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Sustained-release injection containing angiogenic inhibitor

A technology of vascular inhibitors and sustained-release injections, which is applied in the field of anti-cancer sustained-release injections, and can solve problems such as increased resistance to anti-cancer drugs and treatment failure

Inactive Publication Date: 2008-08-06
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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  • Sustained-release injection containing angiogenic inhibitor
  • Sustained-release injection containing angiogenic inhibitor

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0158] Put 80mg of polyphenylpropane (p-carboxyphenylpropane (p-CPP): sebacic acid (SA) at 20:80) copolymer into a container, add 100ml of dichloromethane, dissolve and mix well, then add 10mg of heptane Platinum and leuprolide, after re-shaking, microspheres for injection containing 10% heptaplatin and 10% leuprolide were prepared 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 20cp-300cp (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

[0160] 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:

[0161] (a) 5-20% cisplatin, carboplatin, omaplatin, dexomaplatin, heptaplatin, lobaplatin, nedaplatin or oxaliplatin;

[0162] (b) 5-30% triptorelin, goserelin, leuprolide, anastrozole, edoxifene, milprexifen, tamoxifen, 4-monohydroxytamoxifen , comoxifen, raloxifene, steroid estrogen, anticancer stenol, 4-hydroxytamoxifen, flutamide, aminoglutethimide, pirumide, megestrol, methyl hydroxyprogesterone, clomiphene, toremifene, letrozole, anastrozole, exemestane, or bicalutamide; or

[0163] (c) 5-20% cisplatin, carboplatin, omaplatin, dextro-omaplatin, heptaplatin, lobaplatin, nedaplatin or oxaliplatin and 5-30% triptorelin, goserelin , leuprolide, anastrozole, edoxifene, milprexifen, tamoxifen, 4-monohydroxytamoxifen, comoxifen, raloxifene, steroid antiestrogens, antic...

Embodiment 3

[0166] Put 70 mg of polylactic acid (PLGA, 75:25) with a peak molecular weight of 25,000 into a container, add 100 ml of dichloromethane, dissolve and mix well, add 15 mg of lobaplatin and 15 mg of gefitinib, re-shake and dry in vacuo Remove organic solvents. The dried drug-containing solid composition was frozen and pulverized to make micropowder containing 15% lobaplatin and 15% gefitinib, and then suspended in physiological saline containing 1.5% carboxymethylcellulose sodium to prepare the corresponding mixed Suspension-type sustained-release injection with a viscosity of 220cp-340cp (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 invention relates to a sustained release injection which comprises agiogenesis inhibitor and anticarcinogen sustained release preparation of synergistic agent thereof. The sustained release injection comprises sustained release microspheres and menstruum; wherein, the sustained release microspheres comprise anticancer active principles and sustained release auxiliary material.The menstruum is a special menstruum that contains suspending agent. The anticancer active principles are agiogenesis inhibitor and / or synergistic agent of the agiogenesis inhibitor selected from hormone anticarcinogens and / or platinum compounds; the sustained release auxiliary material is one or the compositions of poly-dl-lactide and copolymer thereof, monomethyl polyethylene glycol and polylactictide copolymer, polyethylene glycol and polylactictide copolymer, terminal carboxyl group polylactic acid and glycolic acid copolymer, di-fatty acid and decanedioic acid copolymer, poly (erucic acid dipolymer decanedioic acid), poly (fumaric acid decanedioic acid), polifeprosan and copolymer of ethylene-vinyl acetate; the viscosity of the suspending agent is 80cp-3,000cp. The sustained release microspheres, which can also be made into sustained release implant to be injected or placed in or around tumor, with the release lasting as long as about 40 days, can be used solely or in combination with chemotherapeutics and / or with non-operative treatments, such as radiotherapy, etc.

Description

(1) Technical field [0001] The invention relates to an anti-cancer slow-release injection containing angiostatin and its synergist, belonging to the technical field of medicines. Specifically, the present invention provides a slow-release injection or slow-release implant loaded with a blood vessel inhibitor and / or its synergist. (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 placement of cisplatin plus systemic carmus...

Claims

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Application Information

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IPC IPC(8): A61K9/00A61K9/08A61K45/06A61K47/34A61P35/00
Inventor 孔庆忠俞建江苏红清
Owner SHANDONG LANJIN PHARMA
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