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Anticancer slow release agent loading both newborn blood vessel and tetrazole violet

A new blood vessel and violet technology, applied in the preparation of sustained-release preparations, sustained-release injections and sustained-release implants, can solve problems such as systemic toxicity and drug resistance limiting applications

Inactive Publication Date: 2007-03-14
SHANDONG LANJIN PHARMA
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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

[0106] 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 Violet tetrazolium and 10 mg marimastat were re-shaken and spray-dried to prepare microspheres for injection containing 10% violet tetrazolium 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

[0108] 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:

[0109] (a) 2-40% of marimastat, SU5416, SU6668, fumagillin or TNP-470 and 2-40% of tetrazole violet, p-iodonitrotetrazole violet or nitrotetrazole violet combination;

[0110] (b) 2-40% of gefitinib, erlotinib, lapatinib, vatalanib, peritinib, carboxyaminotriazole, thalidomide, ranolamid, angiostatin, endostatin , endostatin, imatinib mesylate, semazinil, dasatinib, Avastin, canertinib, sorafenib, sunitinib, Teosta, or penito Combinations of horses with 2-40% of violet tetrazolium, p-iodonitro violet tetrazolium or nitro violet tetrazolium.

Embodiment 3

[0112] Put 70mg of polylactic acid (PLGA, 75:25) with a peak molecular weight of 65,000 into a container, add 100ml of dichloromethane, dissolve and mix well, then add 15mg of fumagillin and 15mg of p-iodonitrotetrazolium violet, Shake again and 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% p-iodonitrotetrazolium violet, and then suspending in physiological saline containing 1.5% sodium carboxymethylcellulose , to prepare 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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Abstract

Disclosed is an anticancer slow release injection carrying both anti-angiogenesis agent and tetrazole Ionone, which comprises slow release micro-balloons and dissolvent, the slow release micro-balloons include anticancer active constituents, slow release auxiliary materials and specific dissolvent containing suspension agent. The anti-angiogenesis agent is selected from Marimastat, Fumagillin, gefinitib, erlotinib, lapatinib, pelinib, Thalidomide, Ranolazine, endostatin, imatinib, Avastin, sorafenib, sunitinib, the slow release auxiliary materials are selected from Polifeprosan, sebacylic acid copolymer, EVAc, polylactic acid and their mixture of copolymer, the viscosity of the suspension adjuvant is 100-3000cp (at 25-30 deg C), and is selected from sodium carboxymethylcellulose. The agent can also be prepared into implanting agent for injection or placement in or around tumor with the effects of selectively increasing local concentration, lowering general reaction of the drugs, suppressing growth of tumor cells and blood vessel, and improving the treatment effect of the non-operative treatment methods such as chemotherapy.

Description

(1) Technical field [0001] The invention relates to a preparation method of a sustained-release agent loaded with angiogenesis inhibitor and violet tetrazolium, and belongs to the technical field of medicines. Specifically, the present invention provides a slow-release preparation of anticancer drugs containing neovascularization inhibitors and / or violet tetrazolium, 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 trea...

Claims

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Application Information

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IPC IPC(8): A61K9/10A61K31/41A61K45/06A61K47/34A61P35/00A61K47/32
Inventor 孔庆忠孙娟俞建江
Owner SHANDONG LANJIN PHARMA
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