Polyvinyl pyrrolidone copolymer as well as preparation method and application thereof

Abstract

The invention relates to a polyvinylpyrrolidone copolymer as well as a preparation method and application thereof. The copolymer is composed of a polyvinylpyrrolidone segment, a soft polymer segment and a polymer segment containing double bonds, and the polyvinylpyrrolidone segment has extremely high water absorption capacity and film-forming property and provides hydrophilicity and film-forming property of the copolymer; the soft polymer segment has good flexibility and can regulate and control the mechanical properties such as Tg, elasticity and toughness of the copolymer; and the polymer segment containing double bonds endows the copolymer with further cross-linking and curing capabilities, so that the precipitation of the polymer is avoided. By reasonably regulating and controlling the structures and proportions of the three components, the performance of the copolymer can be effectively adjusted. For example, when a hydrophobic monomer is used in the soft polymer segment, the hydrophilic and hydrophobic capacities of the copolymer can be regulated and controlled, so that the copolymer has the potential of being applied to coating of a single-layer hydrophilic coating. And when the polymer is used as a hydrophilic coating to be coated on the surface of a macromolecular base material catheter, the polymer has excellent hydrophilic performance, good biocompatibility and low cytotoxicity, can be firmly adhered to a base material after the coating is cured, and is wide in application range.

Description

Technical Field

[0001] The invention relates to the technical field of hydrophilic polymer gel, and in particular to a preparation method of a polyvinyl pyrrolidone copolymer and its application in interventional medical devices. Background Art

[0002] Interventional surgery is a new technology in the field of minimally invasive medicine, and has become one of the three major clinical medicines alongside surgery and internal medicine, while imaging equipment and interventional instruments are the mainstays of interventional medicine. However, for interventional medical devices, such as central venous catheters, cardiovascular catheters, angiographic catheters, and urinary catheters, most catheter base materials are hydrophobic materials, which have insufficient lubrication during use, often causing unnecessary pain to patients due to friction with the human body, and plasma proteins and platelets in the blood will adhere to the catheter surface, causing tissue damage and complications.

[0003] The earliest lubricity treatment was often to apply lubricants such as silicone oil and glycerin to the surface of the catheter, but the coating obtained by this treatment method has poor lubricity, is difficult to last and is not conducive to operation. Therefore, many researchers began to develop hydrophilic coatings. Polyvinyl pyrrolidone (PVP) has extremely strong water absorption and biocompatibility. It is the most commonly used hydrophilic polymer and has been widely used in hydrophilic coatings. Leading manufacturers in the field of hydrophilic coatings in the world all use PVP as one of the main polymers of the coating. The common practice of hydrophilic coatings with PVP as the main body is to use hydrophilic polymers such as PVP and supporting polymers containing multiple polymerizable functional groups as the main polymers at the same time, and to form constraints on PVP by cross-linking between supporting polymers during curing to avoid PVP exudation during the use of the coating. However, due to the relatively weak physical effects such as entanglement and intermolecular forces, severe PVP exudation will still occur after a long period of use, producing insoluble particles and reducing substances, causing harm to patients. WO2008 / 104572 discloses a hydrophilic coating that utilizes the hydrogen abstraction ability of Norrish II type photoinitiators such as benzophenone to capture unstable α-H on the PVP skeleton to improve the adhesion between the coating and the substrate and the cross-linking ability between PVP. However, the cross-linking of PVP by benzophenone requires extremely high PVP concentration and long-term exposure to achieve. Therefore, it is difficult to achieve complete non-leakage of PVP by relying solely on benzophenone cross-linked PVP coatings. CN107405430B discloses a hydrophilic coating with a copolymer PVP-PEG having acrylic functional groups as the main body, which effectively reduces the number and size of particles released from the top coating through chemical cross-linking. However, the performance regulation space of PVP-PEG polymers is small, and both components are strongly hydrophilic polymers, which can only be used in double-layer hydrophilic coatings and need to be used with a primer. In addition, the single-end double-bond terminated PEG in the synthetic raw materials of PVP-PEG is expensive, resulting in a high cost of hydrophilic coatings.

[0004] Therefore, there is still a need for a hydrophilic coating in which the polymer used can undergo sufficient chemical cross-linking to avoid the precipitation of PVP. At the same time, the polymer has the universality of being applicable to both double-layer coatings and single-layer coatings. Summary of the invention

[0005] Based on this, the purpose of the present invention includes providing a method for preparing a polyvinyl pyrrolidone copolymer and its application as a hydrophilic coating in interventional medical devices. The polymer has the universality of being applicable to both double-layer coatings and single-layer coatings, and can also exert a hydrophilic lubricating effect on a variety of substrates.

[0006] The above-mentioned object of the present invention can be achieved through the following technical solutions.

[0007] The first aspect of the present invention provides a polyvinyl pyrrolidone hydrophilic copolymer that can be applied to the surfaces of various substrates and can be used as both a single-layer coating and a double-layer coating. The copolymer is composed of N-vinyl pyrrolidone, a soft monomer, an active monomer 1, and an active monomer 2;

[0008] The soft monomer includes an alkyl or alkoxy-containing olefin monomer;

[0009] The active monomers include vinyl monomers containing hydroxyl, amino, carboxyl, acyl halide, active carbonate, aldehyde, isocyanate, and halogen;

[0010] The active groups in the active monomer 1 and the active monomer 2 can undergo coupling reaction.

