Novel cis-platinum nano biodegradable medicinal composition and preparation method

A cisplatin and nanoparticle technology, applied in the field of medical treatment, can solve the problems of cisplatin difficult to embed, cisplatin cannot be retained, and low water solubility, and achieve the effect of simplified preparation method and easy operation

Inactive Publication Date: 2012-03-14
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Cisplatin is difficult to effectively entrap in liposomes because of its low water solubility
In addition, it is difficult to stabilize liposomal formulations because cisplatin is reported not to be retained in liposomal formulations during storage

Method used

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  • Novel cis-platinum nano biodegradable medicinal composition and preparation method
  • Novel cis-platinum nano biodegradable medicinal composition and preparation method

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0051] In this embodiment, the main operation is to dissolve the injectable sodium carboxymethylcellulose polymer complying with FDA specifications in water with sterile demineralized water, and the prepared concentration is 1.3%; then add cisplatin (0.6%) to the solution Dissolve in medium, react at 37°C for several hours, and form a complex compound derived from the copolymer and cisplatin represented by the following formula; the equivalent ratio of the Pt atom of cisplatin to the carboxyl anion of the copolymer (Pt / COO - ) is 0.3 or more. In this example, cisplatin, which is poorly soluble in water when in unconjugated form, exhibited a greatly improved solubility after conjugation.

[0052] Chemical reaction process:

[0053]

[0054] Sodium Carboxymethyl Cellulose Molecular Structure I:

[0055] The complex described in the present invention means that one or both of the two chloride ions in the CDDP molecule are exchanged by the carboxyl anion of the copolymer to...

Embodiment 2

[0057] 600.1mg of PLGA-mPEG two-block copolymer, the two-block molecular weight is 60,000 and 5,000 respectively, dissolved in 20mL of dichloromethane / acetone, 937.2mg of Span 80 was dissolved in the composite organic phase, the organic phase solution and cisplatin complex Mix the mixture solution to form colostrum; add the colostrum to 100mL 0.3% polyethylene glycol vitamin E succinate solution, and then put the uniformly dispersed mixture solution under high pressure (9,000~16,000psi) in a micro jet homogenizer Internal (suitable sterilization) treatment until a nanoemulsion is obtained (particle size less than 0.2 micron); volatilize for 2-6 hours and pass the submicron emulsion through a 0.2 micron filter to sterilize the emulsion. It was frozen to -80°C under aseptic conditions and lyophilized for 58 hours while warming to 30°C.

[0058]The resulting powder containing 5.7% (w / w) cisplatin was reconstituted with 0.9% aqueous sodium chloride solution to form a cisplatin con...

Embodiment 3

[0060] 600.3mg of PLGA-mPEG two-block copolymer, the two-block molecular weight is 30,000 and 5,000 respectively, dissolved in 20mL of dichloromethane / acetone, 937.5mg of Span 80 was dissolved in the composite organic phase, the organic phase solution and cisplatin complex Mix the mixture solution to form colostrum; add the colostrum to 100mL 0.3% polyethylene glycol vitamin E succinate solution, and then put the uniformly dispersed mixture solution under high pressure (9,000~16,000psi) in a micro jet homogenizer Internal (suitable sterilization) treatment until a nanoemulsion is obtained (particle size less than 0.2 micron); volatilize for 2-6 hours and pass the submicron emulsion through a 0.2 micron filter to sterilize the emulsion. It was frozen to -80°C under aseptic conditions and lyophilized for 58 hours while warming to 30°C.

[0061] The resulting powder containing 5.7% (w / w) cisplatin particles was reconstituted with 0.9% aqueous sodium chloride to form a cisplatin c...

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Abstract

The invention discloses a novel cis-platinum polyethylene glycol-polylactic acid or polylactic acid-glycolic acid (PLA-mPEG or PLGA-mPEG or PLA/PLGA-mPEG) copolymer nano medicament and a new preparation method thereof. The macromolecular material PLA/PLGA-mPEG is used as a support in the nano medicament carrier; and a double-emulsifying method is applied in preparation, meanwhile, polyethylene glycol vitamin E succinate (TPGS) is used as a stabilizing agent, and the solid nano cis-platinum medicament is finally obtained by freeze drying, wherein the medicament can be uniformly distributed in nucleus. The copolymer nano carrier is safe and non-toxic, and meets the requirement of in vivo application of the medicament; and the solid nano medicament can be rehydrated to form emulsion by using physiological saline, so that the medicament has high stability. The preparation method avoids the problems of low cis-platinum entrapment rate and low loading rate and the like in the conventional preparation method, and can be applied to sustained-release or controlled-release preparation of insoluble medicaments.

Description

technical field [0001] The present invention relates to the antitumor preparation of cisplatin and polyethylene glycol-polylactic acid or polylactic acid-glycolic acid (PLA-mPEG or PLGA-mPEG, hereinafter also written together as PLA / PLGA-mPEG) nanoparticles, and relates to a Preparation of emulsions stabilized by TPGS homogenization technique. It produces a sustained-release injectable reconstituted aqueous mixture belonging to the field of medical therapy. The TPGS-stabilized cisplatin emulsions described in the present invention can correct several clinically important application deficiencies of current commercial formulations and can provide beneficial stability and efficacy when compared to commercial products. Background technique [0002] Cisplatin, cis-diamino-dichloroplatinum (CDDP), is a heavy metal complex (complex) containing a central platinum atom surrounded by two chlorine atoms and two cis ammonia molecules. Cisplatin is a periodic non-specific anti-tumor d...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/34A61K9/10A61K9/107A61K9/19A61K33/24A61K47/36A61K47/38A61P35/00
Inventor 程立华林标扬
Owner ZHEJIANG UNIV
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