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A compound sustained release anticancer agent containing angiogenesis inhibitor

A technology of new blood vessels and inhibitors, which is applied in the field of sustained-release injections and implants, compound sustained-release preparations and their preparation, and can solve problems such as systemic toxicity and drug resistance limiting application

Inactive Publication Date: 2006-12-13
JINAN KANGQUAN PHARMA TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, its obvious systemic toxicity and development of drug resistance greatly limit the application of this drug

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0105] 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 Hydroxycamptothecin and 10 mg marimastat were re-shaken and spray-dried to prepare injection microspheres containing 10% hydroxycamptothecin and 10% marimastat. 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

[0107] 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:

[0108] (1) 2-40% hydroxycamptothecin, mitozolomide, 4-carboxytemozolomide, docetaxel, oxaliplatin, heptaplatin, ifosfamide, lomustine, estramustine , formustine, samustine, etoposide, teniposide, vinblastine, anastrozole, fluorouracil, or mitomycin C; or

[0109] (2) 2-40% marimastat, SU5416, SU6668, fumagillin or TNP-470; or

[0110] (3) 2-40% hydroxycamptothecin, mitozolomide, 4-carboxytemozolomide, docetaxel, oxaliplatin, heptaplatin, ifosfamide, lomustine, estramustine , formustine, samustine, etoposide, teniposide, vinblastine, anastrozole, fluorouracil or mitomycin C with 2-40% marimastat, SU5416, SU6668, A combination of fumagillin or TNP-470.

Embodiment 3

[0112] 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 fumagillin and 15 mg of lomustine, and re-shake Dry in vacuo to remove the organic solvent. Freezing and pulverizing the dried drug-containing solid composition to make micropowder containing 15% fumagillin and 15% lomustine, and then suspending in physiological saline containing 1.5% sodium carboxymethylcellulose to obtain the corresponding 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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PUM

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Abstract

Disclosed is an anticancer slow release injection containing anti-angiogenesis, which comprises slow release micro-balloons and dissolvent, wherein the slow release micro-balloons comprises slow release auxiliary materials and anti-angiogenesis selected from Marimastat or fungillin, and cytotoxic drugs selected from hydroxycamptothecine, Mitozolomide, 4-carboxyl temozolomide, docetaxel, Oxaliplatin, Eptaplatin, Ifosfamide, Lomustine, Estramustine, Fotemustine, Semustine, Etoposide, Teniposide, Vinblastine, Anastrozole, fluorouracil or Mitomycin C, the dissolvent being specific dissolvent containing suspension adjuvant. The slow release auxiliary materials are selected from Polifeprosan, poly(lactic acid), poly(erucic aciddipolymer-sebacylic acid) and poly(fumaric acid-sebacylic acid), and EVAc. The viscosity of the suspension adjuvant is 100-3000cp (at 25-30 deg C), and is selected from sodium carboxymethylcellulose.

Description

(1) Technical field [0001] The invention relates to a compound slow-release agent containing angiogenesis inhibitor and a preparation method thereof, belonging to the technical field of medicines. Specifically, the present invention provides a slow-release preparation of anticancer drugs containing angiogenesis inhibitors and / or cytotoxic drugs, mainly slow-release injections and slow-release implants. (2) Background technology [0002] Angiogenesis is necessary for the growth and metastasis of solid tumors. When the diameter of solid tumor is larger than 0.5cm, tumor cells depend on their own vascular system. Tumor cells can obtain nutrients and oxygen from the host through tumor blood vessels, and can continuously transport metastatic cells to the host through tumor blood vessels, and continue to grow and induce blood vessel formation in other parts of the body, leading to tumor metastasis. The emergence of new metastases is the main reason for treatment failure. Theref...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/10A61K45/00A61K47/32A61K47/34A61K47/36A61K47/38A61K47/42A61K31/336A61P35/00A61K47/10A61K47/26
Inventor 田绍兰
Owner JINAN KANGQUAN PHARMA TECH
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