Intravascular stent

Abstract

The invention relates to the technical field of medical instruments, in particular to an intravascular stent. According to the specific technical scheme, the intravascular stent comprises a stent skeleton, after the stent skeleton is subjected to surface treatment, at least one layer of film covering section is arranged outside the stent skeleton, and medicine release sections are arranged at the two ends of the stent skeleton. The problems that in the drug release process of an existing stent, the drug release rate is uneven, biocompatibility is poor, and thrombus and restenosis are caused by a metal stent are solved.

Description

Technical Field

[0001] The present invention relates to the technical field of medical devices, and in particular to a vascular stent. Background Art

[0002] With the development of modern medicine, cardiovascular disease has become one of the major health problems worldwide. In particular, coronary heart disease and peripheral arterial disease often lead to vascular stenosis or blockage, thus affecting blood supply and even endangering life in severe cases. Although traditional treatments such as drug therapy and surgery are effective, they have disadvantages such as large trauma and long recovery time. Therefore, the application of vascular stents came into being and became an effective interventional treatment method.

[0003] Vascular stents are an internal device that supports blood vessels and is mainly used to maintain the patency of the blood vessel lumen and prevent restenosis of the blood vessel. Existing vascular stents are usually made of metal materials, such as stainless steel or nickel-titanium alloy, which have good mechanical strength and elasticity. However, metal stents may cause complications such as thrombosis, inflammatory response and restenosis after implantation. In addition, metal stents have poor biocompatibility, which may cause patient discomfort or long-term complications, limiting their widespread application.

[0004] In order to inhibit complications such as thrombosis, inflammatory response and restenosis, new biomaterials, such as coated stents, have attracted widespread attention. Coated stents can effectively inhibit the proliferation of smooth muscle cells by coating the surface of the stent with biocompatible materials and carrying anti-proliferative drugs, thereby reducing the risk of restenosis. However, the drug release characteristics and long-term biocompatibility of this type of stent still need to be further optimized. To this end, the present invention develops a new vascular stent that has good mechanical properties, superior biocompatibility and effective drug release ability, which can not only improve the performance of existing stents and reduce the risk of complications, but also significantly improve the quality of life of patients. Summary of the invention

[0005] In view of the deficiencies of the prior art, the present invention provides a vascular stent, which aims to solve the problems of uneven drug release rate, poor biocompatibility, and thrombosis and restenosis caused by metal stents during drug release.

[0006] To achieve the above objectives, the present invention is implemented through the following technical solutions:

[0007] The invention discloses a blood vessel stent, comprising a stent frame. After surface treatment, the stent frame is provided with at least one layer of film-coated sections on the outside, and drug-releasing sections are provided at both ends of the stent frame.

[0008] Preferably, the coating segment is arranged in the middle part of the stent skeleton.

[0009] Preferably, the stent skeleton comprises metal or polymer material, the material of the coating section comprises biocompatible material, and the drug in the drug release section is mixed with a polymer matrix.

[0010] Preferably, the metal material includes one of stainless steel, cobalt-chromium alloy, nickel-titanium alloy, and degradable metal, and the polymer material includes a natural polymer material or a synthetic polymer material.

[0011] Preferably, the degradable metal includes one of magnesium alloy, iron alloy, and zinc alloy; the natural polymer material includes one of collagen, elastin, silk fibroin, and chitosan; and the synthetic polymer material includes one of polylactic acid, polycaprolactone, and polylactic acid-glycolic acid copolymer.

[0012] Preferably, the biocompatible material includes a natural polymer material or an artificially synthesized polymer material, the natural polymer material includes one of chitosan and its derivatives, and chitosan, and the artificially synthesized polymer material includes one of polydimethylsiloxane, polylactic acid, polycaprolactone, and thermoplastic polyurethane.

[0013] Preferably, the polymer matrix comprises a non-degradable polymer matrix or a degradable polymer matrix.

[0014] Preferably, the non-degradable polymer matrix includes one of p-xylene, poly(n-butyl methacrylate) and hexafluoropropylene, and the degradable polymer matrix includes one of polylactic acid and poly(lactic acid-glycolic acid copolymer).

[0015] Preferably, the surface treatment is chemical modification or coating with a nano-coating; the chemical modification includes amination treatment or hydroxylation treatment; the nano-coating includes polylactic acid or polyvinyl alcohol.

[0016] Correspondingly, a method for preparing a vascular stent comprises preparing a stent skeleton by electrospinning, preparing a coating section on the stent skeleton, and coating drugs on both ends of the stent skeleton to form a drug release section.