[0011] The mass ratio of N-vinyl pyrrolidone, soft monomer and active monomer 1 is 100:1~40:1~30;

[0012] The molar ratio of the active groups in the active monomer 2 to the active groups in the active monomer 1 is 30-100%.

[0013] The second aspect of the present invention provides a method for preparing the above-mentioned polyvinyl pyrrolidone copolymer, comprising the following steps: N-vinyl pyrrolidone, a soft monomer, and an active monomer 1 are mixed and reacted to obtain a copolymer, and then an active monomer 2 is added for modification to obtain the polyvinyl pyrrolidone copolymer; the reaction formula is as follows:

[0014] Among them, m : n : l = 100 : (5~25) : (5~20);

[0015] R1, and R3 each independently represent a hydrogen atom or a methyl group;

[0016] X1 and X2 each independently represent an ester bond or a methylene group;

[0017] R2 and R4 each independently represent an alkyl group, substituted alkyl group, aryl group, substituted aryl group, alkoxy group, substituted alkoxy group or a combination of several of these groups in any proportion, having 1 to 20 carbon atoms, wherein the alkyl group is one or a combination of several of a straight-chain alkyl group, a branched-chain alkyl group and a cycloalkyl group in any proportion, the alkoxy group is one or a combination of two of a straight-chain alkoxy group and an epoxy group in any proportion, and the substituted alkyl group, substituted aryl group and substituted alkoxy group are alkyl groups, aryl groups and alkoxy groups substituted with halogen atoms, which may be monosubstituted or polysubstituted, and the substituted halogen atoms may be the same or different;

[0018] Y represents one of a methylene group, an ether bond, a carbonyl group, an ester bond, an amide bond, a carbamate bond or an amino group, and Y can be connected to any position of R4;

[0019] Z represents a double bond or a substituted double bond, and Z can be connected to any position of R5.

[0020] The third aspect of the present invention provides a hydrophilic coating solution, comprising: the polyvinyl pyrrolidone copolymer provided in the first aspect of the present invention, a photoinitiator and a solvent.

[0021] The weight content of the polyvinyl pyrrolidone copolymer is 1wt%~10wt%. Preferably, the weight content of the polyvinyl pyrrolidone copolymer is 3wt%~8wt%;

[0022] The weight content of the photoinitiator is 0.01wt%~3wt%. Preferably, the weight content of the photoinitiator is 0.05wt%~1.5wt%;

[0023] The weight content of the solvent is 89wt%~96.9wt%.

[0024] The polymer of the present invention adopts the method of copolymerizing soft monomers with polyvinyl pyrrolidone to solve the problem of poor flexibility and low elasticity of polyvinyl pyrrolidone after film formation, and helps to improve the mechanical properties of the coating film to prevent it from being damaged during use;

[0025] The polymer of the present invention is copolymerized with active monomer 1 and further modified with active monomer 2, so that the copolymer has double bonds, which can further achieve cross-linking and curing between polymers, help to enhance the overall firmness of the coating, and reduce the precipitation of particles or reducing substances, thereby improving the safety of the device;

[0026] The polymer of the present invention can be synthesized in various ways, either by conventional free radical initiated polymerization or by living polymerization; the copolymer has various structures, which can be random copolymers, block copolymers or alternating copolymers. Different polymerization methods and different copolymer structures can be used to meet different needs. For example, conventional free radical initiated polymerization is used, which has low cost and can also meet most of the requirements for hydrophilic coatings.

[0027] The soft monomer in the polymer of the present invention can be a hydrophilic polyether monomer or a completely hydrophobic hydrocarbon monomer, thereby adjusting the overall hydrophilicity and hydrophobicity of the copolymer and making it have a wider range of applications. If a completely hydrophobic monomer is used for copolymerization, the copolymer can be further applied to the design of a single-layer hydrophilic coating. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 is the polyvinyl pyrrolidone copolymer P(VP-BVE-HEA) in one embodiment of the present invention. 1H NMR spectrum, the horizontal axis is the chemical shift δ (denoted as f1), unit ppm;

[0029] Figure 2 is a polyvinyl pyrrolidone copolymer P(VP-BVE-(HEA-g-IEM)) in one embodiment of the present invention. 1 H NMR spectrum, the horizontal axis is the chemical shift δ (denoted as f1), unit ppm;

[0030] Figure 3 is a GPC spectrum of a polyvinyl pyrrolidone copolymer P(VP-BVE-(HEA-g-IEM)) in one embodiment of the present invention;

[0031] Figure 4 A graph showing the change of the water contact angle of the coating over time after the glass plate is coated with the polyvinyl pyrrolidone copolymer coating solution in one embodiment of the present invention;

[0032] Figure 5 This is a full cycle test spectrum of 25 cycles of the lubricity of the coating after coating the Pebax catheter with the polyvinyl pyrrolidone copolymer coating solution in one embodiment of the present invention. DETAILED DESCRIPTION

[0033] The present invention will be further described in detail below in conjunction with the accompanying drawings, embodiments and examples. It should be understood that these embodiments and examples are only used to illustrate the present invention and are not used to limit the scope of the present invention. The purpose of providing these embodiments and examples is to make the understanding of the disclosure of the present invention more thorough and comprehensive. It should also be understood that the present invention can be implemented in many different forms and is not limited to the embodiments and examples described herein. Those skilled in the art can make various changes or modifications without violating the connotation of the present invention, and the equivalent forms obtained also fall within the protection scope of the present invention. For example, the features described or described as part of an embodiment can be combined in another embodiment in a suitable manner to produce a new embodiment. In addition, in the description below, a large number of specific details are given in order to provide a more comprehensive understanding of the present invention. It should be understood that the present invention can be implemented without one or more of these details.

