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In this interview, MaxGXL developer Dr. Keller reveals the details about what MaxGXL is and the effect it is has had on his patients. If you really want to know what MaxGXL could do for you, this is the video you are looking for. He is straight to the point and delivers the information in a very direct format.
 The creator of MaxGXL, Robert Keller MDRobert Keller MD, MS, FACP
Robert Keller MD, MS, FACP, has been named as one of the world’s 2,000 Outstanding Scientists of the 21st Century, and has served on the scientific review panels for the National Institutes of Health and the VA. He has served on the faculties of the Mayo Graduate School of Medicine, the University of Wisconsin and the Medical College of Wisconsin (Marquette Univ.)
Robert Keller has published more than 100 articles in various medical journals. Dr Keller was elected to The Board of Governors of the American Academy of HIV medicine, and serves on the Scientific Advisory Board of the National Hemophilia Federation. The Consumers’ Research Council has named Dr. Keller one of America’s “Top Physicians in 2003, 2004, 2005, 2006 and 2007 in the fields of Internal Medicine, Immunology and Hematology.
MaxGXL has been shown to significantly increase intracellular glutathione. Conducting blood tests in which glutathione levels were measured in white blood cells, MaxGXL creator, Dr. Robert H. Keller was able to verify significant increases in every subject tested.
MaxGXL’s proprietary formula represented such a dramatic breakthrough in raising glutathione levels that the U.S. Patent Office awarded it a composition patent. Composition patents are normally reserved for pharmaceutical drugs. MaxGXL was awarded this patent because it not only raises glutathione levels within each cell, it also enables the liver to recycle the body’s used glutathione to manufacture even more, further increasing the body’s reservoir of glutathione.
UNITED STATES PATENT AND TRADEMARK OFFICE
No title
| United States Patent |
6,262,019 |
|
Keller
, et al.
|
July 17, 2001
|
Method of treatment of glutathione deficient mammals
Abstract
Glutathione (GSH) is a tripeptide of extreme importance as a catalyst,
reductan, and reactant. It can be depleted intracellulary either by
forming a direct complex with an electrophilic agent (accomplished
investigationally by agents such as bromobenzene or diethyl maleate), by
way of inhibition of synthesis, or by subjecting cells to oxidant stress.
Most cells, except for epithelia cells, do not have a direct transport
capacity for intact GSH. Non-epithelial cells must either transport
precursor substrates for GSH synthesis or salvage amino acids from
circulating GSH for reuse in intracellular resynthesis. Dietary cysteine
is a rate limiting substrate for the synthesis of glutathione and also
inhibits GSH efflux. Although GSH is synthesized from precursors in
virtually all cells, the liver is the main source of plasma GSH.
Protection and support of liver function is paramount to elevating GSH
levels. The disclosure is also of a unique combination of nutritional
supplements including n-acetyl cysteine, vitamin C, l-glucosamine,
n-acetyl d-glucosamine, quercitin, sylimarin, Alpha lipoic acid and high
protein, low fat whey that are combined to support various bodily systems
involved in glutathione synthesis, reutilization and storage; all intended
to elevate glutathione concentration in the mammalian cell.
| Inventors: |
Keller; Robert H (Weston, FL), Kirshenbaum; David W (Weston, FL) |
| Assignee: |
Vit-Immune, L. C.
(Hollywood,
FL)
|
| Appl. No.: |
09/302,217 |
| Filed:
|
April 29, 1999 |
| Current U.S. Class: |
514/2 ; 424/49; 424/535; 424/54; 424/655; 514/12; 514/21; 514/23; 514/251; 514/276; 514/7; 530/365; 530/833 |
| Current International Class: |
A23L
1/302 (20060101); A23L 1/305 (20060101); A23L 1/30 (20060101); A61K
31/185 (20060101); A61K 31/197 (20060101); A61K 31/70 (20060101); A61K
31/375 (20060101); A01N 037/18 (); A61K 038/02 () |
| Field of Search: |
514/2,7,12,23,21,251,276 424/54,49,535,655 530/365,833
|
References Cited [Referenced By]
U.S. Patent Documents
Other References
=left>
PROMT
on STN, Information Access Company, 1998: 1310, BioDynamax
Supplement--Ultra Antioxidants Tablets, Product Alert (Dec. 22, 1997)
ISSN:
0740-3801.*
.
"Screening of Potential Chemopreventive Agents Using Biochemical
Markets of Carcinogenesis" by Sheela Sharma, Jill D. Stutzman, Gary J.
Kelloff and Vernon E. Steele, Cancer Resreach 54, 5848-5855, Nov. 15,
1994.
.
