Methods for inhibiting muscle atrophy

• US 9,856,204 B2
• Filed: 05/19/2011
• Issued: 01/02/2018
• Est. Priority Date: 05/20/2010
• Status: Active Grant

• Current Assignee: Department of Veterans Affairs The United States of Government As Represented By, US Department of Veterans Affairs (Government of the United States of America)
• Original Assignee: The United States of America As Represented By The Secretary of Agriculture, University of Iowa Research Foundation
• Inventors: Adams, Christopher M., Kunkel, Steven D., Suneja, Manish, Welsh, Michael
• Primary Examiner(s): QAZI, SABIHA NAIM
• Application Number:
  US13/698,645
• Publication Number:
  US 20130203712A1
• Time in Patent Office: 2,420 Days
• Field of Search: 514169, 5142378, 514510, 514557, 514623, 552510
• CPC Class Codes: A61K 31/19 Carboxylic acids, e.g. valproic acid salicylic acid A61K31/60
• CPC Class Codes: A61K 31/191 having two or more hydroxy groups, e.g. gluconic acid
• CPC Class Codes: A61K 31/198 Alpha-amino acids, e.g. alanine or edetic acid [EDTA] betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00
• CPC Class Codes: A61K 31/215 of carboxylic acids
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: C07C 235/82 with the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a ring other than a six-membered aromatic ring
• CPC Class Codes: C07C 61/29 having a carboxyl group bound to a condensed ring system
• CPC Class Codes: C07C 69/12 Acetic acid esters
• CPC Class Codes: C07C 69/757 having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety
• CPC Class Codes: C07D 265/30 not condensed with other rings
• CPC Class Codes: C07J 53/002 Carbocyclic rings fused

Abstract

In one aspect, the invention relates methods for inhibiting or preventing muscle atrophy or increasing muscle mass by providing to a subject in need thereof an effective amount of ursolic acid, a derivative thereof, or an analog of the ursane scaffold. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Claims

1. A method for increasing skeletal muscle mass in an animal, the method comprising administering to the animal ursolic acid, or a pharmaceutically acceptable salt, hydrate, or solvate thereof, wherein said animal is selected from the group consisting of a primate, domesticated fish, domesticated crustacean, domesticated mollusk, poultry, rabbit, dog, cat, and livestock.

2. The method of claim 1, wherein the ursolic acid or pharmaceutically acceptable salt, hydrate, or solvate thereof is administered to the animal in an amount of greater than or equal to 100 mg per day.

3. The method of claim 1, wherein the animal is a mammal.

4. The method of claim 1, wherein the animal is a human.

5. The method of claim 1, wherein the animal is selected from the group consisting of a dog, cat, pig, cow, horse, goat, bison, sheep, chicken, turkey, duck, goose, and domesticated fish.

6. The method of claim 1, wherein the ursolic acid is present as a pharmaceutically acceptable salt selected from salts derived from aluminum, ammonium, calcium, copper (-ic and -ous), ferric, ferrous, lithium, magnesium, manganese, potassium, sodium, or zinc;

salts of primary, secondary, and tertiary amines; and

salts derived from arginine, betaine, caffeine, choline, N,N′

-dibenzylethylenediamine, diethylamine, 2-diethylaminoethanol, 2-dimethylaminoethanol, ethanolamine, ethylenediamine, N-ethylmorpholinc, N-ethylpiperidine, glucamine, glucosamine, histidine, hydrabamine, isopropylamine, lysine, methylglucamine, morpholine, piperazine, piperidine, polyamine resins, procaine, purines, theobromine, triethylamine, trimethylamine, tripropylamine, or tromethamine.

7. The method of claim 1, wherein the ursolic acid or pharmaceutically acceptable salt, hydrate, or solvate thereof is administered to the animal in an amount of greater than 200 mg per day.

8. The method of claim 1, wherein the ursolic acid or pharmaceutically acceptable salt, hydrate, or solvate thereof is administered to the animal in an amount of greater than 300 mg per day.

9. The method of claim 1, wherein the ursolic acid or pharmaceutically acceptable salt, hydrate, or solvate thereof is administered to the animal in an amount of greater than 400 mg per day.

10. The method of claim 1, wherein the ursolic acid or pharmaceutically acceptable salt, hydrate, or solvate thereof is administered to the animal in an amount of greater than 500 mg per day.

11. The method of claim 1, wherein the ursolic acid or pharmaceutically acceptable salt, hydrate, or solvate thereof is administered to the animal in an amount of greater than 750 mg per day.

12. The method of claim 1, wherein the ursolic acid or pharmaceutically acceptable salt, hydrate, or solvate thereof is administered to the animal in an amount of greater than 1000 mg per day.

13. The method of claim 1, wherein the ursolic acid or pharmaceutically acceptable salt, hydrate, or solvate thereof is administered to the animal in composition that further comprises one or more adjuvants.

14. The method of claim 1, wherein the ursolic acid or pharmaceutically acceptable salt, hydrate, or solvate thereof is administered to the animal in a dosage of from about 0.1 to about 50 mg/kg per day.

15. The method of claim 4, wherein the ursolic acid or pharmaceutically acceptable salt, hydrate, or solvate thereof is administered to the animal in a dosage of from about 0.1 to about 50 mg/kg per day.

16. The method of claim 7, wherein the ursolic acid or pharmaceutically acceptable salt, hydrate, or solvate thereof is administered to the animal in a dosage of from about 0.1 to about 50 mg/kg per day.

17. The method of claim 1, wherein the ursolic acid or pharmaceutically acceptable salt, hydrate, or solvate thereof is administered to the animal in a composition that further comprises a preservative.

18. The method of claim 17, wherein the ursolic acid or pharmaceutically acceptable salt, hydrate, or solvate thereof is administered to the animal in an amount of greater than or equal to 2100 mg per day.

19. The method of claim 17, wherein the animal is selected from a domesticated fish, poultry, pig, cow, horse, goat, bison, sheep, dog, cat, and bison.

20. The method of claim 18, wherein the animal is selected from a domesticated fish, poultry, pig, cow, horse, goat, bison, sheep, dog, cat, and bison.