[0017] The present invention has the following beneficial effects:

[0018] 1. The present invention optimizes the stent surface coating material and structural design to ensure that the middle coating section of the stent after implantation can isolate the direct contact between blood and the stent material, reduce platelet activation and thrombosis, and thus reduce the risk of restenosis. The uncoated ends of the stent provide better fit between the stent and the blood vessel wall, which helps the stent better adapt to the shape and movement of the blood vessel, and improves the stability and long-term effect of the stent. At the same time, at both ends of the surface-treated stent, drugs can be released continuously and stably to achieve the effect of preventing restenosis. The present invention significantly improves the therapeutic effect of the vascular stent and improves the long-term prognosis of patients.

[0019] 2. Although traditional vascular stents can effectively prop open narrow or blocked blood vessels, they cannot provide continuous drug release to prevent complications such as postoperative restenosis of blood vessels. In addition, traditional stents may induce inflammatory reactions and thrombosis, increasing the risk for patients. Therefore, the present invention stores drugs at both ends of the coating, which can not only provide mechanical support, but also concentrate the drugs at both ends of the stent skeleton, ensuring that the drugs reach a higher local concentration in the most serious part of the vascular lesions, thereby improving the efficacy. At the same time, loading drugs only at both ends of the stent skeleton can avoid delaying the coverage of vascular endothelial cells and reduce the risk of thrombosis. The coated drug-delivery vascular stent of the present invention provides a safer and more effective treatment for vascular diseases through its unique design and preparation method, and is expected to replace traditional vascular stents and become a new choice for future vascular interventional treatments.

[0020] 3. The coated drug-delivery vascular stent of the present invention allows drugs to act directly on the vascular wall, and the presence of the coating can also prevent tissue cell penetration. Both methods can effectively prevent vascular restenosis. With further research and clinical trials, this coated drug-delivery vascular stent plays an important role in the field of vascular disease treatment, providing patients with safer and more effective treatment options. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 It is a schematic diagram of the structure of a vascular stent;

[0022] Figure 2 is a relationship diagram between the stretching length and the pulling force of the vascular stent;

[0023] Figure 3 is a relationship diagram between the stretching rate and the tension of the vascular stent;

[0024] Figure 4 This is an application scenario diagram of vascular stents. DETAILED DESCRIPTION

[0025] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0026] Unless otherwise specified, the technical means used in the embodiments are conventional means well known to those skilled in the art.

[0027] The present invention discloses a vascular stent, comprising a stent skeleton, wherein the stent skeleton is provided with at least one coating segment on the outside after surface treatment, and the coating segment is provided in the middle of the stent skeleton. Drug release segments are provided at both ends of the stent skeleton, that is, the drug adheres to the outer surface of both ends of the surface-treated stent skeleton. The provision of the coating segment can help isolate the direct contact between blood and the stent skeleton, thereby reducing the risk of thrombosis. In addition, the presence of the membrane can change the local environment, limit the migration of smooth muscle cells into the stent, and reduce the attachment and growth of cells on the stent surface. The drug in the drug release segment is mixed with a polymer matrix.

[0028] Wherein, the stent skeleton comprises metal or polymer material, the metal material comprises one of stainless steel, cobalt-chromium alloy, nickel-titanium alloy, and degradable metal, and the polymer material comprises natural polymer material or synthetic polymer material. Specifically: the degradable metal comprises one of magnesium alloy, iron alloy, and zinc alloy; the natural polymer material comprises one of collagen, elastin, silk fibroin, and chitosan; the synthetic polymer material comprises one of polylactic acid, polycaprolactone, and polylactic-glycolic acid copolymer.

[0029] Furthermore, the material of the coating section includes a biocompatible material. The biocompatible material includes a natural polymer material or a synthetic polymer material, the natural polymer material includes one of chitosan and its derivatives, and chitosan, and the synthetic polymer material includes one of polydimethylsiloxane, polylactic acid, polycaprolactone, and thermoplastic polyurethane.

[0030] Furthermore, the polymer matrix includes a non-degradable polymer matrix or a degradable polymer matrix. The non-degradable polymer matrix includes one of p-xylene, poly(n-butyl methacrylate) and hexafluoropropylene, and the degradable polymer matrix includes one of polylactic acid and poly(lactic acid-glycolic acid copolymer).

