TOMATIDINE, ANALOGS THEREOF, COMPOSITIONS COMPRISING SAME, AND USES FOR SAME

• US 20160175327A1
• Filed: 12/22/2015
• Published: 06/23/2016
• Est. Priority Date: 08/03/2012
• Status: Active Grant

• Current Assignee: US Department of Veterans Affairs (Government of the United States of America), The United States of America as represented by the Department of Veterans Affairs, Office of the Gen, University of Iowa Research Foundation
• Original Assignee: Michael C. Dyle
• Inventors: Adams, Christopher M., Dyle, Michael C., Welsh, Michael
• Granted Patent: US 10,022,386 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A23K 20/121 containing oxygen or sulfur as hetero atom
• CPC Class Codes: A23L 33/10 using additives addition of substantially indigestible substances A23L33/21
• CPC Class Codes: A23V 2002/00 Food compositions, function of food ingredients or processes for food or foodstuffs
• CPC Class Codes: A61K 31/58 containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin digitoxin A61K31/7048
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: C07J 53/00 Steroids in which the cyclopenta(a)hydrophenanthrene skeleton has been modified by condensation with a carbocyclic rings or by formation of an additional ring by means of a direct link between two ring carbon atoms, including carboxyclic rings fused to the cyclopenta(a)hydrophenanthrene skeleton are included in this class
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: C12Q 2600/136 Screening for pharmacological compounds
• CPC Class Codes: C12Q 2600/158 Expression markers

Abstract

In one aspect, the invention relates to methods for promoting muscle hypertrophy or decreasing adiposity by providing to an animal in need thereof an effective amount of a compound. 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

1-21. -21. (canceled)

22. A method of increasing muscle formation,

increasing muscle protein synthesis,

reducing skeletal muscle atrophy,

increasing the ratio of skeletal muscle to fat, or

decreasing adiposity

in an animal comprising administering to the animal a solution, dispersion, suspension or emulsion comprising not less than 0.05% by weight of a compound having a structure represented by a formula:

23. The method according to claim 22, wherein the compound has a structure represented by the formula E1

24. The method according to claim 23 wherein R⁵¹ is selected from H and C₁-C₆ alkyl.

25. The method according to claim 24 wherein R⁵¹ is H and R⁵⁴ is H.

26. The method according to claim 23 wherein the compound has the structure represented by formula:

27. The method according to claim 22 wherein said solution, dispersion, suspension or emulsion comprises not less than 0.14% by weight of said compound.

28. The method according to claim 22 wherein said solution, dispersion, suspension or emulsion comprises not less than 0.28% by weight of said compound.

29. The method according to claim 23 wherein the compound is present in an amount greater than 5 mg.

30. A composition comprising a compound having a structure represented by a formula:

32. A composition according to claim 30 in the form of a tablet or capsule containing 10 to 500 mg of the compound of formula I or II and at least 10 mg of at least one compound from Group III.

33. A composition according to claim 30 in the form of a food supplement containing at least 10 mg of the compound of formula I or II and at least 10 mg of at least one compound from Group III.

34. A composition according to claim 30 in the form of a food or food supplement for cows, bulls, bison, horses, sheep, goats, pigs, ducks, geese, lamas, camels, dromedary, boars, turkeys, or chickens containing at least 10 mg of the compound of formula I or II and at least 10 mg of at least one compound from Group III.

31. A composition comprising

(a) a compound having a structure represented by a formula:

35. A method of identifying a compound that stimulates muscle hypertrophy and/or reduces skeletal muscle atrophy in an animal, the method comprising the steps of:

(i) selecting a candidate compound;

(ii) determining the effect of the candidate compound on a cell'"'"'s expression levels of a plurality of induced mRNAs and/or repressed mRNAs of a Muscle Atrophy Signature, wherein the candidate compound is identified as suitable for stimulating muscle hypertrophy and/or reducing skeletal muscle atrophy if;

(a) more than one of the induced mRNAs of the Muscle Atrophy Signature are down regulated, compared to expression levels of the induced mRNAs of the Muscle Atrophy Signature in the same type of cell in the absence of the candidate compound; and

/or

(b) more than one of the repressed mRNAs of the Muscle Atrophy Signature are up regulated, compared to expression levels of the repressed mRNAs of the Muscle Atrophy Signature in the same type of cell in the absence of the candidate compound.