U.S. patent application number 15/528990 was filed with the patent office on 2017-11-16 for amino acid compositions for the treatment of symptoms of disease.
This patent application is currently assigned to ENTRINSIC HEALTH SOLUTIONS, LLC. The applicant listed for this patent is ENTRINSIC HEALTH SOLUTIONS, LLC. Invention is credited to Daniel B. DENNISON, Stephen J. GATTO, Sadasivan VIDYASAGAR.
Application Number | 20170326088 15/528990 |
Document ID | / |
Family ID | 56074902 |
Filed Date | 2017-11-16 |
United States Patent
Application |
20170326088 |
Kind Code |
A1 |
VIDYASAGAR; Sadasivan ; et
al. |
November 16, 2017 |
AMINO ACID COMPOSITIONS FOR THE TREATMENT OF SYMPTOMS OF
DISEASE
Abstract
The subject invention provides therapeutic compositions, and
uses thereof for the treatment or amelioration of symptoms of a
disease selected from the group consisting of: Ebola virus
infection, HIV infection, ataxia, environmental enteropathy,
cancer, hangover, inflammatory disease, and porcine epidemic
diarrhea. In preferred embodiments, the composition includes a
combination of one or more amino acids selected from the group
comprising lysine, aspartic acid, glycine, isoleucine, threonine,
tyrosine, valine, tryptophan, asparagine and/or serine.
Inventors: |
VIDYASAGAR; Sadasivan;
(Gainesville, FL) ; GATTO; Stephen J.; (Norwood,
MA) ; DENNISON; Daniel B.; (Tallahassee, FL) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
ENTRINSIC HEALTH SOLUTIONS, LLC |
Norwood |
MA |
US |
|
|
Assignee: |
ENTRINSIC HEALTH SOLUTIONS,
LLC
Norwood
MA
|
Family ID: |
56074902 |
Appl. No.: |
15/528990 |
Filed: |
November 19, 2015 |
PCT Filed: |
November 19, 2015 |
PCT NO: |
PCT/US15/61462 |
371 Date: |
May 23, 2017 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
62083698 |
Nov 24, 2014 |
|
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|
62138051 |
Mar 25, 2015 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61P 29/00 20180101;
A61K 31/405 20130101; A61P 35/00 20180101; A61K 31/198 20130101;
A61P 3/12 20180101; A61P 1/12 20180101; A61P 31/18 20180101; A61K
31/00 20130101; A61K 31/197 20130101; A61P 1/00 20180101; A61P
31/12 20180101; A61K 31/197 20130101; A61K 2300/00 20130101; A61K
31/198 20130101; A61K 2300/00 20130101; A61K 31/405 20130101; A61K
2300/00 20130101 |
International
Class: |
A61K 31/198 20060101
A61K031/198; A61K 31/197 20060101 A61K031/197; A61K 31/405 20060101
A61K031/405 |
Claims
1. A method of treating the symptoms of a disease selected from the
group consisting of: Ebola virus infection, HIV infection, ataxia,
environmental enteropathy, cancer, hangover, inflammatory disease,
and porcine epidemic diarrhea, comprising administering to the
subject, a composition comprising one or more ingredients selected
from lysine, glycine, threonine, tryptophan, valine, treosine,
serine, and tyrosine, as free amino acids or a combination thereof;
wherein the composition does not comprise free amino acid glutamine
or a glutamine-containing dipeptide; wherein the composition does
not comprise glucose or, if glucose is present, the concentration
of glucose is less than 1 g/l and wherein the composition does not
comprises methionine or a methionine-containing dipeptide.
2. The method according to claim 1, wherein the composition further
comprises water.
3. The method according to claim 1, wherein the composition further
comprises aspartic acid, isoleucine, and/or asparagine.
4. The method according to claim 1, wherein the composition
comprises threonine, tyrosine, serine, valine and tryptophan.
5. A method for treating a subject having HIV infection comprising
administering to the subject a composition comprising one or more
ingredients selected from lysine, glycine, threonine, tryptophan,
valine, treosine, serine, and tyrosine, as free amino acids or a
combination thereof; wherein the composition does not comprise free
amino acid glutamine or a glutamine-containing dipeptide; wherein
the composition does not comprise glucose or, if glucose is
present, the concentration of glucose is less than 1 g/l; and
wherein the composition does not comprises methionine or a
methionine-containing dipeptide.
6. The method according to claim 5, wherein the composition does
not comprise one or more ingredients selected from glucose,
glutamine, glutamine-containing dipeptides, and methionine, or, if
one or more of these ingredients is present, glucose is present at
a concentration of less than I g/l, glutamine and/or a
glutamine-containing dipeptide is present at a concentration of
less than 300 mg/l, and methionine is present at a concentration of
less than 300 mg/l.
7. The method according to claim 5, wherein the composition further
comprises water.
8. The method according to claim 5, wherein the composition
comprises threonine, tyrosine, serine, valine and tryptophan.
9. A method for treating a subject having ataxia symptoms
comprising administering to the subject a composition comprising at
least one amino acid that retains or acquires improved absorptive
capacity following the impairment of small intestine epithelial
cells, the amino acids selected from the group consisting of
lysine, glycine, serine, threonine, tryptophan, valine, and
tyrosine, as free amino acids; one or more electrolyte selected
from among the group consisting of sodium, potassium, magnesium and
calcium and wherein the composition does not comprise free amino
acid glutamine or a glutamine-containing dipeptide, or, if free
amino acid glutamine and/or a glutamine-containing dipeptide is
present, the total concentration of the free amino acid glutamine
and the glutamine-containing dipeptide is less than 300 mg/l and
wherein the composition does not comprise glucose or, if glucose is
present, the concentration of glucose is less than 1 g/l.
10. The method of claim 9 wherein the composition comprises
threonine, tyrosine, serine, valine, and tryptophan as free amino
acids.
11. The method of claim 9 wherein the composition further comprises
aspartic acid, isoleucine, and/or asparagine.
12. A method for treating a subject having reduced Villus height
comprising administering to the subject a composition comprising an
amino acid that retains or acquires improved absorptive capacity
following the impairment of small intestine epithelial cells, the
amino acids selected from the group consisting of lysine, glycine,
threonine, tryptophan, serine, valine, and tyrosine, as free amino
acids; and wherein the composition does not comprise free amino
acid glutamine or a glutamine-containing dipeptide, or, if free
amino acid glutamine and/or a glutamine-containing dipeptide is
present, the total concentration of the free amino acid glutamine
and the glutamine-containing dipeptide is less than 300 mg/l and
wherein the composition does not comprise glucose or, if glucose is
present, the concentration of glucose is less than 1 g/l.
13. The method of claim 12 wherein the composition comprises
threonine, tyrosine, serine, valine, and tryptophan as free amino
acids.
14. The method of claim 12 wherein the composition further
comprises aspartic acid, isoleucine, and/or asparagine.
15. A method for the treatment of environmental enteropathy
comprising administering to the subject a composition comprising an
amino acid selected from the group consisting of lysine, glycine,
threonine, serine, tryptophan, valine, and tyrosine, as free amino
acids; and wherein the composition does not comprise free amino
acid glutamine or a glutamine-containing dipeptide, or, if free
amino acid glutamine and/or a glutamine-containing dipeptide is
present, the total concentration of the free amino acid glutamine
and the glutamine-containing dipeptide is less than 300 mg/l and
wherein the composition does not comprise glucose or, if glucose is
present, the concentration of glucose is less than 1 g/l.
16. The method of claim 15 wherein the composition comprises
threonine, tyrosine, serine, valine, and tryptophan as free amino
acids.
17. The method of claim 15 wherein the composition further
comprises aspartic acid, isoleucine, and/or asparagine.
18. A method for the treatment of weight loss caused by cancer
comprising administering to the subject a composition comprising an
amino acid selected from the group consisting of lysine, glycine,
threonine, serine, tryptophan, valine, and tyrosine, as free amino
acids; and wherein the composition does not comprise free amino
acid glutamine or a glutamine-containing dipeptide, or, if free
amino acid glutamine and/or a glutamine-containing dipeptide is
present, the total concentration of the free amino acid glutamine
and the glutamine-containing dipeptide is less than 300 mg/l and
wherein the composition does not comprise glucose or, if glucose is
present, the concentration of glucose is less than 1 g/l.
19. The method of claim 15 wherein the composition comprises
threonine, tyrosine, serine, valine, and tryptophan as free amino
acids.
20. The method of claim 15 wherein the composition further
comprises aspartic acid, isoleucine, and/or asparagine.
21. A method for treating a subject having a hangover comprising
administering to the subject, a composition comprising one or more
ingredients selected from lysine, glycine, threonine, tryptophan,
valine, treosine, serine, and tyrosine, as free amino acids or a
combination thereof; wherein the composition does not comprise free
amino acid glutamine or a glutamine-containing dipeptide; wherein
the composition does not comprise glucose or, if glucose is
present, the concentration of glucose is less than 1 g/l; and
wherein the composition does not comprises methionine or a
methionine-containing dipeptide.
22. The method according to claim 1, wherein the composition
further comprises water.
23. The method according to claim 1, wherein the composition
further comprises aspartic acid, isoleucine, and/or asparagine.
24. The method according to claim 1, wherein the composition
comprises threonine, tyrosine, serine, valine and tryptophan.
25. A method for treating a subject having inflammation comprising
administering to the subject a composition comprising one or more
ingredients selected from lysine, glycine, threonine, tryptophan,
valine, treosine, serine, and tyrosine, as free amino acids or a
combination thereof; wherein the composition does not comprise free
amino acid glutamine or a glutamine-containing dipeptide; wherein
the composition does not comprise glucose or, if glucose is
present, the concentration of glucose is less than 1 g/l; and
wherein the composition does not comprises methionine or a
methionine-containing dipeptide.
26. The method according to claim 5, wherein the composition does
not comprise one or more ingredients selected from glucose,
glutamine, glutamine-containing dipeptides, and methionine, or, if
one or more of these ingredients is present, glucose is present at
a concentration of less than I g/l, glutamine and/or a
glutamine-containing dipeptide is present at a concentration of
less than 300 mg/l, and methionine is present at a concentration of
less than 300 mg/l.
27. The method according to claim 5, wherein the composition
further comprises water.
28. The method according to claim 5, wherein the composition
comprises threonine, tyrosine, serine, valine and tryptophan.
29. A method for treating a subject having a loss of electrolytes
comprising administering to the subject a composition comprising at
least one amino acid that retains or acquires improved absorptive
capacity following the impairment of small intestine epithelial
cells, the amino acids selected from the group consisting of
lysine, glycine, serine, threonine, tryptophan, valine, and
tyrosine, as free amino acids; one or more electrolyte selected
from among the group consisting of sodium, potassium, magnesium and
calcium and wherein the composition does not comprise free amino
acid glutamine or a glutamine-containing dipeptide, or, if free
amino acid glutamine and/or a glutamine-containing dipeptide is
present, the total concentration of the free amino acid glutamine
and the glutamine-containing dipeptide is less than 300 mg/l and
wherein the composition does not comprise glucose or, if glucose is
present, the concentration of glucose is less than 1 g/l.
30. The method of claim 9 wherein the composition comprises
threonine, tyrosine, serine, valine, and tryptophan as free amino
acids.
31. The method of claim 9 wherein the composition further comprises
aspartic acid, isoleucine, and/or asparagine.
32. A method for treating a subject having dehydration comprising
administering to the subject a composition comprising an amino acid
that retains or acquires improved absorptive capacity following the
impairment of small intestine epithelial cells, the amino acids
selected from the group consisting of lysine, glycine, threonine,
tryptophan, serine, valine, and tyrosine, as free amino acids; and
wherein the composition does not comprise free amino acid glutamine
or a glutamine-containing dipeptide, or, if free amino acid
glutamine and/or a glutamine-containing dipeptide is present, the
total concentration of the free amino acid glutamine and the
glutamine-containing dipeptide is less than 300 mg/l and wherein
the composition does not comprise glucose or, if glucose is
present, the concentration of glucose is less than 1 g/l.
33. The method of claim 12 wherein the composition comprises
threonine, tyrosine, serine, valine, and tryptophan as free amino
acids.
34. The method of claim 12 wherein the composition further
comprises aspartic acid, isoleucine, and/or asparagine.
35. A method for enhancing nutrient delivery to a subject
comprising administering to the subject a composition comprising an
amino acid selected from the group consisting of lysine, glycine,
threonine, serine, tryptophan, valine, and tyrosine, as free amino
acids; and wherein the composition does not comprise free amino
acid glutamine or a glutamine-containing dipeptide, or, if free
amino acid glutamine and/or a glutamine-containing dipeptide is
present, the total concentration of the free amino acid glutamine
and the glutamine-containing dipeptide is less than 300 mg/l and
wherein the composition does not comprise glucose or, if glucose is
present, the concentration of glucose is less than 1 g/l.
36. The method of claim 15 wherein the composition comprises
threonine, tyrosine, serine, valine, and tryptophan as free amino
acids.
37. The method of claim 15 wherein the composition further
comprises aspartic acid, isoleucine, and/or asparagine.
38. A method for treating a subject having porcine epidemic
diarrhea comprising administering to the subject a composition
comprising an amino acid selected from the group consisting of
lysine, glycine, threonine, valine, and tyrosine, as free amino
acids; and wherein the composition does not comprise free amino
acid glutamine or a glutamine-containing dipeptide, or, if free
amino acid glutamine and/or a glutamine-containing dipeptide is
present, the total concentration of the free amino acid glutamine
and the glutamine-containing dipeptide is less than 300 mg/l and
wherein the composition does not comprise glucose or, if glucose is
present, the concentration of glucose is less than 1 g/l.
39. The method of claim 18 wherein the composition comprises
threonine, tyrosine, serine, valine, and tryptophan as free amino
acids.
40. The method of claim 18 wherein the composition further
comprises aspartic acid, isoleucine, and/or asparagine.
Description
RELATED APPLICATIONS
[0001] This application is related to application Ser. No.
13/245,430, titled MATERIALS AND METHODS FOR IMPROVING
GASTROINTESTINAL FUNCTION, filed on Sep. 26, 2011, now U.S. Pat.
No. 8,993,522, and claims priority to Provisional Application
62/083,698 titled MATERIALS AND METHODS FOR THE TREATMENT OF
INFLAMMATION, AND ALCOHOL TOXICITY, filed on Nov. 24, 2014, and
Provisional Application 62/138,051 titled MATERIALS AND METHODS FOR
THE TREATMENT OF EBOLA VIRUS SYMPTOMS, filed on Mar. 25, 2015, all
of which are incorporated herein by this reference.
BACKGROUND OF INVENTION
[0002] Hangover. Hangover symptoms typically begin when a person's
blood alcohol drops significantly and is at or near zero. The
symptoms are usually in full effect the morning after a night of
heavy drinking. Depending on what and how much was consumed, the
symptoms may include: fatigue and weakness, thirst, headaches and
muscle aches, nausea, vomiting or stomach pain, poor or decreased
sleep, increased sensitivity to light and sound, dizziness or a
sense of the room spinning, shakiness, decreased ability to
concentrate, mood disturbances, such as depression, anxiety and
irritability, and rapid heartbeat.
