A self-imaging drug-eluting coronary stent with composite metal coating

Abstract

The present invention discloses a coronary stent with a composite metal coating and self-developing drug eluting, comprising a bare metal stent, a pure titanium coating, a pure tantalum coating, a tantalum-silver coating, a drug carrier layer, a drug mixed coating and a drug protective layer, wherein the bare metal stent comprises a stent head end circulation unit, a stent head connecting rod, a stent middle circulation unit, a stent middle connecting rod and a stent end circulation unit. The vascular stent of the present invention effectively solves the material problems of the existing metal stent platform, such as the release of harmful metal ions, poor X-ray fluoroscopic development, poor biocompatibility, and poor radial support; the silver element contained in the material can effectively inhibit the generation of inflammation, and reduce the secondary restenosis problem of the stent after the drug release is completed; the drug coating with a lower concentration and time-sequential control can accurately inhibit the proliferation of smooth muscle cells, shorten the speed of endothelialization of the drug stent, and effectively solve the problem of thrombotic inflammation.

Description

Technical Field

[0001] The invention relates to a vascular stent, in particular to a self-developing drug-eluting coronary vascular stent with a composite metal coating, belonging to the technical field of vascular stent application. Background Art

[0002] Coronary atherosclerotic heart disease is a heart disease caused by atherosclerosis in the coronary arteries to form "plaques", which in turn causes narrowing or blockage of the blood vessel lumen, resulting in myocardial ischemia, hypoxia or necrosis, which is clinically known as "coronary heart disease". Cardiovascular disease is the non-communicable disease with the highest mortality rate in the world, and chronic cardiovascular disease is also the disease that most widely affects people's health, especially in the middle-aged and elderly groups, who often need to use vascular stents.

[0003] At present, the biggest problems and hidden dangers after the clinical implantation of coronary stents are two aspects: the first is the acute thrombosis induced in the coronary vessels during the PTCA operation and in the short term (less than 1 month) of stent implantation; the second is the secondary restenosis after stent implantation. Studies have shown that the main causes of acute thrombosis and restenosis in the stent are: because the implantation of vascular stents requires sufficient pressure to fully expand the stent, the purpose is to achieve a perfect fit between the stent and the inner wall of the blood vessel; however, this operation causes damage to the inner wall of the blood vessel, induces thrombotic factors and inflammatory factors, and causes acute thrombosis and inflammation; in addition, because the vascular stent itself and the drugs that inhibit smooth muscle cells are foreign bodies, they constantly stimulate the vascular smooth muscle layer, induce excessive cell proliferation or inflammatory reaction, and cause thrombosis. At the same time, the coronary metal stents are long-term colonized in the vascular smooth muscle layer and blood. Due to the long-term corrosion of the complex physiological body fluid environment of the human body, the metal stents will release harmful metal ions contained in their own base materials. At present, the main materials of the coronary stents on the market are 316L stainless steel, cobalt-chromium alloy, etc. In coronary stents made of 316L medical stainless steel, the nickel content is generally 10-14%, and in cobalt-chromium alloys, such as L605 cobalt-chromium alloy, the nickel content is generally 9-11%. These may be the causes of thrombosis, inflammation, and secondary restenosis of diseased blood vessels.

[0004] Percutaneous transluminal angioplasty, or PTCA for short, is performed under the guidance of medical imaging equipment. The existing vascular stents are mainly made of 316LVM medical stainless steel, CoCr cobalt-chromium alloy, titanium alloy, and memory alloy, which are biomedical metals with relatively good biological functionality and excellent processing performance. For metal-based stents, the smaller the thickness of the stent and the closer it fits the blood vessel wall, the smaller the shear interference of the stent rod on the blood flow in the blood vessel will be, and the more conducive it will be to avoid the formation of thrombus. Therefore, medicine tends to use metal-based stents with thinner thickness. However, the density of the metal substrate is low, and the image of the stent displayed by the medical imaging equipment is not clear enough. It is difficult to distinguish the position and shape of the stent with the naked eye, resulting in the doctor's inability to accurately position the stent during surgery and postoperative follow-up. Therefore, traditional stents are designed with independent imaging markers at both ends of the stent or at a specific position as a solution. The material of the marker is platinum-iridium alloy, which has a relatively high density. The marker is usually assembled by riveting and welding, and operates in a space of about 100 microns. It is composed of a circular or square dot of about 50 microns x 50 microns, which is still inconvenient to identify and measure. Moreover, due to the difficulty of operation, the marker may fall off, which will increase the clinical risk of foreign body blockage of the distal coronary capillaries.