[0034] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those commonly understood by those skilled in the art of the present invention. The terms used in the specification of the present invention herein are only for the purpose of describing implementation modes and embodiments and are not intended to limit the present invention.

[0035] Example 1

[0036] A polyvinyl pyrrolidone copolymer I, wherein the mass ratio of N-vinyl pyrrolidone, a soft monomer (butyl vinyl ether) and an active monomer 1 (hydroxyethyl acrylate) in the preparation raw materials is 100:10:5; and the active monomer 2 (isocyanatoethyl methacrylate) accounts for 100% of the molar ratio of the active monomer 1 in the copolymer.

[0037] The preparation method is as follows: under a nitrogen environment, 50 g of N-vinyl pyrrolidone, 5 g of butyl vinyl ether, 2.5 g of hydroxyethyl acrylate, 0.2875 g of 2,2'-azobisisobutyronitrile and 575 g of ethanol are added to a flask in sequence, and the mixture is reacted at 80°C for 18 hours. After the reaction is completed, the ethanol is removed by rotary evaporation and dried to obtain copolymer 1 (I). Subsequently, under a nitrogen environment, 50 g of copolymer 1 (I), 3.34 g of isocyanoethyl methacrylate, 14 mg of dibutyltin dilaurate and 270 g of dichloromethane are added to a flask in sequence, and the mixture is reacted at 40°C for 6 hours. After the reaction is completed, the dichloromethane is removed by rotary evaporation, the mixture is washed several times with n-hexane and dried to obtain polyvinyl pyrrolidone copolymer I. The NMR spectra of polyvinyl pyrrolidone copolymer I (1) and polyvinyl pyrrolidone copolymer I are shown as follows: Figure 1 and Figure 2 The GPC spectrum of polyvinyl pyrrolidone copolymer I is as follows: Figure 3 .

[0038] Depend on Figure 1 It can be seen that after the copolymerization of N-vinyl pyrrolidone, butyl vinyl ether and hydroxyethyl acrylate, the double bond peak completely disappeared, indicating the successful preparation of the copolymer. Figure 2 It can be seen that after the reaction of copolymer I (1) and isocyanoethyl methacrylate, the double bond peak of the monomer completely disappeared and a new double bond peak appeared, proving the successful synthesis of copolymer I. Figure 3 This indicates that the molecular weight of copolymer I is Mw ≈ 140,000.

[0039] Example 2

[0040] A polyvinyl pyrrolidone copolymer II, wherein the mass ratio of N-vinyl pyrrolidone, a soft monomer (butyl vinyl ether) and an active monomer 1 (hydroxyethyl acrylate) in the preparation raw materials is 100:5:5; and the active monomer 2 (isocyanatoethyl methacrylate) accounts for 100% of the molar ratio of the active monomer 1 in the copolymer.

[0041] The preparation method is as follows: under a nitrogen environment, 50 g of N-vinyl pyrrolidone, 2.5 g of butyl vinyl ether, 2.5 g of hydroxyethyl acrylate, 0.275 g of 2,2'-azobisisobutyronitrile and 550 g of ethanol are added to a flask in sequence, and the mixture is reacted at 80°C for 18 hours. After the reaction is completed, the ethanol is removed by rotary evaporation and dried to obtain copolymer 1 (II). Subsequently, under a nitrogen environment, 50 g of copolymer 1 (II), 3.34 g of isocyanoethyl methacrylate, 14 mg of dibutyltin dilaurate and 270 g of dichloromethane are added to a flask in sequence, and the mixture is reacted at 40°C for 6 hours. After the reaction is completed, the dichloromethane is removed by rotary evaporation, and the mixture is washed several times with n-hexane and dried to obtain polyvinyl pyrrolidone copolymer II.

[0042] Example 3

[0043] A polyvinyl pyrrolidone copolymer III, wherein the mass ratio of N-vinyl pyrrolidone, soft monomer (butyl vinyl ether) and active monomer 1 (hydroxyethyl acrylate) in the preparation raw materials is 100:15:10; the active monomer 2 (isocyanatoethyl methacrylate) accounts for 100% of the molar ratio of the active monomer 1 in the copolymer.