[0003] Symptoms of hangovers can be attributed to a buildup of
acetaldehyde in the body. Some common hangover symptoms such as
fatigue, stomach irritation and a general sense of illness can be
further attributed to glutamine rebound. Consumption of alcohol
inhibits glutamine. When the drinker stops drinking, the body
produces more glutamine than it needs. Increased glutamine levels
stimulate the brain leading to a loss of sleep and in turn leading
to the fatigue associated with a hangover. Increased amounts of
glutamine may also cause tremors, anxiety, restlessness and
increased blood pressure. Alcohol consumption can damage the
intestinal epithelial cells. In addition, alcohol increases
paracellular permeability (leaky gut).
[0004] Because alcohol is absorbed directly through the stomach,
the cells that line the organ become irritated. The stomach's
irritation may also be a factor in some of the other unpleasant
symptoms of a hangover, such as diarrhea and lack of appetite.
Additionally, alcohol is a diuretic and one of the consequences of
heavy alcohol consumption is dehydration. Cysteine breaks down the
hangover-causing toxin acetaldehyde in the liver's easily depleted
glutathione. Replenishment of potassium lost to alcohol's diuretic
effect is also desirable.
[0005] Traditional hangover remedies are often ineffective, and
some of them may actually exacerbate the symptoms.
[0006] Ebola Symptoms. Ebola hemorrhagic fever (Ebola) is a viral
disease caused by Ebola virus. The disease results in nonspecific
symptoms early and usually causes internal and external bleeding as
the disease progresses. Ebola has a very high mortality rate
ranging from about 50% to 100% of humans infected. Early symptoms
of Ebola are nonspecific and include fever, headache, weakness,
vomiting, diarrhea, stomach discomfort, decreased appetite, and
joint and muscle discomfort. As the disease progresses, patients
may develop other symptoms and signs such as a rash, eye redness,
hiccups, sore throat, cough, chest pain, bleeding both inside and
outside the body (for example, mucosal surfaces, eyes), and
difficulty breathing and swallowing. Ebola symptoms usually appear
from about two to 21 days after exposure. It is unclear why some
patients can survive and others die from this disease, but patients
who die usually have a poor immune response to the virus.
[0007] HIV symptoms. Human Immunodeficiency Virus (HIV) is a virus
that attacks the immune system resulting in a variety of
infections. HIV can also cause a variety of symptoms and some of
these symptoms, like diarrhea, may even occur as a result of
treatment. Diarrhea is one of the most common complications of HIV.
It ranges in severity from occasional loose stools to ongoing
(chronic) cases. Identifying the exact cause of diarrhea in HIV
infection can help you get the right treatments for long-term
management and better quality of life. HIV itself may be a pathogen
that causes diarrhea.
[0008] Ataxia Symptoms. Ataxia is a neurological sign consisting of
lack of voluntary coordination of muscle movements. Ataxia is a
nonspecific clinical manifestation implying dysfunction of the
parts of the nervous system that coordinate movement, such as the
cerebellum. Several possible causes exist for these patterns of
neurological dysfunction. Dystaxia is a mild degree of ataxia.
[0009] Villus Height and Crypt Number. Intestinal villi are small
projections that protrude from the epithelial lining of the
intestinal wall. Each villus is approximately 0.5-1.6 mm in length,
and comprises a plurality of microvilli projecting from the
enterocytes of its epithelium. Each of these microvilli is much
smaller than a single villus. The configuration of the villi
increase the internal surface area of the intestinal walls which
allows for increased absorption. Increased absorptive area is
useful because digested nutrients (including monosaccharide and
amino acids) pass into the semipermeable villi through diffusion,
which is effective only at short distances. In other words,
increased surface area (in contact with the fluid in the lumen)
decreases the average distance travelled by nutrient molecules, so
effectiveness of diffusion increases. The villi are connected to
the blood vessels so the circulating blood then carries these
nutrients away. Villus capillaries collect amino acids and simple
sugars taken up by the villi into the blood stream. Villus lacteals
(lymph capillary) collect absorbed chylomicrons, which are
lipoproteins composed of triglycerides, cholesterol and amphipathic
proteins, and are taken to the rest of the body through the lymph
fluid.
[0010] Crypts are tubular invaginations of the epithelium around
the villi, lined largely with younger epithelial cells which are
involved primarily in secretion. At the base of the crypts are stem
cells, which continually divide and provide the source of all the
epithelial cells in the crypts and on the villi. Intestinal crypts
are found in the epithelia of the small intestine, namely the
duodenum, jejunum and ileum.
[0011] The height of villi and the depth of crypt are considered as
the indicators of intestinal functions. Villus height and crypt
depth are direct representations of the intestinal environment and
may be used as indicators of intestinal health.
[0012] Environmental Enteropathy. Environmental enteropathy is a
condition believed to be due to frequent intestinal infections.
There are often minimal acute symptoms. The condition usually
presents itself with chronic problems with absorbing nutrients
which may result in malnutrition in children and presents with
diarrhea. Environmental enteropathy results in a number of changes
in the intestines including: reduced Villus height, larger and
fewer crypts, increased permeability, and inflammatory cell
build-up within the intestines. These changes result in poor
absorption of food, vitamins and minerals--or "modest
malabsorption.
[0013] Cancer Induced Weight Loss. Weight loss is common among
people with cancer and is often the first noticeable sign of the
disease. a substantial percentage of people with cancer report
unexplained weight loss at the time of diagnosis, and the majority
of people with advanced cancer experience weight loss or wasting,
which is the combination of weight loss and muscle mass loss.
Weight loss and muscle wasting also often come with fatigue,
weakness, loss of energy, and an inability to perform everyday
tasks.
[0014] Norovirus Symptoms. Norovirus is a highly contagious virus.
People contract the virus by ingesting material contaminated with
small amounts of infected feces or fluids. Food and water may be
contaminated during processing or handling. Norovirus causes
inflammation of the stomach or intestines or both and is the most
common cause of gastroenteritis in the United States. The most
common symptoms are .cndot.diarrhea, vomiting, nausea and stomach
pain.
[0015] Food Poisoning Symptoms. Food poisoning refers to any
illness resulting from the consumption of contaminated food,
pathogenic bacteria, viruses, or parasites that contaminate food,
as well as chemical or natural toxins such as poisonous mushrooms.
More than 250 different diseases can cause food poisoning. Some of
the most common diseases are infections caused by bacteria, such as
Campylobacter, Salmonella, Shigella, E. coli O157:H7, Listeria,
Botulism, and Norovirus. A common symptom of food poisoning is
diarrhea.
[0016] Wound Symptoms. There are many types of wounds that can
damage the skin including abrasions, lacerations, rupture injuries,
punctures, and penetrating wounds. The purpose of medical care for
wounds is to prevent complications and preserve function.
Inflammation is the skin's initial response to injury.
BRIEF SUMMARY
[0017] The subject invention provides therapeutic compositions and
methods for improving small intestine function. The subject
composition is useful for the treatment or amelioration of
gastrointestinal injury associated with the loss of small intestine
epithelial cells, particularly in the Villus region and the brush
border, and/or for the treatment or amelioration of diseases or
conditions associated with the alteration of absorptive capacity in
the small intestine.
[0018] Advantageously, the subject therapeutic composition can be
tailored to the misbalanced absorptive state of the
gastrointestinal system caused by the loss of small intestine
epithelial cells and the alteration of transport protein function
in the small intestine. In a preferred embodiment, the subject
composition is formulated for oral administration.
[0019] In one embodiment, the therapeutic composition comprises,
consists essentially of, or consists of, one or more free amino
acids selected from lysine, glycine, threonine, valine, tyrosine,
aspartic acid, isoleucine, tryptophan, asparagine, and serine; and
optionally, therapeutically acceptable carriers, electrolytes,
vitamins, buffering agents, and flavoring agents. The therapeutic
composition is administered via an enteral route. In one
embodiment, the total osmolarity of the composition is from about
230 mosm to 280 mosm, or preferably, about 250 to 260 mosm. In one
embodiment, the composition has a pH from about 7.1 to 7.9,
preferably, about 7.4.
[0020] In a specific embodiment, the composition of the subject
invention does not comprise glucose, glutamine, methionine, and/or
lactose.
[0021] Also provided are methods for treatment or amelioration of
diseases or symptoms associated with the loss of small intestine
epithelial cells, particularly in the Villus region and brush
border, and diseases or symptoms associated with the alteration of
transport protein function in the small intestine epithelium. The
method comprises administering, via an enteral route, to a subject
in need of such treatment, an effective amount of the composition
of the subject invention. Preferably, the subject composition is
administered orally and reaches the intestine of the subject.
[0022] The subject invention also provides methods for preparing
the therapeutic composition, and for screening for nutrients or
electrolytes for inclusion into the subject therapeutic/dietary
composition, by selecting nutrients or electrolytes that retain or
acquire considerable absorptive capacity following the destruction
of small intestine epithelial cells. These methods can be adapted
for use in individual patients, thereby facilitating the
development of compositions and methods specifically designed to
meet the needs of an individual patient.
[0023] Also provided are compositions and methods for treating a
subject having Ebola virus infection comprising administering to
the subject, a composition comprising one or more ingredients
selected from lysine, glycine, threonine, tryptophan, valine,
treosine, serine, and tyrosine, as free amino acids or a
combination thereof; wherein the composition does not comprise free
amino acid glutamine or a glutamine-containing dipeptide; wherein
the composition does not comprise glucose or, if glucose is
present, the concentration of glucose is less than 1 g/l; and
wherein the composition does not comprises methionine or a
methionine-containing dipeptide.
[0024] Also provided is a method for treating a subject having HIV
infection comprising administering to the subject a composition
comprising one or more ingredients selected from lysine, glycine,
threonine, tryptophan, valine, treosine, serine, and tyrosine, as
free amino acids or a combination thereof; wherein the composition
does not comprise free amino acid glutamine or a
glutamine-containing dipeptide; wherein the composition does not
comprise glucose or, if glucose is present, the concentration of
glucose is less than 1 g/l; and wherein the composition does not
comprises methionine or a methionine-containing dipeptide.
[0025] Also provided is a method for treating a subject having
ataxia symptoms comprising administering to the subject a
composition comprising at least one amino acid that retains or
acquires improved absorptive capacity following the impairment of
small intestine epithelial cells, the amino acids selected from the
group consisting of lysine, glycine, serine, threonine, tryptophan,
valine, and tyrosine, as free amino acids; one or more electrolyte
selected from among the group consisting of sodium, potassium,
magnesium and calcium and wherein the composition does not comprise
free amino acid glutamine or a glutamine-containing dipeptide, or,
if free amino acid glutamine and/or a glutamine-containing
dipeptide is present, the total concentration of the free amino
acid glutamine and the glutamine-containing dipeptide is less than
300 mg/l and wherein the composition does not comprise glucose or,
if glucose is present, the concentration of glucose is less than 1
g/l.
[0026] Also provided is a method for treating a subject having
decreased Villus height comprising administering to the subject a
composition comprising an amino acid that retains or acquires
improved absorptive capacity following the impairment of small
intestine epithelial cells, the amino acids selected from the group
consisting of lysine, glycine, threonine, tryptophan, serine,
valine, and tyrosine, as free amino acids; and wherein the
composition does not comprise free amino acid glutamine or a
glutamine-containing dipeptide, or, if free amino acid glutamine
and/or a glutamine-containing dipeptide is present, the total
concentration of the free amino acid glutamine and the
glutamine-containing dipeptide is less than 300 mg/l and wherein
the composition does not comprise glucose or, if glucose is
present, the concentration of glucose is less than 1 g/l.
[0027] Also provided is a method for the treatment of environmental
enteropathy comprising administering to the subject a composition
comprising an amino acid selected from the group consisting of
lysine, glycine, threonine, serine, tryptophan, valine, and
tyrosine, as free amino acids; and wherein the composition does not
comprise free amino acid glutamine or a glutamine-containing
dipeptide, or, if free amino acid glutamine and/or a
glutamine-containing dipeptide is present, the total concentration
of the free amino acid glutamine and the glutamine-containing
dipeptide is less than 300 mg/l and wherein the composition does
not comprise glucose or, if glucose is present, the concentration
of glucose is less than 1 g/l.
[0028] Also provided is a method for the treatment of weight loss
caused by cancer comprising administering to the subject a
composition comprising an amino acid selected from the group
consisting of lysine, glycine, threonine, serine, tryptophan,
valine, and tyrosine, as free amino acids; and wherein the
composition does not comprise free amino acid glutamine or a
glutamine-containing dipeptide, or, if free amino acid glutamine
and/or a glutamine-containing dipeptide is present, the total
concentration of the free amino acid glutamine and the
glutamine-containing dipeptide is less than 300 mg/l and wherein
the composition does not comprise glucose or, if glucose is
present, the concentration of glucose is less than 1 g/l.
DETAILED DISCLOSURE
[0029] The compositions disclosed herein work in disease conditions
associated with reduced absorptive capacity (inhibition of
electroneutral sodium and chloride absorption and/or Villus
damage), enhanced chloride secretion, increased intestinal
permeability and microbial translocation, chronic systemic
inflammation and diarrhea.
[0030] Reduced intestinal nutrient and electrolyte absorption
associated with decreased Villus height further exacerbates GI
toxicity. The presence of unabsorbed nutrients and electrolytes in
the gut lumen lead to osmotic diarrhea. Some nutrients, such as
glucose and specific amino acids (AAs) (Arginine, histidine,
methionine, phenylalanine, leucine, alanine, asparagine, cysteine,
glutamine, glutamic acid), activate active anion secretion and/ or
increase paracellular permeability (Health Phys., 106(6):734-44,
2014). These nutrients were not included in the formulation of the
invention. In addition some of the nutrients e.g., glucose was
shown to increase chloride secretion secondary to increased
intracellular calcium (Am. J. Physiol. Cell Physiol., 2014;
306(7):C687-C697). Glucose-stimulated active chloride secretion
becomes more critical in situations associated with Villus atrophy
as glucose and some of the nutrient absorption occurs in the fully
differentiated and mature Villus tip.
[0031] In preclinical studies using irradiated mice treated with an
oral mixture of the correct AAs; lysine, aspartic acid, glycine,
isoleucine, threonine, tyrosine, valine, tryptophan, serine
decreased the paracellular permeability, plasma endotoxin and
pro-inflammatory cytokine levels, and mortality in mice exposed to
lethal dose of irradiation (13Gy TBI) (Health Phys., 106(6):734-44,
2014).
[0032] In preclinical and in human subjects the compositions
disclosed herein provided benefits in distant organs such as the
lung. The compositions disclosed herein improved the lung function
and radiological clearance. The compositions contain a selection of
amino acids and electrolytes that are included in the generally
recognized as safe (GRAS) list, suggesting that it would pose
minimal risk in the form of toxicity.
