U.S. patent application number 12/702726 was filed with the patent office on 2010-08-12 for dietary supplements containing terpenoid acids of maslinic acid or oleanolic acid and process for enhancing muscle mass in mammals.
Invention is credited to Peter Miller, Augustin T. Romero, Tim Romero.
Application Number | 20100204121 12/702726 |
Document ID | / |
Family ID | 42540926 |
Filed Date | 2010-08-12 |
United States Patent
Application |
20100204121 |
Kind Code |
A1 |
Romero; Augustin T. ; et
al. |
August 12, 2010 |
DIETARY SUPPLEMENTS CONTAINING TERPENOID ACIDS OF MASLINIC ACID OR
OLEANOLIC ACID AND PROCESS FOR ENHANCING MUSCLE MASS IN MAMMALS
Abstract
A process for increasing lean body mass in a mammalian subject
is provided that includes administering to the subject a purified
quantity of maslinic acid, oleanolic acid, or a combination
thereof. The administration can be orally and benefits from
ingestion of an amino acid source such as dietary protein,
oligopeptides, or amino acids. Administration within 2 hours of
muscle-degrading exercise or on a daily basis for a period of time
increases lean body mass.
Inventors: |
Romero; Augustin T.;
(Columbia, TN) ; Romero; Tim; (Columbia, TN)
; Miller; Peter; (Broomfield, CO) |
Correspondence
Address: |
GIFFORD, KRASS, SPRINKLE,ANDERSON & CITKOWSKI, P.C
PO BOX 7021
TROY
MI
48007-7021
US
|
Family ID: |
42540926 |
Appl. No.: |
12/702726 |
Filed: |
February 9, 2010 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
61151369 |
Feb 10, 2009 |
|
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|
Current U.S.
Class: |
514/1.1 ;
514/557 |
Current CPC
Class: |
A23L 33/10 20160801;
A23L 33/19 20160801; A23L 33/185 20160801; A23L 33/175 20160801;
A61K 2300/00 20130101; A61P 43/00 20180101; A61K 31/192 20130101;
A61K 45/06 20130101; A61K 31/192 20130101 |
Class at
Publication: |
514/12 ;
514/557 |
International
Class: |
A61K 38/00 20060101
A61K038/00; A61K 31/19 20060101 A61K031/19 |
Claims
1. A process for increasing lean body mass in a mammalian subject
comprising: administering to said subject a purified quantity of
maslinic acid, oleanolic acid, or a combination thereof.
2. The process of claim 1, wherein administering is orally.
3. The process of claim 1, wherein said purified quantity is only
maslinic acid.
4. The process of claims 1-3, wherein said purified quantity is an
extract containing at least 10 extract weight percent of said
maslinic acid, said oleanolic acid, or a combination thereof.
5. The process of claim 1, further comprising mixing said purified
quantity with at least one dietary supplement additive of protein
or amino acids.
6. The process of claims 1-4, wherein said purified quantity is
devoid of cellulosics, lignins, or alkaloids associated with the
plant from which said extract is derived.
7. The process of claims 1, wherein administering occurs within 2
hours of muscle-degrading exercise.
8. A dietary supplement comprising an active component consisting
of: a purified quantity of maslinic acid, oleanolic acid, or a
combination thereof; a dietary amino acid source of protein
oligopeptides, or amino acids; and a dietary supplement
additive.
9. The supplement of claim 8, wherein said purified quantity is an
extract containing at least 10 extract weight percent of the
maslinic acid, the oleanolic acid, or the combination thereof.
10. The supplement of claim 8, wherein said dietary supplement
additive renders the supplement suitable for oral delivery.
11. The dietary supplement composition of claim 8, wherein said
purified quantity is 0.01%-5 total weight percent.
12. The supplement of claims 8-11, wherein said purified quantity
has a mass of between 0.1 and 5,000 milligrams.
