CN112402080A

CN112402080A - Full-coated degradable carotid artery stent and preparation method thereof

Info

Publication number: CN112402080A
Application number: CN202011265511.8A
Authority: CN
Inventors: 赵古田; 倪中华; 田原; 程洁
Original assignee: Southeast University
Current assignee: Beijing Haoyan Dingye Technology Co.,Ltd.
Priority date: 2020-11-13
Filing date: 2020-11-13
Publication date: 2021-02-26

Abstract

The invention provides a full-coated degradable carotid artery stent and a preparation method thereof, wherein the full-coated degradable carotid artery stent comprises a stent body, a film positioned at the cross section of the inner diameter of the stent body, and a coating positioned at the middle reticular pore part of the stent body and the outer side of the outer diameter, and the stent body is completely coated by the film and the coating to form a closed hollow circular tubular structure with uniform thickness. The preparation method of the full-coated degradable carotid artery stent comprises the following steps: wrapping a Teflon film on a mandrel; coating a film on the Teflon film; sleeving the support body on the thin film; forming a coating on the stent body; and taking down the full-coated degradable carotid artery stent from the mandrel after high-temperature treatment, and removing the Teflon film. The elastic body is fully coated on the stent body, so that the plastic deformation of the stent after being pressed, held and expanded can be reduced, the wall-adhering capability of the stent is improved, and the curative effect on carotid stenosis is improved.

Description

Full-coated degradable carotid artery stent and preparation method thereof

Technical Field

The invention belongs to the field of implanted medical instruments, and particularly relates to a full-coated degradable carotid artery stent and a preparation method thereof.

Background

Carotid stenosis is a common neurosurgical disease with complex and diverse etiologies, and specifically includes atherosclerosis, carotid artery interlayer, vascular lesions associated with inflammation or autoimmunity, and the like. Carotid stenosis can cause a series of ischemic symptoms such as dizziness, disturbance of consciousness, speech disorder and incapability of understanding speech of other people, and is easy to induce stroke, and even serious people can die. The carotid artery stent is a stent implanted in the carotid artery for relieving obstruction of the carotid artery. At present, carotid artery stent implantation becomes one of important technologies for treating carotid stenosis, can effectively relieve carotid obstruction, improves the life quality of patients, and has the advantages of easy operation, small wound and the like. The traditional carotid artery stent is prepared by non-degradable metal materials. The nondegradable metal carotid artery stent has poor histocompatibility, is very easy to cause smooth muscle cell proliferation, has high restenosis rate after implantation, needs repeated treatment, and seriously limits the clinical application range of the stent.

In recent years, with the wide application of biodegradable materials in the field of implanted medical devices, a novel concept of degradable carotid stents has emerged. Compare in traditional non-degradable metal carotid artery support, degradable carotid artery support has following unique advantage: the degradable material can be degraded automatically after relieving the carotid stenosis, and the degradation product can be discharged out of the body through metabolism of a human body, so that the carotid stenosis can be prevented from being taken out or replaced again; has good biocompatibility, does not generate strong rejection reaction with blood vessels, and can prevent the blockage of the stent after the implantation. Therefore, the degradable carotid artery stent has very wide application prospect.

However, the mechanical properties of the degradable material are far inferior to those of the permanent metal material, and the degradable carotid stent can undergo irreversible plastic deformation after being crimped into the delivery system, so that the degradable carotid stent cannot be fully expanded to the diameter before crimping. Therefore, the degradable carotid artery stent is difficult to closely adhere to the vessel wall of a lesion after being implanted, cannot provide enough radial supporting force, and is easy to shift, thereby causing restenosis.

In view of the above-mentioned drawbacks, there is a need to develop a fully covered degradable carotid artery stent, in which an elastomer is fully covered on the stent body to reduce the plastic deformation of the stent after being crimped and expanded, thereby improving the wall-adhering ability of the stent and improving the curative effect on carotid stenosis.

Disclosure of Invention

In order to solve the problems, the invention discloses a full-coated degradable carotid artery stent and a preparation method thereof, which aim to reduce the plastic deformation of the stent after being pressed, held and expanded, improve the wall-adhering capability of the stent and improve the curative effect on carotid stenosis.

