Methods of reducing the body weight of a subject by administering a fatty acid ester of an estrogen or estrogen derivative in an oil and compositions containing the same

Abstract

Compositions and methods for reducing the body weight of a subject are disclosed. The invention is directed to methods for reducing the body weight in a subject comprising administering therapeutically effective amounts of a fatty acid ester of an estrogen or estrogen derivative in an oil. Furthermore the invention is directed to compositions for reducing the body weight in a subject comprising administering therapeutically effective amounts of a fatty acid ester of an estrogen or estrogen derivative in an oil.

1 . A method for reducing body weight in a human comprising administering a composition comprising a therapeutically effective amount of a fatty acid ester of an estrogen or estrogen derivative in an oil. 
     
     
         2 . The method of  claim 1 , wherein the composition is administered orally. 
     
     
         3 . The method of  claim 1 , wherein the estrogen comprises estrone, diethylstilbestrol, estriol, estradiol or ethinyl estradiol. 
     
     
         4 . The method of  claim 1 , wherein the estrogen comprises estrone. 
     
     
         5 . The method of  claim 1 , wherein the estrogen derivative comprises 2-hydroxyestrone or 2-hydroxy-β-estradiol. 
     
     
         6 . The method of  claim 1 , wherein the fatty acid comprises an oleic acid, linoleic acid, linolenic acid, stearic acid, palmitic acid, palmitoleic acid, arachidonic acid, eicosenoic acid, docosenoic acid, or tetracosenoic acid. 
     
     
         7 . The method of  claim 1 , wherein the fatty acid comprises an oleic acid. 
     
     
         8 . The method of  claim 1 , wherein the fatty acid includes an acyl group; and wherein when the estrogen is steroidal and has a steroid ring system with a C-3 position and a hydroxyl group at the C-3 position, the acyl group of the fatty acid is attached to the hydroxyl group at the C-3 position of the steroid ring system in the fatty acid ester. 
     
     
         9 . The method of  claim 1  wherein the fatty acid includes an acyl group; wherein the estrogen comprises estrone, diethylstilbestrol, estriol or ethinyl estradiol; and wherein the fatty acid comprises an oleic acid, linoleic acid, linolenic acid, stearic acid, palmitic acid, palmitoleic acid, arachidonic acid, eicosenoic acid, docosenoic acid, or tetracosenoic acid; and with the proviso that, when the estrogen is steroidal and has a steroid ring system with a C-3 position and a hydroxyl group at the C-3 position, the acyl group of the fatty acid is attached to the hydroxyl group at the C-3 position of the steroid ring system in the fatty acid ester. 
     
     
         10 . The method of  claim 1 , wherein the fatty acid ester of an estrogen or estrogen derivative is a fatty acid monoester. 
     
     
         11 . The method of  claim 1 , wherein the fatty acid ester of an estrogen or estrogen derivative comprises oleoyl-estrone. 
     
     
         12 . The method of  claim 1 , wherein the therapeutically effective amount of the fatty acid ester of an estrogen or estrogen derivative comprises an amount of about 0.000005 mg/kg/day to about 20 mg/kg/day. 
     
     
         13 . The method of  claim 1 , wherein the therapeutically effective amount of the fatty acid ester of an estrogen or estrogen derivative comprises an amount of about 0.00005 mg/kg/day to about 10 mg/kg/day. 
     
     
         14 . The method of  claim 1 , wherein the therapeutically effective amount of the fatty acid ester of estrogen or estrogen derivative comprises an amount of about 0.0005 mg/kg/day to about 2 mg/kg/day. 
     
     
         15 . The method of  claim 1 , wherein the therapeutically effective amount of the fatty acid ester of an estrogen or estrogen derivative comprises an amount of about 0.001 mg/kg/day to about 1 mg/kg/day. 
     
     
         16 . The method of  claim 1 , wherein the fatty acid ester of an estrogen or estrogen derivative comprises about 0.01% to about 99% by weight of the composition. 
     
     
         17 . The method of  claim 1 , wherein the fatty acid ester of an estrogen or estrogen derivative comprises about 0.1% to about 45% by weight of the composition. 
     
     
         18 . The method of  claim 1 , wherein the fatty acid ester of an estrogen or estrogen derivative comprises about 1% to about 15% by weight of the composition. 
     
     
         19 . The method of  claim 1 , wherein the oil comprises a triglyceride. 
     
     
         20 . The method of  claim 1 , wherein the oil comprises an oil derived from a plant. 
     
     
         21 . The method of  claim 1 , wherein the oil comprises canola oil, safflower oil, soybean oil, corn oil, olive oil, sesame oil, rapeseed oil, sunflower oil, rice oil, palm oil, cottonseed oil, linseed oil, tung oil, oiticica oil, castor oil, perilla oil, coconut oil, Labrasol®, Labrafil® M 125CS, Labrafac® CC, Captex® 300-6C, Captex® 300 EP, tallow, lard, stearic acid, fish oil, fish-liver oil, oleic acid, sperm oil, petroleum oil, or combinations thereof. 
     