13. The supplement of claim 8, wherein the protein source is at
least one of a whey protein isolate, a whey protein concentrate, a
free form amino acid, a buckwheat protein, a soy protein isolate or
concentrate, a milk protein isolate or concentrate, a micellar
casein, calcium or other caseinate proteins, or a rice protein or
any combination.
14. The supplement of claim 8, wherein said protein source is 3-52
grams of dietary protein.
15. The dietary supplement of claim 6, wherein the composition is
administered orally.
16. A dietary supplement composition comprising: a maslinic acid
extract containing at least 10% maslinic acids by dry weight,
wherein the maslinic acid extract comprises approximately 0.01%-5%
of the dry weight of the composition; and at least one source of
protein or nitrogen.
17. The dietary supplement composition of claim 16, wherein the
protein comprises whey protein isolate, whey protein concentrate,
free form amino acids, buckwheat protein, soy protein isolate or
concentrate, milk protein isolate or concentrate, micellar casein,
calcium or other caseinate proteins, rice protein or any
combination.
18. The dietary supplement composition of claim 16, wherein the
composition is administered orally.
19. The dietary supplement composition of claim 16, wherein the
maslinic acid comprises approximately 0.01%-5% of the dry weight of
the composition.
20. A method for enhancing nitrogen balance and lean body mass
comprising: administering a composition comprising an extract
containing at least 0.01% maslinic acid by dry weight.
21. The method of claim 20, wherein the composition includes at
least one source of protein or nitrogen.
Description
CROSS-REFERENCE TO RELATED APPLICATION
[0001] This application claims priority of U.S. Provisional Patent
Application Ser. No. 61/151,369 filed Feb. 10, 2009, which is
incorporated herein by reference.
FIELD OF THE INVENTION
[0002] The present invention relates to dietary supplement
compositions containing maslinic acid and methods of enhancing
nitrogen balance and lean body mass in humans and other mammals
through administration thereof.
BACKGROUND OF THE INVENTION
[0003] Proteins in the body are continuously degraded and
synthesized by processes that require energy. In a body, a positive
nitrogen balance occurs when the total nitrogen excreted in the
urine, feces and sweat is less than the total nitrogen ingested.
This positive nitrogen balance must exist for new tissue to be
synthesized.
[0004] Most Americans consume a 12 weight percent protein diet,
while most bodybuilders consume upwards of a 25% to 30% protein
diet. This bodybuilding subgroup, in order to add lean body mass to
their body, must consume additional amounts of protein in order to
maintain a positive nitrogen balance so the body can generate new
tissue. The average sedentary adult, however, only needs to consume
on the order of 30 to 60 grams of dietary protein per day to
balance amino acids consumed by the body, assuming a normal caloric
intake. Factors associated with increased protein requirements
include the following: growth of skeletal tissue or growth during
puberty, etc., low calorie diets, endurance training, strength
training, high muscle-to-fat ratio, and vegetarian diets.
[0005] If protein requirements of the body are not met by dietary
sources, a nitrogen deficit may develop. This deficit results from
urinary nitrogen excretion exceeding the amounts of dietary protein
being consumed. The increase in urinary nitrogen excretion is
caused by catabolism of proteins to provide the essential amino
acids that are not being supplied by dietary sources. A negative
nitrogen balance is caused by: the consumption of an insufficient
quantity of essential amino acid containing protein or the
consumption of protein lacking essential amino acids. In addition
to appropriate quantity and quality of protein consumed, sufficient
energy must also be consumed to support protein metabolism, else a
negative nitrogen balance will develop regardless of the quality or
quantity of protein consumed.
[0006] The most recent indications are that dietary protein in
excess of the current recommended dietary allowance (0.8 grams of
protein per kilogram of body weight per day) is likely needed for
optimal muscle growth. The current recommended daily allowance is
also inadequate for an athlete who trains daily, is still growing,
and/or who is in a peak performance training regime. Indeed, the
benefit of increased levels of dietary protein appears to plateau
at intakes well below the levels typically consumed by many
athletes. Therefore, while a diet high in protein is beneficial for
muscle growth, it may only be beneficial to an extent. Once a
certain intake level is reached, additional protein intake does not
help build muscle mass. Little progress has been made in overcoming
this maximal protein intake plateau through dietary
modifications.
