CN114699564B - Adhesion-enhanced lubricating coating, application thereof and medical intervention catheter - Google Patents
Adhesion-enhanced lubricating coating, application thereof and medical intervention catheter Download PDFInfo
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- CN114699564B CN114699564B CN202210415649.4A CN202210415649A CN114699564B CN 114699564 B CN114699564 B CN 114699564B CN 202210415649 A CN202210415649 A CN 202210415649A CN 114699564 B CN114699564 B CN 114699564B
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- lubricating
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Abstract
Description
技术领域technical field
本发明涉及生物材料技术领域，尤其是涉及一种粘附力增强的润滑涂层、其应用和一种医用介入类导管。The invention relates to the technical field of biomaterials, in particular to a lubricating coating with enhanced adhesion, its application and a medical intervention catheter.
背景技术Background technique
介入类医用导管多采用高分子材料制成，表面能较低、疏水性强且摩擦系数大，在介入人体过程中容易与粘膜、腔道(尤其是血管)和组织产生较大的摩擦，引起腔道粘膜损伤甚至血管壁破裂。为解决导管使用过程中摩擦力过大的问题，可通过在其表面制备亲水润滑涂层，减小穿插过程的摩擦阻力，减轻对粘膜、血管壁的损伤，缓解病人疼痛感，提高使用安全性。Interventional medical catheters are mostly made of polymer materials, which have low surface energy, strong hydrophobicity, and a large friction coefficient. During the intervention in the human body, they are prone to greater friction with mucous membranes, cavities (especially blood vessels) and tissues, causing Lumen mucosal injury and even vessel wall rupture. In order to solve the problem of excessive friction during the use of the catheter, a hydrophilic lubricating coating can be prepared on the surface to reduce the friction resistance during the insertion process, reduce the damage to the mucous membrane and blood vessel wall, relieve the pain of the patient, and improve the safety of use sex.
在导管基底材料表面涂覆一层高附着力的亲水涂层，是提高介入类导管润滑性、降低摩擦力的有效手段。然而，介入类医用导管高分子基底材料种类丰富，包括但不限于聚氯乙烯(PVC)、聚氨酯(TPU)、聚乙烯(PE)、聚丙烯(PP)、乳胶(Latex)、有机硅橡胶、聚醚嵌段聚酰胺(PEBAX)、聚四氟乙烯(PTFE)、聚全氟乙丙烯(FEP)。不同基底材料表面性质差异大，造成常规涂液很难在不同材料表面形成高粘附力润滑涂层。Coating a layer of high-adhesion hydrophilic coating on the surface of the catheter base material is an effective means to improve the lubricity of interventional catheters and reduce friction. However, there are many types of polymer substrate materials for interventional medical catheters, including but not limited to polyvinyl chloride (PVC), polyurethane (TPU), polyethylene (PE), polypropylene (PP), latex (Latex), silicone rubber, Polyether block polyamide (PEBAX), polytetrafluoroethylene (PTFE), polyperfluoroethylene propylene (FEP). The surface properties of different substrate materials vary greatly, making it difficult for conventional coating solutions to form high-adhesion lubricating coatings on the surfaces of different materials.
目前，在基材表面涂覆增粘底层再引入亲水润滑表层已经成为获得稳定涂层的优选方案。国际医用涂层液巨头帝斯曼公司(DSM)，在利WO 2007065722、WO 2008/104573、CN101970583和CN102947376中公开了具有底层(又称初级涂层)和亲水性表涂制品的制备方法。该底层包括由聚氨酯类低聚物、聚乙烯基吡咯烷酮(PVP)、小分子光引发剂构成的预涂层，可与表涂层形成了稳定、牢固的亲水润滑涂层。尽管专利中聚氨酯类低聚物具有较好的粘附性，并具有不饱和基团可实现光固化形成交联结构，但该体系中底涂与基底材料的作用力主要以物理吸附为主，容易出现涂层牢固性低的问题。另外，该体系采用的引发剂为小分子光引发剂，固化后存在易迁移现象，降低涂层的生物学安全性。At present, coating an adhesion-promoting primer on the substrate surface and then introducing a hydrophilic lubricating surface layer has become the preferred solution to obtain a stable coating. The international medical coating liquid giant DSM (DSM) discloses a method for preparing products with a bottom layer (also known as a primary coating) and a hydrophilic surface coating in WO 2007065722, WO 2008/104573, CN101970583 and CN102947376. The bottom layer includes a precoat layer composed of polyurethane oligomers, polyvinylpyrrolidone (PVP) and small molecular photoinitiators, which can form a stable and firm hydrophilic lubricating coating with the surface layer. Although the polyurethane oligomers in the patent have good adhesion and have unsaturated groups that can realize photocuring to form a crosslinked structure, the interaction between the primer and the base material in this system is mainly based on physical adsorption. It is prone to the problem of low coating firmness. In addition, the initiator used in this system is a small molecule photoinitiator, which is easy to migrate after curing, which reduces the biological safety of the coating.
新加坡杰美特涂层液公司在专利WO 2016200337和CN 107405430中公开了一种用于基底材料上的增粘涂料配方，此底涂层可直接应用在不同衬底上，实现衬底和润滑功能层之间有强大的粘附力。该配方包括聚合物粘合促进剂、第一单体或聚合物交联剂和光引发剂。该聚合物粘合促进剂是嵌段共聚物，包含了疏水/亲水性聚合物嵌段和/或疏水/亲水官能团，在固化后可固化聚合物和粘合促进剂可以物理方式互相结合或以包埋方式形成一个互穿聚合物网络结构。底涂层(增粘涂层)也可以与顶涂层(润滑涂层)形成共价键，以构成起稳定的网络涂层。该体系涂层粘附力得到提升，但是底涂与基底材料的作用力仍是以物理作用为主，且小分子引发剂问题没有得到解决。Singapore Gemite Coating Fluid Co., Ltd. discloses a formula for adhesion-promoting coatings on substrate materials in patents WO 2016200337 and CN 107405430. This primer can be directly applied to different substrates to achieve substrate and lubrication functions There is strong adhesion between the layers. The formulation includes a polymeric adhesion promoter, a first monomeric or polymeric crosslinker and a photoinitiator. The polymeric adhesion promoter is a block copolymer containing hydrophobic/hydrophilic polymer blocks and/or hydrophobic/hydrophilic functional groups, the curable polymer and the adhesion promoter can physically bond to each other after curing Or form an interpenetrating polymer network structure by embedding. The base coat (adhesion-promoting coat) can also form covalent bonds with the top coat (lubricity coat) to form a stable network coat. The coating adhesion of this system has been improved, but the interaction between the primer and the base material is still dominated by physical interaction, and the problem of small molecule initiators has not been resolved.
专利CN 109954169公开了一种包含新型可光固化聚氨酯的底涂涂料组合物，其主链上含有叔胺基团，侧链具有不饱和双键基团和光敏基团单元，该可光固化聚氨酯分子上含有多个交联位点，可以形成牢固的聚合物膜，有效提高亲水润滑涂层在基材，尤其是低表面能基材上的粘附。尽管该专利解决了光引发剂析出的问题，但是具有如此特殊结构聚氨酯的制备，涉及到复杂的有机合成过程，技术路线长、反应条件要求苛刻，造成实际生产时技术难度大、综合成本高。Patent CN 109954169 discloses a primer coating composition comprising a novel photocurable polyurethane, the main chain of which contains tertiary amine groups, and the side chain has unsaturated double bond groups and photosensitive group units. The photocurable polyurethane The molecule contains multiple cross-linking sites, which can form a firm polymer film and effectively improve the adhesion of the hydrophilic lubricating coating to the substrate, especially the substrate with low surface energy. Although this patent solves the problem of photoinitiator precipitation, the preparation of polyurethane with such a special structure involves complex organic synthesis process, long technical route and harsh reaction conditions, resulting in high technical difficulty and high comprehensive cost in actual production.
发明内容Contents of the invention
有鉴于此，本发明要解决的技术问题在于提供一种粘附力增强的润滑涂层，本发明提供的粘附力增强的润滑涂层自带光敏结构单元，构建简单，解决了小分子光引发剂残留和迁移的问题。In view of this, the technical problem to be solved by the present invention is to provide a lubricating coating with enhanced adhesion. The lubricating coating with enhanced adhesion provided by the present invention has its own photosensitive structural unit, which is simple in construction and solves the problem of small molecule light. Issues with initiator carryover and migration.
本发明提供了一种粘附力增强的润滑涂层，包括底层涂层和表涂涂层；The invention provides a lubricating coating with enhanced adhesion, comprising a primer coating and a surface coating;
所述底层涂层的原料包括光引发型阴阳离子复合物和溶剂；所述光引发型阴阳离子复合物包括光引发型阳离子物质和阴离子物质；The raw materials of the bottom coating include photoinitiated anion-cation complexes and solvents; the photoinitiate anion-cation complexes include photoinitiate cationic substances and anionic substances;
所述表涂涂层的原料包括亲水性单体、亲水性聚合物和溶剂。The raw materials of the surface coating layer include hydrophilic monomers, hydrophilic polymers and solvents.
优选的，所述光引发型阳离子物质具有式A结构：Preferably, the photoinitiating cationic substance has a structure of formula A:
R选自
R1和R2独立地选自H或C1～C4烷基；R3选自C8～C12烷基；R 1 and R 2 are independently selected from H or C1～C4 alkyl; R 3 is selected from C8～C12 alkyl;
X-选自Cl-或I-。X- is selected from Cl- or I-.
优选的，底层涂层中：Preferably, in the bottom coat:
所述光引发型阳离子物质选自N-(4-苯甲酰苄基)-N,N-二甲基十二烷基-1-溴化铵、4-(4-(二乙基氨基)苯甲酰基)-N,N-二乙基-N-辛基苯基碘化铵、N,N-二甲基-N-辛基-9-氧-9H-硫杂蒽-3-溴化铵和N-癸基-N,N-二甲基-9,10-双氧-9,10-二氢蒽-2-氯化铵中的一种或多种；The photoinitiating cationic substance is selected from N-(4-benzoylbenzyl)-N,N-dimethyldodecyl-1-ammonium bromide, 4-(4-(diethylamino) Benzoyl)-N,N-diethyl-N-octylphenylammonium iodide, N,N-Dimethyl-N-octyl-9-oxo-9H-thioxanthene-3-bromide One or more of ammonium and N-decyl-N,N-dimethyl-9,10-dioxy-9,10-dihydroanthracene-2-ammonium chloride;
所述阴离子物质为低分子量肝素、磺达肝素、透明质酸、软骨素、硫酸皮肤素、硫酸角质素中的一种或多种；The anionic substance is one or more of low molecular weight heparin, fondaparinux, hyaluronic acid, chondroitin, dermatan sulfate, and keratan sulfate;
所述低分子量肝素包括达肝素、那屈肝素、依诺肝素中的一种或多种，平均分子量3000～5000KD；The low molecular weight heparin includes one or more of dalteparin, nadroparin, and enoxaparin, with an average molecular weight of 3000-5000KD;
所述磺达肝素分子量为1700KD；The fondaparinux molecular weight is 1700KD;
所述的透明质酸分子量为400000～1000000KD；The molecular weight of the hyaluronic acid is 400000～1000000KD;
所述溶剂为甲醇、乙醇、异丙醇、三氯甲烷、丙酮和二甲亚砜中的一种或多种。The solvent is one or more of methanol, ethanol, isopropanol, chloroform, acetone and dimethylsulfoxide.
