Pharmaceutical compositions comprising 17-allylamino-17-demethoxygeldanamycin

Abstract

A pharmaceutical formulation comprising (a) 17-allylamino-17-demethoxy-geldanamycin; (b) an ester of d-α-tocopheryl succinate and polyethylene glycol; and (c) a pharmaceutically acceptable, water-miscible organic solvent.

Description

Claims

1. A pharmaceutical formulation comprising (a) 17-allylamino-17-demethoxy-geldanamycin (“17-AAG”); (b) an ester of d-α-tocopheryl succinate and polyethylene glycol; and (c) a pharmaceutically acceptable, water-miscible organic solvent.

2. A formulation according to claim 1, wherein the ester of d-α-tocopheryl succinate and polyethylene glycol has a structure represented by formula (I)

3. A formulation according to claim 1, wherein, in the ester of d-α-tocopheryl succinate and polyethylene glycol, the polyethylene glycol is polyethylene glycol 1000.

4. A formulation according to claim 1, wherein the ester of d-α-tocopheryl succinate and polyethylene glycol is present in an amount of from about 4 to about 10 parts by weight for each part by weight of 17-AAG in the formulation.

5. A formulation according to claim 1, wherein the pharmaceutically acceptable, water-miscible organic solvent is aprotic.

6. A formulation according to claim 1, wherein the pharmaceutically acceptable, water-miscible organic solvent is N,N-dimethylacetamide, N-methyl-2-pyrrolidone, dimethylsulfoxide, or combinations thereof.

7. A formulation according to claim 1, wherein the pharmaceutically acceptable, water-miscible organic solvent is present in an amount of at least 4 parts by weight for each part by weight of 17-AAG in the formulation.

8. A formulation according to claim 1, further comprising a pharmaceutically acceptable aqueous medium.

9. A formulation according to claim 8, wherein the pharmaceutically acceptable aqueous medium is water for injection or 5% dextrose in water for injection.

10. A method for preparing a 17-allylamino-17-demethoxygeldanamycin (“17-AAG”) pharmaceutical formulation ready for administration to a subject, comprising the steps of: (i) providing a pharmaceutical formulation comprising (a) 17-AAG; (b) an ester of d-α-tocopheryl succinate and polyethylene glycol; and (c) a pharmaceutically acceptable, water-miscible organic solvent; and(ii) diluting the pharmaceutical formulation with a pharmaceutically acceptable aqueous medium to produce a diluted pharmaceutical formulation ready for administration to a subject.

11. A method for administering 17-allylamino-17-demethoxygeldanamycin (“17-AAG”) to a subject, comprising the steps of: (i) providing a pharmaceutical formulation comprising (a) 17-AAG; (b) an ester of d-α-tocopheryl succinate and polyethylene glycol; and (c) a pharmaceutically acceptable, water-miscible organic solvent;(ii) diluting the pharmaceutical formulation with a pharmaceutically acceptable aqueous medium to produce a diluted pharmaceutical formulation; and(iii) administering the diluted pharmaceutical formulation to a subject.

12. A method for preparing a 17-allylamino-17-demethoxygeldanamycin (“17-AAG”) pharmaceutical formulation ready for administration to a subject, comprising the steps of: (i) providing a mixture of 17-AAG and an ester of d-α-tocopheryl succinate and polyethylene glycol;(ii) dissolving the mixture of 17-AAG and an ester of d-α-tocopheryl succinate and polyethylene glycol in a pharmaceutically acceptable, water-miscible organic solvent to produce a pharmaceutical formulation; and(iii) diluting the pharmaceutical formulation with a pharmaceutically acceptable aqueous medium to produce a diluted pharmaceutical formulation ready for administration to a subject.

13. A method for administering 17-allylamino-17-demethoxygeldanamycin (“17-AAG”) to a subject, comprising the steps of: (i) providing a mixture of 17-AAG and an ester of d-α-tocopheryl succinate and polyethylene glycol;(ii) dissolving the mixture of 17-AAG and an ester of d-α-tocopheryl succinate and polyethylene glycol in a pharmaceutically acceptable, water-miscible organic solvent to produce a pharmaceutical formulation;(iii) diluting the pharmaceutical formulation with a pharmaceutically acceptable aqueous medium to produce a diluted pharmaceutical formulation; and(iv) administering the diluted pharmaceutical formulation to a subject.

14. A method according to claim 13, wherein the ester of d-α-tocopheryl succinate and polyethylene glycol has a structure represented by formula (I)

15. A method according to claim 14, wherein the polyethylene glycol in the ester of d-α-tocopheryl succinate and polyethylene glycol is polyethylene glycol 1000.

16. A method according to claim 15, wherein the ester of d-α-tocopheryl succinate and polyethylene glycol is present in an amount of from about 4 to about 10 parts by weight for each part by weight of 17-AAG.

17. A method according to claim 13, wherein the pharmaceutically acceptable, water-miscible organic solvent is N,N-dimethylacetamide, N-methyl-2-pyrrolidone, dimethylsulfoxide, or combinations thereof.

18. A method according to claim 17, wherein the pharmaceutically acceptable, water-miscible organic solvent is present in an amount of at least 4 parts by weight for each part by weight of 17-AAG.

19. A method according to claim 13, wherein, in the diluted pharmaceutical formulation, the 17-AAG is present at a concentration of between about 2.5 and about 10 mg/mL.

20. A method according to claim 13, wherein the pharmaceutically acceptable aqueous medium is water for injection or 5% dextrose in water for injection.

21. A kit comprising 17-allylamino-17-demethoxygeldanamycin (“17-AAG”), an ester of d-α-tocopheryl succinate and polyethylene glycol, and a pharmaceutically acceptable, water-miscible organic solvent.

22. A kit according to claim 21, wherein the 17-AAG and the ester of d-α-tocopheryl succinate and polyethylene glycol are contained in a first container and the pharmaceutically acceptable, water-miscible organic solvent is contained in a second container.

23. A kit according to claim 21, wherein the 17-AAG, the ester of d-α-tocopheryl succinate and polyethylene glycol, and the pharmaceutically acceptable, water-miscible organic solvent are contained in respective first, second and third containers.

24. A kit according to claim 21, further comprising a pharmaceutically acceptable aqueous medium.

25. A kit according to claim 21, further comprising instructions for preparing a pharmaceutical formulation comprising 17-AAG ready for administration to a subject using the 17-AAG, the ester of d-α-tocopheryl succinate and polyethylene glycol, and the pharmaceutically acceptable, water-miscible organic solvent in the kit.

26. A kit according to claim 21, wherein the amount of 17-AAG in the kit is a unit dose of 17-AAG.