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An anticancer sustained release injection carrying tumor drug resistance reversal agent and cytotoxic drug simultaneously

A technology for sustained-release injection and drug resistance reversal, which is applied in the preparation of sustained-release injections, sustained-release injections and sustained-release implants, and can solve the problems of accelerated tumor spread and metastasis, large trauma, and complicated operations.

Inactive Publication Date: 2006-12-13
JINAN KANGQUAN PHARMA TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Local application of drugs may solve the problem of drug concentration to some extent. However, surgical operations such as drug implantation are more complicated and traumatic. In addition to easily leading to various complications such as bleeding, infection, and decreased immunity, it may also cause or Accelerate tumor spread and metastasis
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

[0103] Put 80mg of polyphenylpropane (p-CPP: 20:80 of sebacic acid (SA)) copolymer into a container, add 100ml of dichloromethane, dissolve and mix well, then add 10mg Nedaplatin and 10 mg of pemetrexed were re-shaken and spray-dried to prepare microspheres for injection containing 10% nedaplatin and 10% pemetrexed. Then suspend the microspheres in physiological saline containing 15% mannitol to prepare the corresponding suspension-type sustained-release injection with a viscosity of 220cp-460cp (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.

Embodiment 2

[0105] 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:

[0106] (a) 20% of pemetrexed, raltitrexed, noratrexed, nelarabine, tipifarnib, ronafarib, or pentaspodar;

[0107] (b) 20% heptaplatin, nedaplatin, melphalan, 4H-cyclophosphamide peroxide, 2'-hydroxypaclitaxel, 10-deacetylpaclitaxel, 7-epi-paclitaxel, vinorelbine, tamoxicil Fen, methotrexate, doxorubicin, epirubicin, actinomycin D, tamustine, amustine, semustine, or ramustine; or

[0108] (c) 2-40% of pemetrexed, raltitrexed, noratrexed, nelarabine, tipifarnib, ronafarib, or valspodar with 2-40% of heptaplatin, Nedaplatin, melphalan, 4H-cyclophosphamide peroxide, 2'-hydroxy-paclitaxel, 10-deacetyl-paclitaxel, 7-epi-paclitaxel, vinorelbine, tamoxifen, methotrexate, doxorubicin, epi A combination of doxorubicin, actinomycin D, tamustine, amustine, semustine, or ramustin...

Embodiment 3

[0110] Put 70 mg of polylactic acid (PLGA, 75:25) with a peak molecular weight of 65,000 into a container, add 100 ml of dichloromethane, dissolve and mix well, add 15 mg of raltitrexed and 15 mg of tamustine, and re-shake Dry in vacuo to remove the organic solvent. Freezing and pulverizing the dried drug-containing solid composition to make micropowder containing 15% raltitrexed and 15% tamustine, and then suspending in physiological saline containing 1.5% carboxymethylcellulose sodium to prepare the corresponding Suspension-type sustained-release injection with a viscosity of 300cp-400cp (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

Disclosed is an anticancer slow release injection carrying both tumor drug resistance reversal agents and cytotoxic drugs, 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 ingredient is tumor drug resistance reversal agent selected from Pemetrexed, Raltitrexed, Nolatrexed, Nelarabine, Tipifarnib, Ronafarnib or Valspodar, and / or cytotoxic drugs selected from Eptaplatin, Nedaplatin, Melphalan, 4-hydroperoxycyclophosphamide, Vinorelbine, Tamoxifen, Tallimustine, Atrimustine, Semustine, Ranimustine, the slow release auxiliary materials are selected from poly(lactic acid), Polifeprosan, di-aliphatic acid and sebacylic acid copolymer, polyglycolic acid and glycolic acid copolymer, ethylene-vinylacetate copolymer and lactic acid polymer.

Description

(1) Technical field [0001] The invention relates to a preparation method of a sustained-release injection containing a tumor drug resistance reversal agent and a cytotoxic drug, and belongs to the technical field of medicines. Specifically, the present invention provides a slow-release preparation of anticancer drugs containing a tumor resistance reversal agent and / or cytotoxic drug, mainly slow-release injections and slow-release implants. (2) Background technology [0002] As one of the routine cancer treatment methods, drug chemotherapy has been widely used in the treatment of various malignant tumors, and the effect is more obvious. However, its obvious systemic toxicity and the development of drug resistance greatly limit the application of this drug. Among them, the resistance of tumor cells to chemotherapy drugs is an important reason for the failure of clinical chemotherapy. Therefore, finding resistance reversal agents (RRAs) is one of the important strategies for...

Claims

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Application Information

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IPC IPC(8): A61K9/10A61K45/00A61K47/32A61K47/34A61K47/38A61K31/519A61P35/00
Inventor 孔庆新
Owner JINAN KANGQUAN PHARMA TECH
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