U.S. patent application number 13/861030 was filed with the patent office on 2013-08-29 for methods for the use of branched chain amino acids.
This patent application is currently assigned to Nestec S.A.. The applicant listed for this patent is Nestec S.A.. Invention is credited to Norman Alan Greenberg.
Application Number | 20130225510 13/861030 |
Document ID | / |
Family ID | 38006384 |
Filed Date | 2013-08-29 |
United States Patent
Application |
20130225510 |
Kind Code |
A1 |
Greenberg; Norman Alan |
August 29, 2013 |
METHODS FOR THE USE OF BRANCHED CHAIN AMINO ACIDS
Abstract
The invention provides an orally-administrable nutritional
product comprising a dipeptide including a branched chain amino
acids (BCAA). In one embodiment, the nutritional product comprises
a dipeptide selected from at least one of the following:
alanyl-leucine, alanyl-isoleucine, alanyl-valine, glycyl-leucine,
glycyl-isoleucine, and glycyl-valine.
Inventors: |
Greenberg; Norman Alan; (New
Hope, MN) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Nestec S.A.; |
|
|
US |
|
|
Assignee: |
Nestec S.A.
Vevey
CH
|
Family ID: |
38006384 |
Appl. No.: |
13/861030 |
Filed: |
April 11, 2013 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
12901178 |
Oct 8, 2010 |
8486888 |
|
|
13861030 |
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|
12089970 |
Jun 30, 2008 |
7989418 |
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PCT/US2006/041615 |
Oct 26, 2006 |
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12901178 |
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60731450 |
Oct 28, 2005 |
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Current U.S.
Class: |
514/21.91 ;
426/648; 426/72; 562/561 |
Current CPC
Class: |
A23L 33/18 20160801;
A61P 21/00 20180101; A61K 38/05 20130101; A61K 45/06 20130101; A61P
3/02 20180101; C07K 5/06026 20130101 |
Class at
Publication: |
514/21.91 ;
562/561; 426/648; 426/72 |
International
Class: |
A23L 1/305 20060101
A23L001/305; A61K 45/06 20060101 A61K045/06; A61K 38/05 20060101
A61K038/05 |
Claims
1. An orally-administrable nutritional product comprising: at least
one dipeptide including at least one branched chain amino acid,
wherein the at least one dipeptide exhibits a bitterness less than
that of a free branched chain amino acid, and wherein the at least
one dipeptide comprises alanyl-isoleucine.
2. The orally-administrable nutritional product of claim 1, further
comprising at least one of a protein, a fiber, a fatty acid, a
vitamin, a mineral, a carbohydrate, a flavor agent, a medicament,
and a therapeutic agent.
Description
PRIORITY CLAIM
[0001] This application is a continuation of U.S. application Ser.
No. 12/901,178, filed Oct. 8, 2010, which is a continuation of
12/089,970, filed Jun. 30, 2008 now U.S. Pat. No. 7,989,418 issued
Aug. 2, 2011, which is a National Stage of International
Application No. PCT/U.S.2006/041615, filed on Oct. 26, 2006, which
claims priority to U.S. Provisional Appl. No. 60/731,450, filed
Oct. 28, 2005, the entire contents of which are expressly
incorporated herein by reference thereto.
BACKGROUND
[0002] The invention relates generally to use of branched chain
amino acids and more particularly to the use of dipeptides
including branched chain amino acids to reduce bitterness in
orally-administrable nutritional products.
[0003] Amino acids are the monomeric building blocks of proteins,
which in turn comprise a wide range of biological compounds,
including enzymes, antibodies, hormones, transport molecules for
ions and small molecules, collagen, and muscle tissues. Amino acids
are considered hydrophobic or hydrophilic, based upon their
solubility in water, and, more particularly, on the polarities of
their side chains. Amino acids having polar side chains are
hydrophilic, while amino acids having nonpolar side chains are
hydrophobic. The solubilities of amino acids, impart, determines
the structures of proteins. Hydrophilic amino acids tend to make up
the surfaces of proteins while hydrophobic amino acids tend to make
up the water-insoluble interior portions of proteins.
[0004] Of the common 20 amino acids, nine are considered essential
in humans, as the body cannot synthesize them. Rather, these nine
amino acids must be obtained through an individual's diet. A
deficiency of one or more amino acids can cause a negative nitrogen
balance, wherein more nitrogen is excreted than is ingested as
proteins are degraded faster than they are synthesized. Such a
condition can lead to disruption of enzymatic activity and the loss
of muscle mass.