In order to achieve the purpose, the technical scheme of the invention is as follows:

the utility model provides a full tectorial membrane degradable carotid artery support, includes the support body, is located the film of this internal diameter cross section department of support, be located the coating in the netted hole part in support body middle part and the outside diameter, just the film reaches the coating will the support body is complete the cladding and is formed the even hollow circular tubular structure of sealing of a thickness.

Preferably, in the full-coated degradable carotid artery stent, the inner diameter of the stent body is 4-12mm, the length of the stent body is 20-120mm, the degradable high molecular polymer silk threads are woven into a net-shaped pore structure, the diameter of the degradable high molecular polymer silk threads is 0.10-0.30mm, and the degradation period is 12-24 months.

Preferably, in the full-film-covered degradable carotid artery stent, the film is made of polyurethane generated by the cross-linking reaction of poly-L-lactide-caprolactone and hexamethylene diisocyanate, the length of the film is 0.1-0.2mm longer than that of the stent body, the width of the film is equal to the perimeter of the cross section of the inner diameter of the stent body, the thickness of the film is less than or equal to 100 microns, the elongation at break is more than 200% at 25-37 ℃, the plastic deformation is less than 15%, and the degradation period is 3-6 months.

Preferably, in the full-coated degradable carotid artery stent, the coating is made of polyurethane generated by the cross-linking reaction of poly-L-lactide-caprolactone and hexamethylene diisocyanate, the thickness of the outer side of the outer diameter of the stent is less than or equal to 100 microns, and the degradation period is 3-6 months.

The invention also provides a preparation method of the full-coated degradable carotid artery stent, which comprises the following steps:

(1) coating a Teflon film on a mandrel;

(2) coating a film on the Teflon film;

(3) sleeving the support body on the thin film;

(4) coating a coating on the stent body to finally form a full-coated degradable carotid stent;

(5) and (3) carrying out high-temperature treatment on the full-film degradable carotid artery stent and taking the full-film degradable carotid artery stent off the mandrel, and removing the Teflon film.

Preferably, in the preparation method of the full-coated degradable carotid artery stent, the inner diameter of the stent body is 4-12mm, the length of the stent body is 20-120mm, the stent body is woven by degradable high molecular polymer silk threads to form a mesh pore structure, the diameter of the degradable high molecular polymer silk threads is 0.10-0.30mm, and the degradation period is 12-24 months.

Preferably, in the preparation method of the full-film-covered degradable carotid artery stent, the film is prepared by a solution casting method, the film is made of polyurethane generated by crosslinking reaction of poly-L-lactide caprolactone and hexamethylene diisocyanate, the length of the polyurethane is 0.1-0.2mm longer than that of the stent body, the width of the polyurethane is equal to the perimeter of the cross section of the inner diameter of the stent body, the thickness of the polyurethane is less than or equal to 100 mu m, the elongation at break of the polyurethane at 25-37 ℃ is more than 200%, the plastic deformation of the polyurethane is less than 15%, and the degradation period is 3-6 months.

Preferably, in the preparation method of the full-coated degradable carotid artery stent, the coating is prepared by an ultrasonic atomization spraying method, the coating is made of polyurethane generated by crosslinking reaction of poly-L-lactide caprolactone and hexamethylene diisocyanate, the thickness of the outer side of the outer diameter of the stent is less than or equal to 100 microns, and the degradation period is 3-6 months.

Preferably, in the preparation method of the full-coated degradable carotid artery stent, the high-temperature treatment temperature of the full-coated degradable carotid artery stent is 80-160 ℃ and the time is 1-24 hours.

