US2014371187A1PendingUtilityA1

Semi-solid delivery vehicle and pharmaceutical compositions

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Assignee: HERON THERAPEUTICS INCPriority: May 11, 2000Filed: Apr 15, 2014Published: Dec 18, 2014
Est. expiryMay 11, 2020(expired)· nominal 20-yr term from priority
A61P 39/02A61P 29/00A61Q 19/00A61K 9/1647A61K 8/85A61Q 15/00A61Q 17/04A61K 31/439A61K 9/0014A61K 31/765A61K 47/10A61K 31/445A61P 23/00A61K 9/0024A61K 31/573A61K 9/06A61K 8/86A61P 23/02A61P 1/08A61K 9/0019A61K 47/34A61K 45/06A61K 9/08A61K 9/10
67
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Claims

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.

Claims

exact text as granted — not AI-modified
1 . A pharmaceutical composition comprising:
 (A) semi-solid delivery vehicle, comprising:
 (i) a polyorthoester of formula I or formula II 
   
       
         
           
           
               
               
           
         
       
       where: 
       R is a bond, —(CH 2 ) a —, or —(CH 2 ) b —O—(CH 2 ) c —; where a is an integer of 1 to 10, and b and c are independently integers of 1 to 5; 
       R* is a C 1-4  alkyl; 
       n is an integer of at least 5; and 
       A is R 1 , R 2 , R 3 , or R 4 , where 
       R 1  is: 
       
         
           
           
               
               
           
         
       
       where: 
       p is an integer of 1 to 20; 
       R 5  is hydrogen or C 1-4  alkyl; and 
       R 6  is: 
       
         
           
           
               
               
           
         
       
       where: 
       s is an integer of 0 to 30; 
       t is an integer of 2 to 200; and 
       R 7  is hydrogen or C 1-4  alkyl; 
       R 2  is: 
       
         
           
           
               
               
           
         
       
       R 3  is: 
       
         
           
           
               
               
           
         
       
       where: 
       x is an integer of 0 to 30; 
       y is an integer of 2 to 200; 
       R 8  is hydrogen or C 1-4  alkyl; 
       R 9  and R 10  are independently C 1 -C 12  alkylene; 
       R 11  is hydrogen or C 1-6  alkyl and R 12  is C 1 -C 6  alkyl; or R 11  and R 12  together are C 3-10  alkylene; and 
       R 4  is the residue of a diol containing at least one functional group independently selected from amide, imide, urea, and urethane groups; 
       in which at least 0.01 mol percent of the A units are of the formula R 1 ; and
 (ii) a pharmaceutically acceptable, polyorthoester-compatible liquid excipient selected from polyethylene glycol ether derivatives having a molecular weight between 200 and 4000, polyethylene glycol copolymers having a molecular weight between 400 and 4000, mono-, di-, or tri-glycerides of a C 2-19  aliphatic carboxylic acid or a mixture of such acids, alkoxylated tetrahydrofurfuryl alcohols and their C 1-4  alkyl ethers and C 2-19  aliphatic carboxylic acid esters, and biocompatible oils; and 
 (B) an anesthetic agent. 
 
     
     
         2 . The semi-solid delivery vehicle of  claim 1  where the concentration of the polyorthoester ranges from 1% to 99% by weight. 
     
     
         3 . The semi-solid delivery vehicle of  claim 1  where the polyorthoester has a molecular weight between 1,000 and 20,000. 
     
     
         4 . The semi-solid delivery vehicle of  claim 1  where the fraction of the A units that are of the formula R 1  is between 1 and 90 mol percent. 
     
     
         5 . The semi-solid delivery vehicle of  claim 1  where the polyorthoester is of formula I,
 where: 
 none of the units have A equal to R 2 ; 
 R 3  is: 
 
       
         
           
           
               
               
           
         
         where: 
         x is an integer of 0 to 10; 
         y is an integer of 2 to 30; and 
         R 6  is: 
       
       
         
           
           
               
               
           
         
         where: 
         s is an integer of 0 to 10; 
         t is an integer of 2 to 30; and 
         R 5 , R 7 , and R 8  are independently hydrogen or methyl. 
       
     
     
         6 . The semi-solid delivery vehicle of  claim 5  where:
 R 3  and R 6  are both —(CH 2 —CH 2 —O) 2 —(CH 2 —CH 2 )—; 
 R 5  is methyl; and 
 p is 1 or 2. 
 
     
     
         7 . The semi-solid delivery vehicle of  claim 5  where:
 R 3  and R 6  are both —(CH 2 —CH 2 —O) 9 —(CH 2 —CH 2 )—; 
 R 5  is methyl; and 
 p is 1 or 2. 
 
     
     
         8 . The pharmaceutical composition of  claim 1  where the anesthetic agent is selected from the group consisting of bupivacaine, lidocaine, mepivacaine, pyrrocaine and prilocaine. 
     
     
         9 . The pharmaceutical composition of  claim 8 , wherein the concentration of the anesthetic agent in the composition is about 1-5 wt. %. 
     
     
         10 . (canceled) 
     
     
         11 . The pharmaceutical composition of  claim 1  where the fraction of the anesthetic agent is from 0.1% to 60% by weight of the composition. 
     
     
         12 . The pharmaceutical composition of  claim 11  where the fraction of the anesthetic agent is from 0.5 to 40% by weight of the composition. 
     
     
         13 . The pharmaceutical composition of  claim 1  where the composition is in topical, syringable, or injectable form. 
     
     
         14 .- 16 . (canceled) 
     
     
         17 . The pharmaceutical composition of  claim 1  further comprising a glucocorticosteroid to form a combination composition. 
     
     
         18 .- 19 . (canceled) 
     
     
         20 . A method for the treatment of localized pain in a patient in need thereof, the method comprising administering to the patient the composition of  claim 1  via injection. 
     
     
         21 . The method of  claim 20  wherein the anesthetic agent is selected from the group consisting of bupivacaine, lidocaine, mepivacaine, pyrrocaine and prilocaine. 
     
     
         22 . The method of  claim 20  wherein the patient is a human. 
     
     
         23 . The method of  claim 20  wherein the administering comprises applying the composition into a surgical site. 
     
     
         24 . The method of  claim 21 , wherein the anesthetic agent is in the form of a free base. 
     
     
         25 .- 31 . (canceled) 
     
     
         32 . A process for the preparation of the delivery vehicle of  claim 1 , comprising mixing the components (A) and (B) in the absence of a solvent, at a temperature between about 20 and 150° C. 
     
     
         33 . A process for the preparation of the pharmaceutical composition of  claim 1  where the anesthetic agent is in solid form, comprising:
 (1) optionally milling the active agent to reduce the particle size of the active agent; 
 (2) mixing the active agent and the delivery vehicle; and 
 (3) optionally milling the composition from (2) to reduce the particle size of the active agent in the composition. 
 
     
     
         34 . (canceled)

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