Low Blood Glutathione Levels in Healthy Aging Adults, pp 720-725, Calvin A. Long, et al.
.
a-Lipoic Acid: Biological Effects and Clinical Implications, pp 177-183, Trent W. Nichols, Jr. M.D.
.
Glutathione: Systemic Protectant Against Oxidative and Free Radical Damage, pp 155-171, 173-176, Parris M. Kidd, Ph.D.
.
Importance And Regulation of Hepatic Glutathione, pp 251-266, Laurie D. Deleve, M.D., Ph.D. et al.
.
Probiotics in Human Medicine, pp 439-442, R. Fuller.
.
Aids
Wasting Syndrome as an Entero--Metabolic Disorder: The Gut Hypothesis,
pp 40-45, 47-43, Mitchell Kaminski, Jr., M.D., et al.
.
The Effects of L-Glutamine, N-Acetyl-D-Glucosamine, Gamma-Linolenic Acid and Gamma-Oryzanol on Intestinal Permeability.. =left> |
Primary Examiner: Carlson; Karen Cochrane
Assistant Examiner: Tu; Stephen
Attorney, Agent or Firm: Pitney, Hardin, Kipp & Szuch, LLP
Parent Case Text
This application claims the benefit of Provisional No. 60/083,661 filed
Apr. 30, 1998.
Claims
What is claimed is:
1. A composition of matter, which comprises in admixture;
N-acetylcysteine; N-acetyl-d-glucosamine vitamin C whereby the
amount of vitamin C is in an amount of at least 1000 mg. or greater to
facilitate the absorption of N-acetylcysteine across the cellular
membrane; and,
a pharmaceutically acceptable carrier for oral administration.
2. The composition of claim 1 further comprising one or more of
the following substances from the group consisting of alpha-lipoic
acid, sylmarin, quercitin, l-glutamine, a probiotic, and dietary
protein.
3. The composition of claim 1 further comprising alpha-lipoic acid, sylmarin, quercitin, l-glutamine, and a probiotic.
4. The composition of claim 3 further comprising dietary protein.
5. The composition of claim 1 further comprising flavorants.
6. The systematic administration of a pharmaceutically
effective amount of the composition according to claim 1 to a mammal
suffering from low glutathione levels, to stimulate the natural
production of glutathione in the biologically active
cells of the mammal.
7. The systemic administration of a pharmaceutically effective
amount of the composition according to claim 2 to a mammal suffering
from hepatitis, to stimulate the natural production of glutathione in
the biologically active cells of the
mammal.
8. The systemic administration of a pharmaceutically effective
amount of the composition according to claim 2 to a mammal suffering
from HIV, to stimulate the natural production of glutathione in the
biologically active cells of the mammal.
9. The systemic administration of a pharmaceutically effective
amount of the composition according to claim 2 to a mammal suffering
from allergies, to stimulate the natural production of glutathione in
the biologically active cells of the mammal
and to promote the shift of the T-cell balance from TH2 to TH1 and
decrease levels of IgE.
10. The systemic administration of a pharmaceutically
effective amount of the composition according to claim 2 to a mammal to
decrease serum cholesterol and triglycerides.
11. The systemic administration of a pharmaceutically
effective amount of the composition according to claim 2 to a mammal
suffering from one or more of the following illnesses from the group
consisting of chronic viral infections: HIV,
hepatitis C, chronic fatigue, immuno deficiency syndrome, immune
deficiencies, cancer, B-cell malignancies, including lymphomas, chronic
leukemia, myeloma Waldenstrom's and MGUS to improve immune defense
productions and thereby mitigate the progression
of the illnesses to thereby limit fatigue.
12. The systemic administration of a pharmaceutically
effective amount of the composition according to claim 2 to a mammal to
decrease fatigue.
13. The systemic administration of a pharmaceutically
effective amount of the composition according to claim 2 to a mammal to
decrease the biologic effects of stress.
14. The systemic administration of a pharmaceutically
effective amount of the composition according to claim 2 to a mammal to
increase energy and improve physical performance.
15. Administration according to claim 6 wherein a
pharmaceutically effective amount is 0.1 mg/kg to about 50 mg/kg of
body weight of the mammal, daily.
16. Administration according to claim 6 wherein a
pharmaceutically effective amount is 0.5 mg/kg to about 25 mg/kg of
body weight of the mammal, daily.
17. The systemic administration of a pharmaceutically
effective amount of the composition according to claim 2 to a mammal
suffering from low glutathione levels, to stimulate the natural
production of glutathione in the biologically active cells
of the mammal.
18. The systemic administration of a pharmaceutically
effective amount of the composition according to claim 3 to a mammal
suffering from low glutathione levels, to stimulate the natural
production of glutathione in the biologically active cells
of the mammal.