The invention has the beneficial effects that:

1. the support body is completely coated by the elastomer material, and the irreversible plastic deformation of the support after being pressed and held into the conveying system can be greatly reduced through the protection effect of the elastomer film and the coating on the woven net-shaped three-dimensional structure of the support body, and the support can be basically and completely expanded to the diameter before being pressed and held after being released, so that the support can be tightly attached to the vessel wall at the pathological change part, can provide enough radial supporting force, is not easy to shift, and can more effectively prevent restenosis compared with a naked degradable carotid artery support;

2. the thickness of the elastomer film and the thickness of the elastomer coating on the outer side of the stent body are smaller, so that the fully-coated degradable carotid stent has smaller outer diameter, and has good axial flexibility and trafficability in a bent pipeline;

3. the degradation speed of the elastomer film and the coating is higher than that of the stent body, so that the full-coated degradable carotid artery stent can be completely degraded in a specified treatment period, and the carotid artery can be restored to the original normal physiological state as soon as possible.

Drawings

FIG. 1 is a schematic front view of a fully covered degradable carotid stent according to the present invention;

FIG. 2 is a schematic cross-sectional view of the fully-covered degradable carotid stent of the present invention;

FIG. 3 is a schematic flow chart of the preparation method of the full-coated degradable carotid stent of the invention.

List of reference numerals:

a film 10, a stent body 11 and a coating 12.

Detailed Description

The present invention will be further illustrated with reference to the accompanying drawings and specific embodiments, which are to be understood as merely illustrative of the invention and not as limiting the scope of the invention. It should be noted that the terms "front," "back," "left," "right," "upper" and "lower" used in the following description refer to directions in the drawings, and the terms "inner" and "outer" refer to directions toward and away from, respectively, the geometric center of a particular component.

Fig. 1 is a schematic front view of a full-coated degradable carotid stent of the present invention, and fig. 2 is a schematic sectional structure of the full-coated degradable carotid stent of the present invention. As shown in fig. 1 and 2, the full-coated degradable carotid artery stent comprises a stent body 11, a thin film 10 located at the inner diameter cross section of the stent body 11, and a coating 12 located at the middle mesh pore part and the outer diameter outer side of the stent body 11, wherein the stent body 11 is completely coated by the thin film 10 and the coating 12 to form a closed hollow circular tubular structure with uniform thickness.

With continued reference to fig. 1 and 2, the film 10 is 0.1mm to 0.2mm longer than the stent body 11, the width of the film 10 is equal to the perimeter of the cross section of the inner diameter of the stent body 11 (because the film is cut into a rectangular film which can wrap the teflon film for one circle), the thickness of the film 10 is less than or equal to 100 μm, and the thickness of the coating 12 outside the outer diameter of the stent body 11 is less than or equal to 100 μm. The film and the coating with such three-dimensional sizes not only can completely cover the stent body, and play a role in protecting the whole three-dimensional structure of the stent body, but also can ensure that the fully-coated degradable carotid artery stent has smaller outer diameter, so that the fully-coated degradable carotid artery stent has good axial flexibility and trafficability in a bent pipeline.

In addition, the embodiment also provides a preparation method of the full-coated degradable carotid artery stent. Fig. 3 is a flow chart illustrating a method for preparing a full-coated degradable carotid stent of the present invention, which can be prepared by the following method, as shown in fig. 3.

First, a first step S1 is performed to wrap a teflon film around a mandrel. The core shaft is longer than the full-film-coated degradable carotid artery stent by 5 mm-10 mm, the Teflon film is longer than the core shaft by 5 mm-10 mm, the thickness of the Teflon film is 30 mu m-60 mu m, and the core shaft is coated with two layers of Teflon films, so that the diameter of the core shaft is four times the sum of the thicknesses of the Teflon films is equal to the inner diameter of the full-film-coated degradable carotid artery stent. The friction coefficient of the Teflon film is extremely small, so that the full-film-coated degradable carotid artery stent can be prevented from being stuck on the mandrel, and the full-film-coated degradable carotid artery stent can be conveniently taken down from the mandrel.