优选的，所述光引发型阳离子物质和阴离子物质的质量为(20～85)：100；Preferably, the mass of the photoinitiated cationic substance and the anionic substance is (20-85):100;
所述光引发型阴阳离子复合物占底层涂层的质量比为0.02％～25％。The mass ratio of the light-initiated anion-cation complex to the bottom coating is 0.02% to 25%.
所述亲水性单体、亲水性聚合物的质量比为(0.01～15)：(0.01～25)。The mass ratio of the hydrophilic monomer and the hydrophilic polymer is (0.01-15): (0.01-25).
优选的，表涂涂层中：Preferably, in the surface coating:
所述亲水性单体包括聚乙二醇二丙烯酸酯、二甲基丙烯酸二乙二醇酯、三羟甲基丙烷三丙烯酸酯、三羟甲基丙烷三甲基丙烯酸酯和乙氧基化的三羟甲基丙烷三丙烯酸酯中的一种或多种；所述的乙氧基化的三羟甲基丙烷三丙烯酸酯的乙氧基链接数目大于9；The hydrophilic monomers include polyethylene glycol diacrylate, diethylene glycol dimethacrylate, trimethylolpropane triacrylate, trimethylolpropane trimethacrylate, and ethoxylated One or more of the trimethylolpropane triacrylate; the number of ethoxy linkages of the ethoxylated trimethylolpropane triacrylate is greater than 9;
所述的亲水性聚合物选自聚乙烯吡咯烷酮(PVP)、聚乙二醇(PEG)、聚乙烯醇(PVA)、聚丙烯酰胺、聚丙烯酸、聚酰胺、聚醚砜、聚酰亚胺、聚醚酰亚胺和聚酞胺中的一种或多种；Described hydrophilic polymer is selected from polyvinylpyrrolidone (PVP), polyethylene glycol (PEG), polyvinyl alcohol (PVA), polyacrylamide, polyacrylic acid, polyamide, polyethersulfone, polyimide , one or more of polyetherimide and polyamide;
所述溶剂为水、N,N-二甲基甲酰胺、二甲基亚砜、丙酮、乙醇、甲醇和异丙醇中的一种或多种。The solvent is one or more of water, N,N-dimethylformamide, dimethyl sulfoxide, acetone, ethanol, methanol and isopropanol.
本发明提供了上述技术方案任一项所述的粘附力增强的润滑涂层在制备医用介入类导管表面涂层中的应用。The present invention provides the application of the lubricating coating with enhanced adhesion described in any one of the above technical solutions in the preparation of surface coatings for medical intervention catheters.
本发明提供了一种医用介入类导管，涂覆有上述技术方案任一项所述的粘附力增强的润滑涂层。The present invention provides a medical intervention catheter coated with the lubricating coating with enhanced adhesion described in any one of the above technical solutions.
本发明提供了一种涂覆润滑涂层粘附力增强的润滑涂层的医用介入类导管的制备方法，包括：The invention provides a method for preparing a medical intervention catheter coated with a lubricating coating with enhanced adhesion of the lubricating coating, comprising:
A)将光引发型阳离子物质水溶液和阴离子物质水溶液反应，得到阴阳离子复合物；A) reacting photoinitiated cationic substance aqueous solution and anionic substance aqueous solution to obtain anion-cation complex;
B)将阴阳离子复合物溶于溶剂，得到底层涂层溶液；B) dissolving the anion-cation complex in a solvent to obtain a bottom coating solution;
C)将底层涂层溶液负载在医用介入类导管上，进行紫外固化处理，得到具有粘附力增强的底层涂层的医用导管；C) loading the bottom coating solution on the medical interventional catheter, and performing ultraviolet curing treatment to obtain a medical catheter with a bottom coating with enhanced adhesion;
D)将亲水性单体溶液与亲水性聚合物溶液混合，负载到具有粘附力增强的底层涂层的医用导管表面，紫外固化处理，得到涂覆润滑涂层粘附力增强的润滑涂层的医用介入类导管。D) The hydrophilic monomer solution is mixed with the hydrophilic polymer solution, loaded onto the surface of the medical catheter with an enhanced primer coating, and treated with ultraviolet curing to obtain a lubricating lubricant with enhanced adhesion of the coated lubricating coating Coated medical interventional catheters.
优选的，所述步骤A)具体为：光引发型阳离子物质水溶液滴加到阴离子物质水溶液中，沉淀析出，洗涤沉淀，冷冻干燥，得到阴阳离子复合物。Preferably, the step A) specifically includes: adding the aqueous solution of the photoinitiated cationic substance dropwise to the aqueous solution of the anionic substance, precipitation, washing the precipitate, and freeze-drying to obtain an anion-cation complex.
优选的，所述光引发型阳离子物质水溶液中光引发型阳离子物质的浓度为0.1～25g/mL；所述阴离子物质水溶液中阴离子物质的浓度为0.1～50g/mL；所述底层涂层溶液中阴阳离子复合物的浓度为0.02～25g/mL；Preferably, the concentration of photoinitiated cationic substances in the aqueous solution of photoinitiated cationic substances is 0.1-25 g/mL; the concentration of anionic substances in the aqueous solution of anionic substances is 0.1-50 g/mL; The concentration of the anion-cation complex is 0.02-25g/mL;
所述亲水性单体溶液中亲水性单体的质量浓度为0.01％～15％；所述亲水性聚合物溶液中亲水性聚合物的质量浓度为0.01％～25％；The mass concentration of the hydrophilic monomer in the hydrophilic monomer solution is 0.01% to 15%; the mass concentration of the hydrophilic polymer in the hydrophilic polymer solution is 0.01% to 25%;
所述负载的方式选自浸渍、喷雾、旋涂或擦拭。The loading method is selected from dipping, spraying, spin coating or wiping.
优选的，步骤C)所述紫外固化的主透过波长为150～430nm，紫外固化处理的时间为2～15min；Preferably, the main transmission wavelength of the UV curing in step C) is 150-430 nm, and the UV curing treatment time is 2-15 minutes;
所述紫外光的光源为低压汞灯、中压汞灯、高压汞灯和加滤光片中的一种或几种。The light source of the ultraviolet light is one or more of a low-pressure mercury lamp, a medium-pressure mercury lamp, a high-pressure mercury lamp and an optical filter.
与现有技术相比，本发明提供了一种粘附力增强的润滑涂层，包括底层涂层和表涂涂层；所述底层涂层的原料包括光引发型阴阳离子复合物和溶剂；所述光引发型阴阳离子复合物包括光引发型阳离子物质和阴离子物质；所述表涂涂层的原料包括亲水性单体、亲水性聚合物和溶剂。本发明底涂层(增粘涂层)中，在固化后，可固化聚合物和粘合促进剂可以物理方式互相结合或以包埋方式形成一个互穿聚合物网络结构。底涂层(增粘涂层)也可以与顶涂层(润滑涂层)形成共价键，以构成起稳定的网络涂层。本发明所述光引发型阴阳离子复合物型底层在固化时会发生Norrish II反应和重组反应，实现底涂层在基体材料表面的化学键固定以及涂层内部的自身交联，在有效提高低涂层对基底材料粘附性的同时，还增加了提高涂层自身强度，耐磨擦和耐剪切性能提高。Compared with the prior art, the invention provides a lubricating coating with enhanced adhesion, including a primer coating and a surface coating; the raw materials of the primer coating include photoinitiated anion-cation complexes and solvents; The photo-initiated anion-cation complex includes photo-initiated cationic substances and anionic substances; the raw materials of the surface coating layer include hydrophilic monomers, hydrophilic polymers and solvents. In the primer coating (adhesion-promoting coating) of the present invention, after curing, the curable polymer and the adhesion promoter can be physically combined with each other or embedded to form an interpenetrating polymer network structure. The base coat (adhesion-promoting coat) can also form covalent bonds with the top coat (lubricity coat) to form a stable network coat. The light-initiated anion-cation complex type bottom layer of the present invention will undergo Norrish II reaction and recombination reaction when curing, so as to realize the chemical bond fixation of the primer layer on the surface of the base material and the self-crosslinking inside the coating layer, effectively improving the low-coating effect. While the adhesion of the layer to the base material is increased, the strength of the coating itself is improved, and the abrasion resistance and shear resistance are improved.
本发明采用的光引发型阳离子物质自身就含有光敏结构单元，无需再添加小分子光引发剂，且光固化后被交联限制在涂层网络中，从根本上就解决了小分子光引发剂在涂层中的残留、迁移等行业共性问题。同时，由于底层配方的光引发型阳离子物质的存在，本发明可以直接引发润滑表涂中亲水性单体的固化，从而在表涂配方中也可以不添加引发剂，这样就完全解决了光引发剂问题，涂层整体的生物安全性得到保证。与现有的单一润滑功能涂层配方相比，本发明涂层中含有的阳离子物质具有高效抗菌性，同时该阳离子物质处于涂层内层、被外层润滑层包被，可回避裸露型抗菌剂在复杂生理条件下被生物分子钝化失效的问题，因此涂层具有长期抗感染性，减少医用导管相关感染的发生，延长医用导管的服役时间。The photoinitiated cationic substance used in the present invention contains photosensitive structural units itself, no need to add small molecule photoinitiators, and is crosslinked and limited in the coating network after photocuring, which fundamentally solves the problem of small molecule photoinitiators. Common industry problems such as residue and migration in the coating. Simultaneously, due to the existence of the light-initiated cationic substance of the underlying formula, the present invention can directly trigger the curing of the hydrophilic monomer in the lubricating surface coating, so that no initiator can be added in the surface coating formula, thus completely solving the problem of light Initiator issues, the overall biological safety of the coating is guaranteed. Compared with the existing single lubricating function coating formula, the cationic substance contained in the coating of the present invention has high antibacterial properties, and at the same time, the cationic substance is in the inner layer of the coating and is covered by the outer lubricating layer, which can avoid the exposed antibacterial Therefore, the coating has long-term anti-infection properties, reduces the occurrence of medical catheter-related infections, and prolongs the service life of medical catheters.
附图说明Description of drawings
图1为“一种粘附力增强的润滑涂层及其具有润滑抗菌功能的医用介入类导管”涂层构建示意图；Figure 1 is a schematic diagram of the coating construction of "a lubricating coating with enhanced adhesion and a medical interventional catheter with lubricating and antibacterial functions";
图2为“普通涂层”构建示意图；Figure 2 is a schematic diagram of the construction of "ordinary coating";
图3为未处理医用介入管表面的血小板形貌照片；Figure 3 is a photograph of platelet morphology on the surface of an untreated medical interventional tube;
图4为本发明实施例得到的具有粘附力增强的润滑涂层医用介入管表面的血小板形貌照片；Fig. 4 is the platelet topography photo of the surface of the lubricating coating medical intervention tube with enhanced adhesion obtained in the embodiment of the present invention;
图5为未处理医用介入管表面的菌落培养数量照片；Figure 5 is a photo of the number of colony cultures on the surface of an untreated medical interventional tube;
图6为本发明实施例得到的具有粘附力增强的润滑涂层医用介入管表面的菌落培养数量照片；Fig. 6 is a photograph of the number of colonies cultured on the surface of the lubricating coating medical intervention tube with enhanced adhesion obtained in the embodiment of the present invention;
图7为未处理医用介入管表面的细菌粘附和死亡情况照片；Fig. 7 is the photo of bacterial adhesion and death situation on the surface of untreated medical intervention tube;
图8为对照组具有润滑表涂涂层和普通底层涂层医用介入管表面的细菌粘附和死亡情况照片；Fig. 8 is the photo of the bacterial adhesion and death situation on the surface of the control group with lubricating surface coating and common bottom coating medical interventional tube;
图9为本发明实施例得到的具有粘附力增强的润滑涂层医用介入管表面的细菌粘附和死亡情况照片。Fig. 9 is a photograph of bacterial adhesion and death on the surface of a lubricating coating medical interventional tube with enhanced adhesion obtained in an embodiment of the present invention.