[0044] The preparation method is as follows: under a nitrogen environment, 50 g of N-vinyl pyrrolidone, 7.5 g of butyl vinyl ether, 5 g of hydroxyethyl acrylate, 0.3125 g of 2,2'-azobisisobutyronitrile and 625 g of ethanol are added to a flask in sequence, and the mixture is reacted at 80°C for 18 hours. After the reaction is completed, the ethanol is removed by rotary evaporation and dried to obtain copolymer 1 (III). Subsequently, under a nitrogen environment, 50 g of copolymer 1 (III), 6.68 g of isocyanoethyl methacrylate, 27 mg of dibutyltin dilaurate and 280 g of dichloromethane are added to a flask in sequence, and the mixture is reacted at 40°C for 6 hours. After the reaction is completed, the dichloromethane is removed by rotary evaporation, and the mixture is washed several times with n-hexane and dried to obtain polyvinyl pyrrolidone copolymer III.

[0045] Example 4

[0046] A polyvinyl pyrrolidone copolymer IV, wherein the mass ratio of N-vinyl pyrrolidone, a soft monomer (butyl vinyl ether) and an active monomer 1 (hydroxyethyl acrylate) in the preparation raw materials is 100:20:20; and the active monomer 2 (isocyanatoethyl methacrylate) accounts for 100% of the molar ratio of the active monomer 1 in the copolymer.

[0047] The preparation method is as follows: under a nitrogen environment, 50 g of N-vinyl pyrrolidone, 10 g of butyl vinyl ether, 10 g of hydroxyethyl acrylate, 0.35 g of 2,2'-azobisisobutyronitrile and 700 g of ethanol are added to a flask in sequence, and the mixture is reacted at 80°C for 18 hours. After the reaction is completed, the ethanol is removed by rotary evaporation and dried to obtain copolymer 1 (IV). Subsequently, under a nitrogen environment, 50 g of copolymer 1 (IV), 13.36 g of isocyanoethyl methacrylate, 54 mg of dibutyltin dilaurate and 320 g of dichloromethane are added to a flask in sequence, and the mixture is reacted at 40°C for 6 hours. After the reaction is completed, the dichloromethane is removed by rotary evaporation, and the mixture is washed several times with n-hexane and dried to obtain a polyvinyl pyrrolidone copolymer IV.

[0048] Example 5

[0049] A polyvinyl pyrrolidone copolymer V, wherein the raw materials for preparation include N-vinyl pyrrolidone, soft The mass ratio of the monomer (butyl vinyl ether) to the active monomer 1 (hydroxyethyl acrylate) is 100:25:10; the active monomer 2 (isocyanatoethyl methacrylate) accounts for 100% of the molar ratio of the active monomer 1 in the copolymer.

[0050] The preparation method is as follows: under a nitrogen environment, 50 g of N-vinyl pyrrolidone, 12.5 g of butyl vinyl ether, 5 g of hydroxyethyl acrylate, 0.3375 g of 2,2'-azobisisobutyronitrile and 675 g of ethanol are added to a flask in sequence, and the mixture is reacted at 80°C for 18 hours. After the reaction is completed, the ethanol is removed by rotary evaporation and dried to obtain copolymer 1 (V). Subsequently, under a nitrogen environment, 50 g of copolymer 1 (V), 6.68 g of isocyanoethyl methacrylate, 27 mg of dibutyltin dilaurate and 280 g of dichloromethane are added to a flask in sequence, and the mixture is reacted at 40°C for 6 hours. After the reaction is completed, the dichloromethane is removed by rotary evaporation, and the mixture is washed several times with n-hexane and dried to obtain polyvinyl pyrrolidone copolymer V.

[0051] Example 6

[0052] A polyvinyl pyrrolidone copolymer VI, wherein the mass ratio of N-vinyl pyrrolidone, soft monomer (butyl vinyl ether) and active monomer 1 (hydroxyethyl acrylate) in the preparation raw materials is 100:40:20; the active monomer 2 (isocyanatoethyl methacrylate) accounts for 100% of the molar ratio of the active monomer 1 in the copolymer.

[0053] The preparation method is as follows: under a nitrogen environment, 50 g of N-vinyl pyrrolidone, 20 g of butyl vinyl ether, 10 g of hydroxyethyl acrylate, 0.4 g of 2,2'-azobisisobutyronitrile and 800 g of ethanol are added to a flask in sequence, and the mixture is reacted at 80°C for 18 hours. After the reaction is completed, the ethanol is removed by rotary evaporation and dried to obtain copolymer 1 (VI). Subsequently, under a nitrogen environment, 50 g of copolymer 1 (VI), 13.36 g of isocyanoethyl methacrylate, 54 mg of dibutyltin dilaurate and 320 g of dichloromethane are added to a flask in sequence, and the mixture is reacted at 40°C for 6 hours. After the reaction is completed, the dichloromethane is removed by rotary evaporation, and the mixture is washed several times with n-hexane and dried to obtain polyvinyl pyrrolidone copolymer VI.

[0054] Example 7

[0055] A polyvinyl pyrrolidone copolymer VII, wherein the mass ratio of N-vinyl pyrrolidone, soft monomer (butyl vinyl ether) and active monomer 1 (hydroxyethyl acrylate) in the preparation raw materials is 100:45:20; the active monomer 2 (isocyanatoethyl methacrylate) accounts for 100% of the molar ratio of the active monomer 1 in the copolymer.