19. The systemic administration of a pharmaceutically
effective amount of the composition according to claim 1 to a mammal
suffering from low glutathione levels, to stimulate the natural
production of glutathione in the biologically active cells
of the mammal and reduce symptoms of diseases caused by excess
unneutralized free radicals.
20. The systemic administration of a pharmaceutically
effective amount of the composition according to claim 2 to a mammal
suffering from low glutathione levels, to stimulate the natural
production of glutathione in the biologically active cells
of the mammal and reduce symptoms of diseases caused by excess
unneutralized free radicals.
21. The systemic administration of a pharmaceutically
effective amount of the composition according to claim 3 to a mammal
suffering from low glutathione levels, to stimulate the natural
production of glutathione in the biologically active cells
of the mammal and reduce symptoms of diseases caused by excess
unneutralized free radicals.
22. The systemic administration of a pharmaceutically
effective amount of the composition according to claim 19, wherein the
disease is a member of the group consisting of pulmonary oxygen
toxicity, adult respiratory distress syndrome,
broncopulmonery dysplasia, sepis syndrome, Parkinson's disease,
encephalitis, endotoxemia, anoxia induced neuronal damage, ischemic
reperfusion injury, inflammatory diseases, systemic lupus
erythematosis, myocardial infarction, stroke, traumatic
hemorrhage, spinal cord trauma, Crohn's disease, rheumatoid arthritis,
diabetes, cataract formation, uvetis, emphysema, gastric ulcers, oxygen
toxicity, neoplasia, undesired cell apoptosis, radiation sickness.
23. The systemic administration of a pharmaceutically
effective amount of the composition according to claim 20, wherein the
disease is a member of the group consisting of pulmonary oxygen
toxicity, adult respiratory distress syndrome,
broncopulmonery dysplasia, sepis syndrome, Parkinson's disease,
encephalitis, endotoxemia, anoxia induced neuronal damage, ischemic
reperfusion injury, inflammatory diseases, systemic lupus
erythematosis, myocardial infarction, stroke, traumatic
hemorrhage, spinal cord trauma, Crohn's disease, rheumatoid arthritis,
diabetes, cataract formation, uvetis, emphysema, gastric ulcers, oxygen
toxicity, neoplasia, undesired cell apoptosis, radiation sickness.
24. The systemic administration of a pharmaceutically
effective amount of the composition according to claim 21, wherein the
disease is a member of the group consisting of pulmonary oxygen
toxicity, adult respiratory distress syndrome,
broncopulmonery dysplasia, sepis syndrome, Parkinson's disease,
encephalitis, endotoxemia, anoxia induced neuronal damage, ischemic
reperfusion injury, inflammatory diseases, systemic lupus
erythematosis, myocardial infarction, stroke, traumatic
hemorrhage, spinal cord trauma, Crohn's disease, rheumatoid arthritis,
diabetes, cataract formation, uvetis, emphysema, gastric ulcers, oxygen
toxicity, neoplasia, undesired cell apoptosis, radiation sickness.
25. The systemic administration of a pharmaceutically
effective amount of the composition according to claim 1 to a mammal,
to promote the natural production of glutathione in the biologically
active cells of the mammal which accelerates the
detoxification of ethanol and alleviates symptoms associated with
excessive ethanol imbibation.
26. The composition of claim 1 further comprising a probiotic,
said probiotic for promoting the breakdown and absorption of nutrients,
the elimination of toxins and to inhibit the growth of harmful bacteria
in the gastrointestinal tract, thereby
facilitating the absorption of N-acetylcysteine into the
gastrointestinal tract.
27. The probiotic of claim 1, wherein said probiotic is a
composition of "healthy bacteria" containing one or more of said
healthy bacteria selected from the group comprising bifidobacterium
longum, bifidobacterium infantis, lactobacillus
acidophilus, lactobacillus casei, lactobacillus rhamnosus,
saccharomyces boulardi, propionibacteria and enterococci.
28. The composition of claim 2 further comprising 1-glutamine,
said component being an essential dietary component to promote the
support of gastrointestinal growth and function, thus facilitating the
absorption of N-acetylcysteine through the
gastrointestinal tract.
29. The composition of claim 4 wherein N-acetyl-d-glucosamine
promotes the biosynthesis of mucosal glycoproteins which make up the
glycocalyx, a layer of the gut mucosa which acts to protect the tissue
of the gastrointestinal tract while
providing a selectively absorptive surface, thus facilitating the
absorption of N-acetylcysteine into the gastrointestinal tracts.
