia and reperfusion are a major
cause of strokes. There is also increasing evidence that mismatch
of cardiac output during strenuous exercise causes release of free
oxygen radicals, which contribute to muscle damage and induce
fatigue and/or injury. Moreover, it has been reported that the
activity of the anti-oxidant enzymes superoxide dismutase (SOD),
catalase (CAT) and glutathione peroxidase (GSH-Px) is significantly
lower in subjects suffering from migraine. SOD is known to protect
against vasoconstriction or vasospasm induced by superoxide
radicals. Migraine is a potential risk factor or marker for
atherosclerosis-related diseases.
[0015] An example of cell damage caused by oxygen reactions is
damage to the DNA. It is evident that DNA destructive reactions
occur daily in normal man. Most of these are repaired
enzymatically, if not, such cells reproduce out of control, with
resulting neoplasms. However, the long-term aging effects of
endogenous damage, is exemplified by wrinkling and hardening of the
skin and arteries with age. Skin and arteries consist of collagen
and elastin tissue. Collagen is the major protein of white fibers
of the body's connective tissues, cartilage and bone. Elastin is
the major connective tissue of structures such as large blood
vessels and skin. It is elastin that enables these structures to
stretch and resume to original size and shape. Free radical changes
described above yields a pathology, which leads to neoplastic
changes, artherosclerosis and loss of elasticity of the skin. The
pathology is centered on the cell membranes in all organs and
affected by the supply of nutrients, vitamins, and nucleic acids
through the microcirculation. Recent scientific studies have shown
that this mechanism progresses from free radical reactions to
oxidative products, which damages cells and tissues. This
simultaneously affects all cells, tissues and organs throughout the
body and is progressively insidious. These processes involve a
fundamental aspect of homeostasis and cell physiology.
[0016] The clinical significance of the chemical damage generated
in living cells, has been documented. It is therefore necessary to
develop methods to inhibit damage caused by these mechanisms.
[0017] Circulation disorders are common disorders amongst the
populace. It may be a severe medical challenge and may lead to limb
loss and a marked reduction in quality of life. Circulation
disorders are often diagnosed at a late stage of the disease.
Non-healing small wounds are the early characteristics of poor
circulation. Such wounds are often treated without the underlying
cause being correctly diagnosed. This results in ulceration,
discomfort and pain and may lead to limb amputation. Poor
circulation can also manifest itself in a patient being able to
only walk short distances, and be the cause of severe cramps. Other
examples are patients with no feeling in their toes and or feet and
severe discoloration of either the hand or foot.
[0018] A general condition has been identified in this disease as
being part of an autoimmune syndrome manifesting as a general
inflammatory condition of the vascular system, more specifically
vasculitis. Vasculitis may be considered an inflammatory syndrome
with structural alterations of the vascular wall, complicated by
lumen occlusion, leading to tissue ischemia. Vessels of any size
may be altered in systemic vasculitis but in cutaneous forms
alteration affects small vessels, especially those post-capillary.
The various forms differ by age of onset, affected organ, and
presence of periods of remission and exacerbation, amongst other
features. Sometimes they may also be superimposed to other
well-defined diseases, as vascular disorders, identified as
secondary conditions such as neoplasia, allergic reactions, and
infections.
[0019] Infections can promote inflammation of the vascular intima
wall of any diameter and in any organ. Palpable purpura is the most
common manifestation of vasculitis, although erythematous macules,
nodule, ecchimoses, erosions, ulcerations, hemorrhagic blisters,
necrosis, and gangrene may also occur. Skin can be the target organ
in this type of vascular pathology. The relative frequency of
vasculitis of the skin may be the first manifestation of a very
severe systemic disease.
[0020] Relative and or absolute ischemia caused by vascular disease
such as sclerosis resulting from aging, results in compromised poor
blood flow to tissues and cells. This results in a lack of
nutrients and oxygen at cellular level from reaching the cells,
with the resulting symptoms of ageing. This is manifested by such
symptoms as a loss of mental agility, alertness, memory loss and
other conditions commonly seen in senescence. In normal metabolism
most of the metabolic energy is used to maintain gradients across
the cell membrane. The provision of nutrient substrates is
recognized as the best basis for maintaining a level of metabolic
activity and ongoing energy needs in the cell. In these instances
diseases as manifested by neurodegeneration of aging may also be
modulated. Because neuron function can be disrupted by many
substances in the blood, it is necessary to target the central
nervous system by means of carrier fluids capable of breaching the
blood brain barrier by introducing charged and or lipid substances
into the blood may accomplish this. It is known that chemical
communication in the brain may be influenced by norepinephrine,
acetylcholine, serotonin, endorphin and many other naturally
occurring chemicals in the brain.
[0021] The effects of aging may be attributed, on a molecular
level, to the oxidative processes in the cell which is harmful to
proteins, lipids and nucleic acids. By providing sufficient
anti-oxidants, it may be possible to modulate or even reverse the
effects of aging at molecular level. Biological aging processes are
part of the increase in disorder at cellular level with the
acknowledged difference being that in the case of a pathological
multi-system, atrophy or senescence at cellular level, multi-organ
failure may occur. This process is demonstrated by reduction in
cellular mass of the organs and may be seen in the aged on autopsy.
For instance, the human brain can decrease from an average weight
of 1500 grams to less than 1000 grams in advanced age.
[0022] The senescent organ loses many functions, leading to
premature aging, for instance the brain loses its memory retention
capability, cannot react quickly to external stimuli and is unable
to memorize new information. Loss of mass is also demonstrated in
organs such as the liver, kidneys, lymph nodes, skeletal muscle and
bones. Corresponding changes are seen in depleted fat deposits,
skin elasticity, brittle bones, low resistance to infection, lack
of exercise tolerance and reproductive ability. At the cellular
level, aging means inadequate DNA repair, leading to disorder in
cell replication Loss of mitosis in the nucleus of the cell,
followed by a closing of the microcirculation. This results in
so-called cell drop-out and loss of organs, as well as membrane
function, in particular the TNP or transmembrane potential. This
process is progressive and affects all organs and tissues
throughout the body. The etiology and pathogenesis of this
condition involves a universal and fundamental aspect of cell
physiology.
[0023] In any study on aging, two distinct types of cells must be
considered. These include normally dividing cells and post-mitotic
cells, normally dividing cells are those of the skin, hair and
gastrointestinal tract. Thousands of such cells die daily, but are
continually replaced with exact replicas until the time of aging
begins. This begins in the mid-twenties in humans. The second cell
type is that which makes up the central nervous system, brain and
heart. In general, post-mitotic cells do not divide or reproduce.
Humans are born with a fixed number of post-mitotic cells, which
lose function and die daily throughout the human life span. Death,
as a result of aging, occurs when a critical number of post-mitotic
cells lose function within a critical organ, such as the brain.
[0024] Congenital defects and infectious disease can strike
anywhere. One of the most common diseases occurs in the arteries:
atherosclerosis. Blockages can occur in veins as well as in
arteries, but these tend to be caused by blood clots, or thrombi,
rather than by atherosclerosis. Thrombophlebitis (or often called
phlebitis) most commonly involves clotting of blood and
inflammation of a vein in the leg. This can be serious if a portion
of the clot becomes detached, travels through the heart and gets
pumped to the lung where it blocks a pulmonary artery as a
pulmonary embolism. About 10% of people with pulmonary embolism die
within an hour. Clotting of blood in the veins can occur when blood
flow is slow or stagnant. This can occur during long periods of
immobilization such as when a person is confined to a hospital bed,
cramped in a crowded airplane on a long flight or driving for an
extended period.
[0025] Atherosclerosis (hardening of the arteries) occurs
"naturally" with aging as a result of cross-linking of
macromolecules like proteins and polysaccharides. Atherosclerosis
refers to the formation and hardening of fatty plaques (atheromas)
of the inner surface of the arteries. In atherosclerosis, the
arteries not only harden, they narrow, sometimes narrowing so much
that hardly any blood can get through. Such narrows vessels are
easily blocked by constriction or objects in the bloodstream.
[0026] The internal surface of an artery is covered with a single
layer of endothelial cells that are pressed against each other like
flagstones on a terrace. Atherosclerosis begins with injury to
endothelial cells, exposing portions of the artery surface below
the endothelium. Free radicals, chemicals in cigarette smoke or
other irritants could be responsible for the injury, as could
turbulence and mechanical force due to high blood pressure.
Platelets (round cells half as large as red blood cells) clump
around the injured endothelial cells and release prostaglandins,
which cause the endothelial cells to proliferate like cancer.
LDL-cholesterol particles release their fat into the areas made
porous by prostaglandins. Macrophages (scavenger white blood cells)
engorge themselves on oxidized LDL-cholesterol until they become
unrecognizable "foam cells" that invade atheromas. Then the
atheromas are hardened by fibrin (which forms scar tissue) and
finally by calcium patches. A vicious circle often arises with scar
tissue attracting more platelets and LDL-engorged macrophages.
Atherosclerosis can occur in any artery. Most commonly it occurs in
the aorta, the artery that receives blood directly from the heart.
Since the aorta is the largest artery in the body, it is rarely
critically narrowed by atheromas. Nonetheless, atherosclerosis can
contribute to aneurysms (ballooning of an artery, responsible for
only one-fortieth of the mortality rate of heart attack--an aortic
aneurysm killed Albert Einstein, who refused to be operated upon.)
The most frequent life-threatening problems, however, are caused by
the arteries supplying the heart, the brain and the kidneys, in
that order.
[0027] Since the blood is 80% water, fats will not dissolve in the
blood. Therefore, fats need to be attached to carrier molecules to
travel through the bloodstream. The principle carrier molecules for
fat are albumin, chylomicrons, Very Low Density Lipoprotein (VLDL),
Low Density Lipoprotein (LDL) and High Density Lipoprotein (HDL).
Free Fatty Acids (FFAs) are attached to albumin, whereas
triglycerides are mainly transported by chylomicrons and VLDL.
Cholesterol and phospholipid are primarily transported by LDL and
HDL. Cholesterol is supplied to cells primarily by the attachment
of LDL to specific LDL receptors on cell membranes. Thyroid hormone
lowers blood cholesterol by increasing the number of LDL receptors
on cells. For most people, atherosclerosis due to excessive
LDL-cholesterol in the blood is the result of a high level of
dietary saturated fat resulting in high LDL-cholesterol production
by the liver. The primary function of HDL seems to be to remove
excess cholesterol from the bloodstream. LDL can directly release
cholesterol into arterial areas made porous by
prostaglandins--whereas HDL can scoop up this loose cholesterol and
return it to the liver. Thus, HDL deficiency can be as serious an
atherosclerosis risk as LDL-cholesterol excess. A 1% reduction in
blood cholesterol is generally associated with a 2% reduction in
risk of coronary artery disease, within "normal" levels of blood
cholesterol.
[0028] Free fatty acids are a major source of energy for many
organs, including the heart. Triglycerides are hydrolyzed into FFAs
and glycerol by the enzyme lipase, which is found both inside cells
and on the surface of the endothelial cells of capillaries.
Phospholipid is an essential constituent of cell membranes.
Cholesterol is also an essential constituent of cell membranes,
particularly in the nervous system. Cholesterol is also the
principle precursor of cortisone and sex hormones. 93% of
cholesterol is found in cells and only 7% in plasma.
[0029] The coronary calcium scan is a test that assists in showing
whether a patient is at risk of developing a coronary artery
disease (CAD), by determining the presence of plaque (fatty
deposits) in blood vessels. The presence and amount of calcium
detected in a coronary artery indicates the presence and amount of
atherosclerotic plaque. Since calcium deposits appear years before
the development of heart disease symptoms such as chest pain and
shortness of breath, a coronary calcium scan is most useful for
people who are at moderate risk of having a heart attack within the
next 10 years, and may help doctors decide whether a patient needs
treatment. The calcified plaque burden caused by calcium deposits
is measured with the Calcium Score, also called the Agatston
Calcium Score, which is computed for each of the coronary arteries
based upon the volume and density of the calcium deposits. The
calcified plaque burden does not correspond directly to the
percentage of narrowing in the artery but does correlate with the
severity of the underlying coronary atherosclerosis. The score is
then used to determine the calcium percentile, which compares the
calcified plaque burden in a subject to the calcified plaque burden
in other asymptomatic men and women of the same age. The calcium
score, in combination with the percentile, enables the physician to
determine the risk of developing symptomatic coronary artery
disease and to measure the progression of disease and the
effectiveness of treatment.
[0030] A score of zero indicates the absence of calcified plaque
burden and significant coronary artery narrowing, although it does
not entirely rule out the presence of soft, non-calcified plaque or
the possibility of a cardiac event. A subject with a score of zero
has a very low likelihood of a cardiac event over at least the next
3 years. A score greater than zero indicates at least some coronary
artery disease. As the score increases, so does the likelihood of a
significant coronary narrowing and coronary event over the next 3
years, compared to people with lower scores. Similarly, the
likelihood of a coronary event increases with increasing calcium
percentiles.
[0031] Often, there are no symptoms of underlying cardiovascular
diseases and a heart attack or stroke may be the first warning.
Early medical detection and treatment is available, however, is not
always effective. Angiograms, bypass surgery and angioplasty are
invasive and traumatic procedures associated with high cost and
often requiring additional therapy and/or intervention.
[0032] The use of chelating agents of various types to entrap metal
ions useful in magnetic resonance imaging is well known. Generally,
the chelating agents contain a substantial number of unshared
electron pairs or negatively charged or potentially negatively
charged species. Perhaps the simplest among these is
ethylenediaminetetraacetic acid (EDTA) commonly used as a water
softener. However, many such agents are known, including, most
notably, and commonly used, diethylene triamine pentaacetic acid
(DTPA) and tetraazacyclododecanetetraacetic acid (DOTA) and their
derivatives. U.S. Pat. Nos. 5,573,752 and 6,056,939, disclose
derivatives of DOTA which are coupled to a benzyl or phenyl moiety
wherein the phenyl ring is substituted by isothiocyanate. This
isothiocyanate provides a reactive group for coupling to various
additional compounds. As described in these patents, the
isothiocyanate group can be used to couple the chelate to a
targeting agent such as an antibody or fragment thereof.
[0033] However, many conditions and diseases are brought on by
damage at the cellular and intracellular level. Often the
mechanisms for cellular repair are inadequate or so compromised the
cells cannot recover or the mechanisms that cause the damage simply
overwhelm the cell. The clinical significance of the damage
generated in living cells is manifested in a diseased cell or
symptoms of an underlying condition. It would be beneficial to
develop methods to facilitate the inhibition of cellular damage or
boost recovery. The presently disclosed subject matter addresses,
in whole or in part, these and other needs in the art.
SUMMARY
[0034] It is therefore an object of the invention to provide
solutions to the aforementioned needs.
[0035] To this end, the invention provides methods of treating or
ameliorating skin conditions, diabetic conditions, cardiovascular
conditions, cancer or infections by administering a magnetic dipole
stabilized solution (MDSS) are provided. Also provided are methods
of chelating, reducing the amount of metal in a subject, increasing
the amount of excretion of metal from a subject, enhancing
performance and nutritional supplementation by administering a
magnetic dipole stabilized solution (MDSS). Thus, in one
embodiment, the present invention provides a method of treating or
ameliorating a skin condition, a condition associated with
diabetes, a condition associated with a cardiovascular dysfunction,
a cancer, an infection or metal poisoning in a subject in need
thereof comprising administering to the subject by injection a
therapeutically effective amount of a composition comprising a
magnetic dipole stabilized solution. Preferably, the magnetic
dipole stabilized solution is an electroactivated water having a
negative electrical potential of about -990 to about -0.0001 mV,
and comprising stabilized oxidative species selected from the group
consisting of H.sub.2O, O.sub.2, H.sub.2O.sub.2, Cl.sub.2O and
H.sub.3O. In one aspect of the invention, the skin condition is
skin aging, wrinkles, acne, photodamage, rosacea, scars, eczema,
alopecia, hypertrophic scars, keliods, stretch marks or Striae
distensae, psoriasis, pruritus, ehlers-danlos syndrome,
scleroderma, post inflammatory hyperpigmentation, melasma,
alopecia, poikiloderma of civatte, viteligo, skin cancers, skin
dyschromas, burns or blotchy pigmentation. In a preferred aspect of
the invention, the skin condition is acne. In another preferred
aspect of the invention, the skin condition is alopecia.
[0036] In a different aspect of the invention, the condition
associated with diabetes is obesity, hypertension, hyperlipidemia,
fatty liver disease, nephropathy, neuropathy, renal failure,
retinopathy, diabetic ulcer, cataracts, insulin resistance
syndrome, cachexia, a diabetic foot ulcer or a diabetic leg
ulcer.
[0037] In yet another aspect of the invention, the condition
associated with a cardiovascular dysfunction is coronary heart
disease, cerebrovascular disease, hypertension, peripheral artery
disease, occlusive arterial disease, angina, rheumatic heart
disease, congenital heart disease, heart failure, cardiac
insufficiency, palpitations, supraventricular tachycardia,
fibrillation, faintness, dizziness, fatigue, migraine, high levels
of total blood cholesterol and/or LDL cholesterol, low level of HDL
cholesterol, high level of lipoprotein, infections of the heart
such as carditis and endocarditis, diabetic ulcer,
thrombophlebitis, Raynauds disease, claudication, gangrene,
atherosclerosis or peripheral artery disease.
[0038] In one embodiment the metal poisoning is chronic. In a
different embodiment, the metal poisoning is acute. Preferably, the
metal is a heavy metal selected from the group consisting of
calcium, aluminum, beryllium, cadmium, copper, iron, lead, uranium,
plutonium, arsenic, molybdenum and mercury.
[0039] The composition to be administered in the methods of the
invention may further comprise vitamins, salts, acids, vitamers,
amino acids, or mixtures thereof, di-methyl amino ethanol and an
antibiotic. In a preferred aspect of the invention, the antibiotic
is erythromycin or gentamicin. In another preferred aspect of the
invention, the composition to be administered further comprises
lipoic acid and salts or mixtures thereof in an amount of about 250
mg. In yet another preferred aspect of the invention, the
composition to be administered further comprises folic acid in an
amount of about 400 mg. The composition may be administered by
infusion over a period of about 1 minute to about 1 hour. The
infusion may be repeated as necessary over a period of time
selected from about 1 week to about 1 year. In another preferred
aspect of the invention, the composition to be administered further
comprises an anesthetic selected from the group consisting of
lignocaine, bupivacaine, dibucaine, procaine, chloroprocaine,
prilocalne, mepivacaine, etidocaine, tetracaine, lidocaine and
xylocalne, and salts, derivatives and mixtures thereof. In yet
another preferred aspect of the invention, the composition to be
administered further comprises heparin.
[0040] In a preferred embodiment, the composition to be
administered comprises sodium ascorbate, magnesium chloride
2H.sub.2O, 2 di-methyl amino ethanol HCl, thiamine, riboflavine,
nicotinamide, pyridoxine, calcium pantothenate, cyanobalamin, and
electroactivated water.