具体实施方式Detailed ways
本发明提供了一种粘附力增强的润滑涂层、其应用和一种医用介入类导管，本领域技术人员可以借鉴本文内容，适当改进工艺参数实现。特别需要指出的是，所有类似的替换和改动对本领域技术人员来说是显而易见的，它们都属于本发明保护的范围。本发明的方法及应用已经通过较佳实施例进行了描述，相关人员明显能在不脱离本发明内容、精神和范围内对本文的方法和应用进行改动或适当变更与组合，来实现和应用本发明技术。The invention provides a lubricating coating with enhanced adhesion, its application and a medical interventional catheter. Those skilled in the art can learn from the content of this article and appropriately improve the process parameters to realize it. In particular, it should be pointed out that all similar substitutions and modifications are obvious to those skilled in the art, and they all belong to the protection scope of the present invention. The method and application of the present invention have been described through preferred embodiments, and relevant personnel can obviously make changes or appropriate changes and combinations to the method and application herein without departing from the content, spirit and scope of the present invention to realize and apply the present invention Invent technology.
本发明提供了一种粘附力增强的润滑涂层，包括底层涂层和表涂涂层；The invention provides a lubricating coating with enhanced adhesion, comprising a primer coating and a surface coating;
所述底层涂层的原料包括光引发型阴阳离子复合物和溶剂；所述光引发型阴阳离子复合物包括光引发型阳离子物质和阴离子物质；The raw materials of the bottom coating include photoinitiated anion-cation complexes and solvents; the photoinitiate anion-cation complexes include photoinitiate cationic substances and anionic substances;
所述表涂涂层的原料包括亲水性单体、亲水性聚合物和溶剂。The raw materials of the surface coating layer include hydrophilic monomers, hydrophilic polymers and solvents.
本发明所述表涂涂层有润滑功能，能够抗细菌粘附。The surface coating of the invention has a lubricating function and can resist bacterial adhesion.
本发明提供的一种粘附力增强的润滑涂层，包括底层涂层。The invention provides a lubricating coating with enhanced adhesion, which includes a primer coating.
本发明所述底层涂层的原料包括光引发型阴阳离子复合物和溶剂；所述光引发型阴阳离子复合物包括光引发型阳离子物质和阴离子物质；The raw materials of the primer coating in the present invention include photoinitiated anion-cation complexes and solvents; the photoinitiated anion-cation complexes include photoinitiated cationic substances and anionic substances;
本发明所述底层涂层具有季铵盐结构的阳离子杀菌功能，可与表涂涂层的抗粘附功能进行协同作用，提高抗细菌感染效果。由于阳离子物质处于涂层内层、被外层润滑层包被，可回避裸露型抗菌剂在复杂生理条件下被生物分子钝化失效的问题，因此涂层具有长期抗感染性。The bottom coating of the invention has the cationic bactericidal function of the quaternary ammonium salt structure, and can cooperate with the anti-adhesion function of the surface coating to improve the anti-bacterial infection effect. Since the cationic substance is in the inner layer of the coating and covered by the outer lubricating layer, it can avoid the problem that the exposed antibacterial agent is inactivated by biomolecules under complex physiological conditions, so the coating has long-term anti-infection properties.
本发明光引发型阳离子物质具有杀菌性；光引发型阳离子物质自身含有光敏结构单元；底层涂层通过光固化后以化学键固定在基底材料表面；底层涂层通过光固化方式实现涂层内部交联。本发明整个双层结构涂层具有粘附力增强的效果，具有润滑和抗菌功能。The photoinitiated cationic substance of the present invention has bactericidal properties; the photoinitiated cationic substance itself contains a photosensitive structural unit; the bottom coating is fixed on the surface of the base material by chemical bonds after photocuring; the bottom coating realizes internal crosslinking of the coating by photocuring . The entire double-layer structure coating of the present invention has the effect of enhancing adhesion, and has lubricating and antibacterial functions.
按照本发明，所述光引发型阳离子物质具有式A结构：According to the present invention, the photoinitiating cationic substance has a structure of formula A:
R选自
R1和R2独立地选自H或C1～C4烷基；R3选自C8～C12烷基；R 1 and R 2 are independently selected from H or C1～C4 alkyl; R 3 is selected from C8～C12 alkyl;
X-选自Cl-或I-。X- is selected from Cl- or I-.
本发明所述光引发型阳离子物质优选选自N-(4-苯甲酰苄基)-N,N-二甲基十二烷基-1-溴化铵、4-(4-(二乙基氨基)苯甲酰基)-N,N-二乙基-N-辛基苯基碘化铵、N,N-二甲基-N-辛基-9-氧-9H-硫杂蒽-3-溴化铵和N-癸基-N,N-二甲基-9,10-双氧-9,10-二氢蒽-2-氯化铵中的一种或多种。The photoinitiating cationic substance of the present invention is preferably selected from N-(4-benzoylbenzyl)-N,N-dimethyldodecyl-1-ammonium bromide, 4-(4-(diethyl Amino)benzoyl)-N,N-diethyl-N-octylphenylammonium iodide, N,N-dimethyl-N-octyl-9-oxo-9H-thioxanthene-3 - one or more of ammonium bromide and N-decyl-N,N-dimethyl-9,10-dioxy-9,10-dihydroanthracene-2-ammonium chloride.
本发明所述阴离子物质为低分子量肝素、磺达肝素、透明质酸、软骨素、硫酸皮肤素、硫酸角质素中的一种或多种；The anionic substance of the present invention is one or more of low molecular weight heparin, fondaparinux, hyaluronic acid, chondroitin, dermatan sulfate, and keratan sulfate;
具体的，所述低分子量肝素包括达肝素、那屈肝素、依诺肝素中的一种或多种，平均分子量3000～5000KD；所述磺达肝素分子量为1700KD；所述的透明质酸分子量为400000～1000000KD；Specifically, the low molecular weight heparin includes one or more of dalteparin, nadroparin, and enoxaparin, with an average molecular weight of 3000-5000KD; the molecular weight of fondaparinux is 1700KD; the molecular weight of hyaluronic acid is 400000～1000000KD;
本发明底层涂层中，所述溶剂优选为甲醇、乙醇、异丙醇、三氯甲烷、丙酮和二甲亚砜中的一种或多种。In the primer coating of the present invention, the solvent is preferably one or more of methanol, ethanol, isopropanol, chloroform, acetone and dimethyl sulfoxide.
本发明所述光引发型阳离子物质具有杀菌性；其自身含有光敏结构单元；所述底层涂层通过光固化后以化学键固定在基底材料表面；所述底层涂层通过光固化方式实现涂层内部交联。The photoinitiated cationic substance of the present invention has bactericidal properties; it itself contains photosensitive structural units; the bottom coating is fixed on the surface of the base material with chemical bonds after photocuring; crosslinking.
本发明所述光引发型阳离子物质和阴离子物质的质量优选为(20～85)：100。The mass of the photoinitiated cationic substance and the anionic substance in the present invention is preferably (20-85):100.
本发明所述光引发型阴阳离子复合物占底层涂层的质量比为0.02％～25％。The mass ratio of the light-initiated anion-cation complex in the invention to the bottom coating is 0.02% to 25%.
本发明提供的一种粘附力增强的润滑涂层，包括表涂涂层。所述表涂涂层的原料包括亲水性单体、亲水性聚合物和溶剂。The invention provides a lubricating coating with enhanced adhesion, which includes a surface coating. The raw materials of the surface coating layer include hydrophilic monomers, hydrophilic polymers and solvents.
本发明所述表涂涂层具体良好的润滑性能。The surface coating of the present invention has particularly good lubricating properties.
按照本发明，所述亲水性单体、亲水性聚合物的质量比优选为(0.01～15)：(0.01～25)。According to the present invention, the mass ratio of the hydrophilic monomer and the hydrophilic polymer is preferably (0.01-15): (0.01-25).
具体的，所述亲水性单体包括聚乙二醇二丙烯酸酯、二甲基丙烯酸二乙二醇酯、三羟甲基丙烷三丙烯酸酯、三羟甲基丙烷三甲基丙烯酸酯和乙氧基化的三羟甲基丙烷三丙烯酸酯中的一种或多种；所述的乙氧基化的三羟甲基丙烷三丙烯酸酯的乙氧基链接数目大于9。Specifically, the hydrophilic monomers include polyethylene glycol diacrylate, diethylene glycol dimethacrylate, trimethylolpropane triacrylate, trimethylolpropane trimethacrylate and ethylene glycol diacrylate. One or more of oxylated trimethylolpropane triacrylates; the number of ethoxyl linkages of the ethoxylated trimethylolpropane triacrylates is greater than 9.
所述的亲水性聚合物选自聚乙烯吡咯烷酮(PVP)、聚乙二醇(PEG)、聚乙烯醇(PVA)、聚丙烯酰胺、聚丙烯酸、聚酰胺、聚醚砜、聚酰亚胺、聚醚酰亚胺和聚酞胺中的一种或多种；Described hydrophilic polymer is selected from polyvinylpyrrolidone (PVP), polyethylene glycol (PEG), polyvinyl alcohol (PVA), polyacrylamide, polyacrylic acid, polyamide, polyethersulfone, polyimide , one or more of polyetherimide and polyamide;
所述溶剂为水、N,N-二甲基甲酰胺、二甲基亚砜、丙酮、乙醇、甲醇和异丙醇中的一种或多种。The solvent is one or more of water, N,N-dimethylformamide, dimethyl sulfoxide, acetone, ethanol, methanol and isopropanol.
本发明所述亲水性单体通过光引发型阳离子物质提供的光敏结构单元实现交联固定。The hydrophilic monomer of the present invention realizes cross-linking and fixing through the photosensitive structural unit provided by the photoinitiating cationic substance.
本发明提供了上述技术方案任一项所述的粘附力增强的润滑涂层在制备医用介入类导管表面涂层中的应用。The present invention provides the application of the lubricating coating with enhanced adhesion described in any one of the above technical solutions in the preparation of surface coatings for medical intervention catheters.
本发明对于所述医用介入类导管不进行限定，本领域技术人员熟知的即可，包括但不限于球囊导管、造影导管、微导管、中心静脉导管和留置针套管等。The present invention does not limit the medical intervention catheters, which are well known to those skilled in the art, including but not limited to balloon catheters, contrast catheters, microcatheters, central venous catheters, and indwelling needle sleeves.
本发明所述粘附力增强的润滑涂层可以涂覆于医用介入类导管表面，可以解决导管使用过程中摩擦力过大的问题。The lubricating coating with enhanced adhesion of the present invention can be coated on the surface of medical intervention catheters, which can solve the problem of excessive friction during the use of catheters.
本发明的润滑涂料可包括一个底涂层(增粘涂层)和一个顶涂层(润滑涂层)。所述底涂层由固化一个增粘涂料配方所形成，所述增粘涂料配方包括--。在所述底涂层(增粘涂层)中，在固化后，可固化聚合物和粘合促进剂可以物理方式互相结合或以包埋方式形成一个互穿聚合物网络结构。底涂层(增粘涂层)也可以与顶涂层(润滑涂层)形成共价键，以构成起稳定的网络涂层。The lubricious coating of the present invention may comprise a base coat (adhesion-promoting coat) and a top coat (lubricant coat). The base coat is formed by curing an adhesion-promoting coating formulation comprising -. In the base coat (adhesion-promoting coat), after curing, the curable polymer and the adhesion promoter can be physically bonded to each other or entrapped to form an interpenetrating polymer network structure. The base coat (adhesion-promoting coat) can also form covalent bonds with the top coat (lubricity coat) to form a stable network coat.
