Acid containing lipid formulations

Abstract

The present invention relates to compositions forming a low viscosity mixture of: i) a non-polymeric slow-release matrix ii) at least one biocompatible, (preferably oxygen containing) organic solvent; iii) at least one peptide active agent; and iv) at least one lipid soluble acid. The invention further relates to methods of treatment comprising administration of such compositions, especially in treating diabetes, and to pre-filled administration devices and kits containing the formulations.

1 - 21 . (canceled) 
     
     
         22 . A non-aqueous pre-formulation comprising a low viscosity mixture of:
 i) a lipid-based slow-release matrix;   ii) at least one biocompatible, oxygen-containing organic solvent selected from the group consisting of: an alcohol, a ketone, an ester, an ether, an amide or a sulfoxide;   iii) at least one peptide active agent; and   iv) at least one lipid soluble acid.   
     
     
         23 . A non-aqueous pre-formulation as claimed in  claim 22  comprising a low viscosity mixture of:
 a) at least one neutral diacyl lipid and/or a tocopherol; 
 b) at least one phospholipid; 
 c) at least one biocompatible, oxygen-containing organic solvent selected from the group consisting of: an alcohol, a ketone, an ester, an ether, an amide or a sulfoxide; 
 d) at least one peptide active agent; and 
 e) at least one lipid soluble acid; 
 wherein the pre-formulation forms, or is capable of forming, at least one liquid crystalline phase structure upon contact with an aqueous fluid. 
 
     
     
         24 . A non-aqueous pre-formulation as claimed in  claim 22  comprising a low viscosity mixture of:
 a) at least one diacyl glycerol; 
 b) at least one phosphatidyl choline; 
 c) at least one oxygen-containing organic solvent selected from the group consisting of: an alcohol, a ketone, an ester, an ether, an amide or a sulfoxide; 
 d) at least one peptide active agent; and 
 e) at least one lipid soluble acid; 
 wherein the pre-formulation forms, or is capable of forming, at least one liquid crystalline phase structure upon contact with an aqueous fluid. 
 
     
     
         25 . A non-aqueous pre-formulation as claimed in  claim 23  wherein component a) is present at a level of 30-70% by weight. 
     
     
         26 . A non-aqueous pre-formulation as claimed in  claim 23  wherein component b) is present at a level of 30-60% by weight. 
     
     
         27 . A non-aqueous pre-formulation as claimed in  claim 22  wherein the oxygen-containing organic solvent is present at a level of 0.1 to 20% by weight. 
     
     
         28 . A non-aqueous pre-formulation as claimed in  claim 22  wherein said lipid soluble acid is selected from the group consisting of: benzoic acid, citric acid, a sulfonic acid or a hydrohalic acid. 
     
     
         29 . A non-aqueous pre-formulation as claimed in  claim 22  wherein said lipid soluble acid is selected from the group consisting of: benzoic acid, citric acid, methane sulfonic acid, benzene sulfonic acid, toluene sulfonic acid and HCl. 
     
     
         30 . A non-aqueous pre-formulation as claimed in  claim 22  wherein said biocompatible, oxygen-containing organic solvent includes at least one solvent selected from the group consisting of: a ketone, an ester, an ether, an amide and a sulfoxide. 
     
     
         31 . A non-aqueous pre-formulation as claimed in  claim 22  wherein said biocompatible, oxygen-containing organic solvent includes at least one amide selected from the group consisting of: N-methyl pyrrolidone (NMP), 2-pyrrolidone and dimethylacetamide (DMA). 
     
     
         32 . A non-aqueous pre-formulation as claimed in  claim 22  wherein said biocompatible, oxygen-containing organic solvent includes dimethylsulfoxide (DMSO). 
     
     
         33 . A non-aqueous pre-formulation as claimed in  claim 22  which is capable of being dispensed through a needle of 19 awg by manual pressure. 
     
     
         34 . A method of delivery of a peptide active agent to a human or non-human animal body, said method comprising parenterally administering a non-aqueous pre-formulation comprising a low viscosity mixture of:
 i) a non-polymeric slow-release matrix   ii) at least one biocompatible, oxygen-containing organic solvent selected from the group consisting of: an alcohol, a ketone, an ester, an ether, an amide or a sulfoxide;   iii) at least one peptide active agent; and   iv) at least one lipid soluble acid.   
     
     
         35 . A pre-filled administration device containing a pre-formulation as claimed in  claim 22 . 
     
     
         36 . A kit comprising an administration device as claimed in  claim 35 .