[0041] In yet another embodiment, the invention provides a method
of reducing the amount of metal in a subject in need thereof
comprising administering to the subject by injection a composition
comprising a magnetic dipole stabilized solution. In a preferred
aspect, the metal is a heavy metal having an oxidation state of +1,
+2 or +3 selected from the group consisting of calcium, aluminum,
beryllium, cadmium, copper iron, lead, uranium, plutonium, arsenic,
molybdenum and mercury.
[0042] Preferably, the metal is a transition or post-transition
state metal. Even more preferably, the metal is a divalent cation.
In another preferred aspect of the invention, the magnetic dipole
stabilized solution is an electroactivated water having a negative
electrical potential of about -990 to about -0.0001 mV, and
comprising stabilized oxidative species selected from the group
consisting of H.sub.2O, O.sub.2, H.sub.2O.sub.2, Cl.sub.2O and
H.sub.3O. Preferably, the solution comprises lipoic acid and salts
or mixtures thereof in an amount of about 250 mg. In a preferred
aspect of the invention, the composition is administered by
infusion over a period of about 1 minute to about 1 hour. The
infusion is repeated as necessary over a period of time selected
from about 1 week to about 1 year. In a preferred aspect of the
invention, the composition to be administered in the methods of the
invention further comprises an anesthetic and one or more amino
acids or salt thereof.
[0043] In another embodiment, the invention provides a method of
increasing the excretion of metal or one or more toxins from a
subject in need thereof, comprising administering to the subject by
injection an effective amount of a magnetic dipole stabilized
solution. Preferably, the magnetic dipole stabilized solution is an
electroactivated water having a negative electrical potential of
about -990 to about -0.0001 mV, and comprising stabilized oxidative
species selected from the group consisting of H.sub.2O, O.sub.2,
H.sub.2O.sub.2, Cl.sub.2O and H.sub.3O.
[0044] In yet another embodiment, the invention provides a method
of enhancing athletic, cognitive or alertness performance in a
subject in need thereof comprising administering to the subject by
injection an effective amount of magnetic dipole stabilized
solution. Preferably, the magnetic dipole stabilized solution is an
electroactivated water having a negative electrical potential of
about -990 to about -0.0001 mV, and comprising stabilized oxidative
species selected from the group consisting of H.sub.2O, O.sub.2,
H.sub.2O.sub.2, Cl.sub.2O and H.sub.3O. The composition may be
administered by infusion over a period of about 1 minute to about 1
hour. The infusion may be repeated as necessary over a period of
time selected from about 1 week to about 1 year within about 24
hours, within about one week or within about one month of the
performance. In a preferred aspect of the invention, the magnetic
dipole stabilized solution comprises sodium ascorbate, magnesium
chloride 2H.sub.2O, 2 di-methyl amino ethanol HCl, thiamine,
riboflavine, nicotinamide, pyridoxine, calcium pantothenate,
cyanobalamin and electroactivated water. In another preferred
aspect of the invention, the magnetic dipole stabilized solution
comprises from about 100 mg to about 500 mg sodium ascorbate; from
about 100 mg to about 500 mg magnesium chloride 2H.sub.2O; from
about 100 mg to about 500 mg 2 di-methyl amino ethanol HCl; from
about 1 mg to about 100 mg thiamine; from about 1 mg to about 100
mg riboflavine; from about 1 mg to about 300 mg nicotinamide; from
about 1 mg to about 100 mg pyridoxine; from about 1 mg to about 100
mg calcium pantothenate; from about 100 .mu.g to about 500 .mu.g
cyanobalamin; and electroactivated water.
[0045] In a further embodiment, the invention provides a method of
providing nutritional support to a subject in need thereof
comprising administering to the subject by injection an effective
amount of magnetic dipole stabilized solution. Preferably, the
magnetic dipole stabilized solution is an electroactivated water
having a negative electrical potential of about -990 to about
-0.0001 my, and comprising stabilized oxidative species selected
from the group consisting of H.sub.2O, O.sub.22, H.sub.2O.sub.2,
Cl.sub.2O and H.sub.3O. The subject may be a healthy individual, or
may be suffering from a malady selected from the group consisting
of malnutrition, cachexia, diabetes, severe food allergies, short
gut syndrome, cystic fibrosis, pancreatic disease, gastroenteritis,
inflammatory bowel disease, intractable diarrhea, protein
maldigestion, necrotizing enterocolitis, infectious diseases,
hypermetabolism, trauma, eosinophilic gastroenteritis and
gastroesophogeal reflux. In a preferred aspect of the invention,
the magnetic dipole stabilized solution comprises one or more trace
metals selected from the group consisting of Zn, Se, Cu, Mn and Fe.
In a preferred embodiment, the subject receiving nutritional
support has special dietary needs. Preferably, the dietary needs
are associated with athletes, children, obese subjects, subjects
undergoing chemotherapy for cancer, AIDS patients, malnourished
subjects or subjects in a comatose state. In a preferred aspect of
the invention, the magnetic dipole stabilized solution is an
electroactivated water comprising from about 100 mg to about 500 mg
sodium ascorbate; from about 100 mg to about 500 mg magnesium
chloride 2H.sub.2O; from about 100 mg to about 500 mg 2 di-methyl
amino ethanol HCl; from about 1 mg to about 100 mg thiamine; from
about 1 mg to about 100 mg riboflavine; from about 1 mg to about
300 mg nicotinamide; from about 1 mg to about 100 mg pyridoxine;
from about 1 mg to about 100 mg calcium pantothenate; from about
100 .mu.g to about 500 .mu.g cyanobalamin; from about 1 mg to about
20 mg Zn; from about 1 mg to about 100 mg Se; from about 1 mg to
about 1000 mg Cu; from about 0.01 mg to about 10 mg Mn; and from
about 1 mg to about 20 mg Fe. In another preferred aspect of the
invention, the magnetic dipole stabilized solution comprises about
395 mg sodium ascorbate; about 255 mg magnesium chloride 2H.sub.2O;
about 200 mg 2-di-methyl amino ethanol HCl; about 36 mg thiamine;
about 7.3 mg riboflavine; about 100 mg nicotinamide; about 18.2 mg
pyridoxine; about 18.2 mg calcium pantothenate; about 320 .mu.g
cyanobalamin; about 10 mg Zn; about 45 mg Se; about 400 mg Cu;
about 0.3 mg Mn; about 8 mg Fe; and electroactivated water.
[0046] In a different embodiment, the invention provides a kit
comprising a first vial containing a solution comprising vitamins,
salts, acids, vitamers, or mixtures thereof, and a second vial
containing a magnetic dipole stabilized solution comprising
electroactivated water. Preferably, the kit comprises instructions
for use. In a preferred aspect of the invention, the magnetic
dipole stabilized solution has a positive electrical potential
before mixing the contents of the vials. In an even more preferred
aspect of the invention, the magnetic dipole stabilized solution
has a negative electrical potential after combining the first and
second vials. Preferably, the solution in the first vial comprises
sodium ascorbate, magnesium chloride 2H.sub.2O, 2 di-methyl amino
ethanol HCl, thiamine, riboflavine, nicotinamide, pyridoxine,
calcium pantothenate, and cyanobalamin.
[0047] In another embodiment, the invention provides a kit
comprising a first vial containing a magnetic dipole stabilized
solution comprising electroactivated water and one or more selected
from the group consisting of heparin, vitamins, salts, acids,
lipoic acid, folic acid, antibiotic(s) and vitamers, and mixtures
thereof; a second vial containing a magnetic dipole stabilized
solution; and instructions for use. In a preferred aspect of the
invention, the solution in the first vial comprises lipoic acid in
an amount of between about 10 mg and 500 mg. Preferably, the amount
of lipoic acid is between about 100 mg and 400 mg. Even more
preferably, the amount of lipoic acid is about 250 mg. In another
preferred aspect of the invention, the solution in the first vial
comprises sodium ascorbate, magnesium chloride 2H.sub.2O, 2
di-methyl amino ethanol HCl, thiamine, riboflavine, nicotinamide,
pyridoxine, calcium pantothenate, cyanobalamin, lipoic acid, folic
acid, and antibiotic(s).
DETAILED DESCRIPTION
[0048] The present invention will now be described more fully
hereinafter. However, many modifications and other embodiments of
the present invention set forth herein will come to mind to one
skilled in the art to which the invention pertains having the
benefit of the teachings presented in the foregoing descriptions.
Therefore, it is to be understood that the present invention is not
to be limited to the specific embodiments disclosed and that
modifications and other embodiments are intended to be included
within the scope of the appended claims.
[0049] Methods of treating or ameliorating skin conditions,
diabetic conditions, cardiovascular conditions, cancer and
infections by administering a magnetic dipole stabilized solution
(MDSS) are provided. Also provided are methods of chelating,
reducing the amount of metal in a mammal, increasing the amount of
excretion of metal from a mammal, enhancing performance and
nutritional supplementation by administering a magnetic dipole
stabilized solution (MOSS). The MDSS compositions herein possess
properties that when administered to a subject in need thereof
provide a therapeutic or cosmetic effect for the skin, enhance
performance or nutritional support, treat or ameliorate diabetic
conditions, cardiovascular conditions, cancer and infections,
provide chelation, reduce the amount of metal in a subject and
increase metal excretion from a subject. Among other properties,
the compositions are capable of restoring cellular integrity and
transmembrane potential, modulating cellular membrane permeability
and enhancing the transfer of molecules and ions through the cell
membranes. Data provided herein show that these properties have a
beneficial result when administered to a subject for the conditions
described herein. Surprisingly, the MDSS compositions comprising
vitamins or other ingredients described herein are very effective
even for conditions that have not responded to prior treatments.
Because the MDSS compositions are safe and non-toxic, they can be
administered prophylactically to prevent or reduce the likelihood
of onset of the conditions or symptoms described herein. One
example is administration of an MDSS composition subsequent to
exposure to a substance that may lead to an increased risk of
increased metal in the body.
[0050] The purpose of the chelating agent is, of course, to
sequester metals, such as paramagnetic metals, heavy metals or
radionuclides. Heavy metals include toxic metals and elements that
exhibit metallic properties, which would mainly include the
transition metals, some metalloids, lanthanides, and actinides.
Suitable metals include calcium, aluminum, beryllium, cadmium,
copper iron, lead, uranium, plutonium, arsenic and mercury. Other
suitable paramagnetic metals include a lanthanide element of atomic
numbers 58-70 or a transition metal of atomic numbers 21-29, 42 or
44, such as scandium, titanium, vanadium, chromium, manganese,
iron, cobalt, nickel, copper, molybdenum, ruthenium, cerium,
praseodymium, neodymium, promethium, samarium, europium,
gadolinium, terbium, dysprosium, holmium, erbium, thulium, and
ytterbium, most preferably Gd(III), Mn(II), iron, europium and/or
dysprosium. Suitable radionuclides include the radioactive forms
of, for example, Sm, Ho, Y, Pm, Gd, La, Lu, Yb, Sc, Pr, Tc, Re, Ru,
Rh, Pd, Pt, Cu, Au, Ga, In, Sn, and Pb.
[0051] As used herein, the term "metal poisoning" refers to an
excessive buildup of a particular metal in the mammal. The symptoms
of metal poisoning are well known and differ depending on the
particular metal and the mammal. A mammal can be asymptomatic but
nevertheless be suffering from metal poisoning.
[0052] As used herein the term "mammal" refers to humans as well as
all other mammalian animals. As used herein, the term "mammal"
includes a "subject" or "patient" and refers to a warm blooded
animal. It is understood that guinea pigs, dogs, cats, rats, mice,
horses, goats, cattle, sheep, zoo animals, livestock, primates, and
humans are all examples of animals within the scope of the meaning
of the term. As used herein "a mammal in need thereof" may be a
subject whom could have been but is not required to have been
diagnosed as suffering from the condition intended to be treated.
In one aspect, the present method is directed to conditions that
are noticeable to the subject and the subject wishes to treat or
ameliorate the condition without a formal diagnosis. For instance,
a subject wishing to ameliorate alopecia is a subject who has hair
loss or wishes to stave off subsequent hair loss. In another
example, a subject with acne does not necessarily need to be
diagnosed to know that he or she has acne. Alternatively, a subject
could be diagnosed with a skin condition and seek treatment or
amelioration by a method disclosed herein. Clearly, one who suffers
from these conditions has an acute awareness of the problem with or
without a formal diagnosis by medical personnel. Alternatively, one
may be aware of symptoms associated with metal poisoning without
knowing that metal poisoning may be causing the symptoms. One may
wish to have chelation treatment to improve or ameliorate the
symptoms. In other words, a mammal, if human, in need of being
treated can appreciate the purpose for which he or she is being
treated, whether it is to treat a symptom of a known or unknown
cause or the underlying cause with or without formal diagnosis.
Alternatively, a mammal in need thereof is one who has been
diagnosed as having a condition and is in need of specific
treatment.
[0053] As used herein the terms "treating" and "ameliorating" are
intended to refer to all processes wherein there may be a slowing,
interrupting, arresting, or stopping of the progression of the
condition or symptoms and does not necessarily indicate a total
elimination of the underlying condition. The terms also encompass
the administration of a MDSS composition wherein the mammal has a
condition or symptom or a predisposition towards a condition or
symptom, where the purpose is to cure, heal, alleviate, relieve,
alter, improve or affect the condition or symptom or the
predisposition to the same. Also contemplated is preventing the
condition or symptom or the predisposition to the same by
prophylactically administering a MDSS composition as described
herein.
[0054] As used herein, the term "skin condition" means a disorder,
disease or symptom related to the skin. The term "skin" is meant to
describe the outer covering of a mammalian form including, without
limitation, the epidermis, dermis, and subcutaneous tissues. The
skin can include other components such as hair follicles and sweat
glands. A number of skin conditions can be treated according to the
methods of the present invention and include skin disorders of the
hair follicles and sebaceous glands. These and other conditions
include, but are not limited to, intrinsic skin aging, wrinkles,
acne, photodamage, rosacea, scars, hypertrophic scars, keliods,
stretch marks or Striae distensae, psoriasis, nutrient status,
anti-oxidant status, energy status, oxygen status, eicosanoid
staus, leukotriene status, pruritus, ehlers-danlos syndrome,
scleroderma, post inflammatory hyperpigmentation, melasma,
alopecia, poikiloderma of civatte, viteligo, skin cancers, skin
dyschromas, or blotchy pigmentation. Preferably, skin conditions
such as acne, alopecia and burns among others, can be treated
according to the present invention. The skin consists in the widest
organ existing in the human body. Among the functionalized
structures present therein, the vascular system, lymphatic system,
glands and nerves, are detached. Interaction of all its structures
in an orderly manner, confers to the skin a fundamental role on
existence and survival of the livings, constituting an efficient
interface between external ambient and internal organs, which main
function is to protect from water loss, contingent intruders,
strange material, pathogenic organisms and microorganisms. Further
to these functions, skin is able to eliminate a series of
catabolites originating from internal biochemical processes and to
maintain the ideal temperature constant for the adequate
functioning of living organisms.
[0055] Skin is structurally composed of two tissue layers. The
epidermis is the most external layer. It is constituted of a series
of epithelium stratified cell layers, which quantity of keratin
protein proportionally increases on most external layers. This
arrangement makes the most external layers more compact, offering
greater protection in relation to excessive water loss, action of
strange substances and organisms, besides offering greater
resistance to abrasion and injuries. This layer does not contain
any blood vessel and is sustained by fluids of the layer
immediately beneath the dermis, this one presenting irregular
connection arrangements, presenting more complex tissues and
containing blood vessels between a series of specialized
structures.
[0056] Skin integrity can eventually be ruptured, causing a series
of problems with reference to maintenance of the internal functions
of the organism. This rupture can occur due to perforations,
accidental or programmed cuts (surgeries), burns, injuries
resulting from degenerating processes, having diseases, congenital
anomalies or alterations of biochemical processes as a cause,
resulting in ulceration, among others.
[0057] Under normal conditions, the body has mechanisms to repair
and eventually recover, partial or totally, several skin ruptures,
in order to restore its integrity and functionality. This repair
process is directly related with rupture extension, tissues
affected, injury and patient physical condition. Contamination of
exposed tissue by strange substances and live organisms will be
another factor that will influence on the mechanism and the
velocity of the repair process. Skin healing process involves
particular groups of cells and proteins in a complex biochemical
mechanism. This renovation process is generally divided in three
temporary phases known as inflammation, proliferation and
remodeling.
[0058] At the initial stage of inflammation, the platelets present
out of the circulatory system become more active, producing
aggregation. Thus, they signalize the beginning of the repair
process, forming a set of temporary cells to avoid hemorrhage and
prevent bacterial invasion. Blood vessels under growth, infiltrates
in the affected site, discharging various mediator molecules,
including other platelets resulting from growth factors, Willibrand
factor, thrombospondine, fibronectine, fibrinogen,
5-hydroxytriptophan, thromboxane-A2 and adenosine diphosphate
(Kirsner e Eaglstein, J. Dermatol. 151:629-640, 1993). The set of
cells that characterizes the clotting are bonded and provides a
matrix of monocytes, fibroblasts and keratinocytes. Chemostatic
molecules attract the monocytes that are transformed into
macrophages and secreting additional growth factors (Nathan e
Sporn. J. Cell Biol. 113:981-986, 1991). Neutrophyls can assist
these processes secreting degrading enzymes, the elastases and
collagenases, increasing the passage through the basis of cellular
membrane. The most important role of the neutrophyls seems to be
cleaning the affected tissue or defend the area from contingent
intruders, accelerating the process as a whole, removing the dead
cells and platelets. Infiltration of neutrophyls ceases within 48
hours approximately, provided that no bacterial contamination
occurs. The neutrophyls excess is phagocyted by macrophages
resulting from monocytes of the circulatory system. It is believed
that the macrophages are essential for an efficient recovery
process, also being responsible for the phagocytes process of
pathogenic organisms and for the cleaning of other materials
strange to the body. Moreover, they deliver innumerous factors
involved in subsequent events in tissue recovery process.
[0059] The second recovery stage, the proliferation, generally
begins 48 hours after occurring tissue injury. Fibroblasts begin to
proliferate and migrate to the interior of affected space, starting
from the already bond tissues and reaching the end of injury.
Fibroblasts yield collagen and glycosaminoglycans, stimulating a
proliferation of endothelial cells. Endothelial cells will promote
the growth of a new net of blood vessels. Collagenases and
plasminogen activators are secreted from keratinocytes. If the
recovery process is not disturbed, an adequate supply of nutrients
with oxygen, the keratinocytes can migrate to the affected tissue.
It is believed that keratinocytes only migrate on live tissues and,
as a consequence, keratinocytes migrate through areas beneath dead
tissues and in interface between the affected area and that already
recovered. Angiogenesis, formation of new blood vessels in response
to chemotactic signals (Folkman and Klagsbrun, Science 235:442-447,
1987), and fibroplasias, accumulation of fibroblasts and formation
of tissues granulation, also occur during the proliferating
phase.
