CN105457105B - One kind can develop magnesium alloy blood vessel rack - Google Patents

Abstract

The invention relates to the field of medical devices, in particular to an absorbable novel developable magnesium alloy vascular stent for the treatment of stenosis in a blood vessel cavity. The magnesium alloy vascular stent has a structural design for omni-directional and multi-angle imaging under X-rays, and realizes the assembly between the imaging mark and the magnesium alloy vascular stent by means of polymer bonding. Assembled into the reserved development ring, avoiding galvanic corrosion between the development substance and the magnesium alloy substrate, and realizing the visibility of the degradable magnesium alloy vascular stent under X-ray imaging equipment. The invention effectively reduces the influence of the addition of the developing mark on the profile of the stent system, and avoids the breakage of the strut caused by the galvanic corrosion between the developing substance and the matrix of the strut of the magnesium alloy vascular stent, thereby resulting in the loss of the stent. The role of effective support for diseased blood vessels can accurately locate the position of the stent and improve the operability of stent implantation without blind spots.

Description

A kind of visualized magnesium alloy vascular stent

technical field

The invention relates to the field of medical devices, in particular to an absorbable novel developable magnesium alloy vascular stent for the treatment of stenosis in a blood vessel cavity.

Background technique

With the change of people's eating habits, the pressure of work and life is increasing, the environmental pollution is becoming more and more serious, and the number of people suffering from cardiovascular and cerebrovascular diseases is gradually increasing. Coronary heart disease is one of the diseases with higher incidence rate. At present, the way of implanting stents is mostly used to treat coronary heart diseases such as coronary stenosis, and the stents are gradually improved and developed in the application process, from the initial bare metal stent (BMS) (postoperative stenosis rate of 15-30%), to drug-washed stents. With the development and application of destenting (DES) (postoperative stenosis rate of about 10%), with the continuous accumulation of clinical applications, it has been found that the inert metal stent platform has the risk of late thrombosis and restenosis in the long term after implantation. Therefore, degradable stents that can be gradually absorbed by the body after an effective service period have received extensive attention.

In recent years, magnesium-based metals (pure magnesium and magnesium alloys) have very low electrode potential, are very active in the body fluid environment, and are prone to corrosion, and then are safely absorbed and metabolized in the body to achieve biodegradation. Magnesium alloys have excellent mechanical properties, and magnesium is an essential trace element for growth and metabolism in the human body. The above characteristics make it favored by people, and it is expected to become a new generation of degradable implant materials and get clinical application.

In the past 10 years, there have been endless researches on degradable magnesium alloy vascular stents at home and abroad. In 2003, Heublein et al. published the first report using AE21 magnesium alloy as a degradable cardiovascular stent material in Heart magazine. The results of anatomical analysis of 20 degradable magnesium alloy stents implanted in the coronary arteries of 11 pigs at 10 days, 35 days and 56 days confirmed that after the support force of the stents disappeared, the blood vessels showed positive remodeling, which made the blood vessels remodel on the 56th day. The inner diameter of the blood vessel lumen was larger than that on the 35th day; due to the negative charge generated when the magnesium alloy was degraded, thrombus was not easy to form in the stent. Subsequently, Carlo Di Mario reported the animal experiment results of WE43 magnesium alloy stents, 66 WE43 magnesium alloy stents and 33 stainless steel stents were successfully implanted in the coronary arteries of 33 minipigs. Controlled studies found that after 4 weeks and 12 weeks of implantation, the minimum lumen diameter of the magnesium alloy stent group was significantly greater than that of the stainless steel stent control group, indicating that the vascular reconstruction ability after implantation of the magnesium alloy stent was better.

A large number of studies above have shown that magnesium alloys are biologically safe as cardiovascular stent materials, which provides a strong basis for the clinical application of magnesium alloy cardiovascular stents in terms of biological safety. However, magnesium-based metals have a small specific gravity and are invisible materials under X-rays.

At present, patents on magnesium alloy cardiovascular stents are mostly focused on the development of new magnesium alloys, surface modification of magnesium alloys, and optimization of stent structures.

For example, Chinese Invention Patent Publication No. 102220529A discloses a Mg-Zn-Y-Nd magnesium alloy for biodegradable vascular stents, which has excellent corrosion resistance and good plasticity. The Chinese invention patent with the patent publication number 103418035A discloses a method for preparing a surface coating that can control the degradation rate of magnesium alloy stents. Both of these patents focus on solving the problem of poor corrosion resistance of magnesium alloy as a vascular stent material, but there are few reports on the difficulty of accurate positioning of magnesium alloy vascular stents during implantation.

