ZWITTER-IONIC POLYMER AND ITS APPLICATIONS

Abstract

The present disclosure relates to a zwitterionic polymer and the use thereof. Specifically, the present disclosure relates to a zwitterionic polymer, the use thereof as a biocompatible implantable material coating, and a method for preparing the coating. The coating can be used for inhibiting platelet aggregation and platelet adhesiveness caused by the exposure of blood to the surface of a material.

Description

A zwitterionic polymer and its use Technical Field

[0001] The present disclosure belongs to the field of medicine and relates to a zwitterionic polymer and use of the zwitterionic polymer as a coating for a biocompatible implantable material. The coating can inhibit platelet aggregation and platelet adhesion caused by exposure of blood to the surface of the material. Background Art

[0002] The use of implantable materials often requires contact with human blood or body fluids and tissues, such as vascular grafts, catheters, stents, insulation materials for pacemaker and defibrillator wires, as well as extracorporeal bypass circuits and oxygenators. If these implantable materials do not have good biocompatibility, direct contact with body fluids or blood can lead to protein aggregation or thrombosis, further causing a decline in the performance of the medical device and causing serious complications for the patient. For example, the placement of a vascular stent may damage the endothelium and cause an inflammatory response. To address the above issues, a polymeric high molecular material with zwitterions is usually grafted onto the surface of the implantable material to form a coating, thereby improving the biocompatibility of the implantable material.

[0003] Polymers containing 2-methacryloyloxyethylphosphorylcholine (MPC) monomers are a classic class of zwitterionic polymers widely used in implantable materials. Because these polymers can form a bimolecular structure similar to a biological membrane, they can effectively reduce fibrin adsorption and platelet adhesion and activation, thereby significantly improving the material's blood compatibility.

[0004] Patent application WO2001007097A1 discloses a polymer compound, p-(GMA-MPC), formed by copolymerizing MPC and glycidyl methacrylate (GMA). It exhibits excellent biocompatibility and biodegradability, and can be grafted onto the surface of medical devices through a ring-opening reaction with ethylene oxide to form a coating with surface lubricity and blood compatibility. However, recent discoveries indicate that incomplete grafting of the p-(GMA-MPC) polymer during the grafting process can result in free ethylene oxide residues on the surface of the polymer-modified material. Ethylene oxide is cytotoxic, and materials containing coatings containing ethylene oxide groups can cause significant harm to the human body if implanted.

[0005] Therefore, developing materials with better blood compatibility is what those skilled in the art seek.

[0006] Summary of the Invention

[0007] The present disclosure provides a material comprising a substrate and a coating, wherein the coating comprises a polymer, and the polymer comprises a structural unit having a group represented by Formula 1-a, a structural unit having a group represented by Formula 1-b, and a structural unit having a group represented by Formula 1-c.

[0008] in:

[0009] ** represents an end connected to a substrate surface, wherein the substrate surface is optionally treated with a modifier;

[0010] X 1 、X 2 The same or different, each independently selected from -O-, -S- or -N(R d )-;

[0011] Y is selected from -OH, -SH or -N(R e R f );

[0012] R 1 、R 2 、R 3 The same or different, each independently selected from hydrogen, halogen, hydroxyl, thiol, nitro, carboxyl, amino, cyano, C 1-6 Alkyl, C 1-6 Alkoxy, the C 1-6 Alkyl, C 1-6 Alkoxy is optionally selected from halogen, hydroxy, mercapto, nitro, carboxyl, amino, cyano, C 1-6 Alkyl and C 1-6 substituted with one or more alkoxy groups,

[0013] Or, R 1 and R 2 Together with the atoms connected to it, it forms an oxo group, a thio group, a C 3-10 Cycloalkyl, 3- to 10-membered heterocycloalkyl;

[0014] L 1 、L 3 The same or different, each independently selected from a bond, an alkylene or a heteroalkylene, wherein the alkylene or heteroalkylene is optionally selected from C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkoxy, C 1-6 substituted by one or more groups selected from the group consisting of aminoalkoxy, halogen, amino, hydroxy, nitro, cyano, mercapto, carboxyl, oxo, thio, and sulfonyl;

[0015] L 2 is selected from alkylene or heteroalkylene, wherein the alkylene and heteroalkylene are optionally selected from C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 aminoalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Hydroxyalkoxy, C 1-6 substituted by one or more groups selected from the group consisting of aminoalkoxy, halogen, amino, hydroxy, nitro, cyano, mercapto, carboxyl, oxo, thio, and sulfonyl;

[0016] M is an amino acid residue (A), wherein M is optionally selected from halogen, amino, hydroxy, nitro, cyano, amino, sulfhydryl, carboxyl, C 1-6 Alkyl, C 1-6 substituted with one or more alkoxy groups;

[0017] R a 、R b 、R c 、R d 、R e 、R f are the same or different and are each independently selected from hydrogen, halogen, hydroxyl, C 1-6 Alkyl, C 1-6 Alkoxy, the C 1-6 Alkyl or C 1-6 Alkoxy is optionally selected from halogen, hydroxy, cyano, nitro, C 1-6 Alkyl, C 1-6 Alkoxy and C 3-7 The cycloalkyl group is substituted with one or more radicals.

[0018] In some embodiments, the polymer comprises a structural unit represented by formula I-a, a structural unit represented by formula I-b, and a structural unit represented by formula I-c.

[0019] in:

[0020] **Indicates the end connected to the substrate surface;

[0021] R 10 Each is independently selected from hydrogen, halogen, hydroxyl, mercapto, nitro, carboxyl, amino, cyano, C 1-6 Alkyl, C 1-6 Alkoxy, the C 1-6 Alkyl, C 1-6 Alkoxy is optionally selected from halogen, hydroxy, mercapto, nitro, carboxyl, amino, cyano, C 1-6 Alkyl, C1-6 One or more alkoxy groups are substituted;

[0022] L 1 、L 2 、L 3 、R 1 、R 2 、R 3 , M, Y, X 1 、X 2 、R a 、R b 、R c As defined above.

[0023] In certain embodiments, the weight average molecular weight of the polymer is 10,000 to 500,000 Da.

[0024] In certain embodiments, the polymer comprises a structural unit represented by formula Ⅰ-A, a structural unit represented by formula Ⅰ-B, and a structural unit represented by formula Ⅰ-C.

[0025] Wherein, in molar ratio, z:(x+y) is selected from 20:80 to 90:10, R 10 、L 1 、L 2 、L 3 、R 1 、R 2 、R 3 , M, Y, X 1 、X 2 、R a 、R b 、R c As defined above.

[0026] In certain embodiments, the z:(x+y) is selected from the group consisting of 20:80, 25:75, 30:70, 35:65, 40:60, 45:55, 50:50, 55:45, 60:40, 65:35, 70:30, 75:25, and 80:20 in molar ratios. In certain embodiments, the z:(x+y) is selected from the group consisting of 40:60, 45:55, 50:50, 55:45, 60:40, 65:35, and 70:30 in molar ratios.

[0027] In some embodiments, the Y is selected from -OH, -SH. In certain embodiments, the Y is -OH.

[0028] In some embodiments, the L 1 、L 3 Each independently selected from a bond or C 1-6 Alkylene, the C1-6 Alkylene is optionally selected from C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 The alkyl group is substituted by one or more groups of aminoalkyl, halogen, amino, hydroxy, cyano, and mercapto.

[0029] In some embodiments, the L 2 C 1-6 Alkylene, which is optionally selected from C 1-6 Alkyl, C 1- 6 haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 The alkyl group is substituted by one or more groups of aminoalkyl, halogen, amino, hydroxy, cyano, and mercapto.

[0030] In some embodiments, the polymer comprises a structural unit having a group represented by formula 2-a, a structural unit having a group represented by formula 2-b, and a structural unit having a group represented by formula 2-c.

[0031] Wherein: ** indicates the end connected to the substrate surface;

[0032] R 4 、R 5 、R 6 、R 7 、R 8 、R 9 The same or different, each independently selected from hydrogen, halogen, hydroxyl, thiol, nitro, carboxyl, amino, cyano, C 1-6 Alkyl, C 1-6 Alkoxy, C 3-7 Cycloalkyl or 3 to 7 membered heterocycloalkyl, the C 1-6 Alkyl, C 1-6 Alkoxy, cycloalkyl or heterocycloalkyl is optionally selected from halogen, hydroxy, mercapto, nitro, carboxyl, amino, cyano, C 1-6 Alkyl, C 1-6 substituted with one or more alkoxy groups,

[0033] Or, R 4 and R 5 、R 6 and R 7 or R 8 and R 9 Together with the atoms connected to it, it forms an oxo group, a thio group, a C 3-10 Cycloalkyl, 3- to 10-membered heterocycloalkyl;

[0034] a is selected from 0, 1, 2, 3, 4, 5, 6;

[0035] b is selected from 1, 2, 3, 4, 5, 6;

[0036] c is selected from 0, 1, 2, 3, 4, 5, 6;

[0037] X 1 、X 2 、R 1 、R 2 、R 3 , M, R a 、R b 、R c As defined above.

[0038] In some embodiments, the polymer comprises a structural unit represented by formula II-a, a structural unit represented by formula II-b, and a structural unit represented by formula II-c.

[0039] in:

[0040] **Indicates the end connected to the substrate surface;

[0041] X 1 、X 2 、R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 、R 10 , M, R a 、R b 、R c , a, b, c are as defined above.

[0042] In certain embodiments, the polymer comprises a structural unit represented by formula II-A, a structural unit represented by formula II-B, and a structural unit represented by formula II-C.

[0043] in:

[0044] **Indicates the end connected to the substrate surface;

[0045] X 1 、X 2 、R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 、R10 , M, R a 、R b 、R c , a, b, c, x, y, z are as defined above.

[0046] In some embodiments, the X 1 、X 2 Each independently selected from -O- or -N(R d )-, preferably -O-, R d As defined above.

[0047] In some embodiments, the polymer comprises a structural unit having a group represented by formula 3-a, a structural unit having a group represented by formula 3-b, and a structural unit having a group represented by formula 3-c.

[0048] Wherein: ** indicates the end connected to the substrate surface;

[0049] R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 , M, R a 、R b 、R c , a, b, c are as defined above.

[0050] In some embodiments, the polymer comprises a structural unit represented by formula III-a, a structural unit represented by formula III-b, and a structural unit represented by formula III-c.

[0051] Wherein: ** indicates the end connected to the substrate surface;

[0052] R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 、R 10 , M, R a 、R b 、R c , a, b, c are as defined above.

[0053] In certain embodiments, the polymer comprises a structural unit represented by formula III-A, a structural unit represented by formula III-B, and a structural unit represented by formula III-C.

[0054] Wherein: ** indicates the end connected to the substrate surface;

[0055] R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 、R 10 , M, R a 、R b 、R c , a, b, c, x, y, z are as defined above.

[0056] In some embodiments, the R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 are each independently selected from hydrogen, C 1-6 Alkyl, the C 1-6 Alkyl is optionally selected from halogen, hydroxy, mercapto, nitro, carboxyl, amino, cyano, C 1-6 Alkyl, C 1-6 In certain embodiments, R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 Each is independently selected from hydrogen, methyl, ethyl, propyl, butyl, isopropyl, and isobutyl.

[0057] In certain embodiments, the R 10 C 1-6 Alkyl, the C 1-6 Alkyl is optionally selected from halogen, hydroxy, mercapto, nitro, carboxyl, amino, cyano, C 1-6 Alkyl, C 1-6 In certain embodiments, the R 10 Selected from C1-6 Haloalkyl, C 1-6 In certain embodiments, the R 10 Selected from methyl, fluoromethyl, bromomethyl, iodomethyl.

[0058] In certain embodiments, the R a 、R b 、R c Each independently selected from C 1-6 In certain embodiments, the R a 、R b 、R c Each is independently selected from methyl, ethyl, propyl, butyl, isopropyl, and isobutyl.

[0059] In some embodiments, the polymer comprises a structural unit having a group represented by formula 4-a, a structural unit having a group represented by formula 4-b, and a structural unit having a group represented by formula 4-c.

[0060] Wherein: ** indicates the end connected to the substrate surface.

[0061] In some embodiments, the amino acid (A) is selected from glycine, alanine, valine, isoleucine, leucine, methionine, phenylalanine, tryptophan, serine, threonine, cysteine, asparagine, glutamine, tyrosine, aspartic acid, glutamic acid, lysine, arginine, histidine, and taurine. In some embodiments, the amino acid (A) is selected from glycine, phenylalanine, threonine, serine, histidine, and cysteine.

[0062] In some embodiments, the amino acid (A) is selected from glycine, threonine, serine, and cysteine.

[0063] In certain embodiments, the polymer comprises a structural unit represented by formula IV-a, a structural unit represented by formula IV-b, and a structural unit represented by formula IV-c.

[0064] Wherein: ** indicates the end connected to the substrate surface.

[0065] In certain embodiments, the polymer comprises a structural unit represented by formula IV-A, a structural unit represented by formula IV-B, and a structural unit represented by formula IV-C.

[0066] Wherein: ** represents the end connected to the substrate surface, and x, y, and z are as defined above.

