Lipid formulations comprising a thiolated antioxidant

Abstract

The present invention provides a formulation comprising a lipid matrix; at least one thiolated antioxidant; at least one bioactive agent; and optionally at least one chelating agent. The bioactive agent may be a gonadotrophin-releasing hormone (GnRH) agonist; a gonadotrophin-releasing hormone (GnRH) antagonist; a luthenizing hormone releasing hormone (LHRH); and/or a luthenizing hormone releasing hormone (LHRH) related peptide.

What is claimed is: 
     
         1 ) A formulation comprising:
 i) a lipid matrix;   ii) at least one thiolated antioxidant;   iii) at least one of:
 a gonadotrophin-releasing hormone (GnRH) agonist; 
 a gonadotrophin-releasing hormone (GnRH) antagonist; 
 a luthenizing hormone releasing hormone (LHRH); and/or 
 a luthenizing hormone releasing hormone (LHRH) related peptide; and 
   iv) optionally at least one chelating agent.   
     
     
         2 ) A formulation as claimed in  claim 1 , wherein said lipid matrix comprises:
 a) at least one diacyl glycerol and/or tocopherol;   b) at least one phospholipid;   c) at least one oxygenated organic solvent; and   d) optionally at least one fragmentation agent.   
     
     
         3 ) A formulation as claimed in  claim 2 , wherein the lipid matrix is in the form of at least one non-lamellar phase, or generates at least one non-lamellar phase upon exposure to an aqueous fluid. 
     
     
         4 ) A formulation as claimed in  claim 1 , wherein the thiolated antioxidant is selected from the group consisting of a thiolated sugar, thiolated amino acid, a thiolated amino ester, and a thiolated polyol. 
     
     
         5 ) A formulation as claimed in  claim 4 , wherein said thiolated antioxidant is selected from the group consisting of mono-thioglycerol, cysteine, and N-acetyl cysteine. 
     
     
         6 ) A formulation as claimed in  claim 1  additionally comprising a chelating agent. 
     
     
         7 ) A formulation as claimed in  claim 6 , wherein said chelating agent is EDTA. 
     
     
         8 ) A formulation as claimed in  claim 1  additionally comprising a lipid soluble acid. 
     
     
         9 ) A formulation as claimed in  claim 1 , wherein said at least one gonadotrophin-releasing hormone (GnRH) agonist and/or GnRH antagonist is selected from the group consisting of buserelin, luprorelin, goserelin, triptorelin, avorelin, deslorelin, abarelix, and degarelix. 
     
     
         10 ) A method for reducing oxidative degradation in a formulation comprising a lipid matrix and at least one of:
 a gonadotrophin-releasing hormone (GnRH) agonist;   a gonadotrophin-releasing hormone (GnRH) antagonist;   luthenizing hormone releasing hormone (LHRH); and/or   a luthenizing hormone releasing hormone (LHRH) related peptide;   said method comprising adding at least one thiolated antioxidant and optionally at least one chelating agent to the formulation.   
     
     
         11 ) A method according to  claim 10 , wherein said at least one gonadotrophin-releasing hormone (GnRH) agonist and/or GnRH antagonist is selected from the group consisting of buserelin, luprorelin, goserelin, triptorelin, avorelin, deslorelin, abarelix, and degarelix.