[0007] Maslinic acid
(2-.alpha.,3-.beta.-dihydroxyolean-12-en-28-oic acid) and
structurally related oleanolic acid
(3-.beta.-hydroxyolean-12-en-28-oic acid) are widely distributed in
plants. These pentacyclic tri-terpenoid acids (hereafter "PTAs")
are particularly abundant in the surface wax on the fruits and
leaves of olive trees (Oleo europaea) (Bianchi et al., Phytochem.,
37(1), pp. 205-207, 1994) and solid waste from olive oil production
(Garcia-Granados et al., J. Chem. Res.; 2000 (2) pp. 56-57). Loquat
fruit (Eriobotrya japonica) also has considerable quantities of
these terpenoid acids.
[0008] Maslinic acid has been studied as it relates to cell-growth
changes in the liver and white muscle in different situations due
to differences in protein turnover rates and nucleic acid
concentrations (Peragon et al., Comp. Biochem. Physio. Part C:
Toxicology, 147(2), pp. 158-167, 2008). These terpenoid acids have
been implicated as protease inhibitors that may suppress cancers
yet promote astrocytic tumors (Martin et al., Can. Res., 67, pp.
3741, 2007).
[0009] Dietary maslinic acid induces higher protein synthesis in
trout to sustain the generation of new cells and to be exported for
different purposes. At the same time, maslinic acid stimulated the
protein degradation rate, both in relative (KD) and absolute (AD)
terms. The protein-efficiency ratio (PER) and feed-efficiency ratio
(FER) both increased in trout fed maslinic acid concentration at
250 mg kg-1, with respect to a control. (Peragon et al., Can. J.
Fish Aquat. Sci., 55(3), pp. 649-659 (1998).
[0010] The presence of abundant and well-organized rough
endoplasmic reticula as seen by electron microscopy in the
hepatocytes of trout fed 250 mg kg-1 maslinic acid confirms the
prolific biosynthesis of exportable proteins. (Ibid.) The higher
number of white-muscle cells, mediated by increase in the DNA, RNA,
and protein content, seems to result from a stimulation of the
biosynthesis pathways of all this macromolecules similar to those
produced by a growth factor. Maslinic acid fed to trout at 25 and
250 mg kg-1 increased the protein-synthesis rate (KS and AS), while
no significant changes were found in fractional protein-degradation
rate (KB) and only a minor increase in the absolute
protein-degradation rate (AD). These changes in protein-turnover
rates explain the high protein-accumulation rates (KG and AG) found
in trout fed with maslinic acid. (Ibid.) Conflicting studies found
80 mg kg-1 to retard juvenile dentex fish growth (Hidalgo et al.,
Aquacult. Nutri., 12(4), pp. 256-266, 2006).
[0011] In relation to these results, it has been reported that
maslinic acid leads to a high accumulation of glycogen in rainbow
trout liver (Fernandez-Navarro et al., 2006) and can also act as a
new type of glycogen phosphorylase inhibitor (Wen et al., 2005;
2006), the enzyme responsible for glycogen degradation in liver and
white muscle.
[0012] Thus, there exists a need for a dietary supplement
containing PTAs to promote building of muscle mass in a high
protein content diet.
