Compositions and Methods for the Treatment of Sleep Apnea

Abstract

The present invention features a novel therapy for effecting weight loss which involves treating a subject with a sympathomimetic agent (e.g., phentermine or phentermine-like drug) in combination with an anticonvulsant sulfamate derivative (e.g., topiramate) such that the subject experiences weight loss. The combination methods of the present invention also are effective against symptoms associated with Syndrome X. The invention also features pharmaceutical compositions and kits for use in the practice of these novel therapies.

What is claimed: 
     
         1 . A method for treating sleep apnea in a subject comprising administering to the patient a therapeutically effective amount of a carbonic anhydrase inhibitor comprising an anticonvulsant sulfamate derivative in combination with a therapeutically effective amount of a sympathomimetic agent. 
     
     
         2 . The method of  claim 1 , wherein the sympathomimetic agent is a substituted or unsubstituted aromatic amine. 
     
     
         3 . The method of  claim 2 , wherein the sympathomimetic agent is selected from phenylethylamine, epinephrine, norepinephrine, epinine, dopamine, dobutamine, nordefrin, ethylnorepinephrine, isoproterenol, protokyiol, isoetharine, metaproterenol, terbutaline, metaraminol, phenylephrine, tyramine, hydroxyamphetamine, methoxyphenamine, methoxamine, albuterol, amphetamine, methamphetamine, benzphetamine, ephedrine, phenylpropanolamine, mephentermine, phentermine, chlorphentermine, fenfluramine, propylhexedrine, diethylpropion, phenmetrazine, and phendimetrazine. 
     
     
         4 . The method of  claim 3 , wherein the sympathomimetic agent is phentermine. 
     
     
         5 . The method of  claim 1 , wherein the carbonic anhydrase inhibitor is a compound having the structure of formula (I) 
       
         
           
           
               
               
           
         
       
       wherein X is CH 2  or O, R 1 , R 2 , R 3 , R 4 , and R 5  are independently H or C1-C4 alkyl, and further wherein when X is O, then R 2  and R 3 , and/or R 4  and R 5 , may be taken together to form a methylene dioxy linkage of the formula —O—CR 6 R 7 —O— in which R 6  and R 7  are independently H or C 1 -C 3  alkyl, or may be taken together to form a cyclopentyl or cyclohexyl ring. 
     
     
         6 . The method of  claim 5 , wherein X is O, R 1  is H, R 2  and R 3  taken together form the methylene dioxy linkage —O—CH 2 —O—, R 4  and R 5  taken together form the methylene dioxy linkage —O—CH 2 —O—, and the carbonic anhydrase inhibitor is topiramate. 
     
     
         7 . The method of  claim 1 , wherein the carbonic anhydrase inhibitor and the sympathomimetic agent are administered simultaneously. 
     
     
         8 . The method of  claim 7 , wherein the carbonic anhydrase inhibitor and the sympathomimetic agent are administered in a single pharmaceutical formulation. 
     
     
         9 . The method of  claim 8 , wherein the pharmaceutical formulation comprises a controlled release dosage form. 
     
     
         10 . The method of  claim 9 , wherein the controlled release dosage form provides for immediate release of the sympathomimetic agent and delayed release of the carbonic anhydrase inhibitor. 
     
     
         11 . The method of  claim 10 , wherein the controlled release dosage form further provides for sustained release of the carbonic anhydrase inhibitor. 
     
     
         12 . The method of  claim 1 , wherein the carbonic anhydrase inhibitor is topiramate and the sympathomimetic agent is phentermine. 
     
     
         13 . The method of  claim 12 , wherein the therapeutically effective amount of topiramate is from 5 mg to 1000 mg daily and the therapeutically effective amount of phentermine is in the range of about 5 mg to 60 mg daily. 
     
     
         14 . The method of  claim 13 , wherein the therapeutically effective amount of topiramate is at most about 400 mg daily. 
     
     
         15 . The method of  claim 12 , wherein the phentermine and the topiramate are administered simultaneously. 
     
     
         16 . The method of  claim 15 , wherein the phentermine and the topiramate are administered in a single pharmaceutical formulation. 
     
     
         17 . The method of  claim 16 , wherein the pharmaceutical formulation comprises a controlled release dosage form. 
     
     
         18 . The method of  claim 17 , wherein the controlled release dosage form provides for immediate release of the phentermine and delayed release of the topiramate. 
     
     
         19 . The method of  claim 18 , wherein the controlled release dosage form further provides for sustained release of the topiramate. 
     
     
         20 . The method of  claim 18 , wherein release of topiramate is delayed by 4 hours following release of phentermine. 
     
     
         21 . The method of  claim 19 , wherein release of topiramate is delayed by 8 hours following release of phentermine. 
     
     
         22 . The method of  claim 19 , wherein release of topiramate is delayed by 12 hours following release of phentermine. 
     
     
         23 . The method of  claim 19  , wherein a physiologically effective blood level of topiramate is provided over a 4-hour period. 
     
     
         24 . The method of  claim 19 , wherein a physiologically effective blood level of topiramate is provided over an 8-hour period. 
     
     
         25 . The method of  claim 19 , wherein a physiologically effective blood level of topiramate is provided over a 12-hour period. 
     
     
         26 . The method of  claim 14 , wherein the therapeutically effective amount of topiramate is almost about 250 mg daily. 
     
     
         27 . The method of  claim 14 , wherein the therapeutically effective amount of phentermine is in the range of about 5 mg to 15 mg daily. 
     
     
         28 . The method of  claim 26 , wherein the therapeutically effective amount of phentermine is in the range of about 5 mg to about 15 mg daily.