[0033] Treatment Of Alcohol Hangovers
[0034] In one embodiment, the compositions disclosed herein are
used in a method for the treatment of hangovers. Symptoms of
hangovers can be attributed to a buildup of acetaldehyde in the
body. Some common hangover symptoms such as fatigue, stomach
irritation and a general sense of illness can be further attributed
to glutamine rebound. Consumption of alcohol inhibits glutamine
When the drinker stops drinking, the body produces more glutamine
than it needs. Increased glutamine levels stimulate the brain
leading to a loss of sleep leading to the fatigue associated with a
hangover. Increased amounts of glutamine may also cause tremors,
anxiety, restlessness and increased blood pressure. Alcohol
consumption can damage the intestinal epithelial cells. In
addition, alcohol increases paracellular permeability (leaky
gut).
[0035] Because alcohol is absorbed directly through the stomach,
the cells that line the organ become irritated. The stomach's
irritation may also be a factor in some of the other unpleasant
symptoms of a hangover, such as diarrhea and lack of appetite.
Additionally, alcohol is a diuretic in one of the consequences of
heavy alcohol consumption is dehydration. Cysteine breaks down the
hangover-causing toxin acetaldehyde in the liver's easily depleted
glutathione. Replenishment of potassium lost to alcohol's diuretic
effect is also desirable.
[0036] A composition for the treatment of hangover may include one
or more of the following constituents:
[0037] lysine at a concentration of about 730 to 6575 mg/l;
[0038] aspartic acid at a concentration of about 532 to 4792
mg/l;
[0039] glycine at a concentration of about 300 to 2703 mg/l;
[0040] isoleucine at a concentration of about 525 to 4722 mg/l;
[0041] threonine at a concentration of about 476 to 4288 mg/l;
[0042] tyrosine at a concentration of about 725 to 6523 mg/l;
[0043] valine at a concentration of about 469 to 4217 mg/l;
[0044] tryptophan at a concentration of about 817 to 7352 mg/l;
[0045] asparagine at a concentration of about 528 to 4756 mg/l;
and/or
[0046] serine at a concentration of about 420 to 3784 mg/l,
[0047] or a subset of these ingredients. In other embodiments the
composition may include two or more of the disclosed amino acids.
The composition does not contain glutamine, glucose or
carbohydrates that can hydrolyze into glucose in the gut. The
composition increased electrolyte absorption and improved mucosal
barrier functions. The amino acid composition provide for the
regulation of calcium-mediated chloride secretion in the intestinal
epithelium. The amino acid composition initially rehydrates the
vascular and interstitial fluid compartments of the cells in the
gut. Subsequently, the amino acid composition rapidly rehydrates
the vascular, interstitial, and intracellular fluid compartments
throughout the body. The amino acids help move fluid into the fluid
compartments and therefore form a complete rehydration
mechanism.
[0048] In another preferred embodiment, the composition may
comprise a combination of one or more of the following amino
acids:
[0049] threonine at a concentration of between about 1 mg/L-10
gm/L,
[0050] tyrosine at a concentration of between about 1 mg/L-10
gm/L,
[0051] serine at a concentration of between about 1 mg/L-10
gm/L,
[0052] valine at a concentration of between about 1 mg/L-10 gm/L,
and
[0053] tryptophan at a concentration of between about 1 mg/L-10
gm/L.
In other embodiments the composition may include two or more of the
disclosed amino acids.
[0054] In one embodiment the formulation may be formulated for
parenteral administration such as intravenously.
[0055] In a more preferred embodiment the composition may comprise
a combination of one or more of the following amino acids:
[0056] threonine at a concentration of between about 100 mg/L-5
gm/L,
[0057] tyrosine at a concentration of between about 100 mg/L-5
gm/L,
[0058] serine at a concentration of between about 100 mg/L-5
gm/L,
[0059] valine at a concentration of between about 100 mg/L-5 gm/L,
and
[0060] tryptophan at a concentration of between about 100 mg/L-5
gm/L.
[0061] In a most preferred embodiment the composition may comprise
a combination of one or more of the following amino acids:
[0062] threonine at a concentration of between about 0.5 gm/L-2
gm/L,
[0063] tyrosine at a concentration of between about 0.5 gm/L-2
gm/L,
[0064] serine at a concentration of between about 0.5 gm/L-2
gm/L,
[0065] valine at a concentration of between about 0.5 gm/L-2 gm/L,
and
[0066] tryptophan at a concentration of between about 0.5 gm/L-2
gm/L.
In other embodiments the composition may include two or more of the
disclosed amino acids.
[0067] The composition will not contain glucose or a carbohydrate
that may be hydrolyzed into glucose in the gut. Glucose increases
paracellular permeability (leaky gut). In addition glucose may
further dehydrate the tissues.
[0068] The composition will also not contain glutamine, cysteine,
methionine, and/or lactose.
[0069] The subject invention is based, at least in part, on the
discovery that enteral feeding to subjects with only the nutrients
that retain or acquire sufficient absorptive capacity following
excessive alcohol consumption alleviates an array of symptoms
associated with hangovers including, but not limited to, one or
more of the following: fatigue, thirst, headaches and muscle aches,
nausea, vomiting or stomach pain, poor or decreased sleep,
increased sensitivity to light and sound, dizziness or a sense of
the room spinning, rapid heartbeat, red, bloodshot eyes, shakiness,
decreased ability to concentrate, and mood disturbances, such as
depression, anxiety and irritability.
[0070] The amino acids help move fluid into the fluid compartments
and therefore form a complete rehydration mechanism. In one
embodiment the therapeutic composition may be administered via a
parenteral route such as intravenously.
[0071] In one embodiment the composition for the treatment of
hangover may be provided in powder or pill form.
[0072] In one embodiment a method for the treatment of hangovers or
alcohol toxicity comprises administering to the subject, the
composition described above.
[0073] Treatment of Inflammation
[0074] Inflammation is part of the response of vascular tissues to
harmful stimuli, such as pathogens, damaged cells, irritants or
inflammatory diseases. Inflammation is the protective attempt by
the body to remove the damaging stimuli and to trigger the healing
process.
[0075] A composition for the treatment of inflammation may include
one or more of the following constituents:
[0076] lysine at a concentration of about 730 to 6575 mg/l;
[0077] aspartic acid at a concentration of about 532 to 4792
mg/l;
[0078] glycine at a concentration of about 300 to 2703 mg/l;
[0079] isoleucine at a concentration of about 525 to 4722 mg/l;
[0080] threonine at a concentration of about 476 to 4288 mg/l;
[0081] tyrosine at a concentration of about 725 to 6523 mg/l;
[0082] valine at a concentration of about 469 to 4217 mg/l;
[0083] tryptophan at a concentration of about 817 to 7352 mg/l;
[0084] asparagine at a concentration of about 528 to 4756 mg/l;
and/or
[0085] serine at a concentration of about 420 to 3784 mg/l,
or a subset of these ingredients. In other embodiments the
composition may include two or more of the disclosed amino acids.
The amino acid compositions work by correcting the cell shrinkage
that occurs secondary to chloride secretions, and thus correct
mucosal barrier defect and downstream local and systemic
inflammation. The amino acid composition initially rehydrates the
vascular and interstitial fluid compartments of the cells in the
gut. Subsequently, the amino acid composition rapidly rehydrates
the vascular, interstitial, and intracellular fluid compartments
throughout the body. The composition does not contain glutamine,
glucose or carbohydrates that can hydrolyze into glucose in the
gut.
[0086] In another preferred embodiment, the composition for the
treatment of inflammation may comprise a combination of one or more
of the following amino acids:
[0087] threonine at a concentration of between about 1 mg/L-10
gm/L,
[0088] tyrosine at a concentration of between about 1 mg/L-10
gm/L,
[0089] serine at a concentration of between about 1 mg/L-10
gm/L,
[0090] valine at a concentration of between about 1 mg/L-10 gm/L,
and
[0091] tryptophan at a concentration of between about 1 mg/L-10
gm/L.
In other embodiments the composition may include two or more of the
disclosed amino acids. In one embodiment the formulation may be
formulated for parenteral administration such as intravenously.
[0092] In a more preferred embodiment the composition may comprise
a combination of one or more of the following amino acids:
[0093] threonine at a concentration of between about 100 mg/L-5
gm/L,
[0094] tyrosine at a concentration of between about 100 mg/L-5
gm/L,
[0095] serine at a concentration of between about 100 mg/L-5
gm/L,
[0096] valine at a concentration of between about 100 mg/L-5 gm/L
and
[0097] tryptophan at a concentration of between about 100
mg/L-gm./L.
[0098] In a most preferred embodiment the composition may comprise
a combination of one or more of the following amino acids:
[0099] threonine at a concentration of between about 0.5 gm/L-2
gm/L,
[0100] tyrosine at a concentration of between about 0.5 gm/L-2
gm/L,
[0101] serine at a concentration of between about 0.5 gm/L-2
gm/L,
[0102] valine at a concentration of between about 0.5 gm/L-2 gm/L,
and
[0103] tryptophan at a concentration of between about 0.5 gm/L-2
gm/L
[0104] The composition can be used to treat inflammation that is
local (limited to the intestinal tissues) or systemic. The amino
acid mixture ameliorates both types of inflammation.
[0105] The subject invention is based, at least in part, on the
discovery that enteral feeding to subjects with only the nutrients
that retain or acquire sufficient absorptive capacity in cases of
inflammation alleviates an array of symptoms associated with
inflammation including, but not limited to one or more of the
following: pain in the joints or muscles, allergies, asthma, high
blood pressure, blood sugar problems, ulcers and Irritable Bowel
Syndrome (constipation or diarrhea), constant fatigue or lethargy,
skin problems or red, bloodshot eyes, edema, hyperemia, erythema,
bruising, fluid retention, loss of appetite, increased heart rate,
formation of granulomas, fibrinous, pus, or nonviscous serous
fluid, and formation of an ulcer.
[0106] In one embodiment the therapeutic composition may be
administered via a parenteral route such as intravenously. In one
embodiment the composition for the treatment of inflammation may be
provided in powder or pill form.
[0107] In one embodiment a method for the treatment of inflammation
comprises administering to the subject, the composition described
above.
[0108] Electrolyte Replacement
[0109] Electrolytes are certain minerals (e.g., calcium,
bicarbonate chloride, magnesium, manganese, phosphate, potassium,
and sodium ions) essential to human health. As an essential
mineral, an electrolyte cannot be substituted by any other nutrient
in the diet. It has been established that during strenuous
exercise, significant amounts of electrolytes are eliminated, which
may account for systemic losses of Na+, Cl-, K+, Ca++, and HCO3-.
Electrolyte losses may contribute to early exhaustion, fatigue,
muscle cramps, cardiac effects (arrhythmias) and CNS effects
(asthenia).
[0110] An electrolyte replacement composition may be formulated as
a beverage comprising electrolytes such as sodium, chloride,
bicarbonate, calcium, phosphate, manganese, magnesium, and
potassium. In one embodiment an electrolyte replacement composition
may include:
[0111] sodium ion (preferentially as chloride) not more than 250
mg/L;
[0112] potassium ion (preferentially as phosphate) not less than
100 mg/L;
[0113] magnesium (as any nutritionally acceptable salt) not less
than 100 mg/L;
[0114] zinc (as any nutritionally acceptable salt) not more than 30
mg/L;
[0115] manganese (as any nutritionally acceptable complex) not more
than 10 mg/L;
[0116] calcium (as any nutritionally acceptable salt) between 65
and 400 mg/L; and
[0117] one or more free amino acids selected from lysine, glycine,
threonine,
[0118] threonine, valine, tyrosine, aspartic acid, isoleucine,
tryptophan, asparagine,
[0119] and serine; and optionally, therapeutically acceptable
carriers, vitamins,
[0120] buffering agents, and flavoring agents.
In other embodiments the composition may include two or more of the
disclosed amino acids. In other embodiments the composition may
include two or more of the disclosed amino acids. The amino acid
compositions work by correcting the cell shrinkage that occur
secondary to chloride secretions, and thus correct mucosal barrier
defect and downstream local and systemic inflammation. The amino
acid composition initially rehydrates the vascular and interstitial
fluid compartments of the cells in the gut. Subsequently, the amino
acid composition rapidly rehydrates the vascular, interstitial, and
intracellular fluid compartments throughout the body. The amino
acid compositions correct dehydration in vascular, interstitial and
intracellular compartment to restore the intracellular fluid volume
and decrease the cell shrinkage and therefore paracellular
permeability.
[0121] The beverage will not contain glucose or a carbohydrate that
may be hydrolyzed into glucose in the gut.
[0122] The beverage will also not contain glutamine, cysteine,
methionine, and/or lactose.
[0123] The total osmolarity of the beverage composition is from
about 230 mosm to 280 mosm, or preferably, is about 250 to 260
mosm.
[0124] The composition is formulated so that when the ingested
composition is in contact with the villous and brush border of the
small bowel the pH is between 7.1 to 7.9, or any value
therebetween. Preferably, when the ingested composition is in
contact with the villous and brush border of the small bowel the
composition has a pH from about 7.3 to 7.5, more preferably, about
7.4. In some embodiments the beverage composition may have a pH of
between 3-8, provided that when the ingested composition is in
contact with the villous and brush border of the small bowel the pH
is between 7.1 to 7.9.
[0125] In certain specific embodiments, the amino acid component of
the therapeutic composition comprises one or more free amino acids
present at their respective concentrations as follows:
[0126] lysine at a concentration of about 730 to 6575 mg/l;
[0127] aspartic acid at a concentration of about 532 to 4792
mg/l;
[0128] glycine at a concentration of about 300 to 2703 mg/l;
[0129] isoleucine at a concentration of about 525 to 4722 mg/l;
[0130] threonine at a concentration of about 1 to 10,000 mg/L;
[0131] threonine at a concentration of about 476 to 4288 mg/l;
[0132] tyrosine at a concentration of about 725 to 6523 mg/l;
[0133] valine at a concentration of about 469 to 4217 mg/l;
[0134] tryptophan at a concentration of about 817 to 7352 mg/l;
[0135] asparagine at a concentration of about 528 to 4756 mg/l;
and/or
[0136] serine at a concentration of about 420 to 3784 mg/l,
[0137] The total osmolarity of the composition is from about 240
mosm to 280 mosm.
[0138] In another preferred embodiment, the electrolyte replacement
composition may comprise a combination of one or more of the
following amino acids:
[0139] threonine at a concentration of between about 1 mg/L-10
gm/L,
[0140] tyrosine at a concentration of between about 1 mg/L-10
gm/L,
[0141] serine at a concentration of between about 1 mg/L-10
gm/L,
[0142] valine at a concentration of between about 1 mg/L-10 gm/L
and.
[0143] tryptophan at a concentration of between about 1 mg/L-10
gm/L
[0144] In one embodiment the formulation may be formulated for
parenteral administration such as intravenously.
[0145] In a more preferred embodiment the electrolyte replacement
composition may comprise a combination of one or more of the
following amino acids:
[0146] threonine at a concentration of between about 100 mg/L-5
gm/L,
[0147] tyrosine at a concentration of between about 100 mg/L-5
gm/L,
[0148] serine at a concentration of between about 100 mg/L-5
gm/L,
[0149] valine at a concentration of between about 100 mg/L-5 gm/L,
and
[0150] tryptophan at a concentration of between about 100 mg/L-5
gm/L.
