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Compound anticancer sustained-release injection containing vascular inhibitor

A technology of sustained-release injection and vascular inhibitor, applied in the field of compound anti-cancer sustained-release injection, can solve the problems of enhanced tolerance of anti-cancer drugs, treatment failure and the like

Inactive Publication Date: 2009-01-28
JINAN KANGQUAN PHARMA TECH
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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

[0105] Put 80 mg of polylactic acid (PLGA) with a peak molecular weight of 25,000 into a container, add 100 ml of dichloromethane, dissolve and mix well, add 10 mg of imatinib and 10 mg of methotrexate, re-shake, and vacuum dry to remove organic matter. solvent. The dried solid composition is shaped immediately, subpackaged and then sterilized by radiation to obtain the anticancer slow-release product containing 10% imatinib and 10% methotrexate. All are percentages by weight. The drug release time of the anti-solid tumor pharmaceutical composition in physiological saline in vitro is 14-21 days, and the drug release time in mouse subcutaneous is 25-45 days.

Embodiment 2

[0107] As described in Example 1, the difference is that the anticancer active ingredient and weight percentage are one of the following:

[0108](1) 1-50% of gefitinib, erlotinib, lapatinib, vatalanib, peritinib, carboxyaminotriazole, thalidomide, ranolamid, angiostatin, endostatin , endostatin, imatinib mesylate, semazinil, dasatinib, Avastin, canertinib, sorafenib, sunitinib, Teosta, or penito horse;

[0109] (2) 1-50% of fluorouracil, deoxyfluorouridine, 5-deoxyfluorouridine, propylthiouracil, fluorouracil, butylfluorouracil, bisfluridine, 5-fluoropyrimidinol, sodium sulfcaptopurine , mercaptopurine, mercaptopurine, 6-mercaptopurine, 6-aminopurine hydrochloride, glycinethiopurine, thioguanine, methotrexate, flumethotrexate, dioxymethotrexate, 10- Ethyldeazhotrexate, methotrexate, folic acid, 5,10-di-deaza tetrahydrofolate, levofolinic acid calcium, folinic acid calcium, carmofur, tegafur, Youfudine, uracil substitute Fluoride, 8-azaguanine, uracil, thiouracil, topotecan...

Embodiment 3

[0112] 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 Lotinib and 10 mg fluorouracil were re-shaken and spray-dried to prepare microspheres for injection containing 10% erlotinib and 10% fluorouracil. 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.

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PUM

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Abstract

The invention discloses a compound anticancer slow-release injection which contains blood vessel inhibitor and consists of slow-release microspheres and solvent; wherein, the slow-release microspheres comprise anticancer effective ingredients and slow-release auxiliary materials; the solvent is common solvent or special solvent containing a suspending agent; the anticancer effective ingredients are synergists of the blood vessel inhibitor such as gefitinib, erlotinib, lapatinib and futalanib, etc. and the blood vessel inhibitor which is selected from antitumor antibiotics and / or antimetabolic drugs; the slow-release auxiliary materials are selected from one or combination of copolymer of bi-fatty acid and sebacic acid and copolymer of poly-(erucic acid dimmer-sebacic acid), poly-(fumaric acid-sebacic acid), polifeprosan, polyactic acid, polyglycolic acid and glycolic acid, and copolymer of ethylene-vinylacetate; the suspending agent is selected from carboxymethyl cellulose, etc. and has 80cp-3000cp (with the temperature of 20 DEG C to 30 DEG C) of viscosity; the slow-release microspheres also can be made into a slow-release implant, is injected or placed in tumor or around the tumor and is applied separately or is applied with the non-operative treatment of chemoradiotherapy, and the like, in a combining way.

Description

(1) Technical field [0001] The invention relates to a compound anticancer sustained-release injection, which belongs to the technical field of medicines. (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; 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 carmustine in the treatment of rat brain tumors" "Journal of Surgical Oncology" 69 pages 76-82 (1998) (Kong Q et al., J Surg Oncol.1998 Oct; 69(2):76-82). [0003] Local placement of antitumor d...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/00A61K9/08A61K31/517A61K31/513A61K47/34A61P35/00
Inventor 孙娟
Owner JINAN KANGQUAN PHARMA TECH
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