Adhesive coating material, preparation method thereof and drug coating stent

Abstract

The invention relates to the technical field of medical instruments, in particular to an adhesive coating material, a preparation method thereof and a drug coating stent. The adhesive coating material and the drug coating stent comprise a block copolymer (PBMA-b-PVP) containing a polybutyl methacrylate chain segment and a polyvinylpyrrolidone chain segment, the ratio of the total weight of the polybutyl methacrylate chain segment to the total weight of the polyvinylpyrrolidone chain segment is 100: (20-80), the block copolymer has the adjustable chain segment length, and the length of the block copolymer is larger than that of the PBMA-b-PVP. The adhesive has higher bonding strength and adhesion to the metal surface, also has good biocompatibility, and has higher clinical application value.

Description

Technical Field

[0001] The present application relates to the technical field of medical devices, and in particular to an adhesive coating material and a preparation method thereof, and a drug-coated stent. Background Art

[0002] Drug-eluting stents are medical devices used to treat coronary artery disease, designed to reduce the restenosis rate after stent implantation. Drug-eluting stents are made by coating the surface of metal stents with drugs, which are gradually released after stent implantation to exert biological effects on local vascular tissue.

[0003] Drug-eluting stents mainly consist of three parts: a metal stent, an adhesive coating and a drug-loaded layer. The adhesive coating material usually plays the role of fixing and bonding the metal stent and the drug-loaded layer, and plays a vital role in the efficacy of the drug-eluting stent.

[0004] Adhesive coating materials are usually polymers such as methyl acrylate, polylactic acid, chondroitin sulfate, etc. However, the bonding strength and adhesion of the above materials to the metal surface are not high enough, which leads to the risk of coating peeling during the delivery and expansion of drug-coated stents in the body, which may stimulate surrounding tissues and cause inflammatory reactions, thereby increasing the risk of thrombosis.

[0005] Based on this, it is necessary to develop an adhesive coating material with high bonding strength to metal, good adhesion and good biocompatibility. Summary of the invention

[0006] Based on this, one or more embodiments of the present application provide an adhesive coating material and a preparation method thereof and a drug-coated stent. The adhesive coating material of the present application has good adhesion, high bonding strength with the metal substrate and good biocompatibility.

[0007] The technical solution of this application includes the following contents:

[0008] An adhesive coating material comprising a block copolymer comprising a polybutyl methacrylate segment and a polyvinyl pyrrolidone segment;

[0009] Wherein, the total weight ratio of the polybutyl methacrylate chain segment to the polyvinyl pyrrolidone chain segment is 100:(20-80).

[0010] In one embodiment, the adhesive coating material satisfies at least one of the following conditions:

[0011] (1) Number average molecular weight is 28000~45000;

[0012] (2) Weight average molecular weight is 40,000~60,000;

[0013] (3) At 1645cm -1 ~1655cm -1 and 1725cm -1 ~1735cm -1 It has characteristic infrared peaks.

[0014] In one embodiment, the bonding coating material is rated as Grade 0 in the ISO 2409-2019 material adhesion cross-cut test standard.

[0015] A method for preparing the adhesive coating material as described above comprises the following steps:

[0016] Butyl methacrylate is subjected to reversible addition-fragmentation chain transfer polymerization to obtain a first polymer;

[0017] polymerizing the first polymer and vinyl pyrrolidone to obtain the adhesive coating material;

[0018] Wherein, the mass ratio of the first polymer to the vinyl pyrrolidone is 100:(20-80).

[0019] In one embodiment, the step of preparing the first polymer by reversible addition-fragmentation chain transfer polymerization of butyl methacrylate comprises:

[0020] dissolving butyl methacrylate, a first initiator and a chain transfer agent in an organic solvent to obtain a first solution;

[0021] reacting the first solution in a first protective gas at a first heating temperature for a first time to obtain the first polymer;

[0022] Wherein, the first protective gas includes at least one of nitrogen, helium and argon, the first heating temperature is 60° C. to 80° C., and the first time is 1 h to 5 h.

[0023] In one embodiment, the molar ratio of the butyl methacrylate, the first initiator and the chain transfer agent is 100: (0.6-1.0): (0.5-0.8).