所述功能或润滑涂层为复合涂层提供润滑性，所述增粘涂层为复合涂层提供稳定性。通过调整亲水性聚合物在增粘涂层中的疏水取代程度，能保证增粘涂层的表面良好地连接到广泛使用的医疗器械材基，例如金属，聚氨酯(PU)、聚氯乙烯(PVC)、橡胶、尼龙、聚丙烯、聚乙烯热塑性材质，聚乙烯(高密度聚乙烯和低密度聚乙烯)，聚全氟乙丙烯(FEP)、聚(乙烯-四氟乙烯)(ETFE)，聚(对苯二甲酸乙二醇酯)(PET)和有机硅弹性体等，其中一些材料疏水性强(表面能低)，例如PP，HDPE，FEP和ETFE，所以要使亲水涂层溶液自发地扩散在这些材料表面上是困难的。不希望被理论所限制，应理解为这个问题的产生是因为这些疏水基底表面能相对所述溶剂(用作所述衬底的表面涂层的一部份的溶剂)的表面能低。这使得很难有效地浸润基底表面。例如，亲水涂层溶液的表面能比所述衬底的表面能高，所以需要以某种方式修改基底表面的表面能。在这种情况下，要实现良好的粘附力的最常用的方法是预处理，如在基底表面进行表面氧化或产生极性基团的等离子体处理。然而，这种预处理润滑涂层可由固化一个可固化亲水聚合物，一个引发剂，和一个溶剂所形成。将可固化亲水聚合物与交联剂或可固化聚合物一同使用的优点：所述可固化亲水聚合物可与交联剂或可固化聚合物自身交联，使整个聚合物网络结构稳定(由于聚合物组分之间的交联)，且所述医疗器械在人体的身体管腔内移动和放置时，微粒的体积可最小化，脱落和迁移作用也较小。The functional or lubricity coating provides lubricity to the composite coating and the adhesion promoting coating provides stability to the composite coating. By adjusting the degree of hydrophobic substitution of hydrophilic polymers in the adhesion-promoting coating, it can ensure that the surface of the adhesion-promoting coating is well connected to widely used medical device substrates, such as metal, polyurethane (PU), polyvinyl chloride ( PVC), rubber, nylon, polypropylene, polyethylene thermoplastics, polyethylene (high-density polyethylene and low-density polyethylene), perfluoroethylene propylene (FEP), poly(ethylene-tetrafluoroethylene) (ETFE), Poly(ethylene terephthalate) (PET) and silicone elastomers, etc. Some of these materials are highly hydrophobic (low surface energy), such as PP, HDPE, FEP and ETFE, so it is necessary to make the hydrophilic coating solution Spontaneous diffusion is difficult on the surface of these materials. Without wishing to be bound by theory, it is understood that this problem arises because the surface energy of these hydrophobic substrates is low relative to the surface energy of the solvent used as part of the surface coating of the substrate. This makes it difficult to effectively wet the substrate surface. For example, the surface energy of the hydrophilic coating solution is higher than that of the substrate, so the surface energy of the substrate surface needs to be modified in some way. In this case, the most common way to achieve good adhesion is pretreatment, such as surface oxidation on the substrate surface or plasma treatment to generate polar groups. However, the pretreatment lubricious coating can be formed by curing a curable hydrophilic polymer, an initiator, and a solvent. Advantages of using curable hydrophilic polymers with crosslinkers or curable polymers: The curable hydrophilic polymers can be crosslinked with crosslinkers or the curable polymer itself, stabilizing the overall polymer network structure (due to the cross-linking between polymer components), and when the medical device is moved and placed in the body lumen of the human body, the volume of the particles can be minimized, and the shedding and migration effects are also small.
本发明提供了一种医用介入类导管，涂覆有上述技术方案任一项所述的粘附力增强的润滑涂层。The present invention provides a medical intervention catheter coated with the lubricating coating with enhanced adhesion described in any one of the above technical solutions.
上述为具有润滑抗菌功能的医用介入类导管。The above is a medical intervention catheter with lubricating and antibacterial functions.
本发明所述上述技术方案任一项所述的粘附力增强的润滑涂层上述已经有了清楚的描述，在此不再赘述。The lubricating coating with enhanced adhesion according to any one of the above-mentioned technical solutions of the present invention has been clearly described above, and will not be repeated here.
本发明提供了一种涂覆润滑涂层粘附力增强的润滑涂层的医用介入类导管的制备方法，包括：The invention provides a method for preparing a medical intervention catheter coated with a lubricating coating with enhanced adhesion of the lubricating coating, comprising:
A)将光引发型阳离子物质水溶液和阴离子物质水溶液反应，得到阴阳离子复合物；A) reacting photoinitiated cationic substance aqueous solution and anionic substance aqueous solution to obtain anion-cation complex;
B)将阴阳离子复合物溶于溶剂，得到底层涂层溶液；B) dissolving the anion-cation complex in a solvent to obtain a bottom coating solution;
C)将底层涂层溶液负载在医用介入类导管上，进行紫外固化处理，得到具有粘附力增强的底层涂层的医用导管；C) loading the bottom coating solution on the medical interventional catheter, and performing ultraviolet curing treatment to obtain a medical catheter with a bottom coating with enhanced adhesion;
D)将亲水性单体溶液与亲水性聚合物溶液混合，负载到具有粘附力增强的底层涂层的医用导管表面，紫外固化处理，得到涂覆润滑涂层粘附力增强的润滑涂层的医用介入类导管。D) The hydrophilic monomer solution is mixed with the hydrophilic polymer solution, loaded onto the surface of the medical catheter with an enhanced primer coating, and treated with ultraviolet curing to obtain a lubricating lubricant with enhanced adhesion of the coated lubricating coating Coated medical interventional catheters.
本发明提供了一种涂覆润滑涂层粘附力增强的润滑涂层的医用介入类导管的制备方法，包括：将光引发型阳离子物质水溶液和阴离子物质水溶液反应，得到阴阳离子复合物。The invention provides a preparation method of a lubricating coating coated with a lubricating coating with enhanced adhesive force for medical intervention catheters, comprising: reacting an aqueous solution of a photoinitiated cationic substance and an aqueous solution of anionic substances to obtain an anion-cation compound.
本发明所述步骤A)具体为：光引发型阳离子物质水溶液滴加到阴离子物质水溶液中，沉淀析出，洗涤沉淀，冷冻干燥，得到阴阳离子复合物。The step A) of the present invention is specifically: adding the aqueous solution of the photoinitiated cationic substance dropwise into the aqueous solution of the anionic substance to precipitate, wash the precipitate, and freeze-dry to obtain the anion-cation complex.
滴加后有大量白色或淡黄色沉淀从溶液中析出，用蒸馏水或超纯水洗涤沉淀物，冷冻干燥后得到阴阳离子复合物。After the dropwise addition, a large amount of white or light yellow precipitates precipitated from the solution, and the precipitates were washed with distilled water or ultrapure water, and freeze-dried to obtain anion-cation complexes.
本发明对于光引发型阳离子物质和阴离子物质上述已经有了清楚的描述，在此不再赘述。The present invention has clearly described the photo-initiated cationic substance and anionic substance above, and will not repeat them here.
按照本发明，所述光引发型阳离子物质水溶液中光引发型阳离子物质的浓度优选为0.1～25g/mL；更优选为1～23g/mL；According to the present invention, the concentration of the photoinitiated cationic substance in the aqueous solution of the photoinitiated cationic substance is preferably 0.1-25 g/mL; more preferably 1-23 g/mL;
所述阴离子物质水溶液中阴离子物质的浓度优选为0.1～50g/mL；更优选为1～48g/mL。The concentration of the anionic substance in the aqueous solution of the anionic substance is preferably 0.1-50 g/mL; more preferably 1-48 g/mL.
将阴阳离子复合物溶于溶剂，得到底层涂层溶液；本发明所述底层涂层溶液中阴阳离子复合物的浓度优选为0.02～25g/mL；更优选为0.1～12g/mL。The anion-cation complex is dissolved in a solvent to obtain a bottom coating solution; the concentration of the anion-cation complex in the bottom coating solution of the present invention is preferably 0.02-25 g/mL; more preferably 0.1-12 g/mL.
将底层涂层溶液负载在医用介入类导管上。本发明所述负载的方式选自浸渍、喷雾、旋涂或擦拭。The primer coating solution is loaded on medical interventional catheters. The loading method of the present invention is selected from dipping, spraying, spin coating or wiping.
本发明对于所述医用介入类导管不进行限定，本领域技术人员熟知的即可；可以理解为一些材质不同的医用导管，比如：留置针套管，导尿管之类，材质可能是硅胶、乳胶。The present invention does not limit the medical intervention catheters, which are well-known to those skilled in the art; it can be understood as some medical catheters with different materials, such as: indwelling needle sleeves, urinary catheters, etc., the materials may be silica gel, emulsion.
本发明涂层就是涂在上述管上，整根涂也可以，或者涂一半也可以，或者可以选的，涂层质量可以占导管质量的0.2％～25％。The coating of the present invention is just to be coated on above-mentioned pipe, also can be coated on whole, or half also can be coated, or can be chosen, coating quality can account for 0.2%～25% of conduit quality.
而后进行紫外固化处理，得到具有粘附力增强的底层涂层的医用导管。This is followed by UV curing to obtain a medical catheter with an adhesion-enhancing primer coating.
得到的附着有阴阳离子复合物涂层的导管后，本发明将所述附着有复合物的导管进行紫外固化处理，得到粘附力增强的具有交联结构的底层涂层的导管。After obtaining the catheter attached with the anion-cation composite coating, in the present invention, the catheter attached with the composite is subjected to ultraviolet curing treatment, so as to obtain a catheter with a cross-linked bottom layer coating with enhanced adhesion.
在本发明中，所述紫外光的光源优选为低压汞灯、中压汞灯、高压汞灯和加滤光片中的一种或几种。所述紫外固化处理采用的紫外光的主透过波长优选为150～430nm，更优选为200～380nm；所述紫外固化处理的时间优选为2～15min，更优选为3～8min。In the present invention, the ultraviolet light source is preferably one or more of low-pressure mercury lamps, medium-pressure mercury lamps, high-pressure mercury lamps and filters. The main transmission wavelength of the ultraviolet light used in the ultraviolet curing treatment is preferably 150-430 nm, more preferably 200-380 nm; the time of the ultraviolet curing treatment is preferably 2-15 minutes, more preferably 3-8 minutes.
紫外固化处理后，本发明优选将紫外固化处理产物依次进行清洗和干燥。所述清洗条件包括水浴、水浴震荡和超声清洗，本发明优选在水浴振荡的条件下，依次采用乙醇和去离子水进行清洗，得到清洗后的涂层。在本发明中，所述水浴振荡的频率优选为100～200Hz，更优选为120～150Hz；所述乙醇清洗的时间优选为15～60min，更优选为30～40min；所述去离子水清洗的时间优选为10～50min，更优选为25～30min。本发明对所述清洗用的乙醇和去离子水的用量没有特殊的限制。在本发明中，所述干燥优选为真空干燥，所述干燥的时间优选为12～30小时，更优选为24～28小时；所述干燥的温度优选为45～80℃，更优选为60～70℃。After the ultraviolet curing treatment, the present invention preferably washes and dries the ultraviolet curing treatment product in sequence. The cleaning conditions include water bath, water bath vibration and ultrasonic cleaning. In the present invention, under the condition of water bath vibration, ethanol and deionized water are used for cleaning in sequence to obtain the cleaned coating. In the present invention, the frequency of the water bath oscillation is preferably 100-200 Hz, more preferably 120-150 Hz; the ethanol cleaning time is preferably 15-60 min, more preferably 30-40 min; the deionized water cleaning The time is preferably 10 to 50 minutes, more preferably 25 to 30 minutes. In the present invention, there is no special limitation on the amount of ethanol and deionized water used for cleaning. In the present invention, the drying is preferably vacuum drying, and the drying time is preferably 12 to 30 hours, more preferably 24 to 28 hours; the drying temperature is preferably 45 to 80°C, more preferably 60 to 28 hours. 70°C.
