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Anti cancer controlled release formulation of containing interstitial hydrolytic agent

A technology of sustained-release injection and hydrolyzing agent, applied in the field of anti-cancer sustained-release agent, can solve the problems of enhanced tolerance of anti-cancer drugs, limited effective diffusion of drugs, obstacles to tumor chemotherapy, etc., to facilitate drug injection, improve interstitial fluid Conductivity, reducing the effect of complications

Inactive Publication Date: 2007-05-09
SHANDONG LANJIN PHARMA +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The above factors greatly limit the effective diffusion of drugs into solid tumors and tumors, thus constituting the main obstacle to tumor chemotherapy.
[0007] Not only that, the blood vessels in the tumor stroma are not sensitive to conventional chemotherapy drugs, which often leads to the enhancement of tumor cell resistance to anticancer drugs, and the result is treatment failure

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0131] 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 trypsin were re-shaken to prepare microspheres for injection containing 10% of paclitaxel and 10% of trypsin 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

[0133] 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:

[0134] (a) 5% pepsin, collagenase, streptokinase, glycosidase, hyaluronidase in combination with 25% paclitaxel or docetaxel;

[0135] (b) 20% collagenase, streptokinase, glycosidase or hyaluronidase and 10% carmustine, nimustine, bendamustine, garmustine, ramustine, fomo a combination of lomustine, homomustine, lomustine, methyllomustine, uramustine, samustine, semustine, streptozocin, or midazolamide; or

[0136] (c) 20% collagenase, streptokinase or hyaluronidase in combination with 20% vincristine, vinblastine, vinorelbine or vindesine.

[0137] The excipients used are: racemic polylactic acid, racemic polylactic acid / glycolic acid copolymer, monomethyl polyethylene glycol / polylactic acid, monomethyl polyethylene glycol / polylactic acid copolymer, polyethylene glyco...

Embodiment 3

[0139] 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 collagenase and 15 mg of nimustine, re-shake and dry in vacuum Remove organic solvents. Freezing and pulverizing the dried drug-containing solid composition to make micropowder containing 15% collagenase and 15% nimustine, and then suspending in physiological saline containing 1.5% carboxymethylcellulose sodium to prepare the corresponding mixed 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

A slow-release anticancer medicine in the form of injection or implant is disclosed. Said slow-release injection is composed of a special solvent containing suspending aid and the slow-release microballs consisting anticance medicine, iterstitial hydrolyte and slow-releasing auxiliary. Said anticancer medicine is chosen from taxane, alkalating angent and vegetative alkaloide. Said interstitial hydrolyte is chosen from collagenase, relaxin, etc. Said slow-releasing auxiliary is chosen from polylactic acid copolymer, EVAc, polyethanediol, etc.

Description

(1) Technical field [0001] The invention relates to an anticancer slow-release agent containing interstitial hydrolyzing agent, which belongs to the technical field of medicines. Specifically, the invention provides a sustained-release injection and a sustained-release implant containing an interstitial hydrolyzing agent. The anti-cancer slow-release agent can effectively inhibit or destroy the solid tumor stroma and tumor blood vessels, and can inhibit tumor angiogenesis, effectively reduce the tension in the tumor, interstitial pressure, and interstitial viscosity, thereby improving its interstitial fluid conduction. The rate is conducive to the effective diffusion of drugs into solid tumors and tumors. (2) Background technology [0002] Cancer treatment mainly includes surgery, radiotherapy and chemotherapy. Among them, surgical treatment cannot remove scattered tumor cells, so it often recurs or causes tumor cells to spread and metastasize due to surgical stimulation; ...

Claims

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Application Information

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IPC IPC(8): A61K9/00A61K45/06A61K38/46A61K47/34A61P35/00
Inventor 孔庆忠苏红清
Owner SHANDONG LANJIN PHARMA
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