[0067] In certain embodiments, the amino acid (A) is connected to the carbon end of Formula 1-b, Formula 2-b, Formula 3-b, Formula 4-b, Formula I-b, Formula II-b, Formula III-b, IV-b, Formula I-B, Formula II-B, Formula III-B or IV-B through its side chain group, and the side chain group is selected from hydrogen, hydroxyl, carboxyl, amino, and thiol. In certain embodiments, the side chain group is selected from hydrogen, hydroxyl, and thiol. For example, in certain embodiments, the amino acid (A) is cysteine, which is connected to the carbon end of Formula 1-b, Formula 2-b, Formula 3-b, Formula I-b, Formula II-b, Formula III-b, IV-b, Formula I-B, Formula II-B, Formula III-B or IV-B through the side chain group thiol, and in this case M is

[0068] The polymers described herein may contain more than one permutation and combination of the structural units, but all permutations and combinations refer to the same polymer. For example, a polymer containing structural units of Formula IV-A, Formula IV-B, and Formula IV-C may be represented by, but is not limited to, Formula A-1, Formula A-2, or Formula A-3, wherein Formula A-1, Formula A-2, and Formula A-3 all represent the same polymer: wherein x, y, and z are as defined above.

[0069] The triblock polymers described in the present disclosure are all represented by the arrangement and combination order of the structural units shown in Formula A-1. The abbreviations corresponding to Formula A-1, Formula A-2 or Formula A-3 are all P(GMA-cysGMA-MPC).

[0070] In some embodiments, the polymer in the coating of the present disclosure exists in the form of a residue, which is covalently linked to the substrate surface via **, or covalently linked to the substrate surface treated with a modifier via **. For example, the polymer exists in the form of formula A-1, wherein ** represents the end connected to the substrate surface,

[0071] In certain embodiments, the aforementioned polymer is attached to the substrate surface via a bond. In certain embodiments, the aforementioned polymer is attached to the substrate surface via a modifier.

[0072] In some embodiments, the coating further comprises a silane layer comprising the aforementioned modifier. In certain embodiments, the silane layer is an inner coating and is covalently bonded to the substrate surface; and the polymer layer is an outer coating and is covalently bonded to the silane layer.

[0073] In some embodiments, the modifier is a coupling agent represented by formula V, Where: R 11 Selected from C 1-6 Alkyl, C1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 1-6 aminoalkyl; R 12 Selected from C 1-6 Hydroxyalkyl, C 1-6 aminoalkyl, C 1-6 Carboxyalkyl, C 1-6 Mercaptoalkyl, the C 1-6 Hydroxyalkyl, C 1-6 aminoalkyl, C 1-6 Carboxyalkyl, C 1-6 The mercaptoalkyl group is optionally selected from C 1-6 Hydroxyalkyl, C 1-6 aminoalkyl, C 1-6 Carboxyalkyl, C 1-6 The alkyl group is substituted with one or more groups of mercaptoalkyl.

[0074] In some embodiments, the coupling agent is coupled to the 11 In certain embodiments, R 11 C 1-6 In certain embodiments, R 11 is selected from methyl, ethyl, propyl, butyl. In certain embodiments, R 11 For ethyl.

[0075] In some embodiments, the coupling agent is coupled to the 12 Connected to the first end of the aforementioned polymer to form a polymer layer. Specifically, the coupling agent is connected to the first end of the aforementioned polymer to form a polymer layer. 12 The reactive group is connected to the first end of Formula 1-a, Formula 2-a, Formula 3-a, Formula 4-a, Formula I-a, Formula II-a, Formula III-a, Formula IV-a, Formula I-A, Formula II-A, Formula III-A or Formula IV-A, and the reactive group is selected from hydroxyl, amino, carboxyl, and thiol. In certain embodiments, the reactive group is selected from amino, hydroxyl, and thiol. In certain embodiments, the reactive group is amino. For example, in certain embodiments, wherein the coupling agent is connected to the first end of Formula 1-a, Formula 2-a, Formula 3-a, Formula III-a, Formula IV-a, Formula I-A, Formula II-A, Formula III-A or Formula IV-A, the reactive group is selected from hydroxyl, amino, carboxyl, and thiol. 12 The amino group of is connected to the first end of the aforementioned polymer to form a polymer layer. In certain embodiments, the R 12 C 1-6 aminoalkyl, the C 1-6 The aminoalkyl group is optionally selected from C 1-6 Hydroxyalkyl, C 1-6 aminoalkyl, C 1-6 Carboxyalkyl, C 1-6 In certain embodiments, the R 12is selected from methylamino, ethylamino, propylamino, and butylamino. 12 It is propylamino.

[0076] In some embodiments, the coupling agent is selected from 3-aminopropyltrimethoxysilane (KH540), 3-aminopropyltriethoxysilane (KH550), 3-(2-aminoethyl)aminopropyltrimethoxysilane (KH792), 3-(2-aminoethyl)aminopropyltriethoxysilane (KH791), 3-(2-aminoethylamino)propyldimethoxymethylsilane (KH602), 3-hydroxypropyltriethoxysilane, 3-hydroxypropyltrimethoxysilane, 3-mercaptopropyltrimethoxysilane, 3-mercaptopropyltriethoxysilane, 4-(trimethoxysilyl)butyric acid, 4-(triethoxysilyl)butyric acid, bis(2-hydroxyethyl)aminopropyltriethoxysilane, bis(2-hydroxyethyl)aminopropyltrimethoxysilane, and 3-aminopropyltriisopropoxysilane. In certain embodiments, the coupling agent is selected from 3-aminopropyltrimethoxysilane (KH540) and 3-aminopropyltriethoxysilane (KH550). In certain embodiments, the coupling agent is 3-aminopropyltriethoxysilane (KH550).

[0077] On the other hand, the present disclosure also provides a material comprising a substrate and a coating, wherein the coating is formed by reacting a polymer comprising a structural unit having a group represented by Formula 1-d and a structural unit having a group represented by Formula 1-c with the coupling agent defined above, and then reacting with the amino acid (A) defined above.

[0078] in:

[0079] X 3 Selected from -O-, -S- or -N(R d )-;

[0080] R 13 、R 14 、R 15 The same or different, each independently selected from hydrogen, halogen, hydroxyl, thiol, nitro, carboxyl, amino, cyano, C 1-6 Alkyl, C 1-6 Alkoxy, the C 1-6 Alkyl, C 1-6 Alkoxy is optionally selected from halogen, hydroxy, mercapto, nitro, carboxyl, amino, cyano, C 1-6 Alkyl, C 1-6 substituted by one or more groups substituted by alkoxy,

[0081] Or, R 14 and R 15Together with the atoms connected to it, it forms an oxo group, a thio group, a C 3-10 cycloalkyl, 3- to 10-membered heterocycloalkyl,

[0082] R d Each independently selected from hydrogen, halogen, hydroxyl, C 1-6 Alkyl, C 1-6 Alkoxy, the C 1-6 Alkyl or C 1-6 The alkoxy group is optionally substituted by one or more radicals selected from halogen, hydroxy, cyano, nitro, C 1-6 Alkyl, C 1-6 Alkoxy or C 3-7 substituted with a cycloalkyl group.

[0083] In some embodiments, the polymer comprises a structural unit having formula I-d and a structural unit having formula I-c,

[0084] Where: R 10 、L 1 、L 2 、L 3 、X 1 、X 3 、R 13 、R 14 、R 15 、R a 、R b 、R c As defined above.

[0085] In certain embodiments, the weight average molecular weight of the polymer is 10,000 to 500,000 Da.

[0086] In certain embodiments, the polymer comprises a structural unit having the formula I-D and a structural unit having the formula I-C',

[0087] in:

[0088] In terms of molar ratio, m:n is selected from 20:80 to 90:10,

[0089] R a 、R b 、R c 、L 2 、L 3 、R 10 、L 1 、X 1 、X 2 、R 13 、R 14 、R 15 As defined above.

[0090] In certain embodiments, the m:n is selected from the group consisting of 20:80, 25:75, 30:70, 35:65, 40:60, 45:55, 50:50, 55:45, 60:40, 65:35, 70:30, 75:25, and 80:20 in terms of molar ratio. In certain embodiments, the m:n is selected from the group consisting of 40:60, 45:55, 50:50, 55:45, 60:40, 65:35, and 70:30 in terms of molar ratio.

[0091] In some embodiments, the X 3 In certain embodiments, X 3 It is -O-.

[0092] In some embodiments, the group represented by formula 1-d is as represented by formula 2-d, R 13 、R 14 、R 15 As defined above,

[0093] In some embodiments, the polymer comprises a structural unit having formula II-d and a structural unit having formula II-c,

[0094] in:

[0095] R 16 、R 17 The same or different, each independently selected from hydrogen, halogen, hydroxyl, thiol, nitro, carboxyl, amino, cyano, C 1-6 Alkyl, C 1-6 Alkoxy, the C 1-6 Alkyl, C 1-6 Alkoxy is optionally selected from halogen, hydroxy, mercapto, nitro, carboxyl, amino, cyano, C 1-6 Alkyl, C 1-6 substituted with one or more alkoxy groups,

[0096] Or, R 16 and R 17 Together with the atoms connected to it, it forms an oxo group, a thio group, a C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl;

[0097] d is selected from 0, 1, 2, 3, 4, 5, 6;

[0098] R 6 、R 7 、R 8 、R 9 、R 10 、X1 、R 13 、R 14 、R 15 , b are as defined above.

[0099] In some embodiments, the polymer comprises a structural unit having formula II-D and a structural unit having formula II-C',

[0100] Where: X 1 、X 2 、R 13 、R 14 、R 15 、R 16 、R 17 、R 6 、R 7 、R 8 、R 9 、R 10 、R a 、R b 、R c , b, c, d, m, and n are as defined above.

[0101] In some embodiments, the X 3 Selected from -O- or -S-, preferably -O-.

[0102] In some embodiments, the polymer comprises a structural unit having formula III-d and a structural unit having formula III-c.

[0103] Wherein, d is selected from 0, 1, 2, 3, 4, 5, 6,

[0104] R 13 、R 14 、R 15 、R 16 、R 17 、R 6 、R 7 、R 8 、R 9 、R 10 、R a 、R b 、R c , b, c, d are as defined above.

[0105] In some embodiments, the polymer comprises a structural unit represented by formula III-D and a structural unit represented by formula III-C'.

[0106] Where: R 13 、R 14 、R15 、R 16 、R 17 、R 6 、R 7 、R 8 、R 9 、R 10 、R a 、R b 、R c , b, c, d, m, and n are as defined above.

[0107] In some embodiments, the R 13 、R 14 、R 15 are each independently hydrogen.

[0108] In some embodiments, wherein R 16 、R 17 are each independently selected from hydrogen, C 1-6 Alkyl, the C 1-6 Alkyl is optionally selected from halogen, hydroxy, mercapto, nitro, carboxyl, amino, cyano, C 1-6 Alkyl, C 1-6 In certain embodiments, wherein R 16 、R 17 Each is independently selected from hydrogen, methyl, ethyl, propyl, butyl, isopropyl, and isobutyl.

[0109] In some embodiments, the group represented by formula 1-d is represented by formula 3-d,

[0110] In certain embodiments, the polymer comprises a structural unit represented by formula IV-c and a structural unit represented by formula IV-d,

[0111] In certain embodiments, the polymer comprises a structural unit represented by formula IV-C' and a structural unit represented by formula IV-D,

[0112] Wherein, m and n are as defined above.

[0113] In some embodiments, the coupling agent is coupled to the 12 Reacts with the group represented by formula 1-d, formula 2-d or formula 3-d in the polymer. 12The reactive group on the polymer undergoes a ring-opening reaction with the group represented by formula 1-d, formula 2-d, or formula 3-d in the polymer, wherein the reactive group is selected from a hydroxyl group, an amino group, a carboxyl group, and a thiol group. In certain embodiments, the reactive group is selected from an amino group, a hydroxyl group, and a thiol group. In certain embodiments, the reactive group is an amino group.

[0114] On the other hand, the present disclosure also provides a coating, which includes a polymer layer defined above, and the polymer layer contains a polymer having a structural unit with a group shown in Formula 1-a, a structural unit with a group shown in Formula 1-b, and a structural unit with a group shown in Formula 1-c.

[0115] In some embodiments, the polymer comprises a structural unit having a group represented by Formula 2-a, a structural unit having a group represented by Formula 2-b, and a structural unit having a group represented by Formula 2-c.

[0116] In some embodiments, the polymer comprises a structural unit having a group represented by Formula 3-a, a structural unit having a group represented by Formula 3-b, and a structural unit having a group represented by Formula 3-c.

[0117] In some embodiments, the polymer comprises a structural unit having a group represented by Formula 4-a, a structural unit having a group represented by Formula 4-b, and a structural unit having a group represented by Formula 4-c.

[0118] In some embodiments, the polymer comprises a polymer having a structural unit represented by formula I-a, a structural unit represented by formula I-b, and a structural unit represented by formula I-c. In certain embodiments, the polymer comprises a polymer having a structural unit represented by formula I-A, a structural unit represented by formula I-B, and a structural unit represented by formula I-C.

[0119] In some embodiments, the polymer comprises a polymer having a structural unit represented by formula II-a, a structural unit represented by formula II-b, and a structural unit represented by formula II-c. In certain embodiments, the polymer comprises a polymer having a structural unit represented by formula II-A, a structural unit represented by formula II-B, and a structural unit represented by formula II-C.

[0120] In some embodiments, the polymer comprises a structural unit of formula III-a, a structural unit of formula III-b, and a structural unit of formula III-c. In certain embodiments, the polymer comprises a structural unit of formula III-A, a structural unit of formula III-B, and a structural unit of formula III-C.

[0121] In some embodiments, the polymer comprises a structural unit of formula IV-a, a structural unit of formula IV-b, and a structural unit of formula IV-c. In certain embodiments, the polymer comprises a structural unit of formula IV-A, a structural unit of formula IV-B, and a structural unit of formula IV-C.

[0122] In some embodiments, the coating further comprises a silane layer as defined above. The silane layer comprises a coupling agent as defined above.

[0123] On the other hand, the present disclosure also provides a coating, wherein the coating is formed by reacting a polymer comprising a structural unit having a group represented by Formula 1-d and a structural unit having a group represented by Formula 1-c with a coupling agent as defined above, and then reacting with an amino acid (A).