[0060] The third and last recovery stage, the remodeling, starts
when the epithelium is already recovered. In this phase, which can
be extended for many years, the affected tissue obtains its normal
strength, slowly undergoing structural readjustments, always on
account of depth, as well as the extension of the affected area.
Remodeling of tissues is followed by the secretion of cellular
matrix components, including fibronectine, collagen and
proteoglycan, which serve as a support for the cellular migration
and for the tissue. The type III collagen, synthesized at the
initial stages of the recovery process, is substituted by type I
collagen, the most permanent form, by a response proteolitic
process. The affected surface is subsequently coated with an
enlargement process, making the surface smoother. These epithelial
cells are spread at layers underneath the unstructured area, in
order that the affected layers and those above it are slowly
substituted or recovered.
[0061] This complex process of natural regeneration takes
considerable time and can be affected by pathological conditions as
infections, maceration, dry skin and overall patient health. This
can lead to chronic ulcer formation, making this process still
slower. Other severe conditions can be established in tissues
regeneration course. Ischemia, for example, refers to a
pathological condition resulting from a located dysfunction of the
vascular system, resulting in inadequate blood supply with
subsequent damage to the affected cellular tissue.
[0062] The term "acne" is meant to include any skin condition where
a skin pore becomes blocked and/or thereby becomes inflamed. The
term acne includes without limitation superficial acne, including
comedones, inflamed papules, superficial cysts, and pustules; and
deep acne, including deep inflamed modules and pus-filled cysts.
Specific acne conditions can include, but are not limited to, acne
vulgaris, acne comedo, papular acne, premenstrual acne,
preadolescent acne, acne venenata, acne cosmetica, pomade acne,
acne detergicans, acne excoriee, gram negative acne, acne rosacea,
pseudofolliculitis barbae, folliculitis, perioral dermatitis, and
hiddradenitis suppurativa. Acne is a common inflammatory
pilosebaceous disease characterized by comedones, papules,
pustules, inflamed nodules, superficial pus-filled cysts, and (in
extreme cases) canalizing and deep, inflamed, sometimes purulent
sacs. Acne involves an interaction between hormones,
keratinization, sebum, and bacteria that somehow determines the
course and severity of acne. It often begins at puberty, when the
increase in androgens causes an increase in the size and activity
of the pilosebaceous glands. The earliest microscopic change is
thought to be intrafollicular hyperkeratosis, which leads to
blockage of the pilosebaceous follicle with consequent formation of
the comedo, composed of sebum, keratin, and microorganisms,
particularly Propionibacterium acnes. Lipases from P. acnes break
down triglycerides in the sebum to form free fatty acids (FFA),
which irritate the follicular wall. Retention of sebaceous
secretions and dilation of the follicle may lead to cyst
formation.
[0063] Skin conditions also include, but are not limited to,
dermatological conditions linked to disorders of keratinization
involving differentiation and proliferation, in particular, acne
vulgaris, comedonic or polymorphic acne, nodulocystic acne, acne
conglobata, senile acne and secondary acnes such as solar, drug or
occupational acne; for other types of keratinization disorders
especially ichthyoses, ichthyosiform conditions, Darier's disease,
palmoplantar keratoderma, leukoplakia and luecoplakiform conditions
or lichen and lichen planus; dermatological disorders having an
inflammatory or immunoallergic component, in particular, all forms
of psoriases, either cutaneous, mucosal or ungual, and psoriatic
rheumatism, and cutaneous atopy such as eczema or respiratory
atopy, dry skin, inflammation of the skin, solar erythema, skin
allergies or other skin disorders of the epidermis and dermis.
[0064] Psoriasis is a skin condition characterized by hyperplasia
of keratinocytes resulting in thickening of the epidermis and the
presence of red scaly plaques. The lesions in this chronic disease
typically are subject to remissions and exacerbations. There are
several patterns, of which plaque psoriasis is the most common.
Guttate psoriasis, with raindrop shaped lesions scattered on the
trunk and limbs, is the most frequent form in children, while
pustular psoriasis is usually localized to the palms and soles. The
classical inflammatory lesions vary from discrete erythematous
papules and plaques covered with silvery scales, to scaly itching
patches that bleed when the scales are removed. Psoriasis is a
condition in which cell proliferation is increased up to 10 times
the normal rate for an individual. The skin is the largest portion
of the human body which is comprised of cells within three skin
layers. Each of the skin layers is in a constant state of growth
with the outer layer being formed of predominantly dead tissue
which is naturally being discarded at a normal rate. Replacement of
cells from underlying layers is accomplished by cell division and
maturation where cells move upwardly and outwardly at a rate which
varies dependent upon the age, sex, and/or health of an individual.
Psoriasis causes an increased turnover of cells, which in turn
increases the rate of cell growth and cell death. This increased
rate of cell growth and cell death may result in injuries and/or
disorders which accompany the increased synthesis of all tissue
components and further elevate the strain placed upon skin or other
tissue and the bio-synthetic capabilities of the cells within the
affected area.
[0065] The terms eczema and dermatitis are generally used names for
severe inflammation of the skin, usually with redness, swelling,
oozing, rusting or scaling of lesions which are usually itchy.
Eczema may take the form of contact dermatitis (due to skin contact
with the cause) or atopic dermatitis in individuals who are
"atopic" or allergic by nature. If the scalp is involved the
disorder is known as seborrheic dermatitis. Dermatitis can be
caused by chemicals, plants, shoes, clothing, metal compounds and
even medicines used to treat dermatitis. In atopic dermatitis
environmental temperature, humidity changes, bacterial skin
infections, airborne allergens and garments, e.g., wool, may all
bring about dermatitis.
[0066] Alopecia is a skin condition that results in the loss of
hair on the scalp and elsewhere. It usually starts with one or more
small, round, smooth patches and occurs in males and females of all
ages. Loss of hair in one or several small spots is common, but it
is possible to lose all scalp hair (alopecia totalis), or every
hair on the body (alopecia universalis), which is rare.
[0067] The skin condition, rosacea is of an unknown origin. It
usually affects the middle third of the face causing skin redness,
prominent vascularization, papules, pustules and swelling, as well
as a predisposition to flushing and blushing. However, rosacea can
also occur on other parts of the body including the chest, neck,
back, or scalp. The blood vessels near the skin dilate and become
more visible there through, resulting in telangiectasia. The
resulting papules and pustules resemble teenage acne, and are
frequently mistaken for the same. Unlike acne, rosacea does not
have blackheads or whiteheads. Rosacea, however, can occur in all
age groups and in both sexes, where it tends to be more frequent in
women but more severe in men. The flushing and blushing regions of
the face are affected by rosacea. Emotional factors such as
anxiety, embarrassment, or stress may evoke or aggravate rosacea.
In addition, a flare-up may be caused by environmental or climate
variances, and UV exposure is known to aggravate rosacea.
Furthermore, diet is also known to aggravate rosacea. Spicy foods,
alcoholic beverages, hot beverages, and smoking are known to cause
flare-ups. Rosacea is not only an aesthetic complication. Rosacea
is a chronic disease that has rarely been documented to reverse its
progression. If untreated, the condition worsens and spreads.
Untreated rosacea may cause a disfiguring nose condition called
rhinophyma, which is characterized by a bulbous, red nose and
inflamed cheeks. Severe rhinophyma may require surgery, an invasive
procedure that may be avoided by timely treatment. Another problem
of advanced rosacea is ocular. Persons afflicted with rosacea may
experience conjunctivitis, a burning and grittiness of the eyes. If
untreated, it may lead to serious complications such as rosacea
keratitis, which damages the cornea and may impair vision.
[0068] Burns involve a type of skin integrity rupture. Burns
represent one of the most painful processes that can be established
in this tissue, needing the establishment of a coordinated therapy
to help its recovery and pain treatment. Burns can be caused by
several factors, among which, exposure to high or low temperatures,
exposure to chemical compounds, by electricity, by exposure to
radiation and mechanical friction. Burn severity and its risk are
evaluated according to the amount of affected tissue and depth
reached. The amount of affected tissue is represented by the
percentage of burned corporeal surface (BCS). In this type of
evaluation, burns can be divided into small, moderate, large or
massive burns, where regions inferior to 15% of BCS, from 15% up to
49% of BCS, from 50% up to 69% of BCS and over 70% of BCS,
respectively. The extension of the affected area is determined
through Lund-Browder scheme, which takes into consideration the
burn proportion, in accordance with the age of the burned patient.
Another rule that is most used for determining the extension of the
affected area is that known as Wallace Rule or Rule of Nines, a
technique less efficient than the foregoing, however, easy to
memorize, being very much employed in emergency cases. This rule
applies a value equaling nine or nine multiple to the affected
parts, being 9% for each superior member, 9% for the head, 18% for
each inferior member, 18% for each torso face and 1% for the
genitalia.
[0069] The classification as first, second and third degree
corresponds to burn depth. The first-degree injury corresponds to
the burn that affects the skin most external layer (epidermis), not
producing hemodynamic alterations, however the affected region is
found hyperemic in absence of blisters or phlyctenae. This type of
injury can be observed in erythemae resulting from sunrays or
heated water. The second-degree injury affects either the epidermis
as part of the dermis and is mainly characterized by the formation
of blisters or phlyctenae, as those resulting from scalding or
thermal injury resulting from overheated liquid. The third-degree
injury endangers the totality of skin layers (epidermis and dermis)
and, in many cases, can affect other tissues, as the subcutaneous
cellular tissue, muscular tissue and bone tissue. Third-degree
burns are considered as the most severe of all thermal injuries,
producing deforming injuries. For being deeper, it eliminates the
nerve endings responsible for shooting the painful message. These
types of burns need transplanting for recomposing destroyed
tissues, since the structures and organelles necessary for the
natural recovery process, were eliminated. Since burns are wounds
that involve the skin, they develop afore mentioned complex process
of regeneration and recomposition of injured tissue. The speed or
grade of re-epithelization of the affected region is small the
greater the area involved is, considerably increasing the recovery
time, when the injuries start to cover a body surface over 10% or
15%.
[0070] Immediately after the burn trauma, an inflammatory process
develops wherein various agents are delivered, occurring deposition
of fibrins and platelets activated on the wound surface. A matrix
rich in organic material is yielded, able to enclosure bacteria and
other strange substances, which frequently aggravates the case, due
to sepsis that can follow trauma. During this inflammatory process
a great quantity of exudates crop out of the burned region, leading
the patient to an intense loss of liquids, which, depending on the
burn extension and depth, can cause a severe dehydration case. The
inflammatory process extends to adjacent tissues, factor that
endangers the functions of these tissues initially intact.
[0071] Extensive and deep burns cause alterations that are extended
far beyond the affected local, such as anatomic, metabolic,
physiological, endocrinology and immune alterations, requiring
special care. Significant fluid losses, delivery of inflammatory
multi-mediators and contamination by bacteria, occur. When
disseminated in central organs through circulation, bacteria and
inflammatory mediators can cause cardiac endangerment, failure of
gastrointestinal mucous integrity and in extreme cases,
multi-organic failure.
[0072] Hemodynamic alterations that occur after severe thermal
injuries include decrease of cardiac output and reduced volume of
circulating plasma, contributing all to a hypovolemic shock.
Inflammatory mediators (including cytokines, prostaglandin, nitric
oxide and superoxide ions) have been implicated in causing further
damage to tissues. It is believed that despite local benefit, such
mediators induce undesirable effects when reaching significantly
high levels. As an example, a greater damage to tissues can be
caused by delivery of proteolitic enzymes and superoxide ions of
macrophages and activated leucocytes.
[0073] Thus, burns are skin conditions that develop unbalance in a
series of natural organic mechanisms, not limited to endangered
tissues only, but involve numerous organs that can be affected.
Additionally, large thermal injuries induce to a sharp increase in
basal metabolic rate. Large nitrogen corporeal losses, observed in
burned patients, mainly occur due to protein exudation through
burned skin and also by the fact that, under such catabolic stress
situation, corporeal proteins can become the metabolic substrate
used for production of 15 to 20% of total energy required by the
organism. Further to these abnormalities, hormonal levels change
with an increase in cathecolamines, cortisol and glucagons, in the
presence of normal or slightly increased levels of insulin. These
hormonal alterations promote increase of proteolysis and lipolysis.
Thus, the entire complex process is characterized by imbalance. The
quick recovery of the skin of a burned mammal is of utmost
importance for recovery of his normal organic functions.
[0074] Other skin conditions can include dry/chapped skin. Thus,
the methods disclosed herein are useful for treating or
ameliorating the skin against the effects of environmental
conditions.
[0075] As used herein, a "condition associated with diabetes"
includes obesity, hypertension, hyperlipidemia, fatty liver
disease, nephropathy, neuropathy, renal failure, retinopathy,
diabetic ulcer, cataracts, insulin resistance syndromes and
cachexia. Diabetic diseases and conditions that are especially
suited for treating or ameliorating with a MDSS composition as
described herein are ulcers.
[0076] As used herein, "cardiovascular dysfunction" includes
conditions and diseases such as coronary heart disease,
cerebrovascular disease, hypertension, peripheral artery disease,
occlusive arterial disease, angina, rheumatic heart disease,
congenital heart disease, heart failure, cardiac insufficiency,
palpitations, supraventricular tachycardia, fibrillation,
faintness, dizziness, fatigue, migraine, high levels of total blood
cholesterol and/or LDL cholesterol, low level of HDL cholesterol,
high level of lipoprotein, infections of the heart such as carditis
and endocarditis, diabetic ulcer, thrombophlebitis, Raynauds
disease, claudication and gangrene. Diseases and conditions that
are especially suited for treating or ameliorating with a MDSS
composition as described herein are peripheral artery disease and
atherosclerosis.
[0077] As used herein, the term "cancer" refers to a physiological
condition in mammals that is typically characterized by unregulated
cell growth/proliferation. Examples of cancer include but are not
limited to, carcinoma, lymphoma, blastoma, sarcoma, and leukemia.
More particular examples of such cancers include adrenocortical
cancer; bladder cancer; bone cancer; brain cancer; breast cancer;
cancer of the peritoneum; cervical cancer; colon cancer; colorectal
cancer; endometrial or uterine carcinoma; esophogeal cancer; eye
cancer; gallbladder cancer; gastrointestinal cancer; glioblastoma;
various types of head and neck cancer; hepatic carcinoma;
hepatocellular cancer; kidney cancer; laryngeal cancer; liver
cancer; lung cancer, such as, for example, adenocarcinoma of the
lung, small-cell lung cancer, squamous carcinoma of the lung,
non-small cell lung cancer; melanoma and nonmelanoma skin cancer;
myeloproliferative disorders, such as, for example, polycythemia
vera, essential thrombocythemia, chronic idiopathic myelofibrosis,
myeloid metaplasia with myelofibrosis, chronic myeloid leukemia
(CML), chronic myelomonocytic leukemia, chronic eosinophilic
leukemia, hypereosinophilic syndrome, systematic mast cell disease,
atypical CML, or juvenile myelomonocytic leukemia; ovarian cancer;
pancreatic cancer; prostate cancer, including benign prostatic
hyperplasia; rectal cancer; salivary gland carcinoma; squamous cell
cancer; testicular cancer; thyroid cancer; and vulval cancer. Also
contemplated is the use of a MDSS composition as an adjuvant to a
primary therapy against one of the above-listed cancers. A cancer
can be treated or ameliorated by treating or ameliorating a symptom
of the cancer or secondary conditions of the cancer.
[0078] As used herein, the term "anti-infective" includes antiviral
or antibiotic or any biostatic activity, i.e., where the
proliferation of the target species is reduced or eliminated, and
true biocidal activity where the target species are killed.
Furthermore, the terms "microbe" or "antimicrobial" should be
interpreted to specifically encompass bacteria and fungi as well as
other single-celled organisms such as mold, mildew and algae. In
this embodiment, it is preferred that the composition further
comprise an antibiotic. The antibiotic can be an antibiotic
effective against bacteria, including gram-negative and
gram-positive organisms. Antibiotics include tetracycline,
oxytetracycline, metacycline, doxycycline, minocycline,
erythromycin, lincomycin, penicillin G, clindamycin, kanamycin,
chloramphenicol, frathomycin, streptomycin, norfloxacin,
ciprofloxacin, ofloxacin, grepafloxacin, levofloxacin,
sparfloxacin, ampicillin, carbenicillin, methicillin,
cephalosporins, vancomycin, bacitracin, gentamycin, fusidic acid,
ciprofloxin and other quinolones, erythromycin, gentamicin,
sulfonamides, trimethoprim, dapsone, isoniazid, teicoplanin,
avoparcin, synercid, virginiamycin, piperacillin, ticarcillin,
cefepime, cefpirome, rifampicin, pyrazinamide, enrofloxacin,
amikacin, netilmycin, imipenem, meropenem, inezolidcefuroxime,
ceftriaxone, cefadroxil, cefazoline, ceftazidime, cefotaxime,
roxithromycin, cefaclor, cefalexin, cefoxitin, amoxicillin,
co-amoxiclav, mupirocin, cloxacillin, co-trimoxazole,
pharmaceutically acceptable salts thereof, derivatives thereof, and
combinations thereof. Especially preferred agents are erythromycin
and gentamicin. The MDSS composition could alternatively or in
addition to include one or more antiviral, antiseptic or
antimicrobial agents.
[0079] As used herein, the term "metal poisoning" refers to an
excessive buildup of a particular metal in a subject. The symptoms
of metal poisoning are well known and differ depending on the
particular metal and the subject. A subject can be asymptomatic but
nevertheless be suffering from metal poisoning.
[0080] "Athletic performance" refers to any professional or
recreational activity wherein the performer, for example an
athlete, exerts a physical act, such as running, swimming, golf,
bowling, archery, football, baseball, basketball, soccer, hiking,
cycling, dancing and the like. "Cognitive performance" refers to
any activity wherein the performer exerts a mental act and can
include test-taking, focusing, concentrating, memorizing, studying
and the like. A general state of "alertness" refers to the ability
to focus or concentrate on a given task or performance. Alertness
then can be viewed as an ability to stave off fatigue, mental
tiredness or decreasing cognitive performance, such as when
driving, boating, operating equipment, piloting, speech making,
monitoring, police or security work, attending seminars and
classes, working and the like. The magnetic dipole stabilized
solution compositions described herein can be administered
preferably before, but also during, long-lasting sports activities,
any time an energetic boost is desired or when maintenance of
energy levels is desired.
[0081] As used herein, the term "nutrition support" is intended to
mean a composition that provides beneficial components that can
include nutrients. The beneficial components are intended to work
in conjunction with a separate primary nutrient source to meet the
dietary needs of a mammal.
[0082] As used herein, the term "special dietary needs" refers to
any mammal that has a restricted diet. The diet may be restricted
because of allergy, but also because an unrestricted diet would
likely cause the mammal to develop a food-borne condition. For
example, the etiology of a number of gastrointestinal conditions is
caused by the reaction towards certain foods in certain mammals.