[0024] In one embodiment, the preparation method satisfies at least one of the following conditions:

[0025] (1) The chain transfer agent includes at least one of diisopropyl xanthate disulfide, dithiocarbamate, dithiobenzoate and dithiobenzoic acid cyanoisopropyl ester;

[0026] (2) The first initiator includes at least one of azobisisobutyronitrile, azobisisoheptanenitrile and 1,1'-azo(cyanocyclohexane).

[0027] In one embodiment, the step of polymerizing the first polymer and vinyl pyrrolidone to obtain the adhesive coating material comprises:

[0028] dissolving the first polymer, vinyl pyrrolidone and a second initiator in an organic solvent to obtain a second solution;

[0029] reacting the second solution under a second protective gas and a second heating temperature for a second time to obtain a second polymer;

[0030] Wherein, the second protective gas includes at least one of nitrogen, helium and argon, the second heating temperature is 60° C. to 80° C., and the second time is 3 h to 6 h.

[0031] In one embodiment, the mass ratio of the first polymer, the second initiator and the vinyl pyrrolidone is 100:(3-5):(20-80).

[0032] In one embodiment, the second initiator includes at least one of azobisisobutyronitrile, azobisisoheptanenitrile and 1,1'-azo(cyanocyclohexane).

[0033] A drug-coated stent comprises a metal stent substrate and a coating layer coated on the surface of the metal stent substrate;

[0034] The materials for preparing the coating layer include the adhesive coating material and the drug mentioned above.

[0035] The adhesive layer material and drug-coated stent of the present application include a block copolymer (PBMA-b-PVP) containing a polybutyl methacrylate segment and a polyvinyl pyrrolidone segment, which has an adjustable segment length within a certain range, has stronger bonding strength and adhesion to metal surfaces, and also has good biocompatibility and high clinical application value. BRIEF DESCRIPTION OF THE DRAWINGS

[0036] In order to more clearly illustrate the specific implementation methods of the present application or the technical solutions in the prior art, the drawings required for use in the specific implementation methods or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are some implementation methods of the present application. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0037] Figure 1 This is an infrared detection comparison diagram of the adhesive coating material and pure PBMA material prepared in Example 3 of the present application;

[0038] Figure 2This is a H NMR comparison chart of the adhesive coating material prepared in Example 3 of the present application and the pure PBMA material. DETAILED DESCRIPTION

[0039] The present application will be further described below in conjunction with the embodiments and examples. It should be understood that these examples are only used to illustrate the present application and are not intended to limit the scope of the present application. In addition, it should be understood that after reading the content taught in the present application, those skilled in the art may make various changes or modifications to the present application, and these equivalent forms also fall within the protection scope of the claims attached to the present application.

[0040] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those commonly understood by those skilled in the art to which this application belongs. The terms used herein in the specification of this application are only for the purpose of describing specific embodiments and are not intended to limit this application.

[0041] the term

[0042] Unless otherwise specified or incompatible herewith, the terms and phrases used herein shall have the following meanings:

[0043] The term "and / or" used in this article includes any one of two or more related listed items, and also includes any and all combinations of related listed items, and the arbitrary and all combinations include any two related listed items, any more related listed items, or all related listed items. It should be noted that when at least three items are connected by at least two conjunctions selected from "and / or", "or / and", and "and / or", it should be understood that in this application, the technical solution undoubtedly includes technical solutions that are all connected by "logical and", and undoubtedly includes technical solutions that are all connected by "logical or". For example, "A and / or B" includes three parallel solutions of A, B and A+B.

[0044] Herein, "preferred", "preferable", "better", etc. are only used to describe implementation methods or examples with better effects. It should be understood that they do not constitute limitations on the scope of protection of this application.

[0045] In the present application, "further" and the like are used for descriptive purposes to indicate differences in content, but should not be construed as limiting the scope of protection of the present application.

[0046] In this application, the terms "first", "second", etc. are used only for descriptive purposes and cannot be understood as indicating or implying relative importance or quantity, nor can they be understood as implicitly indicating the importance or quantity of the indicated technical features. Moreover, "first", "second", etc. only serve the purpose of non-exhaustive enumeration and description, and it should be understood that they do not constitute a closed limitation on quantity.

[0047] In the present application, the technical features described in an open manner include closed technical solutions composed of the listed features, and also include open technical solutions containing the listed features.

