Degradable metal tube intracavity stent with preset degradation points

Abstract

The invention discloses a degradable metal tube intracavity stent with preset degradation points, and belongs to the technical field of medical instruments. The degradation speed of a specific site of a stent main body material is controlled in a manner of presetting a degradation point. The preset degradation point is realized by electroplating copper particles at a specific site or / and coating the specific site with a polylactic acid coating. The addition of the copper particles can change the electrochemical characteristics at specific sites, so that local primary battery reaction is formed, and local degradation is accelerated; the polylactic acid coating can change the PH characteristic of a specific site and accelerate the degradation speed of the specific site. The stent has the advantages that the degradation speed of the preset degradation point can be controlled, the specific site of the stent rod is preferentially degraded, the structure of the whole stent is changed according to expectation, and the retention time of the whole stent is shortened.

Description

Technical Field

[0001] The invention belongs to the technical field of medical devices, and in particular relates to a degradable metal intraluminal stent with preset degradation points. Background Art

[0002] Intraluminal stents are commonly used clinical devices for treating various luminal stenosis diseases in the human body. They can be used to treat cardiovascular diseases such as atherosclerosis, hemangioma and coronary artery stenosis, as well as luminal problems such as bile duct and urethral stenosis. They are of great significance for the recovery of luminal stenosis diseases in the human body.

[0003] Cardiovascular disease is a major cause of death worldwide, with an incidence of about 30%, which has exceeded the combined incidence of cancer and AIDS, and has gradually become the number one killer of human health. At present, there are three main methods for the treatment of cardiovascular disease: traditional drug therapy, interventional therapy (vascular stent implantation) and surgical treatment. Among them, vascular stent interventional therapy has become the main method for treating vascular stenosis and occlusion in cardiovascular disease due to its minimally invasive, safe and effective nature.

[0004] On the one hand, degradable metal intraluminal stents overcome the problems of traditional inert metal intraluminal stents that require secondary surgery to remove or long-term retention causing complications. On the other hand, they solve the problems of relatively weak mechanical properties of polymer intraluminal stents and difficulty in ensuring the consistency of stent performance during material processing. They have gradually become a hot topic in intraluminal stent research. Existing degradable metals mainly include magnesium and its alloys, zinc and its alloys, and iron and its alloys.

[0005] Patent CN 108754232 A provides a high-strength, high-plasticity, biodegradable Zn-Mn-Li zinc alloy that can be used for various intraluminal stents. Patent CN 116570400 A discloses a degradable zinc alloy for the preparation of anti-restenosis degradable stents for small blood vessel auxiliary suture, which has good biocompatibility, good support force and fatigue strength. In addition, patent CN 221470088U discloses a new type of degradable vascular stent prepared by a composite of a degradable zinc alloy and a polymer material, which has excellent support force and good flexibility. However, for intraluminal stents represented by vascular stents, the time of lumen repair must be earlier than the time of complete degradation of the stent in order to achieve the expected effect. After the lumen is repaired, the stent must also avoid concentrated and rapid degradation to reduce local metabolic pressure and reduce adverse reactions caused by the concentrated and rapid release of degradation products. During this period of time, the lesion site no longer needs the stent to provide support, and the presence of the stent instead restricts the elasticity and physiological activity of the lumen. Patent CN 116747062A combines degradable materials with non-degradable materials, at the expense of the overall degradation performance of the stent material. Although it can reduce the overall retention time of the stent, it also causes the problem of non-degradable parts remaining in the body. After the stent completes the support of the lumen, the contradiction between "slow and safe degradation" and "quick release of the lumen" cannot be overcome by the existing technology. Summary of the invention

[0006] The purpose of the present invention is to provide a degradable metal intraluminal stent with preset degradation points and a preparation method thereof, so as to solve the problem that the overall degradation time of the existing degradable stent is too long and the adverse effect on the recovery of the physiological activity of the lesion lumen is produced.

[0007] The present invention controls the degradation rate of a specific site of the main material of the stent (one of magnesium and its alloys, zinc and its alloys, or iron and its alloys) by presetting a degradation point. The specific site is mainly located at the stress concentration site of the main material of the stent, such as the connecting rib structure of the stent, the crest of the stent support body, the middle ring of the stent, etc. The preset degradation point is achieved by electroplating copper particles (with a standard electrode potential higher than the main metal of the stent) or / and coating a polylactic acid coating at a specific site. The addition of copper particles can change the electrochemical properties at a specific site, form a local galvanic cell reaction, and accelerate local degradation; the polylactic acid coating can change the pH characteristics at a specific site and accelerate the degradation rate of a specific site.

[0008] As a further improvement of the present invention, the preset degradation point is achieved by electroplating copper particles (100-150 particles / mm) on the surface of a specific location.

[0009] As a further improvement of the present invention, the preset degradation points are achieved by preparing copper particles at specific locations by embedding or welding.