Description
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention provides a method of improving glutathione (GSH)
concentrations, both intra and extra-cellularly, in mammals, thereby
improving the cellular and humoral immune response. It comprises oral
administration of a therapeutically
effective amount of nutritional supplement which is composed of
critical and synergistic quantities of amino acids, peptides, and
bioflavanoids.
2. Brief Description of Related Art
Glutathione is a well-known tripeptide, which exists in two
basic forms. The antioxidant form or "reduced glutathione" tripeptide
is conventionally called "glutathione" and abbreviated as "GSH". The
oxidized form is a sulfur-sulfur linked
compound known as glutathione disulfide (GSSG).
Glutathione in its biologically active, reduced form (GSH) has the formula: ##STR1##
and is appropriately named
.gamma.-L-Glutamyl-L-cysteinylglycine. It is ubiquitous in animals,
plants, and microorganisms and being water soluble is found mainly in
the cell cytosol and other aqueous phases of the living system.
Glutathione
often attains millimolar levels inside living cells, which makes it one
of the most highly concentrated intracellular antioxidants.
Glutathione is homeostatically controlled, both inside the
animal cell and outside. Enzyme systems synthesize it, utilize it, and
regenerate it per the gamma-glutamyl cycle. (Meister A. Glutathione,
Ascorbate and Cellular Protection Cancer Res
(Suppl) 1994 (Apr 1); 54:1969S-1975S).
Glutathione is most concentrated in the mammal liver (10 mM),
where the P450 Phase II" enzymes require it to convert fat-soluble
substances into water-soluble GSH conjugates in order to facilitate
their excretion. While providing GSH for their
specific needs, the liver parenchymal cells export GSH to the outside,
where it serves as systemic source of-SH/reducing power.
Briefly, glutathione synthesis occurs within animal cells in
two closely linked enzymatically controlled reactions that utilize
Adenosine Triphosphate (ATP) and draw on nonessential amino acids as
substrates. First, cysteine and glutamate are
combined (by the enzyme gamma-glutamyl cysteinyl synthetase, with
availability of cysteine usually being the rate-limiting factor.
Cysteine is generated from the essential amino acid methionine, from
the degradation of dietary protein, or from turnover
of endogenous proteins. The buildup of GSH acts to feedback-inhibit
this enzyme, thereby helping to ensure homeostatic control over GSH
synthesis.
The second GSH synthesis reaction combines gamma-glutamylcysteine with glycine to generate GSH (catalyzed by GSH synthetase).
With regard to the essentiality of GSH for the survival of the
mammal, substantial information is available from studies on hereditary
GSH depletion in the human, and from experimental depletion and
repletion of GSH in animal models and cell
cultures, see for example: Meister A. Larsson A. Glutathione Synthetase
Deficiency and Other Disorders of the Gamma-Glutamyl Cycle; Scriver CR.
et al eds. The Metabolic and Molecular Bases of Inherited Disease
(Volume I). New York: McGraw-Hill:
1995:1461-1495 (Chapter 43); and Beutler E. Nutritional and Metabolic
Aspects of Glutathione, Annu Rev Nutr 1989;9:287-302.
Reduced GSH levels in mammalian cells are associated with a
wide variety of pathophysiologic states, including hepatic dysfunction,
malignancies, HIV infection, pulmonary disease, Parkinson's disease,
related immunologic illnesses and
physiological conditions; see for example the descriptions in Kidd,
Alternative Medicine Review, Vol. 2, No. 3, pages 156-176 (1997).
The consequences of sustained GSH depletion are fatal. As
cellular GSH is depleted, first individual cells die in those areas
most affected. Then zones of tissue damage begin to appear. Localized
free-radical damage spreads across the tissue
in an ever-widening, self-propagating wave.
An object of this invention is to promote gastrointestinal
absorption and intracellular uptake of components which will maximize
intracellular reduced glutathione production by a mammal including a
human.
SUMMARY OF THE INVENTION
The invention comprises a composition of matter, which comprises in admixture:
N-acetylcysteine;
vitamin C; and
a pharmaceutically acceptable systemic carrier for oral administration.
In preferred embodiments, the invention further comprises one or more of the following:
alpha-lipoic acid;
sylmarin;
quercitin;
l-glutamine;
N-acetyl-d-glucosamine;
a probiotic.
The invention also comprises systemic administration of the
composition of the invention to a mammal suffering from low glutathione
levels, to stimulate the natural production of glutathione in the
biological cells of the mammal.