[0048] In this application, when it comes to numerical intervals (i.e., numerical ranges), unless otherwise specified, the optional numerical distribution is considered continuous within the above numerical interval, and includes the two numerical endpoints (i.e., the minimum and maximum values) of the numerical range, and each numerical value between the two numerical endpoints. Unless otherwise specified, when the numerical interval only refers to integers within the numerical interval, it includes the two endpoint integers of the numerical range, and each integer between the two endpoints. In addition, when multiple ranges are provided to describe features or characteristics, these ranges can be combined. In other words, unless otherwise specified, the ranges disclosed herein should be understood to include any and all subranges included therein.

[0049] In the present application, weight may be μg, mg, g, kg or other mass units known in the chemical industry.

[0050] In this application, the average molecular weight (Mn) is also called the number average molecular weight, which is obtained by adding the molecular weights of all polymer molecules and then dividing by the total number of molecules, reflecting the arithmetic mean of the molecular weights of all molecules in the polymer sample. The weight average molecular weight (Mw), also called the weight average molecular weight, is obtained by adding the product of the molecular weight of each molecule and its number and then dividing by the sum of the products of the molecular weights of all molecules, reflecting the influence of high molecular weight molecules on polymer properties.

[0051] Drug-eluting stent is an important medical device used in coronary intervention to improve vascular patency and prevent restenosis. Its structure mainly includes a metal stent and a coating coated on the surface of the metal stent. The coating is usually composed of polymer materials and drugs. After the stent is placed in the diseased site of the blood vessel, the drug is released from the polymer coating into the cardiovascular wall tissue to exert a biological effect.

[0052] In order to further improve the adhesion and bonding strength of the coating, the present application provides an adhesive coating material, which includes a block copolymer including a polybutyl methacrylate segment and a polyvinyl pyrrolidone segment;

[0053] The total weight ratio of the polybutyl methacrylate chain segment to the polyvinyl pyrrolidone chain segment is 100:(20-80).

[0054] In one embodiment, the total weight ratio of the polybutyl methacrylate segment to the polyvinyl pyrrolidone segment is 100:(20-80), and more preferably 100:(40-60), for example 100:20, 100:30, 100:40, 100:50, 100:60, 100:70, 100:80, etc.

[0055] In one embodiment, the adhesive coating material satisfies at least one of the following conditions:

[0056] (1) Number average molecular weight is 28000~45000;

[0057] (2) Weight average molecular weight is 40,000~60,000;

[0058] (3) At 1645cm -1 ~1655cm -1 and 1725cm -1 ~1735cm -1 It has characteristic infrared peaks.

[0059] Optionally, the number average molecular weight of the adhesive coating material is selected from 28000~45000, and can be further selected from 28000~40000, for example: 28000, 28500, 29600, 30800, 31200, 31300, 31700, 31800, 32200, 32600, 33100, 33500, 33800, 34900, 38700, 40000, 45000, etc.

[0060] Optionally, the weight average molecular weight of the adhesive coating material is selected from 40000~60000, and can be further selected from 40000~55000, for example: 40000, 40400, 41500, 42000, 43100, 43600, 44000, 44500, 45100, 45200, 45300, 45600, 46400, 48900, 52900, 54100, 55000, 60000, etc.

[0061] In one embodiment, the bonding coating material is rated higher than level 2 in the ISO 2409-2019 material adhesion cross-cut test standard. It may further be level 1, and further may be level 0.

[0062] Among them, in the adhesion test, the material of the adhesion layer can be an alloy material such as titanium-nickel alloy, stainless steel 316L, etc., or a polymer such as polylactic acid, etc. These materials are all selected from common materials that can be used to prepare built-in medical devices.

[0063] The above-mentioned adhesive coating material has good biocompatibility. In one embodiment, the relative cell proliferation rate of the adhesive coating material in the cytotoxicity experiment of ASTM 16886-5:2017 standard is 110%~130%, further can be 115%~130%, and further can be 120%~130%, for example, 121.40%, 122.34%, 122.53%, 125.66%, 128.52%, etc.

