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Slow release injection comprising anticancer antibiotics and booster thereof

A technology for sustained-release injections and antibiotics, which is applied in the field of medicine and can solve problems such as treatment failure and increased tolerance

Inactive Publication Date: 2007-03-07
JINAN KANGQUAN 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

[0113] Put 80mg of polyphenylpropanine (p-carboxyphenylpropane (p-CPP): sebacic acid (SA) 20:80) copolymer into the container, add 100ml of dichloromethane, dissolve and mix well, add 10mg Doxorubicin and 10 mg camptothecin were shaken again and spray-dried to prepare injection microspheres containing 10% doxorubicin and 10% camptothecin. Then the microspheres are suspended in physiological saline containing 15% mannitol to prepare the corresponding suspension type sustained-release injection. The viscosity of the injection is 200cp-650cp (20 ℃ -30 ℃ Time). The release time of the sustained-release injection in vitro in physiological saline is 20-30 days, and the release time under the skin of mice is about 30-40 days.

Embodiment 2

[0115] The method and steps of processing into a sustained-release injection are the same as in Example 1, but the difference is that the anti-cancer active ingredients and their weight percentages are:

[0116] (a) 2-40% of camptothecin, hydroxycamptothecin, 9-nitrocamptothecin, podophyllomycin, trihydroxyisoflavone, letotecan, topotecan, irinotecan, eto Poside, teniposide, 14-hydroxydaunorubicin, amrubicin, allorubicin, ditorubicin, esorubicin, rhodorubicin, rhorubicin, or zorubicin ;

[0117](b) 2-40% bleomycin, daunorubicin, adriamycin, triiron adriamycin, epirubicin, 7-O-methyl Noga-4'-epirubicin, Diethoxyacetoxydoxorubicin, Mitomycin C, Actinomycin D, Nocardin, Nocardin, Nocardomycin, Nogamycin, Mitorubin, Polyviscosity Bacteriocin E, Pyrizomycin, Dirithromycin, Antoxomycin, Pelomycin, Puromycin, Spaamycin, Anthramycin, Caminomycin, Puromycin, Axorubicin Bicin, aclamycin-B, idarubicin, serpentine, clarithromycin, adazolam hydrochloride, adazolam, doxorubicin, epirubicin, val...

Embodiment 3

[0120] Put 70mg of polylactic acid (PLGA, 75:25) with a peak molecular weight of 25000 into a container, add 100ml of dichloromethane, dissolve and mix well, add 15mg epirubicin and 15mg hydroxycamptothecin, shake again The organic solvent was removed by vacuum drying. The dried drug-containing solid composition was freeze-pulverized into a micropowder containing 10% epirubicin and 10% hydroxycamptothecin, and then suspended in physiological saline containing 1.5% sodium carboxymethyl cellulose to prepare the corresponding The suspension type sustained-release injection. The viscosity of the injection is 300cp-650cp (at 20℃-30℃). The release time of the sustained-release injection in physiological saline in vitro is 10-15 days, and the release time under the skin of mice is about 30-35 days.

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Abstract

Disclosed is an anticancer slow release injection containing anticancer antibiotics and synergistic agents, which comprises slow release micro-balloons and dissolvent, wherein the slow release microballoons comprise anti-cancer active constituents and slow release auxiliary materials, the dissolvent being specific dissolvent containing suspension adjuvant. The anticancer active constituents include anticancer antibiotics and / or anticancer antibiotic synergistic agent selected from enzyme inhibitor and / or tetrazine-group compounds, the slow release auxiliary materials are selected from the following or their combination: Polifeprosan, di-aliphatic acid and sebacylic acid copolymer, poly(erucic aciddipolymer-sebacylic acid) copolymer, poly(fumaric acid-sebacylic acid) copolymer, poly(lactic acid), polyglycolic acid and glycolic acid copolymer, ethylene-vinylacetate copolymer or their combination. The viscosity of the suspension adjuvant is 100-3000cp (at 25-30 deg C), and is selected from sodium carboxymethylcellulose. The slow release microspheres can also be prepared into slow release implanting agent for injection or placement in or around tumor with improved treating effects of chemotherapy.

Description

(1) Technical field [0001] The invention relates to a sustained-release injection containing an anti-cancer antibiotic and its synergist and a preparation method thereof, and belongs to the technical field of medicines. (2) Background technology [0002] As a commonly used chemotherapeutic drug, anti-cancer antibiotics have been widely used in the treatment of a variety of malignant tumors, and their effects are relatively obvious. However, its unexpected neurotoxicity greatly limits the application of the drug. The blood vessels, connective tissue, matrix protein, 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 spread (see Netti et al. "The effect of extracellular matrix conditions on drug delivery in solid tumors", Cancer Research, Issue 60, pages 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): A61K9/10A61K45/00A61K47/32A61K47/34A61K47/36A61K47/38A61K47/42A61P35/00A61K47/26
Inventor 刘玉燕
Owner JINAN KANGQUAN PHARMA TECH
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