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Anti-coagulation hydrogel material for inducing NO release as well as preparation method and application thereof

A gel material and hydrogel technology, applied in anticoagulant treatment, gel preparation, colloid chemistry, etc. Repair the limited ability and other problems, achieve excellent coagulation performance, improve anticoagulation performance, and achieve remarkable results

Pending Publication Date: 2021-09-03
HUAIYIN INSTITUTE OF TECHNOLOGY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, metal implantation / interventional devices (such as vascular stents) are commonly used clinically, but their biocompatibility has not yet met the ideal requirements. For example, late thrombosis and restenosis after stent implantation seriously affect its clinical treatment effect
Although drug-eluting stents based on polymer materials have played a positive role in the treatment of stenotic cardiovascular diseases, their effects are still poor, mainly because the anti-proliferative drugs released by drug carriers play an important role in inhibiting neointimal hyperplasia. At the same time, it also inhibits the growth of vascular endothelial cells. The carrier material itself does not have the effect of anticoagulant and promoting endothelial repair, and it is easy to cause clinical complications such as late thrombosis. Functional layer is currently an effective means to improve the biocompatibility and clinical performance of materials
[0004] Six-armed polyethylene glycol is a synthetic high molecular polymer with good biocompatibility, which is widely used in the fields of biomaterials and tissue engineering, and has potential applications in the surface coating of artificial blood vessels and vascular stents, but Its anticoagulant properties need to be improved, and its ability to promote vascular endothelial repair is limited due to its excellent anti-biofouling ability and ability to prevent protein adsorption
In the prior art and reports, although there are reports on the combined application of heparin and selenocystamine to promote vascular endothelial repair, most of them are used for surface graft modification of materials, and selenocystamine is introduced into heparin-modified six-arm Polyethylene glycol materials, thus preparing hydrogel materials with the ability to promote endothelial repair, has not yet been reported

Method used

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  • Anti-coagulation hydrogel material for inducing NO release as well as preparation method and application thereof
  • Anti-coagulation hydrogel material for inducing NO release as well as preparation method and application thereof
  • Anti-coagulation hydrogel material for inducing NO release as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] Example 1 Preparation of anticoagulant hydrogel materials that induce NO release

[0035](1) Graft heparin molecules at the end of six-armed polyethylene glycol to obtain an anticoagulant hydrogel material: in a 100mL single-mouth bottle, add 50mL of tetrahydrofuran solution, then add 10g of six-armed polyethylene glycol, fully Dissolve for 1h. Add 1 g of heparin and continue stirring for 10 min, then add 0.03 g of 4-dimethylaminopyridine (DMAP) and 0.2 g of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) , treated in ice bath for 30 minutes, then stirred and reacted at room temperature for 12 hours, and then 50 mL of ice ethanol was added to produce precipitation after rotary evaporation to remove excess water, filtered by suction, and then dried in a vacuum drying oven to obtain heparin-modified six-armed polyethylene glycol hydrogel glue material.

[0036] (2) Graft selenocystamine on the heparin molecule to obtain an anticoagulant hydrogel materi...

Embodiment 2

[0038] The anticoagulant hydrogel material that induces NO release obtained in Example 1 was dissolved in tetrahydrofuran solution to obtain a 10 mg / ml solution, which was prepared into a thin film material by solvent evaporation, and then the thin film material was subjected to infrared spectroscopy at normal temperature. The measuring range is 4000-400cm -1 , the result is as figure 1 as shown, figure 1 It is the infrared spectrogram of the anticoagulant hydrogel material, composed of figure 1 It can be seen that the wavelength of 3480cm -1 There is a broad hydroxyl absorption peak at a wavelength of 2910cm -1 and wavelength 2880cm -1 There are obvious methyl and methylene absorption peaks at a wavelength of 1650cm -1 and a wavelength of 1475cm -1 The absorption peak at is the absorption peak of the amide bond or the absorption peak of the ester group, and the wavelength is 1100cm -1 A strong absorption peak of the C-O group (mainly produced by the C-O in the PEG stru...

Embodiment 3

[0040] The anticoagulant hydrogel material that induced NO release obtained in Example 1 was fully dissolved in tetrahydrofuran solution to form a 20 mg / mL solution, and the hydrogel film material was obtained by solvent evaporation. In the absence of NO donor and the addition of 20 uL of NO donor (10 μM nitrosoglutathione and glutathione), polystyrene was used as the control material to conduct platelet adhesion experiments in vitro. Fresh human whole blood (provided by Huai'an Second People's Hospital) was centrifuged at 1500rpm for 15min to obtain platelet-rich plasma. 200 µL of platelet-rich plasma was dropped on each sample surface to cover the entire surface. After incubation at 37° C. for 2 h, the samples were washed with 0.1 M PBS buffer (pH=7.4). The adhered platelets were fixed with 2.5% glutaraldehyde in PBS solution for 24h, and then washed with PBS buffer. Then use 30%, 50%, 75%, 90%, 100% ethanol solution to dehydrate successively, each time for 10min, after de...

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PUM

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Abstract

The invention discloses an anti-coagulation hydrogel material capable of inducing NO release as well as a preparation method and application thereof. The anti-coagulation hydrogel material capable of inducing NO release is obtained by that heparin is grafted to the tail end of six-arm polyethylene glycol to obtain the anti-coagulation hydrogel material, then selenocystamine is further grafted to heparin molecules to obtain the anticoagulant hydrogel material capable of inducing NO release. Therefore, the anticoagulant hydrogel material for inducing NO release is obtained. The anticoagulant hydrogel material for inducing NO release prepared by the method disclosed by the invention has excellent water absorption performance, the hydrogel material has good anticoagulant performance due to introduced heparin molecules, and grafted selenocystamine can catalyze an endogenous NO donor in blood to release NO molecules, so that the effect of promoting vascular endothelial repair is achieved.

Description

technical field [0001] The invention relates to an anticoagulant hydrogel material capable of inducing NO release, its preparation method and application, and belongs to the field of biomedical polymer materials. Background technique [0002] Cardiovascular and cerebrovascular diseases are still the leading cause of death in the world. For completely occluded vascular diseases, the use of autologous arterial or venous grafts for bypass surgery, or complete replacement of occluded vessels to restore blood supply, is a commonly used clinical treatment However, due to the limited source of autologous blood vessels and the possibility of new trauma, its clinical application is greatly limited. Therefore, the use of artificial vascular grafts to replace occluded blood vessels has always been a research hotspot and difficulty in the treatment of cardiovascular diseases. Currently applied synthetic vascular grafts (such as expanded PTFE, Dacron, etc.) show satisfactory long-term pe...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61L27/20A61L27/18A61L27/50A61L27/52A61L27/54A61L33/10A61L33/06A61L33/00B01J13/00C08G81/00
CPCA61L27/20A61L27/18A61L27/507A61L27/52A61L27/54A61L33/08A61L33/068A61L33/0088A61L33/0064B01J13/0065C08G81/00A61L2300/42A61L2300/236C08L5/10C08L71/02
Inventor 潘长江龚韬张秋阳杨敏慧洪清香柳森
Owner HUAIYIN INSTITUTE OF TECHNOLOGY
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