Next, a second step S2 is performed to wrap the film 10 on the teflon film. The film is prepared by a solution casting method. Specifically, poly-L-lactide-caprolactone and hexamethylene diisocyanate are dissolved in dichloromethane to prepare a solution, the intrinsic viscosity of the poly-L-lactide-caprolactone is 0.5-1.0 dL/g, the mass of the poly-L-lactide-caprolactone is 0.5-1.0 g, the mass ratio of the poly-L-lactide-caprolactone to the hexamethylene diisocyanate is 5: 1-10: 1, and the volume of the dichloromethane is 15-30 ml. Pouring the solution into a glass culture dish with the diameter of 90-100 mm, naturally drying at room temperature until dichloromethane is completely volatilized, and then putting the culture dish and the film into an oven for high-temperature treatment at the temperature of 80-160 ℃ for 1-24 h.

And after the high-temperature treatment is finished, removing the film from the culture dish, wherein the film 10 is made of polyurethane generated by the cross-linking reaction of poly L-lactide-caprolactone and hexamethylene diisocyanate, the elongation at break of the film 10 at 25-37 ℃ is more than 200%, the plastic deformation of the film is less than 15%, and the degradation period of the film is 3-6 months. Therefore, the thin film can not be torn in the process of being pressed and held along with the stent body, can be basically and completely recovered to the size before being pressed and held in the process of being expanded along with the stent body, is degraded earlier than the stent body, and can not be kept in the carotid artery as a foreign body for a long time.

Cutting the film 10 into a rectangular film, so that the rectangular film is 0.1-0.2mm longer than the support body, and the width of the rectangular film is equal to the perimeter of the cross section of the inner side of the support body. The rectangular film is wrapped on the Teflon film, so that the inner side of the bracket body can be completely wrapped, and the technical problem that a coating with good performance can not be prepared on the inner side of the bracket body by adopting an ultrasonic atomization spraying method is solved.

Next, a third step S3 is performed to fit the stent body 11 over the membrane 10. The stent body is woven by degradable high molecular polymer silk threads to form a mesh pore structure. The diameter of the degradable high molecular polymer silk thread is 0.10-0.30mm, the material is poly-L-lactic acid, the degradation period is about 12-24 months, the necessary radial supporting force can be provided, and the degradable high molecular polymer silk thread can be completely degraded in the specified treatment period, so that the carotid can be restored to the original normal physiological state as soon as possible.

Then, a fourth step S4 is performed to form a coating 12 on the stent body. The coating 12 is prepared by an ultrasonic atomization spraying method. 0.25g of poly L-lactide-caprolactone having an intrinsic viscosity of 0.8dL/g was weighed, 50. mu.l of hexamethylene diisocyanate was weighed, and dissolved together in 25ml of methylene chloride to prepare a spray solution. The mandrel is arranged at the designated position of a spraying instrument, the spraying flow is set to be 1-2 ml/h, the rotation speed of the mandrel is 100-200 rpm, the feeding speed is 0.2-0.3 cm/s, and the spraying solution is sprayed to the middle pore mesh part and the outer diameter outer side of the support body 11. And after the spraying is finished, taking down the mandrel, and placing the mandrel in a vacuum drying oven for drying at normal temperature for 3 days to obtain the full-coated degradable carotid artery stent.

Finally, the fifth step S5 is performed, the fully-covered degradable carotid artery stent is subjected to high temperature treatment and is taken down from the mandrel, and the teflon membrane is removed. And (3) placing the full-coated degradable carotid artery stent in an oven, treating for 1-24h at 80-160 ℃, naturally cooling to room temperature, taking down the stent from a mandrel, and removing the Teflon film to obtain the final full-coated degradable carotid artery stent. The material of the coating is polyurethane generated by the cross-linking reaction of poly L-lactide-caprolactone and hexamethylene diisocyanate, and the degradation period of the coating is 3-6 months. Therefore, the coating can not be torn in the process of crimping along with the stent body, can be basically and completely restored to the size before crimping in the process of expanding along with the stent body, is degraded earlier than the stent body, and can not be kept in the carotid artery as a foreign matter for a long time.