[0064] A method for preparing the adhesive coating material as described above comprises the following steps:

[0065] Butyl methacrylate is subjected to reversible addition-fragmentation chain transfer polymerization to obtain a first polymer;

[0066] polymerizing the first polymer and vinyl pyrrolidone to obtain an adhesive coating material;

[0067] Wherein, the mass ratio of the first polymer to vinyl pyrrolidone is 100:(20-80).

[0068] Optionally, the mass ratio of the first polymer to vinyl pyrrolidone can be selected from 100:(20-80), and more preferably 100:(40-60), for example 100:20, 100:30, 100:40, 100:50, 100:60, 100:70, 100:80, etc.

[0069] In one embodiment, the step of preparing the first polymer by reversible addition-fragmentation chain transfer polymerization of butyl methacrylate comprises:

[0070] dissolving butyl methacrylate, a first initiator and a chain transfer agent in an organic solvent to obtain a first solution;

[0071] reacting the first solution in a first protective gas at a first heating temperature for a first time to produce a first polymer;

[0072] The first protective gas includes at least one of nitrogen, helium and argon, the first heating temperature is 60° C. to 80° C., and the first time is 1 h to 5 h.

[0073] Optionally, when the first heating temperature is 60℃~80℃, the second time is 1h~5h. For example, the second temperature is 60℃, 65℃, 70℃, 75℃, 80℃, etc., and for example, the second time is 1h, 2h, 3h, 4h, 5h, etc.

[0074] In one embodiment, the molar ratio of butyl methacrylate, the first initiator and the chain transfer agent is 100: (0.6-1.0): (0.5-0.8).

[0075] Optionally, the molar ratio of butyl methacrylate, the first initiator and the chain transfer agent can be selected from 100: (0.6-1.0): (0.5-0.8), for example 100: 0.6: 0.5, 100: 0.6: 0.6, 100: 0.6: 0.7, 100: 0.6: 0.8, 100: 0.7: 0.5, 100: 0.7: 0.6, 100: 0.7: 0.7, 100: 0.7: : 0.8, 100: 0.8: 0.5, 100: 0.8: 0.6, 100: 0.8: 0.7, 100: 0.8: 0.8, 100: 0.9: 0.5, 100: 0.9: 0.6, 100: 0.9: 0.7, 100: 0.9: 0.8, 100: 1.0: 0.5, 100: 1.0: 0.6, 100: 1.0: 0.7, 100: 1.0: 0.8, etc.

[0076] In one embodiment, the chain transfer agent includes at least one of diisopropyl xanthogen disulfide, dithiocarbamate, dithiobenzoate and cyanoisopropyl dithiobenzoate.

[0077] In one embodiment, the first initiator includes at least one of azobisisobutyronitrile, azobisisoheptanenitrile and 1,1'-azo(cyanocyclohexane).

[0078] In one embodiment, the step of polymerizing the first polymer and vinyl pyrrolidone to obtain the adhesive coating material comprises:

[0079] dissolving the first polymer, vinyl pyrrolidone and an initiator in an organic solvent to obtain a second solution;

[0080] reacting the second solution under a second protective gas and a second heating temperature for a second time to obtain a second polymer;

[0081] The second protective gas includes at least one of nitrogen, helium and argon, the second heating temperature is 60° C. to 80° C., and the second time is 3 h to 6 h.

[0082] Optionally, when the second heating temperature is 60℃~80℃, the second time is 3h~6h. For example, the second temperature is 60℃, 65℃, 70℃, 75℃, 80℃, etc., and for example, the second time is 3h, 4h, 5h, 6h, etc.

[0083] In one embodiment, the mass ratio of the first polymer, the second initiator and vinyl pyrrolidone is 100:(3-5):(20-80).

[0084] Optionally, the mass ratio of butyl methacrylate, the second initiator and vinyl pyrrolidone is 100:(3-5):(20-80), and can further be 100:(3-5):(40-60), for example 100:3:20, 100:3:40, 100:3:60, 100:3:80, 100:4:20, 100:4:40, 100:4:60, 100:4:80, 100:5:20, 100:5:40, 100:5:60, 100:5:80, etc.

[0085] In one embodiment, the second initiator includes at least one of azobisisobutyronitrile, azobisisoheptanenitrile and 1,1'-azo(cyanocyclohexane).

