CA2885527C - Compositions and methods for improving health in animals - Google Patents

Abstract

A method of improving health in an animal includes administering to the animal a nutritional supplement comprising an amino acid secretagogue composition, which stimulates the pituitary gland in the animal to produce growth hormone. The nutritional supplement may be administered orally. The nutritional supplement may comprise L-arginine hydrochloride, L-pyroglutamic acid, L-lysine hydrochloride, and cysteine. When desired, the nutritional supplement may consist essentially of L-arginine hydrochloride, L-pyroglutamic acid, L-lysine hydrochloride, N-acetyl-L-cysteine, L-glutamine, and schizonepeta powder.

Description

COMPOSITIONS AND METHODS FOR IMPROVING HEALTH IN ANIMALS
PRIORITY CLAIM
This application claims the benefit of the filing date of United States Patent Application Serial Number 13/623,113, filed September 20, 2012, for "COMPOSITIONS AND METHODS FOR IMPROVING HEALTH IN
ANIMALS" and United States Patent Application Serial Number 13/623,111, filed September 20, 2012, for "COMPOSITIONS AND METHODS FOR IMPROVING
HEALTH IN CANINES."
TECHNICAL FIELD
Embodiments of the present disclosure generally relate to methods and nutritional supplements for improving health in animals.
BACKGROUND
Growth hormone is an anabolic hormone capable of promoting linear growth, weight gain and whole body nitrogen retention in animals. Growth hormone is produced in somatotroph cells of the anterior pituitary gland of animals and secreted throughout life. It is mainly controlled in the brain by two hypothalamic peptides:
growth hormone releasing hormone (GHRH), which stimulates its secretion and synthesis; and somatostatin, which inhibits them. Growth hormone is known to promote skeletal growth, to increase nitrogen retention and protein synthesis, and to affect glucose and lipid metabolism in animals.
As animal grows older, the growth hormone undergoes considerable decrement resulting in a loss of skeletal muscle mass, osteoporosis, increased fat deposition and decreased lean body mass. It has been demonstrated that the development of these changes can be offset by recombinant growth hormone therapy. However, current recombinant growth hormone therapy has several shortcomings, including frequent subcutaneous or intravenous injections, insulin resistance and impaired glucose tolerance.
Growth hormone has been administered to animals to offset the growth hormone deficiency in aged animals. Furthermore, there are reports of using growth

-2-hormone to boost certain desirable performances of animals. For example, growth hormone has been used to enhance growth performance in animals by increasing lean body mass with an overall improvement in feed efficiency, and to enhance fertility in animals. Additionally, growth hormone has been used to stimulate milk production and achieve an enhanced milk yield in mammals.
U.S. Patent 4,521,409, issued on June 4, 1985 to Bauman, and U.S. Patent 5,004,728, issued on April 2, 1991 to Chalupa disclose the administration of growth hormone to cattle and ruminants to stimulate milk production with an increase in feed to milk conversion. In U.S. Patent 5,416,073, issued on May 16, 1995 to Coy, growth hormone is used to increase milk production in dairy cows and to increase growth rates in animals such as cattle, sheep, and swine.
U.S. Patent 5,008,244, issued on April 16, 1991 to Miller discloses an administration of growth hormone to food-producing animals to increase their fertility by improving embryonic survival and litter size during the reproductive stage of growth. In U.S. Patent 5,583,106, issued on December 10, 1996 to Stanisiewski, an enhanced reproductive performance in cattle is achieved by commencing administration of growth hormone during the early postpartum period.
U.S. Patent 5,637,566, issued on June 10, 1997 to Walker et al. describes the use of growth hormone to improve carcass quality and/or food conversion efficiency in animals. In U.S. Patent 4,792,546, issued on December 20, 1988 to Baker, growth hormone is administered to food-producing animals to increase weight gain and at the same time reduce fat deposition and improve the lean meat to fat ratio.
U.S. Patent 7,361,642, issued on April 22, 2008 to Draghia-Akli, discloses a method for increasing growth hormone in canines. A canine-specific growth hormone releasing hormone (dGHRH) or a nucleic acid molecule that encodes the dGHRH is administered to canines to increase the level of growth hormone secretion. The canines treated with specific growth hormone releasing hormone show increased insulin-like growth factor I, enhanced red blood cells production and hemoglobin concentration, and improved protein metabolism.
Journal of Orthopedic Research 15:519-527 (1997) discloses that a growth hormone secretagogue, MK-0677, elevates levels of serum insulin-like growth factor-I

