Amphiphilic tri-block copolymer taxol bonding medicament and synthesis method thereof

Abstract

The invention relates to an amphipathy block copolymer-Paclitaxel compound and relative preparation, wherein said invention is formed by bonded aliphatic polyester-carbowax-aliphatic polyester block copolymer and Paclitaxel; with hydroxyl carbowax (PEG), solvent and catalyst, it processes the ring-opening polymerization of aliphatic ester to obtain the liphatic polyester-carbowax-aliphatic polyester block copolymer, then converting the hydroxyl grouyp into end carboxyl; with condensating agent, processing genate reaction with Paclitaxel, to obtain the inventive drug. The invention has amphipathy property, to be made into liquid agent or freeze dried. And its block structure can improve the Paclitaxel content, adjusted between 10-40%.

Description

technical field [0001] The invention relates to a class of biodegradable polymer paclitaxel-bonded drugs and a synthesis method thereof, in particular to an amphiphilic triblock copolymer-paclitaxel-bonded drug and a synthesis method thereof. Background technique [0002] Paclitaxel is an antimicrotubule agent extracted from the needles and bark of Taxus brevifolia (for structure see figure 1 ), since Wani et al. first isolated and determined the structure of paclitaxel by chemical and X-ray crystallography in 1971, Phase I clinical research and Phase II and Phase III clinical trials have shown significant antitumor effects on human cancers . This effect was originally discovered in advanced ovarian and breast tumors, and it has been reported in a large number of literatures to have a significant effect on small cell and non-small cell lung cancer, head and neck cancer, and metastatic melanoma. However, the main difficulty in clinical use is that its chemical structure is ...

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Problems solved by technology

[0005] In the Chinese patent (Chinese patent application No. 200410011176.3 and 200610016559.9) that the inventor has applied for, two kinds of polymer-bonded drugs of paclitaxel are disclosed, one is bonded by polyethylene glycol-aliphatic polyester block copolymer and paclitaxel The second is formed by bonding polyester amide-polyethylene glycol-polyester amide triblock copolymer and paclitaxel. In the inventor's Chinese patent application number 200610016614.4, two Affinity, the method for preparing their freeze-dried powder injections. In Chinese patent application 200410011176.3, the effective paclitaxel content is in the range of 5-20%. When the paclitaxel content is high, the molecular weight of the polyethylene glycol segment and the polylactic acid segment Low, thus the amphiphilicity of the whole molecule is limited, which will have a negative impact on the preparation of the following preparations. Therefore, the maximum paclitaxel content that this technology can achieve is limited. Chinese patent application 200610016559.9 connects paclitaxel to the side carboxyl group, thus overcoming the above-mentioned Disadvantages, higher paclitaxel content is allowed, but the synthesis of the carrier polymer is more difficult, and the carboxyl functional group must be protected and deprotected, so it is difficult to achieve large-scale production and clinical practical application. Therefore, the amphiphilic compound with high paclitaxel content The method of polymer-bonded drugs still needs to be improved.

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