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Preparation method of drug-loaded layer-by-layer self-assembly coating

A layer-by-layer self-assembly and coating technology, applied in the field of biomedical materials, can solve problems such as insufficient environmental responsiveness, sudden release of drug molecules, and insufficient coating stability, achieving good environmental responsiveness and low preparation cost , strong applicability

Inactive Publication Date: 2017-05-24
SOUTHWEST JIAOTONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0002] In recent years, cardiovascular diseases have become a major factor that threatens human health, and the number of deaths worldwide ranks first in human disease deaths every year; clinically, percutaneous coronary intervention has become the main treatment for cardiovascular diseases. In the past 30 years, interventional therapy has also undergone development, from early pure balloon dilatation and bare metal stents to the current drug-eluting vascular stent, and the future degradable vascular stent; in order to avoid clinical application A series of complications associated with bare metal stents and drug-eluting stents, including thrombosis, stent restenosis, inflammatory reactions, etc.; usually various modifications are made on the surface of the stent and drugs are loaded to achieve better therapeutic effects ; At present, it is a commonly used modification method to construct a coating and load drugs on the surface of the stent; however, the currently used modification method does not have sufficient stability due to the high ionic strength under physiological conditions and the pH required for assembly conditions If the value is high, the stability of the coating itself is insufficient; the loaded biomolecules cannot effectively perform biological functions for a long time, and it may also cause the burst release of the assembled drug molecules, and it is difficult to make the coating and the substrate firmly bonded only by electrostatic interaction. The coating may be peeled off from the substrate; in addition, the general coating has no environmental responsiveness, and it is difficult to respond to the stimulation of the lesion. regulation; and the environmental pH response of the currently used modification method is not fast enough

Method used

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Examples

Experimental program
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Effect test

preparation example Construction

[0031] A method for preparing a drug-loaded layer-by-layer self-assembled coating, comprising the following steps:

[0032] A, using dopamine to aminate hyaluronic acid to obtain a modified hyaluronic acid solution;

[0033] B, adopt 3,4-dihydroxyphenyl propionic acid to carry out amination modification to chitosan, obtain modified chitosan solution;

[0034] C. Dissolve dopamine in a tris solution of PH=8.5 to form a mixed solution with a dopamine concentration of 2 mg / mL; immerse the base material in the mixed solution and react at a constant temperature for t 1 Wash the base material after a certain time;

[0035] D. Configure a modified hyaluronic acid solution with a concentration of 2 mg / mL and a pH of 5.5, and dissolve the drug to be loaded to obtain a solution S 1 ; Configure a modified chitosan solution with a concentration of 2mg / mL, and dissolve the drug to be loaded to obtain a solution S 2 ; Immerse the matrix material obtained in step C into solution S 2 midd...

Embodiment 1

[0053]A. Dissolve 1 g of hyaluronic acid in 100 mL of morpholine ethanesulfonic acid solution with a concentration of 0.05 mol / L and pH=5.5; respectively add 300 g of carbodiimide and 288 mg of N-hydroxysuccinimide, mix and react for 1 h; then Add 471 mg of dopamine, adjust the pH of the solution to 5.5, continue the reaction for 12 hours, and then use a dialysis bag with a molecular weight cut-off of 3500 for dialysis for 48 hours, change the liquid every 12 hours to remove dopamine that did not participate in the reaction, and store the obtained dialysate in a freezer at -20°C to obtain the modified Hyaluronic acid solution;

[0054] B. Dissolve 1g of chitosan in 100ml of hydrochloric acid with a concentration of 0.1mol / L; add 488mg of morpholineethanesulfonic acid to adjust the pH of the solution to 5.5; add 1.02g of carbodiimide and 1.338g of N-hydroxysuccinimide respectively After amine and 574mg of 3,4-dihydroxyphenylpropionic acid, adjust the pH of the solution to 5.5 a...

Embodiment 2

[0059] A. Dissolve 1 g of hyaluronic acid in 100 mL of morpholine ethanesulfonic acid solution with a concentration of 0.05 mol / L and pH=5.5; respectively add 300 g of carbodiimide and 288 mg of N-hydroxysuccinimide, mix and react for 1 h; then Add 471 mg of dopamine, adjust the pH of the solution to 5.5, continue the reaction for 12 hours, and then use a dialysis bag with a molecular weight cut-off of 3500 for dialysis for 48 hours, change the liquid every 12 hours to remove dopamine that did not participate in the reaction, and store the obtained dialysate in a freezer at -20°C to obtain the modified Hyaluronic acid solution;

[0060] B. Dissolve 1g of chitosan in 100ml of hydrochloric acid with a concentration of 0.1mol / L; add 488mg of morpholineethanesulfonic acid to adjust the pH of the solution to 5.5; add 1.02g of carbodiimide and 1.338g of N-hydroxysuccinimide respectively After amine and 574mg of 3,4-dihydroxyphenylpropionic acid, adjust the pH of the solution to 5.5 ...

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PUM

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Abstract

The invention discloses a preparation method of a drug-loaded layer-by-layer self-assembly coating. The preparation method comprises the following steps: A, performing aminating modification on hyaluronic acid by using dopamine; B, performing aminating modification on chitosan by using 3,4-dihydroxyl phenylpropionic acid; C, dissolving the dopamine in a trimethylol aminomethane solution with a PH value of 8.5 to form a mixed solution with dopamine concentration of 2mg / mL; soaking a matrix material in the mixed solution, reacting for time of t1 at a constant temperature, and washing the matrix material; D, preparing a modified hyaluronic acid solution with concentration of 2mg / mL and a PH value of 5.5, and dissolving a loaded drug into the modified hyaluronic acid solution to obtain a solution S1; preparing a modified chitosan solution with concentration of 2mg / mL, and dissolving the loaded drug to obtain a solution S2; soaking the matrix material obtained in step C into the solution S2 for a time of t2; then soaking in the solution S1 for a time of t3; and E, repeating the step D. The drug-loaded layer-by-layer self-assembly coating has good PH response and stability and is suitable for the matrix materials of any shapes; and moreover, the preparation method has the advantages of simple operation, simpleness of needed equipment, low preparation cost and high applicability.

Description

technical field [0001] The invention relates to the field of biomedical materials, in particular to a method for preparing a drug-loaded layer-by-layer self-assembled coating. Background technique [0002] In recent years, cardiovascular diseases have become a major factor that threatens human health, and the number of deaths worldwide ranks first in human disease deaths every year; clinically, percutaneous coronary intervention has become the main treatment for cardiovascular diseases. In the past 30 years, interventional therapy has also undergone development, from early pure balloon dilatation and bare metal stents to the current drug-eluting vascular stent, and the future degradable vascular stent; in order to avoid clinical application A series of complications associated with bare metal stents and drug-eluting stents, including thrombosis, stent restenosis, inflammatory reactions, etc.; usually various modifications are made on the surface of the stent and drugs are lo...

Claims

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Application Information

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IPC IPC(8): A61L31/10A61L31/16
CPCA61L31/10A61L31/16A61L2300/216A61L2300/606A61L2420/02A61L2420/06
Inventor 赵安莎王浩浩黄楠杨苹
Owner SOUTHWEST JIAOTONG UNIV
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