[0086] In one embodiment, the method for preparing the adhesive coating material comprises the following steps:

[0087] S100: After fully dissolving butyl methacrylate (BMA), an initiator and a chain transfer agent in an organic solvent, reacting them in nitrogen at 60°C to 80°C for 1h to 5h to obtain a first polymer; the molar ratio of butyl methacrylate (BMA), the initiator and the chain transfer agent may be 100: (0.6 to 1.0): (0.5 to 0.8); the first polymer is a macromolecular chain transfer agent homopolymer (PBMA);

[0088] S200: After the first polymer obtained in S100 is fully dissolved in an organic solvent, vinyl pyrrolidone (NVP) and an initiator are added, and the mixture is reacted in nitrogen at 60°C~80°C for 3h~6h to obtain a block copolymer PBMA-b-PVP; the mass ratio of the macromolecular chain transfer agent homopolymer PBMA, vinyl pyrrolidone and the initiator can be 100:(3~5):(20~80).

[0089] An adhesive coating is obtained by dissolving the above adhesive coating material in an organic solvent, coating the film, and drying the film.

[0090] A drug-coated stent comprises a metal stent substrate and a coating layer coated on the surface of the metal stent substrate;

[0091] The materials for preparing the coating layer include the above-mentioned adhesive coating material and drugs.

[0092] It can be understood that in one embodiment, the above-mentioned adhesive coating material is coated on the surface of the metal stent base, and after drying and curing, an adhesive layer is formed, and further a drug-carrying layer can be coated on the adhesive layer to obtain a corresponding drug-coated stent.

[0093] The adhesive layer material and drug-coated stent of the present application include a block copolymer (PBMA-b-PVP) containing a polybutyl methacrylate segment and a polyvinyl pyrrolidone segment, which has an adjustable segment length within a certain range, has stronger bonding strength and adhesion to metal surfaces, and also has good biocompatibility and high clinical application value.

[0094] The following are some specific embodiments.

[0095] For experimental parameters not specified in the following specific embodiments, reference is made to the instructions given in the present application document, and reference may also be made to experimental manuals in the art or other experimental methods known in the art, or to experimental conditions recommended by manufacturers.

[0096] The raw materials and reagents involved in the following specific examples can be obtained from commercial sources, or can be prepared by those skilled in the art according to known methods.

[0097] 1. Preparation of bonding coating materials

[0098] Embodiment 1: This embodiment provides an adhesive coating material and a preparation process thereof, and the preparation method is as follows:

[0099] (1) 100 g of butyl methacrylate, 1.447 g of initiator 1, 1'-azo(cyanocyclohexane), 1.049 g of chain transfer agent diisopropylphosphonium chloride (molar ratio 100:0.8:0.6) and 80 mL of toluene organic solvent were mixed, and after all the raw materials were fully dissolved, the mixture was reacted at 68° C. in nitrogen for 1.5 h to obtain a first polymer;

[0100] (2) 100 g of the first polymer, 50 g of vinyl pyrrolidone, 3 g of initiator AIBN (mass ratio 100:50:3) and 500 mL of toluene organic solvent were mixed, and after all the raw materials were fully dissolved, the mixture was reacted at 68° C. in nitrogen for 3 h to obtain an adhesive coating material.

[0101] Example 2: This example provides an adhesive coating material and a preparation process thereof. The only difference from Example 1 is that in step (2), each raw material is fully dissolved and then reacted in nitrogen at 68° C. for 4 hours.

[0102] Example 3: This example provides an adhesive coating material and a preparation process thereof. The only difference from Example 1 is that in step (2), each raw material is fully dissolved and then reacted in nitrogen at 68° C. for 5 hours.

[0103] Example 4: This example provides an adhesive coating material and a preparation process thereof. The only difference from Example 1 is that in step (2), each raw material is fully dissolved and then reacted in nitrogen at 68° C. for 6 hours.

[0104] Example 5: This example provides an adhesive coating material and a preparation process thereof, which is different from Example 1 only in that in step (1), the chain transfer agent used is dithiobenzoate.

[0105] Example 6: This example provides an adhesive coating material and a preparation process thereof. The only difference from Example 1 is that in step (2), the chain transfer agent used is isopropyl cyanodithiobenzoate.