-3-in canines, which in turn increases the size and strength of the quadriceps muscle in canines during remobilization.
U.S. Publication No. 2008/0119819, published on May 22, 2008 to Hojby, discloses that an administration of growth hormone enhances bone growth factors and fracture healing in canines.
It has also been reported that for adult canines of both sexes, exogenous growth hormone induces a marked increase in new bone formation. (Calcified Tissue Research 10(1):1-13 (1972)).
Other studies have shown that in the canines that were given growth hormone, the quantity of protein in the blood plasma is increased, and the plasma protein pattern is altered. (Endocrinology 53: 134-162 (1953)). Additionally, it is known that growth hormone treatment improves protein metabolism in canines.
DISCLOSURE
The present disclosure includes a nutritional supplement and a method of using the same for improving health in animals, such as canines. The nutritional supplement is an amino acid secretagogue composition, which stimulates the pituitary gland of animals to release growth hormone.
A particular embodiment of the present disclosure relates to a nutritional supplement for improving health in animals, the nutritional supplement comprising L-arginine, L-pyroglutamie acid, L-lysine, and cysteine.
Another particular embodiment relates to a nutritional supplement for improving health in animals, the nutritional supplement consisting essentially of L-arginine hydrochloride, L-pyroglutamic acid, L-lysine hydrochloride, N-acetyl-L-cysteine, L-glutamine and schizonepeta powder.
Other embodiments are drawn to methods of increasing growth hormone in animals, the methods including administering the disclosed nutritional supplement to an animal. In particular embodiments, the method includes orally administering the disclosed nutritional supplement to an animal.
MODE(S) FOR CARRYING OUT THE INVENTION

3a In some embodiments, there is provided use of a nutritional supplement to improve health in a nonhuman mammal, the nutritional supplement comprising: 0.1 to 6 mmol L-arginine; 0.1 to 8 mmol Oxo-proline; 0.1 to 12 mmol L-lysine; 0.001 to 6 mmol N-acetyl L-cysteine; and 0.001 to 6 mmol L-glutamine.
In some embodiments, there is provided use of a nutritional supplement to improve health in a nonhuman mammal, the nutritional supplement comprising: 3.44 mmol L-arginine;
5.30 mmol Oxo-proline; 8.21 mmol L-lysine; 6.13 p,mol N-acetyl L-cysteine; and 6.84 p,mol L-glutamine.
In some embodiments, there is provided a nutritional supplement for use in improving health in a nonhuman mammal, the nutritional supplement comprising: 0.1 to 6 mmol L-arginine; 0.1 to 8 mmol Oxo-proline; 0.1 to 12 mmol L-lysine; 0.001 to 6 mmol N-acetyl L-cysteine; and 0.001 to 6 mmol L-glutamine.
In some embodiments, there is provided a nutritional supplement for use in improving health in a nonhuman mammal, the nutritional supplement comprising: 3.44 mmol L-arginine; 5.30 mmol Oxo-proline; 8.21 mmol L-lysine; 6.13 p,mol N-acetyl L-cysteine; and 6.84 p,mol L-glutamine.
Date Recue/Date Received 2020-12-24