[0005] A number of muscle-wasting conditions have been identified,
for which treatment with amino acid supplements has proved
beneficial. For example, cachexia is a severe body wasting
condition characterized by marked weight loss, anorexia, asthenia,
and anaemia. Cachexia is a common feature of a number of illnesses,
such as cancer, sepsis, chronic heart failure, rheumatoid
arthritis, and acquired immune deficiency syndrome (AIDS). In
addition, it has been found that certain tumors may induce cachexia
through the production of a 24 kDa glycoprotein called
proteolysis-inducing factor (PIF). PIF decreases protein synthesis,
activates protein degradation, and stimulates the
ATP-proteasome-dependent pathway. It has been hypothesized that the
decreased protein synthesis associated with PIF is the result of
PIF's ability to block the translation process of protein
synthesis. Another factor, Angiotensin II (Ang II) has shown
similar effects and may be involved in the muscle wasting observed
in some cases of cachexia. Other muscle wasting diseases and
disorders are known, including, for example, sarcopenia, an
age-related loss of muscle mass.
[0006] Treatment of conditions such as cachexia and sarcopenia
often includes nutritional supplementation, and, in particular,
amino acid supplementation, in an attempt to increase protein
synthesis and/or counteract protein degradation. Branched chain
amino acids (BCAAs), which include valine, leucine, and isoleucine,
are especially useful in such cases, as they have been shown to
function not only as protein building blocks, but also as inducers
of signal transduction pathways that modulate translation
initiation.
[0007] The wasting conditions above are just a few of the
conditions, disorders, and diseases for which amino acid
supplementation has proved beneficial. Amino acid supplementation
has also been used to treat diabetes, hypertension, high levels of
serum cholesterol and triglycerides, Parkinson's disease, insomnia,
drug and alcohol addiction, pain, insomnia, and hypoglycemia.
Supplementation with BCAAs, in particular, has been used to treat
liver disorders, including compromised liver function, including
cirrhosis, gall bladder disorders, chorea and dyskinesia, and
kidney disorders, including uremia. BCAA supplementation has also
proved successful in the treatment of patients undergoing
hemodialysis, resulting in improvements in overall health and
mood.
[0008] Unfortunately, BCAAs exhibit a strongly bitter taste. Some
patients reject oral nutritional supplements containing BCAAs
because of their objectionable taste, despite the physiological
benefits such supplements offer. Attempts to overcome such
rejection have included the addition of masking agents to the
supplement, which attempt to block the perception of bitterness,
and the addition of other strong flavors, such as chocolate mint.
Neither of these attempts has proved satisfactory. Masking agents
generally do not completely block a patient's perception of
bitterness and the addition of other strong flavors, while not
bitter, are often equally objectionable to patients with limited
appetites and/or nausea.
[0009] Accordingly, there is a need in the art for an
orally-administrable nutritional product and method for its
administration that do not suffer from the deficiencies above.
SUMMARY
[0010] The invention provides an orally-administrable nutritional
product comprising a dipeptide including a branched chain amino
acid (BCAA). The nutritional products of the present invention may
be used to maintain or promote a nitrogen balance in an individual
suffering from a disease, disorder, stress, or a consequence of
aging. The products of the present invention may similarly be used
to maintain or promote a nitrogen balance in an otherwise healthy
individual but who may be at risk for developing a nitrogen
imbalance, such as an individual engaged in athletic performance or
other physically strenuous activity. In one embodiment, the
nutritional product comprises a dipeptide selected from at least
one of the following: alanyl-leucine, alanyl-isoleucine,
alanyl-valine, glycyl-leucine, glycyl-isoleucine, and
glycyl-valine.
[0011] A first aspect of the invention provides an
orally-administrable nutritional product comprising: at least one
dipeptide including at least one branched chain amino acid, wherein
the at least one dipeptide exhibits a bitterness less than that of
a free branched chain amino acid.
[0012] A second aspect of the invention provides a method of
treating an individual suffering from at least one of a disease and
a disorder with an orally-administrable nutritional product, the
method comprising: administering to the individual an
orally-administrable nutritional product including: an effective
amount of at least one dipeptide including at least one branched
chain amino acid, wherein the dipeptide exhibits a bitterness less
than that of a free branched chain amino acid.
[0013] The illustrative aspects of the present invention are
designed to solve the problems herein described and other problems
not discussed, which are discoverable by a skilled artisan.
