Anti-cancer composition containing neoformative vascular inhibitor and Eps mycin

Abstract

An anticancer composition containing neovascular inhibitor and epothilone and able to be made into slow-release implant or injection is composed of the slow-release microballs and solvent. Said slow-release microball consists of active anticancer component (neovascular inhibitor and / or epothilone) and slow-release additives (p (LAEG-EOP), p (DAPG-EOP), etc). Said solvent is an ordinary solvent or the special solvent containing the suspending aid.

Description

(1) Technical field

[0001] The invention relates to an anticancer composition containing angiogenesis inhibitor and / or epothilone, belonging to the technical field of medicines. Specifically, the invention relates to a slow-release preparation that can stably release angiogenesis inhibitors and / or epothilone locally in solid tumors, mainly slow-release implants and slow-release injections, which can prolong the drug release time , and can increase drug sensitivity. (2) Background technology

[0002] Local application of chemotherapeutic drugs, especially local sustained release, has become the current research direction and focus of solid tumor chemotherapy. 参见(中国专利申请号200510042234.3、03148624.X、200510042236.2、96116041.1、97107078.4、200510042260.6、200510042261.0、200510042262.5、200510042263.X;美国专利US5651986、RE37410)。

[0003] However, the sustained-release excipients used in the above-mentioned and other existing pharmaceutical preparations more or less cause sudden release or u...

Examples

Embodiment 1

[0105] Put 90, 90 and 80mg p(BHET-EOP / TC), BHET-EOP: TC is 80:20) copolymer into three containers of A, B and C respectively, and then add 100 ml of dichloromethane to each , after dissolving and mixing, add 10mg erlotinib, 10mg epothilone A, 10mg erlotinib and 10mg epothilone A respectively, reshake and prepare 10% erlotinib by spray drying method , 10% epothilone A, and 10% erlotinib and 10% epothilone A microspheres for injection. Then suspend the microspheres in physiological saline containing 15% mannitol to prepare the corresponding suspension-type sustained-release injection. The release time of the slow-release injection in physiological saline in vitro is 40-50 days, and the release time in mice subcutaneously is more than 50 days.

Embodiment 2

[0107] The method step of being processed into slow-release injection is identical with embodiment 1, but difference is that used auxiliary material is the p(BHET-EOP / TC) of 50: 50, containing anticancer active ingredient and weight percent thereof are:

[0108] (1) 5-30% erlotinib or gefitinib;

[0109] (2) 5-30% Epothilone A, Epothilone B, Epothilone C, Epothilone D, Epothilone D, Isopothilone D, Epothilone E or Epothilone F; or

[0110] (3) 5-30% erlotinib or gefitinib and 5-30% epothilone A, epothilone B, epothilone C, epothilone D, epothilone Combinations of Epothilone D, Isopothilone D, Epothilone E or Epothilone F.

Embodiment 3

[0112] Put 70 mg of p(LAEG-EOP) with a peak molecular weight of 10,000-25,000 into three containers of A, B, and C, respectively, and then add 100 ml of dichloromethane to each, dissolve and mix well, and pour into the three containers respectively Add 30mg gefitinib, 30mg epothilone D, 15mg gefitinib and 15mg epothilone D, re-shake and use spray drying method to prepare 30% gefitinib, 30% epothilone D. Microspheres for injection with 15% gefitinib and 15% epothilone D. The dried microspheres are suspended in physiological saline containing 1.5% sodium carboxymethylcellulose to prepare the corresponding suspension-type sustained-release injection. The release time of the slow-release injection in physiological saline in vitro is 55-65 days, and the release time in mice subcutaneously is about 60 days.

(1) Technical field

[0001] The invention relates to an anticancer composition containing angiogenesis inhibitor and / or epothilone, belonging to the technical field of medicines. Specifically, the invention relates to a slow-release preparation that can stably release angiogenesis inhibitors and / or epothilone locally in solid tumors, mainly slow-release implants and slow-release injections, which can prolong the drug release time , and can increase drug sensitivity. (2) Background technology

[0002] Local application of chemotherapeutic drugs, especially local sustained release, has become the current research direction and focus of solid tumor chemotherapy. 参见(中国专利申请号200510042234.3、03148624.X、200510042236.2、96116041.1、97107078.4、200510042260.6、200510042261.0、200510042262.5、200510042263.X;美国专利US5651986、RE37410)。

[0003] However, the sustained-release excipients used in the above-mentioned and other existing pharmaceutical preparations more or less cause sudden release or u...

Examples

Embodiment 1

[0105] Put 90, 90 and 80mg p(BHET-EOP / TC), BHET-EOP: TC is 80:20) copolymer into three containers of A, B and C respectively, and then add 100 ml of dichloromethane to each , after dissolving and mixing, add 10mg erlotinib, 10mg epothilone A, 10mg erlotinib and 10mg epothilone A respectively, reshake and prepare 10% erlotinib by spray drying method , 10% epothilone A, and 10% erlotinib and 10% epothilone A microspheres for injection. Then suspend the microspheres in physiological saline containing 15% mannitol to prepare the corresponding suspension-type sustained-release injection. The release time of the slow-release injection in physiological saline in vitro is 40-50 days, and the release time in mice subcutaneously is more than 50 days.

Embodiment 2

[0107] The method step of being processed into slow-release injection is identical with embodiment 1, but difference is that used auxiliary material is the p(BHET-EOP / TC) of 50: 50, containing anticancer active ingredient and weight percent thereof are:

[0108] (1) 5-30% erlotinib or gefitinib;

[0109] (2) 5-30% Epothilone A, Epothilone B, Epothilone C, Epothilone D, Epothilone D, Isopothilone D, Epothilone E or Epothilone F; or

[0110] (3) 5-30% erlotinib or gefitinib and 5-30% epothilone A, epothilone B, epothilone C, epothilone D, epothilone Combinations of Epothilone D, Isopothilone D, Epothilone E or Epothilone F.

Embodiment 3

[0112] Put 70 mg of p(LAEG-EOP) with a peak molecular weight of 10,000-25,000 into three containers of A, B, and C, respectively, and then add 100 ml of dichloromethane to each, dissolve and mix well, and pour into the three containers respectively Add 30mg gefitinib, 30mg epothilone D, 15mg gefitinib and 15mg epothilone D, re-shake and use spray drying method to prepare 30% gefitinib, 30% epothilone D. Microspheres for injection with 15% gefitinib and 15% epothilone D. The dried microspheres are suspended in physiological saline containing 1.5% sodium carboxymethylcellulose to prepare the corresponding suspension-type sustained-release injection. The release time of the slow-release injection in physiological saline in vitro is 55-65 days, and the release time in mice subcutaneously is about 60 days.