[0124] The amino acid (A) is selected from glycine, alanine, valine, isoleucine, leucine, methionine, phenylalanine, tryptophan, serine, threonine, cysteine, asparagine, glutamine, tyrosine, aspartic acid, glutamic acid, lysine, arginine, histidine, and taurine, preferably glycine, phenylalanine, threonine, serine, histidine, and cysteine, and most preferably glycine, threonine, serine, and cysteine.

[0125] In some embodiments, the polymer comprises a structural unit having a group represented by Formula 2-d and a structural unit having a group represented by Formula 2-c.

[0126] In some embodiments, the polymer comprises a structural unit having a group represented by Formula 3-d and a structural unit having a group represented by Formula 3-c or Formula 4-c.

[0127] In some embodiments, the polymer comprises a structural unit having a group represented by formula I-d and a structural unit having a group represented by formula I-c. In certain embodiments, the polymer comprises a structural unit having a group represented by formula I-d and a structural unit represented by formula I-c'.

[0128] In some embodiments, the polymer comprises a structural unit having a group represented by formula II-d and a structural unit having a group represented by formula II-c. In certain embodiments, the polymer comprises a structural unit having a structural unit represented by formula II-D and a structural unit represented by formula II-C'.

[0129] In some embodiments, the polymer comprises a structural unit having a group represented by formula III-d and a structural unit having a group represented by formula III-c. In certain embodiments, the polymer comprises a structural unit having a structural unit represented by formula III-D and a structural unit represented by formula III-C'.

[0130] In some embodiments, the polymer comprises a structural unit having a group represented by formula IV-d and a structural unit having a group represented by formula IV-c. In certain embodiments, the polymer comprises a structural unit having a structural unit represented by formula IV-D and a structural unit represented by formula IV-C'.

[0131] On the other hand, the present disclosure also provides a method for preparing a coating, comprising: reacting a polymer comprising a structural unit having a group represented by Formula 1-d and a structural unit having a group represented by Formula 1-c with a coupling agent as defined above, and then reacting with an amino acid (A) to form a coating.

[0132] The amino acid (A) is selected from glycine, alanine, valine, isoleucine, leucine, methionine, phenylalanine, tryptophan, serine, threonine, cysteine, asparagine, glutamine, tyrosine, aspartic acid, glutamic acid, lysine, arginine, histidine, and taurine, preferably glycine, phenylalanine, threonine, serine, histidine, and cysteine, and most preferably glycine, threonine, serine, and cysteine.

[0133] In some embodiments, the polymer comprises a structural unit having a group represented by Formula 2-d and a structural unit having a group represented by Formula 2-c.

[0134] In some embodiments, the polymer comprises a structural unit having a group represented by Formula 3-d and a structural unit having a group represented by Formula 3-c or Formula 4-c.

[0135] In some embodiments, the polymer comprises a structural unit having a group represented by formula I-d and a structural unit having a group represented by formula I-c. In certain embodiments, the polymer comprises a structural unit having a group represented by formula I-d and a structural unit represented by formula I-c'.

[0136] In some embodiments, the polymer comprises a structural unit having a group represented by formula II-d and a structural unit having a group represented by formula II-c. In certain embodiments, the polymer comprises a structural unit having a structural unit represented by formula II-D and a structural unit represented by formula II-C'.

[0137] In some embodiments, the polymer comprises a structural unit having a group represented by formula III-d and a structural unit having a group represented by formula III-c. In certain embodiments, the polymer comprises a structural unit having a structural unit represented by formula III-D and a structural unit represented by formula III-C'.

[0138] In some embodiments, the polymer comprises a structural unit having a group represented by formula IV-d and a structural unit having a group represented by formula IV-c. In certain embodiments, the polymer comprises a structural unit having a structural unit represented by formula IV-D and a structural unit represented by formula IV-C'.

[0139] On the other hand, the present disclosure also provides a method for preparing a biocompatible implantable material, comprising: reacting the aforementioned coupling agent through R 11 Connect to the substrate surface of the material to form a silane layer, and the coupling agent is passed through R 12 Reacts with the group represented by formula 1-d, formula 2-d or formula 3-d in the aforementioned polymer to form a polymer layer, and the surface of the substrate is optionally hydroxylated. Specifically, the coupling agent is R 12 The reactive group on the polymer undergoes a ring-opening reaction with the group represented by Formula 1-d, Formula 2-d, or Formula 3-d in the aforementioned polymer, wherein the reactive group is selected from hydroxyl, amino, carboxyl, and thiol. In certain embodiments, the reactive group is selected from amino, hydroxyl, and thiol. In certain embodiments, the reactive group is amino.

[0140] In another aspect, the present disclosure further provides a method for inhibiting platelet aggregation and platelet adhesion caused by exposure of blood to a material surface, the method comprising using the aforementioned material.

[0141] On the other hand, the present disclosure also provides a method for inhibiting platelet aggregation and platelet adhesion caused by exposure of blood to the surface of a material, the method comprising coating the aforementioned coating on the surface of a substrate of the material.

[0142] On the other hand, the present disclosure also provides a method for inhibiting platelet aggregation and platelet adhesion caused by exposure of blood to the surface of a material, the method comprising coating the coating prepared by the aforementioned method on the surface of a substrate of the material.

[0143] In some embodiments, the structural unit represented by Formula I-d or Formula I-D is derived from a monomeric compound selected from:

[0144] In some embodiments, the structural unit represented by Formula II-d or Formula II-D is derived from a monomeric compound selected from:

[0145] In some embodiments, the structural unit represented by formula III-d or formula III-D is derived from a monomeric compound selected from:

[0146] In some embodiments, the structural unit represented by Formula I-b or Formula I-B is derived from a monomeric compound selected from: wherein M is as defined above.

[0147] In some embodiments, the structural unit represented by Formula II-b or Formula II-B is derived from a monomeric compound selected from: wherein M is as defined above.

[0148] In some embodiments, the structural unit represented by Formula III-b or Formula III-B is derived from a monomeric compound selected from:

[0149] wherein M is as defined above.

[0150] In some embodiments, the structural unit represented by Formula I-c, Formula I-C, or Formula I-C' is derived from a monomeric compound selected from:

[0151] In some embodiments, the structural unit represented by Formula II-c, Formula II-C, or Formula II-C' is derived from a monomeric compound selected from:

[0152] In some embodiments, the structural unit represented by formula III-c, III-C, or III-C' is derived from a monomeric compound selected from:

[0153] In another aspect, the present disclosure further provides a method for preparing a biocompatible implantable material, comprising:

[0154] Step 1) hydroxylating the substrate surface of the material;

[0155] Step 2) treating the hydroxylated substrate surface with a coupling agent and curing the substrate to form an inner coating layer, i.e., a silane layer;

[0156] Step 3) preparing the polymer defined above into a polymer solution, first immersing the material treated in step 2) into the polymer solution, and then immersing the material into the amino acid (A) solution defined above, and forming an outer coating layer, i.e., a polymer layer, after curing;

[0157] Step 4) separating and removing the polymer remaining on the surface of the substrate;

[0158] Step 5) Dry the material.

[0159] In some embodiments, in order to apply a polymer layer and / or an optional silane layer to a substrate, the substrate surface of the material can be cleaned first. For example, the substrate surface can first be subjected to ultrasonic treatment and cleaned with a suitable solvent (such as acetone, isopropanol, ethanol, methanol, a combination thereof, etc.). Ultrasonic treatment can occur for a period of time from about 1 minute to about 20 minutes, in some embodiments from about 5 minutes to about 15 minutes. However, in embodiments, ultrasonic treatment can occur for a longer period of time, up to 1 hour, up to 2 hours or more than 2 hours. The solvent for ultrasonic treatment / cleaning can be applied as a mixture, or a single solvent can be applied sequentially one or more times. Ultrasonic treatment can occur at room temperature (e.g., about 21°C) or from about 18°C ​​to about 55°C, in some embodiments from about 40°C to about 50°C, and in some embodiments at a temperature of about 45°C.

[0160] In some embodiments, the hydroxylation described in step 1) occurs after the substrate surface is cleaned. The "hydroxylation" or "hydroxylation of the substrate surface" refers to increasing the number of hydroxyl groups on the substrate surface. The treatment method of "hydroxylation" or "hydroxylation of the substrate surface" is that the surface of the substrate can be hydroxylated by using a variety of different oxidizing agents to treat the surface. The oxidizing agents include acids, bases, peroxides, plasma treatment agents and combinations thereof. The acids include hydrochloric acid, nitric acid, sulfuric acid, hydrofluoric acid, perchloric acid or a combination thereof. The bases include sodium hydroxide, ammonium hydroxide, potassium hydroxide or a combination thereof. In certain embodiments, the oxide is a combination of an acid and a peroxide, preferably a combination of nitric acid and hydrogen peroxide, hydrochloric acid and hydrogen peroxide or sulfuric acid and hydrogen peroxide, most preferably a combination of nitric acid and hydrogen peroxide. In certain embodiments, the oxide is a combination of an alkali and a peroxide, preferably a combination of sodium hydroxide and hydrogen peroxide, ammonium hydroxide and hydrogen peroxide, potassium hydroxide and hydrogen peroxide, most preferably a combination of sodium hydroxide and hydrogen peroxide.

[0161] In certain embodiments, the concentration of the applied oxide may be from about 1% to about 100%. In certain embodiments, the concentration of the applied oxide is from about 15% to about 25%. In certain embodiments, the concentration of the applied oxide is about 20%.

[0162] In certain embodiments, the “hydroxylation” or “substrate surface hydroxylation” treatment method is that the surface of the substrate can be hydroxylated by treatment with sodium hydroxide, nitric acid, sulfuric acid, hydrochloric acid, ammonium hydroxide, hydrogen peroxide, tert-butyl hydroperoxide, potassium dichromate, perchloric acid, oxygen plasma, water plasma, corona discharge, ozone, UV, a combination thereof, or the like.

[0163] In certain embodiments, the hydroxylation reaction may occur at room temperature and continue in the range of from about 0.25 hour to about 4 hours. In certain embodiments, the hydroxylation reaction may occur at room temperature and continue in the range of from about 1 hour to about 2 hours. In certain embodiments, the hydroxylation reaction may occur at room temperature and continue in the range of about 1.5 hours in embodiments.

[0164] In certain embodiments, the hydroxylation reaction can also occur while shaking at from about 100 to about 160 revolutions per minute (rpm). In certain embodiments, the hydroxylation reaction can also occur while shaking at from about 120 rpm to about 140 rpm. In certain embodiments, the hydroxylation reaction can also occur while shaking at about 130 rpm.

[0165] In certain embodiments, the hydroxylation covers about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 90%, or about 100% of the substrate surface.

[0166] After hydroxylation, the substrate may be rinsed with a suitable material such as deionized water, ethanol, methanol, combinations thereof, and the like.

[0167] In some embodiments, the treatment method in step 2) includes: immersing the cleaned surface of the substrate in a coupling agent solution, washing, and then drying the substrate to form a silane layer on the treated surface.

[0168] In certain embodiments, suitable solvents for forming the silane layer include, for example, ethanol, toluene, water, deionized water, methanol, isopropanol, n-butanol, dimethylformamide (DMF), dimethyl sulfoxide (DMSO), ethyl acetate, propylene glycol methyl ether acetate (PM acetate), toluene, chloroform, dichloromethane, combinations thereof, and the like.

[0169] In certain embodiments, the solvent content in the solution for forming the silane layer can be from about 0.1 wt % to about 99.9 wt % of the solution. In certain embodiments, the solvent content can be from about 50 wt % to about 99.8 wt % of the solution. In certain embodiments, the solvent is ethanol / water (95% / 5%).

[0170] In certain embodiments, the concentration of the coupling agent in the solution used to form the silane layer can be from about 0.1% to about 99.9% by weight of the solution. In certain embodiments, the concentration of the coupling agent is from about 0.2% to about 50% by weight of the solution.

[0171] In certain embodiments, the substrate can be immersed in a solution comprising a coupling agent at room temperature for from about 0.5 hours to about 3.5 hours. In certain embodiments, the substrate can be immersed in a solution comprising a coupling agent at room temperature for from 1 hour to about 3 hours. In certain embodiments, the substrate can be immersed in a solution comprising a coupling agent at room temperature for about 2 hours.

[0172] In certain embodiments, the coupling agent solution treated with the substrate may also be shaken at a rate of from about 100 to about 160 revolutions per minute (rpm). In certain embodiments, the coupling agent solution treated with the substrate may also be shaken at a rate of from about 120 to about 140 rpm per minute. In certain embodiments, the coupling agent solution treated with the substrate may also be shaken at a rate of about 130 rpm per minute.

[0173] In certain embodiments, after immersing in the coupling agent solution, the substrate can be soaked or sprayed with a suitable material (such as ethanol, toluene, water, deionized water, methanol, isopropanol, n-butanol, dimethylformamide (DMF), dimethyl sulfoxide (DMSO), ethyl acetate, PM acetate, toluene, chloroform, dichloromethane, combinations thereof, etc.) from 1 to about 5 times, preferably about 3 times.

[0174] In certain embodiments, the surface of the substrate treated with the coupling agent is cured by heating and drying, and the heating temperature may be from about 30°C to about 150°C. In certain embodiments, the heating temperature is from about 60°C to about 100°C. In certain embodiments, the heating temperature is about 80°C. In certain embodiments, the heating may occur for a duration of from about 5 minutes to about 60 minutes, or more than 60 minutes. In certain embodiments, the heating may occur for a duration of from about 15 minutes to about 45 minutes. In certain embodiments, the heating may occur for a duration of about 30 minutes.

