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A kind of polyglutamic acid graft metformin stereostructure nano-micelle and preparation method thereof

A technology of metformin and polyglutamic acid, 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 short drug half-life and low encapsulation rate, and achieve improved encapsulation sealing rate, prolonging half-life, and ensuring stability

Active Publication Date: 2021-07-02
广州大鱼创福科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the existing polyamino acid drug carriers still have defects such as low encapsulation efficiency and short drug half-life.

Method used

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  • A kind of polyglutamic acid graft metformin stereostructure nano-micelle and preparation method thereof
  • A kind of polyglutamic acid graft metformin stereostructure nano-micelle and preparation method thereof
  • A kind of polyglutamic acid graft metformin stereostructure nano-micelle and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] A preparation method of polyglutamic acid grafted metformin stereotactic nano micelles, comprising the steps of:

[0029] (1) After cooling 1g of N-carboxy-L-glutamic acid-cyclic anhydride with liquid nitrogen, vacuumize it, and add 4ml of SOCl under an ice bath in a nitrogen atmosphere 2 , the acid halide reaction was 12h, and after the reaction was finished, the unreacted SOCl was distilled off under reduced pressure 2 , then add 35mlDMF, 8ml triethylamine and 0.7g metformin to react at room temperature for 12h, the reaction product is filtered after precipitation treatment, and after drying, N-(N,N-dimethylcarbamoyl)carbamoyl)-N -Carboxyl-L-glutamic acid-cyclic anhydride;

[0030] (2) After cooling 1g of N-carboxy-D-glutamic acid-anhydride in the ring with liquid nitrogen, vacuumize it, and add 4ml of SOCl under ice bath in a nitrogen atmosphere 2 , the acid halide reaction was 12h, and after the reaction was finished, the unreacted SOCl was distilled off under red...

Embodiment 2

[0034]A preparation method of polyglutamic acid grafted metformin stereotactic nano micelles, comprising the steps of:

[0035] (1) Cool 1g of N-carboxy-L-glutamic acid-cyclic anhydride with liquid nitrogen and then vacuumize, add 3ml of SOCl under ice bath in nitrogen atmosphere 2 , acid halide reaction 4h, after the end of the reaction, the unreacted SOCl was distilled off under reduced pressure 2 , then added 20ml DMF, 5ml triethylamine and 0.5g metformin to react at room temperature for 4h, the reaction product was filtered after precipitation treatment, and dried to obtain N-(N,N-dimethylcarbamoyl)carbamoyl)- N-carboxy-L-glutamic acid-cyclic anhydride;

[0036] (2) After cooling 1g of N-carboxy-D-glutamic acid-anhydride in the ring with liquid nitrogen, vacuumize it, and add 3ml of SOCl under an ice bath in a nitrogen atmosphere 2 , acid halide reaction 4h, after the end of the reaction, the unreacted SOCl was distilled off under reduced pressure 2 , then added 20ml DM...

Embodiment 3

[0040] A preparation method of polyglutamic acid grafted metformin stereotactic nano micelles, comprising the steps of:

[0041] (1) After cooling 1g of N-carboxy-L-glutamic acid-cyclic anhydride with liquid nitrogen, vacuumize it, and add 5ml of SOCl under an ice bath in a nitrogen atmosphere 2 , the acid halide reaction was 24h, and after the reaction was finished, the unreacted SOCl was distilled off under reduced pressure 2 , then add 50mlDMF, 10ml triethylamine and 0.8g metformin to react at room temperature for 24h, the reaction product is filtered after precipitation treatment, and after drying, N-(N,N-dimethylcarbamoyl)carbamoyl)-N -Carboxyl-L-glutamic acid-cyclic anhydride;

[0042] (2) After cooling 1g of N-carboxy-D-glutamic acid-anhydride in the ring with liquid nitrogen, vacuumize it, and add 5ml of SOCl under an ice bath in a nitrogen atmosphere 2 , the acid halide reaction was 24h, and after the reaction was finished, the unreacted SOCl was distilled off under...

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Abstract

The invention belongs to the technical field of biomedical materials, and discloses a preparation method of polyglutamic acid-grafted metformin stereotactic nano-micelle, which comprises respectively adding N-carboxy-L-glutamic acid-anhydride and N-carboxy- D-glutamic acid-anhydride acid halide in the ring, and then condensation reaction with metformin; Glutamic acid-cyclic anhydride and N-(N,N-dimethylcarbamoyl)carbamoyl)-N-carboxy-D-glutamic acid-cyclic anhydride and N-carboxy-L-glutamine Amino acid-cyclic anhydride, N-carboxy-D-glutamic acid-cyclic anhydride for block copolymerization, then add PEG4000, anti-tumor drugs and mix well, and extrude with a filter membrane. The nano micelles prepared by the preparation method of the present invention have a stable structure, high encapsulation efficiency and drug loading rate, and slow drug release rate.

Description

technical field [0001] The invention relates to the technical field of biomedical materials, in particular to a polyglutamic acid-grafted metformin stereotactic nano-micelle and a preparation method thereof. Background technique [0002] The polymer drug delivery system refers to the use of polymer carriers for encapsulation, adsorption or chemical connection of drugs, and the selective distribution and physical and chemical properties of the drug carrier itself are used to deliver the drug to the lesion site, and the drug can be delivered to the lesion through diffusion and other methods. Released slowly, so as to achieve the purpose of treating diseases safely and effectively. However, biocompatibility, biodegradability and safety restrict the use of some pharmaceutical polymer materials, and the development of safe polymer materials with new functions has always been a hot spot in pharmaceutical research. Amino acid is the basic unit of biological functional macromolecul...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/107A61K47/69A61K31/337A61K31/704A61K31/365A61K47/64A61P35/00C08G69/10
CPCA61K9/1075A61K31/337A61K31/365A61K31/704A61K47/34A61P35/00C08G69/10
Inventor 汤佳鹏葛彦刘希文朱俐
Owner 广州大鱼创福科技有限公司
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