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Anticoagulant coating composition as well as preparation method and application thereof

A coating composition and anticoagulant technology, applied in the field of biomedical materials, can solve the problems of long-lasting anticoagulant effect, decreased anticoagulant activity of heparin, weakened anticoagulant activity, etc.

Active Publication Date: 2021-09-14
HEALTH GUARD (SUZHOU) BIOMED TECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the current heparin coating technology still has some problems, such as low stability, short anticoagulant time, and complicated preparation process.
[0003] Chinese patent CN 104902884 A provides a polyvinylpyrrolidone-quaternary ammonium salt heparin compound (PVP-QUAT) coating method. In this method, PVP is firstly coated on the surface of the substrate as a primer, followed by a QUAT layer, synergistically The non-coagulation effect of PVP and the anti-coagulation effect of QUAT are used to achieve the purpose of anti-coagulation of the substrate. However, the heparin coating of this kind of physical coating has poor stability and is easy to fall off. At the same time, the small molecule long-chain quaternary ammonium salt and heparin The formed complex is easily dissociated under physiological conditions due to the interference of various factors such as salt ions, and the anticoagulation time is short
[0004] Chinese patent CN 110665071 A discloses an organosilicon quaternary ammonium salt-heparin electrostatic self-assembled compound, because the organosilicon can be firmly bonded to the surface of the substrate containing a large number of hydroxyl groups, thus reducing the quaternary ammonium salt-heparin complex to a certain extent. However, in essence, its heparin is only adsorbed to the surface of the substrate through physical charge, and it is easy to desorb under physiological conditions or in the presence of salt ions, which leads to its ineffective anticoagulant effect. will last
[0005] Chinese patent CN1448144A and Chinese patent 200910069886.4 use acrylate monomers and glutaraldehyde and other cross-linking treatments to improve the stability of the coating, but the residual problems of toxic monomers and cross-linking agents are still difficult to solve. At the same time, there is also the risk that the coating will not be firmly bonded to the substrate and will fall off
[0006] In Chinese patent CN 110776610 A, antimicrobial polyguanidine molecules and anticoagulant heparin molecules are respectively methacrylated by chemical modification, and then the antimicrobial / anticoagulant molecules are formed by free radical polymerization after combining the two molecules The blood composition coating is finally applied to the surface of the substrate by high temperature curing or ultraviolet curing, which improves the stability of the coating. However, chemical modification of heparin will inevitably lead to weakening of its anticoagulant activity. At the same time, the high temperature conditions used in the subsequent free radical polymerization and the subsequent high temperature curing or UV curing will also cause the decline of the anticoagulant activity of heparin to varying degrees.

Method used

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  • Anticoagulant coating composition as well as preparation method and application thereof
  • Anticoagulant coating composition as well as preparation method and application thereof
  • Anticoagulant coating composition as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0041] Preparation of functional polyether long-chain quaternary ammonium salt polymer materials:

[0042] Preparation of polymer precursor: MeBr 4 Ox monomer (0.1 mol), MeAE 12 Ox (0.2 mol), Catalyst BF 3 •Et 2 O (4.1 mmol), the initiator pentaerythritol (1.0 mmol) was dissolved in anhydrous dichloromethane, reacted in an ice bath for 24 hours, after the reaction was completed, it was washed with acid, salt, and water, and the solvent was removed by rotary evaporation. Vacuum dried for 48h to obtain P[(MeBr 4 Ox)- co -( MeAE 12 Ox)] polymer precursor, yield 90%;

[0043]Preparation of functional polyether long-chain quaternary ammonium salt polymer material: the P[(MeBr obtained above 4 Ox)- co -(MeAE 12 Ox)] Add the polymer precursor to anhydrous acetonitrile solvent, then add N, N-dimethyl octadecylamine (42.7g, 0.2mol), reflux under nitrogen environment for 15h, after the reaction is completed, refine and purify by high vacuum vacuum distillation Discharging to...