Subjects who are nauseous are also likely to have special diets in
order to maintain a healthy nutrition. An example of this is cancer
chemotherapy patients or AIDS patients. These individuals have
difficulty maintaining an appetite or may be suffering from
cachexia. Often children do not have appetites for various reasons
and thus sometimes require a special diet to meet dietary needs.
Individuals who are unconscious for long periods of time, for
instance comatose patients will require special feeding solutions
to maintain nutrition. The magnetic dipole stabilized solutions
described herein can be useful adjuvants for helping to maintain
dietary needs in situations such as these.
[0083] As used herein the term "enhancing performance" is intended
to mean any improvement in performance. Performance can be assessed
in any manner. Certain enhancements are readily measured. For
example, in a timed-event, an improved time can assess an enhanced
performance. Certain performance enhancing properties can be judged
subjectively by the athlete or performer or an observer. In these
instances, an enhanced performance means that the performance was
perceived subjectively to be improved, magnified, faster, better
and the like. The compositions described herein are effective for
enhancing performance without the side effects of conventional
stimulating agents such as caffeine or other substances banned from
athletic competition or substances that a mammal cannot tolerate
ingesting because of nausea or other conditions. Performance can be
an athletic performance, a cognitive performance or a general state
of alertness.
[0084] Thus, in one embodiment, the invention is directed to a
method of treating or ameliorating a skin condition, a condition
associated with diabetes, a condition associated with a
cardiovascular dysfunction, a cancer, an infection, or metal
poisoning in a subject in need thereof, or reducing the amount of
metal in a subject in need thereof, or increasing metal excretion
from a subject in need thereof, or enhancing performance of a
subject or providing nutrition support to a subject in need
thereof, comprising administering to the subject by injection a
magnetic dipole stabilized solution composition. In a preferred
aspect of the invention, the magnetic dipole stabilized solution
comprises sodium ascorbate, magnesium chloride 2H.sub.2O,
2-di-methyl amino ethanol HCl, thiamine, riboflavine, nicotinamide,
pyridoxine, calcium pantothenate cyanobalamin, and electroactivated
water. In a preferred aspect, the magnetic dipole stabilized
solution comprises from about 100 mg to about 500 mg sodium
ascorbate, from about 100 mg to about 500 mg magnesium chloride
2H.sub.2O, from about 100 mg to about 500 mg 2 di-methyl amino
ethanol HCl, from about 1 mg to about 100 mg thiamine, from about 1
mg to about 100 mg riboflavine, from about 1 mg to about 300 mg
nicotinamide, from about 1 mg to about 100 mg pyridoxine, from
about 1 mg to about 100 mg calcium pantothenate, from about 100
.mu.g to about 500 .mu.g cyanobalamin, and electroactivated water.
In another preferred aspect of the invention, the magnetic dipole
stabilized solution further comprises folic acid and/or an
antibiotic. In one aspect of the invention, the treatment or
amelioration of a skin condition comprises contacting the skin area
to be treated or ameliorated with the solution. In a different
aspect of the invention, the magnetic dipole stabilized solution
used for the treatment or prevention of cancer further comprises
vitamin K2.
[0085] In another embodiment, the invention is directed to a method
of treating or ameliorating a skin condition that is an infection,
comprising administering to a subject by injection a magnetic
dipole stabilized solution, wherein the infection is treated or
ameliorated. In this regard the method can be said to be an
anti-infective treatment. In a preferred embodiment, the magnetic
dipole stabilized solution comprises electroactivated water. The
magnetic dipole stabilized solution for injection preferably has a
negative or neutral electric potential.
[0086] In another embodiment, the present disclosure is directed to
a method of treating or ameliorating a skin condition, a condition
associated with diabetes, a condition associated with a
cardiovascular dysfunction, a cancer, an infection, or metal
poisoning in a subject in need thereof, or reducing the amount of
metal in a subject in need thereof, or increasing metal excretion
from a subject in need thereof, or enhancing performance of a
subject or providing nutrition support to a subject in need
thereof, comprising administering to a subject in need thereof by
injection a magnetic dipole stabilized solution composition
comprising, sodium ascorbate, magnesium chloride 2H.sub.2O, 2
di-methyl amino ethanol HCl, thiamine, riboflavine, nicotinamide,
pyridoxine, calcium pantothenate, cyanobalamin, lipoic acid and
electroactivated water. The solution may further include folic acid
and/or an antibiotic.
[0087] In another embodiment, the present invention is directed to
a method of treating or ameliorating a skin condition, a condition
associated with diabetes, a condition associated with a
cardiovascular dysfunction, a cancer, an infection, or metal
poisoning in a subject in need thereof, or reducing the amount of
metal in a subject in need thereof, or increasing metal excretion
from a subject in need thereof, or enhancing performance of a
subject or providing nutrition support to a subject in need
thereof, comprising administering to a subject in need thereof by
injection a magnetic dipole stabilized solution composition
comprising, sodium ascorbate, magnesium chloride 2H.sub.2O, 2
di-methyl amino ethanol HCl, thiamine, riboflavine, nicotinamide,
pyridoxine, calcium pantothenate, cyanobalamin, lipoic acid, folic
acid and electroactivated water. The solution may further include
an antibiotic.
[0088] In another embodiment, the present invention is directed to
a method of treating or ameliorating a skin condition, a condition
associated with diabetes, a condition associated with a
cardiovascular dysfunction, a cancer, an infection, or metal
poisoning in a subject in need thereof, or reducing the amount of
metal in a subject in need thereof, or increasing metal excretion
from a subject in need thereof, or enhancing performance of a
subject or providing nutrition support to a subject in need
thereof, comprising administering to a subject in need thereof by
injection a magnetic dipole stabilized solution composition
comprising, sodium ascorbate, magnesium chloride 2H.sub.2O, 2
di-methyl amino ethanol HCl, thiamine, riboflavine, nicotinamide,
pyridoxine, calcium pantothenate, cyanobalamin, lipoic acid, folic
acid, one or more antibiotics and electroactivated water.
[0089] In another embodiment, the present subject matter is
directed to a composition for treating or ameliorating diseases
comprising sodium ascorbate, magnesium chloride 2H.sub.2O, 2
di-methyl amino ethanol HCl, thiamine, riboflavine, nicotinamide,
pyridoxine, calcium pantothenate, cyanobalamin and electroactivated
water. The composition may further include lipoic acid, folic acid
and/or one or more antibiotics.
[0090] Preferably, sodium ascorbate is present in an amount
equivalent to ascorbic acid from about 0.01 g to about 10 g per
dose (preferably in a 10 ml dose). Preferably, the amount is from
about 0.1 g to about 1.0 g per dose. More preferably, the amount is
from about 0.24 g to about 0.9 g per dose.
[0091] Preferably, magnesium chloride is present in an amount from
about 0.01 g to about 10 g per dose (preferably in a 10 ml dose).
Preferably, the amount is from about 0.1 g to about 1.0 g per dose.
More preferably, the amount is from about 0.5 g to about 0.8 g per
dose.
[0092] Preferably, dimethyl amino ethanol HCl, is present in an
amount from about 0.01 g to about 10 g per dose (preferably in a 10
ml dose). More preferably, the amount is from about 0.1 g to about
1.0 g per dose. Even more preferably, the amount is from about 0.2
g to about 0.87 g per dose.
[0093] Preferably, thiamine is present in an amount from about 0.01
g to about 10 g per dose (preferably in a 10 ml dose). More
preferably, the amount is from about 0.1 g to about 1.0 g per dose.
Even more preferably, the amount is from about 0.12 g to about 0.15
g per dose.
[0094] Preferably, riboflavin is present in an amount from about
0.001 g to about 1.0 g per dose (preferably in a 10 ml dose). More
preferably, the amount is from about 0.01 g to about 1.0 g per
dose. Even more preferably, the amount is from about 0.01 g to
about 0.02 g per dose.
[0095] Preferably, nicotinamide is present in an amount from about
0.01 g to about 10 g per dose (preferably in a 10 ml dose). More
preferably, the amount is from about 0.1 g to about 1.0 g per dose.
Even more preferably, the amount is from about 0.10 g to about 0.15
g per dose.
[0096] Preferably, pyridoxine is present in an amount from about
0.01 g to about 10 g per dose (preferably in a 10 ml dose). More
preferably, the amount is from about 0.1 g to about 1.0 g per dose.
Even more preferably, the amount is from about 0.55 g to about 0.65
g per dose.
[0097] Preferably, calcium pantothenate is present in an amount
from about 0.001 g to about 1.0 g per dose (preferably in a 10 ml
dose). More preferably, the amount is from about 0.01 g to about
1.0 g per dose. Even more preferably, the amount is from about 0.03
g to about 0.04 g per dose.
[0098] Preferably, cyanobalamin is present in an amount from about
0.1 g to about 10 g per dose (preferably in a 10 ml dose). More
preferably, the amount is from about 1 g to about 5 g per dose.
Even more preferably, the amount is from about 1.8 g to about 2.25
g per dose.
[0099] Preferably, vitamin K2 is present in an amount from about
0.01 mg to 125 mg per dose (preferably in a 10 ml dose), including
about 1 mg, about 5 mg, about 20 mg, about 50 mg, about 75 mg and
about 100 mg per dose.
[0100] When lipoic acid, its salts or mixtures thereof are present,
the amount of lipoic acid is preferably from about 10 mg to about
500 mg. Also preferred is an amount from about 100 mg to about 400
mg. More preferably, the amount is from about 250 mg to about 350
mg. Most preferably, the amount is about 250 mg. Solubility
modifiers including, but not limited to, emulsifying agents such as
phosphatidylcholine, can be used if needed to formulate the lipoic
acid in a desired amount.
[0101] When folic acid, its salts or mixtures thereof is present,
the amount of folic acid is preferably from about 0.001 g to about
10 g per dose (preferably in a 10 ml dose), including about 0.01 g,
about 0.1 g, about 1 g and about 5 g per dose. Preferably, the
amount is from about 0.1 g to about 1.0 g per dose. More
preferably, the amount is from about 0.2 g to about 0.5 g per dose.
Solubility modifiers can be used if needed to formulate the lipoic
acid in a desired amount.
[0102] One or more of an antibiotic, antiviral, antimicrobial or
antiseptic agent can be combined with MDSS to form a solution or
the agent(s) can be combined with a MDSS to form a composition. The
agents contemplated are those that are known in the art including,
but not limited to, amoxicillin, levofloxacin, gatifloxacin,
streptomycin, tetracycline, chloramphenicol, fluconazole,
itraconazole and posaconazole. Effective amounts of these agents
are also known. In particular, the MDSS compositions and solutions
comprise erythromycin in about 500 mg per MDSS dose and/or about 30
mg of gentamicin per MDSS dose.
[0103] In a different embodiment, the present invention is directed
to a method of reducing the amount of a metal(s) in a subject in
need thereof, increasing the excretion of a metal(s) or treating or
ameliorating metal poisoning. In one aspect, the metal is a heavy
metal. In another aspect, the metal is selected from the group
consisting of calcium, lead, uranium, plutonium, arsenic,
molybdenum and mercury. In another aspect, the metal has an
oxidation state of +1, +2 or +3. In another aspect, the metal is a
transition or post-transition state metal. In another aspect, the
metal is a divalent cation. Preferably, the metal is selected from
the group consisting of Fe.sup.+3, HG.sup.+2, Cu.sup.+2, Ar.sup.+3,
Pb.sub.+2, Co.sub.+2, Cd.sub.+2 and Mn.sub.+2. In one aspect, the
metal poisoning is acute. In a different aspect, the metal
poisoning is chronic. In a preferred embodiment, the MDSS solution
for chelation comprises glycine. Glycine can complex with divalent
cations and enhance the metal sequestering and/or reducing
effect.
[0104] In another embodiment, the present invention is directed to
a method of increasing the excretion of one or more toxins from a
mammal, comprising administering to a subject by injection an
effective amount of magnetic dipole stabilized solution, wherein
said excretion of one or more toxins is increased. In this
embodiment, the toxins are more soluble in the electroactivated
water and are eliminated from the body by excretion.
[0105] In yet another embodiment, the present invention is directed
to a method of providing nutrition support to a subject in need
thereof, comprising administering to the subject an effective
amount of magnetic dipole stabilized solution. The subject
receiving nutritional support according to the invention may be a
healthy subject, or a subject suffering from a malady selected from
the group consisting of malnutrition, cachexia, diabetes, severe
food allergies, short gut syndrome, cystic fibrosis, pancreatic
disease, gastroenteritis, inflammatory bowel disease, intractable
diarrhea, protein maldigestion, necrotizing enterocolitis,
infectious diseases, hypermetabolism, trauma, eosinophilic
gastroenteritis or gastroesophogeal reflux.
[0106] In another embodiment, the present invention is directed to
a method wherein the magnetic dipole stabilized solution comprises
one or more trace metals selected from the group consisting of Zn,
Se, Cu, Mn and Fe. In a preferred embodiment, the magnetic dipole
stabilized solution is an electroactivated water comprising from
about 100 mg to about 500 mg sodium ascorbate, from about 100 mg to
about 500 mg magnesium chloride 2H.sub.2O, from about 100 mg to
about 500 mg 2 di-methyl amino ethanol HCl, from about 1 mg to
about 100 mg thiamine, from about 1 mg to about 100 mg riboflavine,
from about 1 mg to about 300 mg nicotinamide, from about 1 mg to
about 100 mg pyridoxine, from about 1 mg to about 100 mg calcium
pantothenate, from about 100 .mu.g to about 500 .mu.g cyanobalamin,
from about 1 mg to about 20 mg Zn, from about 1 mg to about 100 mg
Se, from about 1 mg to about 1000 mg Cu, Mn from about 0.01 mg to
about 10 mg, from about 1 mg to about 20 mg Fe and electroactivated
water. In a more preferred embodiment, the magnetic dipole
stabilized solution comprises about 395 mg sodium ascorbate, about
255 tug magnesium chloride 2H.sub.2O, about 200 mg 2-di-methyl
amino ethanol HCl, about 36 mg thiamine, about 7.3 mg riboflavine,
about 100 mg nicotinamide, about 18.2 mg pyridoxine, about 18.2 mg
calcium pantothenate, about 320 .mu.g cyanobalamin, about 10 mg Zn,
about 45 mg Se, about 400 mg Cu, about 0.3 mg Mn, about 8 mg Fe,
and electroactivated water.
[0107] In one aspect of the invention, the subject receiving
nutritional support has special dietary needs. The method comprises
administering to a subject in need thereof by injection an
effective amount of magnetic dipole stabilized solution as
described herein. Preferably, the special dietary needs are
associated with athletes, children, obese subjects, subjects
undergoing chemotherapy for cancer, malnourished subjects or
subjects in a comatose state. In a preferred embodiment, the method
of the invention is for aiding in weight loss. Weight gain is
caused by consuming more calories than the body requires for its
basal metabolic functions and additional activities in which an
individual is involved. The human body stores these excess calories
as fatty deposits (lipids in adipose tissue) throughout the body,
but is not able to readily access these fatty deposits to satisfy
energy needs. To use these stored lipids as an energy source, the
number of calories ingested must be less than the total energy
expenditure of the body (basal metabolic rate plus activity level).
Under hypocaloric conditions the body consumes fat as a source of
fuel, but the switch to energy utilization of stored fat is not
instantaneous. The body has feedback mechanisms that attempt to
preserve existing lipid stores. Therefore, in the interim between
the initial reduction in caloric intake and the conversion of
lipids to energy, the body consumes lean body mass as a source of
energy. Hepatic gluconeogenesis utilizes amino acids from muscle to
generate glucose which the body uses as its preferred energy
source. Hence, the body will consume some muscle tissue as its
energy source during this period of conversion. Reduced caloric
intake usually induces cravings for food that reduce adherence to
weight loss regimens. These cravings are caused by both
psychological and physiological mechanisms. For example, ingested
carbohydrates are absorbed from the digestive tract into the
bloodstream to increase blood glucose levels. In response to the
increase in blood glucose, the pancreas releases insulin to aid in
the transport of glucose into the cells of the body where glucose
is employed as an energy source. However, if the amount of insulin
released is greater than the amount of glucose present (which is
often the case in overweight individuals), then the body reacts by
signaling the brain to ingest more carbohydrates in order to
balance the amount of insulin in the bloodstream. This
insulin-induced craving for carbohydrates is very common during
periods of caloric restriction. The MDSS solutions described herein
can treat or ameliorate the symptoms associated with a reduced
caloric intake.
[0108] In yet another embodiment, the present invention is directed
to a method of treating or ameliorating symptoms related to
menopause. Menopause is a period after the cessation of normal
ovulation cycles, during which normal menstruation ceases. A
decrease in estradiol (E.sub.2) production accompanies menopause,
as the ovaries cease manufacture of E.sub.2. This decrease in
E.sub.2 production results in a shift in hormone balance in the
body, which often gives rise to a variety of symptoms associated
with menopause. Peri-menopause, which is also known as
pre-menopause or the climacteric, is a period prior to menopause
during which normal ovulation cycles gradually give way to
cessation of menses. As the ovulatory cycles lengthen and become
more irregular, the level of E.sub.2 may initially increase, but
will eventually drop with the onset of menopause. Menopausal
symptoms often accompany the drop in E.sub.2 levels. The symptoms
of peri-menopause, menopause and post-menopause include physical
symptoms such as hot flashes and sweating secondary to vasomotor
instability. Additionally, psychological and emotional symptoms may
accompany onset of climacteric, such as fatigue, irritability,
insomnia, inability to concentrate, depression, memory loss,
headache, anxiety and nervousness. Additional symptoms can include
intermittent dizziness, paresthesias, palpitations and tachycardia
as well as nausea, constipation, diarrhea, arthralgia, myalgia,
cold hands and feet and weight gain. In addition, changes to the
genitals, urinary incontinence, vaginal dryness, loss of pelvic
muscle tone, increased risk of cardiovascular disease and
osteoporosis increase with onset of menopause. Hot flashes are
prevalent in, and bothersome to, many peri-menopausal, menopausal
and postmenopausal women. For decades hormone replacement therapy
with estrogens has been the standard treatment for hot flashes, but
many women have abandoned hormone therapy (HT) due to concerns
about potential adverse effects, particularly breast cancer. The
MDSS compositions described herein are useful in treating or
ameliorating one or more of the symptoms described above. In an
embodiment, the method comprises administering to a female subject
in need thereof by injection an effective amount of magnetic dipole
stabilized solution as described herein.
[0109] In another embodiment, the present invention is directed to
a kit comprising a first vial containing a solution comprising one
or more selected from the group consisting of heparin, vitamins,
salts, acids, lipoic acid, folic acid, antibiotic(s) and vitamers,
and mixtures thereof; a second vial containing a magnetic dipole
stabilized solution; and optionally instructions for use.
