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Anti-cancer slow-release agent carried with glucocorticoid hormone and chemical therapy medicine

A technology of glucocorticoids and corticosteroids, which is applied in the direction of drug combination, drug delivery, and non-active components of polymer compounds, can solve problems such as increased resistance of anticancer drugs, limitation of effective drug diffusion, and obstacles to tumor chemotherapy. Improve the conductivity of interstitial fluid, inhibit the formation of new blood vessels, and facilitate the effect of penetration and diffusion

Inactive Publication Date: 2007-08-29
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 entry of drugs into solid tumors and the effective diffusion in 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-carboxyphenylpropane (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 step of being processed into sustained-release injection is the same as that of Example 1, but the difference is that polyphenylene is 50:50; the contained anticancer active ingredient and its weight percentage are: 0.1-10% prednisolone, Methylprednisolone, dexamethasone, betamethasone, triamcinolone, or triamcinolone acetonide with 1-40% of 7-hydroxyl-staurosporine, 7-O-alkylstaurosporine, beta - a combination of methoxystaurosporine, alkylphosphocholine or hexadecylphosphorylcholine.

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

The present invention relates to a anti-cancer slow-release preparation containing glucocorticoid and chemotherapeutic medicine. Said anti-cancer slow-release preparation is a slow-release injection formed from slow-release microsphere and solvent. The slow-release microsphere includes anti-cancer effective component and slow-release auxiliary material, its solvent is a special solvent containing suopension adjuvant. The glucocorticoid is selected from prednisolone, methyl prednisolone, dexamethasone, betamethasone, triamcinolone and triamcinolone acetonide, its chemotherapeutic medicine is selected from phosphoinositide 3-kinase inhibitor and pyrimidine analogues. The slow-release auxiliary material is polylactic acid and its copolymer, polyethylene glycol, carboxyl-terminated polylactic acid copolymer, difatty acid and sebacic acid copolymer, poly (erucidic acid dimer-sebacic acid) and poly (fumaric acid-sebacic acid) biological compatibility macromolecule, and the suspension adjuvant is selected from carboxymethylcellulose sodium, etc. Said invention also can be made into slow-release implantation preparation.

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): A61K9/00A61K45/06A61K47/34A61P35/00A61K47/10A61K47/26A61K47/32A61K47/36A61K47/42
Inventor 孔庆忠邹会凤刘恩祥苏红清
Owner JINAN KANGQUAN PHARMA TECH
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