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Composite slow-releasing anticarcinogen contg. platinum compounds such as sunpla

A technology of compounds and sustained-release agents, which is applied in the field of compound anti-cancer sustained-release agents, can solve problems such as effective drug concentration, limitation, and complicated surgical operations that are difficult to form locally in tumors

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

[0114] Put 80 mg of polylactic acid (PLGA) with a peak molecular weight of 35,000 into a container, add 100 ml of dichloromethane, dissolve and mix well, add 10 mg of sciplatin and 10 mg of methotrexate, 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 slow-release anti-cancer drug containing 10% sibplatin and 10% methotrexate. All are percentages by weight. The drug release time of the anti-solid tumor pharmaceutical composition in physiological saline in vitro is 15-25 days, and the drug release time in mouse subcutaneous is 25-50 days.

Embodiment 2

[0116] As described in Example 1, the difference is that the anticancer active ingredient and weight percentage are one of the following:

[0117] (1) 1-40% of sulfoplatin, dicycloplatin, eplatin, meciplatin, siciplatin or picoplatin and 1-40% of doxorubicin, epirubicin, mitomycin C, actin A combination of Dactinomycin or Dactinomycin; or

[0118] (2) 1-0% of sulfoplatin, dicycloplatin, eplatin, meciplatin, cisiliplatin or picoplatin and 1-40% of fluoxuridine, deoxyfluorouridine, 5-deoxyfluorouridine, propane Thiouracil, fluorouracil, butylfluorouracil, difluoropyrimidine, 5-fluoropyrimidinol, sodium sulfcaptopurine, mercaptopurine, mercaptopurine, 6-mercaptopurine, 6-aminopurine hydrochloride, glycinethiopurine , Thioguanine, methotrexate, flumethotrexate, dioxymethotrexate, 10-ethyldeazhotrexate, methotrexate, folic acid, 5,10-dideazatetrahydrofolate , calcium folinate, calcium folinate, carmofur, tegafur, Youfudine, uracil tegafur, 8-azaguanine, uracil, thiomethouracil, t...

Embodiment 3

[0121] Put 80mg polyphenylene propane (p-CPP: sebacic acid (SA) 20:80) copolymer into a container, add 100ml dichloromethane, dissolve and mix well, then add 10mg bicyclic Platinum and 10 mg of fluorouracil were re-shaken and spray-dried to prepare microspheres for injection containing 10% bicycloplatin and 10% fluorouracil. 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 15-25 days, and the drug release time in mice subcutaneous is about 30-40 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 slow-release agent, which belongs to the technical field of medicines. Specifically, it is a slow-release preparation against solid tumors, including slow-release injections and slow-release implants. (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...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/10A61K31/282A61K31/555A61K45/00A61K47/34A61P35/00
Inventor 孔庆忠张红军邹会风
Owner SHANDONG LANJIN PHARMA
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