[0106] Example 7: This example provides an adhesive coating material and a preparation process thereof, which is different from Example 1 only in that in step (1), the chain initiator used is azobisisoheptanenitrile.

[0107] Example 8: This example provides an adhesive coating material and a preparation process thereof, which is different from Example 1 only in that in step (1), the reaction temperature is 50°C.

[0108] Example 9: This example provides an adhesive coating material and a preparation process thereof, which is different from Example 1 only in that in step (1), the reaction temperature is 85°C.

[0109] Example 10: This example provides an adhesive coating material and a preparation process thereof, which is different from Example 1 only in that in step (2), the reaction temperature is 50°C.

[0110] Example 11: This example provides an adhesive coating material and a preparation process thereof, which is different from Example 1 only in that in step (2), the reaction temperature is 85°C.

[0111] Example 12: This example provides an adhesive coating material and a preparation process thereof. The only difference from Example 1 is that in step (1), the amount of chain transfer agent used is 0.350 g, so that the molar ratio of butyl methacrylate, the first initiator and the chain transfer agent is 100:0.8:0.2.

[0112] Example 13: This example provides an adhesive coating material and a preparation process thereof. The only difference from Example 1 is that in step (1), the amount of chain transfer agent used is 1.748 g, so that the molar ratio of butyl methacrylate, the first initiator and the chain transfer agent is 100:0.8:1.

[0113] Example 14: This example provides an adhesive coating material and a preparation process thereof. The only difference from Example 1 is that in step (1), the amount of the first initiator is 0.724 g, so that the molar ratio of butyl methacrylate, the first initiator and the chain transfer agent is 100:0.4:0.6.

[0114] Example 15: This example provides an adhesive coating material and a preparation process thereof. The only difference from Example 1 is that in step (1), the amount of the first initiator is 2.171 g, so that the molar ratio of butyl methacrylate, the first initiator and the chain transfer agent is 100:1.2:0.6.

[0115] Example 16: This example provides an adhesive coating material and a preparation process thereof. The only difference from Example 1 is that in step (2), the amount of the first polymer used is 100 g and the amount of vinyl pyrrolidone used is 20 g.

[0116] Example 17: This example provides an adhesive coating material and a preparation process thereof. The only difference from Example 1 is that in step (2), the amount of the first polymer used is 100 g and the amount of vinyl pyrrolidone used is 80 g.

[0117] Embodiment 18: This embodiment provides an adhesive coating material and a preparation process thereof, and the preparation method is as follows:

[0118] (1) 100 g of butyl methacrylate, 0.972 g of initiator azobisisobutyronitrile, 1.049 g of chain transfer agent diisopropyl xanthate (molar ratio 100:0.8:0.6) and 80 mL of toluene organic solvent were mixed, and after all the raw materials were fully dissolved, the mixture was reacted at 68° C. in nitrogen for 1.5 h to obtain a first polymer;

[0119] (2) 100 g of the first polymer, 80 g of vinyl pyrrolidone, 3 g of initiator azobisisobutyronitrile (mass ratio 100:80:3) and 500 mL of toluene organic solvent were mixed, and after all the raw materials were fully dissolved, the mixture was reacted at 68° C. in nitrogen for 3 h to obtain an adhesive coating material.

[0120] Example 19: This example provides an adhesive coating material and a preparation process thereof. The only difference from Example 18 is that in step (2), each raw material is fully dissolved and then reacted in nitrogen at 68°C for 4 hours.

[0121] Example 20: This example provides an adhesive coating material and a preparation process thereof. The only difference from Example 18 is that in step (2), after each raw material is fully dissolved, the material is reacted in nitrogen at 68° C. for 5 hours.

[0122] Example 21: This example provides an adhesive coating material and a preparation process thereof. The only difference from Example 18 is that in step (2), after each raw material is fully dissolved, it is reacted in nitrogen at 68°C for 6 hours.

