Compositions of leukaemia inhibitory factor

Abstract

The present invention relates generally to compositions and more particularly to compositions comprising leukaemia inhibitory factor (hereinafter referred to as “LIF”) or derivative or homologues thereof. The compositions of the present invention are particularly useful as compositions which exhibit enhanced stability and/or which exhibit reduced aggregation and/or reduced deamidation of LIF, its derivatives or other active ingredients.

1 . A composition comprising leukaemia inhibitory factor (LIF) or a derivative or homologue thereof and a stabilizing agent facilitating chemical and/or physical stability of LIF in the composition and one or more pharmaceutically acceptable carriers and/or diluents.  
     
     
         2 . A composition according to  claim 1  wherein the stabilizing agent facilitates reduced aggregation of LIF.  
     
     
         3 . A composition according to  claim 1  wherein the stabilizing agent facilitates a reduction in the deamidation of LIF.  
     
     
         4 . A composition according to  claim 1  wherein the pH of the composition is from between about 3.5 and 6.5.  
     
     
         5 . A composition according to  claim 3  wherein the pH of the composition is from between about 3.5 and 6.5.  
     
     
         6 . A composition according to  claim 1  wherein the stabilizing agent is an isotonicity agent, an agent which increases or maintains the conformational stability of LIF or its derivatives of homologues or a surfactant or functional equivalents thereof.  
     
     
         7 . A composition according to  claim 6  wherein the stabilizing agent is an isotonicity agent selected from a polyhydric alcohol, a pharmaceutically acceptable salt, a buffer species, a sugar and a pharmaceutically acceptable polymeric compound.  
     
     
         8 . A composition according to  claim 7  wherein the polyhydric alcohol is sorbitol.  
     
     
         9 . A composition according to  claim 6  wherein the surfactant is an anionic, cationic, amphoteric or non-ionic surfactant.  
     
     
         10 . A composition according to  claim 9  wherein the surfactant is selected from a fatty alcohol, a glyceryl ester and a fatty acid ester of a fatty alcohol or other alcohol.  
     
     
         11 . A composition according to  claim 6  wherein the stabilizing agent is selected from a polysorbate, a polyoxyethylene derivative and a pharmaceutically acceptable polyoxyethylene-polyoxypropylene copolymer.  
     
     
         12 . A composition according to  claim 7  wherein the buffer species is selected from a phosphate, citrate and acetate buffer.  
     
     
         13 . A composition according to  claim 12  wherein the buffer species is a citrate or acetate buffer.  
     
     
         14 . A composition comprising leukaemia inhibitory factor (LIF) and one or more pharmaceutically acceptable carriers and/or diluents and wherein the composition has a pH of between 3.5 and 6.5.  
     
     
         15 . A composition according to  claim 6  wherein the aggregation of LIF over time is reduced.  
     
     
         16 . A composition according to  claim 6  wherein the deamidation of LIF over time is reduced.  
     
     
         17 . A composition according to  claim 14  where the pH is maintained by the presence of a buffer species selection from a phosphate, citrate and acetate buffer.  
     
     
         18 . A composition according to  claim 17  wherein the buffer species is a citrate or acetate buffer.  
     
     
         19 . A composition according to  claim 14  wherein the pH is between from about 4.5 and about 5.5.  
     
     
         20 . A composition according to  claim 1  wherein LIF is present in an amount from about 0.1 μ/ml to about 100 mg/ml.  
     
     
         21 . A method for preparing a composition comprising leukaemia inhibitory factor (LIF) or a derivative or homologue thereof and which exhibits reduced deamidation and/or agglutination of LIF or its derivative or homologues over time said method comprising admixing LIF or its derivative or homologue with a stabilizing agent.  
     
     
         22 . A method according to  claim 21  wherein the stabilizing agent is a isotonicity agent, an agent which increases or maintains the conformational stability of LIF or its derivatives or homologues or a surfactant or functional equivalents thereof.  
     
     
         23 . A method according to  claim 22  wherein the stabilizing agent is an isotonicity agent selected from a polyhydric alcohol, a pharmaceutically acceptable salt, a buffer species, a sugar and a pharmaceutically acceptable polymeric compound.  
     
     
         24 . A method according to  claim 23  wherein the polyhydric alcohol is sorbitol.  
     
     
         25 . A method according to  claim 22  wherein the surfactant is an anionic, cationic, amphoterifc or n on-ionic surfactant.  
     
     
         26 . A method according to  claim 25  wherein the surfactant is selected from a fatty alcohol, glyceryl ester and a fatty acid ester of a fatty alcohol or other alcohol.  
     
     
         27 . A method according to  claim 22  wherein the stabilizing agent is selected from a polysorbate, a polyoxyethylene derivative and a pharmaceutically acceptable polyoxyethylene-polyoxypropylene copolymer.  
     
     
         28 . A method according to  claim 23  wherein the buffer species is selected from a phosphate, citrate and acetate buffer.  
     
     
         29 . A method according to  claim 28  wherein the buffer species is a citrate or acetate buffer.  
     
     
         30 . A method according to  claim 21  further comprising adjusting the pH to between from about 3.5 and about 6.5.  
     
     
         31 . A method according to  claim 30  wherein the pH is between from about 4.5 and about 5.5.  
     
     
         32 . A method according to  claim 21  further comprising admixing one or more pharmaceutically acceptable carriers and/or diluents.  
     
     
         33 . Use of a stabilizing agent in the manufacture of a composition exhibiting improved chemical and/or physical stability of Leukaemia Inhibitory Factor (LIF) or a derivative or homologue thereof.  
     
     
         34 . Use according to  claim 33  wherein the stabiling agent is an isotonicity agent selected from a polyhydric alcohol, a pharmaceutically acceptable salt, a buffer species, a sugar and a pharmaceutically acceptable polymeric compound.  
     
     
         35 . Use according to  claim 34  wherein the polyhydric alcohol is sorbitol.  
     
     
         36 . Use according to  claim 34  wherein the surfactant is an anionic, cationic, amphoteric or non-ionic surfacant.  
     
     
         37 . Use according to  claim 36  wherein the surfactant is selected from a fatty alcohol, glyceryl ester and a fatty acid ester of a fatty alcohol or other alcohol.  
     
     
         38 . Use according to  claim 33  where the stabilizing agent is selected from a polysorbate, a polyoxyethylene derivative or a pharmaceutically acceptable polyoxyethylene-polyoxypropylene copolymer.  
     
     
         39 . Use according to  claim 34  wherein the buffer species is selected from a phosphate, citrate and acetate buffer.  
     
     
         40 . Use according to  claim 39  wherein the buffer species is a citrate or acetate buffer.  
     
     
         41 . Use according to  claim 33  where the pH of the composition is between from about 3.5 to about 6.5.  
     
     
         42 . Use according to  claim 41  wherein the pH is between from about 4.5 and about 5.5  
     
     
         43 . A composition according to  claim 14  wherein LIF is present in an amount from about 0.1 μg/ml to about 100 mg/ml.