[0005] Therefore, existing vascular stents have comprehensive problems such as poor biocompatibility, release of harmful metal ions, poor imaging effect, and insufficient radial support force. Summary of the invention

[0006] In order to solve the above problems, the present invention provides a self-radiographic drug-eluting coronary stent with a composite metal coating.

[0007] The present invention adopts the following technical scheme: a self-developing drug-eluting coronary stent with composite metal coating, comprising a bare metal stent, a pure titanium coating, a pure tantalum coating, a tantalum-silver coating, a drug carrier layer, a drug mixed coating and a drug protective layer, wherein the pure titanium coating is arranged on the outer ring of the bare metal stent, the pure tantalum coating is arranged on the outer ring of the pure titanium coating, the tantalum-silver coating is arranged on the outer ring of the pure tantalum coating, the drug carrier layer is arranged on the outer ring of the tantalum-silver coating, the drug mixed coating is arranged on the outer ring of the drug carrier layer, and the drug protective layer is arranged on the outer ring of the drug mixed coating. The pure titanium coating is used to improve the surface tissue engineering of the bare metal stent, improve the bonding force between the metal coating and the stent itself, and make it firm and durable; the pure tantalum coating is used to embed harmful metal ions of the vascular stent and improve the development effect of the vascular stent under an X-ray machine, making its implant material safer and the surgical field clearer; the high concentration of silver in the tantalum-silver coating can effectively avoid the problem of secondary restenosis of blood vessels caused by the proliferation of fibroblasts and myocytes after the drug release is completed.

[0008] Preferably, the bare metal stent is composed of a stent head end circulation unit, a stent head connecting rod, a stent middle circulation unit, a stent middle connecting rod and a stent end circulation unit.

[0009] Preferably, the bare metal stent has a diameter of 1.5-4.5 mm, a wall thickness of 0.05-0.08 mm, and a length of 5-35 mm.

[0010] Preferably, the pure titanium coating, the pure tantalum coating and the tantalum-silver coating have the same thickness.

[0011] Preferably, the drug carrier layer, the drug mixed coating layer and the drug protective layer have the same thickness.

[0012] Preferably, the drug carrier layer is composed of PLA and PGA.

[0013] Preferably, the drug mixed coating consists of Rapamycin and PLGA.

[0014] Preferably, the drug protection layer is composed of PLA and PGA.

[0015] The present invention also provides a method for manufacturing the self-imaging drug-eluting coronary stent with a composite metal coating, comprising the following steps:

[0016] S1 Design the three-dimensional model of the bracket: First, the three-dimensional model of the bracket data is designed through the three-dimensional design software Pro / Engineer, and then the structural mechanics of the bracket is analyzed through the ANSYS software, and the wall thickness, radial support force, radial and axial yield parameters are designed to obtain the optimized pattern structure;

[0017] S2 manufactures bare stents: according to the pre-designed three-dimensional drawings of the stents, the drawings are converted into two-dimensional processing drawings through CAD software, and then imported into specific laser cutting programming software to form CNC processing programs. The programs are imported into the laser cutting machine for processing, and the laser-processed stents are placed in the electrochemical polishing machine for polishing to obtain bare stents;

[0018] S3 bare stent surface metal coating processing: using PVD physical vapor deposition equipment to coat, successively carry out pure titanium coating, pure tantalum coating, and tantalum silver coating to obtain a composite metal coating stent;

[0019] S4 stent drug spraying: Use ultrasonic atomization sprayer to spray according to the composition and configuration ratio of the drug coating.

[0020] Compared with the prior art, the present invention has the following beneficial effects:

[0021] 1. The designed multifunctional metal coating effectively solves the material problems of the existing metal stent platform, such as the release of harmful metal ions, poor development, poor biocompatibility, and poor radial support. The silver element contained in the material can effectively inhibit the occurrence of inflammation and reduce the problem of secondary restenosis of the stent after the drug release is completed.