[0175] In certain embodiments, the silane layer formed on the substrate surface may have a thickness of less than 50 nm, less than 20 nm, or less than 10 nm. In certain embodiments, the silane layer formed on the substrate surface has a thickness of from about 1 nm to about 10 nm.

[0176] In some embodiments, after the silane layer is formed, the material can be treated with additional components to form an outer coating on the silane layer. For example, a bioactive agent can be bound to the reactive functional groups of the silane layer. Similarly, polymeric and / or monomeric materials can be bound to reactive functional groups on the substrate and / or the silane layer with or without a bioactive agent. The "reactive functional group" refers to a group that is highly reactive with a heterocyclic group and can undergo a ring-opening reaction with the heterocyclic group. The reactive functional group, for example, a hydroxyl, carboxyl, sulfhydryl or amino group, can be converted into a group containing a hydroxyl, sulfhydryl, amino or carboxyl group. In certain embodiments, the heterocyclic group is an epoxy group, for example, ethylene oxide.

[0177] In some embodiments, suitable polymeric and / or monomeric materials that can be used to form an outer coating on the materials of the present disclosure, bonded to the substrate, the aforementioned silane layer, or both, include any material suitable for use in the materials. These materials can provide the materials with desired properties, including reduced procoagulant properties, lubricity, drug delivery, protein or DNA transfer, restenosis prevention, cell and protein adhesion, lubricity, RNA and / or gene transfer, antimicrobial, antifouling, promotion of endothelialization, combinations thereof, and the like.

[0178] In some embodiments, suitable polymeric and / or monomeric materials that can be bonded to the substrate and / or the aforementioned silane layer and used to form an overcoat on the materials of the present disclosure include phosphorylcholine, heterocyclic groups.

[0179] In some embodiments, a suitable polymer may be bonded to the substrate and / or the aforementioned silane layer and used to form an overcoat on the materials of the present disclosure. The polymer is as defined above.

[0180] In some embodiments, the treatment method described in step 3) includes first immersing the material substrate treated with a coupling agent into a polymer solution, where the reactive functional groups on the coupling agent and the heterocyclic groups on the polymer are covalently linked through a ring-opening reaction; immersing the reacted substrate into an amino acid solution for treatment, whereby after sufficient reaction, all the heterocyclic groups in the polymer that have not participated in the reaction are ring-opened; and after curing treatment, a polymer layer is formed on the outermost coating on the surface of the substrate.

[0181] In some embodiments, the polymer used to form the polymer layer can be in a solution, which is then applied to the substrate and / or the aforementioned silane layer. Suitable solvents for forming the solution of the treatment polymer include, for example, ethanol, water, deionized water, methanol, isopropanol, n-butanol, dimethylformamide (DMF), dimethyl sulfoxide (DMSO), ethyl acetate, PM acetate, toluene, chloroform, dichloromethane, combinations thereof, and the like.

[0182] In certain embodiments, the concentration of the polymer solution in the polymer solution used to form the polymer layer can be from about 0.5% to about 95% by weight of the solution. In certain embodiments, the concentration of the polymer solution is from about 1% to about 50% by weight of the solution.

[0183] Polymer can be applied to substrate and / or optional silane layer using various methods (including soaking, spraying, brushing, combinations thereof, etc.). For example, in certain embodiments, the substrate formed with the silane layer can be immersed in a solution comprising the polymer for a period of from about 30 seconds to about 60 minutes at room temperature. In certain embodiments, the period of from about 1 minute to about 30 minutes can be continued. In certain embodiments, the period of from about 45 seconds, about 60 seconds, about 75 seconds, about 90 seconds, about 2 minutes, about 3 minutes, about 4 minutes, about 5 minutes, about 6 minutes, about 7 minutes, about 8 minutes, about 9 minutes, about 10 minutes can be continued.

[0184] In certain embodiments, the concentration of the amino acid solution can be from about 0.1% to about 99.9% by weight of the solution. In certain embodiments, the concentration of the amino acid solution can be from about 1% to about 50% by weight of the solution.

[0185] The substrate that has been soaked in the polymer solution can be immersed in the solution comprising the polymer again at room temperature for from about 1 hour to about 48 hours. In certain embodiments, the duration is about 1 hour, about 2 hours, about 3 hours, about 4 hours, about 5 hours, about 6 hours, about 7 hours, about 8 hours, about 9 hours, about 10 hours, about 11 hours, about 12 hours, about 13 hours, about 14 hours, about 15 hours, about 16 hours, about 17 hours, about 18 hours, about 19 hours, about 20 hours, about 21 hours, about 22 hours, about 23 hours, or about 24 hours.

[0186] In certain embodiments, the surface of the substrate treated with the amino acid solution is cured by heating and drying, and the heating temperature may be from about 30°C to about 150°C. In certain embodiments, the heating temperature is from about 60°C to about 100°C. In certain embodiments, the heating temperature is about 80°C. In certain embodiments, the heating may occur for a duration of from about 5 minutes to about 60 minutes, or more than 60 minutes. In certain embodiments, the heating may occur for a duration of from about 15 minutes to about 45 minutes. In certain embodiments, the heating may occur for a duration of about 30 minutes.

[0187] The material after curing treatment can be washed again.For example, the material can undergo ultrasonic treatment and the cleaning of water, ethanol, methanol, isopropanol, n-butanol, dimethylformamide (DMF), dimethyl sulfoxide (DMSO), ethyl acetate, PM acetate, toluene, chloroform, dichloromethane, toluene, its combination etc. Ultrasonic treatment can occur and continue from about 1 minute to about 10 minutes, or in the time of more than 10 minutes.In certain embodiments, continue from about 2 minutes to about 8 minutes.In certain embodiments, continue about 5 minutes.Ultrasonic treatment can occur at room temperature.

[0188] After this cleaning, the material can be rinsed with a suitable material (such as water, methanol, isopropanol, n-butanol, dimethylformamide (DMF), dimethyl sulfoxide (DMSO), ethyl acetate, PM acetate, toluene, chloroform, dichloromethane, combinations thereof, etc.). The material is then heated to dry, and the heating temperature can be from about 30°C to about 150°C. In certain embodiments, the heating temperature is from about 60°C to about 100°C. In certain embodiments, the heating temperature is about 80°C. In certain embodiments, the heating can occur for a duration of from about 5 minutes to about 60 minutes, or more than 60 minutes. In certain embodiments, the heating can occur for a duration of from about 15 minutes to about 45 minutes. In certain embodiments, the heating can occur for a duration of about 30 minutes.

[0189] The polymer layer on the resulting material can have a thickness of less than about 2000 nanometers. In certain embodiments, it has a thickness of less than about 1000 nanometers. In certain embodiments, it has a thickness of less than about 500 nanometers. In certain embodiments, it has a thickness of less than about 250 nanometers. In certain embodiments, it has a thickness of less than about 100 nanometers. In certain embodiments, it has a thickness of less than about 50 nanometers. In certain embodiments, it has a thickness of less than about 25 nanometers. In certain embodiments, it has a thickness of less than about 10 nanometers. In certain embodiments, it has a thickness of less than about 1 nanometer to about 100 nanometers. In certain embodiments, it has a thickness of less than about 1 nanometer to about 50 nanometers. In certain embodiments, it has a thickness of less than about 1 nanometer to about 25 nanometers. In certain embodiments, it has a thickness of less than about 1 nanometer to about 10 nanometers. In certain embodiments, the polymer layer is the outermost coating of any component (for example, forming the filament of the stent) of the material and / or forms its outer coating.

[0190] As mentioned above, bioactive agents can be added to the materials of the present disclosure as part of the material and / or part of the layer applied according to the present disclosure. As used herein, "bioactive agent" includes any substance or mixture of substances that provides a therapeutic or preventive effect; a compound that affects or participates in tissue growth, cell growth and / or cell differentiation; a compound that may be able to cause or prevent a biological effect (such as an immune response); or a compound that can play any other role in one or more biological processes. A variety of bioactive agents can be incorporated into the material. In addition, any reagent that can enhance tissue repair, limit the risk of restenosis, and modulate the mechanical or physical properties of the material (such as a stent) can be added during the preparation of the material. In certain embodiments, the bioactive agent can be added to the polymer used to form the outer coating of the material.

[0191] Examples of classes of bioactive agents that can be utilized according to the present disclosure include antimicrobial agents, analgesics, anesthetics, antihistamines, anti-inflammatory drugs, cardiovascular drugs, diagnostic agents, sympathomimetics, cholinergics, antimuscarinics, antispasmodics, hormonal agents, growth factors, muscle relaxants, adrenergic nerve blockers, antineoplastic drugs, immunogenic agents, immunosuppressants, steroids, lipids, lipopolysaccharides, polysaccharides, and enzymes. It is also contemplated that combinations of bioactive agents may be used.

[0192] The materials described in the present disclosure include, but are not limited to, stents, filters, stent coatings, grafts, catheters, stent-graft analogs, clips and other fasteners, staples, sutures, pins, screws, prosthetic materials, drug delivery materials, anastomotic rings, surgical blades, contact lenses, intraocular lenses, surgical mesh, knotless wound closure materials, sealants, adhesives, intraocular lenses, anti-adhesive materials, anchors, channels, bone fillers, synthetic tendons, synthetic ligaments, tissue scaffolds, anastomotic materials, hinge plates, abdominal bands, orthopedic hardware, pacemakers, and other implants and implantable materials.

[0193] In some embodiments, the material is a stent, stent graft, or stent analog. Any stent can be treated according to the methods herein. The stent can be a braided stent or other stent forms, such as a laser-cut stent, a rolled stent, a balloon-expandable stent, a self-expanding stent, a knitted stent, or the like.

[0194] In certain embodiments, the braided vascular material such as stent is woven from long filaments, and long filaments are formed by metal alloys and / or other high temperature materials. The gained braid is then heat-treated or "heat-set" at high temperature to reduce the internal stress in the long filaments and / or increase or give the self-expansion ability of stent. The long filaments constituting the tubular body of the stent that has been heat-set are in the state of its minimum stress or stress reduction when the stent is in the configuration during heat-setting. The state of this minimum stress or stress reduction can include expansion or full expansion state. Stent can optionally be configured to serve as " drainer " material for the treatment of aneurysm (such as the aneurysm found in the blood vessel of the artery in other positions (such as peripheral arteries) including in the brain or intracranial or human body).

[0195] For example, according to the present disclosure, a material having a drainage segment may have pores having a "drainage pore size." A "drainage pore size" may refer to an average pore size (in at least one segment of a material) that is sufficiently small to interfere with or inhibit fluid exchange through the pores of the segment. For example, a material (e.g., a stent) may have an active or drainage segment having a drainage pore size when the pores of the drainage segment having a drainage pore size are sized to inhibit blood flow through the sidewall into the aneurysm to a sufficient degree to cause thrombosis or heal the aneurysm when the material / stent is positioned in a blood vessel adjacent to or across the neck of an aneurysm.

[0196] For example, a draining pore size can be achieved when the pores in the draining or active segment (or in the stent generally) have an average pore size of less than about 500 microns when the material (e.g., a stent) is in an expanded state. (When "expanded state" is used herein to specify a braided stent parameter such as pore size, the expanded state is the state in which the stent will self-expand without the application of any external expansion force and without the application of any external longitudinal tensile or compressive force. For simplicity of measurement, such an expanded state can be the state in which the stent will self-expand into a right cylindrical glass tube having an inner diameter that is less than the maximum diameter to which the stent will self-expand in the absence of any restraining forces or external forces). In some embodiments, the average pore size can be less than about 320 microns. Some embodiments disclosed herein implement and provide a material and manufacturing method wherein the material has a draining segment or draining sidewall with reduced thrombogenicity or wherein the material generally possesses draining properties and reduced thrombogenicity.

[0197] Thus, in some embodiments, a material (such as a braided stent) is provided that can have a drainage segment or other portion of the material that provides embolic properties to disrupt blood flow in or into a body space (e.g., an aneurysm) in which (or across) the material is deployed. The porosity and / or pore size of one or more segments of the material can be selected to disrupt blood flow to a sufficient degree to thrombose the aneurysm or other body space.

[0198] For example, some embodiments provide materials (e.g., stents) that can be configured to disrupt blood flow to substantially reduce blood exchange between the parent vessel and the aneurysm (which can cause aneurysm thrombosis). Thus, materials (or components of materials, such as the sidewalls of a stent or segments of such sidewalls) that disrupt blood flow can be considered to have "draining" properties.

[0199] In addition, in some embodiments, the material (e.g., stent) may have a porosity in the range of 5% to 95% and may be used in an expanded braid. In some embodiments, a porosity in the range of 30% to 90% may be used. In addition, a porosity in the range of 50% to 85% may be used. Porosity can be calculated as the percentage of the total surface area open in the stent, where the total surface area is the sum of the open (pore-occupied) surface area and the solid (filament-occupied) surface area.

[0200] Furthermore, in some embodiments, the material (e.g., stent) can have a pore size of from about 20 microns to 300 microns (inscribed diameter). In some embodiments, a pore size of from about 25 microns to 250 microns (inscribed diameter) can be employed. In some embodiments, a pore size of from about 50 microns to 200 microns (inscribed diameter) can be employed.

[0201] In some embodiments, the substrate surface of the material for coating can be composed of optional surface material, and described surface material comprises metal, glass, polymer, ceramic, its combination etc.In some embodiments, described surface material is metal.Although any metal surface can be used, suitable metal can comprise gold, silver, copper, steel, aluminium, titanium, cobalt, chromium, platinum, nickel, its alloy and combination thereof.Suitable alloy can comprise nitinol (nickel titanium), cobalt nickel, cobalt chromium, platinum tungsten and combination thereof.In certain embodiments, described surface material can be activated by hydroxylation.