[0151] In a most preferred embodiment the electrolyte replacement
composition may comprise a combination of one or more of the
following amino acids:
[0152] threonine at a concentration of between about 0.5 gm/L-2
gm/L,
[0153] tyrosine at a concentration of between about 0.5 gm/L-2
gm/L,
[0154] serine at a concentration of between about 0.5 gm/L-2
gm/L,
[0155] valine at a concentration of between about 0.5 gm/L-2 gm/L
and
[0156] tryptophan at a concentration of between about 0.5 gm/L-2
gm/L.
[0157] The presence of the free amino acids provides a more
effective transport of the electrolytes into the body. It was found
that there was an increase in electrolyte and nutrient absorption
secondary to increase in villous height (increasing the surface
area of absorption) in irradiated and non-irradiated mice treated
with the four amino acids mixture for a period of time as short as
four days.
[0158] In one embodiment a method for the replacement of
electrolytes comprises administering to the subject, the
electrolyte replacement composition described above.
[0159] Rehydration Composition
[0160] Strenuous exercise places a metabolic demand on the human
body. One of the consequences of strenuous exercise is the loss of
sweat which can result in dehydration. The resulting loss of water
and electrolytes causes fatigue. Commercial fluid replacement
drinks often contain glucose or fructose, as a supplementary energy
source. It has been found that as the carbohydrate concentration of
a drink increases, the rate of fluid replacement to the body is
decreased.
[0161] A rehydration composition may be formulated as a beverage
comprising:
[0162] sodium ion (preferentially as chloride) not more than 250
mg/L;
[0163] potassium ion (preferentially as phosphate) not less than
100 mg/L;
[0164] magnesium (as any nutritionally acceptable salt) not less
than 100 mg/L;
[0165] zinc (as any nutritionally acceptable salt) not more than 30
mg/L;
[0166] manganese (as any nutritionally acceptable complex) not more
than 10 mg/L;
[0167] calcium (as any nutritionally acceptable salt) between 65
and 400 mg/L; and
[0168] one or more free amino acids selected from lysine, glycine,
threonine, valine,
[0169] tyrosine, aspartic acid, isoleucine. tryptophan, asparagine,
and serine; and
[0170] optionally, therapeutically acceptable carriers, vitamins,
buffering agents, and
[0171] flavoring agents.
In other embodiments the composition may include two or more of the
disclosed amino acids. The amino acid compositions work by
correcting the cell shrinkage that occur secondary to chloride
secretions, and thus correct mucosal barrier defect and downstream
local and systemic inflammation. The amino acid composition
initially rehydrates the vascular and interstitial fluid
compartments of the cells in the gut. Subsequently, the amino acid
composition rapidly rehydrates the vascular, interstitial, and
intracellular fluid compartments throughout the body. The amino
acid compositions correct dehydration in vascular, interstitial and
intracellular compartment to restore the intracellular fluid volume
and decrease the cell shrinkage and therefore paracellular
permeability.
[0172] The beverage will not contain glucose or a carbohydrate that
may be hydrolyzed into glucose in the gut.
[0173] The beverage will also not contain glutamine, cysteine,
methionine, and/or lactose.
[0174] The total osmolarity of the beverage composition is from
about 230 mosm to 280 mosm, or preferably, is about 250 to 260
mosm.
[0175] In certain specific embodiments, the amino acid component of
the rehydration composition comprises one or more free amino acids
present at their respective concentrations as follows:
[0176] lysine at a concentration of about 730 to 6575 mg/l;
[0177] aspartic acid at a concentration of about 532 to 4792
mg/l;
[0178] glycine at a concentration of about 300 to 2703 mg/l;
[0179] isoleucine at a concentration of about 525 to 4722 mg/l;
[0180] threonine at a concentration of about 476 to 4288 mg/l,
[0181] tyrosine at a concentration of about 725 to 6523 mg/l;
[0182] valine at a concentration of about 469 to 4217 mg/l;
[0183] tryptophan at a concentration of about 817 to 7352 mg/l;
[0184] asparagine at a concentration of about 528 to 4756 mg/l;
and/or
[0185] serine at a concentration of about 420 to 3784 mg/l,
[0186] The total osmolarity of the composition is from about 240
mosm to 280 mosm.
[0187] In another preferred embodiment, the rehydration beverage
may comprise a combination of
[0188] threonine at a concentration of between about 1 mg/L-10
gm,
[0189] tyrosine at a concentration of between about 1 mg/L-10
gm/L,
[0190] serine at a concentration of between about 1 mg/L-10
gm/L,
[0191] valine at a concentration of between about 1 mg/L-10 gm/L,
and
[0192] tryptophan at a concentration of between about 1 mg/L-10
gm/L.
[0193] In one embodiment the formulation may be formulated for
parenteral administration such as intravenously.
[0194] In a more preferred embodiment the rehydration beverage may
comprise a combination of one or more of the following amino
acids:
[0195] threonine at a concentration of between about 100 mg/L-5
gm/L,
[0196] tyrosine at a concentration of between about 100 mg/L-5
gm/L,
[0197] serine at a concentration of between about 100 mg/L-5
gm/L,
[0198] valine at a concentration of between about 100 mg/L-5 gm/L,
and
[0199] tryptophan at a concentration of between about 100 mg/L-5
gm/L.
[0200] In a most preferred embodiment the rehydration beverage may
comprise a combination of one or more of the following amino
acids:
[0201] threonine at a concentration of between about 0.5 gm/L-2
gm/L,
[0202] tyrosine at a concentration of between about 0.5 gm/L-2
gm/L,
[0203] serine at a concentration of between about 0.5 gm/L-2
gm/L,
[0204] valine at a concentration of between about 0.5 gm/L-2 gm/L,
and
[0205] tryptophan at a concentration of between about 0.5 gm/L-2
gm/L.
[0206] The presence of the free amino acids provides a more
effective transport of the electrolytes into the body. The amino
acids help to move fluid into the three fluid compartments and
therefore form a complete rehydration mechanism.
[0207] In one embodiment the rehydration beverage has a pH of
between 2.9 to 7.6 and preferably a pH of between 3.8-4.5.
[0208] In one embodiment a rehydration composition is provided with
the foregoing amino acid compositions provided in powder or pill
form.
[0209] In one embodiment a method for rehydration comprises
administering to the subject, the rehydration composition or
rehydration beverage described above.
[0210] Nutrient Delivery
[0211] Absorption of a nutrient is dependent on the food-calorie
content, composition, volume, temperature of diet, amount of fluid
ingested, and the fed status. Nutrients have the potential to alter
gastrointestinal pH, motility, secretions, flora, and mucosal
morphology or function and can consequently be absorbed in higher
or lower amounts.
[0212] In certain specific embodiments, the amino acid component of
the therapeutic composition for enhanced nutrient delivery
comprises one or more free amino acids present at their respective
concentrations as follows:
[0213] lysine at a concentration of about 730 to 6575 mg/l;
[0214] aspartic acid at a concentration of about 532 to 4792
mg/l;
[0215] glycine at a concentration of about 300 to 2703 mg/l;
[0216] isoleucine at a concentration of about 525 to 4722 mg/l;
[0217] threonine at a concentration of about 1 to 10,000 mg/L;
[0218] threonine at a concentration of about 476 to 4288 mg/l;
[0219] tyrosine at a concentration of about 725 to 6523 mg/l;
[0220] valine at a concentration of about 469 to 4217 mg/l;
[0221] tryptophan at a concentration of about 817 to 7352 mg/l;
[0222] asparagine at a concentration of about 528 to 4756 mg/l;
and/or
[0223] serine at a concentration of about 420 to 3784 mg/l.
The total osmolarity of the composition is from about 240 mosm to
280 mosm. In other embodiments the composition may include two or
more of the disclosed amino acids. The amino acid compositions work
by correcting the cell shrinkage that occur secondary to chloride
secretions, and thus correct mucosal barrier defect and downstream
local and systemic inflammation. The amino acid composition
initially rehydrates the vascular and interstitial fluid
compartments of the cells in the gut. Subsequently, the amino acid
composition rapidly rehydrates the vascular, interstitial, and
intracellular fluid compartments throughout the body. The amino
acid compositions correct dehydration in vascular, interstitial and
intracellular compartment to restore the intracellular fluid volume
and decrease the cell shrinkage and therefore paracellular
permeability
[0224] In another preferred embodiment, the therapeutic composition
for enhanced nutrient delivery may comprise a combination of one or
more of the following amino acids:
[0225] threonine at a concentration of between about 1 mg/L-10
gm/L,
[0226] tyrosine at a concentration of between about 1 mg/L-10
gm/L,
[0227] serine at a concentration of between about 1 mg/L-10
gm/L,
[0228] valine at a concentration of between about 1 mg/L-10 gm/L,
and
[0229] tryptophan at a concentration of between about 1 mg/L-10
gm/L.
[0230] In one embodiment the formulation may be formulated for
parenteral administration such as intravenously.
[0231] In a more preferred embodiment the therapeutic composition
for enhanced nutrient delivery may comprise a combination of one or
more of the following amino acids:
[0232] threonine at a concentration of between about 100 mg/L-5
gm/L,
[0233] tyrosine at a concentration of between about 100 mg/L-5
gm/L,
[0234] serine at a concentration of between about 100 mg/L-5
gm/L,
[0235] valine at a concentration of between about 100 mg/L-5 gm/L,
and
[0236] tryptophan at a concentration of between about 100 mg/L-5
gm/L.
[0237] In a most preferred embodiment the therapeutic composition
for enhanced nutrient delivery may comprise a combination of one or
more of the following amino acids:
[0238] threonine at a concentration of between about 0.5 gm/L-2
gm/L,
[0239] tyrosine at a concentration of between about 0.5 gm/L-2
gm/L,
[0240] serine at a concentration of between about 0.5 gm/L-2
gm/L,
[0241] valine at a concentration of between about 0.5 gm/L-2 gm/L,
and
[0242] tryptophan at a concentration of between about 0.5 gm/L-2
gm/L.
[0243] In one embodiment the formulation may be formulated for
parenteral administration such as intravenously.
[0244] Beverage for Geriatric Population
[0245] Older subjects often suffer from protein caloric
malnutrition. The ability of older adults to effectively control
energy intake is affected because of the delayed rate of absorption
of macronutrients. Older adults have a decreased capacity to absorb
nutrients such as vitamin B12 and vitamin D.
[0246] The DRIs for older adults from the Food and Nutrition Board
of the Institute of Medicine are as follows for each age group.
TABLE-US-00001 Male ages 51 to Female ages 51 to Male age 71 or
Female age 71 or 70, per day 70, per day older, per day older, per
day VIT A, 900 mcg VIT A, 700 mcg VIT A, 900 mcg VIT A, 700 mcg VIT
C, 90 mg VIT C, 75 mg VIT C, 90 mg VIT C, 75 mg VIT D, 15 mcg VIT
D, 15 mcg VIT D, 20 mcg VIT D, 20 mcg VIT E, 15 mg VIT E, 15 mg VIT
E, 15 mg VIT E, 15 mg VIT B6, 1.5 mg VIT B6, 1.5 mg VIT B6, 1.7 mg
VIT B6, 1.5 mg VIT B12, 2.4 mcg VIT B12, 2.4 mcg VIT B12, 2.4 mcg
VIT B12, 2.4 mcg Folate, 400 mcg Folate, 400 mcg Folate, 400 mcg
Folate, 400 mcg Iron, 8 mg Iron, 8 mg Iron, 8 mg Iron, 8 mg
Calcium, 1,000 mg Calcium, 1,200 mg Calcium, 1,200 mg Calcium,
1,200 mg Niacin, 14 mg Niacin, 14 mg Niacin, 16 mg Niacin, 14
mg
[0247] In one embodiment of the invention a nutritional composition
for a geriatric population may include proteins, fats, minerals and
Vitamins and free amino acids selected from the group consisting of
lysine (11-21 mosm), aspartic acid (3-13 mosm), glycine (19-29
mosm), isoleucine (19-29 mosm), threonine (19-29 mosm), tyrosine
(0.5-5 mosm), valine (19-29 mosm), tryptophan (5-20 mosm),
asparagine (3-13 mosm), and serine (3-8 mosm), or a subset of these
ingredients. The composition will preferably not contain glutamine
or cysteine. The composition will preferably not contain glucose or
carbohydrates that can hydrolyze into glucose in the gut.
[0248] In another embodiment a nutritional composition for a
geriatric population may include one or more free amino acids
present at their respective concentrations as follows:
[0249] lysine at a concentration of about 730 to 6575 mg/l;
[0250] aspartic acid at a concentration of about 532 to 4792
mg/l;
[0251] glycine at a concentration of about 300 to 2703 mg/l;
[0252] isoleucine at a concentration of about 525 to 4722 mg/l;
[0253] threonine at a concentration of about 1 to 10,000 mg/L;
[0254] threonine at a concentration of about 476 to 4288 mg/l;
[0255] tyrosine at a concentration of about 725 to 6523 mg/l;
[0256] valine at a concentration of about 469 to 4217 mg/l;
[0257] tryptophan at a concentration of about 817 to 7352 mg/l;
[0258] asparagine at a concentration of about 528 to 4756 mg/l;
and/or
[0259] serine at a concentration of about 420 to 3784 mg/l.
In other embodiments the composition may include two or more of the
disclosed amino acids. The amino acid compositions work by
correcting the cell shrinkage that occur secondary to chloride
secretions, and thus correct mucosal barrier defect and downstream
local and systemic inflammation. The amino acid composition
initially rehydrates the vascular and interstitial fluid
compartments of the cells in the gut. Subsequently, the amino acid
composition rapidly rehydrates the vascular, interstitial, and
intracellular fluid compartments throughout the body. The amino
acid compositions correct dehydration in vascular, interstitial and
intracellular compartment to restore the intracellular fluid volume
and decrease the cell shrinkage and therefore paracellular
permeability
[0260] In another preferred embodiment, the nutritional composition
for a geriatric population may comprise a combination of one or
more of the following amino acids:
[0261] threonine at a concentration of between about 1 mg/L-10
gm/L,
[0262] tyrosine at a concentration of between about 1 mg/L-10
gm/L,
[0263] serine at a concentration of between about 1 mg/L-10
gm/L,
[0264] valine at a concentration of between about 1 mg/L-10 gm/L,
and
[0265] tryptophan at a concentration of between about 1 mg/L-10
gm/L.
[0266] In a more preferred embodiment the nutritional composition
for a geriatric population may comprise a combination of one or
more of the following amino acids:
[0267] threonine at a concentration of between about 100 mg/L-5
gm/L,
[0268] tyrosine at a concentration of between about 100 mg/L-5
gm/L,
[0269] serine at a concentration of between about 100 mg/L-5
gm/L,
[0270] valine at a concentration of between about 100 mg/L-5 gm/L,
and
[0271] tryptophan at a concentration of between about 100 mg/L-5
gm/L.
[0272] In a most preferred embodiment the nutritional composition
for a geriatric population may comprise a combination of one or
more of the following amino acids:
[0273] threonine at a concentration of between about 0.5 gm/L-2
gm/L,
[0274] tyrosine at a concentration of between about 0.5 gm/L-2
gm/L,
[0275] serine at a concentration of between about 0.5 gm/L-2
gm/L,
[0276] valine at a concentration of between about 0.5 gm/L-2 gm/L,
and
[0277] tryptophan at a concentration of between about 0.5 gm/L-2
gm/L.