     
         22 . The method of  claim 1 , wherein the oil comprises safflower oil, canola oil or soybean oil. 
     
     
         23 . The method of  claim 1 , wherein the oil comprises about 25% to about 99% by weight of the composition. 
     
     
         24 . The method of  claim 1 , wherein the oil comprises about 75% to about 99% by weight of the composition. 
     
     
         25 . The method of  claim 1 , wherein the oil comprises about 80% to about 99% by weight of the composition. 
     
     
         26 . The method of  claim 1 , wherein the composition further comprises at least one pharmaceutically acceptable excipient. 
     
     
         27 . The method of  claim 1 , wherein the composition is contained in a capsule. 
     
     
         28 . The method of  claim 1 , wherein the reducing body weight comprises treating obesity or treating overweight. 
     
     
         29 . A method of reducing body weight in a human comprising orally administering a composition comprising a therapeutically effective amount of a fatty acid ester of an estrogen or estrogen derivative in an oil, wherein the oil is derived from a plant. 
     
     
         30 . The method of  claim 29 , wherein the fatty acid ester of an estrogen or estrogen derivative comprises oleoyl-estrone. 
     
     
         31 . A method for reducing body weight in a subject comprising orally administering a composition comprising a therapeutically effective amount of a fatty acid ester of estrogen or estrogen derivative in an oil comprising safflower oil, canola oil or soybean oil. 
     
     
         32 . The method of  claim 31 , wherein the fatty acid ester of an estrogen or estrogen derivative comprises oleoyl-estrone. 
     
     
         33 . The method of  claim 32 , wherein the therapeutically effective amount of oleoyl-estrone comprises an amount of about 0.001 mg/kg/day to about 1 mg/kg/day. 
     
     
         34 . The method of  claim 31 , wherein the composition is contained in a capsule. 
     
     
         35 . The method of  claim 31 , wherein the reducing body weight comprises treating obesity or treating overweight. 
     
     
         36 . A method for reducing body weight in a subject comprising orally administering a composition comprising a therapeutically effective amount of oleoyl-estrone in canola oil. 
     
     
         37 . A method for reducing body weight in a subject comprising orally administering a composition comprising a therapeutically effective amount of olcoyl-estrone in safflower oil. 
     
     
         38 . A method for reducing body weight in a subject comprising orally administering a composition comprising a therapeutically effective amount of oleoyl-estrone in soybean oil. 
     
     
         39 . A composition for reducing body weight in a subject comprising a therapeutically effective amount of a fatty acid ester of an estrogen or estrogen derivative in an oil, wherein the composition is contained in a capsule. 
     
     
         40 . The composition of  claim 39 , wherein the composition is a once-a-day capsule. 
     
     
         41 . The composition of  claim 39 , wherein the estrogen comprises estrone, diethylstilbestrol, estriol, estradiol or ethinyl estradiol. 
     
     
         42 . The composition of  claim 39 , wherein the estrogen comprises estrone. 
     
     
         43 . The composition of  claim 39 , wherein the estrogen derivative comprises 2-hydroxyestrone or 2-hydroxy-β-estradiol. 
     
     
         44 . The composition of  claim 39 , wherein the fatty acid comprises an oleic acid, linoleic acid, linolenic acid, stearic acid, palmitic acid, palmitoleic acid, arachidonic acid, eicosenoic acid, docosenoic acid, or tetracosenoic acid. 
     
     
         45 . The composition of  claim 39 , wherein the fatty acid comprises an oleic acid. 
     
     
         46 . The composition of  claim 39 , wherein the fatty acid includes an acyl group; and wherein when the estrogen is steroidal and has a steroid ring system with a C-3 position and a hydroxyl group at the C-3 position, the acyl group of the fatty acid is attached to the hydroxyl group at the C-3 position of the steroid ring system in the fatty acid ester. 
     
     
         47 . The composition of  claim 39 , wherein the fatty acid includes an acyl group; wherein the estrogen comprises estrone, diethylstilbestrol, estriol or ethinyl estradiol; and wherein the fatty acid comprises an oleic acid, linoleic acid, linolenic acid, stearic acid, palmitic acid, palmitoleic acid, arachidonic acid, eicosenoic acid, docosenoic acid, or tetracosenoic acid; and with the proviso that, when the estrogen is steroidal and has a steroid ring system with a C-3 position and a hydroxyl group at the C-3 position, the acyl group of the fatty acid is attached to the hydroxyl group at the C-3 position of the steroid ring system in the fatty acid ester. 
     
     
         48 . The composition of  claim 39 , wherein the fatty acid comprises a fatty acid monoester. 
     