[0123] Example 22: This example provides an adhesive coating material and a preparation process thereof. The preparation method is as follows:

[0124] (1) 100 g of butyl methacrylate, 0.972 g of initiator azobisisobutyronitrile, 0.969 g of chain transfer agent dithiocarbamate (molar ratio 100:0.8:0.8) and 80 mL of organic solvent were mixed, and after all the raw materials were fully dissolved, the mixture was reacted at 65° C. for 3 h in nitrogen to obtain a first polymer;

[0125] (2) 100 g of the first polymer, 80 g of vinyl pyrrolidone, 3 g of initiator azobisisobutyronitrile (mass ratio 100:80:3) and 500 mL of toluene organic solvent were mixed, and after all the raw materials were fully dissolved, the mixture was reacted at 68° C. in nitrogen for 3 h to obtain an adhesive coating material.

[0126] Example 23: This example provides an adhesive coating material and a preparation process thereof. The only difference from Example 22 is that in step (1), each raw material is fully dissolved and then reacted in nitrogen at 65°C for 5 hours.

[0127] 2. Performance Test

[0128] (1) Molecular weight detection

[0129] The number average molecular weight and weight average molecular weight of the adhesive coating materials of Examples 1 to 23 are shown in Table 1.

[0130] Table 1

[0131]

[0132] (2) Infrared detection

[0133] The adhesive coating material of Example 3 was selected for infrared detection and compared with the infrared detection result of polybutyl methacrylate. The comparison result is shown in Figure 1 .according to Figure 1 It can be found that the bonding coating material is better than polybutyl methacrylate at 1730cm -1 There are infrared characteristic peaks around 1650cm -1 New infrared characteristic peaks were generated on the left and right, indicating the existence of two different carbonyl stretching vibrations in the material, which can prove that vinyl pyrrolidone was successfully prepared on the polymer main chain.

[0134] (3) Nuclear magnetic resonance testing

[0135] The adhesive coating material of Example 3 was subjected to H NMR detection and compared with the NMR detection result of polybutyl methacrylate. The comparison result is shown in Figure 2 .according to Figure 2 It can be found that at about 2ppm~4ppm, the adhesive coating material has an obvious peak, which is attributed to the peak of the vinyl pyrrolidone segment in the copolymer material, indicating that the polybutyl methacrylate-vinyl pyrrolidone block copolymer has been successfully prepared.

[0136] (4) Biocompatibility

[0137] Cytotoxicity experiments were conducted according to ASTM 16886-5:2017. Mouse fibroblast cell line L929 cells were used to evaluate the toxicity of each embodiment with a concentration range of 0-1000 ppm. The values ​​of all experimental groups were normalized with the control cells. As shown in Table 2, after 72 h of co-culture of the material and cells, it can be seen that the relative cell proliferation rate of all embodiments is greater than that of nickel-titanium metal materials, and the biocompatibility is better.

[0138] Table 2

[0139]

[0140] (5) Adhesion test of adhesive coating

[0141] According to ISO 2409-2019 standard, the adhesion test of the adhesive coating material was carried out. The solutions of PBMA and the adhesive coating materials of each embodiment were prepared with equal volumes and concentrations, and coated on the surfaces of the titanium-nickel alloy sheet, stainless steel 316L, and polylactic acid sheet, respectively. The coating was cross-cut with a stainless steel cutter, and the surface was adhered with 3M tape. After holding for 10 seconds, a constant force was manually applied to pull the tape, and then the remaining area of ​​the coating was observed, and the adhesion result was graded.

[0142] The adhesion test classification of the adhesive coatings of various embodiments and comparative examples is shown in Table 3. Classification 0, 1, 2, 3, 4, and 5 represent adhesion from high to low, with a total of six levels. As shown in Table 3, the adhesion of all embodiments is significantly improved relative to polybutyl methacrylate.

[0143] Table 3

[0144]

[0145] All documents mentioned in this application are cited as references in this application, just as each document is cited as reference separately. Unless they conflict with the application purpose and / or technical solution of this application, the cited documents involved in this application are cited with all contents and all purposes. When the cited documents are involved in this application, the definitions of relevant technical features, terms, nouns, phrases, etc. in the cited documents are also cited. When the cited documents are involved in this application, the examples and preferred methods of the cited relevant technical features can also be incorporated into this application as references, but are limited to the implementation of this application. It should be understood that when the cited content conflicts with the description in this application, the present application shall prevail or be modified adaptively according to the description of this application.

