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Slow released compound anticancer prepn

A technology for sustained-release injections and sustained-release implants, which can be used in anti-tumor drugs, pharmaceutical formulations, liquid delivery, etc., and can solve the problems of poor curative effect, difficult operation, and many complications.

Inactive Publication Date: 2007-01-03
JINAN SHUAIHUA PHARMA TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, solid sustained-release implants (Chinese Patent No. ZL96115937.5; ZL97107076.8) and existing sustained-release microspheres for the treatment of brain tumors (ZL00809160.9) or U.S. Patent (US5,651,986) all have inadequacies. Easy operation, poor curative effect, many complications, etc.

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0119] Put 80mg of polyphenylpropane (p-CPP: 20:80 of sebacic acid (SA)) copolymer into a container, add 100ml of dichloromethane, dissolve and mix well, then add 10mg Paclitaxel and 10 mg of bendamustine were re-shaken to prepare microspheres for injection containing 10% of paclitaxel and 10% of bendamustine by spray-drying method. Then suspend the microspheres in physiological saline containing 15% mannitol to prepare the corresponding suspension-type sustained-release injection with a viscosity of 220cp-460cp (at 20°C-30°C). The drug release time of the slow-release injection in physiological saline in vitro is 10-15 days, and the drug release time in mice subcutaneous is about 20-30 days.

Embodiment 2

[0121] The method step of being processed into sustained-release injection is the same as in Example 1, but the difference is that the contained anticancer active ingredients and their weight percentages are:

[0122] (1) 2-40% of bendamustine or formustine and 2-40% of camptothecin, procarbazine, paclitaxel, tumor canning, cyclophosphamide, O6-butylguanine, O6-Methylguanine, O6-Alkylguanine, O6-Benzylxanthine, Irinotecan, Vincristine, Leuprolide, Colchicine, Aminotriazole, Butylthionine Thioxime, A combination of O6-benzylguanine and O4-benzylfolate;

[0123] (2) 2-40% tamustine or estramustine and 2-40% camptothecin, procarbazine, paclitaxel, tumor canning, cyclophosphamide, O6-butylguanine, O6 -Methylguanine, O6-Alkylguanine, O6-Benzylxanthine, Irinotecan, Vincristine, Leuprolide, Colchicine, Aminotriazole, Butylthionine Thioxime, O6 - a combination of benzylguanine, O4-benzylfolate;

[0124] (3) 2-40% carmustine or nimustine and 2-40% camptothecin, procarbazine, paclita...

Embodiment 3

[0128] Put 70 mg of polylactic acid (PLGA, 75:25) with a peak molecular weight of 65,000 into a container, add 100 ml of dichloromethane, dissolve and mix well, add 15 mg of carmustine and 15 mg of cyctonin, re-shake and vacuum Dry to remove organic solvent. Freezing and pulverizing the dried drug-containing solid composition to make a micropowder containing 15% carmustine and 15% cycopenia, and then suspending in physiological saline containing 1.5% carboxymethylcellulose sodium to prepare the corresponding Suspension-type sustained-release injection with a viscosity of 300cp-400cp (at 20°C-30°C). The drug release time of the slow-release injection in physiological saline in vitro is 10-15 days, and the drug release time in mice subcutaneous is about 20-30 days.

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Abstract

The slow released compound anticancer injection consists of slow released microsphere and solvent. The slow released microsphere includes effective anticancer component and slow releasing supplementary material, and the solvent is special solvent containing suspending agent. The effective anticancer component is bendamustine and cell toxicant medicine, and the cell toxicant medicine is selected from taxane, alkaylating agent, topomerase inhibitor, etc. The slow releasing supplementary material is polylactic acid and its copolymer, polyethylene glycol-polylactic acid copolymer, EVAc, etc. The .suspending agent is carboxymethyl cellulose sodium, etc. and has viscosity of 100-3000 cp at 20-30 deg.c. The slow released microsphere may be also prepared into slow released implanting agent. The present invention has lowered systemic reaction and raised local concentration for 30-50 days, and may be used alone effectively and in enhancing the curative effect of chemotherapy, radiotherapy and other non-operative treatment.

Description

(1) Technical field [0001] The invention relates to a compound anticancer slow-release agent and a preparation method thereof, belonging to the technical field of medicines. Specifically, the present invention provides a slow-release anticancer drug containing bendamustine and cytotoxic drugs, mainly slow-release injections and slow-release implants. (2) Background technology [0002] As one of the conventional treatment methods for cancer, chemotherapy drugs have been widely used in the treatment of various malignant tumors, and the effect is relatively obvious. However, its obvious systemic toxicity greatly limits the application of this drug. [0003] Due to the excessive expansion and hyperplasia of solid tumors, the interstitial pressure, tissue elastic pressure, fluid pressure and interstitial viscosity are all higher than those of the surrounding normal tissues. Therefore, it is difficult for conventional chemotherapy to form an effective drug concentration in the tu...

Claims

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Application Information

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IPC IPC(8): A61K9/10A61K45/00A61K31/4184A61K31/664A61K47/34A61K47/38A61P35/00A61K47/26
Inventor 孔庆霞
Owner JINAN SHUAIHUA PHARMA TECH
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