Purification method of polyethylene glycol monomethyl ether-polylactic acid amphiphilic block copolymer for injection

A technology of polyethylene glycol monomethyl ether and amphiphilic block, which is applied in the field of medicine and chemical industry, can solve the problems of poor reconstitution stability, slow dissolution and difficult production of polymer micellar freeze-dried preparations, and improve reconstitution Effects of stability, improvement of physical properties, and improvement of solubility

Active Publication Date: 2018-04-17
XINAN PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This preparation method has the following disadvantages: 1) the tin content is higher in the product; 2) the product is a white blocky solid with large particle size differences and is slow to dissolve in a solvent; 3) the polymer micelles made from this product are freeze-dried The reconstitution stability of the preparation is poor, and the drug is quickly precipitated from the micelles, which is difficult to meet the requirements of clinical application; 4) The recrystallization solvent ether is flammable and explosive, which makes it difficult to produce the product in a clean GMP workshop, and microbial control cannot be guaranteed , it is difficult to be directly used in the preparation of lyophilized preparations for injection

Method used

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  • Purification method of polyethylene glycol monomethyl ether-polylactic acid amphiphilic block copolymer for injection
  • Purification method of polyethylene glycol monomethyl ether-polylactic acid amphiphilic block copolymer for injection
  • Purification method of polyethylene glycol monomethyl ether-polylactic acid amphiphilic block copolymer for injection

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Experimental program
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Effect test

Embodiment 1

[0020] Embodiment 1, preparation polyethylene glycol monomethyl ether-polylactic acid amphiphilic block copolymer (average molecular weight 4000)

[0021] Polyethylene glycol monomethyl ether (molecular weight 2000) and lactide were vacuum-dried for 12 hours under the conditions of a vacuum degree greater than 0.095MPa and a temperature of 40°C, and set aside; weigh polyethylene glycol monomethyl ether (molecular weight 2000) Add 30g of lactide, 30g of lactide and 0.15ml of stannous octoate into the reaction bottle, repeatedly fill with nitrogen, vacuumize, and then raise the temperature to 140°C for 6 hours; after the reaction is completed, cool to room temperature to obtain polyethylene glycol monomethyl ether -The crude product of polylactic acid amphiphilic block copolymer, recrystallize the crude product with dichloromethane-diethyl ether, filter the product and vacuum-dry it at room temperature for 72 hours to obtain polyethylene glycol monomethyl ether-polylactic acid am...

Embodiment 2

[0022] Embodiment 2, preparation polyethylene glycol monomethyl ether-polylactic acid amphiphilic block copolymer (average molecular weight 3000)

[0023] Polyethylene glycol monomethyl ether (molecular weight 2000) and lactide were vacuum-dried for 12 hours under the conditions of a vacuum degree greater than 0.095MPa and a temperature of 40°C, and set aside; weigh polyethylene glycol monomethyl ether (molecular weight 2000) Add 30g of lactide, 15g of lactide and 0.15ml of stannous octoate into the reaction bottle, repeatedly fill with nitrogen, vacuumize, and then raise the temperature to 140°C for 6 hours; after the reaction is completed, cool to room temperature to obtain polyethylene glycol monomethyl ether -The crude product of polylactic acid amphiphilic block copolymer, recrystallize the crude product with dichloromethane-diethyl ether, filter the product and vacuum-dry it at room temperature for 72 hours to obtain polyethylene glycol monomethyl ether-polylactic acid am...

Embodiment 3

[0024] Embodiment 3: prepare polyethylene glycol monomethyl ether-polylactic acid amphiphilic block copolymer (average molecular weight 6000)

[0025] Polyethylene glycol monomethyl ether (molecular weight 2000) and lactide were vacuum-dried for 12 hours under the conditions of a vacuum degree greater than 0.095MPa and a temperature of 40°C, and set aside; weigh polyethylene glycol monomethyl ether (molecular weight 2000) Add 20g of lactide, 40g of lactide and 0.15ml of stannous octoate into the reaction bottle, repeatedly fill with nitrogen, vacuumize, and then raise the temperature to 140°C for 6 hours; after the reaction is completed, cool to room temperature to obtain polyethylene glycol monomethyl ether -The crude product of polylactic acid amphiphilic block copolymer, recrystallize the crude product with dichloromethane-diethyl ether, filter the product and vacuum-dry it at room temperature for 72 hours to obtain polyethylene glycol monomethyl ether-polylactic acid amphip...

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Abstract

The invention discloses a method for purifying a polyethylene glycol monomethyl ether-polylactic acid amphiphilic block copolymer for injection, which comprises dissolving the polyethylene glycol monomethyl ether-polylactic acid amphiphilic block copolymer in water Prepare an aqueous solution, and the obtained aqueous solution is used for strong acid cation exchange resin column chromatography, eluted with water, and the obtained eluate is sterilized by filtration with a microporous membrane, and freeze-dried to obtain purified polyethylene glycol monomethyl ether-poly Lactic acid amphiphilic block copolymer; the purification method can reduce the tin content of poly(ethylene glycol monomethyl ether-polylactic acid amphiphilic block copolymer); improve its physical properties and improve solubility; The reconstitution stability of the prepared polymer micelle freeze-dried preparation; it can also remove microorganisms to ensure that the microorganisms do not exceed the standard.

Description

technical field [0001] The invention belongs to the technical field of medicine and chemical industry, and relates to a method for purifying pharmaceutical excipients. Background technique [0002] Solubilizing hydrophobic drugs with surfactants to increase drug water solubility is a conventional technical means in the field of pharmaceutical preparations. For example, docetaxel can be solubilized with polysorbate 80. However, this solubilization method has disadvantages such as high incidence of allergies and poor formulation stability. For example, the oleic acid contained in polysorbate 80 has certain allergies, and patients often need desensitization treatment before using the docetaxel preparation made from it; and when the docetaxel injection is compatible with the infusion, the best It is best to use normal saline, which should be used within 120 minutes after preparation. If it is compatible with 5% glucose solution, it should be used within 60 minutes. [0003] Th...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C08G63/90C08G63/664A61K9/51A61K47/34
Inventor 汪现廖祥伟秦少容郭敏贾利军王明辛龙涛郑飞鸣
Owner XINAN PHARMA
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