Due to its low specific gravity, magnesium alloy materials are invisible under X-rays. Therefore, the accurate positioning of magnesium alloy stents during implantation and postoperative follow-up has become another problem that needs to be solved urgently. It is a simple, easy and effective method to prepare a developing mark on the magnesium alloy vascular stent to realize the positioning of the stent under X-ray. However, magnesium-based metal materials have a very low electrode potential, and when in contact with a large amount of metal materials, they will be corroded as anodes (galvanic corrosion). Therefore, in order not to sacrifice the transportability of the stent system, shorten the service life of the stent, and achieve accurate intraoperative and postoperative positioning, it is necessary to arrange the distribution of the imaging markers on the stent structure, and take effective methods to realize the integration of imaging markers and magnesium. Bonding of Alloy Vascular Stents.

Contents of the invention

The purpose of the present invention is to obtain a new type of imageable magnesium alloy vascular stent on the basis of ensuring the effectiveness of the stent during the service period, to realize the visibility of the degradable magnesium alloy vascular stent under X-rays, and to solve the problem of magnesium alloy vascular stents. Problems not visible under X-ray during vascular stent implantation and postoperative follow-up.

Technical scheme of the present invention is:

A new type of imageable magnesium alloy vascular stent, the magnesium alloy vascular stent has a structural design for omnidirectional and multi-angle imaging under X-rays, and realizes the assembly between the imaging mark and the magnesium alloy vascular stent through polymer bonding , the development mark is assembled into the reserved development ring through a polymer binder, so as to avoid galvanic corrosion between the development material and the magnesium alloy substrate.

The novel imageable magnesium alloy vascular stent has a structural design for omnidirectional and multi-angle imaging under X-rays. There are 2 developing rings on the side, and 4 developing rings are distributed at both ends of the bracket.

In the novel imageable magnesium alloy vascular stent, the assembly between the imaging mark and the magnesium alloy vascular stent is realized through polymer bonding, and a medical degradable polymer material with poor water permeability is selected as the imaging mark and the magnesium alloy vascular stent The size of the development mark is smaller than the size of the development ring reserved at both ends of the stent, so that the development mark wrapped by the adhesive and the development ring reserved for the stent are perfectly matched.

In the novel developable magnesium alloy vascular stent, the polymer binder is a biomedical-grade degradable polymer material, including: polylactic acid, poly-L-lactic acid, polyracemic lactic acid, polycaprolactone, polysan One or more of methyl carbonates.

In the novel developable magnesium alloy vascular stent, the diameter of the developing mark is 0.2-0.5 mm, and the inner diameter of the developing ring is 0.05-0.15 mm larger than the diameter of the developing mark.

The novel imageable magnesium alloy vascular stent realizes omni-directional and multi-angle visibility under X-rays during stent implantation and follow-up, without sacrificing the grip size of the stent system. Under the premise, the service period of the magnesium alloy vascular stent can be effectively extended.

Design idea of the present invention is:

Firstly, four developing rings are prefabricated at both ends of the main support structure of the magnesium alloy vascular stent, and the four developing rings are distributed in a crossing manner. Then, the developing marker is embedded into the prefabricated developing ring by physical bonding, wherein the binder is a medical-grade degradable polymer material, which should be a polymer material with poor water permeability. The preparation of the novel developable magnesium alloy vascular stent includes the distribution position of the developed markers and the bonding of the developed markers and the magnesium alloy vascular stent. The marker can locate the position of the stent more precisely, and can avoid the influence of the final crimping size of the stent system due to the addition of the imaging marker; the imaging marker is bonded to the magnesium alloy vascular stent by using a medical-grade degradable polymer adhesive , which not only realizes the assembly of the imaging marker on the magnesium alloy vascular stent, but also reduces the probability of galvanic corrosion between the imaging marker and the magnesium alloy substrate. This new type of imageable magnesium alloy vascular stent has the characteristics of accurate positioning under X-ray during implantation and follow-up. The addition of imaging markers does not affect the final crimping size of the stent, which solves the problem caused by the addition of imaging markers. The resulting galvanic corrosion ensures the service life of the magnesium alloy vascular stent.

Features and beneficial effects of the present invention are:

1. A new type of developable magnesium alloy vascular stent provided by the present invention, the development mark is located outside the support structure of the main body of the stent, and the stent has four development marks, which are distributed in a cross shape. The design of this new type of stent structure with a development ring is key to the invention. This new type of stent can realize all-round and multi-angle accurate positioning of the magnesium alloy vascular stent under X-ray without sacrificing the crimping diameter, and solves the problem that the magnesium alloy vascular stent cannot be seen under X-ray.