     
         49 . The composition of  claim 39 , wherein the fatty acid ester of an estrogen or estrogen derivative comprises oleoyl-estrone. 
     
     
         50 . The composition of  claim 39 , wherein the therapeutically effective amount of the fatty acid ester of an estrogen or estrogen derivative comprises an amount of about 0.000005 mg/kg/day to about 20 mg/kg/day. 
     
     
         51 . The composition of  claim 39 , wherein the therapeutically effective amount of the fatty acid ester of an estrogen or estrogen derivative comprises an amount of about 0.00005 mg/kg/day to about 10 mg/kg/day. 
     
     
         52 . The composition of  claim 39 , wherein the therapeutically effective amount of the fatty acid ester of an estrogen or estrogen derivative comprises an amount of about 0.0005 mg/kg/day to about 2 mg/kg/day. 
     
     
         53 . The composition of  claim 39 , wherein the therapeutically effective amount of the fatty acid ester of an estrogen or estrogen derivative comprises an amount of about 0.001 mg/kg/day to about 1 mg/kg/day. 
     
     
         54 . The composition of  claim 39 , wherein the fatty acid ester of an estrogen or estrogen derivative comprises about 0.01% to about 99% by weight of the composition. 
     
     
         55 . The composition of  claim 39 , wherein the fatty acid ester of an estrogen or estrogen derivative comprises about 0.1% to about 45% by weight of the composition. 
     
     
         56 . The composition of  claim 39 , wherein the fatty acid ester of an estrogen or estrogen derivative comprises about 1% to about 15% by weight of the composition. 
     
     
         57 . The composition of  claim 39 , wherein the oil comprises a triglyceride. 
     
     
         58 . The composition of  claim 39 , wherein the oil comprises an oil derived from a plant. 
     
     
         59 . The composition of  claim 39 , wherein the oil comprises, canola oil, safflower oil, soybean oil, corn oil, olive oil, sesame oil, rapeseed oil, sunflower oil, rice oil, palm oil, cottonseed oil, linseed oil, tung oil, oiticica oil, castor oil, perilla oil, coconut oil, Labrasol<, Labrafil® M 125CS, Labrafac® CC, Captex® 300-6C, Captex® 300 EP, tallow, lard, stearic acid, fish oil, fish-liver oil, oleic acid, sperm oil, petroleum oil, or combinations thereof. 
     
     
         60 . The composition of  claim 39 , wherein the oil comprises safflower oil, canola oil or soybean oil. 
     
     
         61 . The composition of  claim 39 , wherein the oil comprises about 25% to about 99% by weight of the composition. 
     
     
         62 . The composition of  claim 39 , wherein the oil comprises about 75% to about 99% by weight of the composition. 
     
     
         63 . The composition of  claim 39 , wherein the oil comprises about 80% to about 99% by weight of the composition. 
     
     
         64 . The composition of  claim 39 , further comprising at least one pharmaceutically acceptable excipient. 
     
     
         65 . A composition for reducing body weight in a subject comprising a therapeutically effective amount of a fatty acid ester of an estrogen or estrogen derivative in an oil, wherein the oil is derived from a plant and wherein the composition is contained in a capsule. 
     
     
         66 . The composition of  claim 65 , wherein the fatty acid ester of an estrogen or estrogen derivative comprises oleoyl-estrone. 
     
     
         67 . A composition for reducing body weight in a subject comprising a therapeutically effective amount of a fatty acid ester of an estrogen or estrogen derivative in an oil comprising safflower oil, canola oil or soybean oil and wherein the composition is suitable for oral administration. 
     
     
         68 . The composition of  claim 67 , wherein the fatty acid ester of an estrogen or estrogen derivative comprises oleoyl-estrone. 
     
     
         69 . The composition of  claim 68 , wherein oleoyl-estrone is present in an amount of about 0.001 mg/kg/day to about 1 mg/kg/day. 
     
     
         70 . The composition of  claim 67 , wherein the composition is contained in a capsule. 
     
     
         71 . A composition for reducing body weight in a subject comprising a therapeutically effective amount of oleoyl-estrone in safflower oil, wherein the composition is suitable for oral administration. 
     
     
         72 . The composition of  claim 71 , wherein the composition is contained in a capsule. 
     
     
         73 . A composition for reducing body weight in a subject comprising a therapeutically effective amount of oleoyl-estrone in canola oil, wherein the composition is suitable for oral administration. 
     
     
         74 . The composition of  claim 73 , wherein the composition is contained in a capsule. 
     
     
         75 . A composition for reducing body weight in a subject comprising a therapeutically effective amount of oleoyl-estrone and soybean oil, wherein the composition is suitable for oral administration. 
     
     
         76 . The composition of  claim 75 , wherein the composition is contained in a capsule.