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Preparation method of dextran-based ROS-responsive camptothecin polymer prodrug

A technology of dextran and camptothecin, which is applied in the direction of pharmaceutical formulations, medical preparations with non-active ingredients, medical preparations containing active ingredients, etc., can solve the problems of strong toxic side effects, poor water solubility, non-selectivity, etc. Achieve high drug loading rate, effective treatment, and good stability

Inactive Publication Date: 2019-08-16
SOUTHWEST UNIV
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  • Abstract
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Problems solved by technology

[0002] The most common problems of anticancer drug molecules including camptothecin are poor water solubility, small molecular size and non-selectivity. In the process of drug delivery, there are poor blood circulation stability, low drug bioavailability, strong side effects and Low medical efficiency and other issues

Method used

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  • Preparation method of dextran-based ROS-responsive camptothecin polymer prodrug
  • Preparation method of dextran-based ROS-responsive camptothecin polymer prodrug
  • Preparation method of dextran-based ROS-responsive camptothecin polymer prodrug

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Embodiment 1

[0030] Example 1 Preparation of dextran-based ROS-responsive camptothecin polymer prodrug DCPT

[0031] like figure 1 The synthetic schematic shown is for the preparation of the dextran-based ROS-responsive camptothecin polymer prodrug DCPT, including the following steps:

[0032](1) Preparation of Dex-Br: Under argon atmosphere, 1 g of dextran (Dex) dissolved in 10 mL of ionic liquid 1-allyl-3-methylimidazole chloride was cooled to 0 °C, and then Add 7 mL of N-methylpyrrolidone (NMP) and 7 mL of N,N-dimethylformamide (DMF), followed by slowly adding 10 mL of 2-bromoisobutyryl bromide (BIBB), ice bath for 0.5- 2h, then warmed to room temperature (25°C) and reacted in the dark for 12-72h, then precipitated in deionized water, dissolved the obtained precipitate with acetone, and repeated the purification three times to obtain a light yellow intermediate product, which was dried in a vacuum drying oven (25-30°C). ), then the obtained pale yellow intermediate product was dissolv...

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Abstract

The invention particular discloses a preparation method and biological application of dextran-based ROS-responsive camptothecin polymer prodrug. The preparation method includes following synthesis steps: (1), utilizing Dextran to synthesize a starlike ATRP initiator (Dextran-Br) through two-step reaction; (2), utilizing esterification reaction to synthesize hydrophobic ROS-responsive prodrug CPTMA; (3), utilizing ATRP polymerization reaction to introduce a hydrophobic block CPTMA and a hydrophilic block OEGMA. The polymer prodrug prepared by the method has the advantages of high micelle stability and high drug loading capacity, can selectively release camptothecin under response of excessive ROS in a tumor environment and can effectively overcome the defects of poor water solubility and serious toxic and side effect of hydrophobic drug in a drug delivery system, thereby realizing effective accumulation at a tumor position so as to achieve the objective of tumor inhibiting.

Description

technical field [0001] The present invention relates to the field of chemical drugs and biological applications, in particular to the preparation of a class of ROS-responsive camptothecin polymer prodrugs based on glucan and their application in drug delivery. Background technique [0002] The most common problems of anticancer drug molecules, including camptothecin, are poor water solubility, small molecular size, and non-selectivity. During drug delivery, there are poor blood circulation stability, low drug bioavailability, strong toxic side effects, and Medical inefficiency and other issues. Chemotherapy is the most widely used method in tumor treatment, but it is accompanied by many side effects. In order to obtain the best therapeutic effect and reduce damage to normal tissues, many nanomaterials have been developed for tumor treatment. The delivery of hydrophobic nano-drugs to tumor sites in the form of drug carriers can not only maintain drug activity and achieve tum...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/107A61K31/4745A61K47/61A61P35/00C08F293/00
CPCA61K9/1075A61K31/4745A61K47/61A61P35/00C08F293/005C08F2438/01
Inventor 许志刚马宪彬张天白霜
Owner SOUTHWEST UNIV
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