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Composite slow-releasing anticarcinogen injection contg. platinum compounds

A technology of slow-release injections and compounds, applied in the field of medicine, can solve the problems of complicated surgical operations, large trauma, and decreased immunity, and achieve the effect of increasing drug concentration, reducing drug concentration, and reducing complications

Inactive Publication Date: 2006-11-15
SHANDONG LANJIN PHARMA +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Due to the excessive expansion and hyperplasia of solid tumors, the interstitial pressure, tissue elastic pressure, fluid pressure and interstitial viscosity are all higher than those of the surrounding normal tissues. Therefore, it is difficult for conventional chemotherapy to form an effective drug concentration in the tumor. See Kong Qingzhong "Intratumoral placement of cisplatin plus systemic carmustine in the treatment of rat brain tumors" "Journal of Surgical Oncology" 69 pages 76-82 (1998) (Kong Q et al., J Surg Oncol.1998 Oct; 69( 2): 76-82), simply increasing the dosage is limited by systemic reactions
Local application of drugs may solve the problem of drug concentration to some extent (Chinese patent), however, surgical operations such as drug implantation are more complicated and traumatic, and in addition to easily leading to various complications such as bleeding, infection, and decreased immunity, It can also cause or accelerate the spread and metastasis of tumors
In addition, the preparation and expensive costs before and after the operation often affect its effective implementation.

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0119] Put 80 mg of polylactic acid (PLGA) with a peak molecular weight of 25,000 into a container, add 100 ml of dichloromethane, dissolve and mix well, add 10 mg of eplatin and 10 mg of gemcitabine, re-shake, and then vacuum-dry to remove the organic solvent. The dried solid composition is shaped immediately, subpackaged and then sterilized by radiation to obtain the anticancer slow-release product containing 10% eplatin and 10% gemcitabine. All are percentages by weight. 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 mouse subcutaneous is 25-45 days.

Embodiment 2

[0121] As described in Example 1, the difference is that the anticancer active ingredient and weight percentage are one of the following:

[0122] (a) 2-40% sulfoplatin, dicycloplatin, eberplatin, meciplatin, cisiliplatin or picoplatin and 2-40% bleomycin, daunorubicin, diethoxyacetyl doxorubicin Nocardycin, Nocardycin, Nocardycin, Nocardycin, Mitomycin, Polymyxin E, Pilithromycin, Dirithromycin, Antramycin, Pelomycin, puromycin, spamycin, anthramycin, caminomycin, puromycin, azurarubicin, aclarubicin-B, edarubicin, serpentin , clarithromycin, adazol hydrochloride, adazol, doxorubicin, epirubicin, valrubicin, pirarubicin, loxanthrone, loxoanthrone, mitoxantrone , a combination of pyroxantrone, tiloxantrone, or clozocin; or

[0123] (b) 2-40% of cisplatin, dicycloplatin, eperplatin, meciplatin, ciciplatin or picoplatin and 2-40% of pemetrexed, pemetrexed disodium, lumitrexed, Carmofur, tegafur, temozolomide, zalcitabine, emtricitabine, galocitabine, ibacitabine, ancitabine, ...

Embodiment 3

[0126] Put 80mg of polyphenylpropane (p-carboxyphenylpropane (p-CPP): sebacic acid (SA) at 20:80) copolymer into a container, add 100ml of dichloromethane, dissolve and mix well, then add 10mg of dichloromethane Platinum and 10 mg of doxorubicin were re-shaken and spray-dried to prepare microspheres for injection containing 10% scubaplatin and 10% doxorubicin. Then suspend the microspheres 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 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

A slow-release anticancer injection contains the slow-release microspheres and solvent. Said slow-release microsphere contains the active anticancer component chosen from 6 Pt compounds including bicycloplatinum, etc and 2 synergists including anticancer antibiotic or antimetabolic medicine, and the slow-release auxiliary.

Description

(1) Technical field [0001] The invention relates to a compound anticancer sustained-release injection, which belongs to the technical field of medicines. (2) Background technology [0002] As a class of commonly used chemotherapeutic drugs, platinum compounds have been widely used in the treatment of various malignant tumors, and the effect is relatively obvious. However, its obvious systemic toxicity greatly limits the application of this drug. Not only that, blood vessels, connective tissue, matrix proteins, fibrin, and collagen in the tumor stroma not only provide scaffolds and essential nutrients for the growth of tumor cells, but also affect the effect of chemotherapy drugs on the surrounding tumor and tumor tissue. Penetration and diffusion within (see Netti et al. "The influence of the status of the extracellular matrix on the movement of drugs in solid tumors" "Cancer Research" 60 pp. 2497-503 (2000) (Netti PA, Cancer Res.2000, 60 (9): 2497-503)). Due to the exces...

Claims

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Application Information

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IPC IPC(8): A61K9/10A61K31/282A61K31/555A61K45/00A61K47/34A61P35/00
Inventor 孔庆忠刘恩祥张婕
Owner SHANDONG LANJIN PHARMA
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