-4-The present disclosure relates to methods and nutritional supplements for improving health in animals. The nutritional supplement is an amino acid secretagogue composition, which stimulates the pituitary gland in an animal to produce growth hormone. Increased production of growth hormone in animals may prevent the loss of skeletal muscle mass, osteoporosis, increased fat deposition, decreased lean body mass, and other disorders. The supplement of the present disclosure may work as a dietary supplement by assisting the animal's ability to secrete growth hormone naturally in a manner which is safe and effective.
As used herein, the term "animal" means any species of the kingdom Animalia, including mammals, avians, reptiles or amphibians. It may include a food-producing animal (e.g., chicken, turkeys, ducks, geese, guinea henspig, cattle, lambs, fish, etc.); a pet, such as dog and cat; or a working animal, such as horse.
As used herein, the term "mammal" means a warm blooded vertebrate, including non-human animals such as murine, porcine, canine and feline. It may include ungulates or hooved animals (e.g., cattle, goats, pigs, horse, sheep, etc.);
rodents (e.g., guinea pigs, hamsters, mice, rats, etc.); lagomorphs such as rabbits;
primates (e.g., monkeys, baboons, humans, etc.); or the like. By way of non-limiting examples, mammal may include cattle, sheep, goat, or swine.
A particular embodiment of the present disclosure relates to a nutritional supplement for improving health of animals, the nutritional supplement including L-lysine, L-arginine, oxo-proline, and at least one of cysteine and glutamine.
The supplement may additionally include both cysteine and glutamine and/or schizonepeta powder. In particular embodiments, a functional dosage may include L-arginine at a level between 0.1-6 mmol, oxo-proline at a level between 0.1-8 mmol, and/or the L-lysine in an amount between 0.1-12 mmol. The cysteine and/or glutamine may be contained at a level between 0.001-6 mmol. The cysteine may be n-acetyl L-cysteine, and the glutamine may be L-glutamine. The amino acids may be delivered as non-toxic salts thereof, effective complexes thereof, stable chelates thereof, active esters thereof, functional derivatives thereof, or mixtures thereof, which are effective to increase growth hormone levels in animals. The nutritional supplement may be present in an amount of 2.9 grams. Dosages are generally calculated in the range of about 20-50 gms per kg of body weight of the animal. The nutritional supplement may be

-5-administered to animals orally. The supplement may be in any acceptable and known oral formulation including, but are not limited to, powder, tablet, capsule, or liquid form.
Another particular embodiment relates to a nutritional supplement for improving health of animals, the nutritional supplement consisting essentially of L-lysine HC1, L-arginine HC1, oxo-proline, N-acetyl L-cysteine, L-glutamine, and schizonepeta (aerial parts) powder. In particular embodiments, a functional dosage may include L-arginine HCl at a level between 0.1-6 mmol, and oxo-proline at a level between 0.1-8 mmol, and/or the L-lysine HC1 in an amount between 0.1-12 mmol.
The n-acetyl L-cysteine and/or L-glutamine may be contained at a level between 0.001-6 mmol. In another particular embodiment, a functional dosage may include L-argininc HC1 at a level between 2.5-4.5 mmol, oxo-proline between 4-6 mmol, and/or the L-lysine HC1 in an amount between 7-9 mmol. The n-acetyl L-cystcine and/or L-glutamine may be contained at a level between 0.001-0.5 mmol. The nutritional supplement may be administered to animals orally. The supplement may be in any acceptable and known oral formulation including, but are not limited to, powder, tablet, capsule, or liquid form.
Other embodiments are drawn to methods of increasing growth hormone in animals, the methods including administering the disclosed nutritional supplement to an animal. In particular embodiments, the method includes orally administering the disclosed nutritional supplement to an animal. The amount of dosage and frequency of administration may be varied according to many factors including, but are not limited to, animal species, ages and health.
The disclosed nutritional supplements may be administered to an animal to improve health, including by: increasing growth performance; enhancing lean body mass with an overall improvement in feed efficiency; improving reproductively performance; stimulating milk production; boosting milk yield; or combinations thereof.
In accordance with the "consist essentially of' and "consisting essentially of' language, the nutritional supplement is essentially limited to the aforementioned ingredients and does not include any additional active ingredients intended to add nutritional content (e.g., vitamins, minerals, etc.), but may include additional

