Methods and Related Compositions for Reduction of Fat and Skin Tightening

Abstract

Compositions and methods useful in the reduction of localized fat deposits and tightening of loose skin in subjects in need thereof using pharmacologically active detergents are disclosed. The pharmacologically active detergent compositions can additionally include anti-inflammatory agents, analgesics, dispersion or anti-dispersion agents and pharmaceutically acceptable excipients. The pharmacologically active detergent compositions are useful for treating localized accumulations of fat including, for example, lower eyelid fat herniation, lipodystrophy and fat deposits associated with cellulite and do not require surgical procedures such as liposuction.

1 . A pharmaceutical solution for subcutaneous injection comprising:
 a therapeutically effective amount of a bile acid or salt thereof;   a pharmaceutical excipient; and   optionally a lipid, wherein the ratio of the lipid and bile acid or bile salt is less than 1% w/w and wherein the solution does not include lipase or colipase.   
     
     
         2 . The solution of  claim 1  wherein said solution further comprises a second therapeutic agent selected from the group consisting of: anti-microbial agents, vasoconstrictors, anti-thrombotic agents, anti-coagulation agents, suds-depressants, anti-inflammatory agents, analgesics, dispersion agents, anti-dispersion agents, penetration enhancers, steroids, tranquilizers, muscle relaxants, and anti-diarrhea agents. 
     
     
         3 . The solution of  claim 1  wherein said solution is in a container that contains up to 500 mL of solution. 
     
     
         4 . The solution of  claim 1  wherein said bile acid is selected from the group consisting of: deoxycholic acid, cholic acid, chenodeoxycholic acid, 7-alpha-dehydroxylate chenodeoxycholic acid, lithocholic acid, ursodeoxycholic acid, dihydroxytaurin acid, trihydroxytaurine acid, and glycine conjugates of any of the above. 
     
     
         5 . The solution of  claim 1  wherein said bile salt comprises a cation selected from the group consisting of sodium (Na + ), potassium (K + ), lithium (Li + ), magnesium (Mg 2+ ), calcium (Ca 2+ ), barium (Ba 2+ ), strontium (Sr 2+ ), and ammonium (NH 4+ ). 
     
     
         6 . The solution of  claim 1  wherein said bile salt comprises an alkali metal or an alkaline earth metal. 
     
     
         7 . The solution of  claim 6  wherein said alkali metal is selected from the group consisting of alkali metal is sodium (Na + ), potassium (K + ) and lithium (Li + ). 
     
     
         8 . The solution of  claim 6  wherein said alkaline earth metal is selected from the group consisting of magnesium (Mg 2+ ), calcium (Ca 2+ ), barium (Ba 2+ ), and strontium (Sr 2+ ). 
     
     
         9 . The solution of  claim 1  wherein said bile acid salt is sodium deoxycholate. 
     
     
         10 . The solution of  claim 1  comprising up to 5% w/w lipids. 
     
     
         11 . The solution of  claim 1  wherein said lipid is phosphatidylcholine. 
     
     
         12 . The solution of  claim 1  wherein said bile acid or bile salt is at a concentration of about 0.001% w/w to about 10% w/w. 
     
     
         13 . The solution of  claim 1  wherein said bile acid or salt thereof is at a concentration of about 0.01% w/w to about 5% w/w. 
     
     
         14 . The solution of  claim 1  wherein said solution is aqueous. 
     
     
         15 . The solution of  claim 1  wherein said therapeutically effective amount is effective for fat dissolution or skin tightening. 
     
     
         16 . A method for reducing the appearance of a skin condition in a skin region of a subject comprising:
 administering locally to said skin region a composition comprising:
 (i) a skin-tightening effective amount of at least one bile acid or bile salt, 
 (ii) a pharmaceutical excipient, and 
 (iii) optionally a lipid. 
   
     
     
         17 . The method of  claim 16  wherein said administering step involves delivering said composition via a subcutaneous or transdermal injection. 
     
     
         18 . The method of  claim 16  wherein said administering step involves delivering said composition via a dermal patch, a pump, or subdermal depot. 
     
     
         19 . The method of  claim 16  wherein said administering step involves delivering said composition topically or subcutaneously. 
     
     
         20 . The method of  claim 16  wherein said skin condition is selected from the group consisting of: loose skin, skin aging, irregularities of the skin, and wrinkles. 
     
     
         21 . The method of  claim 16  wherein said region of skin is under eye, under chin, under arm, buttock, cheek, brow, calf, back, thigh, ankle, or stomach. 
     
     
         22 . The method of  claim 16  wherein said bile acid is deoxycholic acid. 
     
     
         23 . The method of  claim 16  wherein said bile salt is sodium deoxycholate. 
     