The term "low glutathione levels" as used herein means a blood
glutathione level below about 440 .mu.g glutathione/10.sup.10
erythrocytes, determined by the colorimetric method of Beutler et al.,
Improved Method for the Determination of Blood
Glutathione, J. Lab. Clin. Med., 61;882-8(1963). Normal levels in
humans ranges from about 440 to 654 .mu.g/10.sup.10 erythrocytes.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS OF THE INVENTION
Recently, there have been many scientific papers published
discussing the direct relationship between decreased glutathione levels
and the progression of many chronic diseases. Glutathione functions as
an antioxidant, antitoxin and protector of
red blood cells, and is extremely important to the immune system. It
neutralizes free radicals minimizing the damage they cause and is
profoundly important for cellular homeostasis.
As with other cell types, the proliferation, growth, and
differentiation of immune cells is dependent on GSH. Both the T and the
B lymphocytes require adequate levels of intracellular GSH to
differentiate, and healthy humans with relatively low
lymphocyte GSH were found to have significantly lower CD4 counts;
Kinscherf R. Fischbach T. Mihm S. et al. Effect of glutathione
depletion and oral N-acetylcysteine treatment on CD4+ and CD8+ cells.
FASEB J 1994;8:448-451. Intracellular GSH is also
required for the T-cell proliferative response to mitogenic
stimulation, for the activation of cytotoxic T "killer" cells, and for
many specific T-cell functions, including DNA synthesis for cell
replication, as well as for the metabolism of
interleukin-2 which is important for the mitogenic response; Wu D.
Meydani S N, Sastre J. et al. In-vitro glutathione supplementation
enhances interleukin-2 production and mitogenic response of peripheral
blood mononuclear cells from young and old
subjects; J Nutr 1994;124:655-663.
In summary, it has been demonstrated that decreased levels of
glutathione may be a result of various types of prolonged stress,
increased free radical formation and hyperactivity of the immune
system. These factors in turn compromise the health
of mammalian cells. Despite the apparent importance of adequate
glutathione levels, little emphasis has heretofore been placed on
replacing depleted stores. Some glutathione comes from the diet but the
majority is made in the liver.
Studies have demonstrated that oral glutathione
supplementation is not well absorbed by many of the mammal's cells and
does not replenish losses inside cells where it is most needed; Witschi
A. Reddy S. Stofer B. et al. The systemic availability
of Oral Glutathione. Eur. J Clin. Pharmacol. 1992;43:667-669.
The sulfur-containing amino acid l-cysteine is the precursor
that most limits the cellular biosynthesis of GSH. When substituted
into the diet in place of the total protein allowance it was effective
in raising GSH levels (see Witschi et al.,
supra.)
Glutathione esters, synthetic compounds prepared by linking
the glycol end of GSH into ester bonds, have been the subject of much
research by Meister, Anderson, supra., as potential oral GSH delivery
compounds (see also U.S. Pat. No.
4,784,685). These esters do appear to be effective GSH delivery
vehicles, but have the disadvantage that they yield alcohols in vivo
when their ester bonds are broken, and their safety over the long term
has yet to be satisfactorily demonstrated.
We have discovered that to efficiently raise the level of
glutathione intracellularly, it is necessary to employ several
different mechanisms that work simultaneously. First, essential
elements needed by the body for the manufacture of
glutathione must be introduced. Second, gastro-intestinal health of the
mammal must be optimal to facilitate nutrient absorption. Third, the
liver function must be supported and protected as the liver is the
glutathione "manufacturing and storage
house". Lastly, recycling existing glutathione and enhancing enzymatic
reactions that promote glutathione synthesis are also important
functions which are advantageous to support.
The essential element needed by the mammalian cell to
manufacture glutathione (GSH) is N-acetylcysteine (NAC). It has proven
to be the most efficient dietary source of glutathione precursor. It is
a precursor and the main limiting factor
necessary for the body to manufacture reduced glutathione. NAC is well
absorbed by the intestine and readily converted by the mammalian cell
(particularly in the liver) to glutathione.
The absorption of N-acetylcysteine (NAC) and transport across
the cellular membrane is facilitated by the presence of ascorbic acid
(vitamin C). Vitamin C maximizes NAC transport across biological cell
membranes and helps to conserve existing
glutathione stores within the cell cytosol.
The utilization of N-acetylcysteine within the biological cell
to synthesize glutathione is improved by the presence of alpha lipoic
acid. Alpha lipoic acid increases the cell's ability to make
glutathione. It enables the key enzyme required
for glutathione synthesis to work under optimum conditions and induces
a substantial increase in intracellular reduced glutathione; see Busse
E. Zimmer G. Schopohl B, et al. Influence of alpha-lipoic acid on
intracellular glutathione in vitro and in
vivo; Arzneimittel-Forschung 1992;42:829-831; and Han D. Handelman G.