SUMMARY OF THE INVENTION
[0013] A process for increasing lean body mass in a mammalian
subject is provided that includes administering to the subject a
purified quantity of maslinic acid, oleanolic acid, or a
combination thereof. The administration can be orally and benefits
from ingestion of an amino acid source such as dietary protein,
oligopeptides, or amino acids. Administration within 2 hours of
muscle-degrading exercise or on a daily basis for a period of time
increases lean body mass.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0014] The present invention has utility as a dietary supplement
for increasing muscle mass in a mammalian subject. While the
specific mechanism in the mammalian subject is unknown, an
inventive supplement when administered to a mammalian subject
allows additional consumed protein to help build muscle mass
relative to a control not consuming an inventive dietary
supplement. It is noted that other pentacyclic tri-terpenoid acids
do not exhibit the effects of an inventive dietary supplement. As
this class of compounds includes a variety of compounds identified
in plant signaling, there are numerous identified pentacyclic
tri-terpenoid acids. Other pentacyclic tri-terpenoid acids known
illustratively include ursolic acid, boswelic acid, and tormatic
acid.
[0015] Maslinic acid has an alpha ring hydroxyl group at the two
position relative to a hydrogen at that position in oleanolic acid.
Owing to the structural similarity therebetween, and commonality in
natural sources, it has been found that maslinic acid, oleanolic
acid, or a combination thereof is operative in the present
invention to increase muscle mass in a mammalian subject,
especially in instances when the mammalian subject is metabolically
active and working muscles and simultaneously consuming a high
protein diet.
[0016] According to the present invention, a mammalian subject is
defined to include a horse, cow, pig, goat, rabbit, rat, mouse,
cat, dog, non-human primate, and a human.
[0017] A purified quantity of maslinic acid, oleanolic acid, or a
combination thereof is extracted from various natural sources or
synthetically produced. Among natural sources, numerous plants
produce maslinic acid and/or oleanolic acid. As noted above, olive
root, olive leaves, and loquat fruit produce maslinic and oleanolic
acids in high concentration.
[0018] Regardless of the natural source, the inventive composition
acids are readily extracted with polar aprotic solvents such as
methylene chloride, C1-C6 alcohols, C3-C6 ketones, tetrahydrofuran,
formamid, C3-C16 esters, nitrogen-containing heterocyclics, and
combinations thereof. In particular, it is appreciated that crude
extraction from macerated plant material in a first solvent
followed by a secondary extraction from the inventive
acid-containing fraction serves to further purify the inventive
acids. A methylene chloride initial extraction followed by a
methanol extraction is exemplary of such extraction processes (Juan
et al., J. Nutri., 136, p. 2554, first column, 1-2, 2006).
[0019] As used herein, a "purified quantity" with respective to an
inventive acid of maslinic acid, oleanolic acid, or a combination
thereof is defined as being substantially free of lignins,
alkaloids, cellulosic material, and plant enzymes operating on
maslinic acid or oleanolic acid as enzymatic substrates. It is
noted that a given quantity of inventive acid is more effective
upon being administered in a purified quantity relative to
consumption of an equivalent inventive acid containing amount of
olive fruit. Without intending to be bound to a particular theory,
plant polymeric materials such as lignins and cellulosic material
tend to bind the inventive acids. The resulting extract in a
biocompatible solvent is readily administered as an elixir, aqueous
solution, slurried with protein or other additives, or lyophilized
to a powder. Regardless of the form of a purified inventive acid,
the inventive acid is readily formulated in a pharmaceutical
dietary supplement formulation in solid, semi-solid, or liquid
dosage forms, such as, for example, tablets, chewables,
suppositories, pills, capsules, powders, liquids, or suspensions,
and may be provided in unit dosages suitable for a single
administration. Time release preparations are also contemplated as
effective dosage formulations as detailed in the art. For example,
time release formulations are provided in U.S. Pat. No. 5,096,714;
U.S. Pat. No. 5,229,131; and U.S. Pat. No. 5,026,559. The
compositions may include an effective amount of a selected
substrate in combination with a pharmaceutically acceptable carrier
and, in addition, may include other medicinal agents,
pharmaceutical agents, carriers, or diluents.