[0010] As a further improvement of the present invention, the preset degradation point is achieved by coating a polylactic acid coating of a specific shape (the specific shape includes a rectangle, an ellipse, or a special shape that expands 1-3 mm around the contour of the specific site) at the specific site.

[0011] As a further improvement of the present invention, the preset degradation point is achieved by electroplating copper particles at specific locations and coating a polylactic acid coating.

[0012] As a further improvement of the present invention, the preset degradation point can be realized by combining the design of the local structure of the stent body, such as setting a gap, a pit or a concave structure of a specific shape at the point.

[0013] Compared with the prior art, the present invention has the following advantages:

[0014] The present invention can control the degradation speed of preset degradation points and achieve preferential degradation of specific sites of stent rods, so that the overall structure of the stent changes as expected, thereby reducing the retention time of the overall stent.

[0015] The novel degradable metal intraluminal stent of the present invention has an appropriately accelerated corrosion rate at a preset degradation point and does not produce adverse reactions caused by rapid degradation.

[0016] The copper particles and polylactic acid involved in the material design can improve the biocompatibility of the stent in the body. The addition of copper particles improves the antibacterial properties of the material and is less likely to cause inflammatory reactions after implantation.

[0017] The new biodegradable metal intraluminal stent designed with this material has slightly improved mechanical properties. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] The present invention will be further described below with reference to the accompanying drawings and embodiments, in which:

[0019] Figure 1 The invention is to select a specific site 1 having a specific concave structure on a zinc alloy rod material 2 simulating an intraluminal stent rod structure.

[0020] Figure 2 It is a left side view of the first embodiment.

[0021] Figure 3 It is a front view of the first embodiment.

[0022] Figure 4 It is a left side view of the second embodiment.

[0023] Figure 5It is a front view of the second embodiment.

[0024] Figure 6 It is a left side view of the third embodiment.

[0025] Figure 7 It is a front view of the third embodiment.

[0026] Figure 8 It is a front view of the fourth embodiment.

[0027] In the figure, specific site 1, zinc alloy rod material 2, electroplated copper particles 3, polylactic acid coating 4, zinc alloy intrauterine stent partial structure 5 ( DETAILED DESCRIPTION

[0028] In order to make the purpose, technical solution and advantages of the present invention more clear, the present invention is further described in detail below in combination with embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not used to limit the present invention.

[0029] The present invention will be further described in detail below with reference to the accompanying drawings and a number of specific embodiments.

[0030] Embodiment 1:

[0031] like Figure 2 , 3 As shown, the novel degradable metal intraluminal stent rod material of the first embodiment of the present invention realizes the preset degradation point by electroplating copper particles 3 at a specific site 1. First, the non-specific site area is covered with a selected mask material, and then the copper particles are electroplated in the specific site area by using a local electroplating technology. In the process, the uniformity of electroplating is gradually improved by optimizing the electroplating process parameters, such as current density, electroplating time, etc. The comparison results of the effect of electroplated copper particles on the degradation rate of zinc alloy in different specific site areas of the same zinc alloy sheet and the same specific site area of ​​different zinc alloy sheets show that the electroplating of copper particles significantly increases the degradation rate of zinc alloy in the specific site area, and the degradation rate of the specific site area of ​​the unplated copper particles is 7%-12% for 12 weeks, while the degradation rate of the specific site area of ​​the electroplated copper particles can reach 20%-27% for 12 weeks, and within a certain range, the content of the electroplated copper particles increases, and the degradation rate is accelerated accordingly. Therefore, this embodiment can significantly increase the degradation rate at the specific site by controlling the content of the electroplated copper particles at the specific site, so that it is degraded preferentially over the non-specific site area, thereby changing the overall structure of the material. At the same time, the antibacterial results of the zinc alloy stent material before and after electroplating copper particles showed that the addition of copper particles improved the antibacterial properties of the material and could reduce the risk of infection after stent implantation. The mechanical properties test results before and after electroplating copper particles showed that the tensile strength of the material increased slightly with the addition of copper particles.

[0032] Embodiment 2:

[0033] like Figure 4 , 5 As shown, the novel degradable metal intraluminal stent rod material of the second embodiment of the present invention realizes the preset degradation point by coating the polylactic acid coating 4 at the specific site 1. First, the non-specific site area is covered with the selected mask material, and then the polylactic acid coating is coated in the specific site area using the precision dispensing technology. The precision dispensing technology can control the positioning and time with extremely high precision, so as to ensure the uniformity of the polylactic acid coating coating. Through the comparison results of the effect of the polylactic acid coating on the degradation rate of the zinc alloy in different specific site areas of the same zinc alloy sheet and the same specific site area of ​​different zinc alloy sheets, it is obtained that the presence of the polylactic acid coating significantly increases the degradation rate of the zinc alloy in the specific site area, and the degradation rate of the specific site area not coated with the polylactic acid coating is 7%-12% in 12 weeks, while the degradation rate of the specific site area coated with the polylactic acid coating can reach 18%-24% in 12 weeks, and within a certain range, the thickness of the polylactic acid coating increases, and the degradation rate is accelerated accordingly. Therefore, this embodiment can control the degradation rate at a specific site by controlling the thickness of the polylactic acid coating at the specific site, so that it degrades preferentially over the non-specific site area, thereby changing the overall structure of the material. At the same time, the mechanical properties test results before and after the polylactic acid coating are applied show that the tensile strength of the material is slightly improved as the thickness of the polylactic acid coating increases.