[0031] Furthermore, the surface treatment of the stent skeleton is chemical modification or coating with a nano coating. The chemical modification includes amination or hydroxylation, and the specific operation process of the chemical modification is the prior art; the nano coating includes polylactic acid or polyvinyl alcohol. For example, the chemical modification [1-3] and the coating of the nano coating [4,5] can be carried out with reference to the following prior art:

[0032] [1]J.Ha,J.Ko,J.Ahn,Y.Jeong,et al,Nanotransfer Printing of FunctionalNanomaterials on Electrospun Fibers for Wearable Healthcare Applications.Adv.Funct.Mater.2024,34,2401404.

[0033] [2]S.Pan,F.Zhang,P.Cai,et al,Mechanically Interlocked Hydrogel-Elastomer Hybrids for On-Skin Electronics.Adv.Funct.Mater.2020,30,1909540.

[0034] [3]Q.Cheng,B.Lee,K.Komvopoulos,et al,Plasma Surface ChemicalTreatment of Electrospun Poly(l-Lactide)Microfibrous Scaffolds for EnhancedCell Adhesion,Growth,and Infiltration.Tissue Eng.Pt.A.2013,19(9-10):1188-1198.

[0035] [4]N.Nhlapo,T.Dzogbewu,O.Smidt,Nanofiber polymers for coatingtitanium-based biomedical implants.Fibers,2022,10(4):36.

[0036] [5]B.Mavis,T.Demirta M.Gümü derelio lu,etal.Synthesis,characterization and osteoblastic activity of polycaprolactone nanofiberscoated with biomimetic calcium phosphate.Acta biomaterialia,2009,5(8):3098-3111.

[0037] As one embodiment, the drugs include antiproliferative drugs, anti-inflammatory drugs and antiplatelet drugs, which can be effectively released into the surrounding tissues and migrate to the vascular endothelium, inhibit the proliferation and migration of smooth muscle cells, slow down the process of intimal hyperplasia, and prevent the occurrence of restenosis. Among them, antiproliferative drugs include paclitaxel, sirolimus, pinaverium bromide, milrinone, rosiglitazone, etc. Anti-inflammatory drugs include paclitaxel, cilostazol, adiponectin, ring finger protein 10, statins, etc. Statins include lovastatin, atorvastatin, rosuvastatin, pitavastatin, etc. Antiplatelet drugs include aspirin, clopidogrel, cilostazol, ticagrelor, etc. Of course, other drugs of the same kind with similar effects can also be replaced.

[0038] The present invention discloses a method for preparing a vascular stent, wherein a stent skeleton is prepared by electrospinning, and a coating section is prepared on the stent skeleton, and drugs are coated on both ends of the stent skeleton to form drug release sections. The coating section and drug release section on the surface of the stent skeleton can adopt a multi-segment structure design, and the drug release section is loaded with drugs required for treating vascular diseases, and is responsible for the storage and release of drugs, such as anti-proliferative drugs, anti-inflammatory drugs and anti-platelet drugs. The release rate of the drug can be controlled by adjusting the ratio of the drug to the polymer matrix. The coating section uses biocompatible materials and can be a single layer or a multi-layer. The mechanical properties and durability of the coated stent skeleton can be regulated by the number of coating layers.

[0039] The present invention will be further described below in conjunction with specific embodiments.

[0040] Example 1

[0041] The specific structure of the prepared vascular stent is shown in the attached figure, using paclitaxel as the drug, thermoplastic polyurethane elastomer as the coating material, and nickel-titanium alloy as the stent skeleton material. Figure 1 As shown. The length of the stent is about 7 cm and the diameter is about 0.6 cm. The coating layer 12 is evenly covered on the nickel-titanium alloy stent frame 11. The drug 13 (such as paclitaxel) is combined with the surface-modified stent frame and evenly coated on the surface of the stent frame, so that after the stent is implanted in the blood vessel, the drug can directly act on the blood vessel wall to reduce the risk of restenosis.

[0042] Different ratios of paclitaxel and PLGA mixtures were coated on the surface of the stent skeleton to evaluate the effect of different ratios on the drug release rate. For drug release, increasing the proportion of polymer matrix can slow down the drug release rate. By adjusting the ratio, the local concentration of the drug can be increased and the rate of drug release can be controlled, thereby reducing the risk of restenosis while maintaining the efficacy and biological activity of the drug.