[0022] 2. The designed low concentration and time-controlled drug coating can accurately inhibit smooth muscle cell proliferation and shorten the endothelialization rate of the drug stent, thereby effectively solving the problem of thrombotic inflammation. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 It is a schematic diagram of the overall structure of the present invention;

[0024] Figure 2 This is a schematic diagram of the unfolded structure of the bare metal stent of the present invention;

[0025] Figure 3 It is a schematic diagram of the side structure of the bare metal stent of the present invention.

[0026] In the figure: 1. stent head end circulation unit, 2. stent head connecting rod, 3. stent middle circulation unit, 4. stent middle connecting rod, 5. stent end circulation unit, 6. metal bare stent, 7. pure titanium coating, 8. pure tantalum coating, 9. tantalum silver coating, 10. drug carrier layer, 11. drug mixed coating, 12. drug protective layer. DETAILED DESCRIPTION

[0027] The technical solution of the present invention is further described below with reference to the accompanying drawings and through specific implementation methods.

[0028] See also Figure 1-3 As shown, a self-radiographic drug-eluting coronary stent with a composite metal coating includes a bare metal stent 6, a pure titanium coating 7, a pure tantalum coating 8, a tantalum-silver coating 9, a drug carrier layer 10, a drug mixed coating 11, and a drug protective layer 12. The pure titanium coating 7 is arranged on the outer ring of the bare metal stent 6, the pure tantalum coating 8 is arranged on the outer ring of the pure titanium coating 7, the tantalum-silver coating 9 is arranged on the outer ring of the pure tantalum coating 8, the drug carrier layer 10 is arranged on the outer ring of the tantalum-silver coating 9, the drug mixed coating 11 is arranged on the outer ring of the drug carrier layer 10, and the drug protective layer 12 is arranged on the outer ring of the drug mixed coating 11. The bare metal stent 6 is composed of a stent head end circulation unit 1, a stent head connecting rod 2, a stent middle circulation unit 3, a stent middle connecting rod 4, and a stent end circulation unit 5.

[0029] The stent structure is designed using three-dimensional design software. The stent involved in the present invention is designed using Pro / Engineer and CAD software. The size and model of the bare stent are shown in Table 1.

[0030] Table 1

[0031]

[0032] The bare metal stent 6 is processed by a laser cutting machine, and the stent processed by laser is put into an electrochemical polishing machine for polishing to finally obtain a bare stent. The multifunctional metal coating on the surface of the bare stent is processed by using PVD physical vapor deposition equipment, and the coating processing parameters are set within the range shown in Table 2.

[0033] Table 2

[0034]

[0035] The drug carrier layer 10, the drug mixed coating layer 11 and the drug protective layer 12 are coated using an ultrasonic atomization sprayer according to the parameter conditions shown in Table 3.

[0036] Table 3

[0037]

[0038] The main components of the drug coating and their configuration ratios are shown in Table 4.

[0039] Table 4

[0040]

[0041] The present invention first designs a three-dimensional model of the stent data through the three-dimensional design software Pro / Engineer, and then analyzes the structural mechanics of the stent through the ANSYS software to design a flower-shaped structure with the most optimized theoretical parameters (wall thickness, radial support force, radial and axial yield, etc.). The present invention designs a unique three-layer nano-level metal coating, which is: a pure titanium coating 7, which is used to improve the surface tissue engineering of the bare stent, improve the bonding force between the metal coating and the stent itself, and make it strong and durable; a pure tantalum coating 8, which is used to embed harmful metal ions of the stent and improve the development effect of the stent under the X-ray machine, making its implant material safer and the surgical field clearer; a tantalum silver coating 9, a high concentration of silver element inhibits the proliferation of fibroblasts. This research theory has been verified in the treatment of skin and tissue burns, thereby effectively avoiding the clinical problem of secondary restenosis of blood vessels caused by the proliferation of fibroblasts and muscle cells after the drug release is completed. The drug coating designed by the present invention has a lower concentration and sequential control, and PLA and PGA with different molecular weights are selected to form a PLGA carrier, and Rapamycin is mixed into PLGA. Through in vitro liquid phase simulation experiments, the most reasonable drug design curve is designed to completely release the drug within 90 days. Thus, the vascular stent can inhibit smooth muscle hyperplasia while quickly completing stent endothelialization; thereby effectively reducing the onset time of thrombosis and inflammation and the use of anticoagulant drugs, reducing the surgical risk of doctors and alleviating the economic burden on patients.