     
         24 . The method of  claim 16  wherein said bile salt is sodium deoxycholate and is up to 5% w/w. 
     
     
         25 . The method of  claim 16  wherein the ratio of said lipid and said bile acid or bile salt is up to 1% w/w. 
     
     
         26 . The method of  claim 16  wherein said lipid is phosphatidylcholine. 
     
     
         27 . The method of  claim 16  wherein said lipid is phosphatidylcholine and is up to 5% w/w. 
     
     
         28 . The method of  claim 16  wherein said composition is an aqueous solution. 
     
     
         29 . The method of  claim 18  wherein said aqueous solution has total volume up to 500 mL. 
     
     
         30 . A method for reducing a subcutaneous fat deposit in a subject comprising:
 administering locally to said subcutaneous fat deposit a composition comprising:
 (i) a fat-dissolving effective amount of one or more bile acids or bile salts; 
 (ii) a pharmaceutical or veterinary excipient; and 
 (iii) optionally a lipid, wherein the ratio of the lipid and bile acid or bile salt is up to 1% w/w and wherein the composition does not include lipase or colipase. 
   
     
     
         31 . The method of  claim 30  wherein said condition is selected from the group consisting of obesity, fat redistribution syndrome, eyelid fat herniation, lipomas, Dercum's disease, lipodystrophy, buffalo hump lipodystrophy, dorsocervical fat, visceral adiposity, breast enlargement, hyperadiposity, diffused body fat around trunk and arms, and fat deposits associated with cellulite. 
     
     
         32 . The method of  claim 30  wherein said bile acid is selected from the group consisting of deoxycholic acid, cholic acid, chenodeoxycholic acid, 7-alpha-dehydroxylate chenodeoxycholic acid, lithocholic acid, ursodeoxycholic acid, dihydroxytaurin acid, trihydroxytaurine acid, and glycine conjugates of any of the above. 
     
     
         33 . The method of  claim 30  wherein said bile salt comprises a cation selected from the group consisting of sodium (Na + ), potassium (10, lithium (Li + ), magnesium (Mg 2+ ), calcium (Ca 2+ ), barium (Ba 2+ ), strontium (Sr 2+ ), and ammonium (NH 4+ ). 
     
     
         34 . The method of  claim 30  wherein said bile salt comprises an alkali metal or an alkaline earth metal. 
     
     
         35 . The method of  claim 34  wherein said alkali metal is sodium (Na + ), potassium (K + ) or lithium (Li + ). 
     
     
         36 . The method of  claim 34  wherein said alkaline earth metal is magnesium (Mg 2+ ), calcium (Ca 2+ ), barium (Ba 2+ ), or strontium (Sr 2+ ). 
     
     
         37 . The method of  claim 30  wherein said bile salt is sodium deoxycholate. 
     
     
         38 . The method of  claim 30  wherein said method does not include performing surgery on said subject. 
     
     
         39 . The method of  claim 30  wherein said composition is administered locally under eye, under chin, under arm, buttock, calf, back, thigh, or stomach of said subject. 
     
     
         40 . The method of  claim 30  wherein said administering is by a subcutaneous or transdermal injection. 
     
     
         41 . The method of  claim 30  wherein said subject is a human, cat, dog or horse. 
     
     
         42 . The method of  claim 30  wherein said subject is human HIV patient 
     
     
         43 . The method of  claim 30  wherein said composition includes up to 5% w/w lipids. 
     
     
         44 . The method of  claim 30  wherein said lipid is phosphatidylcholine and wherein said composition includes up to 5% w/w of said lipid. 
     
     
         45 . The method of  claim 30  wherein said composition comprises about 0.001% w/w to about 10% w/w of said bile acid or bile salt. 
     
     
         46 . The method of  claim 30  wherein said composition comprises between about 0.01% w/w and about 5% w/w of said bile acid or bile salt. 
     
     
         47 . The method of  claim 30  wherein said composition is in solution. 
     
     
         48 . The method of  claim 47  wherein said solution is aqueous 
     
     
         49 . A syringe loadable container comprising:
 a fat-dissolving or skin-tightening effective amount of a bile acid or a bile salt;   a pharmaceutical or veterinary excipient; and   optionally a lipid wherein the ratio of said bile acid or bile salt to said lipid is greater than 1% w/w and wherein the solution does not contain lipase or colipase.   
     
     
         50 . The syringe loadable container of  claim 47  wherein said bile salt is sodium deoxycholate. 
     
     
         51 . The syringe loadable container of  claim 47  further comprising an organic solvent. 
     
     
         52 . The syringe loadable container of  claim 47  comprising up to 10 g of said bile acid or bile salt.