2. The degradable vascular stent involved in the present invention is a magnesium alloy vascular stent, and the developing mark is fixed in the prefabricated developing ring on the magnesium alloy vascular stent by using a medical-grade degradable polymer material. A polymer binder with poor water permeability is used to separate the imaging marker from the magnesium alloy vascular stent mesh, so as to avoid the damage of the stent structure caused by galvanic corrosion.

3. The distribution of the developing marks in the present invention can not only avoid damage to the support structure of the main body of the stent during the crimping process, but also further reduce the possibility of disintegration of the stent structure due to galvanic corrosion between the developing marks and the stent mesh, That is, the service period of the visualized magnesium alloy vascular stent is effectively guaranteed.

Description of drawings

Fig. 1. Structural diagram of the novel developable magnesium alloy vascular stent of the present invention. In the figure, 1 magnesium alloy vascular stent; 2 developing ring.

Fig. 2. The developing effect diagram of the developable magnesium alloy vascular stent of the present invention during the implantation process.

Detailed ways

In a specific embodiment, the present invention provides a novel developable magnesium alloy vascular stent. First, design a structure with prefabricated developing rings at both ends of the main support structure of the magnesium alloy vascular stent. The number of developing rings should be an even number, uniformly and cross-distributed at both ends of the stent, and each developing ring is located at the top of the peak at the end of the stent. Then carry out laser cutting according to the designed structure, pickling to remove slag, polishing, surface protection treatment, and then assemble the developing material and support rod by physical bonding method, and finally dry and heat treatment.

The material of the degradable magnesium alloy vascular stent involved in the present invention includes: pure magnesium and magnesium alloys, including Mg-Mn, Mg-Al-Zn, Mg-Al-Mn, Mg-Al-Si, Mg-Al-RE, Mg -Al-Ca, Mg-Al-Ca-RE, Mg-Al-Sr, Mg-Zn-Zr, Mg-Zn-Al, Mg-Zn-Al-Ca, Mg-Zn-Mn, Mg-RE-Zr , Mg-RE, Mg-RE-Mn, Mg-RE-Zn, Mg-Zn-Cu and other magnesium alloy systems. The types of vascular stents involved in the present invention include: coronary artery stents, intracranial stents, peripheral stents and magnesium alloy implanted medical devices that require image observation under X-rays. According to the present invention, the distribution pattern of the developing rings reserved for developing markers at both ends of the bracket is crossed and evenly distributed. The developing markers involved in the present invention are metal substances with large specific gravity such as metal tantalum (Ta), metal gold (Au), metal platinum (Pt), metal tungsten (W). This kind of material has the characteristic of being clearly visualized under X-ray under the condition of small size. The medical-grade hydrophobic polymer material involved in the present invention includes polylactic acid (PLA), poly-L-lactic acid (PLLA), polyracemic lactic acid (PDLLA), polycaprolactone (PCL), polytrimethylene carbonate One or more of (PTMC). The solvent used for dissolving the high molecular polymer includes: chloroform, dichloromethane, acetone, ethyl acetate, tetrahydrofuran, etc., and the high molecular polymer is prepared into a polymer solution with a concentration of 1～5wt% (preferably 2～5wt%) .

The following examples will further illustrate the present invention, but do not limit the present invention thereby.

Example 1:

(1) Structural design of a new type of imageable magnesium alloy stent

Four developing rings 2 are reserved at both ends of the main supporting structure of the magnesium alloy vascular stent 1 that has been structurally optimized, and the four developing rings 2 are respectively distributed across the two ends of the magnesium alloy vascular stent 1 , as shown in FIG. 1 . Among them, the developing ring 2 is located on the outside of the main support structure, and four points are crossed to achieve accurate positioning close to the edge of the support, and it can be positioned regardless of the angle of the support, and it also avoids sacrificing the support system because it is located in the main support structure profile and damage to the coating during the crimping process.

(2) Bracket processing

According to the structure provided in (1), the AZ31B magnesium alloy vascular stent was processed by laser cutting, and then pickled, polished, and dried for later use. Surface protection treatment for bare magnesium alloy stents. The above is the preliminary preparation for assembling the development mark.