[0278] The composition of the foregoing embodiment provides for
enhanced absorption of nutrients as a result of the presence of the
free amino acids.
[0279] In one embodiment a method for delivering nutrition to a
geriatric patient comprises administering to the subject, the
nutritional composition described above.
[0280] Drug Delivery System
[0281] During drug delivery, drugs must pass or permeate through
epithelial cells in order to be absorbed into the circulatory
system. One particular cellular barrier that may prevent absorption
of a given drug is the cell membrane. Cell membranes are
essentially lipid bilayers which form a semipermeable membrane.
Pure lipid bilayers are generally permeable only to small,
uncharged solutes. Ionization of a molecule will affect its
absorption, since ionic molecules are charged. Solubility favors
charged species, and permeability favors neutral species. Some
molecules have special exchange proteins and channels to facilitate
movement from the lumen into the circulation.
[0282] A composition to augment drug delivery and enhance
pharmacokinetics thereby enhancing drug availability may include
one or more of the following constituents:
[0283] lysine at a concentration of about 730 to 6575 mg/l;
[0284] vaspartic acid at a concentration of about 532 to 4792
mg/l;
[0285] glycine at a concentration of about 300 to 2703 mg/l;
[0286] isoleucine at a concentration of about 525 to 4722 mg/l;
[0287] threonine at a concentration of about 1 to 10,000 mg/L;
[0288] threonine at a concentration of about 476 to 4288 mg/l;
[0289] tyrosine at a concentration of about 725 to 6523 mg/l;
[0290] valine at a concentration of about 469 to 4217 mg/l;
[0291] tryptophan at a concentration of about 817 to 7352 mg/l;
[0292] asparagine at a concentration of about 528 to 4756 mg/l;
and/or
[0293] serine at a concentration of about 420 to 3784 mg/l,
[0294] or a subset of these ingredients. The composition does not
contain glutamine, glucose or carbohydrates that can hydrolyze into
glucose in the gut. In other embodiments the composition may
include two or more of the disclosed amino acids. The amino acid
compositions work by correcting the cell shrinkage that occur
secondary to chloride secretions, and thus correct mucosal barrier
defect and downstream local and systemic inflammation. The amino
acid composition initially rehydrates the vascular and interstitial
fluid compartments of the cells in the gut. Subsequently, the amino
acid composition rapidly rehydrates the vascular, interstitial, and
intracellular fluid compartments throughout the body. The amino
acid compositions correct dehydration in vascular, interstitial and
intracellular compartment to restore the intracellular fluid volume
and decrease the cell shrinkage and therefore paracellular
permeability
[0295] In another preferred embodiment, the composition to augment
drug delivery and enhance pharmacokinetics may comprise a
combination of one or more of the following amino acids:
[0296] threonine at a concentration of between about 1 mg/L-10
gm/L,
[0297] tyrosine at a concentration of between about 1 mg/L-10
gm/L,
[0298] serine at a concentration of between about 1 mg/L-10
gm/L,
[0299] valine at a concentration of between about 1 mg/L-10 gm/L,
and
[0300] tryptophan at a concentration of between about 1 mg/L-10
gm/L.
[0301] In one embodiment the formulation may be formulated for
parenteral administration such as intravenously.
[0302] In a more preferred embodiment the composition may comprise
a combination of one or more of the following amino acids:
[0303] threonine at a concentration of between about 100 mg/L-5
gm/L,
[0304] tyrosine at a concentration of between about 100 mg/L-5
gm/L,
[0305] serine at a concentration of between about 100 mg/L-5
gm/L,
[0306] valine at a concentration of between about 100 mg/L-5 gm/L,
and
[0307] tryptophan at a concentration of between about 100 mg/L-5
gm/L.
[0308] In a most preferred embodiment the composition may comprise
a combination of one or more of the following amino acids:
[0309] threonine at a concentration of between about 0.5 gm/L-2
gm/L,
[0310] tyrosine at a concentration of between about 0.5 gm/L-2
gm/L,
[0311] serine at a concentration of between about 0.5 gm/L-2
gm/L,
[0312] valine at a concentration of between about 0.5 gm/L-2 gm/L
and
[0313] tryptophan at a concentration of between about 0.5 gm/L-2
gm/L.
[0314] In one embodiment the composition to augment drug delivery
and enhance pharmacokinetics thereby enhancing drug availability
may be delivered in powder or pill form.
[0315] In one embodiment a method for enhancing drug delivery
comprises administering to the subject, the composition to augment
drug delivery and enhance pharmacokinetics described above.
[0316] Treatment of Dehydration Caused by Diabetes
[0317] People with diabetes have an increased risk of dehydration
as high blood glucose levels lead to decreased hydration in the
body. Diabetes insipidus, a form of diabetes that is not linked
with high blood sugar levels, also carries a higher risk of
dehydration. If blood glucose levels are higher than normal for a
prolonged period of time, the kidneys will attempt to remove some
of the excess glucose from the blood and excrete this as urine.
When the kidneys lose the glucose through the urine, a large amount
of water is also lost, causing dehydration. When a person with type
2 diabetes becomes severely dehydrated and is not able to drink
enough fluids to make up for the fluid losses, they may develop
Hyperosmolar nonketotic diabetic coma, a life-threatening
complication.
[0318] In one embodiment, the compositions disclosed herein are
used in a method for the treatment of dehydration caused by
diabetes.
[0319] A composition for the treatment of dehydration caused by
diabetes may include one or more of the following constituents:
[0320] lysine at a concentration of about 730 to 6575 mg/l;
[0321] aspartic acid at a concentration of about 532 to 4792
mg/l;
[0322] glycine at a concentration of about 300 to 2703 mg/l;
[0323] isoleucine at a concentration of about 525 to 4722 mg/l;
[0324] threonine at a concentration of about 1 to 10,000 mg/L;
[0325] threonine at a concentration of about 476 to 4288 mg/l;
[0326] tyrosine at a concentration of about 725 to 6523 mg/l;
[0327] valine at a concentration of about 469 to 4217 mg/l;
[0328] tryptophan at a concentration of about 817 to 7352 mg/l;
[0329] asparagine at a concentration of about 528 to 4756 mg/l;
and/or
[0330] serine at a concentration of about 420 to 3784 mg/l,
or a subset of these ingredients. The composition does not contain
glutamine, glucose or carbohydrates that can hydrolyze into glucose
in the gut. The amino acid compositions work by correcting the cell
shrinkage that occur secondary to chloride secretions, and thus
correct mucosal barrier defect and downstream local and systemic
inflammation. The amino acid composition initially rehydrates the
vascular and interstitial fluid compartments of the cells in the
gut. Subsequently, the amino acid composition rapidly rehydrates
the vascular, interstitial, and intracellular fluid compartments
throughout the body. The amino acid compositions correct
dehydration in vascular, interstitial and intracellular compartment
to restore the intracellular fluid volume and decrease the cell
shrinkage and therefore paracellular permeabilityln other
embodiments the composition may include two or more of the
disclosed amino acids.
[0331] In another preferred embodiment, the composition may
comprise a combination of one or more of the following amino
acids:
[0332] threonine at a concentration of between about 1 mg/L-10
gm/L,
[0333] tyrosine at a concentration of between about 1 mg/L-10
gm/L,
[0334] serine at a concentration of between about 1 mg/L-10
gm/L,
[0335] valine at a concentration of between about 1 mg/L-10 gm/L,
and
[0336] tryptophan at a concentration of between about 1 mg/L-10
gm/L.
In one embodiment the formulation may be formulated for parenteral
administration such as intravenously.
[0337] In a more preferred embodiment the composition may comprise
a combination of one or more of the following amino acids:
[0338] threonine at a concentration of between about 100 mg/L-5
gm/L,
[0339] tyrosine at a concentration of between about 100 mg/L-5
gm/L,
[0340] serine at a concentration of between about 100 mg/L-5
gm/L,
[0341] valine at a concentration of between about 100 mg/L-5 gm/L,
and
[0342] tryptophan at a concentration of between about 100 mg/L-5
gm/L.
[0343] In a most preferred embodiment the composition may comprise
a combination of one or more of the following amino acids:
[0344] threonine at a concentration of between about 0.5 gm/L-2
gm/L,
[0345] tyrosine at a concentration of between about 0.5 gm/L-2
gm/L,
[0346] serine at a concentration of between about 0.5 gm/L-2
gm/L,
[0347] valine at a concentration of between about 0.5 gm/L-2 gm/L
and
[0348] tryptophan at a concentration of between about 0.5 gm/L-2
gm/L.
[0349] The composition will not contain glucose or a carbohydrate
that may be hydrolyzed into glucose in the gut. Glucose increases
paracellular permeability (leaky gut). In addition glucose may
further dehydrate the tissues.
[0350] The composition will also not contain glutamine, cysteine,
methionine, and/or lactose.
[0351] The subject invention is based, at least in part, on the
discovery that enteral feeding to subjects with only the nutrients
that retain or acquire sufficient absorptive capacity in cases of
diabetes improves mucosal healing, restores small intestine
function, enhances fluid retention, and alleviates an array of
associated disease symptoms including, but not limited to,
malabsorption, diarrhea, nausea, vomiting, electrolyte imbalance,
and dehydration.
[0352] In one embodiment the composition for the treatment of
dehydration caused by diabetes may be delivered in powder or pill
form.
[0353] In one embodiment a method for the treatment of dehydration
caused by diabetes comprises administering to the subject, the
composition for the treatment of dehydration caused by diabetes
described above.
[0354] Treatment of Porcine Epidemic Diarrhea
[0355] In one embodiment, the compositions disclosed herein are
used in a method for the treatment of Porcine epidemic diarrhea.
Porcine Epidemic Diarrhea Virus (PEDV) is a coronavirus that
infects the cells lining the small intestine of a pig, causing
porcine epidemic diarrhea, a condition of severe diarrhea and
dehydration. Older hogs mostly get sick and lose weight after being
infected, whereas newborn piglets usually die within five days of
contracting the virus. PEDV cannot be transmitted to humans, nor
contaminate the human food supply.
[0356] In a field trial with 10 piglets, all infected with the PEDV
where 5 piglets were treated with the composition described below,
it was found that the 5 piglets treated with the composition all
survived while the five piglets not treated all died.
[0357] A composition for the treatment of porcine epidemic diarrhea
may include one or more of the following constituents:
[0358] lysine at a concentration of about 730 to 6575 mg/l;
[0359] aspartic acid at a concentration of about 532 to 4792
mg/l;
[0360] glycine at a concentration of about 300 to 2703 mg/l;
[0361] isoleucine at a concentration of about 525 to 4722 mg/l;
[0362] threonine at a concentration of about 476 to 4288 mg/l;
[0363] tyrosine at a concentration of about 725 to 6523 mg/l;
[0364] valine at a concentration of about 469 to 4217 mg/l;
[0365] tryptophan at a concentration of about 817 to 7352 mg/l;
[0366] asparagine at a concentration of about 528 to 4756 mg/l;
and/or
[0367] serine at a concentration of about 420 to 3784 mg/l,
or a subset of these ingredients. In other embodiments the
composition may comprise two or more of the listed amino acids. The
composition does not contain glutamine, glucose or carbohydrates
that can hydrolyze into glucose in the gut. The amino acid
compositions work by correcting the cell shrinkage that occur
secondary to chloride secretions, and thus correct mucosal barrier
defect and downstream local and systemic inflammation. The amino
acid composition initially rehydrates the vascular and interstitial
fluid compartments of the cells in the gut. Subsequently, the amino
acid composition rapidly rehydrates the vascular, interstitial, and
intracellular fluid compartments throughout the body. The amino
acid compositions correct dehydration in vascular, interstitial and
intracellular compartment to restore the intracellular fluid volume
and decrease the cell shrinkage and therefore paracellular
permeability.
[0368] In another preferred embodiment, the composition may
comprise a combination of one or more of the following amino
acids:
[0369] threonine at a concentration of between about 1 mg/L-10
gm/L,
[0370] tyrosine at a concentration of between about 1 mg/L-10
gm/L,
[0371] serine at a concentration of between about 1 mg/L-10
gm/L,
[0372] valine at a concentration of between about 1 mg/L-10 gm/L,
and
[0373] tryptophan at a concentration of between about 1 mg/L-10
gm/L.
[0374] In one embodiment the formulation may be formulated for
parenteral administration such as intravenously.
[0375] In a more preferred embodiment the composition may comprise
a combination of one or more of the following amino acids:
[0376] threonine at a concentration of between about 100 mg/L-5
gm/L,
[0377] tyrosine at a concentration of between about 100 mg/L-5
gm/L,
[0378] serine at a concentration of between about 100 mg/L-5
gm/L,
[0379] valine at a concentration of between about 100 mg/L-5 gm/L,
and
[0380] tryptophan at a concentration of between about 100 mg/L-5
gm/L.
[0381] In a most preferred embodiment the composition may comprise
a combination of one or more of the following amino acids:
[0382] threonine at a concentration of between about 0.5 gm/L-2
gm/L,
[0383] tyrosine at a concentration of between about 0.5 gm/L-2
gm/L,
[0384] serine at a concentration of between about 0.5 gm/L-2
gm/L,
[0385] valine at a concentration of between about 0.5 gm/L-2 gm/L
and
[0386] tryptophan at a concentration of between about 0.5 gm/L-2
gm/L.
[0387] The composition will not contain glucose or a carbohydrate
that may be hydrolyzed into glucose in the gut. Glucose increases
paracellular permeability (leaky gut). In addition glucose may
further dehydrate the tissues.
[0388] The composition will also not contain glutamine, cysteine,
methionine, and/or lactose.
[0389] The subject invention is based, at least in part, on the
discovery that enteral feeding to subjects with only the nutrients
that retain or acquire sufficient absorptive capacity following
infection with PEDV.
[0390] In one embodiment the composition for the treatment of
porcine epidemic diarrhea may be delivered in powder or pill
form.
[0391] In one embodiment a method for the treatment of porcine
epidemic diarrhea comprises administering to the subject, one of
the compositions for the treatment of porcine epidemic diarrhea
described above.
[0392] Treatment of Environmental Enteropathy
[0393] Environmental enteropathy is a subclinical condition caused
by constant fecal-oral contamination and resulting in blunting of
intestinal villi and intestinal inflammation. Environmental
enteropathy may cause the failure of nutritional interventions and
oral vaccines. Environmental enteropathy may result in increased
intestinal permeability, malabsorption, impaired gut immune
function, and oral vaccine failure.
[0394] In one embodiment, the compositions disclosed herein are
used in a method for the treatment of environmental
enteropathy.