[0202] In some embodiments, at least a portion of the surface of the substrate of the material is coated with a coating as described herein. The coating comprises a polymer layer and / or a silane layer. The coating may cover from about 1% to about 100% of the substrate surface. In certain embodiments, at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, at least about 95%, at least about 95%, or about 100% of the substrate surface may be coated.

[0203] The present disclosure also includes various deuterated forms of the polymer or its pharmaceutically acceptable salt, wherein each available hydrogen atom in the polymer can be independently replaced by a deuterium atom. Those skilled in the art will know how to synthesize the deuterated forms of the polymer or its pharmaceutically acceptable salt of the present disclosure.

[0204] The present disclosure also includes isotopically labeled polymers, where one or more atoms in the polymer are replaced by an atom having an atomic mass or mass number different from the atomic mass or mass number most commonly found in nature. Examples of isotopes that can be used in the polymers of the present disclosure include isotopes of hydrogen, carbon, nitrogen, oxygen, fluorine, iodine, and chlorine, e.g. 3 H. 11 C. 14 C. 18 F. 123 I or 125 I.

[0205] Polymers of the present disclosure can be in the form of pharmaceutically acceptable salts. However, it should be understood that non-pharmaceutically acceptable salts also fall within the scope of the present disclosure, because these can be used as intermediates in the preparation of pharmaceutically acceptable salts or may be useful in storage or transportation. Suitable pharmaceutically acceptable salts include, but are not limited to, salts of pharmaceutically acceptable inorganic acids (such as hydrochloric acid, sulfuric acid, phosphoric acid, nitric acid, carbonic acid, boric acid, sulfamic acid and hydrobromic acid), or salts of pharmaceutically acceptable organic acids (such as acetic acid, propionic acid, butyric acid, tartaric acid, maleic acid, hydroxymaleic acid, fumaric acid, citric acid, lactic acid, mucic acid, gluconic acid, benzoic acid, succinic acid, oxalic acid, phenylacetic acid, methanesulfonic acid, toluenesulfonic acid (toluenesulphonic), benzenesulfonic acid, salicylic acid, sulfanilic acid (sulphanilic), aspartic acid, glutamic acid, ethylenediaminetetraacetic acid, stearic acid, palmitic acid, oleic acid, lauric acid, pantothenic acid, tannic acid, ascorbic acid and valeric acid). Basic salts include, but are not limited to, those formed with pharmaceutically acceptable cations such as sodium, potassium, lithium, calcium, magnesium, ammonium, and alkylammonium.

[0206] Unless stated otherwise, the following terms used in the specification and claims have the following meanings.

[0207] The term "halogen" refers to fluorine, chlorine, bromine or iodine.

[0208] The term "hydroxy" refers to -OH.

[0209] The term "amino" refers to -NH2.

[0210] The term "cyano" refers to -CN.

[0211] The term "nitro" refers to -NO2.

[0212] The term "oxo" or "oxo" refers to "=0".

[0213] The term "thio" or "thio" refers to "=S".

[0214] The term "carbonyl" refers to C=O.

[0215] The term "carboxy" refers to -C(O)OH.

[0216] The term "halo" refers to substitution with one or more atoms selected from fluorine, chlorine, bromine, and iodine.

[0217] The term "alkyl" refers to a straight or branched chain saturated hydrocarbon group having 1 to 6 carbon atoms. Where appropriate, the alkyl group may have a specified number of carbon atoms, for example, C 1-4 Alkyl, including alkyl groups having 1, 2, 3 or 4 carbon atoms in a straight or branched arrangement. Examples of suitable alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, 2-methylbutyl, 3-methylbutyl, 4-methylbutyl, n-hexyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 5-methylpentyl, 2-ethylbutyl, 3-ethylbutyl, heptyl, octyl, nonyl and decyl. Unless otherwise specified, alkyl groups may be substituted or unsubstituted.

[0218] The term "hydroxyalkyl" refers to an alkyl group substituted with one or more hydroxy groups, wherein alkyl is as defined above.

[0219] The term "aminoalkyl" refers to an alkyl group substituted with one or more amino groups, wherein alkyl is as defined above.

[0220] The term "carboxyalkyl" refers to an alkyl group substituted with one or more carboxyl groups, wherein alkyl is as defined above.

[0221] The term "haloalkyl" refers to an alkyl group substituted with one or more halogens (eg, fluorine, chlorine, bromine, iodine), wherein alkyl is as defined above.

[0222] The term "alkoxy" refers to -O-(alkyl), wherein alkyl is as defined above. Non-limiting examples of alkoxy include methoxy, ethoxy, propoxy, butoxy, cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, and cyclohexyloxy. Unless otherwise specified, alkoxy groups may be substituted or unsubstituted.

[0223] The term "haloalkoxy" refers to an alkoxy group substituted with one or more halogens (eg, fluorine, chlorine, bromine, iodine), wherein alkoxy is as defined above.

[0224] The term "aminoalkoxy" refers to an alkoxy group substituted with one or more amino groups, wherein alkoxy is as defined above.

[0225] The term "hydroxyalkoxy" refers to an alkoxy group substituted with one or more hydroxy groups, wherein alkoxy is as defined above.

[0226] The term "monovalent group" refers to a compound from which a univalent atom or group is "formally" eliminated.

[0227] The term "subunit" refers to an atom or group of atoms formed by "formally" eliminating two monovalent or one divalent atoms from a compound.

[0228] The term "alkylene" refers to the portion remaining after removing two hydrogen atoms from an alkane molecule, including straight and branched chain subgroups of 1 to 20 carbon atoms. Non-limiting examples include methylene (-CH2-), ethylene (e.g., -CH2CH2- or -CH(CH3)-). Unless otherwise specified, an alkylene group may be substituted or unsubstituted.

[0229] The term "heteroalkylene" refers to an alkylene group in which one or more -CH2- atoms are replaced by a heteroatom selected from N, O, and S; wherein the alkylene group is as defined above. Unless otherwise specified, a heteroalkylene group may be substituted or unsubstituted.

[0230] The term "cycloalkyl" or "carbocycle" refers to a saturated or unsaturated cyclic hydrocarbon. The cycloalkyl ring may include the specified number of carbon atoms. For example, a 3- to 8-membered cycloalkyl group includes 3, 4, 5, 6, 7, or 8 carbon atoms. Examples of suitable cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, 1,4-cyclohexadienyl, cycloheptyl, and cyclooctyl. Unless otherwise specified, a cycloalkyl group or carbocycle may be substituted or unsubstituted.

[0231] The term "cycloalkylene" refers to a divalent cyclic hydrocarbon radical derived from a cycloalkyl radical. For example Unless otherwise specified, a cycloalkylene group may be substituted or unsubstituted.

[0232] The term "heterocycloalkyl," "heterocyclyl," or "heterocycle" refers to a cyclic hydrocarbon in which one to four carbon atoms have been replaced by heteroatoms independently selected from N, N(R), S, S(O), S(O)2, and O. The heterocycle may be saturated or unsaturated. Examples of suitable heterocyclyl groups include oxiranyl, tetrahydrofuranyl, tetrahydrothienyl, pyrrolidinyl, pyrrolinyl, pyrazolinyl, pyranyl, piperidinyl, dithiole, oxathiole, dioxanyl, dioxinyl, morpholinyl, and oxazinyl. Unless otherwise specified, the heterocycloalkyl or heterocycle may be substituted or unsubstituted.

[0233] The term "heterocyclylene" refers to a divalent heterocyclic group; wherein the heterocyclic group is as defined above. Such heterocyclylene groups include, but are not limited to, piperidine-1,4-diyl, piperazine-1,4-diyl, tetrahydrofuran-2,4-diyl, tetrahydrofuran-3,4-diyl, azetidine-1,3-diyl, and pyrrolidine-1,3-diyl. Wherein, the heterocyclic group is as defined above.

[0234] The term "aryl" or "aromatic ring" refers to a monocyclic or bicyclic aromatic ring system containing 6 to 12 ring carbon atoms. Examples of aryl groups include, but are not limited to, phenyl and naphthyl. "Aryl" as used herein may include fused ring systems, including, for example, ring systems in which an aromatic ring is fused to a cycloalkyl ring. Examples of such fused ring systems include, for example, indane and indene. Unless otherwise specified, an aryl group or aromatic ring may be substituted or unsubstituted.

[0235] The term "arylene" refers to a group derived by removing two hydrogen atoms from the same or two different carbon atoms of a parent aryl group. The arylene group includes, but is not limited to, phenylene. Wherein, aryl is defined as above.

[0236] The term "heteroaryl" or "heteroaromatic ring" refers to an aromatic group containing 5 to 10 ring carbon atoms in which one or more ring carbon atoms are replaced by at least one heteroatom such as -O-, -N- or -S-; wherein the "aryl" is as defined above. Heteroaryl groups include, but are not limited to, acridinyl, carbazolyl, cinnolinyl, quinoxalinyl, quinazolinyl, pyrazolyl, indolyl, benzotriazolyl, furanyl, thienyl, phenylthio, 3,4-propylenedioxythiophenyl, benzothienyl, benzofuranyl, benzodioxane, benzodioxine, quinolinyl, isoquinolinyl, oxazolyl, isoxazolyl, imidazolyl, pyrazinyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrahydroquinoline, thiazolyl, isothiazolyl, 1,2,4-triazolyl, 1,2,3-triazolyl, 1,2,4-oxadiazolyl, 1,2,4-thiadiazolyl, 1,3,5-triazinyl, 1,2,4-triazinyl, 1,2,4,5-tetrazinyl, and tetrazolyl. Unless otherwise specified, a heteroaryl group or heteroaryl ring may be substituted or unsubstituted.

[0237] The term "heteroarylene" refers to a group derived by removing two hydrogen atoms from the same or two different atoms of a parent heteroaryl group. Such heteroarylene groups include, but are not limited to, pyridylene, pyrrolylene, thiazolylene, and imidazolylene groups. Heteroaryl is defined as above.

[0238] The term "optionally" or "optionally" means that the event or circumstances described subsequently may but need not occur, and the description includes instances where the event or circumstances occur or do not occur. For example, "the substrate surface is optionally treated with a modifier" means that the substrate surface can be treated with a modifier but does not have to be treated with a modifier. The term "all oxirane groups" refers to all oxirane groups carried by the polymer. For example, "all oxirane groups in Formula 1a are covalently bonded to the reactive functional groups via a ring-opening reaction" means that all oxirane groups contained in all structural units of Formula 1a in the polymer react fully with the reactive functional groups, so that all oxirane groups are covalently bonded to the reactive functional groups via a ring-opening reaction.

[0239] The term "substituted" means that one or more hydrogen atoms, preferably up to 5, more preferably 1 to 3 hydrogen atoms in a group are replaced independently of one another by a corresponding number of substituents. It goes without saying that the substituents are only in their possible chemical positions and a person skilled in the art can determine (by experiment or theory) which substitutions are possible or impossible without undue effort.

[0240] The term "substituent" includes but is not limited to halogen, hydroxy, oxo, amino, cyano, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C1-6 alkyl, 3- to 6-membered cycloalkyl, 3- to 6-membered heterocycloalkyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl.

[0241] The term "pharmaceutical composition" refers to a mixture containing one or more compounds described herein, or their physiologically / pharmaceutically acceptable salts or prodrugs, together with other chemical components, as well as other components such as physiologically / pharmaceutically acceptable carriers and excipients. The purpose of a pharmaceutical composition is to facilitate administration to an organism, facilitating absorption of the active ingredient and thereby exerting its biological activity.

[0242] With respect to a drug or pharmacologically active agent, the term "effective amount" refers to a non-toxic amount of the drug or agent sufficient to achieve the desired effect. The determination of an effective amount varies from person to person, depending on the age and general condition of the subject, as well as the specific active substance. The appropriate effective amount in each individual case can be determined by those skilled in the art through routine experimentation.

[0243] The term "pharmaceutically acceptable" refers to those compounds, materials, compositions and / or dosage forms that are, within the scope of sound medical judgment, suitable for use in contact with patient tissues without excessive toxicity, irritation, allergic response, or other problems or complications, commensurate with a reasonable benefit / risk ratio, and effective for the intended use.

[0244] As used herein, the singular form "a," "an," and "the" include plural references and vice versa unless the context clearly dictates otherwise.

[0245] In the chemical structures of the compounds disclosed herein, the bond No configuration is specified, i.e. the bond Can be or include both Two configurations. In the chemical structure of the compound disclosed in the present invention, the bond The configuration is not specified, that is, it can be Z configuration or E configuration, or contain both configurations.

[0246] Any isotope-labeled derivatives of the compounds or pharmaceutically acceptable salts thereof, or isomers thereof, described herein are covered by the present disclosure. Atoms that can be isotopically labeled include, but are not limited to, hydrogen, carbon, nitrogen, oxygen, phosphorus, fluorine, chlorine, iodine, and the like. They can be labeled with isotopes. 2 H(D), 3 H. 11 C. 13 C. 14 C. 15 N. 18 F. 31 P. 32 P. 35 S. 36 Cl and 125Unless otherwise indicated, when a position is specifically designated as deuterium (D), the position is understood to have an abundance of deuterium at least 3000 times greater than the natural abundance of deuterium, which is 0.015% (i.e., at least 45% deuterium incorporation). BRIEF DESCRIPTION OF THE DRAWINGS

[0247] Figure 1 shows the connection between the coupling agent, polymer and the metal substrate surface.

[0248] Figure 2 shows the polymer P (GMA-MPC) 1 H-NMR spectrum. DETAILED DESCRIPTION

[0249] The present disclosure is further described and explained below with reference to examples, but these examples are not intended to limit the scope of the present disclosure.

