Pharmaceutical Compositions Comprising Dextran with a Molecular Weight of 1.0-100 Kda and Processes for Their Preparation

1 . A process for preparing a pharmaceutical composition suitable for the controlled release, in the body of a mammal, of a biologically active substance, 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 substance selected from proteins into the aqueous solution of (a) to produce a liquid composition; and

(c) bringing the liquid composition thus obtained to solidify by gradually eliminating water from the liquid composition by evaporation or extraction.

2 . The process of claim 1 , wherein the molecular weight of said dextran is 1-70 kDa.

3 . The process of claim 1 , wherein said dextran is present at a concentration within the range of 50-75% by weight.

4 . The process of claim 1 , wherein water is eliminated from the liquid composition by evaporation.

5 . The process of claim 4 wherein the evaporation is performed at temperature of from 0 to 50° C.

6 . The process of claim 5 wherein the evaporation is performed at temperature of from 20 to 37° C.

7 . The process of claim 4 , wherein the rate of evaporation is 0.1-75% by weight of the liquid composition of step (b) per hour.

8 . The process of claim 1 , wherein water is eliminated from the liquid composition by extraction.

9 . The process of claim 8 , wherein the 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 the liquid composition.

10 . The process of claim 1 , wherein the biologically active substance is dissolved or suspended in the aqueous solution of (a).

11 . The process of claim 1 , wherein the biologically active substance is introduced into said aqueous solution of (a) in an amount so as to be present at a concentration of 0.01 to 25% by weight in the liquid composition.

12 . An article for biomedical applications comprising a composition prepared by the process of claim 1 .

13 . The article of claim 12 wherein said article is in the form of a hard pharmaceutical capsule.

14 . The article of claim 12 wherein said article is in the form of a hard medical device.

15 . The article of claim 12 wherein said article is in the form of a hard medical prosthesis.

16 . The article of claim 14 , wherein said hard medical device is selected from the group consisting of a plate, a screw and a pin.

17 . A method of treatment of a disease or disorder in a mammal in need of such treatment, comprising obtaining a pharmaceutical composition according to the process of claim 1 and administering said composition to said mammal.

18 . The method of claim 17 , wherein said disease or disorder is diabetes.

19 . The method of claim 17 , wherein said composition is administered to said mammal orally.

20 . The method of claim 17 , wherein said biologically or pharmaceutically active substance is selected from the group consisting of proteins, polypeptides, peptides, organic molecules, oligonucleotides and polynucleotides

21 . The method of claim 17 , wherein said biologically or pharmaceutically active substance is insulin or a derivative thereof.

22 . The method of claim 17 , wherein said mammal is a human.

23 . The process of claim 1 , wherein said biologically or pharmaceutically active substance is selected from the group consisting of proteins, polypeptides, peptides, organic molecules, oligonucleotides and polynucleotides

24 . The process of claim 1 , wherein said biologically or pharmaceutically active substance is insulin or a derivative thereof.

25 . 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 said implant is formed in situ in the body of said mammal.

26 . The implant of claim 25 , wherein said liquid composition further comprises at least one biologically or pharmaceutically active substance dissolved or suspended therein.

27 . The implant of claim 26 , wherein said biologically or pharmaceutically active substance is present at a concentration of from 0.01 to 25% by weight of the liquid composition.

28 . The implant of claim 26 , wherein said biologically or pharmaceutically active substance is selected from the group consisting of proteins, polypeptides, peptides, organic molecules, oligonucleotides and polynucleotides.

29 . The implant of claim 25 or claim 26 , wherein said dextran is present in the liquid composition at a concentration within the range of 50-75% by weight.

30 . The implant of claim 29 , wherein said dextran is present in said liquid composition at a concentration within the range of 60-70% by weight.

31 . The implant of claim 25 or claim 26 , wherein said liquid composition is sterile.

32 . The implant of claim 25 or claim 26 , wherein said liquid composition is introduced into the body of said mammal by injection.

33 . The implant of claim 32 , wherein said injection is performed using a 25-gauge or finer needle.

34 . The implant of claim 25 or claim 26 , 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.

35 . The implant of claim 26 , wherein said biologically or pharmaceutically active substance is insulin or a derivative thereof.

36 . A method of treatment of a disease or disorder in a mammal in need of such treatment, comprising forming the implant of claim 25 in the body of said mammal.

37 . A method of treatment of a disease or disorder in a mammal in need of such treatment, comprising forming the implant of claim 26 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.

38 . The method of claim 36 or claim 37 , wherein said disease or disorder is diabetes.

39 . The method of claim 37 , wherein said biologically or pharmaceutically active substance is insulin or a derivative thereof.

40 . The method of claim 36 or claim 37 , wherein said mammal is a human.