Preferably, the first vial contains one or more selected from the
group consisting of vitamins, salts, acids and vitamers and
mixtures thereof. Preferably in one aspect of this embodiment, the
magnetic dipole stabilized solution contained in the kit is
electroactivated water. In another aspect, the first vial
preferably comprises lipoic acid and the amount of lipoic acid is
preferably from about 10 mg to about 500 mg. Preferably, the amount
of lipoic acid is from about 100 mg to about 400 mg. More
preferably, the amount of lipoic acid is from about 250 mg to about
350 mg. Most preferably, the amount of lipoic acid is about 250 mg.
Solubility modifiers can be used if needed to formulate the
ingredients, including the lipoic acid, in a desired amount.
[0110] In a preferred embodiment, the kit contains a first vial
comprising sodium ascorbate, magnesium chloride 2H.sub.2O, 2
di-methyl amino ethanol HCl, thiamine, riboflavine, nicotinamide,
pyridoxine, calcium pantothenate and cyanobalamin. Optionally, the
first vial can contain folic acid, lipoic acid and/or an
antibiotic, such as erythromycin or gentamicin.
[0111] In another embodiment, the present subject matter is
directed to a kit comprising, a first vial containing a solution
comprising, from about 100 mg to about 500 mg sodium ascorbate,
from about 100 mg to about 500 mg magnesium chloride 2H.sub.2O,
from about 100 mg to about 500 mg 2 di-methyl amino ethanol HCl,
from about 1 mg to about 100 mg thiamine, from about 1 mg to about
100 mg riboflavine, from about 1 mg to about 300 mg nicotinamide,
from about 1 mg to about 100 mg pyridoxine, from about 1 mg to
about 100 mg calcium pantothenate, from about 100 .mu.g to about
500 .mu.g cyanobalamin, from about 1 mg to about 20 mg Zn, from
about 1 mg to about 100 mg Se, from about 1 mg to about 1000 mg Cu,
from about 0.01 mg to about 10 mg Mn and from about 1 mg to about
20 mg Fe, and a second vial containing a magnetic dipole stabilized
solution; and optionally instructions for use. In a preferred
embodiment, the magnetic dipole stabilized solution is
electroactivated water. Preferably, the magnetic dipole stabilized
solution comprises electroactivated water.
[0112] Electroactivated water can be prepared using methods,
apparatus, and systems disclosed in, for example, Van Kalken et
al., International Patent Application No. PCT/US2011/020691, Davis
et al. U.S. Pat. No. 7,374,645, and/or Daly et al. U.S. Pat. No.
7,691,249, which are incorporated herein by reference. The ORP of
the electroactivated water is that of the neutral anolyte, which
has a positive ORP, preferably above +100 mV. Also preferred are
values of above +200 mV, above +300 mV, +400 mV, above +500 mV,
+600 mV, above +700 mV, +800 mV, above +900 mV and +1000 mV. The
magnetic dipole stabilized solution for injection however
preferably has a negative or neutral electric potential once
additional components, e.g., vitamins are combined to the contents
of vials in a kit are combined. In a preferred embodiment of this
aspect, the negative potential is below about -990 mV. In a
preferred embodiment, the potential is from about -990 mV to about
-0.0001 mV. More preferably, the potential is from about -150 mV to
about -5 mV. Also more preferred is a potential from about -120 mV
to about -20 mV. Most preferably, the potential is about -70
mV.
[0113] In one embodiment, the MDSS composition comprises
2-(diethylamino)-N-(2,6-dimethylphenyl) acetamide or derivatives
thereof. Not to be bound by theory, the MDSS can hydrolyze the
active ingredient in situ thereby enhancing its effect on channel
blocking, cyclooxigenase activity and enzyme induction. More
particularly, when 2-(diethylamino)-N-(2,6-dimethylphenyl)
acetamide is present in the MDSS solution, it can be hydrolysed in
situ to form the analogues of formula (I):
##STR00001##
wherein, R.sub.1 is an alkyl, carboxamide or aminocarbamyl moiety;
and R.sub.2 is a methyl, ethyl, methoxy or carbonyl moiety. The
pharmaceutical composition may include between 2.5% and 3.5% of the
active ingredient and may have a pH of about 2.5 to about 3.5.
[0114] In an embodiment, a method is provided for activating a
pharmaceutical composition in situ, the pharmaceutical composition
including an active ingredient selected from the group consisting
of 2-(diethylamino)-N-(2,6-dimethylphenyl) acetamide and its
analogues, pharmaceutically acceptable salts, metabolites and
esters thereof; and a carrier in the form of a magnetic dipole
stabilized solution having anti-microbial properties; wherein a
source of carbon dioxide is provided in the pharmaceutical
composition prior to administration thereof. The source of carbon
dioxide may be sodium bicarbonate. It is envisaged that the
introduction of a source of carbon dioxide shall enhance the
activity of the ionized portion of the active ingredient so as to
thereby increase the efficacy of the pharmaceutical
composition.
[0115] The magnetic dipole stabilized solution can further comprise
other components. Specifically, the magnetic dipole stabilized
solution, which preferably comprises electroactivated water,
further comprises one or more independently selected from the group
consisting of vitamins, salts, acids, amino acids or salts thereof,
vitamers, di-methyl amino ethanol, anesthetic(s), stabilized
oxidative species, heparin and lipoic acid, and mixtures thereof.
Thus, in some embodiments, the pharmaceutical composition may
further include nutrients suitable as cofactors for enzymes,
vitamins suitable for rapid cellular energy production, pH
modifiers and buffer components. The nutrients may be selected from
the group consisting of amino acids, carbohydrates and lipids, and
a combination thereof. In some embodiments, the combination of
nutrients with MDSS can result in a synergistically enhanced effect
of the active ingredient. More particularly, the nutrients are
electro activated by the MDSS and improved delivery across the cell
membrane thereof.
[0116] Carbohydrates, such as simple or complex sugars or cyclic
oligosaccharides, can be a component of a MDSS composition.
Preferably, the carbohydrate is fructose or a cyclodextrin, such a
betacyclodextrin or hydroxypropyl cyclodextrin. When present, the
cyclodextrin is in an amount of from about 0.001 to about 10 mg.
Preferably, the amount is from about 0.05 to about 1.0 mg. Most
preferably, the amount is from about 0.01 to about 0.5 mg.
[0117] Other compounds and molecules that can be a component of a
MDSS solution are molecules, which also referred to as minerals.
Those that are needed by the body in relatively large amounts are
sodium, potassium, chlorine, calcium, phosphorus and magnesium.
Those that are needed in smaller amounts are "trace" minerals and
include selenium, iron, zinc, manganese, molybdenum, chromium,
fluoride, iodine, copper and the like.
[0118] Another component of a MDSS composition can be one or more
amino acids or salts or esters thereof. Preferably, the amino
acid(s) is selected from the group consisting of glycine, alanine,
arginine, glutamic acid and tyrosine and salts or esters
thereof.
[0119] A preferred component is lipoic acid. Lipoic acid can be a
racemic mixture or can be separated into its R and S enantiomers.
The R enantiomer form of lipoic acid is preferred because it is the
natural form. It has the structure:
##STR00002##
[0120] Buffer components selected from the group consisting of
phosphoric acid and its salts or acetic acid and its salts, and pH
modifiers selected from the group consisting of succinic acid,
sulphuric acid, hydrochloric acid, sodium hydroxide, sodium
bicarbonate and ethanolamine compounds, may also be included in the
composition.
[0121] Oxidative species which can be in the composition are
selected from the group consisting of H.sub.2O, O.sub.2,
H.sub.2O.sub.2, Cl.sub.2O, H.sub.3O, O.sub.3 and ClO3.
[0122] An effective amount is the amount required to provide the
subject with an improvement in a symptom or underlying condition.
Many conditions can have subjective markers to gauge improvement,
such as in the case of alopecia and acne. Therefore an effective
amount is an amount that provides an improvement as gauged by the
subject or by the provider. Some conditions have clinical markers.
In these cases, an effective amount is an amount that provides an
improvement by way of markers determined by clinical assessment.
This, of course, is only one way of gauging an improvement in the
symptom or condition to be treated. Finally, some conditions can
have improvement based on subjective and/or clinical markers. The
MDSS compositions will generally be used in an amount effective to
achieve the intended result, for example in an amount effective to
treat, prevent the particular condition in the first place or
ameliorate the symptoms. MDSS compositions can be administered
therapeutically to achieve therapeutic benefit or prophylactically
to achieve prophylactic benefit. By therapeutic benefit is meant
eradication or amelioration of the underlying disorder being
treated and/or eradication or amelioration of one or more of the
symptoms associated with the underlying disorder such that the
patient reports an improvement in feeling or condition,
notwithstanding that the patient can still be afflicted with the
underlying disorder. For example, administration of a MDSS
composition to a patient suffering from a skin condition provides
therapeutic benefit not only when the underlying skin condition is
eradicated or ameliorated, but also when the patient reports a
decrease in the severity or duration of the symptoms associated
with the skin condition. Therapeutic benefit also includes halting
or slowing the progression of the disease, regardless of whether
improvement is realized.
[0123] A therapeutically effective amount of the compositions of
the present invention will generally mean administration of from
about 0.001 ml/kg to about 1.0 ml/kg (weight of active
solution/body weight of mammal). Preferably the amount is from
about 0.01 ml/kg to about 1.0 ml/kg. However, an effective amount
may vary from mammal to mammal and can easily be adjusted by one of
ordinary skill by varying the volume and frequency of
administrations. The amount of composition administered will depend
upon a variety of factors, including, for example, the particular
indication being treated, the mode of administration, whether the
desired benefit is prophylactic or therapeutic, the severity of the
indication being treated and the age and weight of the patient, the
bioavailability of the particular composition, and the like.
Determination of an effective dosage is well within the
capabilities of those skilled in the art coupled with the general
and specific examples disclosed herein. When used prophylactically,
the same principles and guidelines of dosing apply. The
administration can occur in one infusion, but more preferably is
delivered over one to five infusions per week, lasting for several
weeks or months.
[0124] Practice of the method of the present invention comprises
administering to a subject a therapeutically effective amount of a
MDSS composition in any suitable systemic or local formulation, in
an amount effective to deliver a dosage. In practicing the method
of treatment or use of the present methods, a therapeutically
effective amount of a MDSS composition is administered to a mammal
either alone or in combination with other therapies. A preferred
combination in all embodiments includes a method of administering a
magnetic dipole stabilized solution combined with a separate
vitamin regimen. As used herein, the term "regimen" means a
deliberate administration or consumption of one or more vitamin(s)
either as a single dose or as daily or weekly dosages. In these
embodiments, the vitamins can be administered or consumed in any
fashion to provide a mammal with the desired amount of vitamin(s).
In these embodiments, the MDSS composition itself may or may not
include vitamins. In other words, it is contemplated that the
methods include administration of an MDSS composition in
combination with vitamins, wherein the vitamins are administered or
consumed in a separate composition either contemporaneous with the
administration of an MDSS composition or at a different time. The
period of time between the MDSS administration and the vitamin(s)
administration or consumption can be a day, a week or more. The
MDSS therapies described herein are preferably provided in
administrations over weeks. Thus, any vitamin regimen within that
time is contemplated in the methods described herein. More
preferred time periods are MDSS administration within about one
week of vitamin(s) administration or consumption. More preferably,
an MDSS administration is within about one day of the vitamin(s)
administration or consumption. Preferably, the vitamin regimen
comprises a vitamin supplement or multivitamin consumed orally as a
one-time dose or daily or weekly doses. Particularly preferred are
vitamin regimens that provide a multivitamin or a composition
comprising one or more of the vitamins disclosed herein in the
disclosed amounts. More specifically, the vitamins are selected
from families of vitamins selected from the group consisting of A
(2000 to 25000 IU/dose), B1 (10 to 100 mg/dose), B2 (1 to 400
mg/dose), B3 (10 to 200 mg/dose), B5 (25 to 100 mg/dose), B6 (1 to
200 mg/dose), B12 (0.4 to 1500 .mu.g/dose), C (10 to 2000 mg/dose),
D (200 to 800 IU/dose), E (6 to 800 IU/dose) and K (70 to 500
.mu.g/dose) and vitamers thereof. Also contemplated are combination
therapies that include other supplements such as an antioxidant,
beta-carotene, chromium picolinate, co-enzyme Q-10, conjugated
linoleic acid, fish oil, iodine, L-arginine, Lecithin, L-lysine,
Lutein, trace metals, soy isoflavones, glucosamine, chondroitin,
melatonin, St. John's wort, pantothenic acid and
S-adenosylmethionine. Again, just as described above for
vitamin(s), these supplements are administered in combination with
MDSS but not necessarily at the same time or in the same
composition.
[0125] Routes of administration for a therapeutically effective
amount of an MDSS composition include, but are not limited to,
intravenous or parenteral administration, oral administration,
topical administration, transmucosal administration and transdermal
administration. For intravenous or parenteral administration, i.e.,
injection or infusion, the MDSS composition may also contain
suitable pharmaceutical diluents and carriers, such as water,
saline, dextrose solutions, fructose solutions, ethanol, or oils of
animal, vegetative, or synthetic origin. It may also contain
preservatives, and buffers as are known in the art. When a
therapeutically effective amount is administered by intravenous,
cutaneous or subcutaneous injection, the solution can also contain
components to adjust pH, isotonicity, stability, and the like, all
of which is within the skill in the art. A MDSS composition for
intravenous, cutaneous, or subcutaneous injection should contain,
in addition to peptide an isotonic vehicle such as Sodium Chloride
Injection, Ringer's Injection, Dextrose Injection, Dextrose and
Sodium Chloride Injection, Lactated Ringer's Injection Citrate
Buffer pH 5.5, or other carriers, diluents and additives as known
in the art. As described fully elsewhere herein, the pharmaceutical
composition of the present invention may also contain stabilizers,
preservatives, buffers, antioxidants, or other additive known to
those of skill in the art. The pharmaceutical compositions are
formulated for intravenous or parenteral administration. Typically,
compositions for intravenous or parenteral administration comprise
a suitable sterile solvent, which may be an isotonic aqueous buffer
or pharmaceutically acceptable organic solvent. As described fully
elsewhere herein, where necessary, the compositions can also
include a solubilizing agent. Compositions for intravenous or
parenteral administration can optionally include a local anesthetic
to lessen pain at the site of the injection. Generally, the
ingredients are supplied either separately or mixed together in
unit dosage form in a hermetically sealed container such as an
ampoule or sachette. The pharmaceutical compositions for
administration by injection or infusion can be dispensed, for
example, with an infusion bottle containing, for example, sterile
pharmaceutical grade water or saline. Where the pharmaceutical
compositions are administered by injection, an ampoule of sterile
water for injection, saline, or other solvent such as a
pharmaceutically acceptable organic solvent can be provided so that
the ingredients can be mixed prior to administration.
[0126] The duration of intravenous therapy using the pharmaceutical
composition of the present invention will vary, depending on the
condition being treated or ameliorated and the condition and
potential idiosyncratic response of each individual mammal. The
duration of each infusion is from about 1 minute to about 1 hour.
The infusion can be repeated within 24 hours. Thus, a mammal can
receive about 1 to about 5 infusions per day. Preferably, the
number of infusions per day is 1 or 2. The period between each
infusion can be 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 hours or
more. Alternatively, the infusions can be given one after another
without a substantial period in between. In one embodiment, the
infusion lasts about 45 minutes. The dose may be repeated 2-3 times
a week depending on the severity of the relative or absolute
deficits of nutrients in the patient. A clinical assessment may be
necessary in order to establish the status, but can be limited to a
review of medical history, subjective review of symptoms, the
subjective opinion of the mammal when human or review of any
specific deficits.
[0127] Systemic formulations include those designed for
administration by injection, e.g., subcutaneous, intravenous,
intramuscular, intrathecal or intraperitoneal injection. Useful
injectable preparations include sterile suspensions, solutions or
emulsions of the active compound(s) in aqueous or oily vehicles.
The compositions also can contain solubilizing agents, formulating
agents, such as suspending, stabilizing and/or dispersing agent.
The formulations for injection can be presented in unit dosage
form, e.g., in ampules or in multi-dose containers, and can contain
added preservatives. For prophylactic administration, the compound
can be administered to a patient at risk of developing one of the
previously described conditions or diseases. Alternatively,
prophylactic administration can be applied to avoid the onset of
symptoms in a patient suffering from or formally diagnosed with the
underlying condition.
[0128] The amount of compound administered will depend upon a
variety of factors, including, for example, the particular
indication being treated, the mode of administration, whether the
desired benefit is prophylactic or therapeutic, the severity of the
indication being treated and the age and weight of the patient, the
bioavailability of the particular active compound, and the like.
Determination of an effective dosage is well within the
capabilities of those skilled in the art coupled with the general
and specific examples disclosed herein.
[0129] Oral administration of an MDSS composition can be
accomplished using dosage forms including, but not limited to,
capsules, caplets, solutions, suspensions and/or syrups. Such
dosage forms are prepared using conventional methods known to those
in the field of pharmaceutical formulation and described in the
pertinent texts, e.g., in Remington: The Science and Practice of
Pharmacy (2000), supra.
[0130] The dosage form may be a capsule, in which case the active
agent-containing composition may be encapsulated in the form of a
liquid. Suitable capsules may be either hard or soft, and are
generally made of gelatin, starch, or a cellulosic material, with
gelatin capsules preferred. Two-piece hard gelatin capsules are
preferably sealed, such as with gelatin bands or the like. See, for
e.g., Remington: The Science and Practice of Pharmacy (2000),
supra, which describes materials and methods for preparing
encapsulated pharmaceuticals.
[0131] Capsules may, if desired, be coated so as to provide for
delayed release. Dosage forms with delayed release coatings may be
manufactured using standard coating procedures and equipment. Such
procedures are known to those skilled in the art and described in
the pertinent texts (see, for e.g., Remington: The Science and
Practice of Pharmacy (2000), supra). Generally, after preparation
of the capsule, a delayed release coating composition is applied
using a coating pan, an airless spray technique, fluidized bed
coating equipment, or the like. Delayed release coating
compositions comprise a polymeric material, e.g., cellulose
butyrate phthalate, cellulose hydrogen phthalate, cellulose
proprionate phthalate, polyvinyl acetate phthalate, cellulose
acetate phthalate, cellulose acetate trimellitate, hydroxypropyl
methylcellulose phthalate, hydroxypropyl methylcellulose acetate,
dioxypropyl methylcellulose succinate, carboxymethyl
ethylcellulose, hydroxypropyl methylcellulose acetate succinate,
polymers and copolymers formed from acrylic acid, methacrylic acid,
and/or esters thereof.
[0132] Sustained-release dosage forms provide for drug release over
an extended time period, and may or may not be delayed release.