[0056] The preparation method is as follows: under a nitrogen environment, 50 g of N-vinyl pyrrolidone, 22.5 g of butyl vinyl ether, 10 g of hydroxyethyl acrylate, 0.4125 g of 2,2'-azobisisobutyronitrile and 825 g of ethanol are added to a flask in sequence, and the mixture is reacted at 80°C for 18 hours. After the reaction is completed, the ethanol is removed by rotary evaporation and dried to obtain copolymer 1 (VII). Subsequently, under a nitrogen environment, 50 g of copolymer 1 (VII), 13.36 g of isocyanoethyl methacrylate, 54 mg of dibutyltin dilaurate and 320 g of dichloromethane are added to a flask in sequence, and the mixture is reacted at 40°C for 6 hours. After the reaction is completed, the dichloromethane is removed by rotary evaporation, and the mixture is washed several times with n-hexane and dried to obtain polyvinyl pyrrolidone copolymer VII.

[0057] Example 8

[0058] A polyvinyl pyrrolidone copolymer VIII, wherein the mass ratio of N-vinyl pyrrolidone, soft monomer (butyl acrylate) and active monomer 1 (hydroxyethyl acrylate) in the preparation raw materials is 100:15:15; the active monomer 2 (isocyanatoethyl methacrylate) accounts for 100% of the molar ratio of the active monomer 1 in the copolymer.

[0059] The preparation method is as follows: under a nitrogen environment, 50 g of N-vinyl pyrrolidone, 7.5 g of butyl acrylate, 7.5 g of hydroxyethyl acrylate, 0.325 g of 2,2'-azobisisobutyronitrile and 650 g of ethanol are added to a flask in sequence, and the mixture is reacted at 80°C for 18 hours. After the reaction is completed, the ethanol is removed by rotary evaporation and dried to obtain copolymer 1 (VIII). Subsequently, under a nitrogen environment, 50 g of copolymer 1 (VIII), 10.11 g of isocyanoethyl methacrylate, 41 mg of dibutyltin dilaurate and 300 g of dichloromethane are added to a flask in sequence, and the mixture is reacted at 40°C for 6 hours. After the reaction is completed, the dichloromethane is removed by rotary evaporation, and the mixture is washed several times with n-hexane and dried to obtain polyvinyl pyrrolidone copolymer VIII.

[0060] Comparative Example 1

[0061] A polyvinyl pyrrolidone copolymer IX, wherein the mass ratio of N-vinyl pyrrolidone to soft monomer (butyl vinyl ether) in the preparation raw materials is 100:10.

[0062] The preparation method is as follows: under nitrogen environment, 50 g of N-vinyl pyrrolidone, 5 g of butyl vinyl ether, 0.275 g of 2,2'-azobisisobutyronitrile and 550 g of ethanol are added to a flask in sequence, and reacted at 80° C. for 18 hours. After the reaction is completed, ethanol is removed by rotary evaporation and dried to obtain copolymer IX.

[0063] Comparative Example 2

[0064] A polyvinyl pyrrolidone copolymer X, wherein the mass ratio of N-vinyl pyrrolidone to active monomer 1 (hydroxyethyl acrylate) in the preparation raw material is 100:10; the active monomer 2 (isoxylethyl methacrylate) accounts for 100% of the molar ratio of the active monomer 1 in the copolymer.

[0065] The preparation method is as follows: under a nitrogen environment, 50 g of N-vinyl pyrrolidine, 5 g of hydroxyethyl acrylate, 0.275 g of 2,2'-azobisisobutyronitrile and 550 g of ethanol are added to a flask in sequence, and the mixture is reacted at 80°C for 18 hours. After the reaction is completed, the ethanol is removed by rotary evaporation and dried to obtain a copolymer 1 (X). Subsequently, under a nitrogen environment, 50 g of copolymer 1 (X), 6.68 g of isocyanoethyl methacrylate, 28 mg of dibutyltin dilaurate and 280 g of dichloromethane are added to a flask in sequence, and the mixture is reacted at 40°C for 6 hours. After the reaction is completed, the dichloromethane is removed by rotary evaporation, and the mixture is washed several times with n-hexane and dried to obtain a polyvinyl pyrrolidone copolymer X.

[0066] Examples 9-16 and Comparative Examples 3-4 are methods for preparing hydrophilic coating solutions using the polyvinyl pyrrolidone copolymers synthesized in Examples 1-8 and Comparative Examples 1-2. The specific method is as follows:

[0067] 5 parts by mass of polyvinyl pyrrolidone copolymer, 0.08 parts by mass of photoinitiator 2959, 0.16 parts by mass of benzophenone, 1 part by mass of poly(acrylamide-co-acrylic acid) sodium salt (Mw≈100,000) and 93.76 parts by mass of ethanol were mixed uniformly to obtain the hydrophilic coating solution containing the polyvinyl pyrrolidone copolymer.

[0068] Table 1. Composition of different hydrophilic coating solutions

[0069] Comparative Example 5

[0070] A method for preparing a hydrophilic coating of polyvinyl pyrrolidone. The details are as follows:

[0071] 5 parts by mass of polyvinyl pyrrolidone K30, 0.08 parts by mass of photoinitiator 2959, 0.16 parts by mass of benzophenone, 1 part by mass of poly(acrylamide-co-acrylic acid) sodium salt (Mw≈100,000) and 93.76 parts by mass of ethanol were uniformly mixed to obtain the hydrophilic coating solution containing polyvinyl pyrrolidone.

