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Dual functional polymer nanometer glue bunch and preparing method and application in preparing medicine for treating second narrow blood vessel

A nano-micelle and polymer technology, applied in the preparation of drugs for the treatment of vascular restenosis, bifunctional polymer nano-micelle and its preparation field, can solve the problem of short retention time, lack of tissue and organ targeting, and drug /Problems such as low bioavailability of gene nanoparticles to achieve high-efficiency treatment, best therapeutic effect, and improved bioavailability

Inactive Publication Date: 2008-07-23
INST OF BIOMEDICAL ENG CHINESE ACAD OF MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, this technology has the disadvantages of low bioavailability of drug / gene nanoparticles, short retention time in blood circulation, and lack of tissue and organ targeting.

Method used

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  • Dual functional polymer nanometer glue bunch and preparing method and application in preparing medicine for treating second narrow blood vessel

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] A kind of bifunctional polymer nanomicelle is made by following method:

[0037] (1) Mix PLGA / PEG and GPIIb / IIIa with a molar ratio of 1:1, and react for 18 hours at 35° C. under the catalysis of DCC, so that GPIIb / IIIa is connected to PLGA / PEG through an amide bond, and the DCC and The molar ratio of PLGA / PEG is 0.01:1; the amount of binding target molecules is monitored by titration method; NMR, mass spectrometry, infrared and elemental analysis, GPC and other means are used to verify the reaction degree and yield of each step of the reaction, and the purity of the product , the degree of substitution of the terminal group, the content of the terminal amino group, etc. Using surface infrared spectroscopy and multifunctional electron spectroscopy (XPS) to measure the surface functional group content of nanomicelles, thereby determining the surface GPIIb / IIIa content;

[0038] (2) the aqueous solution of the acidic fibroblast growth factor that concentration is 1mg / ml ...

Embodiment 2

[0042] A kind of bifunctional polymer nanomicelle is made by following method:

[0043](1) Mix PLA / PEG with a molar ratio of 1:1.5 and GPIIb / IIIa, and react for 48 hours at 30° C. under the catalysis of DCC, so that GPIIb / IIIa is connected to PLA / PEG through an amide bond, and the DCC and The molar ratio of PLA / PEG is 0.001:1;

[0044] (2) the aqueous solution of basic fibroblast growth factor that concentration is 0.001mg / ml is injected into the acetone solution of the product prepared in step (1) that concentration is 1000mg / ml by volume ratio, mixes 2 hours , into a homogeneous suspension;

[0045] (3) adding the acetone solution of the product prepared in step (1) with a concentration of 1000 mg / ml into the acetone solution of paclitaxel with a concentration of 10 mg / ml in a ratio of 1:50 by volume;

[0046] (4) Add the solution prepared in step (3) to the homogeneous suspension prepared in step (2) according to the specific volume ratio of 5:1, stir for 6 hours, and dia...

Embodiment 3

[0048] A kind of bifunctional polymer nanomicelle is made by following method:

[0049] (1) Mix PGA / PEG and GPIIb / IIIa with a molar ratio of 1:5, catalyzed by DCC, react for 4 hours at 37° C., so that GPIIb / IIIa is connected to PGA / PEG through an amide bond, and the DCC and The molar ratio of PGA / PEG is 0.05: 1;

[0050] (2) the aqueous solution of the epidermal growth factor that concentration is 100mg / ml is injected into the dichloromethane solution that concentration is the product that step (1) prepares of 0.01mg / ml by volume ratio, mix 1 hour, into a homogeneous suspension;

[0051] (3) the dichloromethane solution of the product prepared by the step (1) that the concentration is 100mg / ml is added to the dichloromethane solution of the matrix metalloproteinase inhibitor with a concentration of 100mg / ml in a ratio of 1: 20 by volume middle;

[0052] (4) According to the specific volume ratio of 50~0.1:1, the solution prepared in step (3) was added to the homogeneous sus...

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Abstract

The invention discloses a difunctional polymer nano-micelle, a preparation thereof and application in preparing a therapeutic drug for restenosis thereof. The difunctional polymer nano-micelle is prepared by the steps: (1) GPIIb / IIIa is connected on an amphiphilic block copolymer through amide linkage; (2) aqueous solution of the drug that improves vascular endothelial growth is injected into chloroform solution of the product prepared in step one to form even suspension; (3) the chloroform solution of the product prepared in step one is added into the chloroform solution of a drug inhibiting the proliferation of smooth muscle cells; (4) the solution prepared in step three is added into the even suspension prepared in step two, and then stirred and dried to form the difunctional polymer nano-micelle. The surface of the micelle is chemically coupled with platerlet membrane glocoprotein (GPIIb / IIIa) so as to really and specifically target the difunctional polymer nano-micelle to the hemadostenosis parts and provide a guarantee for directly acting the drug on lesion locations.

Description

technical field [0001] The invention relates to a polymer nanomicelle, its preparation method and application, in particular to a bifunctional polymer nanomicelle, its preparation method and its application in the preparation of medicaments for treating vascular restenosis. Background technique [0002] A survey and analysis of the causes of death in my country shows that in recent years, cardiovascular diseases accounted for 40% of the deaths among Chinese people. That is to say, one out of every three deaths was caused by cardiovascular Vascular disease. Cardiovascular disease has become an important killer that endangers the health of Chinese people. Therefore, the prevention and treatment of such diseases is extremely urgent. [0003] With the help of balloon dilation, the drug-loaded and gene nanoparticles are delivered to the damaged blood vessel site, and the treatment of restenosis has a significant effect. Moreover, the method is also applicable to diabetic blood ...

Claims

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Application Information

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IPC IPC(8): A61K9/00A61K47/48A61K38/18C08G81/00A61P9/10A61K31/405A61K31/41A61K31/155A61K31/337A61K31/436A61K31/4439A61K35/60A61K38/55A61K47/59A61K47/60
Inventor 杨菁宋存先
Owner INST OF BIOMEDICAL ENG CHINESE ACAD OF MEDICAL SCI
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