[0020] In a solid composition embodiment, conventional nontoxic
solid carriers may include, for example, pharmaceutical grades of
mannitol, lactose, starch, magnesium stearate, sodium saccharine,
talc, cellulose, glucose, sucrose and magnesium carbonate. Liquid
pharmaceutically administrable compositions may, for example, be
prepared by dissolving or dispersing an active compound with
optimal pharmaceutical adjuvants in an excipient, such as water,
saline, aqueous dextrose, glycerol, or ethanol, to form a solution
or suspension. For example, the pharmaceutical composition may
contain minor amounts of nontoxic auxiliary substances such as
wetting or emulsifying agents, pH buffering agents, for example,
sodium acetate or triethanolamine oleate. Actual methods of
preparing such dosage forms are known, or will be apparent, to
those skilled in this art. (Remington's, 20.sup.th edition, pp.
721-979, 2000).
[0021] In an oral administration embodiment, fine powders or
granules may contain diluting, dispersing, or surface active
agents. The fine powders or granules may be presented in water or
in syrup, in capsules or sachets in the dry state, or in a
nonaqueous solution or suspension. Suspending agents may also be
included in tablets, which may include binders and lubricants in a
suspension. Flavoring, preserving, suspending, thickening, or
emulsifying agents may be also included to modify the taste and
texture of the composition. The tablets and granules provided for
oral administration may further be coated for ease of digestion.
(Ibid., pp. 858-902).
[0022] Preferably, the inventive acid dietary supplement
composition is combined with one or more protein sources. Such
sources may include whey protein isolate, whey protein concentrate,
free form amino acids, buckwheat protein, soy protein isolate or
concentrate, milk protein isolate or concentrate, micellar casein,
calcium or other caseinate proteins, rice protein, or any
combination of the above. More preferably the protein contains
quantities of essential amino acids.
[0023] It is further contemplated that variable dosing regiments
are operative in the method of treatment. While in some instances a
single dose treatment may be effective in producing therapeutic
effects, in other instances a treatment period in the range of, for
example, 6 weeks to 3 months may be utilized. The composition may
be administered orally, parentally, or intravenously by
intramuscular, intraperitoneal, or transdermally injection.
Injectables may be prepared in conventional forms, either liquid
solutions or suspensions, solid forms suitable for solution or
prior to injection, or as suspension in liquid prior to injection
or as emulsions. The dose of the dietary supplement composition may
vary depending on the age, weight, general condition of the user.
For example, human 65 kg male dosage is in the range of 0.1-5,000
mg of equivalent of dry maslinic acid or oleanolic acid per day may
be an effective range. Preferred doses for a human 65 kg male range
from 10 to 500 mg per day. Optionally, the inventive maslinic acid
is present from 0.01%-5% of the dry total weight of the
composition.
[0024] It is contemplated that variable dosing regiments are
operative in the inventive processes. While in some instances a
single dose of inventive composition as a dietary supplement, for
example, may be effective in producing therapeutic effects, in
other instances a treatment period in the range of, for example, 6
weeks to 3 months may be utilized. An inventive composition is
optionally delivered to a subject daily, weekly, biweekly, monthly,
or any subdivision therebetween or for longer periods. In some
embodiments a subject ingests an inventive composition daily.
Optionally, an inventive composition is delivered one, two, three,
four, five, or more times per day.
[0025] The composition is optionally administered orally,
parentally, or intravenously by intramuscular, intraperitoneal, or
transdermally injection. Injectables may be prepared in
conventional forms, either liquid solutions or suspensions, solid
forms suitable for solution or prior to injection, or as suspension
in liquid prior to injection or as emulsions. The dose of the
dietary supplement composition may vary depending on the age,
weight, general condition of the user. Several forms of
administration are operable herein illustratively including
ingestion, inhalation, or injection. Typical administrations are by
oral ingestion. Ingestion is optionally with or without other food.
In some embodiments an inventive composition is administered to a
subject along with a protein rich food or within 1 hour prior or
following administration illustratively by eating a protein rich
food. Carbohydrate rich foods are foods that in ingestible
quantities include greater than about 5 grams of protein.