[0072] Test Example 1

[0073] The coating on the glass plate and its adhesion and water contact angle test are as follows:

[0074] The coating solutions of Examples 9 to 16 and Comparative Examples 3 to 5 were coated on a glass plate using a 50 μm wire bar coater, and then 2 Cured under UV light intensity for 300s.

[0075] Test Method

[0076] Adhesion test method: According to GB / T 5210-2006, the adhesion test of the coating is carried out by using the paint and varnish pull-off adhesion test.

[0077] Water contact angle test: The sessile drop method is used to continuously test the water contact angle at a frequency of once per second.

[0078] The coating solutions of Examples 9 to 16 and Comparative Examples 3 to 5 were coated according to the above steps. The results of the layer adhesion test and water contact angle test after coating are shown in Table 2. The coating solution of Example 9 was coated according to the above steps. The coating water contact angle of the coating was continuously monitored as shown in Table 2. Figure 4 .

[0079] Table 2

[0080] The coating adhesion strength test results of Examples 9 to 16 in Table 2 show that the coating after cross-linking and curing of the polyvinyl pyrrolidone copolymer has excellent film-forming ability and high adhesion strength. Figure 4 The change in the water contact angle of the coating of Example 9 shows that the coating has good water absorption capacity. After the soft monomer (butyl vinyl ether), active monomer 1 (hydroxyethyl acrylate) and N-vinyl pyrrolidone are copolymerized, the water absorption capacity of PVP itself is not affected. In addition, the water contact angle value of the coating after water absorption can reach below 20°, which has very good hydrophilicity. Except for Example 15, Examples 10~11 and 16 all have good water absorption capacity and very good hydrophilicity, and as the proportion of soft monomers increases, the water absorption speed slows down and the water contact angle decreases slowly, but they all have good hydrophilicity in the end; and the poor performance of Example 15 is caused by the excessively high proportion of soft monomers (butyl vinyl ether) in the polyvinyl pyrrolidone copolymer.

[0081] Tensile mechanical properties test: The coating solutions of Examples 9 to 16 and Comparative Examples 3 to 5 were injected into a polytetrafluoroethylene plate with a groove of 20 mm × 10 mm × 3 mm. 2 The samples were irradiated with ultraviolet light of 500 s for curing to obtain tensile test specimens. The tensile mechanical properties of the specimens were tested at a tensile rate of 100 mm / min. The results are shown in Table 3.

[0082] Table 3

[0083] Comparative Example 5 in Table 3 is polyvinyl pyrrolidone, which has high tensile strength and elastic modulus, and low elongation at break. Comparative Example 4 is a copolymer modified by polyvinyl pyrrolidone, hydroxyethyl acrylate and isoethyl methacrylate, which can reduce the tensile strength and elastic modulus to a certain extent, and slightly improve the elongation at break. After the introduction of soft monomers, such as Comparative Example 3 and Examples 9 to 16, the tensile strength and elastic modulus dropped significantly, the elongation at break and the yield strain increased significantly, and the amplitude of change increased with the increase in the proportion of soft monomers. For hydrophilic coatings, a tensile strength of more than 5 MPa can meet the coating strength requirements, and a higher yield strain means that the coating has better elasticity, and the coating will not be damaged or peeled off due to bending deformation during the use of instruments such as guidewire catheters.

[0084] Test Example 2

[0085] The coating on the Pebax catheter is tested for lubricity, firmness, insoluble particles and reducing substances. The specific methods are as follows:

[0086] After the catheter is completely immersed in the coating solution of Examples 9 to 16 and Comparative Examples 3 to 5, it is lifted out of the coating solution at a speed of 10 mm / s. After being completely lifted, the catheter sample coated with the coating solution is heated at 30 mW / cm 2 The film was cured by irradiating it with ultraviolet light for 300 seconds.

[0087] Test Method

[0088] Lubricity test: According to the test method for static and dynamic friction coefficients of plastic films and sheets of ASTM D1894, the friction coefficient of the catheter coated with the hydrophilic coating was tested.

[0089] Test temperature: 37℃; Clamping force: 300g; Pulling speed: 10mm / s; The lubricity test is repeated a certain number of times and the friction coefficient for each test cycle is calculated based on the measured friction force.

[0090] Robustness test: If the sample remains lubricated after 25 lubrication test cycles (test described above), the coating is considered stable. If there is a significant change in the measured friction force, the coating is considered unstable. In the lubricity test, as the measured friction value increases, the coating may fall off the sample surface.

[0091] Insoluble particle test: According to the insoluble particle inspection method of "Chinese Pharmacopoeia" 0903, the microscopic counting method is used to detect particles larger than 10μm and 25μm.

[0092] Reducing substance test: According to GB-T 14233.1 Inspection methods for medical infusion, blood transfusion and injection equipment Part 1: Chemical analysis methods, the reducing substances (oxidizable substances) are tested by direct titration method.

[0093] The test results of lubricity, firmness, insoluble particles and reducing substances of the coatings of Examples 9 to 16 and Comparative Examples 3 to 5 after coating according to the above steps are shown in Table 4. The full cycle test results of lubricity of the coatings of Example 9 after coating according to the above steps for 25 cycles are shown in Table 4. Figure 5 .