将亲水性单体溶液与亲水性聚合物溶液混合，负载到具有粘附力增强的底层涂层的医用导管表面。A solution of a hydrophilic monomer is mixed with a solution of a hydrophilic polymer and loaded onto the surface of a medical catheter with an adhesion-enhancing primer coating.
本发明所述亲水性单体溶液中的溶剂优选为水、N,N-二甲基甲酰胺、二甲基亚砜、丙酮、乙醇、甲醇和异丙醇中的一种或多种。The solvent in the hydrophilic monomer solution of the present invention is preferably one or more of water, N,N-dimethylformamide, dimethyl sulfoxide, acetone, ethanol, methanol and isopropanol.
本发明所述亲水性单体溶液中亲水性单体的质量浓度为0.01％～15％；更优选为0.1～10g/mL。所述亲水性聚合物溶液中亲水性聚合物的质量浓度为0.01％～25％；更优选为1～15g/mL。The mass concentration of the hydrophilic monomer in the hydrophilic monomer solution of the present invention is 0.01%-15%; more preferably 0.1-10 g/mL. The mass concentration of the hydrophilic polymer in the hydrophilic polymer solution is 0.01%-25%; more preferably 1-15g/mL.
而后进行紫外固化处理，得到涂覆润滑涂层粘附力增强的润滑涂层的医用介入类导管。Then perform ultraviolet curing treatment to obtain a medical interventional catheter coated with a lubricating coating with enhanced adhesive force.
所述紫外固化处理采用的紫外光的主透过波长优选为150～430nm，更优选为200～380nm；所述紫外固化处理的时间优选为2～15min，更优选为3～8min。The main transmission wavelength of the ultraviolet light used in the ultraviolet curing treatment is preferably 150-430 nm, more preferably 200-380 nm; the time of the ultraviolet curing treatment is preferably 2-15 minutes, more preferably 3-8 minutes.
紫外固化处理后，本发明优选将紫外固化处理产物依次进行清洗和干燥。所述清洗条件包括水浴、水浴震荡和超声清洗，本发明优选在水浴振荡的条件下，依次采用乙醇和去离子水进行清洗，得到清洗后的涂层。在本发明中，所述水浴振荡的频率优选为100～200Hz，更优选为120～150Hz；所述乙醇清洗的时间优选为15～60min，更优选为30～40min；所述去离子水清洗的时间优选为10～50min，更优选为25～30min。本发明对所述清洗用的乙醇和去离子水的用量没有特殊的限制。在本发明中，所述干燥优选为真空干燥，所述干燥的时间优选为12～30小时，更优选为24～28小时；所述干燥的温度优选为45～80℃，更优选为60～70℃。After the ultraviolet curing treatment, the present invention preferably washes and dries the ultraviolet curing treatment product in sequence. The cleaning conditions include water bath, water bath vibration and ultrasonic cleaning. In the present invention, under the condition of water bath vibration, ethanol and deionized water are used for cleaning in sequence to obtain the cleaned coating. In the present invention, the frequency of the water bath oscillation is preferably 100-200 Hz, more preferably 120-150 Hz; the ethanol cleaning time is preferably 15-60 min, more preferably 30-40 min; the deionized water cleaning The time is preferably 10 to 50 minutes, more preferably 25 to 30 minutes. In the present invention, there is no special limitation on the amount of ethanol and deionized water used for cleaning. In the present invention, the drying is preferably vacuum drying, and the drying time is preferably 12 to 30 hours, more preferably 24 to 28 hours; the drying temperature is preferably 45 to 80°C, more preferably 60 to 28 hours. 70°C.
本发明提供了一种粘附力增强的润滑涂层，包括底层涂层和表涂涂层；所述底层涂层的原料包括光引发型阴阳离子复合物和溶剂；所述光引发型阴阳离子复合物包括光引发型阳离子物质和阴离子物质；所述表涂涂层的原料包括亲水性单体、亲水性聚合物和溶剂。本发明底涂层(增粘涂层)中，在固化后，可固化聚合物和粘合促进剂可以物理方式互相结合或以包埋方式形成一个互穿聚合物网络结构。底涂层(增粘涂层)也可以与顶涂层(润滑涂层)形成共价键，以构成起稳定的网络涂层。本发明所述光引发型阴阳离子复合物型底层在固化时会发生Norrish II反应和重组反应，实现底涂层在基体材料表面的化学键固定以及涂层内部的自身交联，在有效提高低涂层对基底材料粘附性的同时，还增加了提高涂层自身强度，耐磨擦和耐剪切性能提高。The invention provides a lubricating coating with enhanced adhesion, comprising a primer coating and a surface coating; the raw material of the primer coating includes a photoinitiative anion-cation complex and a solvent; the photoinitiation anion-cation The complex includes photoinitiated cationic substances and anionic substances; the raw materials of the surface coating layer include hydrophilic monomers, hydrophilic polymers and solvents. In the primer coating (adhesion-promoting coating) of the present invention, after curing, the curable polymer and the adhesion promoter can be physically combined with each other or embedded to form an interpenetrating polymer network structure. The base coat (adhesion-promoting coat) can also form covalent bonds with the top coat (lubricity coat) to form a stable network coat. The light-initiated anion-cation complex type bottom layer of the present invention will undergo Norrish II reaction and recombination reaction when curing, so as to realize the chemical bond fixation of the primer layer on the surface of the base material and the self-crosslinking inside the coating layer, effectively improving the low-coating effect. While the adhesion of the layer to the base material is increased, the strength of the coating itself is improved, and the abrasion resistance and shear resistance are improved.
本发明采用的光引发型阳离子物质自身就含有光敏结构单元，无需再添加小分子光引发剂，且光固化后被交联限制在涂层网络中，从根本上就解决了小分子光引发剂在涂层中的残留、迁移等行业共性问题。同时，由于底层配方的光引发型阳离子物质的存在，本发明可以直接引发润滑表涂中亲水性单体的固化，从而在表涂配方中也可以不添加引发剂，这样就完全解决了光引发剂问题，涂层整体的生物安全性得到保证。与现有的单一润滑功能涂层配方相比，本发明涂层中含有的阳离子物质具有高效抗菌性，同时该阳离子物质处于涂层内层、被外层润滑层包被，可回避裸露型抗菌剂在复杂生理条件下被生物分子钝化失效的问题，因此涂层具有长期抗感染性，减少医用导管相关感染的发生，延长医用导管的服役时间。The photoinitiated cationic substance used in the present invention contains photosensitive structural units itself, no need to add small molecule photoinitiators, and is crosslinked and limited in the coating network after photocuring, which fundamentally solves the problem of small molecule photoinitiators. Common industry problems such as residue and migration in the coating. Simultaneously, due to the existence of the light-initiated cationic substance of the underlying formula, the present invention can directly trigger the curing of the hydrophilic monomer in the lubricating surface coating, so that no initiator can be added in the surface coating formula, thus completely solving the problem of light Initiator issues, the overall biological safety of the coating is guaranteed. Compared with the existing single lubricating function coating formula, the cationic substance contained in the coating of the present invention has high antibacterial properties, and at the same time, the cationic substance is in the inner layer of the coating and is covered by the outer lubricating layer, which can avoid the exposed antibacterial Therefore, the coating has long-term anti-infection properties, reduces the occurrence of medical catheter-related infections, and prolongs the service life of medical catheters.
为了进一步说明本发明，以下结合实施例对本发明提供的一种粘附力增强的润滑涂层、其应用和一种医用介入类导管进行详细描述。In order to further illustrate the present invention, a lubricating coating with enhanced adhesion provided by the present invention, its application and a medical interventional catheter are described in detail below in conjunction with examples.
实施例1Example 1
A)配制浓度为0.8g/mL的N-(4-苯甲酰苄基)-N的水溶液，配制浓度为1.5g/mL的肝素钠溶液；将上述N-(4-苯甲酰苄基)-N的水溶液逐滴滴加到10ml的肝素钠溶液中，直至溶液中析出大量白色沉淀，静置2h后，过滤得到白色沉淀物。用超纯水洗涤沉淀物3次，冷冻干燥后得到阴阳离子复合物。A) preparation concentration is the aqueous solution of N-(4-benzoylbenzyl)-N of 0.8g/mL, preparation concentration is the heparin sodium solution of 1.5g/mL; )-N aqueous solution was added dropwise to 10ml of heparin sodium solution until a large amount of white precipitate was deposited in the solution, and after standing for 2 hours, the white precipitate was obtained by filtration. The precipitate was washed three times with ultrapure water, and the anion-cation complex was obtained after freeze-drying.
B)将所述步骤A)得到的阴阳离子复合物溶于乙醇溶液中，制备浓度为8g/mL的阴阳离子复合物溶液；将聚氨酯中心静脉导管(重量为X0)在上述复合物溶液中浸泡45min，在25℃放置使乙醇溶剂完全挥发，得到物理吸附阴阳离子复合物的涂层的中心静脉导管(重量为X1)。B) Dissolve the anion-cation complex obtained in the step A) in ethanol solution to prepare an anion-cation complex solution with a concentration of 8g/mL; soak the polyurethane central venous catheter (weight is X0) in the above-mentioned complex solution For 45 minutes, place at 25° C. to completely volatilize the ethanol solvent to obtain a central venous catheter (weight X1 ) coated with physically adsorbed anion-cation complexes.
C)将负载有复合物的中心静脉导管至于波长为365nm、功率为320W的高压汞灯下照射5min，N-(4-苯甲酰苄基)-N在紫外激发下与肝素钠和基底发生结合反应，在中心静脉导管表面得到粘附力增强的具有交联结构的底层涂层。随后将中心静脉导管在150Hz的水浴超声条件下，先后用乙醇、去离子水各清洗3次，每次8min；然后在60℃，真空干燥24h后得到模量适中的具有交联结构的涂层的中心静脉导管((重量为X2)。C) Irradiate the central venous catheter loaded with the complex under a high-pressure mercury lamp with a wavelength of 365nm and a power of 320W for 5 minutes, and N-(4-benzoylbenzyl)-N reacts with heparin sodium and substrate under ultraviolet excitation. The combination reaction results in a primer coating with a cross-linked structure with enhanced adhesion on the surface of the central venous catheter. Then the central venous catheter was washed with ethanol and deionized water three times, each time for 8 minutes, under 150 Hz water-bath ultrasonic conditions; and then dried in vacuum at 60°C for 24 hours to obtain a coating with a moderate modulus and a cross-linked structure Central venous catheter ((weight is X2).
D)配制浓度为0.2g/mL的聚乙二醇水溶液，配制浓度为1g/mL二甲基丙烯酸二乙二醇酯溶液，将上述溶液混合后，浸涂到固定有增粘底层的中心静脉导管表面，用波长为365nm、功率为330W的高压汞灯照射8min，随后用乙醇、去离子水超声振荡洗涤，得到具有润滑表涂涂层和粘附力增强的底层涂层的双层涂层结构的中心静脉导管(重量为X3)。D) Prepare a polyethylene glycol aqueous solution with a concentration of 0.2g/mL, prepare a solution of diethylene glycol dimethacrylate with a concentration of 1g/mL, mix the above solutions, and dip-coat it on the central vein with the viscosifying bottom layer fixed The surface of the catheter was irradiated with a high-pressure mercury lamp with a wavelength of 365nm and a power of 330W for 8 minutes, followed by ultrasonic washing with ethanol and deionized water to obtain a double-layer coating with a lubricating surface coating and a primer coating with enhanced adhesion Structured central venous catheter (weight X3).