[0026] In some embodiments of the inventive processes, greater
amounts of the inventive composition are initially administered to
the subject's diet in order to increase or enhance muscle size or
strength (loading period), followed by a maintenance period during
which the amounts of inventive composition are relatively
decreased. The loading period optionally extends several weeks. In
some embodiments a loading period is one, two, three, four, five,
six or more weeks. Optionally, a loading period is from one day to
six weeks or more, as well as any period therebetween as desired by
either the subject, the trainer, physician, or other depending on
the desired outcome and rapidity of desired results. Once a desired
muscle strength, size, or endurance has been obtained, lower
amounts of the inventive composition, illustratively a maintenance
period, are optionally administered to the subject to maintain or
improve the results. In some embodiments the inventive composition
is administered to a subject immediately following an exercise
period. On non-workout days, the inventive composition is
optionally administered anytime during the day, illustratively,
upon awakening or otherwise during the morning hours.
[0027] The following tables are intended to illustrate a particular
embodiment of the invention and are not intended to limit the scope
of the appended claims, in any way.
TABLE-US-00001 TABLE 1 Powder 10% by wt. maslinic acid extract 50
mg (5 mg maslinic acid) Whey Protein Isolate 40 g Natural Flavors
200 mg Thickening agents 100 mg Sucralose 50 mg
TABLE-US-00002 TABLE 2 Powder 10% by wt. maslinic acid extract +
200 mg (20 mg maslinic acid, 3% by wt. oleanolic acid 6 mg
oleanolic acid) L-Leucine 4000 mg L-Isoleucine 2000 mg L-Valine
2000 mg Flavors 400 mg Citric Acid 250 mg Sucralose 50 mg
TABLE-US-00003 TABLE 3 Maslinic acid 100 mg Whey Protein Isolate 30
g Whey Protein Concentrate 5 g Calcium Caseinate 5 g Aminogen 1000
mg L-Glutamine 1000 mg Flavors 500 mg Thickening Agents 500 mg
Dextrose 30 g
TABLE-US-00004 TABLE 4 Oleanolic acid 500 mg Maslinic acid 700 mg
Whey Protein Isolate 30 g Whey Protein Concentrate 5 g Calcium
Caseinate 5 g Aminogen 1000 mg L-Glutamine 1000 mg Flavors 500 mg
Thickening Agents 500 mg Dextrose 30 g
[0028] The present invention is further detailed with respect to
the following nonlimiting examples. These examples are not intended
to limit the interpretation or scope of the appended claims.
Example 1
[0029] The inventive composition of Table 1 is administered in a
double-blind study to a group of 6 body builders, with 4 body
builders acting as negative controls. Each subject consumed a diet
composed of between 25 and 30 total weight percent protein with the
controls receiving the composition provided in Table 1 with the
exception of the maslinic acid extract. The compositions are
administered once daily for 6 weeks. The test subjects at the end
of the trial show a 2% increase in lean body mass relative to the
control group.
Example 2
[0030] The trial of Example 1 is repeated with the inventive
composition of Table 2 substituted for that of Table 1 while a
repeat study control group received the Table 2 formulation lacking
inventive acid with a comparable result to that of Example 1.
Example 3
[0031] The procedure of Example 1 is repeated with the composition
taken orally within 2 hours of completing the most strenuous
exercise routine of the day with comparable results to that of
Example 1.
Example 4
[0032] The procedure of Example 1 is repeated with the inventive
composition of Table 4. After 2 weeks of administration, test
subjects had a lean body mass increase of 0.3% relative to controls
who consumed the Table 4 composition exclusive of oleanolic acid
and maslinic acid.
[0033] Patent documents and publications mentioned in the
specification are indicative of the levels of those skilled in the
art to which the invention pertains. These documents and
publications are incorporated herein by reference to the same
extent as if each individual document or publication was
specifically and individually incorporated herein by reference.
[0034] The foregoing description is illustrative of particular
embodiments of the invention, but is not meant to be a limitation
upon the practice thereof. The following claims, including all
equivalents thereof, are intended to define the scope of the
invention.
* * * * *