Amphipathic amino acid block copolymer and preparation method and application thereof

A block copolymer and amphiphilic technology, which is applied in the biodegradable amphiphilic amino acid block copolymer as a drug carrier, in the field of preparation of the carrier, the technology is mature, the tumor targeting is increased, and the nanomicelle is stable. Effect

Inactive Publication Date: 2012-06-20
CHINA PHARM UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The present invention uses L-aspartic acid and L-phenylalanine to prepare amphiphilic amino acid blo

Method used

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  • Amphipathic amino acid block copolymer and preparation method and application thereof
  • Amphipathic amino acid block copolymer and preparation method and application thereof
  • Amphipathic amino acid block copolymer and preparation method and application thereof

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Experimental program
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Effect test

Embodiment 1

[0062] Embodiment 1: Preparation of L-aspartic acid-β benzyl ester internal anhydride and L-phenylalanine internal anhydride

[0063]References (Prompruk K, Govender T, Zhang S, et al.Synthesis of a novel PEG-block-poly(aspartic acid-statphenylalanine) copolymer shows potential for formation of a micellar drug carrier[J].International Journal ofPharmaceutics, 2005, 297(1-2):242-253.) proceed. Among them, L-aspartic acid-β benzyl ester and L-phenylalanine were purchased from Shanghai Hanhong Chemical Co., Ltd., and triphosgene was purchased from Shanghai Jingchun Reagent Co., Ltd.

[0064] (1) Preparation of L-phenylalanine internal acid anhydride: Add 10g of L-phenylalanine to 100ml of anhydrous tetrahydrofuran, stir magnetically, heat up to 50°C, then add 15g of triphosgene, the suspension becomes clear, and fill with nitrogen for 30min. To remove hydrogen chloride gas and remaining phosgene generated by the reaction, the reaction solution was concentrated, poured into exces...

Embodiment 2

[0070] Embodiment 2: the preparation of amphiphilic amino acid block copolymer

[0071] Dissolve 10g of L-aspartic acid-benzyl ester cyclic acid anhydride in 20mL of dimethylformamide, add 8mg of n-propylamine and stir at room temperature for 72h, add absolute ethanol to precipitate, collect the precipitate, weigh 1g of dimethylformamide after vacuum drying Add 0.95 g of L-phenylalanine cyclic anhydride, continue to stir at room temperature for 72 hours, add ethanol to precipitate, collect the precipitate, add 2M NaOH 5 mL after vacuum drying, stir at room temperature for 4 hours, dialyze with distilled water for 24 hours, freeze-dry Instantly. Yield 19.7%. 1 HNMR determination, by calculating the chemical shift peak area of ​​the methine proton at the α-position of the aspartic acid segment, the chemical shift peak area of ​​the methine proton at the α-position of the phenylalanine segment and the chemical shift peak of the methyl proton in the terminal propyl group The are...

Embodiment 3

[0074] Embodiment 3: the preparation of amphiphilic amino acid block copolymer

[0075] Dissolve 10g of L-aspartic acid-β benzyl ester cyclic anhydride in 20mL of dimethylformamide, add 500mg of n-butylamine and stir at room temperature for 12h, add absolute ethanol to precipitate, collect the precipitate, dry it in vacuum, weigh 1g with two Dissolve 10mL of methylformamide, add 1.2g of L-phenylalanine internal anhydride and continue stirring at room temperature for 12h, add absolute ethanol for precipitation, collect the precipitate, dry it in vacuum, add 0.5M NaOH 5mL, stir at room temperature for 1h, dialyze with distilled water for 24h, It can be obtained by freeze-drying. Yield 45.6%. 1 HNMR determination, by calculating the chemical shift peak area of ​​the methine proton at the α-position of the aspartic acid segment, the chemical shift peak area of ​​the methine proton at the α-position of the phenylalanine segment and the chemical shift peak of the methyl proton in t...

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Abstract

The invention relates to amphipathic amino acid block copolymer and a preparation method and application thereof. The invention discloses the amphipathic amino acid block copolymer with a general formula (I) and salt thereof, wherein m is a positive integer in the range of 1 to 200; n is a positive integer in the range of 1 to 150; X is active terminal ammonia; and Y is alkali metal. The block copolymer can be prepared by performing reaction of anhydride of one amino acid and the active terminal ammonia, then performing reaction of the obtained product and anhydride of another amino acid and removing benzyl by adopting alkali hydroxide. Micelle prepared from the polymer has low critical micelle concentration, is not influenced by pH, has high stability and high drug-loading rate, can be used as a carrier of an organic medicament and waterinsoluble or insoluble and amphipathic medicaments, and is used for endovascular or intramuscular injection, oral administration and tract or external application drug administration. The preparation method is simple. The process is mature. The amphipathic amino acid block copolymer is suitable for large-scale continuous production.

Description

technical field [0001] The invention belongs to the field of pharmaceutical preparations, and relates to a biodegradable amphiphilic amino acid block copolymer as a drug carrier, and also relates to a preparation method and application of the carrier. Background technique [0002] The research of modern drug delivery system is inseparable from the use of new materials, especially pharmaceutical polymer materials, chitosan, hyaluronic acid, gelatin, starch, sodium alginate, albumin, cellulose, polylactic acid, polyvinyl alcohol , acrylics, polyesters, polyethers, etc. have shown unique advantages in pharmacy. However, biocompatibility, biodegradability and safety restrict the use of pharmaceutical polymer materials, and the development of safe and new functional polymer materials belongs to the hot field of pharmaceutical research. Amino acid is the basic unit of biological functional macromolecular protein, and the basic substance that constitutes the protein required by th...

Claims

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Application Information

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IPC IPC(8): C08G69/14C08G69/16A61K47/34
Inventor 周建平陈飞虎汤继辉姚静石静波臧洪梅
Owner CHINA PHARM UNIV
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