Methods of treating nausea utilizing semi-solid delivery vehicle compositions comprising granisetron

Abstract

A semi-solid delivery vehicle contains a polyorthoester and an excipient, and a semi-solid pharmaceutical composition contains an active agent and the delivery vehicle. The pharmaceutical composition may be a topical, syringable, or injectable formulation; and is suitable for local delivery of the active agent. Methods of treatment are also disclosed.

What is claimed is: 
     
         1 . A method for the prevention of nausea and vomiting in a patient in need thereof comprising administering to the patient a pharmaceutical composition comprising:
 (A) a semi-solid delivery vehicle, comprising:
 (i) a polyorthoester of formula I: 
   
       
         
           
           
               
               
           
         
       
       where:
 R* is ethyl; 
 n is an integer of 5 to 1000; and 
 A is R 1  or R 3 , where R 1  is: 
 
       
         
           
           
               
               
           
         
       
       where:
 p is an integer of 1 to 20; 
 R 5  is hydrogen; and 
 R 6  is: 
 
       
         
           
           
               
               
           
         
       
       where:
 s is an integer of 0 to 10; 
 R 3  is: 
 
       
         
           
           
               
               
           
         
       
       where:
 x is an integer of 0 to 30; 
 in which about 0.05 to 30 mol percent of the A units are of the formula R 1 ; and
 (ii) polyethylene glycol monomethyl ether; and 
 
 (B) granisetron in an amount of 1 to 5 weight % of the composition. 
 
     
     
         2 . The method of  claim 1 , wherein the nausea and vomiting is associated with chemotherapy. 
     
     
         3 . The method of  claim 1 , wherein the nausea and vomiting is acute or delayed. 
     
     
         4 . The method of  claim 1 , wherein the composition is administered to the patient in combination with another antiemetic. 
     
     
         5 . The method of  claim 3 , wherein the composition is administered to the patient in combination with another antiemetic. 
     
     
         6 . The method of  claim 1 , wherein the administering is by injection. 
     
     
         7 . The method of  claim 1 , wherein the administering is by subcutaneous injection. 
     
     
         8 . The method of  claim 7 , wherein the administering is by a syringe with a 16 to 25 gauge needle. 
     
     
         9 . The method of  claim 1 , wherein the polyethylene glycol monomethyl ether has a molecular weight between 200 and 4000. 
     
     
         10 . The method of  claim 9 , wherein the total concentration of the polyethylene glycol monomethyl ether is 5 to 60 weight % of the composition. 
     
     
         11 . The method of  claim 1 , wherein the polyethylene glycol monomethyl ether is polyethylene glycol monomethyl ether 550. 
     
     
         12 . The method of  claim 9 , wherein the polyethylene glycol monomethyl ether is polyethylene glycol monomethyl ether 550. 
     
     
         13 . The method of  claim 1 , wherein the composition comprises 78.4 weight % polyorthoester, 19.6 weight % polyethylene glycol monomethyl ether and 2 weight % granisetron. 
     
     
         14 . The method of  claim 1 , wherein p is an integer of 1 to 7 in a portion of the units of formula I. 
     
     
         15 . The method of  claim 1 , wherein x is 2 in a portion of the units of formula I. 
     
     
         16 . The method of  claim 1 , wherein s is 2 in a portion of the units of formula I. 
     
     
         17 . The method of  claim 1 , wherein the total concentration of the polyethylene glycol monomethyl ether is 5% to 80% weight percent of the composition. 
     
     
         18 . The method of  claim 1 , wherein about 0.1 to 25 mol percent of the A units are of the formula R 1 .