[0094] Table 4

[0095] The results in Table 4 show that the PVP coating of Comparative Example 5 has very good lubricity, but because the PVPs are not cross-linked, the coating falls off in the second cycle of the lubricity test, and the firmness is very poor. The copolymer modified by N-vinyl pyrrolidone and hydroxyethyl acrylate and isocyanoethyl methacrylate in Comparative Example 4 has a cross-linkable double bond, and the coating formed is a cross-linked coating. The lubricity does not show a significant decrease compared to the PVP coating of Comparative Example 5, but it also falls off in the 18th cycle. This may be due to the poor mechanical properties of the coating, and the coating is damaged during multiple friction tests. The coating of Comparative Example 3 is only a copolymer coating of N-vinyl pyrrolidone and butyl acrylate, and the copolymers are not cross-linked. Therefore, although the hydrophilic lubricity is good, the firmness is very poor, and it falls off in the third cycle. The coatings of Examples 9-16 are all polyvinyl pyrrolidone copolymer coatings of the present invention, which have excellent lubricity and firmness. This is because the soft monomer can adjust the mechanical properties of the coating, making it have very good elasticity and deformation resistance, and the polymerizable double bonds give the copolymer the ability to further crosslink, thereby improving the toughness of the coating and preventing it from falling off. However, when the content of the soft monomer in the copolymer is too high, such as in Example 15, the hydrophilic lubricity will be greatly affected.

[0096] In addition, when the copolymer in the coating is a cross-linkable copolymer, such as Examples 9-16 and Comparative Example 4, the insoluble particles and reducing substances of the coating are greatly reduced, and the coating has very good safety. However, the coating whose copolymer is not cross-linkable, such as Comparative Examples 3 and 5, has very high insoluble particles and reducing substances.

[0097] The above embodiments only express several implementation methods of the present invention, which is convenient for understanding the technical solution of the present invention in detail, but it cannot be understood as limiting the scope of protection of the present invention. It should be pointed out that for ordinary technicians in this field, without departing from the concept of the present invention, several variations and improvements can be made, which all belong to the protection scope of the present invention. In addition, it should be understood that after reading the above teaching content of the present invention, those skilled in the art can make various changes or modifications to the present invention, and the equivalent forms obtained also fall within the protection scope of the present invention. It should also be understood that the technical solutions obtained by those skilled in the art on the basis of the technical solution provided by the present invention through logical analysis, reasoning or limited experiments are all within the protection scope of the claims attached to the present invention. Therefore, the protection scope of the patent of the present invention shall be based on the content of the attached claims, and the description and drawings can be used to explain the content of the claims.

Claims

1. A polyvinyl pyrrolidone copolymer, characterized in that The structural formula of the polyvinyl pyrrolidone copolymer is shown in Formula 1: ； In Formula 1, R1, and R3 each independently represent a hydrogen atom or a methyl group; X1 and X2 each independently represent an ester bond or a methylene group; R2 and R4 each independently represent an alkyl group, a substituted alkyl group, an aryl group, a substituted aryl group, an alkoxy group, a substituted alkoxy group, or a combination of several of these groups in any proportion, having 1 to 20 carbon atoms, wherein the alkyl group is one or a combination of several of a straight-linked alkyl group, a branched alkyl group, and a cycloalkyl group in any proportion; the alkoxy group is one or a combination of two of a straight-linked alkoxy group and an epoxy group in any proportion; the substituted alkyl group, the substituted aryl group, and the substituted alkoxy group are alkyl groups, aryl groups, and alkoxy groups substituted with halogen atoms, which may be monosubstituted or polysubstituted, and the substituted halogen atoms may be the same or different; Y represents one of a methylene group, an ether bond, a carbonyl group, an ester bond, an amide bond, a carbamate bond, or an amino group, and Y may be connected to any position of R4; Z represents a double bond or a substituted double bond, and Z may be connected to any position of R5.

2. The polyvinyl pyrrolidone copolymer according to claim 1, characterized in that The polyvinyl pyrrolidone copolymer is prepared by the following method: N-vinyl pyrrolidone, a soft monomer, and an active monomer 1 are mixed, reacted to obtain a copolymer, and then an active monomer 2 is added for modification to obtain the polyvinyl pyrrolidone copolymer; The soft monomer includes an alkyl or alkoxy-containing olefin monomer; The active monomers include vinyl monomers containing hydroxyl, amino, carboxyl, acyl halide, active carbonate, aldehyde, isocyanate, and halogen; The active groups in the active monomer 1 and the active monomer 2 can undergo coupling reaction; The mass ratio of N-vinyl pyrrolidone, soft monomer and active monomer 1 is 100:1~40:1~30; The molar ratio of the active groups in the active monomer 2 to the active groups in the active monomer 1 is 30-100%.

3. The copolymer according to claim 1, characterized in that The chemical structure of the alkyl or alkoxy-containing olefin monomer is shown in Formula 2: ； In Formula 2, R1 and R2 each independently represent a hydrogen atom or a methyl group; X represents an ester bond or a methylene group; R3 represents an alkyl group, a substituted alkyl group, an aryl group, a substituted aryl group, an alkoxy group, a substituted alkoxy group, or a combination of several of these groups in any proportion, having 1 to 20 carbon atoms, wherein the alkyl group is one or a combination of several of a straight-link alkyl group, a branched alkyl group, and a cycloalkyl group in any proportion; the alkoxy group is one or a combination of two of a straight-link alkoxy group and an epoxy group in any proportion; the substituted alkyl group, the substituted aryl group, and the substituted alkoxy group are alkyl groups, aryl groups, and alkoxy groups substituted with halogen atoms, which may be monosubstituted or polysubstituted, and the substituted halogen atoms may be the same or different; R4 represents a hydrogen atom, a methyl group, or one of X-R3.

