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Compound anticancer sustained releasing agent containing mesenchyme hydrolytic reagent

A technology of hydrolysis agent and slow-release agent, which is applied in the field of anti-cancer slow-release agents, can solve the problems of increased resistance of anti-cancer drugs, limitation of effective drug diffusion, obstacles to tumor chemotherapy, etc., to facilitate drug injection and improve interstitial fluid conductivity and reduce complications

Inactive Publication Date: 2007-05-16
JINAN KANGQUAN PHARMA TECH
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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

[0135] Put 80 mg of polylactic acid (PLGA, 50:50) with a molecular weight peak of 25000 into a container, add 100 ml of dichloromethane, dissolve and mix, add 10 mg of hyaluronidase and 10 mg of gemcitabine, shake again, and remove by vacuum drying Organic solvents. The dried solid composition is immediately shaped, and then sterilized by radiation after being subpackaged to obtain an anticancer sustained release containing 10% hyaluronidase and 10% gemcitabine. All are weight percentages. 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 mice subcutaneously is 25-45 days.

Embodiment 2

[0137] As described in Example 1, the difference is that the excipients are polylactic acid (PLGA, 75:25) with a molecular weight peak of 45,000, and the anticancer active ingredients and weight percentages are: 5% elastase, trypsin, pepsin, chain Mycoproteinase, dispase, bromelain, chymotrypsin, clostripain, plasmin, cathepsin-G, plasminogen activator, collagenase, streptokinase, glycosidase, hyaluronidase, lysozyme, relaxation Peptide, Interferon, Fibrin, Gefitinib, Erlotinib, Lapatinib, Votalanib, Peritinib, Carboxyaminotriazole, Thalysin, Ranolamide, Angiostatin, Endostatin , endostatin, imatinib mesylate, simatinib, dasatinib, Avastin, canatinib, sorafenib or sunitinib with 30% bleomycin, dasatinib Norubicin, Nogamycin, Puromycin, Arubicin, Idarubicin, Clarithromycin, Adazolar, Doxorubicin, Epirubicin, Valrubicin, Pirarubicin Star, losanthraquinone, losoxantrone, mitoxantrone, piranthrone, tiloxantrone, or a combination of lorzocin.

Embodiment 3

[0139] Put 70 mg of polystyrene (p-carboxyphenyl propane (p-CPP): sebacic acid (SA) as 20: 80) copolymer into a container, add 100 ml of dichloromethane, dissolve and mix well, add 10 mg of collagen Enzyme and 20 mg of doxorubicin, re-shake and spray-dry to prepare microspheres for injection containing 10% collagenase and 20% doxorubicin. Then, the microspheres were suspended 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 release time of the sustained-release injection in physiological saline in vitro is 10-15 days, and the release time of the sustained-release injection under the skin of mice is about 20-30 days.

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PUM

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Abstract

Disclosed is a compound anticancer slow release injection of mesenchyme hydrolytic reagent which comprises slow release microspheres and dissolvent, wherein the slow release microballoons comprise anti-cancer active constituents and slow release auxiliary materials, the dissolvent being specific dissolvent containing suspension adjuvant. The anticancer active ingredient is the combination of mesenchyme hydrolytic reagent selected from collagenase, hyaluronidase, lysozyme, relaxin, plaxmin, gefinitib and erlotinib with anti-cancer drugs selected from anti-cancer antibiotic drugs and/or antimetabolites. The slow release auxiliary materials are selected from polylactic acid and its copolymer, di-aliphatic acid and sebacylic acid copolymer, poly(erucic aciddipolymer-sebacylic acid), poly(fumaric acid-sebacylic acid), Polifeprosan, EVAc or their combination, the viscosity of the suspension adjuvant is 80-3000cp. The slow release microspheres can also be prepared into slow release implanting agent, for injection or placement in or around tumor with a release period of about 40 days. The slow release injection and slow release implanting agent can be used independently for effectively suppressing tumor accretion, or used in combination with non-operative methods such as chemotherapy and/or radiotheraphy with the function of improving their treatment effects.

Description

(1) Technical field [0001] The invention relates to an anticancer sustained-release agent containing an interstitial hydrolyzing agent, belonging to the technical field of medicines. Specifically, the present invention provides a sustained-release injection and a sustained-release implant containing an interstitial hydrolyzing agent. The anti-cancer sustained-release agent can effectively inhibit or destroy the solid tumor stroma and tumor blood vessels, and can inhibit tumor neovascularization, effectively reduce the tension, interstitial pressure and interstitial viscosity in the tumor, thereby improving the interstitial fluid conduction. The rate of drug entry into solid tumors and the effective diffusion within the tumor are favorable. (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 metast...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/00A61K45/06A61K38/46A61K47/34A61P35/00
Inventor 孙娟张红军俞建江邹会风
Owner JINAN KANGQUAN PHARMA TECH
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