Embodiment 2

[0048] Preparation of functional polyether long-chain quaternary ammonium salt polymer solution: Dissolve 20g of functional polyether long-chain quaternary ammonium salt polymer material in 100mL water to prepare 20% (w / v) functional polyether long-chain quaternary ammonium salt Salt polymer solution;

[0049] Prepare heparin sodium solution: dissolve 10g heparin sodium in 100mL water to prepare 10% (w / v) heparin sodium solution;

[0050] Preparation of functional polyether long-chain quaternary ammonium salt polymer-heparin composition: under stirring conditions, add the functional polyether long-chain quaternary ammonium salt polymer solution dropwise to 10% under stirring conditions (w / v) concentration of heparin sodium solution, a white precipitate of the composition was obtained; then the white precipitate was separated by suction filtration, washed with water three times, and finally the white precipitate was vacuum-dried for 24 hours to obtain a functional polyether lon...

Embodiment 3

[0052] Preparation of functional polyether long-chain quaternary ammonium salt polymer solution: Dissolve 50g of functional polyether long-chain quaternary ammonium salt polymer material in 100mL water to prepare 50% (w / v) functional polyether long-chain quaternary ammonium salt Salt polymer solution;

[0053] Prepare heparin sodium solution: dissolve 20g heparin sodium in 100mL water to prepare 20% (w / v) heparin sodium solution;

[0054] Preparation of functional polyether long-chain quaternary ammonium salt polymer-heparin composition: under stirring conditions, add the functional polyether long-chain quaternary ammonium salt polymer solution dropwise to 20% under stirring conditions (w / v) concentration of heparin sodium solution, a white precipitate of the composition was obtained; then the white precipitate was separated by suction filtration, washed with water three times, and finally the white precipitate was vacuum-dried for 24 hours to obtain a functional polyether lon...

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Abstract

The invention relates to an anticoagulant coating composition. The composition is prepared by compounding functional polyether long-chain quaternary ammonium salt macromolecules and heparin or heparin derivatives. The invention further provides a preparation method of the anticoagulant coating composition. The preparation method comprises the following process steps: A, preparing a polymer precursor; B, preparing a functional polyether long-chain quaternary ammonium salt high polymer material; and C, preparing the anticoagulant coating composition, including a, preparing a functional polyether long-chain quaternary ammonium salt polymer solution, b, preparing a heparin sodium solution, and c, preparing the functional polyether long-chain quaternary ammonium salt polymer-heparin composition. The invention further provides application of the anticoagulant coating composition. The composition is applied to a base material or various instruments made of the base material. Compared with the prior art, the composition has the advantages that the performance is firmer and more stable, the anticoagulant effect is greatly prolonged, and polyethylene glycol molecules on the upper side chain of the composition can achieve the effects of buffering and protecting in the contact process of the base material and a blood coagulation matrix, so that the base material also has a lasting anticoagulant effect.

Description

technical field [0001] The invention belongs to the field of biomedical materials, in particular to an anticoagulant coating composition and its preparation method and application. Background technique [0002] Heparin coating technology is a method to improve the blood and biocompatibility of medical equipment. It has been applied to the surfaces of various medical equipment such as extracorporeal circulation devices, vascular stents, and intraocular lenses, and achieved good results. However, the current heparin coating technology still has certain problems, such as low stability, short anticoagulant time, complex preparation process and other limitations. [0003] Chinese patent CN 104902884 A provides a polyvinylpyrrolidone-quaternary ammonium salt heparin compound (PVP-QUAT) coating method. In this method, PVP is firstly coated on the surface of the substrate as a primer, followed by a QUAT layer, synergistically The non-coagulation effect of PVP and the anti-coagulati...

Claims

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Application Information

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IPC IPC(8): A61L33/06A61L33/08A61L33/00A61L31/16A61L31/10C08G65/333
CPCA61L33/0011A61L31/10A61L31/16A61L33/08A61L33/068A61L33/0076C08G65/33306C08G2150/00A61L2300/236A61L2300/606A61L2420/06
Inventor 吴亮亮蔡湫亭刘静范忠鹏
Owner HEALTH GUARD (SUZHOU) BIOMED TECH CO LTD
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