(3) Press grip experiment

Press the magnesium alloy stent equipped with the development mark onto the matching balloon, the diameter of the stent system is 1.1 mm after the pressing, the deformation of the whole structure of the stent is uniform after the pressing, and no damage to the protective coating occurs .

Example 2:

(1) Development mark assembly

First, a chloroform solution of polycaprolactone (PCL) with a concentration of 4 wt % was prepared. The selected development mark and the reserved development ring are both circular in design, and the circumference of the development mark is 0.05mm smaller than the inner circumference of the reserved development ring. Fit the developer marker wrapped with polycaprolactone into the prefabricated developer ring, the developer marker and the developer ring match well, and dry.

(2) In vitro immersion test

The processed novel developable magnesium alloy vascular stent was soaked in PBS buffer solution for 14 days at a soaking ratio of 1.25cm ² /mL, and no obvious corrosion was found on the magnesium alloy substrate in contact with the developed mark.

(3) In vivo imaging effect test experiment

The processed new imageable magnesium alloy vascular stent system was implanted into the iliac artery of the experimental animal pig. During the process of stent implantation and follow-up angiography, the position of the stent can be accurately located on the X-ray image screen, as shown in Figure 2. The positions marked with circles in FIG. 2 are the positions of the developing rings at both ends of the stent, which can realize accurate positioning of the magnesium alloy vascular stent after implantation. The delivery process of the stent system was smooth, and there was no phenomenon that the developing ring of the stent was lifted.

The results of the examples show that two development rings with pre-installed development marks are respectively reserved at both ends of the main body of the magnesium alloy stent, and the four development rings are distributed in a cross pattern (as shown in Figure 1). Angles can be accurately positioned. The development mark is assembled into the reserved development ring through the medical degradable polymer binder, which aims to avoid the galvanic corrosion between the development mark and the magnesium alloy substrate through the barrier effect of the polymer binder, and realize the Visibility of degraded magnesium alloy vascular stents under X-ray imaging equipment.

In addition, the present invention adopts a novel method of distributing the developing rings at both ends of the support structure of the main body of the stent, which effectively reduces the impact of the addition of the developing marks on the crimping profile of the stent system. Thereby, it avoids the breakage of the strut caused by galvanic corrosion between the developing substance and the base of the strut of the magnesium alloy stent, which leads to the loss of the effective support of the stent to the diseased blood vessel; The maneuverability of entry, there is no blind spot. Therefore, the problem of being invisible under X-rays during the implantation of the degradable magnesium alloy stent and the problem of galvanic corrosion between the developing substance and the magnesium alloy matrix are solved.

Claims (4)

1. An imageable magnesium alloy vascular stent, characterized in that the magnesium alloy vascular stent has a structural design for omni-directional and multi-angle imaging under X-rays, and realizes the imaging mark and magnesium alloy vascular stent through polymer bonding. Assembling between the brackets, the development mark is assembled into the reserved development ring through a polymer adhesive to avoid galvanic corrosion between the development material and the magnesium alloy substrate; The structural design with all-round and multi-angle imaging under X-ray is to set the imaging ring with the pre-assembled imaging mark on the outside of the main support structure of the magnesium alloy vascular stent, with 2 imaging rings on each side and 4 imaging rings intersecting each other. Distributed at both ends of the bracket; To achieve the assembly between the imaging marker and the magnesium alloy stent by means of polymer bonding, a medical degradable polymer material with poor water permeability is selected as the adhesive for the imaging marker and the magnesium alloy stent, and the method of physical bonding is adopted. Embed the development marker into the prefabricated development ring, the development marker is metal tantalum, metal gold, metal platinum or metal tungsten, the size of the development mark is smaller than the size of the development ring reserved at both ends of the bracket, so that the development mark wrapped by the adhesive A perfect match with the reserved developing ring of the bracket. 2. According to the developable magnesium alloy vascular stent according to claim 1, it is characterized in that the polymer binder is a biomedical-grade degradable polymer material, including: polylactic acid, polycaprolactone, polytrimethylene One or two or more of the base carbonates. 3. The developable magnesium alloy vascular stent according to claim 1, wherein the diameter of the developed mark is 0.2-0.5 mm, and the inner diameter of the developed ring is larger than the diameter of the developed mark by 0.05-0.15 mm. 4. The imageable magnesium alloy vascular stent according to claim 1, characterized in that, the magnesium alloy vascular stent realizes omnidirectional and multi-angle visibility under X-rays during stent implantation and later follow-up, and On the premise of not sacrificing the crimping size of the stent system, the service life of the magnesium alloy vascular stent can be effectively extended.