6 PCMJS2013/060986 ingredients not intended to add nutritional content such as ingredients intended to fulfill a non-nutritional purpose (e.g., coloring, fillers, flavoring, an ingredient for maintaining the structural form, etc.).
Each ingredient of the nutritional supplement may be prepared in accordance with any method known to one of ordinary skill in the art. Alternatively, each ingredient may be obtained in a fully prepared from a commercially available source.
The nutritional supplement may be in any suitable oral administration form, including but not limited to: a chewable form, a liquid form, a spray form, a capsule form, a suppository form, dissolvable wafer, and a powder form.
Irrespective of the structural form of the nutritional supplement, the ingredients of the nutritional supplement may be distributed homogeneously or non-homogeneously within the nutritional supplement.
The nutritional supplement may be administered to an animal on a regular basis, such as a weekly or monthly intake at a dosage tailored to the animal's needs;
i.e., the nutritional supplement may be administered regularly as multiples (Ix, 2x, etc.) of the structural units (pills, tablets, capsules, etc.) in accordance with the needs of the animal. For example, an elderly animal is likely to need higher daily doses than does a young animal. Alternatively, the nutritional supplement may be administered on an as-needed basis at a dosage tailored to the animal's needs, such as administering the nutritional supplement to cattle during the early postpartum period to enhance reproductively performance. Veterinarian counseling may be beneficial for arriving at a desirable or optimal dosage tailored to the animal's needs.
The combination of types of amino acids, mass ranges, and specific formulations may be selected to be synergistically balanced and of adequate quantity to achieve the desired physiological effect, namely, growth hormone release.
Improper combinations of the amino acids may be ineffective. The component amino acids are synergistic in the sense that several of them when combined together, synergistically stimulate the release of human growth hormone. The combination may also be chosen to reduce or inhibit chemical combination or reaction between the amino acids.
EXAMPLES
Example 1

-7-The short-term effects of the disclosed supplement on the growth hormone level in animals are tested two hours after administration. The animal subjects are administered the capsules of supplement (SER0VITALO) or an identical looking placebo. SER0VITALO is a blend of 1-lysine HC1, 1-arginine HCL, oxo-proline, N-acetyl-l-cysteine, 1-glutamine, and schizonepeta (aerial parts) powder.
Animal subjects are administered approximately 35 gms per kg of body weight. Blood is drawn at 15, 30, 60 and 90 and 120 minutes for assay. The growth hormone level is measured at each time point using the Siemens Immulite 2000 (intra-assay CV
was 3.72%, inter-assay CV was 5.70%, and the detection limit for GH was 0.05ng/m1). The 15 and 120 minute time points are additionally assayed for triiodothyronine (T3) as informative for mechanistic investigations.
The mean growth hormone in the animal subjects are increased more than 600% after the administration of supplement from 0.17 at baseline to 1.33ng/m1 at 120 minutes, while there is are no increases observed in the mean growth hormone of the animal subjects after the administration of placebo.
The growth hormone levels from baseline to 120 minutes (the growth hormone level at 120 minutes minus the growth hormone level at 0 minute), are increased about two fold when compared to the administration of a placebo. Overall, 120 minutes after the administration of the supplement, the growth hormone levels are significantly higher in absolute levels or by AUC.
Furthermore, the animals that were administered SERoVrrALO will exhibit a deceased reduction inT3 by nearly one-half over the same time period, compared to the animals administered with the placebo. These results affirm that somatostatin inhibition plays a mechanistic role in the ability of SEROVITAL to induce significant increases in serum growth hormone levels in animal subjects.
These findings demonstrate that a specialized low-dose amino acid supplement can significantly increase short-term growth hormone levels in animals.
Example 2 The effect of the nutritional supplement on endurance and fat metabolism in animals are investigated. Each animal subject is measured for baseline weight, height, body fat percent and resting metabolic rate. Then, each animal subject is administered

