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Anticancer composition containing platinum compound and bortezomib

A technology of bortezomib and its composition, which is applied in the field of anticancer composition, and can solve the problems of toxic reaction, inability to effectively kill tumor cells, burst release, etc.

Inactive Publication Date: 2009-01-07
济南基福医药科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the sustained-release excipients used in the existing above-mentioned and other pharmaceutical preparations more or less cause sudden release or uneven release of the drug when the drug is released.
Some drugs are released too slowly, which is not enough to obtain effective drug concentration in the local area, so they cannot effectively kill tumor cells; some release drugs too fast, often causing burst release, which is likely to cause systemic toxic reactions like conventional injections

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0108] Put 90, 90 and 80 mg of PLGA (50:50) copolymers into three containers of A, B and C respectively, then add 100 ml of dichloromethane to each, dissolve and mix well, then add 10 mg of cisplatin, 10 mg of Bortezomib, 10mg cisplatin and 10mg bortezomib were re-shaken to prepare microspheres for injection containing 10% cisplatin, 10% bortezomib, and 10% cisplatin and 10% bortezomib by spray drying . 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 44-55 days, and the release time in mice subcutaneously is more than 55 days.

Embodiment 2

[0110] The method step of being processed into slow-release injection is identical with embodiment 1, but difference is that used adjuvant is the PLGA of 75: 25, containing anticancer active ingredient and weight percent thereof are:

[0111] (1) A combination of 20% cisplatin, oxaliplatin, carboplatin or nedaplatin and 10% bortezomib;

[0112] (2) Combination of 15% cisplatin or carboplatin and 5% bortezomib;

[0113] (3) A combination of 10% cisplatin, nedaplatin, oxaliplatin or carboplatin and 2.5% bortezomib.

Embodiment 3

[0115] 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 carboplatin, 30mg bortezomib, 15mg carboplatin and 15mg bortezomib, re-shake and use spray drying method to prepare 30% carboplatin, 30% bortezomib, 15% carboplatin and 15% bortezomib microspheres for injection. The dried microspheres are suspended in physiological saline containing 1.5% sodium carboxymethylcellulose to prepare the corresponding suspension-type sustained-release injection. The drug release time of the sustained release injection in physiological saline in vitro is 50-65 days, and the drug release time in mice subcutaneous is about 60 days.

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PUM

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Abstract

An anticancer composition comprising a platinum compound and bortezomib is in form of a sustained-released injection and comprises sustained-released microspheres and a solvent. The sustained-released microspheres comprise an anticancer effective ingredient and a sustained-released adjuvant, and the solvent is a common solvent or a special solvent containing a suspending agent. The suspending agent has a viscosity of 100-3,000cp (20-30 DEG C) and is selected from sodium carboxymethyl cellulose, etc.; the platinum compound is selected from cisplatin, carboplatin and oxaliplatin; and the sustained-released adjuvant is a copolymer or a blend selected from poly(phosphate ester)s such as p(LAEG-EOP) and p(DAPG-EOP), PLA, PLGA, polyphosphate ester-polylactic acid, polifeprosan, poly(erucic acid dimmer-sebacic acid) and poly(fumaric acid-sebacic acid). The anticancer composition can also be made into a sustained-released implant, which can sustain effective drug concentration for more than 40 days by intratumoral or peritumoral injection or placement, and can distinctly reduce the systemic reaction of the drug and selectively enhance the curative effect of non-operative treatments such as chemotherapy and radiotherapy.

Description

(1) Technical field [0001] The invention relates to an anticancer composition containing platinum compounds and bortezomib, which belongs to the technical field of medicines. Specifically, the invention relates to a sustained-release preparation capable of stably releasing platinum compounds and bortezomib locally in solid tumors, mainly sustained-release implants and sustained-release injections, which can prolong the drug release time and increase Drug sensitivity. (2) Background technology [0002] Despite extensive research, the pathogenesis of cancer is not well understood. In less than 20 years, the incidence of cancer in my country has increased by 69%, and the death rate has increased by 29.4%. In 2006, 3 million people died of cancer in my country. The incidence of cancer is increasing year by year and tends to be younger. According to the latest statistics from the World Health Organization, the global incidence of cancer will increase by 50% by 2020, and the nu...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/00A61K31/69A61K45/00A61K47/30A61P35/00A61K38/05
Inventor 张伟孔庆新孔庆伦
Owner 济南基福医药科技有限公司
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