[0146] The technical features of the above-mentioned implementation modes and examples can be combined in any appropriate manner. To make the description concise, not all possible combinations of the technical features in the above-mentioned implementation modes and examples are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0147] The above-described embodiments only express several implementation methods of the present application, but they cannot be understood as limiting the scope of the patent application. It should be pointed out that, for those of ordinary skill in the art, without departing from the concept of the present application, several variations and improvements can also be made, which all belong to the protection scope of the present application. In addition, it should be understood that after reading the above-mentioned teaching content of the present application, those skilled in the art can make various changes or modifications to the present application, and the equivalent forms obtained also fall within the protection scope of the present application. It should also be understood that the technical solutions obtained by those skilled in the art on the basis of the technical solutions provided in the present application through logical analysis, reasoning or limited experiments are all within the protection scope of the claims attached to the present application. Therefore, the protection scope of the patent of the present application shall be based on the attached claims, and the description can be used to interpret the content of the claims.

Claims

1. An adhesive coating material, characterized in that: It includes a block copolymer comprising a polybutyl methacrylate segment and a polyvinyl pyrrolidone segment; Wherein, the total weight ratio of the polybutyl methacrylate chain segment to the polyvinyl pyrrolidone chain segment is 100:(20-80).

2. The adhesive coating material according to claim 1, characterized in that The block copolymer satisfies at least one of the following conditions: (1) Number average molecular weight is 28000~45000; (2) Weight average molecular weight is 40,000~60,000; (3) At 1645cm -1 ~1655cm -1 and 1725cm -1 ~1735cm -1 It has characteristic infrared peaks.

3. The adhesive coating material according to claim 1 or 2, characterized in that: The bonding coating material is rated as Grade 0 under the ISO2409-2019 material adhesion cross-cut test standard.

4. A method for preparing the adhesive coating material according to any one of claims 1 to 3, characterized in that: The steps include: Butyl methacrylate is subjected to reversible addition-fragmentation chain transfer polymerization to obtain a first polymer; polymerizing the first polymer and vinyl pyrrolidone to obtain the adhesive coating material; Wherein, the mass ratio of the first polymer to the vinyl pyrrolidone is 100:(20-80).

5. The preparation method according to claim 4, characterized in that: The step of preparing a first polymer by reversible addition-fragmentation chain transfer polymerization of butyl methacrylate comprises: dissolving butyl methacrylate, a first initiator and a chain transfer agent in an organic solvent to obtain a first solution; reacting the first solution in a first protective gas at a first heating temperature for a first time to obtain the first polymer; Wherein, the first protective gas includes at least one of nitrogen, helium and argon, the first heating temperature is 60° C. to 80° C., and the first time is 1 h to 5 h.

6. The preparation method according to claim 5, characterized in that: The molar ratio of the butyl methacrylate, the first initiator and the chain transfer agent is 100:(0.6-1.0):(0.5-0.8).

7. The preparation method according to claim 5 or 6, characterized in that: At least one of the following conditions is met: (1) The chain transfer agent includes at least one of diisopropyl xanthate disulfide, dithiocarbamate, dithiobenzoate and dithiobenzoic acid cyanoisopropyl ester; (2) The first initiator includes at least one of azobisisobutyronitrile, azobisisoheptanenitrile and 1,1'-azo(cyanocyclohexane).

8. The preparation method according to claim 4, characterized in that: The step of polymerizing the first polymer and vinyl pyrrolidone to obtain the adhesive coating material comprises: dissolving the first polymer, vinyl pyrrolidone and a second initiator in an organic solvent to obtain a second solution; reacting the second solution under a second protective gas and a second heating temperature for a second time to obtain a second polymer; Wherein, the second protective gas includes at least one of nitrogen, helium and argon, the second heating temperature is 60° C. to 80° C., and the second time is 3 h to 6 h.

9. The preparation method according to claim 8, characterized in that: The mass ratio of the first polymer, the second initiator and the vinyl pyrrolidone is 100:(3-5):(20-80).

10. The preparation method according to claim 8 or 9, characterized in that: The second initiator includes at least one of azobisisobutyronitrile, azobisisoheptanenitrile and 1,1'-azo(cyanocyclohexane).

11. A drug-eluting stent, characterized in that: It comprises a metal support base and a coating layer coated on the surface of the metal support base; The material for preparing the coating layer includes the adhesive coating material and the drug according to any one of claims 1 to 3.

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