Composition Comprising An Epothilone And Methods For Producing A Composition Comprising An Epothilone

1 - 42 . (canceled)

43 . A method of preparing a composition comprising an epothilone, the method comprising:

(I)

(a) dissolving the epothilone in an organic solvent,

and

b) dissolving a cyclodextrin in an aqueous solution;

optionally

c) adjusting the pH of the resulting mixture of b) to a pH of 5 to 9 by an inorganic acid;

and

d) mixing the resulting solutions a) and b) or a) and c);

optionally

e) sterile filtering d);

and

f) drying the resultant solution to remove the solvent, resulting in a solid composition;

or

(II)

a) dissolving the epothilone in an organic solvent,

and

b) evaporating said organic solvent to prepare a powder;

and

c) dissolving a cyclodextrin in an aqueous solution;

optionally

d) adjusting the pH of the resulting mixture c) to a pH of 5 to 9 by an inorganic acid;

and

e) dissolving the resulting powder b) in the resulting solution c) or d);

optionally

f) sterile filtering e);

and

g) removing the solvent from the resultant solution, resulting in a solid composition.

44 . A method of producing a composition according to claim 43 , comprising

(I)

(a) dissolving the epothilone in an organic solvent,

and

b) dissolving a cyclodextrin in an aqueous solution;

optionally

c) adjusting the pH of the resulting mixture of b) to a pH of 5 to 9 by an inorganic acid;

and

d) mixing the resulting solutions a) and b) or a) and c);

optionally

e) sterile filtering d);

and

f) drying the resultant solution to remove the solvent, resulting in a solid composition.

45 . The method of producing a composition according to claim 43 , comprising

a) dissolving the epothilone in an organic solvent,

and

b) evaporating said organic solvent to prepare a powder;

and

c) dissolving a cyclodextrin in an aqueous solution;

optionally

d) adjusting the pH of the resulting mixture c) to a pH of 5 to 9 by an inorganic acid;

and

e) dissolving the resulting powder b) in the resulting solution c) or d);

optionally

f) sterile filtering e);

and

g) removing the solvent from the resultant solution, resulting in a solid composition.

46 . The method according to claim 43 , further comprising adding a pharmaceutically acceptable excipient to the composition selected from the group consisting of; sorbitol; xylitol; 2-Amino-2-hydroxymethyl-1,3-propandiol; the acid form and salts of citric acid, acetic acid, histidine, malic acid, phosphoric acid, tartaric acid, succinic acid, 2-(N-morpholino)ethanesulfonic acid, 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid, imidazole, lactic acid, glutaric acid and glycylglycine.

47 . The method according to claim 43 , wherein 2-hydroxypropyl-β-cyclodextrin is dissolved.

48 . The method according to claim 43 , wherein sulfobutyl ether-β-cyclodextrin is dissolved.

49 . The method according to claim 43 , comprising adding a pH regulator, which is 2-Amino-2-hydroxymethyl-1,3-propandiol, an acid form or salt of citric acid, acetic acid, histidine, malic acid, phosphoric acid, tartaric acid, succinic acid, 2-(N-morpholino)ethanesulfonic acid, 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid, imidazole, lactic acid, glutaric acid or glycylglycine.

50 . The method according to claim 43 , wherein the molar ratio of epothilone to cyclodextrin is about 1:70 to 1:100.

51 . The method according to claim 43 , wherein the molar ratio of epothilone to cyclodextrin is about 1:75 to 1:100.

52 . The method according to claim 43 , wherein the molar ratio of epothilone to cyclodextrin is about 1:75 to 1:80.

53 . The method according to claim 43 , wherein the molar ratio of epothilone to cyclodextrin is about 1:77.7.

54 . The method according to claim 43 , wherein the composition comprises sagopilone; 2-hydroxypropyl-β-cyclodextrin; hydrochloric acid; ethanol; and water for injection.

55 . The method according to claim 43 , wherein the organic solvent in step (a) is an alcohol.

56 . The method according to claim 43 , wherein the organic solvent in step (a) is ethanol.

57 . The method according to claim 43 , wherein the epothilone is sagopilone.

58 . The method according to claim 43 , wherein the epothilone is sagopilone, which is in amorphous form.

59 . The method according to claim 43 , wherein the composition is in the form of a lyophilisate.

60 . The method according to claim 43 , wherein the composition comprises an aqueous solution comprising 75-100% of water by volume.

61 . The method according to claim 43 , which comprises dissolving 2-hydroxypropyl-β-cyclodextrin or sulfobutyl ether-β-cyclodextrin in an aqueous solution together with mannitol and trometamol.

62 . The method according to claim 43 , wherein the cyclodextrin is 2-hydroxypropyl-β-cyclodextrin or sulfobutyl ether-β-cyclodextrin.