实施例2Example 2
A)配制浓度为3g/mL-的N-二乙基-N-辛基苯基碘化铵的丙酮溶液，配制浓度为12g/mL的透明质酸钠水溶液；将上述N-二乙基-N-辛基苯基碘化铵的水溶液逐滴滴加到25ml的透明质酸钠溶液中，直至溶液中析出大量白色沉淀，静置3.5h后，过滤得到白色沉淀物。用超纯水洗涤沉淀物3次，冷冻干燥后得到阴阳离子复合物。A) preparation concentration is the acetone solution of N-diethyl-N-octylphenyl ammonium iodide of 3g/mL-, the preparation concentration is the sodium hyaluronate aqueous solution of 12g/mL; The above-mentioned N-diethyl- The aqueous solution of N-octylphenylammonium iodide was added dropwise to 25ml of sodium hyaluronate solution until a large amount of white precipitates were precipitated in the solution. After standing still for 3.5 hours, the white precipitates were obtained by filtration. The precipitate was washed three times with ultrapure water, and the anion-cation complex was obtained after freeze-drying.
B)将所述步骤A)得到的阴阳离子复合物溶于丙酮溶液中，制备浓度为12g/mL的阴阳离子复合物溶液；将聚氨酯静脉留置针套管(重量为X0)在上述复合物溶液中浸泡60min，在25℃放置使丙酮溶剂完全挥发，得到物理吸附阴阳离子复合物的涂层的静脉留置针套管(重量为X1)。B) The anion-cation complex obtained in the step A) is dissolved in acetone solution to prepare an anion-cation complex solution with a concentration of 12g/mL; the polyurethane intravenous indwelling needle sleeve (weight is X0) in the above-mentioned complex solution Soak in the medium for 60 minutes, and place it at 25° C. to completely volatilize the acetone solvent to obtain an intravenous indwelling needle sleeve (weight X1) with a coating of physically adsorbing anion-cation complexes.
C)将负载有复合物的静脉留置针套管至于波长为235nm、功率为380W的高压汞灯下照射3min，N-二乙基-N-辛基苯基碘化铵在紫外激发下与透明质酸钠和基底发生结合反应，在静脉留置针套管表面得到粘附力增强的具有交联结构的底层涂层。随后将静脉留置针套管在120Hz的水浴超声条件下，先后用乙醇、去离子水各清洗3次，每次15min；然后在65℃，真空干燥24h后得到模量适中的具有交联结构的涂层的静脉留置针套管(重量为X2)。C) The venous indwelling needle cannula loaded with the compound is irradiated under a high-pressure mercury lamp with a wavelength of 235nm and a power of 380W for 3min, and N-diethyl-N-octylphenylammonium iodide is excited with the transparent Sodium hyaluronate reacts with the substrate, and a bottom coating with a cross-linked structure with enhanced adhesion is obtained on the surface of the cannula of the venous indwelling needle. Then, the cannula of the intravenous indwelling needle was washed with ethanol and deionized water three times, each time for 15 minutes, under the condition of 120 Hz water bath ultrasonic; Coated venous cannula (weight X2).
D)配制浓度为2.5g/mL的聚丙烯酰胺乙醇溶液，配制浓度为1.8g/mL三羟甲基丙烷三丙烯酸酯溶液，将上述溶液混合后，浸涂到固定有增粘底层的静脉留置针套管表面，用波长为365nm、功率为330W的高压汞灯照射8min，随后用乙醇、去离子水超声振荡洗涤，得到具有润滑表涂涂层和粘附力增强的底层涂层的双层涂层结构的静脉留置针套管(重量为X3)。D) Prepare a polyacrylamide ethanol solution with a concentration of 2.5g/mL, and prepare a trimethylolpropane triacrylate solution with a concentration of 1.8g/mL. After mixing the above solutions, dip-coat it on a vein with a viscous bottom layer fixed. The surface of the needle sleeve is irradiated with a high-pressure mercury lamp with a wavelength of 365nm and a power of 330W for 8 minutes, and then washed with ethanol and deionized water by ultrasonic oscillation to obtain a double-layer coating with a lubricating surface coating and a bottom coating with enhanced adhesion. Coated venous cannula (weight X3).
实施例3Example 3
A)配制浓度为0.5g/mL-的N-二甲基十二烷基-1-溴化铵的乙醇溶液，配制浓度为1.5g/mL的软骨素甲醇溶液；将上述N-二甲基十二烷基-1-溴化铵的水溶液逐滴滴加到5ml的软骨素溶液中，直至溶液中析出大量白色沉淀，静置1.5h后，过滤得到白色沉淀物。用超纯水洗涤沉淀物3次，冷冻干燥后得到阴阳离子复合物。A) preparation concentration is the ethanol solution of N-dimethyldodecyl-1-ammonium bromide of 0.5g/mL-, preparation concentration is the chondroitin methanol solution of 1.5g/mL; The aqueous solution of dodecyl-1-ammonium bromide was added dropwise to 5ml of chondroitin solution until a large amount of white precipitates were precipitated in the solution. After standing for 1.5 hours, the white precipitates were obtained by filtration. The precipitate was washed three times with ultrapure water, and the anion-cation complex was obtained after freeze-drying.
B)将所述步骤A)得到的阴阳离子复合物溶于甲醇溶液中，制备浓度为0.8g/mL的阴阳离子复合物溶液；将PVC导尿管(重量为X0)在上述复合物溶液中浸泡60min，在25℃放置使甲醇溶剂完全挥发，得到物理吸附阴阳离子复合物的涂层的PVC导尿管(重量为X1)。B) the anion-cation complex obtained in the step A) is dissolved in methanol solution to prepare an anion-cation complex solution with a concentration of 0.8g/mL; PVC urinary catheter (weight is X0) in the above-mentioned complex solution Soak for 60 minutes, place at 25° C. to completely volatilize the methanol solvent, and obtain a PVC catheter (weight X1) coated with physically adsorbed anion-cation complexes.
C)将负载有复合物的PVC导尿管至于波长为240nm、功率为200W的中压汞灯下照射8min，N-二甲基十二烷基-1-溴化铵在紫外激发下与软骨素和基底发生结合反应，在PVC导尿管表面得到粘附力增强的具有交联结构的底涂涂层。随后将PVC导尿管在180Hz的水浴超声条件下，先后用乙醇、去离子水各清洗3次，每次20min；然后在50℃，真空干燥24h后得到模量适中的具有交联结构的涂层的PVC导尿管(重量为X2)。C) The PVC catheter loaded with the compound is irradiated for 8 minutes under a medium-pressure mercury lamp with a wavelength of 240nm and a power of 200W, and N-dimethyldodecyl-1-ammonium bromide reacts with cartilage under ultraviolet excitation. The combination reaction between the pigment and the substrate, and a primer coating with a cross-linked structure with enhanced adhesion are obtained on the surface of the PVC catheter. Subsequently, the PVC catheter was washed with ethanol and deionized water three times, each time for 20 minutes, under 180 Hz water-bath ultrasonic conditions; Layer PVC catheter (weight is X2).
D)配制浓度为0.3g/mL的聚乙烯吡咯烷酮甲醇溶液，配制浓度为1.2g/mL聚乙二醇二丙烯酸酯溶液，将上述溶液混合后，浸涂到固定有增粘底层的静脉留置针套管表面，用波长为246nm、功率为330W的高压汞灯照射3min，随后用乙醇、去离子水超声振荡洗涤，得到具有润滑表涂涂层和粘附力增强的底涂涂层的双层涂层结构的PVC导尿管(重量为X3)。D) Prepare a methanol solution of polyvinylpyrrolidone with a concentration of 0.3g/mL, prepare a solution of polyethylene glycol diacrylate with a concentration of 1.2g/mL, mix the above solutions, and dip-coat it on the intravenous indwelling needle fixed with the viscosifying bottom layer The surface of the sleeve is irradiated with a high-pressure mercury lamp with a wavelength of 246nm and a power of 330W for 3 minutes, and then washed with ethanol and deionized water by ultrasonic oscillation to obtain a double-layer coating with a lubricating surface coating and a primer coating with enhanced adhesion. Coated PVC catheter (weight X3).
实施例4Example 4
A)配制浓度为1.5g/mL的N-(4-苯甲酰苄基)-N的丙酮溶液，配制浓度为1.5g/mL的透明质酸钠水溶液；将上述N-(4-苯甲酰苄基)-N的水溶液逐滴滴加到8ml的透明质酸钠溶液中，直至溶液中析出大量白色沉淀，静置2h后，过滤得到白色沉淀物。用超纯水洗涤沉淀物3次，冷冻干燥后得到阴阳离子复合物。A) preparation concentration is the acetone solution of N-(4-benzoylbenzyl)-N of 1.5g/mL, preparation concentration is the sodium hyaluronate aqueous solution of 1.5g/mL; Acylbenzyl)-N aqueous solution was added dropwise to 8ml of sodium hyaluronate solution until a large amount of white precipitate was precipitated in the solution, and after standing for 2 hours, the white precipitate was obtained by filtration. The precipitate was washed three times with ultrapure water, and the anion-cation complex was obtained after freeze-drying.
B)将所述步骤A)得到的阴阳离子复合物溶于乙醇溶液中，制备浓度为8g/mL的阴阳离子复合物溶液；将聚氨酯静脉留置针套管(重量为X0)在上述复合物溶液中浸泡60min，在25℃放置使乙醇溶剂完全挥发，得到物理吸附阴阳离子复合物的涂层的静脉留置针套管(重量为X1)。B) The anion-cation complex obtained in the step A) is dissolved in ethanol solution to prepare an anion-cation complex solution with a concentration of 8g/mL; the polyurethane intravenous indwelling needle cannula (weight is X0) in the above-mentioned complex solution Immerse in medium for 60 min, place at 25° C. to completely volatilize the ethanol solvent, and obtain a venous indwelling needle sleeve (weight X1) coated with physically adsorbed anion-cation complexes.
C)将负载有复合物的静脉留置针套管至于波长为365nm、功率为320W的高压汞灯下照射3min，N-(4-苯甲酰苄基)-N在紫外激发下与透明质酸钠和基底发生结合反应，在静脉留置针套管表面得到粘附力增强的具有交联结构的底涂涂层。随后将静脉留置针套管在150Hz的水浴超声条件下，先后用乙醇、去离子水各清洗3次，每次8min；然后在60℃，真空干燥24h后得到模量适中的具有交联结构的涂层的静脉留置针套管((重量为X2)。C) The intravenous indwelling needle cannula loaded with the complex is irradiated for 3 minutes under a high-pressure mercury lamp with a wavelength of 365nm and a power of 320W, and N-(4-benzoylbenzyl)-N reacts with hyaluronic acid under ultraviolet excitation Sodium reacts with the substrate, and a primer coating with a cross-linked structure with enhanced adhesion is obtained on the surface of the venous indwelling needle sleeve. Then, the cannula of the intravenous indwelling needle was washed with ethanol and deionized water three times, each time for 8 minutes, under the condition of 150 Hz water bath ultrasonic; Coated IV Catheter Cannula ((Weight X2).
