Biodegradable polypeptide vesicle loaded with hemoglobin and preparation method thereof

A hemoglobin and biodegradation technology, applied in the direction of peptide/protein components, non-active ingredients of polymer compounds, medical preparations containing active ingredients, etc., can solve the problems of immunogenicity and rejection, and achieve excellent biological Degradability, long circulation time in the body, and good stability

Inactive Publication Date: 2009-05-20
CHANGCHUN INST OF APPLIED CHEMISTRY - CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Albumin is also a biodegradable material, but as a natural protein, its immunogenicity and rejection are difficult to resolve
A recent Chinese patent application (Application No. 200810050914.3, "A biodegradable nanoparticle bonded to hemoglobin molecules and its preparation method") discloses a red blood cell substitute with polyethylene glycol-polycarbonate-polylactic acid as the carrier. The hemoglobin molecule is chemically bonded to the polycarbonate block, so it exists in the form of nano-micelle in the water system. The hemoglobin is between the hydrophilic shell and the hydrophobic core of the micelle. Although it has the function of carrying oxygen, it is There is still a certain gap with hemoglobin in the overall structure

Method used

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  • Biodegradable polypeptide vesicle loaded with hemoglobin and preparation method thereof
  • Biodegradable polypeptide vesicle loaded with hemoglobin and preparation method thereof
  • Biodegradable polypeptide vesicle loaded with hemoglobin and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] Embodiment 1: Synthesis of amino-terminated poly(N-benzyloxycarbonyl lysine) (PZLL)

[0027]Put 2.0g of N-benzyloxycarbonyllysine NCA into an ampoule baked by flame, ventilate with nitrogen three times, seal it and add 20ml of DMF with a syringe, after dissolving, add the DMF solution of n-hexylamine in proportion , Reacted in a 30°C oil bath for 72h with stirring. The reactant was settled with excess ether to obtain transparent and viscous PZLL, which was redissolved in chloroform and settled with excess ether to obtain a white solid. Pure amino-terminated PZLL was obtained by vacuum drying at 40°C for 24 hours.

Embodiment 2

[0028] Example 2: Synthesis of poly(Z-lysine)-polyphenylalanine two-block copolypeptide (PZLL-b-PPA)

[0029] Add the poly(Z-lysine) and phenylalanine NCA of the terminal amino group in proportion to the ampoule that has been baked with flame, and ventilate with nitrogen three times, add DMF (2wt%) with a syringe after sealing, and stir The reaction was carried out in an oil bath at 30° C. for 24 hours, and the subsequent treatment process was as shown in Example 1.

Embodiment 3

[0030] Example 3: Deprotection of PZLL-b-PPA

[0031] Deprotection of PZLL-b-PPA was achieved with hydrogen bromide. PZLL-b-PPA was dissolved in trifluoroacetic acid (0.04g / ml), then passed into hydrogen bromide gas, bubbling reaction for 30 minutes, continued stirring reaction in ice bath for 12 hours, and settled with excess ether to obtain the deprotected product. Vacuum-dried at 40°C for 24 hours to obtain polylysine-polyphenylalanine (PLL-b-PPA), its H NMR spectrum is shown in the attached Figure 4 .

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Abstract

The invention provides a polypeptide vesicle carried with hemoglobin and a preparation method thereof. The hemoglobin is wrapped in the vesicle, and the wall of the vesicle consists of polylysine-polyphenylalanine di-block copolypeptide. Firstly, hexyl amine is taken as an initiating agent, poly(Z-lysine) is obtained through ring-opening polymerization of N-benzyloxycarbonyl(Z)lysineN-carbonyl carboxylic acid anhydride, then a terminal amino group of the poly(Z-lysine) is used to initiate the ring-opening polymerization of phenylalanineN-carbonyl carboxylic acid anhydride to obtain poly(Z-lysine)-polyphenylalanine, the poly(Z-lysine)-polyphenylalanine is deprotected and then is self-assembled in an aqueous solution to form a vesicle and wrap the hemoglobin, and the vesicle with the hemoglobin is obtained. The vesicle is formed by directly assembling amphiphilic block copolypeptide in the aqueous solution, and no organic solvent needs to be used, so the biological activity of the hemoglobin is better maintained.

Description

technical field [0001] The invention relates to a biodegradable hemoglobin-loaded polypeptide vesicle and a preparation method thereof, in particular to a hemoglobin biodegradable amphiphilic block copolymerized peptide vesicle and a preparation method thereof, belonging to the field of biomedical materials. Background technique [0002] Blood transfusion is an indispensable medical method for clinical operations, disaster relief and battlefield rescue. Relying on people to donate blood not only faces the problem of shortage of blood sources, but also due to the complexity of blood types, blood transfusion must be strictly matched. Security is threatened. In recent years, the demand for blood has been increasing, but safe and effective blood sources have become increasingly scarce. Therefore, in recent decades, blood substitutes have always been the research and development focus of the international scientific community and business circles. Blood substitutes refer to ar...

Claims

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Application Information

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IPC IPC(8): A61K47/42A61K9/50A61K38/42A61P7/08C08J3/00C08L77/00C08L89/00C08G69/16C08G69/48
Inventor 景遐斌孙静黄宇彬石全陈学思
Owner CHANGCHUN INST OF APPLIED CHEMISTRY - CHINESE ACAD OF SCI
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