阅读说明：本技术 一种涂层支架及其制备方法 (Coated stent and preparation method thereof ) 是由 成立萍 赵振心 于 2021-08-25 设计创作，主要内容包括：本发明公开了一种涂层支架及其制备方法,该涂层支架呈网状结构,构成网状结构的部件由三层结构组成,内层为支架层、中间层为抗凝血改性层、最外层为纳米短肽涂层；该涂层支架不仅能抗凝血,起到防止血栓的作用,而且能够促进血管细胞的快速内皮化,能有效的促进血管病变区域的细胞再生；且整个生产工艺简单、对环境无污染、成本低。(The invention discloses a coating bracket and a preparation method thereof, wherein the coating bracket is of a net structure, and a component forming the net structure consists of three layers of structures, wherein the inner layer is a bracket layer, the middle layer is an anticoagulation modified layer, and the outermost layer is a nano short peptide coating; the coating stent not only has anticoagulation and has the function of preventing thrombus, but also can promote the rapid endothelialization of blood vessel cells and effectively promote the cell regeneration of a blood vessel pathological change area; and the whole production process is simple, has no pollution to the environment and has low cost.)

1. A coated stent (1) in the form of a mesh (2) characterized by: the components of the net structure consist of three layers, wherein the inner layer is a bracket layer (3), the middle layer is an anticoagulation modified layer (4), and the outermost layer is a nano short peptide coating (5); the nano short peptide coating is in discontinuous arrangement; the preparation method of the coating bracket comprises the following specific steps:

processing the bracket: the bracket can be woven by a knitting machine or cut by tubular materials;

plasma deposition construction of stent surface modification: and (3) performing oxygen plasma glow discharge treatment on the processed bracket: the discharge power is 20-300W, the treatment time is 2-30min, and the oxygen flow is 100 ml/min-800 ml/min; reacting the oxygen-treated stent with a polyol or a substance containing a carboxylic acid functional group; and (3) continuing to perform carboxyl activation treatment after the reaction is finished: finally, the activated stent is subjected to plasma deposition modification of anticoagulant substances: the plasma deposition temperature is 10-180 ℃, the glow discharge deposition time is 2-45min, and the discharge power is 50-300W;

short peptide coating: and continuously carrying out discontinuous spraying on the surface modified anticoagulant modified layer to ensure that the short peptide reacts with part of the anticoagulant coating by utilizing a covalent bond.

2. The coated stent of claim 1 wherein: the inner layer of the coating support network structure is composed of metal or polymer wires with the diameter of 0.01 mm-0.60 mm; the diameter of the coating support is 1.0-30.0 mm.

3. The coated stent of claim 1 characterized by: the anticoagulation modified layer is one or a mixture of more of heparin, polyethylene glycol, phosphorylcholine, hydroxyethyl cellulose, chitosan and derivatives thereof, and albumin.

4. The coated stent of claim 1 wherein: the nano short peptide coating is one or a mixture of several of nano short peptides RGD, YIGSR, REDV, CAG and SVVYGLR which can promote the regeneration of the vascular intima.

5. The coated stent of claim 1 wherein said anticoagulant modified layer has a thickness of no greater than 200 nm.

6. The coated stent of claim 1, wherein the nano-short peptide coating has a thickness of 10 to 200 nm.

Technical Field

The invention belongs to the technical field of medical instruments, and particularly relates to a coated stent and a preparation method thereof.

Background

With the development of economic technology, the living standard of people is higher and higher, the change of life style of people leads to the very frequent occurrence of cardiovascular and cerebrovascular diseases, and the cardiovascular diseases are the leading factors of human death in the present and the later quite long time. The current main treatment means for cardiovascular diseases include drug treatment, surgical treatment, interventional therapy and the like. The intravascular stent intervention is one of the common methods for clinically dealing with cardiovascular diseases at present due to the characteristics of small wound, obvious immediate effect after operation, long-time effect after operation and the like. In the development and use process of more than 30 years, the vascular stent is subjected to drug eluting stents, fully degradable stents and various novel functional stents by the original percutaneous balloon angioplasty. However, despite the change, the current vascular stents still face the problems of restenosis and late thrombosis after implantation, and the research on the surface modification of the vascular stent is repeated.