D)配制浓度为3.5g/mL的聚乙烯吡咯烷酮异丙醇溶液，配制浓度为1g/mL二甲基丙烯酸二乙二醇酯溶液，将上述溶液混合后，浸涂到固定有增粘底层的静脉留置针套管，用波长为365nm、功率为330W的高压汞灯照射10min，随后用乙醇、去离子水超声振荡洗涤，得到具有润滑表涂涂层和粘附力增强的底涂涂层的双层涂层结构的静脉留置针套管(重量为X3)。D) Prepare a polyvinylpyrrolidone isopropanol solution with a concentration of 3.5g/mL, and prepare a solution with a concentration of 1g/mL diethylene glycol dimethacrylate. After mixing the above solutions, dip-coat it on the substrate fixed with an adhesion-promoting bottom layer. The venous indwelling needle cannula was irradiated with a high-pressure mercury lamp with a wavelength of 365nm and a power of 330W for 10 minutes, and then washed with ethanol and deionized water by ultrasonic oscillation to obtain a lubricating surface coating and a primer coating with enhanced adhesion. Intravenous indwelling cannula with double-coated structure (weight is X3).
实施例5性能测试Embodiment 5 performance test
1)涂层粘附力测试：1) Coating adhesion test:
将实施例1-4制得的负载阴阳离子复合物中间体涂层的医用介入类导管(重量X1)、负载粘附力增强的交联结构的底涂涂层的医用介入类导管(重量X2)和负载润滑表涂涂层和粘附力增强的底涂涂层的双层涂层结构的医用介入类导管(重量X3)和对照组负载普通涂层的医用介入导管(重量Y1)分别在超声波清洗机中处理10min和60min后，在60℃下，真空干燥24h后，称重(重量即为X4、X5、X6和Y2)。计算涂层存留率，对于负载中间体涂层的医用介入类导管其计算公式为：涂层留存率1(％)＝(X4-X0/X1-X0)×100％；对于负载粘附力增强的交联结构的底涂涂层的医用介入类导管其计算公式为：涂层留存率2(％)＝(X5-W0/X2-W0)×100％；对于负载润滑表涂涂层和粘附力增强的底涂涂层的双层涂层结构的医用介入类导管其计算公式为：涂层留存率3(％)＝(X6-W0/X3-W0)×100％；对于对照组负载普通涂层的医用介入导管其计算公式为：涂层留存率4(％)＝(Y2-W0/Y1-W0)×100％。结果如表1所示，表1为本发明实施例1-4得到的具有润滑表涂涂层和粘附力增强的底涂涂层的双层涂层结构的医用介入类导管的涂层存留率。The medical intervention catheter (weight X1) of the load anion-cation complex intermediate coating that embodiment 1-4 makes, the medical intervention catheter (weight X2) of the primer coating of the cross-linked structure that load adhesion strengthens ) and the medical interventional catheter (weight X3) of the double-layer coating structure of the load lubricating surface coating and the adhesion-enhancing primer coating and the medical interventional catheter (weight Y1) of the control group loaded with ordinary coatings respectively in After being treated in an ultrasonic cleaning machine for 10 min and 60 min, they were dried in vacuum at 60°C for 24 h, and then weighed (the weights are X4, X5, X6 and Y2). Calculate the coating retention rate, the calculation formula for medical intervention catheters loaded with intermediate coatings is: coating retention rate 1 (%) = (X4-X0/X1-X0) × 100%; for the enhanced adhesion of the load The calculation formula for medical intervention catheters with a cross-linked primer coating is: coating retention rate 2 (%) = (X5-W0/X2-W0) × 100%; The calculation formula of the medical intervention catheter with the double-layer coating structure of the primer coating with enhanced adhesion is: coating retention rate 3 (%)=(X6-W0/X3-W0)×100%; for the control group load The calculation formula for medical interventional catheters with common coatings is: coating retention rate 4 (%)=(Y2-W0/Y1-W0)×100%. The results are shown in Table 1, and Table 1 is the coating retention of the medical intervention catheter with a double-layer coating structure of a lubricating surface coating and an adhesion-enhanced primer coating obtained in Examples 1-4 of the present invention Rate.
表1本发明实施例1-4得到的具有润滑表涂涂层和粘附力增强的底涂涂层的双层涂层结构的医用介入类导管的涂层存留率Table 1 The coating retention rate of the medical intervention catheter with the double-layer coating structure of the lubricating surface coating and the primer coating with enhanced adhesion obtained in Examples 1-4 of the present invention
由表1可以看出，本发明所述的具有润滑表涂涂层和粘附力增强的底涂涂层的双层涂层结构的医用介入类导管的涂层存留率在超声10min、60min后分别高达99.5％、98.8％，而仅以物理方式负载的中间体涂层的留置针套管涂层存留率分别为43.2％、26.1％，其中对照组负载普通涂层的医用介入类导管的涂层留存率分别为62.1％、46.4％，说明本发明提供的润滑表涂涂层和粘附力增强的底涂涂层的双层涂层结构具有更高的基体附着力和涂层自身的稳定性。As can be seen from Table 1, the coating retention rate of the medical interventional catheter with a double-layer coating structure of a lubricating surface coating and an adhesion-enhanced primer coating according to the present invention is after ultrasonic 10min, 60min They were as high as 99.5% and 98.8% respectively, while the retention rate of the indwelling needle sleeve coating of the intermediate coating loaded only in physical way was 43.2% and 26.1% respectively. Layer retention rate is 62.1%, 46.4% respectively, illustrates that the two-layer coating structure of lubricating surface coating provided by the present invention and the primer coating of adhesion enhancement have higher substrate adhesion and the stability of coating itself sex.
2)涂层润滑性测试1：2) Coating lubricity test 1:
本发明采用MXD-02摩擦系数仪对实施例1中具有润滑表涂涂层和粘附力增强的底涂涂层的双层涂层结构的医用介入类导管(实施例组)、具有相同润滑表涂涂层和普通底涂涂层的双层涂层结构的医用介入类导管(对照组)以及未改性医用介入类导管(未改性组)进行摩擦系数的测试。首先分别将以上3组医用介入类导管超声清洗3次，每次15min，然后固定在凹槽板上，向储水槽注入水直至试样完全浸泡其中。将200g的标准滑块轻放入于试样上方，由传感器连接杆拖动滑块以100mm/min的速度运动，测出动摩擦系数，重复以上步骤，结果如表2-1和2-2所示，表2-1和2-2为粘附力增强的润滑涂层及其具有润滑抗菌功能的医用介入类导管的摩擦系数。The present invention adopts MXD-02 coefficient of friction meter to have the medical intervention catheter (embodiment group) of the double-layer coating structure of the primer coating layer of lubricating surface coating and adhesion enhancement in embodiment 1, have the same lubrication The friction coefficient of the medical interventional catheter (control group) and the unmodified medical interventional catheter (unmodified group) with the double-layer coating structure of the surface coating and the ordinary primer coating were tested. First, the above three groups of medical interventional catheters were ultrasonically cleaned 3 times, each time for 15 minutes, and then fixed on the groove plate, and water was poured into the water storage tank until the samples were completely immersed in it. Put the 200g standard slide block lightly on the sample, drag the slide block by the connecting rod of the sensor to move at a speed of 100mm/min, measure the coefficient of dynamic friction, repeat the above steps, the results are shown in Table 2-1 and 2-2 Tables 2-1 and 2-2 show the friction coefficients of lubricating coatings with enhanced adhesion and medical intervention catheters with lubricating and antibacterial functions.
表2-1粘附力增强的润滑涂层及其具有润滑抗菌功能的医用介入类导管的摩擦系数(第一次清洗)Table 2-1 Friction coefficients of lubricating coatings with enhanced adhesion and medical interventional catheters with lubricating and antibacterial functions (first cleaning)
表2-2粘附力增强的润滑涂层及其具有润滑抗菌功能的医用介入类导管的摩擦系数(第二次清洗)Table 2-2 Friction coefficients of lubricating coatings with enhanced adhesion and medical interventional catheters with lubricating and antibacterial functions (the second cleaning)
实验结果表明，多次的超声清洗和水中浸泡对实施例1粘附力增强的润滑涂层及其具有润滑抗菌功能的医用介入类导管涂层的粘附力和润滑性能没有影响，摩擦系数无明显变化，粘附力增强的润滑涂层及其具有润滑抗菌功能的医用介入类导管的摩擦系数仅为普通导尿管的百分之一左右，这说明润滑涂层与管壁结合牢固，涂层稳定性强。经过多次超声清洗后，而普通底涂涂层的导管，因底涂涂层粘附力低，涂层不牢固导致润滑表涂涂层脱落，随着超声清洗次数的增多，润滑性能下降，摩擦系数逐渐增大。The experimental results show that repeated ultrasonic cleaning and immersion in water have no effect on the adhesion and lubricating properties of the lubricating coating with enhanced adhesion in Example 1 and the medical intervention catheter coating with lubricating and antibacterial functions, and the friction coefficient has no effect. Significant changes, the friction coefficient of the lubricating coating with enhanced adhesion and the medical interventional catheter with lubricating and antibacterial functions is only about one percent of that of ordinary urinary catheters, which shows that the lubricating coating is firmly combined with the tube wall. Layer stability is strong. After several times of ultrasonic cleaning, the lubricating surface coating falls off due to the low adhesion of the primer coating and the weak coating of the ordinary primer coating. With the increase of the number of ultrasonic cleaning, the lubricating performance decreases. The coefficient of friction increases gradually.
3)涂层润滑性测试2：3) Coating lubricity test 2:
本发明采用MXD-02摩擦系数仪对实施例1中具有润滑表涂涂层和粘附力增强的底涂涂层的双层涂层结构的医用介入类导管(实施例组)、仅具有粘附力增强的底涂涂层的单层涂层医用介入类导管(对照组)以及未改性医用介入类导管(未改性组)进行摩擦系数的测试。首先分别将以上3组医用介入类导管用清水浸泡30s，然后固定在凹槽板上，向储水槽注入水直至试样完全浸泡其中。将200g的标准滑块轻放入于试样上方，由传感器连接杆拖动滑块以100mm/min的速度运动，测出动摩擦系数，结果如表3所示，表3为具有润滑表涂涂层和粘附力增强的底涂涂层的双层涂层结构的医用介入类导管与仅具有粘附力增强的底涂涂层的单层涂层医用介入类导管的摩擦系数。The present invention adopts MXD-02 coefficient of friction instrument to have the medical intervention catheter (embodiment group) of the double-layer coating structure of the priming coating layer that has lubricating surface coating layer and adhesion enhancement in embodiment 1, only has adhesion The single-layer coated medical intervention catheter (control group) with enhanced adhesion and the unmodified medical intervention catheter (unmodified group) were tested for coefficient of friction. First, soak the above three groups of medical interventional catheters in clean water for 30s, then fix them on the groove plate, and pour water into the water storage tank until the samples are completely immersed in it. Put a 200g standard slider lightly on top of the sample, drag the slider to move at a speed of 100mm/min by the connecting rod of the sensor, and measure the coefficient of dynamic friction. The results are shown in Table 3. The coefficient of friction of a medical interventional catheter with a double-coated structure of two layers and an adhesion-enhancing primer coating versus a single-layer medical interventional catheter with only an adhesion-enhancing primer coating.
