Pharmaceutical compositions comprising dextran with a molecular weight of 1.0-100 kda and processes for their preparation

Abstract

A solid or semisolid implant obtainable by providing a liquid composition comprising an aqueous solution of dextran with molecular weight of 1.0-100 kDa and introducing the liquid composition into the body of a mammal, whereby the implant is formed in situ in the body of the mammal. A process for preparing a composition useful for biomedical application, comprising the steps of providing a liquid composition comprising an aqueous solution of dextran having a molecular weight of 1-100 kDa; and bringing the liquid composition to solidify; whereby water is gradually eliminated from the liquid composition during the solidification. A biomedical article prepared from the composition.

1 . A solid or semisolid implant obtainable by providing a liquid composition comprising an aqueous solution of dextran with molecular weight of 1.0-100 kDa at a concentration within the range of 25-75% by weight and introducing the liquid composition into the body of a mammal, whereby said implant is formed in situ in the body of said mammal. 
     
     
         2 . The implant of  claim 1 , wherein said liquid composition further comprises at least one biologically or pharmaceutically active substance dissolved or suspended therein. 
     
     
         3 . The implant of  claim 2 , wherein said biologically or pharmaceutically active substance is present at a concentration of from 0.01 to 25% by weight of the liquid composition. 
     
     
         4 . The implant of  claim 2 , wherein said biologically or pharmaceutically active substance is selected from the group consisting of proteins, polypeptides, peptides, organic molecules, oligonucleotides and polynucleotides. 
     
     
         5 . The implant of  claim 1  or  claim 2 , wherein said dextran is present in said liquid composition at a concentration within the range of 60-70% by weight. 
     
     
         6 . The implant of  claim 1  or  claim 2 , wherein said liquid composition is introduced into the body of said mammal by injection. 
     
     
         7 . The implant of  claim 1  or  claim 2 , wherein said liquid composition has been freeze-dried and is rehydrated to the initial water concentration before introducing it into the body of said mammal. 
     
     
         8 . The implant of  claim 2 , wherein said biologically or pharmaceutically active substance is insulin or a derivative thereof. 
     
     
         9 . A method of treatment of a disease or disorder in a mammal in need of such treatment, comprising forming the implant of  claim 1  in the body of said mammal and permitting the release of said at least one biologically or pharmaceutically active substance into the body of said mammal. 
     
     
         10 . The method of  claim 9 , wherein said disease or disorder is diabetes. 
     
     
         11 . The method of  claim 9 , wherein said biologically or pharmaceutically active substance is insulin or a derivative thereof. 
     
     
         12 . The method of  claim 9 , wherein said mammal is a human. 
     
     
         13 . A process for preparing a composition, said composition being suitable for the controlled release of a biologically active protein in the body of a mammal, said process comprising:
 a. providing an aqueous solution of dextran having a molecular weight of 1-100 kDa at a concentration within the range of 25-75% by weight;   b. introducing a biologically active protein into the aqueous solution of (a) to form a liquid composition; and   c. forming a solid matrix from said dextran in said liquid composition by bringing said dextran in said liquid composition to a solid form by gradually eliminating water from said liquid composition by evaporation or extraction, thereby providing a composition in which said biologically active protein is contained within said solid matrix.   
     
     
         14 . The process of  claim 13 , wherein the molecular weight of dextran is 1-70 kDa. 
     
     
         15 . The process of  claim 13 , wherein dextran is present in said aqueous solution of (a) at a concentration within the range of 50-75% by weight. 
     
     
         16 . The process of  claim 13 , wherein water is eliminated from said liquid composition by evaporation. 
     
     
         17 . The process of  claim 16 , wherein said evaporation is performed at temperature of from 0° C. to 50° C. 
     
     
         18 . The process of  claim 17 , wherein said evaporation is performed at temperature of from 20° C. to 37° C. 
     
     
         19 . The process of  claim 16 , wherein the rate of evaporation is 0.10-75% by weight of said liquid composition per hour. 
     
     
         20 . The process of  claim 13 , wherein water is eliminated from said liquid composition by extraction. 
     
     
         21 . The process of  claim 20 , wherein said extraction is performed by adding 1-10 parts by weight of ethanol, liquid polyethylene glycol (PEG), or liquid polypropylene glycol (PPG), to 1 part by weight of said liquid composition. 
     
     
         22 . The process of  claim 13 , wherein said biologically active protein is dissolved or suspended in said aqueous solution. 
     
     
         23 . The process of  claim 13 , wherein said biologically active protein is introduced in an amount so as to be present at a concentration of 0.01 to 25% by weight in said liquid composition. 
     
     
         24 . The process of  claim 13 , wherein said protein is insulin. 
     
     
         25 . An article for biomedical applications comprising a composition prepared by the process of  claim 13 . 
     
     
         26 . The article of  claim 25 , wherein said article is in the form of a hard pharmaceutical capsule. 
     
     
         27 . The article of  claim 25 , wherein said protein is insulin. 
     
     
         28 . The article of  claim 25 , wherein said protein is insulin and said article is in the form of a hard pharmaceutical capsule.