Generally, the cardiovascular stent is made of stainless steel, titanium and its alloy, NiTi alloy and other materials, but these materials have poor blood compatibility, and easily cause thrombosis after implantation, thereby causing a greater risk; meanwhile, with the development of modern medical technology, the promotion of the rapid growth of cardiovascular endothelial cells has become the gold standard for treating cardiovascular diseases.

Therefore, the stent coating is designed to realize the combination of the anticoagulation performance and the bioactive functional molecules, on one hand, the anticoagulation performance of the stent can be met, on the other hand, the bioactivity of the bioactive molecules can be maintained, the rapid endothelialization of blood vessel cells is promoted, and the stent coating has great significance for further improving the stent curative effect, reducing complications and improving the life quality of patients.

Disclosure of Invention

The invention aims to overcome the defects in the prior art and provide a coated stent which has good antithrombotic and cardiovascular stent endothelialization promoting performances in interventional therapy. The preparation process is simple, low in cost and suitable for automatic production. Greatly improving the production efficiency and the economic cost.

In order to achieve the purpose, the technical scheme of the invention is to provide a coating stent which is in a net structure, wherein the net structure forming part is composed of three layers, the inner layer is a stent layer, the middle layer is an anticoagulation modified layer, the outermost layer is a nano short peptide coating, and the nano short peptide coating is discontinuously arranged; the preparation method of the coating bracket comprises the following specific steps:

(1) processing the bracket: the bracket can be woven by a knitting machine or cut by tubular materials;

(2) plasma deposition construction of stent surface modification: and (3) performing oxygen plasma glow discharge treatment on the processed bracket: the discharge power is 20-300W, the treatment time range is 2-45min, and the oxygen flow is 100 ml/min-800 ml/min; reacting the oxygen-treated stent with a polyol or a substance containing a carboxylic acid functional group; and (3) continuing to perform carboxyl activation treatment after the reaction is finished: finally, the activated stent is subjected to plasma deposition modification of anticoagulant substances: the plasma deposition temperature is 10-180 ℃, the glow discharge deposition time is 2-60 min, and the discharge power is 50-300W;

(3) short peptide coating: and continuously carrying out discontinuous spraying on the surface modified anticoagulant modified layer to ensure that the short peptide reacts with part of the anticoagulant coating by utilizing a covalent bond.

Further, the inner layer of the support network structure is composed of metal or polymer wires with the diameter of 0.01 mm-0.08 mm; the diameter of the coating support is 1.0-30.0 mm.

Furthermore, the anticoagulation modified layer is one or a mixture of more of heparin, polyethylene glycol, phosphorylcholine, hydroxyethyl cellulose, chitosan and derivatives thereof, and albumin.

Furthermore, the nano short peptide coating is one or a mixture of several of nano short peptides RGD, YIGSR, REDV, CAG, SVVYGLR and RADA-16 which can promote the regeneration of the vascular intima.

Further, the thickness of the anticoagulation modified layer is not more than 200 nm; the thickness of the nano short peptide coating is 10-200 nm.

Compared with the prior art, the invention has the following beneficial effects: the coating stent not only has anticoagulation and has the function of preventing thrombus, but also can promote the rapid endothelialization of blood vessel cells and effectively promote the cell regeneration of a blood vessel pathological change area; and the whole production process is simple, has no pollution to the environment and has low cost.

Drawings

FIG. 1 is a schematic view of the structure of the coated stent of the present invention.

FIG. 2 is a schematic structural view of the coated stent of the present invention in a final released state in a diseased region.

FIG. 3 is a schematic view of the axial structure of the wire of the coated stent of the present invention.

