Paclitaxel polymer micelle by using refined amphiphilic block copolymer as carrier

A technology of block copolymer and polymer glue, applied in the directions of drug combination, liquid delivery, powder delivery, etc., can solve the problems of the influence of the kinetic stability of the micelle system and the difficulty of controlling the tin content of the polymer.

Inactive Publication Date: 2014-05-07
LIVZON PHARM GRP INC
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0004] Chinese patent CN1524581 discloses a kind of polymer micelle system, and its polymer is polyethylene glycol monomethyl ether-polyester block copolymer, but used catalyst stannous octoate in the synthesis of this polymer, makes polymer in It is difficult to control the tin content of the polymer, and studies have shown that excessive tin content in the polymer has a significant impact on the kinetic stability of the micellar system

Method used

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  • Paclitaxel polymer micelle by using refined amphiphilic block copolymer as carrier
  • Paclitaxel polymer micelle by using refined amphiphilic block copolymer as carrier
  • Paclitaxel polymer micelle by using refined amphiphilic block copolymer as carrier

Examples

Experimental program
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Effect test

Embodiment 1

[0026] Synthesis and Molecular Weight Determination of Polyethylene Glycol Monomethyl Ether-Poly(D, L) Lactide Block Copolymer as the Carrier of Paclitaxel Polymer Micelles.

[0027] D, L-lactide: purchased from Shandong Daigang Biotechnology Co., Ltd., vacuum-dried in phosphorus pentoxide at room temperature for 24 hours before use; mPEG2000: purchased from Sigma-Aldrich, dried in vacuum with phosphorus pentoxide at room temperature before use 24 hours; stannous octoate: available from Sigma-Aldrich.

[0028] 1. Synthesis of polyethylene glycol monomethyl ether poly-polylactide block copolymer:

[0029] A polyethylene glycol monomethyl ether-poly(D, L) lactide block copolymer with a mass ratio of 50 / 50 was prepared by ring-opening polymerization. Weigh 5 g of polyethylene glycol monomethyl ether and 5 g of D, L-lactide, place them in a sealed reactor, raise the temperature to 120-140 ° C under nitrogen flow to melt the solid, add 50 mg of stannous octoate, and raise the temp...

Embodiment 2

[0038] This example is a comparison of tin content in polyethylene glycol monomethyl ether poly-polylactide block copolymer before and after refining (cation exchange resin treatment).

[0039] The tin content in the polymer was determined by inductively coupled plasma emission spectrometry (ICP-AES). Working conditions of inductively coupled plasma atomic emission spectrometry (ICP-AES) instrument: generator power is 1300W, argon gas purity is 99.999%, cooling gas flow rate is 15L / min, auxiliary device flow rate is 0.2L / min, atomizer flow rate is 0.80L / min, the lifting volume of the test solution is 1.5mL / min, the integration time is 2-10s, and the axial observation method is adopted. The analytical spectral lines of tin element are 189.927nm respectively. The sample digestion adopts the microwave digestion method: the heating power is 1000W, the temperature is raised to 200°C, and the heating time is 15min; the temperature is kept at 200°C, and the holding time is 20min. T...

Embodiment 3

[0043] Preparation of paclitaxel-polyethylene glycol monomethyl ether-poly(D, L) lactide block copolymer micelles and study on particle size stability

[0044] 1. Preparation of paclitaxel polyethylene glycol monomethyl ether-poly(D, L) lactide block copolymer micelles

[0045] Put paclitaxel 300mg and paclitaxel polyethylene glycol monomethyl ether-poly(D, L) lactide block copolymer block copolymer (mass ratio 5:5) 1500mg in an eggplant-shaped bottle, add methanol 15ml to dissolve completely , heated in a water bath at 50°C and evaporated to dryness under reduced pressure, and was attached to the bottom of the bottle in the form of a transparent film. Add 30ml of water for injection, heat in a water bath at 50°C, and rotate the film to hydrate for 15 minutes to obtain light blue opalescent micelles. Filter with a 0.22 μm filter membrane, dispense 3ml into vials, and freeze-dry to obtain white loose needle-like powder.

[0046] 2. Comparison of particle size stability of mic...

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Abstract

The invention provides a paclitaxel polymer micelle drug-loading system. The polymer is an amphiphilic block copolymer, optimally methoxy polyethylene glycol-poly(D,L) lactide, which is subjected to cationic exchange resin treatment and low in tin content (less than 100ppm); the paclitaxel and the methoxy polyethylene glycol-poly(D,L) lactide are dissolved in an organic solvent and concentrated until being dry, and the residue is hydrated to obtain the micelle; the obtained micelle is lyophilized to obtain lyophilized powder. According to the micelle, the polymer is refined (cationic exchange resin treatment), so that the content of tin in the polymer due to introduce of a catalyst is remarkably reduced, and the grain diameter stability of the paclitaxel polymer micelle prepared from the refined methoxy polyethylene glycol-poly(D,L) lactide is remarkably improved.

Description

technical field [0001] The invention relates to a refining process of an amphiphilic block copolymer and a preparation method of a paclitaxel polymer micelle with the copolymer as a carrier and a freeze-dried preparation thereof. Background technique [0002] Paclitaxel has very poor water solubility, and the presence of EL and ethanol have limited its clinical application. Therefore, the development of suitable paclitaxel delivery system, instead of The mixed solvent of EL and ethanol has become the key to expand the clinical application of paclitaxel. In recent years, there have been many reports on the drug delivery system of paclitaxel: Chinese patent CN1526387A discloses a paclitaxel vesicle injection; CN101612121A discloses a paclitaxel microemulsion; Chinese patent CN101015525A utilizes phospholipids and cholesterol to prepare a paclitaxel liposome; Chinese patent CN101829062A prepares a paclitaxel sustained-release microsphere with chitosan as a carrier; The FD...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/10A61K9/19A61K31/337A61K47/34A61P35/00
Inventor 王燕清苏日佳周月广吴起娟解荷芝刘亦江涂增清陈嘉璐李敬豪
Owner LIVZON PHARM GRP INC
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