Marcocci, et al. Lipoic Acid Increases de novo Synthesis of Cellular
Glutathione by Improving Cystine Utilization, Biofactors
1997;6:321-338. 1995:29: 1263-73.
As mentioned above, support of liver function in the mammal
being treated for low glutathione levels is advantageous. For this
purpose, there may be orally administered to the mammal the following:
A. Sylimarin serves to improve and restore liver function. It
quenches free radicals, reduces potential toxicity, and stimulates
protein synthesis necessary to create new liver cells. Also known as
"silibin", "silybin" or "silybinin", Silymarin
is a generic term for extract from the mature fruits of Silybum
marianum (sometimes Carduus marianus), commonly known as milk thistle;
see Madaus AG publication: Legalon. Koln, Germany, 1989 and Valenzuela
A, et al. Silymarin Protection Against Hepatic
Lipin Peroxidation Induced by Acute Ethanol Intoxication in Rats,
Biochemical Pharmacology, 1985:34(12):2209-2212. Sylimarin is available
under the trade name Legalon.RTM., from Madaus AG, (Jarrow Formulas,
Inc.; Madaus, 1989).
B. Quercetin
[2-(3,4-Dihydroxyphenyl)-3,5,7-trihydroxy-4H-1-benzopyran-4-one] is
used for its ability to eliminate toxic compounds found in the liver.
It has anti-hepatotoxic, antiviral, anti-inflammatory and antibacterial
properties. It may be
synthesized by the method of Shakhova et al., Zh. Obsheh. Khim., 32,
390 (1962).
Advantageously, the following nutritionals are also employed in the method of the invention.
L-glutamine is an essential dietary component for the support
of gastrointestinal growth and function and it is utilized as fuel in
the small intestines. It is used by the intestinal tract in large
amounts for energy during periods of
physiological stress. It has been shown to preserve liver glutathione
after lethal hepatic injury and nourish tissues in the GI tract, liver
and immune system, see for example; Souba, W.W., et al. The Role of
Glutamine in Maintaining a Healthy Gut and
Supporting the Metabolic Response to Injury and Infection. J. Of
Surgical Res., 990:48(4):83-91.
N-acetyl-d-glucosamine (NAG) is a key precursor in the
biosynthesis of mucosal glycoproteins that form glycocalyx. The
glycalyx is the most superficial, highly viscous layer of the gut
mucosa that comes in contact with intestinal contents. The
glycoprotein layer acts to protect the underlying tissues from exposure
to enzymes, acid and bacterial assault while providing a selectively
absorptive surface, Wilmore, D. W., et al, The gut: a Central Organ
After Surgical Stress; Surgery 1988: 104,
(5):917-23.
Probiotics or "healthy bacteria" are necessary as they
breakdown nutrients, eliminate toxins and inhibit harmful bacteria that
enter mammalian systems through the GI tract. The term "Probiotic" is
defined herein as "A live microbial food
supplement which beneficially affects the host mammal by improving its
microbial balance". Representative of healthy bacteria are isolates of
bifidobacteria, lactobacilli, such as Lactobacillus acidophilus and
Lactobacillus casei, propionibacteria, and
enterococci. Lactobacilli are preferred in the composition and method
of the invention (see Perdigon, G. et al., Immunology 63:17-23 (1988)).
More preferably Lactobacillus rhamnosus, Lactobacillus casei,
Bifidobacterium longum, Bifidobacterium
infantis, Lactobacillus acidophillus, and Saccharomyces boulardi are
used.
Finally, a source of dietary protein is preferred and
advantageous to supplement the nutritional needs of the mammal. We have
found that the compositions of the invention and the method herein
described are optimized by inclusion of a
biologically active whey protein composition comprising an undenatured
whey protein concentrate obtained from raw mammalian milk. This
concentrate contains substantially all of the heat labile whey protein
found in the raw milk. Representative of
concentrate which are commercially available include Promod.TM.,
available from Ross Laboratories, Division of Abbott Laboratories,
Chicago, Ill. Concentrates may also be prepared by the method described
in U.S. Pat. No. 5,290,571, incorporated herein
by reference thereto. The undenatured whey protein concentrates also
contain a rich variety of immunoglobulins which boast the immunologic
response of the mammal treated with the concentrates; see for example
U.S. Pat. No. 5,456,924 which is
incorporated herein by reference thereto.
A high protein, low fat whey has immuno-supportive properties.
It is rich in naturally active immunoglobulins, essential amino acids
and other important nutrients critical for proper nutrient utilization
within the gut.
We have discovered that the ingredients described above work
synergistically to provide the necessary nutrients required for
glutathione production while supporting the mammal's ability to produce
and preserve existing stores of GSH. The effect
of the admixture of ingredients is far more significant than the
individual ingredients alone.