[0043] When preparing vascular stents, the coating segment is prepared by electrospinning technology. Thermoplastic polyurethane elastomer is spun onto the metal stent. Thermoplastic polyurethane is dissolved in a mixed solution of N,N-dimethylformamide and tetrahydrofuran, the volume ratio of N,N-dimethylformamide and tetrahydrofuran is 3:1, and the mass fraction of thermoplastic polyurethane is 10% to obtain a mixed solution. The mixed solution is loaded into a syringe and placed on an electrospinning machine. Under the action of a high-voltage electrostatic field, the solution is squeezed out of the needle of the syringe and forms a charged droplet. Due to the action of the electric field force, the droplet is stretched into a long and thin jet. The solvent evaporates as the jet flies to the collection plate, and finally solid nanofibers are formed and coated on the stent skeleton. The coating thickness is about 0.1mm. After being tested by a tensile tester, the stent can be stretched by 8mm under continuous application of tension, and the diameter is reduced from 6.2mm to 1.5mm after stretching. The relationship between the stretching length and the tension is as follows Figure 2 The bracket was reciprocated and stretched 500 times using a flexible electronic tester, with each stretching length of 8 mm and a stretching speed of 3 mm / s. After the cycle test, the stretching instrument was used to test again. The stretching rate hardly changed. At this time, the relationship between the stretching rate and the tension is as shown in Figure 3 shown.

[0044] Application scenarios of coated drug-delivery vascular stents include Figure 4 As shown. The stent can fit tightly to the blood vessel 61. Thermoplastic polyurethane 63 coated on the outer surface of the metal stent 62 can prevent tissue cell penetration and prevent the occurrence of intimal hyperplasia from the source, thereby achieving the purpose of treating restenosis in the stent. Paclitaxel 64 is evenly coated on both ends of the stent. When the stent is implanted in the blood vessel, paclitaxel will gradually be released from the outside to the inside. Paclitaxel 64 in contact with the blood vessel wall can completely inhibit the proliferation of vascular smooth muscle and can also achieve the effect of preventing restenosis of the blood vessel. The safety and effectiveness of the stent and the drug are evaluated by cell proliferation experiments, cell migration experiments, cytotoxicity experiments and in vitro drug release experiments.

[0045] The embodiments described above are only descriptions of the preferred modes of the present invention, and are not intended to limit the scope of the present invention. Without departing from the design spirit of the present invention, various modifications and improvements made to the technical solutions of the present invention by ordinary technicians in this field should all fall within the protection scope determined by the claims of the present invention.

Claims

1. A vascular stent, comprising a stent frame, characterized in that: After the surface treatment, the stent skeleton is provided with at least one layer of coating segment on the outside, and drug release segments are provided at both ends of the stent skeleton.

2. A vascular stent according to claim 1, characterized in that: The coating section is arranged in the middle part of the stent frame.

3. A vascular stent according to claim 1, characterized in that: The stent framework comprises metal or polymer material, the material of the coating section comprises biocompatible material, and the drug in the drug release section is mixed with a polymer matrix.

4. A vascular stent according to claim 3, characterized in that: The metal material includes one of stainless steel, cobalt-chromium alloy, nickel-titanium alloy, and degradable metal; the polymer material includes natural polymer material or synthetic polymer material.

5. A vascular stent according to claim 4, characterized in that: The degradable metal includes one of magnesium alloy, iron alloy and zinc alloy; the natural polymer material includes one of collagen, elastin, silk fibroin and chitosan; the synthetic polymer material includes one of polylactic acid, polycaprolactone and polylactic acid-glycolic acid copolymer.

6. A vascular stent according to claim 3, characterized in that: The biocompatible material includes a natural polymer material or an artificially synthesized polymer material. The natural polymer material includes one of chitosan and its derivatives, and chitosan. The artificially synthesized polymer material includes one of polydimethylsiloxane, polylactic acid, polycaprolactone, and thermoplastic polyurethane.

7. The vascular stent according to claim 3, characterized in that: The polymer matrix includes a non-degradable polymer matrix or a degradable polymer matrix.

8. A vascular stent according to claim 7, characterized in that: The non-degradable polymer matrix includes one of p-xylene, poly(n-butyl methacrylate) and hexafluoropropylene, and the degradable polymer matrix includes one of polylactic acid and poly(lactic acid-glycolic acid copolymer).

9. The vascular stent according to claim 1, characterized in that: The surface treatment is chemical modification or coating of a nano coating; the chemical modification includes amination treatment or hydroxylation treatment; the nano coating includes polylactic acid or polyvinyl alcohol.

10. A method for preparing a vascular stent according to any one of claims 1 to 9, characterized in that: The stent skeleton is prepared by electrospinning, and a coating segment is prepared on the stent skeleton. Drugs are coated on both ends of the stent skeleton to form drug release segments.

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