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Anti-cancer medicine sustained-released injection loaded with platinum compound and synergist thereof

A technology for sustained-release injections and anticancer drugs, which is applied in the fields of compound anticancer drug sustained-release agents, compound anticancer drug sustained-release injections, sustained-release injections and sustained-release implants, and can solve the problems of treatment failure and anticancer drug resistance. Receptivity enhancement and other issues

Inactive Publication Date: 2009-03-11
SHANDONG LANJIN PHARMA +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

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

[0149] Put 80mg polyphenylene propane (p-CPP: sebacic acid (SA) 20:80) copolymer into a container, add 100ml methylene chloride, dissolve and mix well, then add 10mg Epplatin and 7-hydroxyl-staurosporine, re-shake and spray-dry to prepare microspheres for injection containing 10% eplatin and 10% 7-hydroxyl-staurosporine. Then suspend the microspheres in physiological saline containing 15% mannitol to prepare the corresponding suspension-type sustained-release injection. 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

[0151] 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:

[0152] (1) 1-40% of cisplatin, bicycloplatin, eberplatin, meciplatin, cisplatin or picoplatin;

[0153] (2) 1-40% of sulfoplatin, bicycloplatin, eplatin, meciplatin, cisplatin or picoplatin and 1-40% of 7-hydroxyl-staurosporine, 7-O-alkyl - combinations of staurosporine, beta-methoxystaurosporine, alkylphosphocholine or hexadecylphosphocholine;

[0154] (3) 1-40% of sulfoplatin, bicycloplatin, eplatin, meciplatin, siciplatin or picoplatin and 1-40% of O4-benzyl folic acid, 2,4,5-triamino-6- Benzyloxypyrimidine, 2,4-diamino-6-benzyloxy-5-nitrosopyrimidine, 2,4-diamino-6-benzyloxy-5-bromopyrimidine, 2-amino-4- Benzyloxy-5-nitropyrimidine, 2-amino-4-benzyloxy-6-methyl-5-nitropyrimidine, 2,4-diamino-6-benzyloxy-s-triazine or - Combinations of 2-amino-O4-benzylpteridine; ...

Embodiment 3

[0158] 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, then add 15 mg of Siciplatin and 15 mg of 7-ethyl-10-hydroxycamptotheca Alkali, shake again and dry in vacuo to remove organic solvents. The dried drug-containing solid composition is frozen and pulverized to make micropowder containing 15% cisciplatin and 15% 7-ethyl-10-hydroxycamptothecin, and then suspended in a physiological solution containing 1.5% sodium carboxymethylcellulose. In saline, the corresponding suspension-type sustained-release injection was prepared. The drug release time of the slow-release injection in physiological saline in vitro is 20-35 days, and the drug release time in mice subcutaneous is about 35-50 days.

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PUM

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Abstract

A anticarcinogenic slow release injection carrying platinum compounds and a synergist thereof is composed of slow release microspheres and a dissolvant, wherein, the slow release microspheres comprise anticancer active components and a slow release adjuvant, and the dissolvant is a special dissolvant containing a suspending agent. The anticancer active component comprises platinum compounds such as sunpla, dicycloplatin, eptaplatin, (cis-amminedichloro(2-methylpyridine) platinum, camphoramine chloroacetic platinum or picoplatin, and the like, and a cytotoxic drug selected from a phosphoinositide 3-kinase inhibitor, pyrimidine analogue and / or a DNA repair enzyme inhibitor; the slow release adjuvant is biocompatible macromolecules such as polylactic acid and copolymer thereof, polyethylene glycol, carboxyl end polylactic acid copolymer, copolymer of dienoic fatty acid and sebacic acid, poly (erucic acid dimer-sebacic acid), poly (fumaric acid-sebacic acid), polifeprosan, polylactic acid, EVAc, and the like, and the suspending agent has the viscosity of 100cp-3,000cp (at the temperature of 20-30 DEG C) and is selected from sodium carboxymethyl cellulose, and the like. The slow release microspheres can also be made into a slow release implant. The slow release injection is injected or placed in tumors or around the tumors, which can improve the curative effects of non-operative therapies such as radiotherapy, chemotherapy, and the like.

Description

(1) Technical field [0001] The invention relates to a sustained-release injection of a compound anticancer drug, belonging to the technical field of medicines. Specifically, the present invention provides a sustained-release compound anticancer drug containing platinum compounds and their synergists, mainly sustained-release injections and sustained-release implants. (2) Background technology [0002] Currently, 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; radiotherapy and traditional chemotherapy are not selective, and it is difficult to form an effective drug concentration or therapeutic dose in the local tumor, resulting in poor efficacy and high toxicity. Simply increasing the dose of drugs or radiation is limited by systemic toxicity. See Kong Qingzhong et al. "Intratumoral place...

Claims

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Application Information

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IPC IPC(8): A61K9/08A61K9/00A61K31/555A61K31/553A61P35/00
Inventor 孔庆忠张红军俞建江
Owner SHANDONG LANJIN PHARMA
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