Generally, as will be appreciated by those of ordinary skill in the
art, sustained-release dosage forms are formulated by dispersing a
drug within a matrix of a gradually bioerodible (hydrolyzable)
material such as an insoluble plastic, a hydrophilic polymer, or a
fatty compound. Insoluble plastic matrices may be comprised of, for
example, polyvinyl chloride or polyethylene. Hydrophilic polymers
useful for providing a sustained release coating or matrix
cellulosic polymers include, without limitation: cellulosic
polymers such as hydroxypropyl cellulose, hydroxyethyl cellulose,
hydroxypropyl methyl cellulose, methyl cellulose, ethyl cellulose,
cellulose acetate, cellulose acetate phthalate, cellulose acetate
trimellitate, hydroxypropylmethyl cellulose phthalate,
hydroxypropylcellulose phthalate, cellulose hexahydrophthalate,
cellulose acetate hexahydrophthalate, and carboxymethylcellulose
sodium; acrylic acid polymers and copolymers, preferably formed
from acrylic acid, methacrylic acid, acrylic acid alkyl esters,
methacrylic acid alkyl esters, and the like, e.g. copolymers of
acrylic acid, methacrylic acid, methyl acrylate, ethyl acrylate,
methyl methacrylate and/or ethyl methacrylate, with a terpolymer of
ethyl acrylate, methyl methacrylate and trimethylammonioethyl
methacrylate chloride (sold under the tradename Eudragit RS)
preferred; vinyl polymers and copolymers such as polyvinyl
pyrrolidone, polyvinyl acetate, polyvinylacetate phthalate,
vinylacetate crotonic acid copolymer, and ethylene-vinyl acetate
copolymers; zein; and shellac, ammoniated shellac, shellac-acetyl
alcohol, and shellac n-butyl stearate. Fatty compounds for use as a
sustained release matrix material include, but are not limited to,
waxes generally (e.g., carnauba wax) and glyceryl tristearate.
[0133] Topical administration of an MDSS composition can be
accomplished using any formulation suitable for application to the
body surface, and may comprise, for example, an ointment, cream,
gel, lotion, solution, paste or the like, and/or may be prepared so
as to contain liposomes, micelles, and/or microspheres. Preferred
topical formulations herein are ointments, creams, and gels.
[0134] Ointments, as is well known in the art of pharmaceutical
formulation, are semisolid preparations that are typically based on
petrolatum or other petroleum derivatives. The specific ointment
base to be used, as will be appreciated by those skilled in the
art, is one that will provide for optimum drug delivery, and,
preferably, will provide for other desired characteristics as well,
e.g., emolliency or the like. As with other carriers or vehicles,
an ointment base should be inert, stable, nonirritating and
nonsensitizing. As explained in Remington: The Science and Practice
of Pharmacy (2000), supra, ointment bases may be grouped in four
classes: oleaginous bases; emulsifiable bases; emulsion bases; and
water-soluble bases. Oleaginous ointment bases include, for
example, vegetable oils, fats obtained from animals, and semisolid
hydrocarbons obtained from petroleum. Emulsifiable ointment bases,
also known as absorbent ointment bases, contain little or no water
and include, for example, hydroxystearin sulfate, anhydrous lanolin
and hydrophilic petrolatum. Emulsion ointment bases are either
water-in-oil (MO) emulsions or oil-in-water (O/W) emulsions, and
include, for example, cetyl alcohol, glyceryl monostearate, lanolin
and stearic acid. Preferred water-soluble ointment bases are
prepared from polyethylene glycols of varying molecular weight
(See, e.g., Remington: The Science and Practice of Pharmacy (2002),
supra).
[0135] Creams, as also well known in the art, are viscous liquids
or semisolid emulsions, either oil-in-water or water-in-oil. Cream
bases are water-washable, and contain an oil phase, an emulsifier
and an aqueous phase. The oil phase, also called the "internal"
phase, is generally comprised of petrolatum and a fatty alcohol
such as cetyl or stearyl alcohol. The aqueous phase usually,
although not necessarily, exceeds the oil phase in volume, and
generally contains a humectant. The emulsifier in a cream
formulation is generally a nonionic, anionic, cationic or
amphoteric surfactant.
[0136] As will be appreciated by those working in the field of
pharmaceutical formulation, gels-are semisolid, suspension-type
systems. Single-phase gels contain organic macromolecules
distributed substantially uniformly throughout the carrier liquid,
which is typically aqueous, but also, preferably, contain an
alcohol and, optionally, an oil. Preferred "organic
macromolecules," i.e., gelling agents, are crosslinked acrylic acid
polymers such as the "carbomer" family of polymers, e.g.,
carboxypolyalkylenes that may be obtained commercially under the
Carbopol.RTM. trademark. Also preferred are hydrophilic polymers
such as polyethylene oxides, polyoxyethylene-polyoxypropylene
copolymers and polyvinylalcohol; cellulosic polymers such as
hydroxypropyl cellulose, hydroxyethyl cellulose, hydroxypropyl
methylcellulose, hydroxypropyl methylcellulose phthalate, and
methylcellulose; gums such as tragacanth and xanthan gum; sodium
alginate; and gelatin. In order to prepare a uniform gel,
dispersing agents such as alcohol or glycerin can be added, or the
gelling agent can be dispersed by trituration, mechanical mixing,
and/or stirring.
[0137] Various additives, known to those skilled in the art, may be
included in the topical formulations. For example, solubilizers may
be used to solubilize certain active agents. For those drugs having
an unusually low rate of permeation through the skin or mucosal
tissue, it may be desirable to include a permeation enhancer in the
formulation; suitable enhancers are as described elsewhere
herein.
[0138] Transmucosal administration of an MDSS composition can be
accomplished using any type of formulation or dosage unit suitable
for application to mucosal tissue. For example, an MDSS composition
may be administered to the buccal mucosa in an adhesive patch,
sublingually or lingually as a cream, ointment, or paste, nasally
as droplets or a nasal spray, or by inhalation of an aerosol
formulation or a non-aerosol liquid formulation.
[0139] Preferred buccal dosage forms will typically comprise a
therapeutically effective amount of an MDSS composition and a
bioerodible (hydrolyzable) polymeric carrier that may also serve to
adhere the dosage form to the buccal mucosa. The buccal dosage unit
is fabricated so as to erode over a predetermined time period,
wherein drug delivery is provided essentially throughout. The time
period is typically in the range of from about 1 hour to about 72
hours. Preferred buccal delivery preferably occurs over a time
period of from about 2 hours to about 24 hours. Buccal drug
delivery for short-term use should preferably occur over a time
period of from about 2 hours to about 8 hours, more preferably over
a time period of from about 3 hours to about 4 hours. As needed
buccal drug delivery preferably will occur over a time period of
from about 1 hour to about 12 hours, more preferably from about 2
hours to about 8 hours, most preferably from about 3 hours to about
6 hours. Sustained buccal drug delivery will preferably occur over
a time period of from about 6 hours to about 72 hours, more
preferably from about 12 hours to about 48 hours, most preferably
from about 24 hours to about 48 hours. Buccal drug delivery, as
will be appreciated by those skilled in the art, avoids the
disadvantages encountered with oral drug administration, e.g., slow
absorption, degradation of the active agent by fluids present in
the gastrointestinal tract and/or first-pass inactivation in the
liver.
[0140] The "therapeutically effective amount" of an MDSS
composition in the buccal dosage unit will of course depend on the
potency of an MDSS composition and the intended dosage, which, in
turn, is dependent on the particular individual undergoing
treatment, the specific indication, and the like. The buccal dosage
unit will generally contain from about 1.0 wt. % to about 60 wt. %
active agent, preferably on the order of from about 1 wt. % to
about 30 wt. % active agent. With regard to the bioerodible
(hydrolyzable) polymeric carrier, it will be appreciated that
virtually any such carrier can be used, so long as the desired drug
release profile is not compromised, and the carrier is compatible
with an MDSS composition and any other components of the buccal
dosage unit. Generally, the polymeric carrier comprises a
hydrophilic (water-soluble and water-swellable) polymer that
adheres to the wet surface of the buccal mucosa. Examples of
polymeric carriers useful herein include acrylic acid polymers and
co, e.g., those known as "carbomers" (Carbopol.RTM., which may be
obtained from B. F. Goodrich, is one such polymer). Other suitable
polymers include, but are not limited to: hydrolyzed
polyvinylalcohol; polyethylene oxides (e.g., Sentry Polyox.RTM.
water soluble resins, available from Union Carbide); polyacrylates
(e.g., Gantrez.RTM., which may be obtained from GAF); vinyl
polymers and copolymers; polyvinylpyrrolidone; dextran; guar gum;
pectins; starches; and cellulosic polymers such as hydroxypropyl
methylcellulose, (e.g., Methocel.RTM., which may be obtained from
the Dow Chemical Company), hydroxypropyl cellulose (e.g.,
Klucel.RTM., which may also be obtained from Dow), hydroxypropyl
cellulose ethers (see, e.g., U.S. Pat. No. 4,704,285 to Alderman),
hydroxyethyl cellulose, carboxymethyl cellulose, sodium
carboxymethyl cellulose, methyl cellulose, ethyl cellulose,
cellulose acetate phthalate, cellulose acetate butyrate, and the
like.
[0141] Other components may also be incorporated into the buccal
dosage forms described herein. The additional components include,
but are not limited to, disintegrants, diluents, binders,
lubricants, flavoring, colorants, preservatives, and the like.
Examples of disintegrants that may be used include, but are not
limited to, cross-linked polyvinylpyrrolidones, such as
crospovidone (e.g., Polyplasdone.RTM. XL, which may be obtained
from GAF), cross-linked carboxylic methylcelluloses, such as
croscarmelose (e.g., Ac-di-sol.RTM., which may be obtained from
FMC), alginic acid, and sodium carboxymethyl starches (e.g.,
Explotab.RTM., which may be obtained from Edward Medell Co., Inc.),
methylcellulose, agar bentonite and alginic acid. Suitable diluents
are those which are generally useful in pharmaceutical formulations
prepared using compression techniques, e.g., dicalcium phosphate
dihydrate (e.g., Di-Tab.RTM., which may be obtained from Stauffer),
sugars that have been processed by cocrystallization with dextrin
(e.g., co-crystallized sucrose and dextrin such as Di-Pak.RTM.,
which may be obtained from Amstar), calcium phosphate, cellulose,
kaolin, mannitol, sodium chloride, dry starch, powdered sugar and
the like. Binders, if used, are those that enhance adhesion.
Examples of such binders include, but are not limited to, starch,
gelatin and sugars such as sucrose, dextrose, molasses, and
lactose. Particularly preferred lubricants are stearates and
stearic acid, and an optimal lubricant is magnesium stearate.
[0142] Sublingual and lingual dosage forms include creams,
ointments and pastes. The cream, ointment or paste for sublingual
or lingual delivery comprises a therapeutically effective amount of
the selected active agent and one or more conventional nontoxic
carriers suitable for sublingual or lingual drug administration.
The sublingual and lingual dosage forms of the present invention
can be manufactured using conventional processes. The sublingual
and lingual dosage units are fabricated to disintegrate rapidly.
The time period for complete disintegration of the dosage unit is
typically in the range of from about 10 seconds to about 30
minutes, and optimally is less than 5 minutes.
[0143] Other components may also be incorporated into the
sublingual and lingual dosage forms described herein. The
additional components include, but are not limited to binders,
disintegrants, wetting agents, lubricants, and the like. Examples
of binders that may be used include water, ethanol,
polyvinylpyrrolidone; starch solution gelatin solution, and the
like. Suitable disintegrants include dry starch, calcium carbonate,
polyoxyethylene sorbitan fatty acid esters, sodium lauryl sulfate,
stearic monoglyceride, lactose, and the like. Wetting agents, if
used, include glycerin, starches, and the like. Particularly
preferred lubricants are stearates and polyethylene glycol.
Additional components that may be incorporated into sublingual and
lingual dosage forms are known, or will be apparent, to those
skilled in this art (See, e.g., Remington: The Science and Practice
of Pharmacy (2000), supra).
[0144] Other preferred compositions for sublingual administration
include, for example, a bioadhesive to retain an MDSS composition
sublingually; a spray, paint, or swab applied to the tongue; or the
like. Increased residence time increases the likelihood that the
administered invention can be absorbed by the mucosal tissue.
[0145] Transdermal administration of MDSS compositions through the
skin or mucosal tissue can be accomplished using conventional
transdermal drug delivery systems, wherein the agent is contained
within a laminated structure (typically referred to as a
transdermal "patch") that serves as a drug delivery device to be
affixed to the skin.
[0146] Transdermal drug delivery may involve passive diffusion or
it may be facilitated using electrotransport, e.g., iontophoresis.
In a typical transdermal "patch," the drug composition is contained
in a layer, or "reservoir," underlying an upper backing layer. The
laminated structure may contain a single reservoir, or it may
contain multiple reservoirs. In one type of patch, referred to as a
"monolithic" system, the reservoir is comprised of a polymeric
matrix of a pharmaceutically acceptable contact adhesive material
that serves to affix the system to the skin during drug delivery.
Examples of suitable skin contact adhesive materials include, but
are not limited to, polyethylenes, polysiloxanes, polyisobutylenes,
polyacrylates, polyurethanes, and the like.
[0147] Alternatively, the drug-containing reservoir and skin
contact adhesive are separate and distinct layers, with the
adhesive underlying the reservoir which, in this case, may be
either a polymeric matrix as described above, or it may be a liquid
or hydrogel reservoir, or may take some other form.
[0148] The backing layer in these laminates, which serves as the
upper surface of the device, functions as the primary structural
element of the laminated structure and provides the device with
much of its flexibility. The material selected for the backing
material should be selected so that it is substantially impermeable
to the active agent and any other materials that are present, the
backing is preferably made of a sheet or film of a flexible
elastomeric material. Examples of polymers that are suitable for
the backing layer include polyethylene, polypropylene, polyesters,
and the like.
[0149] During storage and prior to use, the laminated structure
includes a release liner. Immediately prior to use, this layer is
removed from the device to expose the basal surface thereof, either
the drug reservoir or a separate contact adhesive layer, so that
the system may be affixed to the skin. The release liner should be
made from a drug/vehicle impermeable material.
[0150] Transdermal drug delivery systems may in addition contain a
skin permeation enhancer. That is, because the inherent
permeability of the skin to some drugs may be too low to allow
therapeutic levels of the drug to pass through a reasonably sized
area of unbroken skin, it is necessary to co-administer a skin
permeation enhancer with such drugs. Suitable enhancers are well
known in the art and include, for example, those enhancers listed
below in transmucosal compositions.
[0151] As stated above, the MDSS compositions described herein may
include vitamins and vitamers, which is a substance(s) that has
vitamin-like activity. Vitamins selected from the group consisting
of the water soluble and lipid soluble group, and a combination of
two or more thereof may also be added to the pharmaceutical
composition. Preferably the pharmaceutical composition includes
ascorbic acid. It is envisaged that the ascorbic acid will increase
the negative and stabilize the anti-oxidant properties of the
formulation. Ascorbic acid is included as a strong anti-oxidant
component and to maintain the structural integrity of connective
tissue, including epithelial basement membranes and to promote
wound healing. It may also play a distinct role as an agent with
strong anti-inflammatory actions. The oxidized form of the vitamin
has been shown to transfer intracellularly where some of it is
reduced within the cell. Deficiencies of other B group and A and E
are also protected by this vitamin. The B Group of Vitamins has
been shown to be important in human food intake, and plays an
important role acting as co-enzymes in cellular metabolism and
energy production. The entire B group of vitamins is included in
the formulation in order to ensure that all vitamins are present so
that any deficiencies may addressed in the patient population to be
treated with this product. The B group vitamins are always found
together to occur naturally together in foods and are included for
this reason. The B group includes: 1) Thiamine (B1), which plays an
important role in energy production within the cell, specifically
as co-enzyme in metabolism of carbohydrates. At least 24 enzymes
are known to use thiamine as a co-enzyme; 2) Riboflavin (B2) in the
form of flavin mononucleotide and flavin adenine dinucleotide are
part of all dehydrogenase enzymes. Deficiency of this vitamin
causes inflammation of the mouth, tongue, dermatitis, defective
vision and blood dyscrasias; 3) Niacinamide (B3) is included, as
part of the B group of vitamins as deficiency syndromes in clinical
pellagra are well known clinical manifestations of deficiencies.
The deficiency states of this vitamin are associated with
intestinal diseases and alcohol misuse. It also occurs in diabetes
mellitus and carcinoid syndrome. The active forms of this vitamin
include the nicotinamide dinucleotides NAD and NADP, which are the
co-enzymes and co-substrates for numerous dehydrogenases
responsible for oxidation-reduction systems within the human cell,
which are indispensable for energy production. The formation of
nicotinic acid from the administered nicotinamide in the
formulation produce nicotinic acid possessing additional actions
not shared by nicotinamide, such as inhibition of cholesterol
synthesis; 4) Calcium D-Pantothenate (B5), pantothenic acid forms a
major part of the molecule of co-enzyme A, which is important in
the energy producing metabolic cycles in the mitochondria of all
cells. The effect of this vitamin on various disease syndromes has
been recognized. Such as its use in neurotoxicity produced by
streptomycin and its use in diabetic neuropathy, skin diseases and
adynamic ileus; and 5) Pyridoxine (B6) is widely utilized as a
co-enzyme in over 40 types of enzymatic reactions. The most
important of these are the transamination reactions and the
influence of pyridoxine on tryptophane metabolism. Kynureminase
which is a the enzyme used to identify pyridoxine deficiencies,
loses its activity when pyridoxine is not present and may result in
secondary nicotinic acid deficiency as a result of lack of the
kynureminase conversion of nicotinic acid from tryptophane.
[0152] Cyanocobalamin (B12) is used because of the frequent reports
of mal-absorption of cyanocobalamin, caused by poor dietary habits
senescence and certain drugs (metformin) used as a hypoglycemic
agent in diabetes mellitus. This vitamin is essential for normal
erythropoeisis to occur and recent findings have also implicated
this vitamin with improvement of neuronal transmission in motor
neuron disease.
[0153] Vitamin K is a fat soluble vitamin. There are two naturally
occurring forms of the vitamin. Vitamin K1 is the dietary Vitamin K
and is abundant in green leafy vegetables, whereas vitamin K2 is
present in tissues. Vitamin K2 is synthesized by bacteria. It is
found mainly in fermented products like fermented soybeans, cheese,
curds and to some extent also in meat and meat products (Thijssen,
H. H., M. J. Drittij-Reijnders, and M. A. Fischer, 1996,
Phylloquinone and menaquinone-4 distribution in rats: synthesis
rather than uptake determines menaquinone-4 organ concentrations, J
Nutr 126:537-43). Vitamin K2 is found in animals as menaquinone. It
is the human activated form of vitamin K and is said to promote the
healing of bone fractures. It is essential for the carboxylation of
glutamate residues in many calcium binding proteins such as
calbindin and osteocalcin. These proteins are involved in calcium
uptake and bone mineralization. There is no established daily
dosage for vitamin K2 but only for Vitamin K1. A typical
therapeutic oral dose for vitamin K2 for osteoporosis is 45 mg/day.