[0395] A composition for the treatment of environmental enteropathy
may include one or more of the following constituents:
[0396] lysine at a concentration of about 730 to 6575 mg/l;
[0397] aspartic acid at a concentration of about 532 to 4792
mg/l;
[0398] glycine at a concentration of about 300 to 2703 mg/l;
[0399] isoleucine at a concentration of about 525 to 4722 mg/l;
[0400] threonine at a concentration of about 476 to 4288 mg/l;
[0401] tyrosine at a concentration of about 725 to 6523 mg/l;
[0402] valine at a concentration of about 469 to 4217 mg/l;
[0403] tryptophan at a concentration of about 817 to 7352 mg/l;
[0404] asparagine at a concentration of about 528 to 4756 mg/l;
and/or
[0405] serine at a concentration of about 420 to 3784 mg/l,
[0406] or a subset of these ingredients. The composition does not
contain glutamine, glucose or carbohydrates that can hydrolyze into
glucose in the gut. The amino acid compositions work by correcting
the cell shrinkage that occur secondary to chloride secretions, and
thus correct mucosal barrier defect and downstream local and
systemic inflammation. The amino acid composition initially
rehydrates the vascular and interstitial fluid compartments of the
cells in the gut. Subsequently, the amino acid composition rapidly
rehydrates the vascular, interstitial, and intracellular fluid
compartments throughout the body. The amino acid compositions
correct dehydration in vascular, interstitial and intracellular
compartment to restore the intracellular fluid volume and decrease
the cell shrinkage and therefore paracellular permeability.
[0407] In another preferred embodiment, the composition may
comprise a combination of one or more of the following amino
acids:
[0408] threonine at a concentration of between about 1 mg/L-10
gm/L,
[0409] tyrosine at a concentration of between about 1 mg/L-10
gm/L,
[0410] serine at a concentration of between about 1 mg/L-10
gm/L,
[0411] valine at a concentration of between about 1 mg/L-10 gm/L
and
[0412] tryptophan at a concentration of between about 1 mg/L-10
gm/L.
[0413] In one embodiment the formulation may be formulated for
parenteral administration such as intravenously.
[0414] In a more preferred embodiment the composition may comprise
a combination of one or more of the following amino acids:
[0415] threonine at a concentration of between about 100 mg/L-5
gm/L,
[0416] tyrosine at a concentration of between about 100 mg/L-5
gm/L,
[0417] serine at a concentration of between about 100 mg/L-5
gm/L,
[0418] valine at a concentration of between about 100 mg/L-5 gm/L,
and
[0419] tryptophan at a concentration of between about 100 mg/L-5
gm/L.
[0420] In a most preferred embodiment the composition may comprise
a combination of one or more of the following amino acids:
[0421] threonine at a concentration of between about 0.5 gm/L-2
gm/L,
[0422] tyrosine at a concentration of between about 0.5 gm/L-2
gm/L,
[0423] serine at a concentration of between about 0.5 gm/L-2
gm/L,
[0424] valine at a concentration of between about 0.5 gm/L-2 gm/L,
and
[0425] tryptophan at a concentration of between about 0.5 gm/L-2
gm/L.
[0426] The composition will not contain glucose or a carbohydrate
that may be hydrolyzed into glucose in the gut. Glucose increases
paracellular permeability (leaky gut). In addition glucose may
further dehydrate the tissues.
[0427] The composition will also not contain glutamine, cysteine,
methionine, and/or lactose.
[0428] The subject invention is based, at least in part, on the
discovery that enteral feeding to subjects with only the nutrients
that retain or acquire sufficient absorptive capacity in cases of
environmental enteropathy improves mucosal healing, restores small
intestine function, enhances fluid retention, and alleviates an
array of associated disease symptoms including, but not limited to,
malabsorption, diarrhea, nausea, vomiting, electrolyte imbalance,
and dehydration.
[0429] In one embodiment the composition for the treatment of
environmental enteropathy may be delivered in powder or pill
form.
[0430] In one embodiment a method for the treatment of
environmental enteropathy comprises administering to the subject,
one of the compositions for the treatment of environmental
enteropathy described above.
[0431] Augmentation of Immunization Efficiencies
[0432] Immunization is a process by which the immune system becomes
fortified against an agent. When the immune system is exposed to
foreign molecules it will develop an immune response, and it will
also develop the ability to quickly respond to a subsequent
encounter because of immunological memory. This is a function of
the adaptive immune system. T lymphocytes, B lymphocytes, and the
antibodies B lymphocytes produce memory B lymphocytes and memory T
lymphocytes that are responsible for the immune system response to
a second encounter with a foreign molecule. Passive immunization is
when these elements are introduced directly into the body, instead
of when the body itself has to make these elements.
[0433] A composition for augmenting immunization efficiencies
includes one or more of the following constituents:
[0434] lysine at a concentration of about 730 to 6575 mg/l;
[0435] aspartic acid at a concentration of about 532 to 4792
mg/l;
[0436] glycine at a concentration of about 300 to 2703 mg/l;
[0437] isoleucine at a concentration of about 525 to 4722 mg/l;
[0438] threonine at a concentration of about 1 to 10,000 mg/L;
[0439] threonine at a concentration of about 476 to 4288 mg/l;
[0440] tyrosine at a concentration of about 725 to 6523 mg/l;
[0441] valine at a concentration of about 469 to 4217 mg/l;
[0442] tryptophan at a concentration of about 817 to 7352 mg/l;
[0443] asparagine at a concentration of about 528 to 4756 mg/l;
and/or
[0444] serine at a concentration of about 420 to 3784 mg/l,
[0445] or a subset of these ingredients. In other embodiments the
composition comprises two or more of the listed amino acids. The
amino acid compositions work by correcting the cell shrinkage that
occur secondary to chloride secretions, and thus correct mucosal
barrier defect and downstream local and systemic inflammation. The
amino acid composition initially rehydrates the vascular and
interstitial fluid compartments of the cells in the gut.
Subsequently, the amino acid composition rapidly rehydrates the
vascular, interstitial, and intracellular fluid compartments
throughout the body. The amino acid compositions correct
dehydration in vascular, interstitial and intracellular compartment
to restore the intracellular fluid volume and decrease the cell
shrinkage and therefore paracellular permeability. The composition
does not contain glutamine, glucose or carbohydrates that can
hydrolyze into glucose in the gut.
[0446] In another preferred embodiment, the composition to improve
immunization efficiencies may comprise a combination of one or more
of the following amino acids:
[0447] threonine at a concentration of between about 1 mg/L-10
gm/L,
[0448] tyrosine at a concentration of between about 1 mg/L-10
gm/L,
[0449] serine at a concentration of between about 1 mg/L-10
gm/L,
[0450] valine at a concentration of between about 1 mg/L-10 gm/L
and
[0451] tryptophan at a concentration of between about 1 mg/L-10
gm/L.
[0452] In one embodiment the formulation may be formulated for
parenteral administration such as intravenously.
[0453] In a more preferred embodiment the composition may comprise
a combination of one or more of the following amino acids:
[0454] threonine at a concentration of between about 100 mg/L-5
gm/L,
[0455] tyrosine at a concentration of between about 100 mg/L-5
gm/L,
[0456] serine at a concentration of between about 100 mg/L-5
gm/L,
[0457] valine at a concentration of between about 100 mg/L-5 gm/L.
and
[0458] tryptophan at a concentration of between about 100 mg/L-5
gm/L.
[0459] In a most preferred embodiment the composition may comprise
a combination of one or more of the following amino acids:
[0460] threonine at a concentration of between about 0.5 gm/L-2
gm/L,
[0461] tyrosine at a concentration of between about 0.5 gm/L-2
gm/L,
[0462] serine at a concentration of between about 0.5 gm/L-2
gm/L,
[0463] valine at a concentration of between about 0.5 gm/L-2 gm/L
and
[0464] tryptophan at a concentration of between about 0.5 gm/L-2
gm/L.
[0465] In one embodiment the composition to improve immunization
efficiencies may be delivered in powder or pill form.
[0466] In one embodiment a method for augmenting immunization
efficiencies comprises administering to the subject, one of the
compositions for the improvement of immunization efficiencies
described above.
[0467] Treatment of the Effects of Irradiation
[0468] Gastrointestinal toxicity can occur following irradiation of
abdominal or other malignancies in cases where normal
gastrointestinal structures are located within the radiation
therapy (RT) field. These toxicities may limit the maximum dose of
RT and chemotherapy. Side effects of RT include early (acute)
toxicity, such as diarrhea and nausea.
[0469] A composition for the treatment of the effects of
irradiation includes one or more of the following constituents:
[0470] lysine at a concentration of about 730 to 6575 mg/l;
[0471] aspartic acid at a concentration of about 532 to 4792
mg/l;
[0472] glycine at a concentration of about 300 to 2703 mg/l;
[0473] isoleucine at a concentration of about 525 to 4722 mg/l;
[0474] threonine at a concentration of about 476 to 4288 mg/l;
[0475] tyrosine at a concentration of about 725 to 6523 mg/l;
[0476] valine at a concentration of about 469 to 4217 mg/l;
[0477] tryptophan at a concentration of about 817 to 7352 mg/l;
[0478] asparagine at a concentration of about 528 to 4756 mg/l;
and/or
[0479] serine at a concentration of about 420 to 3784 mg/l,
[0480] or a subset of these ingredients. In other embodiments the
composition comprises two or more of the listed amino acids. The
amino acid compositions work by correcting the cell shrinkage that
occur secondary to chloride secretions, and thus correct mucosal
barrier defect and downstream local and systemic inflammation. The
amino acid composition initially rehydrates the vascular and
interstitial fluid compartments of the cells in the gut.
Subsequently, the amino acid composition rapidly rehydrates the
vascular, interstitial, and intracellular fluid compartments
throughout the body. The amino acid compositions correct
dehydration in vascular, interstitial and intracellular compartment
to restore the intracellular fluid volume and decrease the cell
shrinkage and therefore paracellular permeability. The composition
does not contain glutamine, glucose or carbohydrates that can
hydrolyze into glucose in the gut.
[0481] In another preferred embodiment, the composition for the
treatment of the effects of irradiation may comprise a combination
of one or more of the following amino acids:
[0482] threonine at a concentration of between about 1 mg/L-10
gm/L,
[0483] tyrosine at a concentration of between about 1 mg/L-10
gm/L,
[0484] serine at a concentration of between about 1 mg/L-10
gm/L,
[0485] valine at a concentration of between about 1 mg/L-10 gm/L,
and
[0486] tryptophan at a concentration of between about 1 mg/L-10
gm/L.
[0487] In one embodiment the formulation may be formulated for
parenteral administration such as intravenously.
[0488] In a more preferred embodiment the composition may comprise
a combination of one or more of the following amino acids:
[0489] threonine at a concentration of between about 100 mg/L-5
gm/L,
[0490] tyrosine at a concentration of between about 100 mg/L-5
gm/L,
[0491] serine at a concentration of between about 100 mg/L-5
gm/L,
[0492] valine at a concentration of between about 100 mg/L-5 gm/L,
and
[0493] tryptophan at a concentration of between about 100 mg/L-5
gm/L.
[0494] In a most preferred embodiment the composition may comprise
a combination of one or more of the following amino acids:
[0495] threonine at a concentration of between about 0.5 gm/L-2
gm/L,
[0496] tyrosine at a concentration of between about 0.5 gm/L-2
gm/L,
[0497] serine at a concentration of between about 0.5 gm/L-2
gm/L,
[0498] valine at a concentration of between about 0.5 gm/L-2 gm/L
and
[0499] tryptophan at a concentration of between about 0.5 gm/L-2
gm/L.
[0500] It was found that there was an increase in the crypt number,
crypt height, villous length and villous number in irradiated and
non-irradiated mice treated with the amino acids mixture for a
period of time as short as four days.
[0501] In one embodiment the composition for the treatment of the
effects of irradiation may be delivered in powder or pill form.
[0502] In one embodiment a method for the treatment the effects of
irradiation comprises administering to the subject, one of the
compositions for the treatment of the effects of irradiation
described above.
[0503] Treatment of Ebola Symptoms
[0504] In one embodiment the composition decreases stool volume and
frequency in acute diarrheal situations, rapidly corrects
dehydration and tightens the mucosal barrier. Such effects are
effective in correcting the fluid loss in patients with Ebola
virus.
[0505] A composition for the treatment of Ebola virus infection
symptoms may include one or more of the following constituents:
[0506] lysine at a concentration of about 730 to 6575 mg/l;
[0507] aspartic acid at a concentration of about 532 to 4792
mg/l;
[0508] glycine at a concentration of about 300 to 2703 mg/l;
[0509] isoleucine at a concentration of about 525 to 4722 mg/l;
[0510] threonine at a concentration of about 476 to 4288 mg/l;
[0511] tyrosine at a concentration of about 725 to 6523 mg/l;
[0512] valine at a concentration of about 469 to 4217 mg/l;
[0513] tryptophan at a concentration of about 817 to 7352 mg/l;
[0514] asparagine at a concentration of about 528 to 4756 mg/l;
and/or
[0515] serine at a concentration of about 420 to 3784 mg/l,
or a subset of these ingredients. In other embodiments the
composition comprises two or more of the listed amino acids. The
amino acid compositions work by correcting the cell shrinkage that
occur secondary to chloride secretions, and thus correct mucosal
barrier defect and downstream local and systemic inflammation. The
amino acid composition initially rehydrates the vascular and
interstitial fluid compartments of the cells in the gut.
Subsequently, the amino acid composition rapidly rehydrates the
vascular, interstitial, and intracellular fluid compartments
throughout the body. The amino acid compositions correct
dehydration in vascular, interstitial and intracellular compartment
to restore the intracellular fluid volume and decrease the cell
shrinkage and therefore paracellular permeability. The composition
does not contain glutamine, glucose or carbohydrates that can
hydrolyze into glucose in the gut. The amino acids help move fluid
into the three fluid compartments and therefore form a complete
rehydration mechanism.
[0516] In another preferred embodiment, the composition may
comprise a combination of one or more of the following amino
acids:
[0517] threonine at a concentration of between about 1 mg/L-10
gm/L,
[0518] tyrosine at a concentration of between about 1 mg/L-10
gm/L,
[0519] serine at a concentration of between about 1 mg/L-10
gm/L,
[0520] valine at a concentration of between about 1 mg/L-10 gm/L,
and
[0521] tryptophan at a concentration of between about 1 mg/L-10
gm/L.
[0522] In one embodiment the formulation may be formulated for
parenteral administration such as intravenously.
[0523] In a more preferred embodiment the composition may comprise
a combination of one or more of the following amino acids:
[0524] threonine at a concentration of between about 100 mg/L-5
gm/L,
[0525] tyrosine at a concentration of between about 100 mg/L-5
gm/L,
[0526] serine at a concentration of between about 100 mg/L-5
gm/L,
[0527] valine at a concentration of between about 100 mg/L-5 gm/L,
and
[0528] tryptophan at a concentration of between about 100 mg/L-5
gm/L.
[0529] In a most preferred embodiment the composition may comprise
a combination of one or more of the following amino acids:
[0530] threonine at a concentration of between about 0.5 gm/L-2
gm/L, tyrosine at a concentration of between about 0.5 gm/L-2 gm/L,
serine at a concentration of between about 0.5 gm/L-2 gm/L, valine
at a concentration of between about 0.5 gm/L-2 gm/L, and tryptophan
at a concentration of between about 0.5 gm/L-2 gm/L.