This invention also relates also to pharmaceutical dosage unit
forms for systemic administration (oral, topical administration) which
are useful in treating mammals, including humans. The term "dosage unit
form" as used in this specification and
in the claims refers to physically discrete units suitable as unitary
dosage for mammalian subjects, each unit containing a predetermined
quantity of the essential active ingredient; calculated to produce the
desired effect in combination with the
required pharmaceutical means which adapt said ingredient for systemic
administration. Examples of dosage unit forms in accordance with this
invention are tablets, capsules, orally administered liquid
preparations in liquid vehicles, suppositories, and
dry preparations for the extemporaneous preparation of preparations in
a liquid vehicle. Solid diluents or carriers for the solid oral
pharmaceutical dosage unit forms are selected from the group consisting
of lipids, carbohydrates, proteins and mineral
solids, for example, starch, sucrose, kaolin, dicalcium phosphate,
gelatin, acacia, corn syrup, corn starch, talc and the like. Capsules,
both hard and soft, are formulated with conventional diluents and
excipients, for example, edible oils, talc,
calcium carbonate, calcium stearate, magnesium stearate and the like.
Liquid pharmaceutical preparations for oral administration may be
prepared in water or aqueous solutions which advantageously contain
suspending agents, such as for example, sodium
carboxymethylcellulose, methylcellulose, acacia, polyvinyl pyrrolidone,
polyvinyl alcohol and the like.
Such preparations must be stable under the conditions of
manufacture and storage, and ordinarily contain in addition to the
basic solvent or suspending liquid, preservatives in the nature of
bactericidal and fungicidal agents, for example,
parabens, chlorobutanol, benzyl alcohol, phenol, thimerosal, and the
like. In many cases it is preferable to include isotonic agents, for
example, sugars or sodium chloride. Carriers and vehicles include
vegetable oils, water, ethanol, and polyols, for
example, glycerol, propylene glycol, liquid polyethylene glycol, and
the like.
The pharmaceutical dosage unit forms are prepared in
accordance with the preceding general description to provide an
effective amount of the essential active ingredient per dosage unit
form in admixture with the means for adaptation to systemic
administration. In general, the unit dose form will contain 3 to 73
percent by weight of the essential active ingredient.
It will be appreciated that the exact dosage of the essential
active ingredient constituting an effective amount for treatment of a
mammal according to the method of the invention will vary greatly
depending on the specific nature of the clinical
condition being treated, severity of the condition, species of mammal,
age, weight and condition of the mammal, mode of administration of the
dosage form and the specific formulation being administered. The exact
dose required for a given situation may
be determined by administration of a trial dose and observation of the
clinical response. In general, an effective amount to be administered
will be within a range of from about 0.1 mg. per kg. to about 50 mg.
per kg. of body weight of the
recipient, daily. Preferably 0.5 mg./kg. to about 25 mg./kg. daily is
provided. In most instances, a single month of administration will
effect a noticeable response and bring about the result desired. In
cases such as the treatment of immunological
conditions however, it may be desirable to repeat the administrations
several times daily over longer periods of time.
The following examples and preparations describe the manner
and process of making and using the invention and set forth the best
mode contemplated by the inventor of carrying out the invention but are
not to be construed as limiting.
EXAMPLE 1
A mixture of the following ingredients is prepared by hand mixing:
Ingredient Quantity N-acetylcysteine 1,000 to 20,000 mg
vitamin C 5,000 to 50,000 mg alpha-lipoic acid 100 to 2,500 mg sylmarin
100 to 2,500 mg Quercetin 100 to 2,500 mg l-glutamine 500 to 2,000 mg
N-acetyl-d-glucosamine 500 to 2,000 mg whey protein concentrate 1,000
to 20,000 mg Lactobacillus acidophilus Twenty Million to One Billion
CFU; Schiff Products, Inc., Salt Lake City, Utah. orange essence flavor
Adjust to taste
The mixture which constitutes the essential active ingredient
of a preferred embodiment of the invention, together with a flavorant
may be compounded into wafers, tablets or capsules containing 750 to
14,000 mg of active ingredient. In an
uncompounded form, the powder dry mixture may be orally administered to
a human (one teaspoonful, once or twice daily) as a dietary supplement
or as recommended by a health care professional. Alternatively, the dry
powder may be mixed with juice, water
or food to facilitate administration.