[0250] Experimental methods in the examples disclosed herein that do not specify specific conditions are generally performed under conventional conditions or according to the conditions recommended by the raw material or product manufacturers. Reagents that do not specify their specific sources are conventional reagents purchased from the market.

[0251] The structures of the compounds were determined by nuclear magnetic resonance (NMR) or mass spectrometry (MS). NMR measurements were performed using a Bruker AVANCE-400 NMR spectrometer. The solvents used were deuterated dimethyl sulfoxide (DMSO-d6), deuterated chloroform (CDCl3), and deuterated methanol (CD3OD). The internal standard was tetramethylsilane (TMS). Chemical shifts were calculated based on a 10 -6 The units are given in ppm.

[0252] MS was measured using a FINNIGAN LCQAd (ESI) mass spectrometer (manufacturer: Thermo, model: Finnigan LCQ advantage MAX).

[0253] High performance liquid chromatography (HPLC) was performed using an Agilent 1200DAD high pressure liquid chromatograph (Sunfire C18 150×4.6 mm column) and a Waters 2695-2996 high pressure liquid chromatograph (Gimini C18 150×4.6 mm column).

[0254] The thin layer chromatography silica gel plate uses Yantai Huanghai HSGF254 or Qingdao GF254 silica gel plate. The silica gel plate used in thin layer chromatography (TLC) adopts a specification of 0.15mm-0.2mm. The specification of thin layer chromatography separation and purification products adopts 0.4mm-0.5mm silica gel plate.

[0255] Column chromatography generally uses Yantai Huanghai 200-300 mesh silica gel as the carrier.

[0256] The known starting materials disclosed herein can be synthesized by methods known in the art, or can be purchased from ABCR GmbH & Co. KG, Acros Organnics, Aldrich Chemical Company, Accela ChemBio Inc, Darui Chemicals, and other companies.

[0257] Unless otherwise specified in the examples, all reactions were carried out under an argon or nitrogen atmosphere.

[0258] Argon atmosphere or nitrogen atmosphere means that the reaction bottle is connected to an argon or nitrogen balloon with a capacity of about 1 L.

[0259] Hydrogen atmosphere means that the reaction bottle is connected to a hydrogen balloon with a capacity of about 1L.

[0260] The pressurized hydrogenation reaction uses a Parr 3916EKX hydrogenator and a Qinglan QL-500 hydrogen generator or an HC2-SS hydrogenator.

[0261] The hydrogenation reaction is usually carried out by evacuating the chamber and filling it with hydrogen, and the operation is repeated three times.

[0262] A CEM Discover-S 908860 microwave reactor was used for the microwave reaction.

[0263] Unless otherwise specified in the examples, the solution in the reaction refers to an aqueous solution.

[0264] Unless otherwise specified in the examples, the reaction temperature is room temperature.

[0265] Room temperature is the most suitable reaction temperature, and the temperature range is 20℃~30℃.

[0266] Preparation of PBS buffer solution with pH=6.5 in the embodiment: 8.5 g of KH2PO4, 8.56 g of K2HPO4.3H2O, 5.85 g of NaCl, and 1.5 g of EDTA were placed in a bottle, the volume was adjusted to 2 L, and all the solution was dissolved by ultrasonication and shaken to obtain the solution.

[0267] The eluent system for column chromatography and the developing solvent system for thin-layer chromatography used to purify the compound include: A: dichloromethane and isopropanol system, B: dichloromethane and methanol system, C: petroleum ether and ethyl acetate system. The volume ratio of the solvent is adjusted according to the polarity of the compound, and a small amount of triethylamine and acidic or alkaline reagents can also be added for adjustment.

[0268] Some compounds of the present disclosure were characterized by Q-TOF LC / MS using an Agilent 6530 accurate mass quadrupole-time of flight mass spectrometer and an Agilent 1290-Infinity ultra-performance liquid chromatograph (Agilent Poroshell 300SB-C8 5 μm, 2.1×75 mm column).

[0269] Example 1. Preparation of P(GMA-MPC) solution

[0270] Step 1) Synthesis of polymer

[0271] 3.0 g of MPC (purchased from TCI, batch KDW4G-PB) and 0.36 g of GMA (purchased from Adamas, batch P1909690) were dissolved in 50.0 ml of anhydrous ethanol, placed in a three-necked flask equipped with a thermometer and condenser, and purged with nitrogen for 30 minutes. Subsequently, 0.1 g of azobisisobutyronitrile (purchased from Adamas, batch P1871519) was added at 60°C, and polymerization was carried out for 10 to 20 hours. After completion of the polymerization, the polymer was precipitated in tetrahydrofuran and dried under vacuum at 40°C to recover a white powder. Proton spectroscopy confirmed that the molar ratio of MPC in the resulting polymer was 70%.

[0272] 1 H-NMR (400MHz, CD3OD): δ4.35,-COOCH2CH-; δ4.24,-COOCH2CH2O-; δ4.11,-OCH2CH2N(CH3)3; δ3.76,- OCH2CH2N(CH3)3; δ3.33, -CH2N(CH3)3; δ3.14, -CHOCH2; δ2.91 and δ2.74, -CHOCH2; δ2.00 and δ1.92, -CH2-C.

[0273] Determine the molecular weight of polymers

[0274] 2 mg of the obtained polymer was dissolved in 1 g of a 0.1 mol / L sodium nitrate aqueous solution.

[0275] Test conditions: column: Shodex (SB-806M HQ), mobile phase: 0.1 mol / L sodium nitrate aqueous solution, standard substance: polyethylene glycol, detection: differential refractive index detector 1260RID, calculation of weight-average molecular weight: molecular weight calculation program (Agilent Cirrus GPC Software), flow rate: 1.0 mL / min, column temperature: 30°C, injection volume: 20 uL, test time: 25 min.

[0276] The obtained polymer had a number average molecular weight of 25,884, a weight average molecular weight of 45,702, and a molecular weight distribution of 1.77.

[0277] Step 2) Preparation of polymer solution

[0278] The obtained polymer was dissolved in anhydrous ethanol to prepare a P(GMA-MPC) solution with a weight content of 5%.

[0279] Example 2: Coating a silane layer on the surface of a substrate

[0280] Titanium-nickel alloy products were ultrasonically cleaned with ethanol and deionized water, then rinsed with diluted 35% nitric acid and hydrogen peroxide, and then rinsed with deionized water. The products were then soaked in a 99.5% ethanol aqueous solution containing 20% ​​by weight of 3-aminopropyltriethoxysilane, rinsed with deionized water, and then dried at 80°C for 20 to 40 minutes to cure.

[0281] Example 3: Coating a polymer layer P (GMA-MPC) on the surface of a substrate

[0282] The metal treated in Example 2 was immersed in the P(GMA-MPC) solution prepared in Example 1 for 5-20 minutes and cured at 80°C for 20 minutes to 1 hour. The metal surface was then washed with anhydrous ethanol for 10 minutes during ultrasonic treatment to eliminate non-covalently bonded polymers. The washed metal surface was dried at approximately 80°C for 20-40 minutes.

[0283] Example 4: Coating a polymer layer P (GMA-cysGMA-MPC) on the surface of a substrate

[0284] The metal treated in Example 2 was immersed in the P(GMA-MPC) solution prepared in Example 1 for 5-20 minutes, then immersed in a 0.1-2% cysteine ​​(Cys) solution in pH 7.2 PBS for at least 16 hours, and then cured at 80°C for 20 minutes to 1 hour. The metal surface was then washed with ethanol during ultrasonic treatment to eliminate non-covalently bonded polymers. The washed metal surface was dried at approximately 80°C for 20-40 minutes.

[0285] Example 5. Preparation of P(GMA-MPC) solution

[0286] Step 1) Synthesis of polymer

[0287] 37.5 g of MPC (purchased from TCI, batch KDW4G-PB) and 12.1 g of GMA (purchased from Adamas, batch P1909690) were dissolved in 2000 ml of anhydrous ethanol, placed in a three-necked flask equipped with a thermometer and condenser, and purged with nitrogen for 30 minutes. Then, 1.2 g of azobisisobutyronitrile (purchased from Adamas, batch P1871519) was added at 60°C, and polymerization was carried out for 10 to 20 hours. After completion of the polymerization, the polymer was precipitated in tetrahydrofuran and dried in vacuo at 40°C to recover a white powder. Proton spectroscopy confirmed that the molar ratio of MPC in the resulting polymer was 52%.

[0288] 1 H-NMR (400MHz, CD3OD): δ4.35,-COOCH2CH-; δ4.24,-COOCH2CH2O-; δ4.11,-OCH2CH2N(CH3)3; δ3.76,- OCH2CH2N(CH3)3; δ3.33, -CH2N(CH3)3; δ3.14, -CHOCH2; δ2.91 and δ2.74, -CHOCH2; δ2.00 and δ1.92, -CH2-C.

[0289] Determine the molecular weight of polymers

[0290] 2 mg of the obtained polymer was dissolved in 1 g of a 0.1 mol / L sodium nitrate aqueous solution.

[0291] Test conditions: column: Shodex (SB-806M HQ), mobile phase: 0.1 mol / L sodium nitrate aqueous solution, standard substance: polyethylene glycol, detection: differential refractive index detector 1260RID, calculation of weight-average molecular weight: molecular weight calculation program (Agilent Cirrus GPC Software), flow rate: 1.0 mL / min, column temperature: 30°C, injection volume: 20 uL, test time: 25 min.

[0292] The obtained polymer had a number average molecular weight of 18,277, a weight average molecular weight of 37,760, and a molecular weight distribution of 2.07.

[0293] Step 2) Preparation of polymer solution

[0294] The obtained polymer was dissolved in ethanol to prepare a P(GMA-MPC) solution with a weight content of 5%.

[0295] Example 6: Coating a polymer layer P (GMA-MPC) on the surface of a substrate

[0296] The metal treated in Example 2 was immersed in the P(GMA-MPC) solution prepared in Example 5 for 5-20 minutes and cured at 80°C for 20 minutes to 1 hour. The metal surface was then washed with ethanol for 10 minutes during ultrasonic treatment to eliminate non-covalently bound polymers. The metal was then immersed in the P(GMA-MPC) solution prepared in Example 5 for 5-20 minutes and cured at 80°C for 20 minutes to 1 hour. The metal surface was then washed with ethanol for 10 minutes during ultrasonic treatment to eliminate non-covalently bound polymers. Finally, the washed metal surface was dried at approximately 80°C for 20-40 minutes.

[0297] Example 7: Coating a polymer layer P (GMA-cysGMA-MPC) on the surface of a substrate

[0298] The metal treated in Example 2 was immersed in the P(GMA-MPC) solution prepared in Example 5 for 5-20 minutes and cured at 80°C for 20 minutes to 1 hour. The metal surface was then washed with ethanol for 10 minutes during ultrasonic treatment to eliminate non-covalently bound polymers. The metal was then immersed in the P(GMA-MPC) solution prepared in Example 5 for 5-20 minutes and cured at 80°C for 20 minutes to 1 hour. The metal surface was then washed with ethanol for 10 minutes during ultrasonic treatment to eliminate non-covalently bound polymers.

[0299] The treated metal was then immersed in a 0.1-2% cysteine ​​(Cys) solution in PBS (pH 7.2) for at least 16 hours. The metal surface was then washed with ethanol during ultrasonic treatment to eliminate non-covalently bound polymers. The washed metal surface was then dried at approximately 80°C for 20-40 minutes.

[0300] Example 8: Coating a polymer layer P (GMA-glyGMA-MPC) on the surface of a substrate

[0301] The metal treated in Example 2 was immersed in the P(GMA-MPC) solution prepared in Example 5 for 5-20 minutes and cured at 80°C for 20 minutes to 1 hour. The metal surface was then washed with ethanol for 10 minutes during ultrasonic treatment to eliminate non-covalently bound polymers. The metal was then immersed in the P(GMA-MPC) solution prepared in Example 5 for 5-20 minutes and cured at 80°C for 20 minutes to 1 hour. The metal surface was then washed with ethanol for 10 minutes during ultrasonic treatment to eliminate non-covalently bound polymers.

[0302] The treated metal was then immersed in a 0.1-2% glycine (gly) solution in PBS (pH 7.2) for at least 16 hours. The metal surface was then washed with ethanol during ultrasonic treatment to eliminate non-covalently bound polymers. The washed metal surface was then dried at approximately 80°C for 20-40 minutes.

[0303] Example 9: Coating a polymer layer P (GMA-serGMA-MPC) on the surface of a substrate

[0304] The metal treated in Example 2 was immersed in the P(GMA-MPC) solution prepared in Example 5 for 5-20 minutes and cured at 80°C for 20 minutes to 1 hour. The metal surface was then washed with ethanol for 10 minutes during ultrasonic treatment to eliminate non-covalently bound polymers. The metal was then immersed in the P(GMA-MPC) solution prepared in Example 5 for 5-20 minutes and cured at 80°C for 20 minutes to 1 hour. The metal surface was then washed with ethanol for 10 minutes during ultrasonic treatment to eliminate non-covalently bound polymers.

[0305] The treated metal was then immersed in a 0.1-2% serine (ser) solution in PBS (pH 7.2) for at least 16 hours. The metal surface was then washed with ethanol during ultrasonic treatment to eliminate non-covalently bound polymers. The washed metal surface was then dried at approximately 80°C for 20-40 minutes.

[0306] Example 10: Coating a polymer layer P (GMA-gluGMA-MPC) on the surface of a substrate

[0307] The metal treated in Example 2 was immersed in the P(GMA-MPC) solution prepared in Example 5 for 5-20 minutes and cured at 80°C for 20 minutes to 1 hour. The metal surface was then washed with ethanol for 10 minutes during ultrasonic treatment to eliminate non-covalently bound polymers. The metal was then immersed in the P(GMA-MPC) solution prepared in Example 5 for 5-20 minutes and cured at 80°C for 20 minutes to 1 hour. The metal surface was then washed with ethanol for 10 minutes during ultrasonic treatment to eliminate non-covalently bound polymers.

