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Medicine carrying material of poly ion complexes micelle, preparation and application thereof

A technology of polyion complexes and micelles is applied in the field of medicine, which can solve the problems of reducing the immunogenicity of protein and polypeptide drugs, reducing the immune response of drugs, and the difficulty of protein recognition in micelles, and achieving high safety and biocompatibility. , the preparation process is simple, the effect of easy mass production

Inactive Publication Date: 2008-12-03
SHENYANG PHARMA UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At the same time, the micelles are not easy to be swallowed by the reticuloendothelial system, which reduces the probability of drug clearance through the liver, thereby improving its stability, maintaining its activity, prolonging the plasma half-life of the drug, and improving its bioavailability. On the other hand, the presence of the PEG layer Make the micelles difficult to be recognized by proteins in the blood, reduce the immune response of the drug, and thus reduce the immunogenicity of protein and polypeptide drugs

Method used

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  • Medicine carrying material of poly ion complexes micelle, preparation and application thereof
  • Medicine carrying material of poly ion complexes micelle, preparation and application thereof
  • Medicine carrying material of poly ion complexes micelle, preparation and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0023] Weigh 1.367g of PAHy and dissolve it in distilled water, add 4g of polyethylene glycol (mPEG-CHO) with aldehyde group at one end and monomethyl ether at the other end, adjust the pH value of the reaction medium to 6 with 10% acetic acid solution, and stir at room temperature After reacting for 24h, add 0.53g NaBH 3 CN, adjust the pH value to 6 with 10% acetic acid solution again, and react at room temperature for 48h. The reaction solution was dialyzed for 3 days and freeze-dried to obtain mPEG-g-PAHy.

[0024]

[0025] (where n+m=200, n / (n+m)×100%=6%)

[0026] Dissolve 25 mg of graft copolymer in 12 mL of distilled water, adjust the pH value to 3.5 with acetic acid solution, dissolve 50 mg of small interfering RNA in a buffer solution of pH 5.0-8.0, add the small interfering RNA solution dropwise to the grafted solution under stirring at room temperature The branch copolymer solution was stirred for 15 minutes, and the polyion complex drug-loaded micelles were obt...

Embodiment 2

[0028] Weigh 1.367g PAHy and dissolve it in distilled water, add 8g mPEG-CHO, adjust the pH value of the reaction medium to 6 with 10% acetic acid solution, stir at room temperature for 24h, add 1.06g NaBH 3 CN, adjust the pH value to 6 with 10% acetic acid solution again, and react at room temperature for 48h. The reaction solution was dialyzed for 3 days and freeze-dried to obtain mPEG-g-PAHy.

[0029]

[0030] (where n+m=250, n / (n+m)×100%=12%)

[0031]Dissolve 25 mg of graft copolymer in 12 mL of distilled water, adjust the pH value to 3.5 with acetic acid solution, dissolve 50 mg of small interfering RNA in a buffer solution of pH 5.0-8.0, add the small interfering RNA solution dropwise to the grafted solution under stirring at room temperature The branch copolymer solution was stirred for 15 minutes, and the polyion complex drug-loaded micelles were obtained after freeze-drying. Measure its particle diameter and distribution with dynamic light scattering method, the ...

Embodiment 3

[0033] Weigh 1.367g PAHy and dissolve it in 30mL distilled water, add 12g mPEG-CHO, adjust the pH value of the reaction medium to 6 with 10% acetic acid solution, stir at room temperature for 24h, add NaBH 3 CN1.59g, adjust the pH value to 6 with 10% acetic acid solution again, and react at room temperature for 48h. The reaction solution was dialyzed for 3 days and freeze-dried to obtain mPEG-g-PAHy.

[0034]

[0035] (where n+m=300, n / (n+m)×100%=18%)

[0036] Dissolve 0.025g graft copolymer in 12mL distilled water, adjust the pH value to 3.5 with acetic acid solution, dissolve 50mg small interfering RNA in pH5.0-8.0 buffer solution, add the small interfering RNA solution dropwise under stirring at room temperature Stir in the graft copolymer solution for 15 minutes, and freeze-dry to obtain the drug-loaded micelles of the polyion complex. Measure its particle diameter and distribution with dynamic light scattering method, the average particle diameter (intensity diameter...

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Abstract

The invention provides a polyion composition micelle medicine carrying material. In the material, the molecular weight of the polymer is controllable, thus the size, the medicine carrying quantity and the medicine releasing speed of the micelle are controllable, so that the invention provides a base for the research in medicine controlled-release carriers. The medicine carrying material is graft copolymer polyethylene glycol-graft-poly radix asparagi hydrazide formed by modifying radix asparagi hydrazide through single methyl ether polyethylene glycol (see the structural formula); in the structure of the polyethylene glycol-graft-poly radix asparagi hydrazide, n plus m is between 200 and 400. The whole preparation process of the micelle is very simple and easy for mass production. The polyion composition micelle medicine carrying material can be applied to the preparation of polyion composition micelles used for the intravascular injection or the intramuscular injection of albumen polypeptide drugs or nucleic acid drugs with negative charges.

Description

technical field [0001] The invention belongs to the technical field of medicine, relates to a polyion complex micellar drug-loaded material and its preparation method and application, in particular to the use of copolymer polyethylene glycol-graft-polyaspartic acid hydrazide (mPEG-g-PAHy ) with positively charged characteristics and negatively charged nucleic acid drugs to form a polyion complex micelle drug-loading system and its preparation method and application, and also relates to the preparation method of the copolymer. Background technique [0002] As a new drug delivery system, polyion complex micelles (PIC) have received extensive attention in recent years. The micelles are nanoparticles that are spontaneously assembled in aqueous solution by some block copolymers or graft copolymers with hydrophilic segments and charged segments and drugs. The reason for the formation of micelles is that the The charged drug is electrostatically combined with the oppositely charge...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/34
Inventor 姜同英王思玲刘佳
Owner SHENYANG PHARMA UNIVERSITY
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