Therapeutic dose for cancer patients is 25 mg/day, but usually is
in the range of 45 mg/day. Unlike for coagulation, we need much
higher levels of vitamin K for complete gamma-carboxylation of
osteocalcin. Vitamin K deficiency is associated with reduced hip
bone mineral density and increased fracture risk in healthy elderly
women. Animal studies have shown that the most potent form of
vitamin K is vitamin K2, which was administered to rats at 0.1
mg/kg orally. Vitamin K2, in the form of menaquinone-4, is the most
biologically active form. Vitamin K2 is a cofactor of
gamma-carboxilase and thus essential for the carboxylation of
glutamate residues in many calcium binding proteins such as
calbindin and osteocalcin (Shearer, M. J., 1992, Vitamin K
metabolism and nutriture, Blood Rev 6:92-104). These proteins are
involved in calcium uptake and bone mineralization, hence vitamin
K2 is said to promote the healing of bone fractures (Hara, K., Y.
Akiyama, T. Nakamura, S. Murota, and I. Morita, 1995, The
inhibitory effect of vitamin K2 (menatetrenone) on bone resorption
may be related to its side chain, Bone 16:179-84).
[0154] Unlike for coagulation, a much higher level of vitamin K is
needed for complete gamma-carboxylation of osteocalcin (Booth, S.
L., and J. W. Suttie, 1998, Dietary intake and adequacy of vitamin
K, J. Nutr 128:785-8). Vitamin K deficiency is associated with
reduced hip bone mineral density and increased fracture risk in
healthy elderly women. Animal studies have shown that the most
potent form of vitamin K is vitamin K2, which was administered to
rats at 0.1 mg/kg orally (Akiyama, Y., K. Hara, A. Matsumoto, S.
Takahashi, and T. Tajima, 1995, Comparison of intestinal absorption
of vitamin K2 (menaquinone) homologues and their effects on blood
coagulation in rats with hypoprothrombinaemia, Biochem Pharmacol
49:1801-7). Vitamin K2, in the form of menaquinone-4, is the most
biologically active form. It has been extensively studied in the
treatment of osteoporosis. In one of these studies, 241
osteoporotic women were given 45 mg/day vitamin K2 and 150 mg
elemental calcium. After two years, vitamin K2 was shown to
maintain lumbar bone mineral density, significant lower fracture
incidence (10% versus 30% in the control group (Shiraki, M., Y.
Shiraki, C. Aoki, and M. Miura, 2000, Vitamin K2 (menatetrenone)
effectively prevents fractures and sustains lumbar bone mineral
density in osteoporosis, J Bone Miner Res 15:515-21).
[0155] Vitamin K2, but not K1, may inhibit the calcification of
arterial plaque. In 1996, animal studies involving rats found high
dose of Vitamin K2 (100 mg/kg body weight daily) inhibited the
increase in calcium in both kidneys and aorta induced by megadose
of synthetic vitamin D (Seyama, Y., M. Horiuch, M. Hayashi, and Y.
Kanke, 1996, Effect of vitamin K2 on experimental calcinosis
induced by vitamin D2 in rat soft tissue, Int J Vitam Nutr Res
66:36-8). A similar study was conducted with rabbits. High dose of
Vitamin K2 (1-10 mg/kg daily for 10 weeks) inhibited the
atherosclerotic plaque progression in the aorta and pulmonary
arteries (Kawashima, H., Y. Nakajima, Y. Matubara, J. Nakanowatari,
T. Fukuta, S. Mizuno, S. Takahashi, T. Tajima, and T. Nakamura,
1997, Effects of vitamin K2 (menatetrenone) on atherosclerosis and
blood coagulation in hypercholesterolemic rabbits, Jpn J Pharmacol
75:135-43). Vitamin K2 was also seen to reduce total cholesterol
levels, lipid peroxidation, ester cholesterol deposition in the
aorta and factor X activity in plasma compared to the control
group. A study involving more than 500 postmenopausal women
investigated the relation between vitamin K1 and K2 intake and
coronary calcification. Sixty-two percent of the women sampled for
the study had coronary calcification. Only Vitamin K2 intake was
associated with the trend toward decreasing coronary calcification
(Beulens, J. W., M. L. Bots, F. Atsma, M. L. Bartelink, M. Prokop,
J. M. Geleijnse, J. C. Witteman, D. E. Grobbee, and Y. T. van der
Schouw, 2009, High dietary menaquinone intake is associated with
reduced coronary calcification, Atherosclerosis 203:489-93).
[0156] Both in vivo and in vitro studies have demonstrated that
Vitamin K2 has anticancer effect. A multi-cancer study in Japan was
performed to test the effect of Vitamin K2 on MDS and post-MDS
acute myeloid leukemia patients. Vitamin K2 dosage ranged from
20-135 mg/day orally or 10-50 mg/day intravenously. Vitamin K2 was
effective in reducing blast cell numbers in bone marrow and/or
peripheral blood in .about.71% of those receiving other medication
concomitantly (Takami, A., S, Nakao, Y. Ontachi, H. Yamauchi, and
T. Matsuda, 1999, Successful therapy of myelodysplastic syndrome
with menatetrenone, a vitamin K2 analog, Int J Hemotol 69:24-6).
Another study involving 121 patients with hepatocellular carcinoma
undergoing conventional therapy has shown that when patients were
given 45 mg/day oral vitamin K2, there was a significant increase
in survival (Jancin, B, 2002, Vitamin K cuts hepatocellular CA
mortality, Fam Pract News 32). A recent study demonstrated that
there is inverse association between vitamin K2 and prostate
cancer. Higher intake of vitamin K2 might reduce prostate cancer
risk by 35%. The association was stronger with advanced prostate
cancer incidents. Interestingly, Vitamin K2 from dairy products had
stronger effect compared to other sources of vitamin K2 like meat
and meat products (Nimptsch, K., S. Rohrmann, and J. Linseisen.
2008. Dietary intake of vitamin K and risk of prostate cancer in
the Heidelberg cohort of the European Prospective Investigation
into Cancer and Nutrition (EPIC-Heidelberg), Am J Clin Nutr
87:985-92).
[0157] Magnesium Chloride is required in relatively large
concentrations in normal metabolism. It is recognized that
deficiency of magnesium is rare unless it is accompanied by severe
losses in other electrolytes such as in vomiting and diarrhea. It
is however frequently recognized as deficient in the modern diet
with symptoms such as muscle tremors and weakness. This mineral is
important in many enzymatic reactions and will stabilize excitable
membranes. Administered intravenously, magnesium may produce an
anesthetic action and this is indirect evidence of its action on
the vascular wall endothelial component to stabilize and normalize
the surface of the vascular wall.
[0158] Heparin is an anti-thrombotic agent capable of reducing
platelet aggregation. It may also play a role in vascular
endothelial normalization because heparin is related to chondroiten
sulphate, which appears naturally as a constituent in the vascular
wall and plays a role in the endothelium, which is not fully
understood. It has strong anti-inflammatory actions, which appears
to be strongly stimulated in formulations described herein because
of the presence of carbonic acid capable of neutralizing the acidic
charge of heparin. Heparin is a dextrorotary glycosaminoglycan,
consisting in a mixture of various polysacharidic chains, composed
of repeated D-glucosamine units and also L-idurcnic acid or
D-glucuronic acid. Its molecular weight ranges between 6,000
Daltons to 30,000 Daltons, which will depend on either the
obtainment source or the methodology, employed for its isolation.
The ability in prolonging the blood clotting time is the most known
heparin property. Further to the anti-clotting activity, it also
shows enzymatic antiproteolitic activity antithrombin, platelet
antilyse, thrombolitic, antiserotonergic, and antihistaminic.
[0159] Formulations can comprise one or more anesthetics. Patient
discomfort or phlebitis and the like can be managed using
anesthetic at the site of injection. If used, the anesthetic can be
administered separately or as a component of the composition. One
or more anesthetics, if present in the composition, is selected
from the group consisting of lignocaine, bupivacaine, dibucaine,
procaine, chloroprocaine, prilocalne, mepivacaine, etidocaine,
tetracaine, lidocaine and xylocalne, and salts, derivatives or
mixtures thereof.
[0160] Formulations can comprise other ingredients for the
treatment of the organism as a whole. For example, an anti-oxidant
additive and/or pro-oxidant additive can be present. The latter may
be an agent that acts as a preventive, while the former may be an
agent that acts to treat a specific medical condition.
[0161] Kits are described comprising a magnetic dipole stabilized
solution for injection. In this embodiment, the solution is
provided as a sterile composition in a vial. The vial can
preferably be an injection vial with a membrane that is suitable
for inserting a syringe to pull the solution from the vial or a
soft I.V. infusion bag. The solution can be provided as a
concentrated solution to which a diluent is added prior to
injection. The diluent can be sterile water. The kit may further
comprise a pre-filled container which contains the diluent. In a
preferred embodiment, a soft infusion bag is pre-filled with
diluent. Alternatively, the magnetic dipole stabilized solution
vial can contain a solution that is at a concentration which is
suitable for injection without any dilution. Preferably, the
solution for injection is isotonic. That is, the solution can
contain salt, carbohydrates, such as glucose, NaHCO.sub.3 or amino
acids, such as glycine, and is isotonic with blood plasma.
[0162] In some embodiments, the kits comprise a first vial
containing a magnetic dipole stabilized solution and a second vial
containing components to be admixed with the solution to prepare a
composition for injection. The components are listed above.
Preferably, the components and the solution are combined just prior
to administration. Preferably, in this embodiment, the kit
comprises a first container containing a solution comprising one or
more selected from the group consisting of vitamins, salts, acids
and vitamers, and mixtures thereof; and a second container
containing a magnetic dipole stabilized solution. As described
herein, it is preferable that the magnetic dipole stabilized
solution is electroactivated water. Additionally, the containers
can be vials or bags or a combination of both.
[0163] Each kit described herein may further comprise instructions
for use. The instructions will, of course, depend upon the kit
itself and whether a diluent is to be used or other components to
be admixed with the magnetic dipole stabilized solution prior to
administration.
[0164] According to U.S. Pat. No. 7,588,488, there are three types
of electrolyzed water, which can be prepared by electrolysis of
water having ions dissolved therein. While not strictly defining,
the inventors can generally describe that Type A water is a
disinfectant that kills a large variety of bacteria, viruses,
molds, and spores within seconds of contact. When negatively
charged ions migrate to the anode, the fluid around the anode
develops a reduced pH in the approximate range of 1.8 to 4.9 and an
ORP in the approximate range of +950 to +1450 millivolts (mV). Type
A water can be produced as a continuous stream of clear solution
having a pH of 1.8 to 4.9, an ORP of +950 to +1450 mV, and
containing 8 to 200 parts per million (ppm) of HOCl. When Type A
water comes in contact with organic material its pH increases, its
ORP drops, and the HOCl dissipates or gases off, thus returning to
ordinary water having a small amount of free chlorine (Cl).
So-called Type B water is an effective emulsifier and cleaner
having antimicrobial properties. It is capable of saponifying
surfaces upon contact. Type B water is an alkaline water stream and
can be produced as a continuous stream of clear solution produced
around the negative electrode, i.e., cathode, during electrolysis.
This Type B water is basic with a pH in the approximate range of
9.1 to 12.2. The ORP of Type B water is in the approximate range of
+100 to -980 mV. Type B water also contains sodium hydroxide (NaOH)
ions in the approximate range of 8 to 200 ppm. Type B water is
effective in emulsifying oils and lipids and leaves no residue.
Safety and toxicity tests show that Type B water is nontoxic at a
pH of 9.5 to 12.2 and an ORP from -350 to -950 mV. So-called Type C
water is essentially a form of stabilized Type A water with a
longer shelf life. Type C solution has an ORP in the approximate
range of 0 to +900 mV, a pH value in the approximate range of 5.5
to 8.2, and contains HOCl in the approximate range of 8 to 80
ppm.
[0165] As described above, the electro-activated solutions with a
stable positive or negative oxidation-reduction potential may be
prepared by any method known in the art. Preferably, sterile,
purified water is electro-activated using an open plate
palladium-coated electrode in a ceramic-type housing of a module
containing ferrous and non-ferrous alloys capable of imparting a
fixed magnetic field of at least 7.5 Gauss over a period of time,
generally at least 1.75 minutes, at a particular flow rate,
generally at least 0.75 liter/minute. The electro-activated water
thus obtained has an initial positive oxidation-reduction potential
(ORP). Positively charged anolyte water is a carrier for the
species formed during electroactivation. The use of negatively
charged catholyte water is also contemplated. The electroactivated
solution for injection will preferably have a negative potential
from about -990 mV to about -0.0001 mV. The negative potential is
prepared by mixing the positively charged anolyte water with other
components described herein to prepare the MDSS solution for
injection. The MDSS for injection can have an ORP of -70 mV and is
preferably aqueous in nature.
[0166] The present subject matter is based on the unexpected
discovery that the MDSS compositions described herein are useful in
treating, ameliorating and preventing many conditions and diseases
and symptoms thereof. Without being bound to any theory, it is
believed that the compositions improve oxygen delivery to the
arteries, veins and cardiac muscle and the transport of
anti-oxidants and minerals to the bloodstream by causing changes in
the concentration gradient of the cellular membranes which in turn
modulate transport of physiological ions, such as sodium and
potassium. In addition, it is believed that the MDSS compositions
improve membrane permeability and thus increases the rate of
transport of the minerals and anti-oxidants in the solution.
Furthermore, injection of the compositions into the bloodstream
provides for the fast and prompt reaching of high levels of
nutrients, anti-oxidants and minerals in the blood. It is believed
that as a result of these properties of the MDSS compositions
described herein, the compositions are surprisingly effective
against a number of conditions and diseases.
[0167] The methods of the invention include systemic application of
magnetic dipole stabilized solutions (MDSS) containing stabilized
oxidative species selected from the group consisting of H.sub.2O,
O.sub.2, H.sub.2O.sub.2, Cl.sub.2O, H.sub.3O, O.sub.3 and ClO.sub.2
as described herein.
[0168] The present invention is further described herein by the
following non-limiting examples which further illustrate the
invention, and are not intended, nor should they be interpreted to,
limit the scope of the invention.
Examples
1. Method of Preparing Magnetic Dipole Stabilized Solution
(MDSS)
[0169] The following table describes the preparation of MDSS (also
referred to as electroactivated water).
TABLE-US-00001 Preferred Values 1. FORMULA Sodium Chloride
USP/EP/BP 50 g to 200 g/L Sodium Bicarbonate USP/EP/BP 20 to 96 g/L
Water for Injection USP 1000 mL 2. PREPARATION Collect Water for
Injection in a suitable, pre-sterilized and depyrogenated glass
container. Add Sodium Chloride and Sodium Bicarbonate (pre-weighed
quantities) to the WFI and mix until completely dissolved. Addition
of heat may be required at a temperature not exceeding 37.degree.
C. Check concentrations of sodium chloride and sodium bicarbonate
Limits: NaCl: 50-200 g/L NaHCO.sub.3: 20-96 g/L Release solution
for use in MDS preparation Prepare fluid path with pre-sterilized
components, couplers and tubing. Check machine set-up to deliver
suitable flow-rate Limit: 20 mL to 250 mL per minute Discard 2
Litres of initial effluent. Measure oxidation reduction potential
(ORP) ORP: 450-1500 mV Measure solution pH pH: 3.20-7.60 Determine
surface tension Limit: 45-66 dynes/cm Determine ionic species:
HClO, ClO.sub.2, O.sub.3, O.sub.2, HO.sub.2 Limit: NLT 0.01%
Collect prepared solvent in pre-sterilized container 3. QUALITY
Measure oxidation reduction potential (ORP) ORP: 450-1500 mV
CONTROL Measure solution pH pH: 3.20-7.60 Determine surface tension
Limit: 45-66 dynes/cm Determine ionic species: HClO, ClO.sub.2,
O.sub.3, O.sub.2, HO.sub.2 Limit: NLT 0.01%
2. Specific Formulations
[0170] a. In one embodiment, a specific formulation for injection
comprises:
TABLE-US-00002 Concentration/dose Comment Imidazole HCl 10 mg
Lidocaine HCl 200 mg Calcium Gluconate 200 mg Thiamine 15 mg
Riboflavine 3 mg Nicotinamide 150 mg Pyridoxine 7.5 mg Dexpanthenol
7.5 mg Ascorbate Na 50.0 mg Dextrose 5% Caloric source Benzyl
Alcohol 0.5% Preservative Tetracycline HCl 350 mg Water 20 ml
[0171] b. In one embodiment, a two-container formulation for
injection comprises:
TABLE-US-00003 Concentration/dose Comment VIAL 1 Lidocaine HCl 200
mg Thiamine 15 mg Riboflavine 3 mg Nicotinamide 150 mg Pyridoxine
7.5 mg Dexpanthenol 7.5 mg Ascorbic acid 50.0 mg Calcium gluconate
0.2 g Dextrose 5% Benzyl Alcohol 0.5% Neutral bicarbonate ECA ORP
400-700; pH 7.0 VIAL 2 Heparin Na 1000 I.U. Sodium Bicarbonate 8.5%
Anolyte + ORP Solvent & preservative
[0172] c. In one embodiment, a two-container formulation for
injection comprises:
[0173] Container 1 is a vial, which contains a MDSS as described
herein as a multi-component injection including a multivitamin
combination with minerals, a single amino acid, amino-acetic acid
and a local anaesthetic (lidocaine). Container 2 comprises a
carrier solution/solvent system, used for dissolution of the
components in a physiological buffer which, when combined with
Container 1, stabilizes the components for effective delivery to
the biophase. This solvent system is prepared from sterile Water
For Injection (WFI), which contains a small amount of carbonic
acid, derived from NaHCO.sub.3. The solvent carries a strong
positive or negative electrical charge, as selected for the
application. The charge may be monitored by accurate oxidation
potential measurements to be at least 800 milli Volts. During
dissolution and filling of the injection, the charge may be
diminished to about -400 to about -700 milli volts and during
storage and shelf life may diminish further to about -70 milli
Volts, which is still considered as adequate and effective. The
local anaesthetic action is employed to stabilize the membrane of
the vascular endothelial cells by blocking of the sodium channels
and providing vascular wall relaxation. Both containers are to be
diluted before use. The final dose is 200 ml containing 0.9% Sodium
Chloride Injection. The final dose can be provided in an infusion
bag.