In conclusion, in the fully-coated degradable carotid artery stent and the preparation method thereof provided by the invention, the stent body is completely coated by the elastomer material, the irreversible plastic deformation of the stent after being pressed and held in the delivery system is greatly reduced, and the stent can be basically and completely expanded to the diameter before being pressed and held after being released, so that the stent can be tightly attached to the vessel wall at the pathological change part, can provide enough radial supporting force, is not easy to displace, and can more effectively prevent restenosis than a naked degradable carotid artery stent; meanwhile, the full-film-coated degradable carotid artery stent has good axial flexibility and trafficability in a bent pipeline; the full-coated degradable carotid artery stent can be completely degraded in a specified treatment period, so that the carotid artery can be restored to the original normal physiological state as soon as possible.

The technical means disclosed in the invention scheme are not limited to the technical means disclosed in the above embodiments, but also include the technical scheme formed by any combination of the above technical features.

Claims

1. The full-film-coated degradable carotid artery stent is characterized by comprising a stent body, a film positioned at the cross section of the inner diameter of the stent body, and a coating positioned at the middle part of the stent body, wherein the middle part of the stent body is provided with mesh pores, and the coating is positioned at the outer side of the outer diameter of the stent body, and the stent body is completely coated with the film to form a closed hollow round tubular structure with uniform thickness.

2. The full-coated degradable carotid stent of claim 1, wherein the inner diameter of the stent body is 4-12mm, the length is 20-120mm, a mesh-like pore structure is formed by weaving degradable high molecular polymer silk threads, the diameter of the degradable high molecular polymer silk threads is 0.10-0.30mm, and the degradation period is 12-24 months.

3. The full-film degradable carotid stent of claim 1, wherein the material of the thin film is polyurethane formed by the cross-linking reaction of poly-L-lactide-caprolactone and hexamethylene diisocyanate, the length of the thin film is 0.1-0.2mm longer than that of the stent body, the width of the thin film is equal to the circumference of the cross section of the inner diameter of the stent body, the thickness of the thin film is less than or equal to 100 μm, the elongation at break of the thin film at 25-37 ℃ is more than 200%, the plastic deformation of the thin film is less than 15%, and the degradation period is 3-6 months.

4. The full-coated degradable carotid stent of claim 1, wherein the material of the coating is polyurethane generated by the cross-linking reaction of poly-L-lactide-caprolactone and hexamethylene diisocyanate, the thickness of the outer side of the outer diameter of the stent is less than or equal to 100 μm, and the degradation period is 3-6 months.

5. A preparation method of a full-coated degradable carotid artery stent is characterized by comprising the following steps:

(1) coating a Teflon film on a mandrel;

(2) coating a film on the Teflon film;

(3) sleeving the support body on the thin film;

6. The method for preparing the full-coated degradable carotid artery stent of claim 5, wherein the inner diameter of the stent body is 4-12mm, the length is 20-120mm, a mesh-shaped pore structure is formed by weaving degradable high molecular polymer silk threads, the diameter of the degradable high molecular polymer silk threads is 0.10-0.30mm, and the degradation period is 12-24 months.

7. The method for preparing the full-film degradable carotid artery stent of claim 5, wherein the film is prepared by a solution casting method, the film is made of polyurethane generated by the cross-linking reaction of poly-L-lactide-caprolactone and hexamethylene diisocyanate, the length of the polyurethane is 0.1-0.2mm longer than the length of the stent body, the width of the polyurethane is equal to the perimeter of the cross section of the inner diameter of the stent body, the thickness of the polyurethane is less than or equal to 100 μm, the elongation at break of the polyurethane at 25-37 ℃ is more than 200%, the plastic deformation of the polyurethane is less than 15%, and the degradation period is 3-6 months.

8. The method for preparing the full-coated degradable carotid stent of claim 5, wherein the coating is prepared by ultrasonic atomization spraying, the material is polyurethane generated by cross-linking reaction of poly-L-lactide-caprolactone and hexamethylene diisocyanate, the thickness of the outer side of the outer diameter of the stent is less than or equal to 100 μm, and the degradation period is 3-6 months.

9. The method for preparing the full-coated degradable carotid stent of claim 5, wherein the temperature of the high-temperature treatment of the full-coated degradable carotid stent is 80-160 ℃ and the time is 1-24 h.