[0308] The treated metal was then immersed in a 0.1-2% glutamic acid (glu) solution in PBS (pH 7.2) for at least 16 hours. The metal surface was then washed with ethanol during ultrasonic treatment to eliminate non-covalently bound polymers. The washed metal surface was then dried at approximately 80°C for 20-40 minutes.

[0309] Example 11: Coating a polymer layer P (GMA-lysGMA-MPC) on the surface of a substrate

[0310] The metal treated in Example 2 was immersed in the P(GMA-MPC) solution prepared in Example 5 for 5-20 minutes and cured at 80°C for 20 minutes to 1 hour. The metal surface was then washed with ethanol for 10 minutes during ultrasonic treatment to eliminate non-covalently bound polymers. The metal was then immersed in the P(GMA-MPC) solution prepared in Example 5 for 5-20 minutes and cured at 80°C for 20 minutes to 1 hour. The metal surface was then washed with ethanol for 10 minutes during ultrasonic treatment to eliminate non-covalently bound polymers.

[0311] The treated metal was then immersed in a 0.1-2% lysine (Lys) solution in PBS (pH 7.2) for at least 16 hours. The metal surface was then washed with ethanol during ultrasonic treatment to eliminate non-covalently bound polymers. The washed metal surface was dried at approximately 80°C for 20-40 minutes.

[0312] Example 12: Preparation of P(GMA-MPC) solution

[0313] Step 1) Synthesis of polymer

[0314] 1.0 g of MPC (purchased from TCI, batch KDW4G-PB) and 0.72 g of GMA (purchased from Adamas, batch P1909690) were dissolved in 30.0 ml of anhydrous ethanol, placed in a three-necked flask equipped with a thermometer and condenser, and purged with nitrogen for 30 minutes. Subsequently, 0.05 g of azobisisobutyronitrile (purchased from Adamas, batch P1871519) was added at 60°C, and polymerization was carried out for 10 to 20 hours. After completion of the polymerization, the polymer was precipitated in tetrahydrofuran and dried in vacuo at 40°C to recover a white powder. Proton spectroscopy confirmed that the molar ratio of MPC in the resulting polymer was 42%.

[0315] 1 H-NMR (400MHz, CD3OD): δ4.35,-COOCH2CH-; δ4.24,-COOCH2CH2O-; δ4.11,-OCH2CH2N(CH3)3; δ3.76,- OCH2CH2N(CH3)3; δ3.33, -CH2N(CH3)3; δ3.14, -CHOCH2; δ2.91 and δ2.74, -CHOCH2; δ2.00 and δ1.92, -CH2-C.

[0316] Determine the molecular weight of polymers

[0317] 2 mg of the obtained polymer was dissolved in 1 g of a 0.1 mol / L sodium nitrate aqueous solution.

[0318] Test conditions: Column: Shodex (SB-806M HQ), Mobile phase: 0.1 mol / L sodium nitrate aqueous solution, Standard substance: Polyethylene glycol, Detection: Differential refractive index detector 1260RID, Weight average molecular weight calculation: Molecular weight calculation program (Agilent Cirrus GPC Software), Flow rate: 1.0 mL / min, Column temperature: 30°C, Injection volume: 20 μL, Test time: 25 min.

[0319] The obtained polymer had a number average molecular weight of 10,665, a weight average molecular weight of 23,912, and a molecular weight distribution of 2.24.

[0320] Step 2) Preparation of polymer solution

[0321] The obtained polymer was dissolved in ethanol to prepare a P(GMA-MPC) solution with a weight content of 5%.

[0322] Example 13: Coating a polymer layer P (GMA-MPC) on the surface of a substrate

[0323] The metal treated in Example 2 was immersed in the P(GMA-MPC) solution prepared in Example 12 for 5-20 minutes and cured at 80°C for 20 minutes to 1 hour. The metal surface was then washed with ethanol for 10 minutes during ultrasonic treatment to eliminate non-covalently bound polymers. The metal was then immersed in the P(GMA-MPC) solution prepared in Example 12 for 5-20 minutes and cured at 80°C for 20 minutes to 1 hour. The metal surface was then washed with ethanol for 10 minutes during ultrasonic treatment to eliminate non-covalently bound polymers. Finally, the washed metal surface was dried at approximately 80°C for 20-40 minutes.

[0324] Example 14: Coating a polymer layer P (GMA-cysGMA-MPC) on the surface of a substrate

[0325] The metal treated in Example 2 was immersed in the P(GMA-MPC) solution prepared in Example 12 for 5-20 minutes and cured at 80°C for 20 minutes to 1 hour. The metal surface was then washed with ethanol for 10 minutes during ultrasonic treatment to eliminate non-covalently bound polymers. The metal was then immersed in the P(GMA-MPC) solution prepared in Example 12 for 5-20 minutes and cured at 80°C for 20 minutes to 1 hour. The metal surface was then washed with ethanol for 10 minutes during ultrasonic treatment to eliminate non-covalently bound polymers.

[0326] The treated metal was then immersed in a 0.1-2% cysteine ​​(Cys) solution in PBS (pH 7.2) for at least 16 hours. The metal surface was then washed with ethanol during ultrasonic treatment to eliminate non-covalently bound polymers. The washed metal surface was then dried at approximately 80°C for 20-40 minutes.

[0327] Biological evaluation

[0328] The present disclosure is further described and explained below in conjunction with test examples, but these embodiments are not intended to limit the scope of the present disclosure.

[0329] Test Example 1: Cytotoxicity Test

[0330] The cytotoxicity test was performed according to the MTT method 2.0 and evaluated based on the cell survival rate.

[0331] 1. Instruments and reagents

[0332] 2. Experimental methods

[0333] 1) Preparation of MTT solution

[0334] MTT powder was diluted to a concentration of 1 mg / mL with MEM medium without phenol red and additives, and sterilized by filtration through a 0.22 μm microporous filter membrane.

[0335] 2) Preparation of culture medium

[0336] L929 cells were cultured in MEM medium containing 10% fetal bovine serum (FBS) and antibiotics (penicillin 100 U / ml, streptomycin 100 μg / ml) in a 37°C, 5% CO2 incubator. After the cells grew to approximately 80%, they were pre-washed with PBS solution, the pre-wash solution discarded, and the cells were digested with 0.25% trypsin (containing EDTA). When the cells shrank and became rounded and the intercellular spaces became larger, complete medium (89% MEM medium + 10% FBS + 1% antibiotics) was added to terminate the digestion. The cells were gently pipetted to dislodge them, and the cell suspension was then transferred to a centrifuge tube and centrifuged (1000 rpm, 3 min). The supernatant was discarded, and the pelleted cells were added to complete medium to prepare a single-cell suspension. The cells were redispersed in the culture medium for later use.

[0337] 3) Cell seeding

[0338] Take 10uL of single cell suspension and 10μL of 0.25% trypan blue dye (configuration ratio is 1:1) in a centrifuge tube and mix thoroughly. Use a pipette to take 10μL of the mixture and add it to the cell counting plate. Count the cells using a cell counter. Calculate the cell density according to the formula "number of cells in single cell suspension / ml = cell count result × 2" and adjust the cell concentration to 1.0×10 6 The single cell suspension of 100 cells / ml was prepared for use.

[0339] 4) Preparation of extract

[0340] Test samples: metal products containing polymer coatings obtained in Examples 3 and 4.

[0341] Blank control: MEM culture medium containing 10% fetal bovine serum (no sample added).

[0342] Negative control: high-density polyethylene (extracted at a ratio of 0.2 g negative control plus 1 mL cell culture medium); solvent: MEM culture medium containing 10% fetal bovine serum.

[0343] Positive control: 20% DMSO solution; solvent: MEM culture medium containing 10% fetal bovine serum.

[0344] Place the test sample in a sterile centrifuge tube, add MEM culture medium containing 10% fetal bovine serum, place on a 37°C air bath shaker with a vibration frequency of 60 rpm, and extract for 24 hours.

[0345] Set up blank control, negative control and positive control, and place them under the same extraction conditions and time as the test samples.

[0346] 5) Cell culture

[0347] The extract was added to a 96-well plate and cultured for 24 h. The cell status and number were observed under an inverted microscope to confirm that there was no obvious microscopic difference between the cells in each well.

[0348] The original culture medium was aspirated, and 100 μL of the test sample extract was added to each of the 6 wells in each column (except the outer wells). The negative control solution, positive control solution, and blank control solution were cultured in a cell culture incubator (37° C., 5% CO 2 ) for 24 h.

[0349] 6) MTT assay

[0350] After 24 hours of incubation, remove the 96-well plate from the CO2 incubator and observe the cell morphology and number under a microscope to make a preliminary qualitative judgment on the test results. Any abnormalities such as large cell detachment or abnormal cell status should be recorded and used to correct the final data, or the test results may be discarded.

[0351] Use a pipette to add 50 μL of 1 mg / mL MTT solution to each well and continue incubating in a CO2 incubator for 2 hours. Aspirate the supernatant and add 100 μL of isopropanol solution to each well. Shake on a microplate shaker for 10 minutes or until the formazan crystals are completely dissolved. Wipe the bottom of the 96-well plate clean with a dust-free cloth. Measure absorbance on a microplate reader at a primary wavelength of 570 nm and a reference wavelength of 630 nm. Calculate cell viability (Via b.%) according to the following formula:

[0352] Wherein, OD570e is the average absorbance value of the 100% extract of the test sample (or positive or negative control), and OD570b is the average absorbance value of the blank control.

[0353] 3. Experimental results

[0354] Table 1. Cell survival rate

[0355] Test Example 2: Testing the Coagulation Performance of Metal Products with Different Polymer Coatings Using the Platelet Adhesion Method

[0356] 1. Instruments and reagents

[0357] 2. Experimental Animals

[0358] 3. Experimental methods

[0359] Centrifuge the rabbit whole blood in a centrifuge for 10 minutes, take the supernatant into a centrifuge tube; centrifuge again for 10 minutes, discard half of the plasma on the top of the centrifuge tube, and obtain rabbit platelet-rich plasma (PRP). Gently rinse the sample surface with PBS buffer, place it in a 24-well microplate, add fresh PRP to immerse the metal product, and incubate it in a constant temperature box at 37°C for 2 hours. After incubation, wash the metal product three times with PBS buffer, add 2.5% glutaraldehyde solution to fix the platelets on the surface of the metal product, and place it in a refrigerator for 24 hours. The fixed sample is washed three times with PBS buffer and soaked in 20%, 40%, 60%, 80%, and 100% ethanol solutions for 10 minutes in sequence.

[0360] After the metal products were dehydrated and dried at room temperature, a scanning electron microscope was used to observe the platelet adhesion and activation on the metal product surface. The experimental results are shown in the following table:

[0361] Table 2. Anticoagulation test results

[0362] Test Example 3: Testing the Coagulation Performance of Metal Products with Different Polymer Coatings Using the Platelet Adhesion Method

[0363] 1. Instruments and reagents

[0364] 2. Experimental Animals

[0365] 3. Experimental methods

[0366] Centrifuge the rabbit whole blood in a centrifuge for 10 minutes, take the supernatant into a centrifuge tube; centrifuge again for 10 minutes, discard half of the plasma on the top of the centrifuge tube, and obtain rabbit platelet-rich plasma (PRP). Gently rinse the sample surface with PBS buffer, place it in a 24-well microplate, add fresh PRP to immerse the metal product, and incubate it in a constant temperature box at 37°C for 2 hours. After incubation, wash the metal product three times with PBS buffer, add 2.5% glutaraldehyde solution to fix the platelets on the surface of the metal product, and place it in a refrigerator for 24 hours. The fixed sample is washed three times with PBS buffer and soaked in 20%, 40%, 60%, 80%, and 100% ethanol solutions for 10 minutes in sequence.

[0367] After the metal products were dehydrated and dried at room temperature, a scanning electron microscope was used to observe the platelet adhesion and activation on the metal product surface. The experimental results are shown in the following table:

[0368] Table 3. Anticoagulation test results

[0369] Test Example 4: Testing the Coagulation Performance of Metal Products Containing Different Polymer Coatings Using the Platelet Adhesion Method

[0370] 1. Instruments and reagents

[0371] 2. Experimental Animals

[0372] 3. Experimental methods

[0373] Centrifuge the rabbit whole blood in a centrifuge for 10 minutes, take the supernatant into a centrifuge tube; centrifuge again for 10 minutes, discard half of the plasma on the top of the centrifuge tube, and obtain rabbit platelet-rich plasma (PRP). Gently rinse the sample surface with PBS buffer, place it in a 24-well microplate, add fresh PRP to immerse the metal product, and incubate it in a constant temperature box at 37°C for 2 hours. After incubation, wash the metal product three times with PBS buffer, add 2.5% glutaraldehyde solution to fix the platelets on the surface of the metal product, and place it in a refrigerator for 24 hours. The fixed sample is washed three times with PBS buffer and soaked in 20%, 40%, 60%, 80%, and 100% ethanol solutions for 10 minutes in sequence.