EXAMPLE 2
Three dosage units in powder form, each containing 500 mg of
essential active ingredient (e.g an amount of the mixture of Example 1,
supra. were prepared from the following ingredients:
essential active ingredient 1500 g starch (Rx-1500) 300 g
magnesium stearate, USP 39 g colloidal silicic acid 19.5 g Avicel .RTM.
pH 102. q.s. to 3900 g
The essential active ingredient was ground through a 0.25 mm
sieve opening screen. The powdered active ingredient, with 50% of the
total amount of magnesium stearate be used, colloidal silicic acid and
Avicel.RTM. pH 10.2 were passed through a
40 mesh sieve, mixed for 20 minutes and then slugged. The slugs were
broken down by forcing through a screen No. 11, and mixed with the
remaining magnesium stearate.
One dosage given orally 1-4 times a day is useful in the
relief of immuno-deficiency in adult humans provoked by infective
disease, or other etiological causes.
EXAMPLE 3
Three thousand dosage units for oral use, each containing 750
mg of the essential active ingredient, were prepared from the following
ingredients:
essential active ingredient 750 g colloidal silicic acid 30 g
magnesium stearate USP 30 g microcrystalline cellulose 150 g lactose 90
g
In accordance with the active ingredient potency, the amount
of lactose was adjusted to achieve a weight of 900 mg for each dosage
unit. The ingredients were passed through a 40 mesh sieve and mixed for
30 minutes. The powder may be mixed into
a drink or inserted into hard gelatin capsules No. 0 and filled using
Zanazi, model RV-59 equipment. The capsules should be preserved in
airtight, light-resistant containers.
When administered to a human adult suffering from low levels
of glutathione (GSH) 1 to 4 dosage units daily, the level is adjusted
upward to a normal range.
EXAMPLE 4
A mixture of the following ingredients is formed into a powdered dosage form in the following proportion:
Ingredient Quantity Vitamin C (ascorbate) 1000 mg N-acetyle
cysteine 1500 mg L-Glutamine 3000 mg N-acetyle d-glucosamine 500 mg
Alpha Lipoic acid (ALA) 75 mg Quercetin 75 mg Sylimarine 100 mg Whey
protein 500 mg Conjugated linoteic acid
(CLA) 500 mg Orange flavor 380 mg Rice syrup 1516 mg Malic acid 7.8 mg
Citric acid 7.8 mg Stevia 455 mg GI Balance (Probiotic) 300 mg
Our studies have shown that the administration of the above
dosage unit (one rounded teaspoon) mixed into a liquid 1-4 times
(preferably 2 times) a day is useful in the relief of immuno-deficiency
in adult humans provoked by infective disease, or
other etiological causes. For example, the inventive composition can be
used effectively to improve heptatic function e.g. decreased
inflamation (ALT) in patients with chronic hepatitis C and patients who
are receiving protease inhibitors as part of
HAART therapy for HIV. Both groups demonstrated an increase in intra
lymphocyte GSH levels after the administration of the inventive
composition.
Our studies have shown systemic administration of the
composition results in an improvement in T lymphocyte function which
correlates directly with an increased intra lymphocyte GSH. In
addition, our data demonstrates that the inventive
composition and method shifts the T-cell balance from TH2 (allergy
producing) to TH1 (viral/tumor killing) and the increases intra
lymphocyte GSH correlate directly with decreased levels of IgE the
immunoglobulin associated with allergies. Further
studies have revealed the following:
Systemic administration of the composition increases natural
killer cell function which is considered a primitive first line of
cellular immune defense.
Systemic administration of the composition decreases serum
cholesterol and triglycerides of between 10 and 20% in patients with a
variety of hyperlipidemias and a decrease in myalgias associated with
illness and exercise and improved muscle
recovery after exercise.
Systemic administration of the composition decreases fatigue
in patients suffering from a variety of illnesses including but not
limited to chronic viral infections, HIV, hepatitis C, chronic fatigue,
immuno deficiency syndrome, immune
deficiencies, cancer, B-cell malignancies, including lymphomas, chronic
leukemia, myeloma Waldenstrom's and MGUS. This makes the composition
function as both a pharmaceutical and a therapeutic substance for
patients suffering from the debilitating
conditions.
Initial studies have shown that the systemic administration of
the inventive composition also increases energy in people without
illness who are exposed to increased stress.
As such, the combination formulated will improve hepatic
function in conditions associated with chronic viral infections, as
well as any condition associated with increased hepatic work or stress.
Thus by the present invention its advantages will be realized
and although preferred embodiments have been disclosed and described in
detail herein, its scope should not be limited thereby rather its scope
should be determined by that of the
appended claims.
* * * * *
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"Shortly after I started taking MaxGXL, I started experiencing overall increased energy and quicker recovery after training 5 to 7 hours a day. I can now see myself being an extreme endurance athlete for years to come thanks to MaxGXL."
Video Interview With Dr. Keller & Health Professionals Section