4. The copolymer according to claim 1-2, characterized in that The chemical structure of the active monomer is shown in Formula 3: ； In Formula 3, R1 and R2 each independently represent a hydrogen atom or a methyl group; X represents an ester bond or a methylene group or an imino group; R3 represents an alkyl group, a substituted alkyl group, an aryl group, a substituted aryl group, an alkoxy group, a substituted alkoxy group, or a combination of several of these groups in any proportion, wherein the alkyl group is one or more of a straight-chain alkyl group, a branched alkyl group, and a cycloalkyl group in any proportion; the alkoxy group is one or more of a straight-chain alkoxy group and an epoxy group in any proportion; the substituted alkyl group, the substituted aryl group, and the substituted alkoxy group are alkyl groups, aryl groups, and alkoxy groups substituted with halogen atoms, which may be monosubstituted or polysubstituted, and the substituted halogen atoms may be the same or different; Y represents a hydroxyl group, an amino group, a carboxyl group, an acyl halide group, an activated carbonate group, an aldehyde group, an isocyanate group, or a halogen group connected to any position of R3; the number of hydroxyl groups, amino groups, carboxyl groups, acyl halide groups, activated carbonate groups, aldehyde groups, isocyanate groups, and halogen groups may be one or more; R4 represents a hydrogen atom, a methyl group, or One of them.

5. The copolymer according to claim 1-2, characterized in that The raw materials for preparing the polyvinyl pyrrolidone copolymer also include an initiator; The initiators include azo initiators, peroxide initiators and redox initiators.

6. The copolymer according to claim 1-2, characterized in that The raw materials for preparing the polyvinyl pyrrolidone copolymer also include a solvent; The solvent includes one or more combinations of any proportions selected from the group consisting of methanol, ethanol, isopropanol, n-butanol, isobutanol, amyl alcohol, ethylene glycol methyl ether, ethylene glycol butyl ether, propylene glycol butyl ether, diethylene glycol methyl ether, diethylene glycol dimethyl ether, dipropylene glycol methyl ether, N-methylpyrrolidone, N,N-dimethylformamide, N,N-dimethylacetamide, diethyl ether, diisopropyl ether, 1,2-dimethoxyethane, dibutyl ether, tetrahydrofuran, anisole, phenethyl ether, diphenyl ether, chloroform, carbon tetrachloride, dichloromethane, 1,2-dichloroethane, chlorobenzene, ethyl acetate, propyl acetate, butyl acetate, methyl propionate, acetone, methyl ethyl ketone, diethyl ketone, methyl isobutyl ketone, cyclohexanone, acetonitrile, benzonitrile, dimethyl sulfoxide and cyclopentane sulfone.

7. The copolymer according to claim 1-2, characterized in that The preparation method of the polyvinyl pyrrolidone copolymer comprises: dissolving N-vinyl pyrrolidone, a soft monomer, an active monomer 1 and an initiator in a solvent 1 in proportion, and performing a polymerization reaction to obtain a copolymer 1; then dissolving the copolymer 1 and an active monomer 2 in a solvent 2 in proportion, and performing a modification reaction to obtain the polyvinyl pyrrolidone copolymer.

8. The copolymer according to claim 1-2, characterized in that The polyvinyl pyrrolidone copolymer can be applied to a hydrophilic coating.

9. The hydrophilic coating according to claim 19, characterized in that: The hydrophilic coating solution comprises a polyvinyl pyrrolidone copolymer, a photoinitiator and a solvent; The weight content of the polyvinyl pyrrolidone copolymer is 1wt%~10wt%. Preferably, the weight content of the polyvinyl pyrrolidone copolymer is 3wt%~8wt%; The weight content of the photoinitiator is 0.01wt%~3wt%. Preferably, the weight content of the photoinitiator is 0.05wt%~1.5wt%; The weight content of the solvent is 89wt%~96.9wt%.

10. The hydrophilic coating solution according to claim 19-20, characterized in that: The photoinitiator comprises a combination of one or more of a Norrish I type photoinitiator and a Norrish II type photoinitiator in any proportion; The Norrish I type photoinitiator includes benzoin and its derivatives, benzil and its derivatives, acetophenone derivatives, α-hydroxyketone derivatives, α-aminoketone derivatives, acylphosphine derivatives, benzoylformate and oxime ester photoinitiators; The Norrish II type photoinitiator includes benzophenone and its derivatives, thioxanthone and its derivatives, anthraquinone and its derivatives, coumarin and its derivatives, and ferrocene photoinitiators; The mass ratio of the Norrish type I photoinitiator to the Norrish type II photoinitiator is 1:0.5-3. Preferably, the mass ratio of the Norrish type I photoinitiator to the Norrish type II photoinitiator is 1:1-2.

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