DETAILED DESCRIPTION
[0014] As indicated above, the present invention relates to the use
of a dipeptide including a branched chain amino acid (BCAA) to
reduce bitterness in an orally-administrable nutritional
product.
[0015] As used herein, the terms "treatment" and "treat" refer to
both prophylactic or preventive treatment and curative or
disease-modifying treatment, including treatment of patients at
risk of contracting a disease or suspected to have contracted a
disease, as well as patients who are ill or have been diagnosed as
suffering from a disease or medical condition. The terms
"treatment" and "treat" also refer to the maintenance and/or
promotion of health in an individual not suffering from a disease
but who may be susceptible to the development of an unhealthy
condition, such as nitrogen imbalance, due to, for example,
strenuous physical activity. Consequently, an "effective amount" is
an amount that treats a disease or medical condition in an
individual or, more generally, provides a nutritional,
physiological, or medical benefit to the individual.
[0016] Surprisingly, it has been found that dipeptides of a
branched chain amino acid (BCAA) and a second amino acid do not
exhibit the bitterness of the free branched chain amino acid. A
dipeptide is formed by the joining of the a-carboxyl group of one
amino acid to the a-amino group of another amino acid. In one
preferred dipeptide of the present invention, the second amino acid
is alanine. In another preferred dipeptide of the present
invention, the second amino acid is glycine. The preferred
dipeptides according to the present invention, therefore, are
alanyl-leucine, alanyl-isoleucine, alanyl-valine, glycyl-leucine,
glycyl-isoleucine, and glycyl-valine. It should be recognized,
however, that any amino acid may be used in the dipeptides of the
present invention, including a second BCAA. The dipeptides of the
present invention may be produced by any known or later-developed
method, including synthetic production.
[0017] Equal molar concentrations of free leucine and the
alanyl-leucine dipeptide were tasted after being dissolved in water
and after being added to a standard vanilla oral nutritional
supplement. In each instance, the alanyl-leucine dipeptide was
found to exhibit less bitterness than free leucine. The tests were
repeated, comparing free isoleucine to the alanyl-isoleucine
dipeptide and free valine to the alanyl-valine dipeptide. Again, in
each instance, the dipeptide was found to exhibit less bitterness
than the free BCAA. The dissolved, alanyl-leucine dipeptide was
also compared to Novartis' RESOURCE.RTM. Support.RTM., a
nutritional product containing approximately 3.2 g of free leucine
per 8 oz. serving. The dissolved alanyl-leucine dipeptide exhibited
less bitterness than RESOURCE.RTM. Support.RTM..
[0018] Accordingly, the present invention includes
orally-administrable nutritional products that substitute, in whole
or in part, a dipeptide including a BCAA for the free BCAA normally
used. As noted above, preferred dipeptides include one of alanine
and glycine and a BCAA, specifically alanyl-leucine,
alanyl-isoleucine, alanyl-valine, glycyl-leucine,
glycyl-isoleucine, and glycyl-valine dipeptides. The
orally-administrable nutritional product of the present invention
may further contain any number of ingredients that provide a
nutritional, physiological, or medical benefit to an individual.
Such ingredients include, for example, proteins, soluble and/or
insoluble fibers, fatty acids, vitamins, minerals, sugars and/or
other carbohydrates, flavor agents, and medicaments or other
therapeutic agents. The present invention further includes methods
for the administration of such orally-administrable nutritional
products to an individual.
[0019] The products and methods of the present invention may be
used, therefore, to treat an individual suffering from one or more
of the following: cachexia, cancer, tumor-induced weight loss,
sepsis, chronic heart failure, rheumatoid arthritis, acquired
immune deficiency syndrome (AIDS), sarcopenia, diabetes,
hypertension, high levels of serum cholesterol, high levels of
triglycerides, Parkinson's disease, insomnia, drug addiction,
alcohol addiction, pain, insomnia, hypoglycemia, compromised liver
function, including cirrhosis, gall bladder disorders, chorea,
dysidnesia, and a kidney disorder, including uremia. In addition,
the products and method of the present invention may be used to
treat an individual undergoing hemodialysis.
[0020] The foregoing description of various aspects of the
invention has been presented for purposes of illustration and
description. It is not intended to be exhaustive or to limit the
invention to the precise form disclosed, and obviously, many
modifications and variations are possible. Such modifications and
variations that may be apparent to a person skilled in the art are
intended to be included within the scope of the invention as
defined by the accompanying claims.
* * * * *