[0174] d. In one embodiment, a specific formulation. REV-1 for
injection:
TABLE-US-00004 Concentration per dose Comment Sodium ascorbate 395
mg Magnesium chloride 2 H.sub.2O 255 mg 2-di methyl amino ethanol
HCl 200 mg Thiamine 36 mg Riboflavine 7.3 mg Nicotinamide 100 mg
Pyridoxine 18.2 mg Calcium pantothenate 18.2 mg Cyanocobalamin 320
.mu.g ECA water ORP > 800 10 ml Solvent & preservative
[0175] e. In one embodiment, a specific formulation for injection
comprises:
TABLE-US-00005 Formulation Optional Per dose Total Dose ingredients
Ascorbic acid 1000 mg 1000 mg Sodium ascorbate/ Ascorbic acid
2-dimethyl amino 300 mg 300 mg 2-dimethyl amino ethanol ethanol
Aminoacetic acid Ca-d-pantothenate 2.40 mg 2.40 mg
Ca-d-pantothenate Niacinamide 1100 mg 1100 mg Niacinamide Nicotinic
acid Pyridoxine 1100 mg 1100 mg Pyridoxine Riboflavin 300 mg 300 mg
Riboflavin NAD/co Q10 Thiamine 60.50 mg 60.50 mg Thiamine
Cyanocobalamin 1500 .mu.g 1500 .mu.g Cyanocobalamin Magnesium 0.6 g
+ 0.4 g 0.90 g Vial I + vial II Magnesium sulphate 4.05 mM
Mg.sup.++ sulphate Sodium 0.85 g 0.85 g Buffer vial II Sodium
Bicarbonate Bicarbonate Heparin Na -- 1000 IU/ml Heparin Na MDSS
Water 10 ml ORP > 900 mV Activator MDSS Water pH 5.5-7.6 Alfa
lipoic acid Vitamin E Dose/10 ml 75 mg Phosphatidile serine 150 mg
Glycerophosphatidile choline Ca + Mg 200 mg Acetyl-L- carnitine
Ca-d-pantothenate 2.40 mg 1000 mg L tyrosine Niacinamide 1100 mg 20
mg 5 HTP 850 mg Aspartic acid Pyridoxine 1100 mg 0.2 mg selenium
Riboflavin 300 mg 0.1 mg copper 1 mg zinc 0.1 mg iodine 500 mg
glutathione
[0176] f. In one embodiment, a specific formulation for injection
comprises:
TABLE-US-00006 Ingredient Amount Molar Hydrochloride salt of
2-(diethylamino)-N- 0.055M-0.076M (2,6-dimethylphenyl) acetamide
Fructose 3.5 to 5.5% Nicotinic Acid 0.95 to 1.25% Thiamine 0.85 to
1.45% Riboflavin 0.15 to 0.19% Folic Acid 0.25 to 0.55% Pyridoxine
0.15 to 0.19% Ascorbic acid 2.30 to 2.50% Cyanocobalamin 0.05 to
0.07% MDSS to 10 ml.
[0177] All of the above ingredients in this specific formulation
are combined into a solution of MDSS that results in a negative
electrical potential of preferably about -120 mV to about -20 mV.
Most preferably, the potential is about -70 mV. The ingredients are
introduced into the vehicle by addition of ascorbic acid followed
by the vitamin and carbohydrate constituent. Then, the non-ionized
lipid soluble components, previously solubilized in a high speed
mixer for about 5 minutes by means of beta cyclodextrin. The
ingredients are combined by slow agitation with addition of an
inert gas such as nitrogen to the mixture so as to minimize
oxidation from taking place. The resultant solution is then
transferred to a glass 10 ml vial under an inert atmosphere such as
nitrogen. Each vial is then sealed by means of a stopper and an
aluminium cap, which is crimped around the seal so as to ensure
that the seal is hermetic.
[0178] g. In one embodiment, a specific formulation for injection
comprises:
TABLE-US-00007 Amount (Molar Ingredient concentration)
Hydrochloride salt of 2-(diethylamino)-N- 0.055M-0.076
(2,6-dimethylphenyl) acetamide Beta Cyclodextrin hydrate 0.01-0.05
Hydrochloric acid to pH 3.2 Nicotinic Acid 0.95 to 1.25% Thiamine
0.85 to 1.45% Riboflavin 0.15 to 0.19% Folic Acid 0.25 to 0.55%
Pyridoxine 0.15 to 0.19% Ascorbic acid 2.30 to 2.50% Cyanocobalamin
0.05 to 0.07% Magnetic Dipole Stabilized Solution to 10 ml
[0179] h. In one embodiment, a specific formulation for injection
comprises:
TABLE-US-00008 Amount Molar Ingredient concentration Hydrochloride
salt of 2-(diethylamino)-N- 0.055M-0.076M (2,6-dimethylphenyl)
acetamide Betacyclodextrin hydrate 0.01-0.50 mg Sodium Chloride
380-450 mg Phosphate buffer to pH 7.0 Nicotinic Acid 0.95 to 1.25%
Thiamine 0.85 to 1.45% Riboflavin 0.15 to 0.19% Folic Acid 0.25 to
0.55% Pyridoxine 0.15 to 0.19% Ascorbic acid 2.30 to 2.50%
Cyanocobalamin 0.05 to 0.07% Magnetic Dipole Stabilized Solution to
10 ml to 10 ml
[0180] i. In one embodiment, a specific formulation for injection
comprises:
TABLE-US-00009 Amount Molar Ingredient concentration Hydrochloride
salt of 2-(diethylamino)-N- 0.055M-0.076M (2,6-dimethylphenyl)
acetamide Hydroxypropylcyclodextri n 0.01-0.50 mg Sodium Chloride
380-450 mg Phosphate buffer to pH 7.0 Sodium Hydroxide to pH 7.4
Nicotinic Acid 0.95 to 1.25% Thiamine 0.85 to 1.45% Riboflavin 0.15
to 0.19% Folic Acid 0.25 to 0.55% Pyridoxine 0.15 to 0.19% Ascorbic
acid 2.30 to 2.50% Cyanocobalamin 0.05 to 0.07% Mannitol 2.5%
Magnetic Dipole Stabilized Solution to 10 ml to 10 ml
3. Clinical Data
[0181] a. Effect of the Formulations of the Invention on Different
Diseases and Conditions
TABLE-US-00010 No. Std. Symptom or of Follow Dosage of Improvement
Condition Diagnosis patients up Freq. Formulation Care Stage Score
General Interviews 50 or Some 1-2 .times. REV-1 N/A 1 2 or better
Indications and more patients per (Cosmetic, consultations are week
chronic returning fatigue, stress for etc.) treatment Diabetic
ulcer Consultation 10 or Yes 14 Heparin Yes 3 New growth of more (1
.times. included plus toe nail and week) buffered totally pain free
anolyte Mid shaft Yes 12 Heparin Yes 4 Able to walk fracture non (1
.times. included plus without a healing week) buffered crutch
within 6 anolyte weeks Heart disease Yes 12 REV-1 Yes 4 Chest pains
(3 .times. disappeared week) Coronary MRI + ECG 1 Yes 7 REV-1 Yes 3
Normal heart artery disease function Perivascular Consultation + 2
Yes 27 Heparin Yes 2 Patient fully disease scan (1 .times. included
plus mobile, pain affecting week) buffered free and able to lower
limbs anolyte drive Coronary MRI + ECG 1 Yes 14 REV-1 Yes 3 Heart
disease artery disease (1 .times. cured after 14 week) weeks Severe
Scan and 1 Yes 40 Heparin Yes 4 Fully mobile intermittent Doppler
(1 .times. included plus and able to claudication. week) buffered
work after 25 (Femoral anolyte weeks artery) Peri-vascular Scan and
1 Yes 18 Heparin Yes 3 Pain free and disease Doppler (2 .times.
included plus wound of week) buffered previous anolyte amputation
healed Diabetic with Clinical 1 Yes 24 REV-1 Yes 2 Marked renal (2
.times. improvement insufficiency week) after 12 weeks Painful leg
Consultation 1 Yes 7 intra- Heparin Yes 3 Totally pain after
arterial included plus free and able to amputation injections
buffered wear prosthesis and fall on anolyte patella Ulcer on toe
Consultation 1 Yes 17 Heparin Yes 4 Fully mobile (1 .times.
included plus after 8 weeks week) buffered and pain free anolyte
Buergers Consultation 1 Yes 16 REV-1 Yes 4 Lesions disease (1
.times. completely week) healed and pain free Coronary MRI + ECG 1
Yes 32 REV-1 Yes 3 (80- VEF from 10% artery disease (1 .times. year
to 51% week) old improvement patient) Small Consultation 1 Yes 3
REV-1 Yes 2 Ulcer totally varicose vein (1 .times. disappeared
ulcer week) Intermittent Scan and 1 Yes 14 REV-1 Yes 3 Fully
mobile, claudication Doppler (1 .times. no cramping week) Heart
disease MRI + ECG 1 Yes 150 REV-1 Yes 3 No more chest (2 .times.
pains week) Large ulcer on Consultation 1 Yes 14 REV-1 Yes 4 Ulcer
indicates mid shaft (1 .times. closure. Had week) been present for
14 years Arterial & Consultation 1 Yes 26 Heparin Yes 2 Fully
recovered venous and Doppler (1 .times. included plus circulation
week) buffered disorder anolyte Gangrenous Consultation 1 Yes 40
Heparin Yes 4 Walking fine foot (2 .times. included plus (severe
following week) buffered developed partial anolyte gangrene)
amputation Severe burns Consultation 1 Yes 15 REV-1 Yes 3 Treated
on on both legs (2 .times. right leg only - week) after 10 weeks
improvement and no infection Calcium Scan, MRI, 20 Yes 12-18 REV-1
Yes 1-3 See summary Agatston clinical (1-2 .times. report Score
Patients blood tests week) (Study) Performance Consultation 1 Yes
12 REV-1 Yes 1 Improvement enhancement (1 .times. (+ Vit. C) in
athletic week) performance (Ongoing) and general circulation
Hearing loss Auditory 1 Yes 12 REV-1 Yes 3 Dramatic in one ear
impairment (1 .times. improvement week) Chronic Consultation 1 Yes
20 REV-1 Yes 4 Dramatic fatigue and (2 .times. improvement in poly-
week) general health pharmacy (Ongoing) including user, low iron
increase in levels ferritin levels Severe Very high 1 Yes 12 REV-1
Yes 4 Dramatic and diabetic Type Agatston (1 .times. sustained II,
heart score week) improvement in disease Calcium score and control
of sugar levels Severe High risk 1 Yes 80 REV-1 Yes 3 Dramatic and
diabetic Type cardiac (Voluntary) (2 .times. sustained II, heart
disease and week) improvement in disease - Diabetes (Ongoing)
Calcium score Genetic Type II and control of predisposition sugar
levels
[0182] b. Treatment and Amelioration of Symptoms of Acne.
[0183] Three patients were given 1 or 2 infusions a week of REV-1
for a minimum of ten weeks. The results show:
[0184] One patient had an improved acne condition after just the
4th treatment.
[0185] One patient had less obvious scarring due to acne.
[0186] One patient had improved facial color.
[0187] Hydration of the skin improved in two patients. As a result,
less moisturizer was needed.
[0188] Two patients had less wrinkles during and after
treatment.
[0189] c. Metal Ion Removal
[0190] The following describes the ability of a MDSS composition to
remove metal ions. Twenty male and female individuals between the
ages of 24 and 63 were randomly selected for the treatment, based
on age, physical activity and body mass index (BMI). Subjects with
a family history of cardiovascular diseases, diabetes mellitus or
cancer were included in the treatment. The individuals were
subjected to a complete physical examination, blood and urine
analyses, calcium score measurement and radiological
examination.
[0191] The coronary calcium scan is a test that detects the
presence and amount of calcium in a coronary artery and correlates
that data to plaque formation. The calcium score was 0 in nine
subjects; 1 in one subject; 24 in two subjects; 32 in one subject;
40 in one subject; 42 in one subject; 46 in one subject; 57 in one
subject; 155 in one subject; 482 in one subject; and 1668 in one
subject. The radiological study performed on the twenty individuals
showed that individuals with a calcium score of 0 had no calcified
plaques, whereas subjects with a calcium score between 24 and 57
had calcified plaques in the left anterior descending artery (LAD).
Subjects with a calcium score of 155 or 482 showed calcification in
the right coronary artery (RCA) and left anterior descending artery
(LAD). The patient with a calcium score of 1668 showed
calcification of the right coronary artery, left main artery, left
anterior descending artery (LAD), the diagonal and circumflex
arteries.
[0192] All subjects had their blood pressure and pulse taken before
and after each treatment session and treated with a magnetic dipole
stabilized solution which is an electro-activated solution prepared
as follows.
[0193] An electro-activated aqueous solution is prepared using an
open plate palladium-coated electrode in a ceramic-type housing of
a module containing ferrous and non-ferrous alloys capable of
imparting a fixed magnetic field of at least 7.5 Gauss over a
period of time of at least 1.75 minutes at a flow rate of at least
0.75 liter/minute. The electro-activated water thus obtained, which
has an initial positive oxidation-reduction potential (ORP) in a
range between +700 mV and +900 mV, is then collected in a
sterilized, air-free and endotoxin-free vessel and used to prepare
Solution A and Solution B. Both solutions are used as a diluent for
vitamins, salts and minerals.
[0194] 1.0 liter of Solution A is prepared by dissolving the
following vitamins, salts and minerals:
TABLE-US-00011 Magnesium Sulphate hexahydrate 60.2 g/L
2-diethylaminoaceto, xylidide 30.0 g/L Niacinamide 9.90 g/L
Puridoxin HCl 9.90 g/L Riboflavin-5-phosphate sodium 0.19 g/L
Thiamin HCl 6.05 g/L Cyanocobalamin crystalline 0.18 g/L
Electrochemically activated water+ 007.50 ml
[0195] Ascorbic acid, which is a strong anti-oxidant, is added in a
concentration of 88.0 g/L and 95.0 g/L, respectively, to reach a
stable, negative ORP in a range between -500 mV and -900 mV.
[0196] To prepare Solution B, sodium bicarbonate, sodium chloride,
magnesium sulfate and calcium are added to increase ionization and
produce a stably charged anti-inflammatory solution. A stabilizer
may be also added to the solution in an amount of 0.5% mass/volume
to increase conductive ionization and produce a stably charged
solution with a stable, positive oxidation-reduction potential in a
range between +500 mV and +900 mV. The stabilizer may be mixed into
the solution by agitation or a sonicator bath and the solution is
immediately sealed to prevent entry of oxygen.
[0197] 1.0 liter of Solution B is prepared by dissolving the
following salts and minerals:
TABLE-US-00012 Sodium Bicarbonate USP 86.70 g/L Magnesium Sulphate
hexahydrate 20.2 g/L Electrochemically activated water+ 998.5
ml
[0198] Both solutions A and B are stable for a period of at least
12 months when stored at 20 degrees-34 degrees Celsius.
[0199] Solution A and Solution B are then mixed immediately prior
to administration to produce a stable composition with a stable
negative oxidation-reduction potential (ORP) in a range between -50
mV and -150 mV, a stable pH between 6.6 and 7.9, and a conductivity
in the range between 11 and 14 mS/cm.
[0200] The final mixture thus obtained comprises the following
ingredients:
TABLE-US-00013 Magnesium sulfate hexahydrate 0.5-10% Sodium
Bicarbonate 0.5-10% Ascorbic Acid 5.0-20% Niacinamide 0.2-2.0%
Pyridoxin HCl 0.005-0.2% Calcium D Pantothenate 0.01-2.0% Thiamin
HCl 0.1-1.0% Riboflavin 0.01-0.1% Cyanocobalamin 0.001-0.1%
Magnetic Dipole Stabilized Water 5.0-500 ml 2-di-ethylaminoethanol
1.0-3.0%
[0201] The solution was administered to each subject by intravenous
injection in an amount of 100 ml of sterile diluent (0.9% sodium
chloride injection) for 35 to 55 minutes once or twice a week for a
period ranging from two weeks to two months.
[0202] The calcium score was measured in the individuals subjected
to the treatment with the electro-activated solution at the end of
treatment. Table 3 below shows the calcium score of nine
individuals with an initial medium to high calcium score before and
after 12 treatment sessions. The data in Table 1 clearly show a
positive effect of the treatment on individuals with an initial
calcium score of 46 and above.
TABLE-US-00014 Calcium Score Percentage Calcium Score After 12
Treatment of Increase Patient Before Treatment Sessions or Decrease
1 24 25 4% Increase 2 24 26 8% Increase 3 32 31 3% Decrease 4 40 42
5% Increase 5 46 29 37% Decrease 6 57 40 29% Decrease 7 155 121 22%
Decrease 8 482 441 9% Decrease 5 1668 1539 8% Decrease
[0203] The magnetic dipole stabilized solutions described herein
are surprisingly effective at removing metal ions. Especially
preferred magnetic dipole stabilized solutions for this purpose
further comprise lipoic acid in the amounts described elsewhere
herein.
[0204] d. General Malnutrition
[0205] The following describes the ability of a MDSS composition to
treat malnutrition symptoms. A dose of one infusion per week
containing the REV-1+formulation described above was administered.
The trial lasted ten weeks. Subject Data: The subjects had
malnutrition problems. Some subjects presented with type II
diabetic symptoms. Results: One patient stated feeling very good
after treatment. Prior to treatment, skin color of ankles was blue.
After treatment, the color is pink. Another patient presented with
improved hydration in the eyes (electroactivated water was used as
eye drops as well), and increased blood circulation. Another
patient reported feeling very good with improvement in blood supply
to areas of a hand injury. Another patient reports overall
well-being and improvements at the same weight, indicating a
positive nutritional effect. Other patients report feeling more
energetic. One patient reported feeling more energetic and pain in
the heel area had improved.
[0206] e. Improved Athletic Performance
[0207] The formulation, REV-1 was administered to a subject. The
subject received 1 treatment per week up to two weeks prior to the
event at which time the subject received two treatments per week
until the event. After only four treatments, subject noticed an
improved running time for 91 km as compared to time before
treatment. In a follow-up trial, the subject was given six
treatments one year later and again the subject reported higher
energy levels during the race.
[0208] Throughout this specification and the claims, the words
"comprise," "comprises," and "comprising" are used in a
non-exclusive sense, except where the context requires
otherwise.
[0209] As used herein, the term "about," when referring to a value
is meant to encompass variations of, in some embodiments .+-.20%,
in some embodiments .+-.10%, in some embodiments .+-.5%, in some
embodiments .+-.1%, in some embodiments .+-.0.5%, and in some
embodiments .+-.0.1% from the specified amount, as such variations
are appropriate to perform the disclosed methods or employ the
disclosed compositions.
[0210] All publications, patent applications, patents, and other
references are herein incorporated by reference to the same extent
as if each individual publication, patent application, patent, and
other reference was specifically and individually indicated to be
incorporated by reference. It will be understood that, although a
number of patent applications, patents, and other references are
referred to herein, such reference does not constitute an admission
that any of these documents forms part of the common general
knowledge in the art.
[0211] Although the foregoing subject matter has been described in
some detail by way of illustration and example for purposes of
clarity of understanding, it will be understood by those skilled in
the art that certain changes and modifications can be practiced
within the scope of the appended claims.
[0212] Having thus described in detail preferred embodiments of the
present invention, it is to be understood that the invention
defined by the above paragraphs is not to be limited to particular
details set forth in the above description as many apparent
variations thereof are possible without departing from the spirit
or scope of the present invention.
* * * * *