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Anti-cancer sustained release agent loaded with glucocorticoid and chemical curing medicine

A technology of glucocorticoids and corticosteroids, applied in drug delivery, drug combination, antineoplastic drugs, etc., can solve problems such as increased resistance to anticancer drugs, limitation of effective drug diffusion, and obstacles to tumor chemotherapy, so as to improve interstitial Liquid conductivity, inhibiting the formation of new blood vessels, facilitating penetration and diffusion

Inactive Publication Date: 2009-06-10
JINAN KANGQUAN PHARMA TECH +1
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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 interstitium are not sensitive to conventional chemotherapy drugs, which often lead to the enhancement of tumor cell resistance to anticancer drugs, local chemotherapy is often complicated by local edema, and the result is treatment failure

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0147] Put 80 parts of polyphenylpropane (p-CPP: sebacic acid (SA) at 20:80) copolymer into a container, add 100 ml of dichloromethane, dissolve and mix well, then add 10 parts of dexamethasone and 10 parts of 7-hydroxyl-staurosporine, shake up again and prepare the injection containing 10% dexamethasone and 10% 7-hydroxyl-staurosporine with spray drying method Microspheres. Then suspend the microspheres in physiological saline containing 15% mannitol to prepare the corresponding suspension-type sustained-release injection. The drug release time of the slow-release injection in the physiological saline in vitro is 30-55 days, and the drug release time in the mouse subcutaneous is about 30 days.

Embodiment 2

[0149] The method steps for processing into sustained-release injections are the same as in Example 1, but the difference is that polyphenylene is 50:50; the anti-cancer active ingredients and their weight percentages are: 0.1-10% prednisolone, Methylprednisolone, dexamethasone, betamethasone, triamcinolone, or triamcinolone acetonide with 1-40% of 7-hydroxy-staurosporine, 7-O-alkyl-staurosporine , β-methoxystaurosporine, alkylphosphocholine or a combination of hexadecylphosphocholine.

Embodiment 3

[0151] 80 mg of polylactic acid (PLA) with a peak molecular weight of 20,000-40,000 is put into a container, 100 ml of methylene chloride is added, after dissolving and mixing, 5 mg of prednisolone and 15 mg of 7-ethyl-10-hydroxycamptothecin are added, Shake again and dry in vacuo to remove the organic solvent. The dried drug-containing solid composition is frozen and pulverized to make micropowder containing 5% prednisolone and 15% 7-ethyl-10-hydroxycamptothecin, and then suspended in 1.5% sodium carboxymethylcellulose In physiological saline, the corresponding suspension-type sustained-release injection was prepared. The drug release time of the slow-release injection in physiological saline in vitro is 20-35 days, and the drug release time in mice subcutaneous is about 35-50 days.

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PUM

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Abstract

A anti-cancer slow-release agent co-loaded with glucocorticosteroid and chemotherapy medicament is a slow-release injection agent composed of slow-release microsphere and solvent, wherein, the slow-release microsphere comprises anti-cancer effective ingredient and slow-release auxiliary materials, the solvent is the special solvent containing suspending agent. The glucocorticosteroid is selected from prednisolone, methylprednisolone, dexamethasone, betamethasone, omcilon or triamcinoloneAcetonide, the chemotherapy medicament is selected from phosphoinositide 3-kinase restrainer and pyrimidine analogue or the like; the slow-release auxiliary materials are polylactic acid and copolymer thereof, polyethyleneglycol, polylactide-COOH copolymer, 2-aliphatic acid, sebacic acid polyester, poly(erucic acid dimmer-sebacic acid), poly(fumaric acid-sebacic acid), polyphenyl and polylactic acid or the like biocompatibility high molecules; the suspending agent viscosity is 100cp-3000cp (20 DEG C-30DEG C) and the suspending agent is selected from sodium carboxymethyl cellulose. The anti-cancer effective compositin and the slow-release microsphere can be made into a slow-release implantation agent, by intra-tumor injection or tumor circumference injection or arrangement, the tumor growth can be effectively inhibited, the edema can be alleviated, and the curative effects of the chemotherapy and the radiation therapy can be reinforced.

Description

(1) Technical field [0001] The invention relates to an anticancer slow-release agent containing glucocorticoid and chemotherapy drugs, belonging to the technical field of medicines. Specifically, the invention provides a sustained-release injection and a sustained-release implant containing glucocorticoid. The anti-cancer slow-release agent can effectively inhibit or destroy the solid tumor stroma and tumor blood vessels, and can inhibit tumor angiogenesis, effectively reduce the tension in the tumor, interstitial pressure, and interstitial viscosity, thereby improving its interstitial fluid conduction. It is conducive to the effective diffusion of drugs into solid tumors and tumors, and can also increase drug sensitivity. (2) Background technology [0002] Traditional chemotherapy is not selective, and it is difficult to form an effective drug concentration or therapeutic dose locally in the tumor. The effect is poor and the toxicity is high. Simply increasing the drug or ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/00A61K9/10A61K45/06A61K47/30A61P35/00
Inventor 孔庆忠邹会凤刘恩祥苏红清
Owner JINAN KANGQUAN PHARMA TECH
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