-8-with the supplement SEROVITALO, which is a blend of 1-lysine HC1, 1-arginine HC1, oxo-proline, N-acetyl-l-cysteine, 1-glutamine, and schizonepeta (aerial parts) powder for 2 weeks before being measured again for weight, height, body fat percent and resting metabolic rate. The measurements before and after the administration of the supplement are analyzed.
Mean VO2max of the animal subjects increases compared to baseline. After the period of supplementation with SEROVITALO, the mean RMR increases compared to baseline (P=0.165). Estimated daily calorie expenditure also increases.
After two weeks of supplementation with the supplement SER0VITALO, both RMR and estimated daily calorie expenditure of the animal subjects tend to increase, evidencing the potential of the supplement to impart long-term fat burning effects.
Additionally, endurance as measured by VO2max in the post-absorptive state significantly improves. Overall, the animal subjects administered with the SERoVITAL(R) supplement will show enhanced parameters of endurance, energy, and vitality.
Example 3 The effect of the nutritional supplement on lean body mass and weight change of animals is studied. The animal subjects in the first group are given daily doses of the nutritional supplement for 6 months at different dosing concentrations of active ingredients, while the animal subjects in the second group are given placebo.
Weight, percent lean body mass, and percent fat body mass are chosen as primary measures of body composition at the 6 month analysis period. The weight, body composition, and physical performance (including endurance) of the animal subjects are determined before and after the treatment, along with hormonal data analysis.
The animal subjects treated with the nutritional supplement show a sustained increase in lean body mass and an improved physical performance.
While embodiments of the present invention have been described herein for purposes of illustration, many modifications and changes will become apparent to those skilled in the art. Accordingly, the appended claims are intended to encompass all such modifications and changes as fall within the true spirit and scope of this invention.

Claims (16)

CLAIMS:

1. Use of a nutritional supplement in a nonhuman mammal, the nutritional supplement comprising:
0.1 to 6 mmol L-arginine;
0.1 to 8 mmol Oxo-proline;
0.1 to 12 mmol L-lysine;
0.001 to 6 mmol N-acetyl L-cysteine; and 0.001 to 6 mmol L-glutamine.

2. The use according to claim 1, which is an oral use.

3. The use according to claim 1 or 2, wherein about 20 to about 50 gms/kg of the nutritional supplement is to be used.

4. The use according to any one of claims 1 to 3, wherein the nutritional supplement is in powder, tablet, capsule, liquid, or wafer form.

5. The use according to any one of claims 1 to 4, wherein the nutritional supplement is for administration once a week or once a month.

6. The use according to any one of claims 1 to 5, wherein the use is for at least one of following in the mammal: increasing growth performance, enhancing lean body mass, improving reproductively performance, stimulating milk production, boosting milk yield, and increasing a feed efficiency.

7. The use according to any one of claims 1 to 6, wherein the nonhuman mammal is a canine.
Date Recue/Date Received 2020-11-12

8. Use of a nutritional supplement in a nonhuman mammal, the nutritional supplement comprising:
3.44 mmol L-arginine;
5.30 mmol Oxo-proline;
8.21 mmol L-lysine;
6.13 prnol N-acetyl L-cysteine; and 6.84 jimol L-glutamine.

9. The use according to claim 8, which is an oral use.

10. The use according to claim 8 or 9, wherein about 20 to about 50 gms/kg of the nutritional supplement is to be used.

11. The use according to any one of claims 8 to 10, wherein the nutritional supplement is in powder, tablet, capsule, liquid, or wafer form.

12. The use according to any one of claims 8 to 11, wherein the nutritional supplement is for administration once a week or once a month.

13. The use according to any one of claims 8 to 12, wherein the use is for at least one of following in the mammal: increasing growth performance, enhancing lean body mass, improving reproductively performance, stimulating milk production, boosting milk yield, and increasing a feed efficiency.

14. The use according to any one of claims 8 to 13, wherein the mammal is a canine.
Date Recue/Date Received 2020-11-12

15. A nutritional supplement for use in a nonhuman mammal, the nutritional supplement comprising:
0.1 to 6 mmol L-arginine;
0.1 to 8 mmol Oxo-proline;
0.1 to 12 mmol L-lysine;
0.001 to 6 mmol N-acetyl L-cysteine; and 0.001 to 6 mmol L-glutamine.

16. A nutritional supplement for use in a nonhuman mammal, the nutritional supplement comprising:
3.44 mmol L-arginine;
5.30 mmol Oxo-proline;
8.21 mmol L-lysine;
6.13 lamol N-acetyl L-cysteine; and 6.84 Ilmol L-glutamine.
Date Recue/Date Received 2020-11-12