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Slow-release injecta containing platinums compound and its synergist

A sustained-release injection and compound technology, applied in the field of medicine, can solve problems such as treatment failure and increased tolerance

Inactive Publication Date: 2006-10-25
JINAN SHUAIHUA PHARMA TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The latter often leads to increased resistance of tumor cells to anticancer drugs, with consequent treatment failure

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0129] Put 80mg polyphenylene propane (p-CPP: sebacic acid (SA) 20:80) copolymer into the container, add 100ml dichloromethane, dissolve and mix well, then add 10mg Cisplatin and 10 mg camptothecin were re-shaken and spray-dried to prepare microspheres for injection containing 10% cisplatin and 10% camptothecin. 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 physiological saline in vitro is 15-25 days, and the drug release time in mice subcutaneous is about 30-40 days.

Embodiment 2

[0131] 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:

[0132] (1) 2-20% cisplatin, carboplatin, omaplatin, dexomaplatin, heptaplatin, lobaplatin, nedaplatin, or oxaliplatin; or

[0133] (2) 2-40% cisplatin, carboplatin, omaplatin, dextro-omaplatin, heptaplatin, lobaplatin, nedaplatin or oxaliplatin and 5-30% camptothecin, hydroxycamptothecin, Letotecan, topotecan, irinotecan, etoposide, teniposide, amrubicin, arubicin, rhodorubicin, ryrubicin, zorubicin, valerubicin A combination of Bixing or Idarbixing.

Embodiment 3

[0135] Put 70 mg of polylactic acid (PLGA, 75:25) with a peak molecular weight of 25,000 into a container, add 100 ml of dichloromethane, dissolve and mix well, add 15 mg of carboplatin and 15 mg of O6-benzylguanine, re-shake and vacuum Dry to remove organic solvent. Freezing and pulverizing the dried drug-containing solid composition to make micropowder containing 10% carboplatin and 10% O6-benzylguanine, and then suspending in physiological saline containing 1.5% sodium carboxymethylcellulose to obtain the corresponding Suspension-type sustained-release injections. 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 30-35 days.

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Abstract

The present invention relates to a slow-released injection containing platinum compound and its synergist. It is composed of slow-released microsphere and solvent, the slow-released microsphere includes anticancer effective component and slow-released auxiliary material, the solvent is general one or special solvent containing suspension adjuvant. The anticancer effective component includes platinum compound and platinum compound synergist, the platinum compound synergist is topoisomerase inhibitor, guanine analogues and / or tetrazine compound, the slow-released auriliary material is one selected from polylactic acid, copolymer of polyglycollic acid and glycolic acid, ethylene-vinylacetate copolymer, difatty acid and sebacic acid copolymer, poly (erucic acid dimmer-sebacic acid) copolymer and poly (fumaric acid-sebacic acid) copolymer or their combination. The viscosity of suspension adjuvant is 100 cp-3000 cp (20 deg.C-30 deg.C), and said suspension adjuvant is selected from sodium cellulose glycollate. The slow-released microsphere also can be made into the slow-released implant preparation.

Description

(1) Technical field [0001] The invention relates to a sustained-release injection containing a platinum compound and / or its synergist and a preparation method thereof, belonging to the technical field of medicines. (2) Background technology [0002] As a commonly used chemotherapeutic drug, platinum compounds have been widely used in the treatment of various malignant tumors, and the effect is relatively obvious. However, its unexpected neurotoxicity greatly limits the application of this drug. 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 penetration of chemotherapy drugs around the tumor and in the tumor tissue and diffusion (see Netti et al. "The influence of the status of the extracellular matrix on the delivery of drugs in solid tumors" "Cancer Research" 60 pp. 2497-503 (2000) (Netti PA, Cancer Res.2000, 60 (9) : 2497-503)...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/10A61K31/282A61K31/555A61K45/00A61K47/26A61K47/32A61K47/34A61K47/36A61K47/38A61K47/42
Inventor 孔庆伦
Owner JINAN SHUAIHUA PHARMA TECH
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