[0034] Embodiment 3:

[0035] like Figure 6 , 7 As shown, the novel degradable metal intraluminal stent rod material of the third embodiment of the present invention realizes preset degradation points by electroplating copper particles and coating with polylactic acid coating at specific locations. In this embodiment, the method used in Example 1 and Example 2 is adopted, and copper particles are electroplated and polylactic acid coating is applied on the material at the same time. In the specific implementation process, the degradation rate of the material can be controlled by adjusting the position and ratio of copper particles and polylactic acid coating. Through a series of experimental studies conducted on zinc alloy plates, as shown in FIG. Figure 7 As shown, when the copper particles are mainly distributed in the gray area on the stent, and other specific site areas are covered by the polylactic acid coating, there is a better degradation speed and degradation form, which is more conducive to the stent to ensure mechanical properties within the expected time, and after achieving mechanical properties, it can be degraded in the specific site area in time, thereby changing the overall structure of the material. The comprehensive degradation rate of this embodiment is 20%-25% at 12 weeks.

[0036] Embodiment 4:

[0037] like Figure 8As shown, the novel degradable metal intraluminal stent of the fourth embodiment of the present invention. By selecting the method of presetting degradation points by copper particles and polylactic acid coating in the third embodiment, a presetting degradation point is constructed on a degradable zinc alloy intrauterine stent for clinical application. The position and proportion of the copper particles and the polylactic acid coating are adjusted on the basis of the third embodiment, and the implementation scheme of the copper particles and polylactic acid coating of the intrauterine stent with the best degradation rate is obtained through in vitro degradation test and mechanical property test. The test results show that for the zinc alloy intrauterine stent that does not implement this scheme, the degradation process time is relatively long, and it takes about four months or more to completely degrade, because the endometrium can be well recovered after one to two months of stent implantation. Therefore, the subsequent retention of the stent will have an adverse effect on the further recovery of the intrauterine cavity. The intrauterine stent that implements this scheme can be rapidly degraded at the preset degradation point position in about two months, so that the stent as a whole disintegrates, and the stent is decomposed into several smaller fragments that can be quickly discharged from the body. The implementation of this scheme can greatly reduce the retention time of the zinc alloy intrauterine stent in the uterine cavity after achieving the expected supporting function, thereby avoiding the adverse reactions caused by long-term retention in the subsequent recovery of the uterine cavity.

Claims

1. A degradable metal intraluminal stent with preset degradation points, characterized in that: At a specific site of the main material of the stent, the degradation rate of the site is controlled by presetting the degradation point. The presetting of the degradation point is achieved by electroplating copper particles at the specific site or / and coating the specific site with a polylactic acid coating. The addition of copper particles changes the electrochemical properties at the specific site, forming a local galvanic cell reaction and accelerating the local degradation. The polylactic acid coating changes the pH characteristics at specific sites and accelerates the degradation rate of the specific sites. The specific sites are located at the stress concentration areas of the main material of the stent, including the connecting rib structure of the stent, the crest of the stent support body, and the middle ring of the stent.

2. The degradable metal intraluminal stent with preset degradation points according to claim 1, characterized in that: The preset degradation point is achieved by electroplating 100-150 copper particles / mm on the surface of the specific location.

3. The degradable metal intraluminal stent with preset degradation points according to claim 1, characterized in that: The preset degradation points are achieved by preparing copper particles at specific locations by embedding or welding.

4. The degradable metal intraluminal stent with preset degradation points according to claim 1, characterized in that: The preset degradation point is achieved by coating a polylactic acid coating of a specific shape at a specific location, wherein the specific shape includes a rectangle, an ellipse, or a special shape that is enlarged by 1-3 mm around the outline of the stress concentration site.

5. The degradable metal intraluminal stent with preset degradation points according to claim 1, characterized in that: The preset degradation point is achieved by electroplating copper particles at specific locations and applying a polylactic acid coating.

6. The degradable metal intraluminal stent with preset degradation points according to claim 1, characterized in that: The preset degradation point can be realized by combining the design of the local structure of the stent body, including setting a gap, a pit or a concave structure of a specific shape at the point.

7. The degradable metal intraluminal stent with preset degradation points according to claim 1, characterized in that: The main material of the bracket is one of magnesium and its alloy, zinc and its alloy or iron and its alloy; the standard electrode potential of the electroplated copper particles is higher than that of the main metal of the bracket.

8. The degradable metal intraluminal stent with preset degradation points according to claim 1, characterized in that: The stent is used in natural cavities of the human body such as blood vessels, bile ducts and urethra.

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