[0374] After the metal products were dehydrated and dried at room temperature, a scanning electron microscope was used to observe the platelet adhesion and activation on the metal product surface. The experimental results are shown in the following table:

[0375] Table 4. Anticoagulation test results

Claims

1. A material comprising a substrate and a coating, wherein the coating comprises a polymer, and the polymer comprises a structural unit having a group represented by formula 1-a, a structural unit having a group represented by formula 1-b, and a structural unit having a group represented by formula 1-c, where ** represents the end connected to the surface of the substrate, wherein the surface of the substrate is optionally treated with a modifier; X 1 and X 2 are the same or different and each is independently selected from -O-, -S-, or -N(R d )-; Y is selected from -OH, -SH or -N(R e R f ); R 1 , R 2 and R 3 are the same or different and each is independently selected from hydrogen, halogen, hydroxyl, mercapto, nitro, carboxyl, amino, cyano, C 1-6 alkyl or C 1-6 alkoxy, while C 1-6alkyl and C 1-6 alkoxy optionally substituted with one or more groups selected from halogen, hydroxyl, mercapto, nitro, carboxyl, amino, cyano, C 1-6 alkyl and C 1-6 alkoxy, alternatively, R 1 and R 2 together with the atom to which they are bonded, they form an oxo group, a thio group, C 3-10 cycloalkyl or 3-10-membered heterocycloalkyl; L 1 and L 3 are the same or different and each is independently selected from a bond, alkylene or heteroalkylene, wherein alkylene and heteroalkylene are optionally substituted with one or more groups selected from C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 aminoalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 1-6 hydroxyalkoxy, C 1-6 aminoalkoxy, halogen, amino, hydroxyl, nitro, cyano, mercapto, carboxyl, oxo, thio or sulfonyl; L 2selected from alkylene or heteroalkylene, wherein alkylene and heteroalkylene are optionally substituted with one or more groups selected from C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 aminoalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 1-6 hydroxyalkoxy, C 1-6 aminoalkoxy, halogen, amino, hydroxyl, nitro, cyano, mercapto, carboxyl, oxo, thio or sulfonyl; M is an amino acid residue (A), wherein M is optionally substituted with one or more groups selected from halogen, amino, hydroxyl, nitro, cyano, amino, mercapto, carboxyl, C 1-6 alkyl or C 1-6 alkoxy; R a , R b , R c , R d , R e and R f are the same or different and each is independently selected from hydrogen, halogen, hydroxyl, C 1-6 alkyl or C 1-6 alkoxy, while C 1-6alkyl or C 1-6 alkoxy optionally substituted with one or more groups selected from halogen, hydroxyl, cyano, nitro, C 1-6 alkyl, C 1-6 alkoxy and C 3-7 cycloalkyl.

2. The material according to claim 1, wherein the polymer comprises a structural unit represented by formula Ia, a structural unit represented by formula Ib, and a structural unit represented by formula Ic, where ** represents the end connected to the substrate surface; each R 10 independently selected from hydrogen, halogen, hydroxyl, mercapto, nitro, carboxyl, amino, cyano, C 1-6 alkyl or C 1-6 alkoxy, while C 1-6 alkyl and C 1-6 alkoxy optionally substituted with one or more groups selected from halogen, hydroxyl, mercapto, nitro, carboxyl, amino, cyano, C 1-6 alkyl or C 1-6 alkoxy; L 1 , L 2 , L3 , R 1 , R 2 , R 3 , M, Y, X 1 , X 2 , R a , R b , and R c are as defined in paragraph 1.

3. The material according to claim 1 or 2, where Y is selected from -OH or -SH, preferably -OH.

4. Material according to any of paragraphs 1-3, where each of L 1 and L 3 independently selected from the bond or C 1-6 alkylene, while C 1-6 alkylene is optionally substituted with one or more groups selected from C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 aminoalkyl, halogen, amino, hydroxyl, cyano or mercapto.

5. Material according to any of paragraphs 1-4, where L 2 represents C 1-6 alkylene optionally substituted with one or more groups selected from C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 aminoalkyl, halogen, amino, hydroxyl, cyano or mercapto.

6. Material according to any of paragraphs 1-5, where each of X 1 and X 2 independently selected from -O- or -N(R d )-, preferably -O-, wherein R d is as defined in paragraph 1.

7. The material according to any one of claims 1-6, wherein the polymer comprises a structural unit having a group represented by formula 3-a, a structural unit having a group represented by formula 3-b, and a structural unit having a group represented by formula 3-c, where ** represents the end connected to the substrate surface; R 4 , R 5 , R 6 , R 7 , R 8 and R 9 are the same or different and each is independently selected from hydrogen, halogen, hydroxyl, mercapto, nitro, carboxyl, amino, cyano, C 1-6 alkyl, C 1-6 alkoxy, C3-7cycloalkyl or 3-7-membered heterocycloalkyl, wherein C 1-6alkyl, C 1-6 alkoxy, C 3-7 cycloalkyl or 3-7-membered heterocycloalkyl are optionally substituted with one or more groups selected from halogen, hydroxyl, mercapto, nitro, carboxyl, amino, cyano, C 1-6 alkyl or C 1-6 alkoxy, alternatively, R 4 and R 5 , R 6 and R 7 or R 8 and R 9 together with the atom to which they are bonded, they form an oxo group, a thio group, C3- 10 cycloalkyl or 3-10-membered heterocycloalkyl; a is selected from 0, 1, 2, 3, 4, 5, or 6; b is selected from 1, 2, 3, 4, 5, or 6; c is selected from 0, 1, 2, 3, 4, 5, or 6; R 1 , R 2 , R 3 , M, R a , R b , and R c are as defined in any of the preceding paragraphs.

8. The material according to any one of claims 1-7, wherein the polymer comprises a structural unit represented by formula III-a, a structural unit represented by formula III-b, and a structural unit represented by formula III-c, where ** represents the end connected to the substrate surface; R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , M, R a , R b , R c , a, b and c are as defined in paragraph 7.

9. The material according to any one of claims 1 to 8, wherein the amino acid (A) is selected from glycine, alanine, valine, isoleucine, leucine, methionine, phenylalanine, tryptophan, serine, threonine, cysteine, asparagine, glutamine, tyrosine, aspartic acid, glutamic acid, lysine, arginine, histidine or taurine, preferably from glycine, phenylalanine, threonine, serine, histidine or cysteine, most preferably from glycine, threonine, serine or cysteine.

10. The material according to any one of claims 1-9, wherein the polymer comprises a structural unit having a group represented by formula 4-a, a structural unit having a group represented by formula 4-b, and a structural unit having a group represented by formula 4-c, where ** represents the end connected to the substrate surface.

11. The material according to any one of claims 1-10, wherein the polymer comprises a structural unit represented by formula IV-a, a structural unit represented by formula IV-b, and a structural unit represented by formula IV-c, where ** represents the end connected to the substrate surface.

12. The material of claim 11, wherein the polymer comprises a structural unit represented by formula IV-A, a structural unit represented by formula IV-B, and a structural unit represented by formula IV-C, where ** represents the end connected to the substrate surface; the molar ratio z: (x+y) is selected from the range from 20:80 to 90:10, preferably 40:60, 45:55, 50:50, 55:45, 60:40, 65:35 or 70:30, most preferably 70:

30.

13. The material according to any one of paragraphs 1-12, wherein the modifier is a binding agent represented by formula V, , Where: R 11 selected from C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl or C 1-6 aminoalkyl; R 12 selected from C 1-6 hydroxyalkyl, C 1-6 aminoalkyl, C 1-6 carboxyalkyl or C 1-6 mercaptoalkyl, where C 1-6 hydroxyalkyl, C 1-6 aminoalkyl, C 1-6 carboxyalkyl and C 1-6 mercaptoalkyl optionally substituted with one or more groups selected from C 1-6 hydroxyalkyl, C 1-6 aminoalkyl, C 1-6 carboxyalkyl or C 1-6 mercaptoalkyl.

14. Material according to item 13, where R 11 represents C 1-6 alkyl, preferably methyl, ethyl, propyl or butyl, most preferably ethyl, the binding agent is bound to the substrate surface via R 11with the formation of a silane layer, while the surface of the substrate is optionally hydroxylated.

15. Material according to item 13 or 14, where R 12 represents C 1-6 aminoalkyl, wherein C 1-6 aminoalkyl is optionally substituted with one or more groups selected from C 1-6 hydroxyalkyl, C 1-6 aminoalkyl, C 1-6 carboxyalkyl or C 1-6 mercaptoalkyl, preferably methylamino, ethylamino, propylamino or butylamino, most preferably propylamino, the coupling agent is linked to the **-end of the polymer as defined in any one of claims 1 to 12 via an amino group present in R 12 , with the formation of a polymer layer.

16. The material according to any one of paragraphs. 13-15, wherein the binding agent is selected from 3-aminopropyltrimethoxysilane (KH540), 3-aminopropyltriethoxysilane (KH550), 3-(2-aminoethyl)aminopropyltrimethoxysilane (KH792), 3-(2-aminoethyl)aminopropyltriethoxysilane (KH791), 3-(2-aminoethylamino)propyldimethoxymethylsilane (KH602), 3-hydroxypropyltriethoxysilane, 3-hydroxypropyltrimethoxysilane, 3-mercaptopropyltrimethoxysilane, 3-mercaptopropyltriethoxysilane, 4-(trimethoxysilyl)butyric acid, 4-(triethoxysilyl)butyric acid, bis(2-hydroxyethyl)aminopropyltriethoxysilane, bis(2-hydroxyethyl)aminopropyltrimethoxysilane or 3-aminopropyltriisopropoxysilane, preferably 3-aminopropyltrimethoxysilane (KH540) or 3-aminopropyltriethoxysilane (KH550), most preferably 3-aminopropyltriethoxysilane (KH550).

17. A material comprising a substrate and a coating, wherein the coating is obtained by reacting a polymer comprising a structural unit having a group represented by formula 1-d and a structural unit having a group represented by formula 1-e with a binding agent as defined in any one of claims 13-16, and then reacting with an amino acid (A) as defined in claim 9, Where X 3 selected from -O-, -S-, or -N(R d )-; R 13 , R 14 and R 15 are the same or different and each is independently selected from hydrogen, halogen, hydroxyl, mercapto, nitro, carboxyl, amino, cyano, C- 1-6 alkyl or C- 1-6 alkoxy, while C 1-6 alkyl and C 1-6 alkoxy optionally substituted with one or more groups selected from halogen, hydroxyl, mercapto, nitro, carboxyl, amino, cyano, C 1-6 alkyl or C 1-6 alkoxy, alternatively, R 14 and R 15 together with the atom to which they are bonded, they form an oxo group, a thio group, C 3-10 cycloalkyl or 3-10-membered heterocycloalkyl; formula 1-c and R d are as defined in paragraph 1.

18. The material according to claim 17, wherein the polymer comprises a structural unit represented by formula Id and a structural unit represented by formula Ic, where: formula Ic, R 10 , L 1 , X 1 , X 3 , R 13 , R 14 and R 15 are as defined in paragraph 17.

19. Material according to paragraph 17 or 18, where X 3 selected from -O- or -S-, preferably -O-.

20. The material according to any one of paragraphs 17-19, wherein the polymer comprises a structural unit represented by formula IV-c and a structural unit represented by formula IV-d, 21. The material of claim 20, wherein the polymer comprises a structural unit represented by formula IV-C' and a structural unit represented by formula IV-D, wherein the molar ratio m:n is selected from the range from 20:80 to 90:10, preferably 40:60, 45:55, 50:50, 55:45, 60:40, 65:35 or 70:30, most preferably 70:

30.

22. A coating comprising a polymer, wherein the polymer comprises a polymer as defined in any one of claims 1 to 21.

23. The coating according to claim 22, also containing a binding agent represented by formula V, , Where R 11 selected from C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl or C 1-6 aminoalkyl; R 12 selected from C 1-6 hydroxyalkyl, C 1-6 aminoalkyl, C 1-6 carboxyalkyl or C 1-6 mercaptoalkyl, where C 1-6 hydroxyalkyl, C1-6 aminoalkyl, C 1-6 carboxyalkyl and C 1-6 mercaptoalkyl optionally substituted with one or more groups selected from C 1-6 hydroxyalkyl, aminoalkyl, C 1-6 carboxyalkyl or C 1-6 mercaptoalkyl.

24. A method for producing a coating according to claim 22 or 23, comprising: reacting a polymer containing a structural unit having a group represented by formula 1-d and a structural unit having a group represented by formula 1-c with a coupling agent as defined in any one of claims 13-16, and subsequently reacting with an amino acid (A), where amino acid (A) is selected from glycine, alanine, valine, isoleucine, leucine, methionine, phenylalanine, tryptophan, serine, threonine, cysteine, asparagine, glutamine, tyrosine, aspartic acid, glutamic acid, lysine, arginine, histidine or taurine, preferably from glycine, phenylalanine, threonine, serine, histidine or cysteine, most preferably from glycine, threonine, serine or cysteine.

25. A method for producing a coating according to claim 22 or 23, comprising: reacting a polymer containing a structural unit represented by formula IV-d and a structural unit represented by formula IV-c with a coupling agent as defined in claim 14 or 15, and subsequently reacting with an amino acid (A), where: amino acid (A) is selected from glycine, alanine, valine, isoleucine, leucine, methionine, phenylalanine, tryptophan, serine, threonine, cysteine, asparagine, glutamine, tyrosine, aspartic acid, glutamic acid, lysine, arginine, histidine or taurine, preferably from glycine, phenylalanine, threonine, serine, histidine or cysteine, most preferably from glycine, threonine, serine or cysteine.

26. A method for inhibiting platelet aggregation and adhesion caused by contact of blood with the surface of a material, comprising using a material according to any one of claims 1-21.

27. A method for inhibiting platelet aggregation and adhesion caused by contact of blood with the surface of a material, comprising applying a coating according to claim 22 or 23 to the surface of a substrate of the material.

28. A method for inhibiting platelet aggregation and adhesion caused by contact of blood with the surface of a material, comprising applying a coating obtained by the method according to claim 24 or 25 to the surface of the substrate of the material.

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