FIG. 4 is a cross-sectional view of a radial cross-section of a coated stent wire according to the invention

Detailed Description

In order to make the aforementioned objects, features and advantages of the present invention comprehensible, embodiments accompanied with figures are described in detail below. In describing the embodiments of the present invention in detail, the drawings are not necessarily to scale, and the drawings are not intended to limit the invention.

Example 1

As shown in fig. 1, 2 and 3, the coating stent of the invention is in a network structure, the components of the network structure consist of three layers, the inner layer is a stent layer, the middle layer is an anticoagulation modified layer, and the outermost layer is a nano short peptide coating; the inner layer of the support network structure is composed of metal or polymer wires with the diameter of 0.01 mm; the diameter of the coating bracket is 3.0 mm.

As shown in fig. 3 and 4, the coating stent of the present invention is composed of three layers, wherein the middle layer is an anticoagulation modification layer, and the anticoagulation modification layer is one or a mixture of several of heparin, polyethylene glycol, phosphorylcholine, hydroxyethyl cellulose, chitosan and its derivatives, and albumin; the thickness of the anticoagulation modified layer is 10 nm. The nano short peptide coating is one or a mixture of several of nano short peptides RGD, YIGSR, REDV, CAG, SVVYGLR and RADA-16 which can promote the regeneration of the vascular intima. The thickness of the nano short peptide coating is 20 nm.

The coated stent of the present invention is used in combination with an introducer sheath, a delivery guidewire, a microcatheter, a guiding catheter, etc., all of which are well known to those skilled in the art.

The coating stent has contractility, is shrunk and fixed in the micro catheter in a delivery state, and has the appearance shown in figure 1 in a free release state; and the release state in the vessel of the lesion area is shown in fig. 2; the stent is accurately placed in a diseased region under the influence of a developing point, wherein an anticoagulation modified layer in the middle layer can effectively prevent thrombosis of cerebral arterial vessel walls at an aneurysm; the outer layer of nano short peptide layer which is distributed without segments can well promote the growth of endothelial cells of the vascular wall.

Example 2

The coated stent shown in fig. 1 was prepared by the following process: the support network structure is woven by a warp knitting machine; firstly, performing oxygen plasma glow discharge treatment on the processed stent network structure: the discharge power is 100W, the treatment time is 30min, and the oxygen flow is 500 ml/min; reacting the oxygen-treated stent with dicarboxylic acid polyethylene glycol; and (3) after the reaction is finished, continuously performing carboxyl activation treatment by using N-hydroxysuccinimide and carbodiimide hydrochloride: and then carrying out plasma deposition modification on the activated stent by using an anticoagulant substance phosphorylcholine: the plasma deposition temperature is 70 ℃, the glow discharge deposition time is 45min, and the discharge power is 300W. And finally, continuously carrying out discontinuous spraying on the short peptide RGD on the surface modified anticoagulant modified layer, so that the short peptide RGD reacts with a part of anticoagulant coating by utilizing a covalent bond.

Example 3

The coated stent shown in fig. 1 was prepared by the following process: the stent network structure is formed by cutting a nickel-titanium tube; firstly, performing oxygen plasma glow discharge treatment on the processed stent network structure: the discharge power is 20W, the treatment time is 30min, and the oxygen flow is 100 ml/min; reacting the support subjected to the oxygen treatment with polyacrylic acid; and (3) after the reaction is finished, continuously performing carboxyl activation treatment by using N-hydroxysuccinimide and carbodiimide hydrochloride: and then the activated stent is subjected to plasma deposition modification of anticoagulant substance heparin: the plasma deposition temperature is 105 ℃, the glow discharge deposition time is 20min, and the discharge power is 200W. And finally, continuously carrying out discontinuous spraying on the short peptide RADA-16 on the surface modified anticoagulant modified layer, so that the short peptide RADA-16 reacts with a part of the anticoagulant coating by utilizing a covalent bond.

The above description is only for the purpose of describing the preferred embodiments of the present invention, and is not intended to limit the scope of the present invention, and any variations and modifications made by those skilled in the art based on the above disclosure are within the scope of the appended claims.