[0531] The composition will not contain glucose or a carbohydrate
that may be hydrolyzed into glucose in the gut. Glucose increases
paracellular permeability (leaky gut). In addition glucose may
further dehydrate the tissues.
[0532] The composition will also not contain glutamine, cysteine,
methionine, and/or lactose.
[0533] In one embodiment a method for the treatment of symptoms of
Ebola virus infection comprises administering to the subject, one
of the compositions for the treatment of Ebola virus infection
described above.
[0534] TREATMENT OF HIV SYMPTOMS
[0535] In one embodiment, the compositions disclosed herein are
used in a method for the treatment of HIV infection symptoms.
[0536] A composition for the treatment of HIV infection symptoms
may include one or more of the following constituents:
[0537] lysine at a concentration of about 730 to 6575 mg/l;
[0538] aspartic acid at a concentration of about 532 to 4792
mg/l;
[0539] glycine at a concentration of about 300 to 2703 mg/l;
[0540] isoleucine at a concentration of about 525 to 4722 mg/l;
[0541] threonine at a concentration of about 476 to 4288 mg/l;
[0542] tyrosine at a concentration of about 725 to 6523 mg/l;
[0543] valine at a concentration of about 469 to 4217 mg/l;
[0544] tryptophan at a concentration of about 817 to 7352 mg/l;
[0545] asparagine at a concentration of about 528 to 4756 mg/l;
and/or
[0546] serine at a concentration of about 420 to 3784 mg/l,
or a subset of these ingredients. In other embodiments the
composition comprises two or more of the listed amino acids. The
amino acid compositions work by correcting the cell shrinkage that
occurs secondary to chloride secretions, and thus correct mucosal
barrier defect and downstream local and systemic inflammation. The
amino acid composition initially rehydrates the vascular and
interstitial fluid compartments of the cells in the gut.
Subsequently, the amino acid composition rapidly rehydrates the
vascular, interstitial, and intracellular fluid compartments
throughout the body. The amino acid compositions correct
dehydration in vascular, interstitial and intracellular compartment
to restore the intracellular fluid volume and decrease the cell
shrinkage and therefore paracellular permeability. The composition
does not contain glutamine, glucose or carbohydrates that can
hydrolyze into glucose in the gut. The amino acids help move fluid
into the three fluid compartments and therefore form a complete
rehydration mechanism.
[0547] In another preferred embodiment, the composition may
comprise a combination of one or more of the following amino
acids:
[0548] threonine at a concentration of between about 1 mg/L-10
gm/L,
[0549] tyrosine at a concentration of between about 1 mg/L-10
gm/L,
[0550] serine at a concentration of between about 1 mg/L-10
gm/L,
[0551] valine at a concentration of between about 1 mg/L-10 gm/L,
and
[0552] tryptophan at a concentration of between about 1 mg/L-10
gm/L.
In one embodiment the formulation may be formulated for parenteral
administration such as intravenously.
[0553] In a more preferred embodiment the composition may comprise
a combination of one or more of the following amino acids:
[0554] threonine at a concentration of between about 100 mg/L-5
gm/L,
[0555] tyrosine at a concentration of between about 100 mg/L-5
gm/L,
[0556] serine at a concentration of between about 100 mg/L-5
gm/L,
[0557] valine at a concentration of between about 100 mg/L-5 gm/L,
and
[0558] tryptophan at a concentration of between about 100 mg/L-5
gm/L.
[0559] In a most preferred embodiment the composition may comprise
a combination of one or more of the following amino acids:
[0560] threonine at a concentration of between about 0.5 gm/L-2
gm/L,
[0561] tyrosine at a concentration of between about 0.5 gm/L-2
gm/L,
[0562] serine at a concentration of between about 0.5 gm/L-2
gm/L,
[0563] valine at a concentration of between about 0.5 gm/L-2 gm/L,
and
[0564] tryptophan at a concentration of between about 0.5 gm/L-2
gm/L.
[0565] The composition will not contain glucose or a carbohydrate
that may be hydrolyzed into glucose in the gut. Glucose increases
paracellular permeability (leaky gut). In addition glucose may
further dehydrate the tissues.
[0566] The composition will also not contain glutamine, cysteine,
methionine, and/or lactose.
[0567] The subject invention is based, at least in part, on the
discovery that enteral feeding to subjects with only the nutrients
that retain or acquire sufficient absorptive capacity alleviates
symptoms associated with HIV infection.
[0568] In one embodiment a method for the treatment of HIV symptoms
comprises administering to the subject, one of the compositions for
the treatment of HIV symptoms described above.
[0569] Treatment of Ataxia Symptoms
[0570] In one embodiment, the compositions disclosed herein are
used in a method for the treatment of Ataxia symptoms.
[0571] A composition for the treatment of Ataxia symptoms may
include one or more of the following constituents:
[0572] lysine at a concentration of about 730 to 6575 mg/l;
[0573] aspartic acid at a concentration of about 532 to 4792
mg/l;
[0574] glycine at a concentration of about 300 to 2703 mg/l;
[0575] isoleucine at a concentration of about 525 to 4722 mg/l;
[0576] threonine at a concentration of about 476 to 4288 mg/l;
[0577] tyrosine at a concentration of about 725 to 6523 mg/l;
[0578] valine at a concentration of about 469 to 4217 mg/l;
[0579] tryptophan at a concentration of about 817 to 7352 mg/l;
[0580] asparagine at a concentration of about 528 to 4756 mg/l;
and/or
[0581] serine at a concentration of about 420 to 3784 mg/l,
or a subset of these ingredients. In other embodiments the
composition comprises two or more of the listed amino acids. The
amino acid compositions work by correcting the cell shrinkage that
occurs secondary to chloride secretions, and thus correct mucosal
barrier defect and downstream local and systemic inflammation. The
amino acid composition initially rehydrates the vascular and
interstitial fluid compartments of the cells in the gut.
Subsequently, the amino acid composition rapidly rehydrates the
vascular, interstitial, and intracellular fluid compartments
throughout the body. The amino acid compositions correct
dehydration in vascular, interstitial and intracellular compartment
to restore the intracellular fluid volume and decrease the cell
shrinkage and therefore paracellular permeability. The composition
does not contain glutamine, glucose or carbohydrates that can
hydrolyze into glucose in the gut. The amino acids help move fluid
into the three fluid compartments and therefore form a complete
rehydration mechanism.
[0582] In another preferred embodiment, the composition may
comprise a combination of one or more of the following amino
acids:
[0583] threonine at a concentration of between about 1 mg/L-10
gm/L,
[0584] tyrosine at a concentration of between about 1 mg/L-10
gm/L,
[0585] serine at a concentration of between about 1 mg/L-10
gm/L,
[0586] valine at a concentration of between about 1 mg/L-10 gm/L,
and
[0587] tryptophan at a concentration of between about 1 mg/L-10
gm/L.
In one embodiment the formulation may be formulated for parenteral
administration such as intravenously.
[0588] In a more preferred embodiment the composition may comprise
a combination of one or more of the following amino acids:
[0589] threonine at a concentration of between about 100 mg/L-5
gm/L,
[0590] tyrosine at a concentration of between about 100 mg/L-5
gm/L,
[0591] serine at a concentration of between about 100 mg/L-5
gm/L,
[0592] valine at a concentration of between about 100 mg/L-5 gm/L,
and
[0593] tryptophan at a concentration of between about 100 mg/L-5
gm/L.
[0594] In a most preferred embodiment the composition may comprise
a combination of one or more of the following amino acids:
[0595] threonine at a concentration of between about 0.5 gm/L-2
gm/L,
[0596] tyrosine at a concentration of between about 0.5 gm/L-2
gm/L,
[0597] serine at a concentration of between about 0.5 gm/L-2
gm/L,
[0598] valine at a concentration of between about 0.5 gm/L-2 gm/L,
and
[0599] tryptophan at a concentration of between about 0.5 gm/L-2
gm/L.
[0600] The composition will not contain glucose or a carbohydrate
that may be hydrolyzed into glucose in the gut. Glucose increases
paracellular permeability (leaky gut). In addition glucose may
further dehydrate the tissues.
[0601] The composition will also not contain glutamine, cysteine,
methionine, and/or lactose.
[0602] The subject invention is based, at least in part, on the
discovery that enteral feeding to subjects with only the nutrients
that retain or acquire sufficient absorptive capacity alleviates
symptoms associated with Ataxia.
[0603] In one embodiment a method for the treatment of Ataxia
symptoms comprises administering to the subject, one of the
compositions for the treatment of Ataxia symptoms described
above.
[0604] Method for Increasing Villus Height and Crypt Number
[0605] In one embodiment, the compositions disclosed herein are
used in a method for increasing Villus height and crypt
numbers.
[0606] A composition to promote the increase of Villus height and
crypt numbers may include one or more of the following
constituents:
[0607] lysine at a concentration of about 730 to 6575 mg/l;
[0608] aspartic acid at a concentration of about 532 to 4792
mg/l;
[0609] glycine at a concentration of about 300 to 2703 mg/l;
[0610] isoleucine at a concentration of about 525 to 4722 mg/l;
[0611] threonine at a concentration of about 476 to 4288 mg/l;
[0612] tyrosine at a concentration of about 725 to 6523 mg/l;
[0613] valine at a concentration of about 469 to 4217 mg/l;
[0614] tryptophan at a concentration of about 817 to 7352 mg/l;
[0615] asparagine at a concentration of about 528 to 4756 mg/l;
and/or
[0616] serine at a concentration of about 420 to 3784 mg/l,
or a subset of these ingredients. In other embodiments the
composition comprises two or more of the listed amino acids. The
amino acid compositions work by correcting the cell shrinkage that
occurs secondary to chloride secretions, and thus correct mucosal
barrier defect and downstream local and systemic inflammation. The
amino acid compositions correct dehydration in vascular,
interstitial and intracellular compartment to restore the
intracellular fluid volume and decrease the cell shrinkage and
therefore paracellular permeability. The amino acid composition
initially rehydrates the vascular and interstitial fluid
compartments of the cells in the gut. Subsequently, the amino acid
composition rapidly rehydrates the vascular, interstitial, and
intracellular fluid compartments throughout the body. The
composition does not contain glutamine, glucose or carbohydrates
that can hydrolyze into glucose in the gut. The amino acids help
move fluid into the three fluid compartments and therefore form a
complete rehydration mechanism.
[0617] In another preferred embodiment, the composition may
comprise a combination of one or more of the following amino
acids:
[0618] threonine at a concentration of between about 1 mg/L-10
gm/L,
[0619] tyrosine at a concentration of between about 1 mg/L-10
gm/L,
[0620] serine at a concentration of between about 1 mg/L-10
gm/L,
[0621] valine at a concentration of between about 1 mg/L-10 gm/L,
and
[0622] tryptophan at a concentration of between about 1 mg/L-10
gm/L.
In one embodiment the formulation may be formulated for parenteral
administration such as intravenously.
[0623] In a more preferred embodiment the composition may comprise
a combination of one or more of the following amino acids:
[0624] threonine at a concentration of between about 100 mg/L-5
gm/L,
[0625] tyrosine at a concentration of between about 100 mg/L-5
gm/L,
[0626] serine at a concentration of between about 100 mg/L-5
gm/L,
[0627] valine at a concentration of between about 100 mg/L-5 gm/L,
and
[0628] tryptophan at a concentration of between about 100 mg/L-5
gm/L.
[0629] In a most preferred embodiment the composition may comprise
a combination of one or more of the following amino acids:
[0630] threonine at a concentration of between about 0.5 gm/L-2
gm/L,
[0631] tyrosine at a concentration of between about 0.5 gm/L-2
gm/L,
[0632] serine at a concentration of between about 0.5 gm/L-2
gm/L,
[0633] valine at a concentration of between about 0.5 gm/L-2 gm/L,
and
[0634] tryptophan at a concentration of between about 0.5 gm/L-2
gm/L.
[0635] The composition will not contain glucose or a carbohydrate
that may be hydrolyzed into glucose in the gut. Glucose increases
paracellular permeability (leaky gut). In addition glucose may
further dehydrate the tissues.
[0636] The composition will also not contain glutamine, cysteine,
methionine, and/or lactose.
[0637] The subject invention is based, at least in part, on the
discovery that enteral feeding to subjects with only the nutrients
that retain or acquire sufficient absorptive capacity increase
Villus height and crypt number.
[0638] In one embodiment a method for the promotion of increased
Villus height and crypt number comprises administering to the
subject, one of the compositions for the promotion of increased
Villus height and crypt number described above.
[0639] Treatment of Environmental Enteropathy
[0640] In one embodiment, the compositions disclosed herein are
used in a method for the treatment of environmental enteropathy
symptoms.
[0641] A composition for the treatment of environmental enteropathy
symptoms may include one or more of the following constituents:
[0642] lysine at a concentration of about 730 to 6575 mg/l;
[0643] aspartic acid at a concentration of about 532 to 4792
mg/l;
[0644] glycine at a concentration of about 300 to 2703 mg/l;
[0645] isoleucine at a concentration of about 525 to 4722 mg/l;
[0646] threonine at a concentration of about 476 to 4288 mg/l;
[0647] tyrosine at a concentration of about 725 to 6523 mg/l;
[0648] valine at a concentration of about 469 to 4217 mg/l;
[0649] tryptophan at a concentration of about 817 to 7352 mg/l;
[0650] asparagine at a concentration of about 528 to 4756 mg/l;
and/or
[0651] serine at a concentration of about 420 to 3784 mg/l,
or a subset of these ingredients. In other embodiments the
composition comprises two or more of the listed amino acids. The
amino acid composition initially rehydrates the vascular and
interstitial fluid compartments of the cells in the gut.
Subsequently, the amino acid composition rapidly rehydrates the
vascular, interstitial, and intracellular fluid compartments
throughout the body. The amino acid compositions work by correcting
the cell shrinkage that occurs secondary to chloride secretions,
and thus correct mucosal barrier defect and downstream local and
systemic inflammation. The amino acid compositions correct
dehydration in vascular, interstitial and intracellular compartment
to restore the intracellular fluid volume and decrease the cell
shrinkage and therefore paracellular permeability. The composition
does not contain glutamine, glucose or carbohydrates that can
hydrolyze into glucose in the gut. The amino acids help move fluid
into the three fluid compartments and therefore form a complete
rehydration mechanism.
[0652] In another preferred embodiment, the composition may
comprise a combination of one or more of the following amino
acids:
[0653] threonine at a concentration of between about 1 mg/L-10
gm/L,
[0654] tyrosine at a concentration of between about 1 mg/L-10
gm/L,
[0655] serine at a concentration of between about 1 mg/L-10
gm/L,
[0656] valine at a concentration of between about 1 mg/L-10 gm/L,
and
[0657] tryptophan at a concentration of between about 1 mg/L-10
gm/L.
In one embodiment the formulation may be formulated for parenteral
administration such as intravenously.