[0042] The above disclosure is only a specific embodiment of the present invention, but the present invention is not limited thereto, and any changes that can be conceived by those skilled in the art should fall within the protection scope of the present invention.

Claims

1. A self-radiographic drug-eluting coronary stent with a composite metal coating, characterized in that: The invention comprises a bare metal stent (6), a pure titanium coating (7), a pure tantalum coating (8), a tantalum-silver coating (9), a drug carrier layer (10), a drug mixed coating (11) and a drug protective layer (12), wherein the pure titanium coating (7) is arranged on the outer ring of the bare metal stent (6), the pure tantalum coating (8) is arranged on the outer ring of the pure titanium coating (7), the tantalum-silver coating (9) is arranged on the outer ring of the pure tantalum coating (8), the drug carrier layer (10) is arranged on the outer ring of the tantalum-silver coating (9), the drug mixed coating (11) is arranged on the outer ring of the drug carrier layer (10), and the drug protective layer (12) is arranged on the outer ring of the drug mixed coating (11); The pure titanium coating (7) is used to improve the surface tissue engineering of the bare metal stent (6), increase the bonding strength between the metal coating and the stent itself, and make it strong and durable; The pure tantalum coating (8) is used to embed harmful metal ions of the vascular stent and improve the development effect of the vascular stent under an X-ray machine, making the implantation material safer and the surgical field clearer; The high concentration of silver in the tantalum-silver coating (9) can effectively prevent the problem of secondary restenosis of blood vessels caused by the proliferation of fibroblasts and myocytes after the drug is released; The bare metal stent (6) is composed of a stent head end circulation unit (1), a stent head connecting rod (2), a stent middle circulation unit (3), a stent middle connecting rod (4) and a stent end circulation unit (5); The drug carrier layer (10) is composed of PLA and PGA, and the mass ratio of the two is 45:65; The drug mixed coating (11) is composed of Rapamycin and PLGA, and the mass ratio of the two is 35:65; The drug protection layer (12) is composed of PLA and PGA, and the mass ratio of the two is 50:

50.

2. The self-radiographic drug-eluting coronary stent with composite metal coating according to claim 1, characterized in that: The bare metal stent (6) has a diameter of 1.5-4.5 mm, a wall thickness of 0.05-0.08 mm, and a length of 5-35 mm.

3. The self-radiographic drug-eluting coronary stent with composite metal coating according to claim 1, characterized in that: The pure titanium coating (7), the pure tantalum coating (8) and the tantalum-silver coating (9) have the same thickness.

4. The self-radiographic drug-eluting coronary stent with composite metal coating according to claim 1, characterized in that: The drug carrier layer (10), the drug mixed coating (11) and the drug protective layer (12) have the same thickness.

5. The method for manufacturing a self-imaging drug-eluting coronary stent with a composite metal coating according to any one of claims 1 to 4, characterized in that: The steps include: S1 Design the three-dimensional model of the bracket: First, the three-dimensional model of the bracket data is designed through the three-dimensional design software Pro / Engineer, and then the structural mechanics of the bracket is analyzed through the ANSYS software, and the wall thickness, radial support force, radial and axial yield parameters are designed to obtain the optimized pattern structure; S2 manufactures bare stents: according to the pre-designed three-dimensional drawings of the stents, the drawings are converted into two-dimensional processing drawings through CAD software, and then imported into specific laser cutting programming software to form CNC processing programs. The programs are imported into the laser cutting machine for processing, and the laser-processed stents are placed in the electrochemical polishing machine for polishing to obtain bare stents; S3 bare stent surface metal coating processing: using PVD physical vapor deposition equipment to coat, in sequence, pure titanium coating (7), pure tantalum coating (8), and tantalum silver coating (9) to obtain a composite metal coating stent; S4 stent drug spraying: Use ultrasonic atomization sprayer to spray according to the composition and configuration ratio of the drug coating.

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