[0658] In a more preferred embodiment the composition may comprise
a combination of one or more of the following amino acids:
[0659] threonine at a concentration of between about 100 mg/L-5
gm/L,
[0660] tyrosine at a concentration of between about 100 mg/L-5
gm/L,
[0661] serine at a concentration of between about 100 mg/L-5
gm/L,
[0662] valine at a concentration of between about 100 mg/L-5 gm/L,
and
[0663] tryptophan at a concentration of between about 100 mg/L-5
gm/L.
[0664] In a most preferred embodiment the composition may comprise
a combination of one or more of the following amino acids:
[0665] threonine at a concentration of between about 0.5 gm/L-2
gm/L,
[0666] tyrosine at a concentration of between about 0.5 gm/L-2
gm/L,
[0667] serine at a concentration of between about 0.5 gm/L-2
gm/L,
[0668] valine at a concentration of between about 0.5 gm/L-2 gm/L,
and
[0669] tryptophan at a concentration of between about 0.5 gm/L-2
gm/L.
[0670] The composition will not contain glucose or a carbohydrate
that may be hydrolyzed into glucose in the gut. Glucose increases
paracellular permeability (leaky gut). In addition glucose may
further dehydrate the tissues.
[0671] The composition will also not contain glutamine, cysteine,
methionine, and/or lactose.
[0672] The subject invention is based, at least in part, on the
discovery that enteral feeding to subjects with only the nutrients
that retain or acquire sufficient absorptive capacity alleviates
symptoms associated with environmental enteropathy.
[0673] In one embodiment a method for the treatment of
environmental enteropathy symptoms comprises administering to the
subject, one of the compositions for the treatment of environmental
enteropathy symptoms described above.
[0674] Treatment of Weight Loss Caused by Cancer
[0675] In one embodiment, the compositions disclosed herein are
used in a method for the treatment of weight loss caused by
cancer.
[0676] A composition for the treatment of weight loss caused by
cancer may include one or more of the following constituents:
[0677] lysine at a concentration of about 730 to 6575 mg/l;
[0678] aspartic acid at a concentration of about 532 to 4792
mg/l;
[0679] glycine at a concentration of about 300 to 2703 mg/l;
[0680] isoleucine at a concentration of about 525 to 4722 mg/l;
[0681] threonine at a concentration of about 476 to 4288 mg/l;
[0682] tyrosine at a concentration of about 725 to 6523 mg/l;
[0683] valine at a concentration of about 469 to 4217 mg/l;
[0684] tryptophan at a concentration of about 817 to 7352 mg/l;
[0685] asparagine at a concentration of about 528 to 4756 mg/l;
and/or
[0686] serine at a concentration of about 420 to 3784 mg/l,
or a subset of these ingredients. In other embodiments the
composition comprises two or more of the listed amino acids. The
amino acid compositions work by correcting the cell shrinkage that
occurs secondary to chloride secretions, and thus correct mucosal
barrier defect and downstream local and systemic inflammation. The
amino acid composition initially rehydrates the vascular and
interstitial fluid compartments of the cells in the gut.
Subsequently, the amino acid composition rapidly rehydrates the
vascular, interstitial, and intracellular fluid compartments
throughout the body. The amino acid compositions correct
dehydration in vascular, interstitial and intracellular compartment
to restore the intracellular fluid volume and decrease the cell
shrinkage and therefore paracellular permeability. The composition
does not contain glutamine, glucose or carbohydrates that can
hydrolyze into glucose in the gut.
[0687] In another preferred embodiment, the composition may
comprise a combination of one or more of the following amino
acids:
[0688] threonine at a concentration of between about 1 mg/L-10
gm/L,
[0689] tyrosine at a concentration of between about 1 mg/L-10
gm/L,
[0690] serine at a concentration of between about 1 mg/L-10
gm/L,
[0691] valine at a concentration of between about 1 mg/L-10 gm/L,
and
[0692] tryptophan at a concentration of between about 1 mg/L-10
gm/L.
In one embodiment the formulation may be formulated for parenteral
administration such as intravenously.
[0693] In a more preferred embodiment the composition may comprise
a combination of one or more of the following amino acids:
[0694] threonine at a concentration of between about 100 mg/L-5
gm/L,
[0695] tyrosine at a concentration of between about 100 mg/L-5
gm/L,
[0696] serine at a concentration of between about 100 mg/L-5
gm/L,
[0697] valine at a concentration of between about 100 mg/L-5 gm/L,
and
[0698] tryptophan at a concentration of between about 100 mg/L-5
gm/L.
[0699] In a most preferred embodiment the composition may comprise
a combination of one or more of the following amino acids:
[0700] threonine at a concentration of between about 0.5 gm/L-2
gm/L,
[0701] tyrosine at a concentration of between about 0.5 gm/L-2
gm/L,
[0702] serine at a concentration of between about 0.5 gm/L-2
gm/L,
[0703] valine at a concentration of between about 0.5 gm/L-2 gm/L,
and
[0704] tryptophan at a concentration of between about 0.5 gm/L-2
gm/L.
[0705] The composition will not contain glucose or a carbohydrate
that may be hydrolyzed into glucose in the gut. Glucose increases
paracellular permeability (leaky gut). In addition glucose may
further dehydrate the tissues.
[0706] The composition will also not contain glutamine, cysteine,
methionine, and/or lactose.
[0707] The subject invention is based, at least in part, on the
discovery that enteral feeding to subjects with only the nutrients
that retain or acquire sufficient absorptive capacity alleviates
the symptom of weight loss caused by cancer.
[0708] In one embodiment a method for the treatment of weight loss
caused by cancer comprises administering to the subject, one of the
compositions for the treatment of weight loss caused by cancer
described above.
[0709] Treatment of Norovirus Symptoms
[0710] In one embodiment, the compositions disclosed herein are
used in a method for the treatment of norovirus symptoms such as
diarrhea.
[0711] A composition for the treatment of norovirus symptoms may
include one or more of the following constituents:
[0712] lysine at a concentration of about 730 to 6575 mg/l;
[0713] aspartic acid at a concentration of about 532 to 4792
mg/l;
[0714] glycine at a concentration of about 300 to 2703 mg/l;
[0715] isoleucine at a concentration of about 525 to 4722 mg/l;
[0716] threonine at a concentration of about 476 to 4288 mg/l;
[0717] tyrosine at a concentration of about 725 to 6523 mg/l;
[0718] valine at a concentration of about 469 to 4217 mg/l;
[0719] tryptophan at a concentration of about 817 to 7352 mg/l;
[0720] asparagine at a concentration of about 528 to 4756 mg/l;
and/or
[0721] serine at a concentration of about 420 to 3784 mg/l,
or a subset of these ingredients. In other embodiments the
composition comprises two or more of the listed amino acids. The
amino acid compositions work by correcting the cell shrinkage that
occurs secondary to chloride secretions, and thus correct mucosal
barrier defect and downstream local and systemic inflammation. The
amino acid composition initially rehydrates the vascular and
interstitial fluid compartments of the cells in the gut.
Subsequently, the amino acid composition rapidly rehydrates the
vascular, interstitial, and intracellular fluid compartments
throughout the body. The amino acid compositions correct
dehydration in vascular, interstitial and intracellular compartment
to restore the intracellular fluid volume and decrease the cell
shrinkage and therefore paracellular permeability. The composition
does not contain glutamine, glucose or carbohydrates that can
hydrolyze into glucose in the gut.
[0722] In another preferred embodiment, the composition may
comprise a combination of one or more of the following amino
acids:
[0723] threonine at a concentration of between about 1 mg/L-10
gm/L,
[0724] tyrosine at a concentration of between about 1 mg/L-10
gm/L,
[0725] serine at a concentration of between about 1 mg/L-10
gm/L,
[0726] valine at a concentration of between about 1 mg/L-10 gm/L,
and
[0727] tryptophan at a concentration of between about 1 mg/L-10
gm/L.
In one embodiment the formulation may be formulated for parenteral
administration such as intravenously.
[0728] In a more preferred embodiment the composition may comprise
a combination of one or more of the following amino acids:
[0729] threonine at a concentration of between about 100 mg/L-5
gm/L,
[0730] tyrosine at a concentration of between about 100 mg/L-5
gm/L,
[0731] serine at a concentration of between about 100 mg/L-5
gm/L,
[0732] valine at a concentration of between about 100 mg/L-5 gm/L,
and
[0733] tryptophan at a concentration of between about 100 mg/L-5
gm/L.
[0734] In a most preferred embodiment the composition may comprise
a combination of one or more of the following amino acids:
[0735] threonine at a concentration of between about 0.5 gm/L-2
gm/L,
[0736] tyrosine at a concentration of between about 0.5 gm/L-2
gm/L,
[0737] serine at a concentration of between about 0.5 gm/L-2
gm/L,
[0738] valine at a concentration of between about 0.5 gm/L-2 gm/L,
and
[0739] tryptophan at a concentration of between about 0.5 gm/L-2
gm/L.
[0740] The composition will not contain glucose or a carbohydrate
that may be hydrolyzed into glucose in the gut. Glucose increases
paracellular permeability (leaky gut). In addition glucose may
further dehydrate the tissues.
[0741] The composition will also not contain glutamine, cysteine,
methionine, and/or lactose.
[0742] The subject invention is based, at least in part, on the
discovery that enteral feeding to subjects with only the nutrients
that retain or acquire sufficient absorptive capacity alleviates
the symptom of noravirus infection.
[0743] In one embodiment a method for the treatment of the symptoms
of norovirus infection comprises administering to the subject, one
of the compositions for the treatment of norovirus infection
symptoms described above.
[0744] Treatment of Food Poisoning Symptoms
[0745] In one embodiment, the compositions disclosed herein are
used in a method for the treatment of the symptoms of food
poisoning such as diarrhea.
[0746] A composition for the treatment of the symptoms of food
poisoning may include one or more of the following
constituents:
[0747] lysine at a concentration of about 730 to 6575 mg/l;
[0748] aspartic acid at a concentration of about 532 to 4792
mg/l;
[0749] glycine at a concentration of about 300 to 2703 mg/l;
[0750] isoleucine at a concentration of about 525 to 4722 mg/l;
[0751] threonine at a concentration of about 476 to 4288 mg/l;
[0752] tyrosine at a concentration of about 725 to 6523 mg/l;
[0753] valine at a concentration of about 469 to 4217 mg/l;
[0754] tryptophan at a concentration of about 817 to 7352 mg/l;
[0755] asparagine at a concentration of about 528 to 4756 mg/l;
and/or
[0756] serine at a concentration of about 420 to 3784 mg/l,
or a subset of these ingredients. In other embodiments the
composition comprises two or more of the listed amino acids. The
amino acid compositions work by correcting the cell shrinkage that
occurs secondary to chloride secretions, and thus correct mucosal
barrier defect and downstream local and systemic inflammation. The
amino acid composition initially rehydrates the vascular and
interstitial fluid compartments of the cells in the gut.
Subsequently, the amino acid composition rapidly rehydrates the
vascular, interstitial, and intracellular fluid compartments
throughout the body. The amino acid compositions correct
dehydration in vascular, interstitial and intracellular compartment
to restore the intracellular fluid volume and decrease the cell
shrinkage and therefore paracellular permeability. The composition
does not contain glutamine, glucose or carbohydrates that can
hydrolyze into glucose in the gut.
[0757] In another preferred embodiment, the composition may
comprise a combination of one or more of the following amino
acids:
[0758] threonine at a concentration of between about 1 mg/L-10
gm/L,
[0759] tyrosine at a concentration of between about 1 mg/L-10
gm/L,
[0760] serine at a concentration of between about 1 mg/L-10
gm/L,
[0761] valine at a concentration of between about 1 mg/L-10 gm/L,
and
[0762] tryptophan at a concentration of between about 1 mg/L-10
gm/L.
In one embodiment the formulation may be formulated for parenteral
administration such as intravenously.
[0763] In a more preferred embodiment the composition may comprise
a combination of one or more of the following amino acids:
[0764] threonine at a concentration of between about 100 mg/L-5
gm/L,
[0765] tyrosine at a concentration of between about 100 mg/L-5
gm/L,
[0766] serine at a concentration of between about 100 mg/L-5
gm/L,
[0767] valine at a concentration of between about 100 mg/L-5 gm/L,
and
[0768] tryptophan at a concentration of between about 100 mg/L-5
gm/L.
[0769] In a most preferred embodiment the composition may comprise
a combination of one or more of the following amino acids:
[0770] threonine at a concentration of between about 0.5 gm/L-2
gm/L,
[0771] tyrosine at a concentration of between about 0.5 gm/L-2
gm/L,
[0772] serine at a concentration of between about 0.5 gm/L-2
gm/L,
[0773] valine at a concentration of between about 0.5 gm/L-2 gm/L,
and
[0774] tryptophan at a concentration of between about 0.5 gm/L-2
gm/L.
[0775] The composition will not contain glucose or a carbohydrate
that may be hydrolyzed into glucose in the gut. Glucose increases
paracellular permeability (leaky gut). In addition glucose may
further dehydrate the tissues.
[0776] The composition will also not contain glutamine, cysteine,
methionine, and/or lactose.
[0777] The subject invention is based, at least in part, on the
discovery that enteral feeding to subjects with only the nutrients
that retain or acquire sufficient absorptive capacity alleviates
the symptom of food poisoning.
[0778] In one embodiment a method for the treatment of the symptoms
of food poisoning comprises administering to the subject, one of
the compositions for the treatment of food poisoning symptoms
described above.
[0779] Treatment of Wounds
[0780] The foregoing compositions may also be used as a topical
application for wounds. The amino acid composition described above
serves to reduce inflammation and enhance healing.
[0781] In one embodiment a method for the treatment of wounds
comprises topically applying to the subject, one of the
compositions described above.
[0782] The terms "a" and "an" and "the" and similar referents as
used in the context of describing the invention are to be construed
to cover both the singular and the plural, unless otherwise
indicated herein or clearly contradicted by context.
[0783] Recitation of ranges of values herein are merely intended to
serve as a shorthand method of referring individually to each
separate value falling within the range, unless otherwise indicated
herein, and each separate value is incorporated into the
specification as if it were individually recited herein. Unless
otherwise stated, all exact values provided herein are
representative of corresponding approximate values (e.g., all exact
exemplary values provided with respect to a particular factor or
measurement can be considered to also provide a corresponding
approximate measurement, modified by "about," where
appropriate).
[0784] The use of any and all examples, or exemplary language
(e.g., "such as") provided herein, is intended merely to better
illuminate the invention and does not pose a limitation on the
scope of the invention unless otherwise indicated. No language in
the specification should be construed as indicating any element is
essential to the practice of the invention unless as much is
explicitly stated.
[0785] The description herein of any aspect or embodiment of the
invention using terms such as "comprising", "having," "including"
or "containing" with reference to an element or elements is
intended to provide support for a similar aspect or embodiment of
the invention that "consists of," "consists essentially of," or
"substantially comprises" that particular element or elements,
unless otherwise stated or clearly contradicted by context (e.g., a
composition described herein as comprising a particular element
should be understood as also describing a composition consisting of
that element, unless otherwise stated or clearly contradicted by
context).
[0786] It should be understood that the examples and embodiments
described herein are for illustrative purposes only and that
various modifications or changes in light thereof will be suggested
to persons skilled in the art and are to be included within the
spirit and purview of this application.
* * * * *