表3具有润滑表涂涂层和粘附力增强的底涂涂层的双层涂层结构的医用介入类导管与仅具有粘附力增强的底涂涂层的单层涂层医用介入类导管的摩擦系数Table 3 Medical interventional catheters with double-layer coating structure of lubricating surface coating and adhesion-enhancing primer coating and single-layer medical interventional catheters with only adhesion-enhancing primer coating coefficient of friction
实验结果表明，具有粘附力增强的底涂涂层的单层涂层医用介入类导管不具备良好的润滑性能，摩擦系数与未改性样品相比无明显变化。具有润滑表涂涂层和粘附力增强的底涂涂层的双层涂层结构的医用介入类导管具有很好的润滑性能，润滑涂层通过底涂涂层作用与导管管壁结合牢固，二者在润滑性能方面有显著性差异。The experimental results show that the single-layer coated medical interventional catheters with the adhesion-enhanced primer coating do not have good lubricating properties, and the friction coefficient does not change significantly compared with the unmodified samples. The medical interventional catheter with a double-layer coating structure of a lubricating surface coating and a primer coating with enhanced adhesion has good lubricating properties. The lubricating coating is firmly bonded to the catheter wall through the action of the primer coating. There is a significant difference between the two in terms of lubricating properties.
4)涂层安全性测试4) Coating Safety Test
将实施例1-4制得的负载润滑表涂涂层和粘附力增强的底涂涂层的双层涂层结构的医用介入类导管(实施例组)、负载相同润滑表涂涂层和普通底涂涂层的医用介入导管(对照组)以及未改性医用介入类导管(未改性组)进行引发剂析出检测试验。其中，负载相同润滑表涂涂层和普通底涂涂层的医用介入导管(对照组)是通过小分子光引发剂固定到导管表面。分别将以上3组样品在温度60℃，功率200w的超声条件下水溶液浸泡6h，取浸泡后的溶液通过红外分光光度计检测每组样品吸光度情况，根据峰值变化判断小分子光引发剂析出情况。表4为具有润滑表涂涂层和粘附力增强的底涂涂层的双层涂层结构的医用介入类导管的引发剂析出情况The medical intervention catheter (embodiment group) of the double-layer coating structure of the load lubricating surface coating and the primer coating of adhesion enhancement made by Examples 1-4, the same lubricating surface coating of the load and The medical interventional catheter with ordinary primer coating (control group) and the unmodified medical interventional catheter (unmodified group) were subjected to the initiator precipitation detection test. Among them, the medical interventional catheter (control group) loaded with the same lubricating surface coating and ordinary primer coating was fixed to the catheter surface by a small molecule photoinitiator. The above three groups of samples were soaked in aqueous solution for 6 hours under ultrasonic conditions with a temperature of 60°C and a power of 200w, and the soaked solution was taken to detect the absorbance of each group of samples by an infrared spectrophotometer, and the precipitation of the small molecule photoinitiator was judged according to the peak value change. Table 4 is the initiator precipitation situation of the medical intervention type catheter with the double-layer coating structure of the primer coating with lubricating surface coating and adhesion enhancement
表4具有润滑表涂涂层和粘附力增强的底涂涂层的双层涂层结构的医用介入类导管的引发剂析出情况Table 4 has the initiator precipitation situation of the medical intervention catheter of the double-layer coating structure of the primer coating of lubricating surface coating and adhesion enhancement
实验结果表明，经过长时间的浸泡具有润滑表涂涂层和粘附力增强的底涂涂层的双层涂层结构的医用介入类导管无引发剂析出，表明光引发型阴阳离子复合物型底层在固化时会发生Norrish II反应和重组反应，实现底涂层在基体材料表面的化学键固定以及涂层内部的自身交联，在有效提高低涂层对基底材料粘附性的同时，还增加了提高涂层自身强度，提高涂层的安全性能。The experimental results show that after a long time of immersion, there is no initiator precipitation in the medical interventional catheter with a double-layer coating structure of a lubricating surface coating and an adhesion-enhancing primer coating, indicating that the photo-initiated anion-cation complex type When the bottom layer is cured, Norrish II reaction and recombination reaction will occur to realize the chemical bond fixation of the bottom layer on the surface of the base material and the self-crosslinking inside the coating. While effectively improving the adhesion of the low coating to the base material, it also increases In order to improve the strength of the coating itself and improve the safety performance of the coating.
5)抗凝血性测试：5) Anticoagulation test:
将实施例1～4制得的双层涂层结构的医用介入类导管在新鲜制得的富含血小板血浆中37℃孵化60min后，采用扫描电子显微镜拍摄置针套管表面的血小板形貌。为确保实验真实性和可信性，进行3次重复实验的平均值来得出数据，其中，未进行处理的留置针套管作为阴性对照组(厂家：山东威高集团医用高分子制品股份有限公司)。结果如图3～4所示，图3为未处理套管表面的血小板形貌照片，图4为本发明实施例2得到的具有双层涂层结构的留置针套管表面的血小板形貌照片。After incubating the medical interventional catheters with double-layer coating structure prepared in Examples 1-4 at 37° C. for 60 min in freshly prepared platelet-rich plasma, the morphology of platelets on the surface of the needle sleeve was photographed with a scanning electron microscope. In order to ensure the authenticity and credibility of the experiment, the average value of three repeated experiments was carried out to obtain the data, wherein the indwelling needle sleeve without treatment was used as the negative control group (manufacturer: Shandong Weigao Group Medical Polymer Products Co., Ltd. ). The results are shown in Figures 3 to 4, Figure 3 is a photo of platelet topography on the surface of an untreated sleeve, and Figure 4 is a photo of platelet topography on the surface of an indwelling needle sleeve with a double-layer coating structure obtained in Example 2 of the present invention .
由图3～4可以看出，未处理留置针套管表面粘附有大量血小板，且血小板呈现铺展、完全铺展的激活状态。本发明实施例2得到的具有双层涂层结构留置针套管表面的粘附有少数的血小板，且血小板呈现圆形、梭形的未激活状态。考虑血小板粘附和激活在凝血过程中发挥着重要作用，说明本发明提供的具有润滑表涂涂层和粘附力增强的底涂涂层的双层涂层结构留置针套管可以减少凝血现象的发生概率。It can be seen from Figures 3 to 4 that a large number of platelets adhered to the surface of the untreated indwelling needle cannula, and the platelets were in an activated state of spreading and fully spreading. A small number of platelets adhered to the surface of the cannula of the indwelling needle with a double-layer coating structure obtained in Example 2 of the present invention, and the platelets are in a round and spindle-shaped inactive state. Considering that platelet adhesion and activation play an important role in the coagulation process, it shows that the indwelling needle cannula with double-layer coating structure provided by the present invention with a lubricating top coating and an adhesion-enhancing primer coating can reduce coagulation probability of occurrence.
6)抗菌性测试1：6) Antibacterial test 1:
将实施例1～4制得的具有双层涂层结构的医用介入导管和未涂层处理的医用介入导管灭菌，无菌实验条件下，在浓度为1X106cfu/mL的金黄色葡萄球菌的LB营养液中培养24h，随后取出导管，进行低功率超声处理、稀释，取稀释后的菌液在固体LB平板培养中37℃培养12h，对平板培养基上的菌落进行计数，测定医用导管表面的细菌数量，图5为未涂层处理医用导管培养后的菌落情况，图6为具有双层涂层结构的医用介入导管培养后的菌落情况。进行3次重复实验取平均值，结果如表4所示。The medical interventional catheters with double-layer coating structure and the uncoated medical interventional catheters prepared in Examples 1-4 were sterilized, and under sterile experimental conditions, Staphylococcus aureus at a concentration of 1X10 Cultivate in the LB nutrient solution for 24 hours, then take out the catheter, perform low-power ultrasonic treatment and dilution, take the diluted bacterial solution and culture it on a solid LB plate at 37°C for 12 hours, count the colonies on the plate medium, and determine the medical catheter The number of bacteria on the surface, Figure 5 is the colony situation after the culture of the uncoated medical catheter, and Figure 6 is the colony situation after the culture of the medical interventional catheter with a double-layer coating structure. The average value of 3 repeated experiments was carried out, and the results are shown in Table 4.
表5医用导管表面的活细菌数量Table 5 The number of viable bacteria on the surface of medical catheters
由表5可以看出，即便不加润滑油，粘附力增强的润滑涂层及其具有润滑抗菌功能的医用介入类导管就可以有效降低导管表面的活细菌数量。往粘附力增强的润滑涂层及其具有润滑抗菌功能的医用介入类导管中注入润滑油后，医用导管的表面的活细菌数量进一步降低，维持在很低的水平。It can be seen from Table 5 that even without lubricating oil, the lubricating coating with enhanced adhesion and the medical interventional catheter with lubricating and antibacterial functions can effectively reduce the number of live bacteria on the surface of the catheter. After injecting lubricating oil into the lubricating coating with enhanced adhesion and the medical interventional catheter with lubricating and antibacterial functions, the number of live bacteria on the surface of the medical catheter is further reduced and maintained at a very low level.
7)抗菌性测试2：7) Antibacterial test 2:
在无菌试验操作环境中，37℃培养金黄色葡萄球菌，将实施例1所述的具有润滑表涂涂层和粘附力增强的底层涂层的双层涂层结构的医用介入类导管(实施例组)、具有润滑表涂涂层和普通底层涂层的双层涂层结构的医用介入类导管(对照组)和未涂层处理的医用介入导管(未改性组)浸泡在金黄色葡萄球菌浓度为1X 106cfu/mL的LB溶液中，37℃培养6h后取出，用4％多聚甲醛固定4h，乙醇梯度脱水后，采用扫描电子显微镜观察实施例组和对照组医用介入类导管表面细菌粘附和死亡情况，如图7、图8和图9。In the aseptic test operating environment, Staphylococcus aureus was cultivated at 37°C, and the medical interventional catheter with a double-layer coating structure of a lubricating surface coating and an adhesion-enhancing primer described in Example 1 ( Example group), the medical intervention catheter (control group) and the uncoated medical intervention catheter (unmodified group) with the double-layer coating structure of the lubricating surface coating coating and the common bottom coating are soaked in golden yellow Staphylococcus concentration is 1X 10 6 cfu/mL LB solution, cultured at 37°C for 6 hours, taken out, fixed with 4% paraformaldehyde for 4 hours, and dehydrated with ethanol gradient, using scanning electron microscope to observe the medical interventional products of the example group and the control group Bacterial adhesion and death on the catheter surface are shown in Figure 7, Figure 8 and Figure 9.
实验结果表明，图7为未改性组医用导管表面细菌粘附和死亡情况，结果表明未涂层处理的医用导管表面粘附了大量的细菌，形态为活细菌；图8为对照组具有润滑表涂涂层和普通底层涂层的双层涂层结构的医用介入类导管表面细菌情况，结果表明润滑表涂涂层有效抑制细菌粘附，只有少量细菌粘附在导管表面，因底层涂层不具有杀菌功能，所以粘附的细菌形态完整都是活细菌，表面对照组导管表面涂层只具有抗粘附功能；图9为实施例组具有润滑表涂涂层和粘附力增强的底层涂层的双层涂层结构的医用介入类导管表面细菌情况，结果表明润滑表涂涂层有效抑制细菌粘附，只有少量细菌粘附在导管表面，且底层涂层具有杀菌功能，所以粘附的细菌形态破裂为死细菌，表明实施例组导管表面涂层为抗杀结合表面。The experimental results show that Figure 7 shows the adhesion and death of bacteria on the surface of the medical catheter in the unmodified group. Bacteria on the surface of medical interventional catheters with a double-layer coating structure of surface coating and ordinary primer coating. The results show that the lubricating surface coating effectively inhibits bacterial adhesion, and only a small amount of bacteria adheres to the surface of the catheter. It does not have a bactericidal function, so the adhered bacteria are completely live bacteria, and the surface coating of the control group catheter only has anti-adhesion function; Figure 9 is the bottom layer with a lubricating surface coating and enhanced adhesion in the embodiment group Bacteria on the surface of medical interventional catheters with a double-layer coating structure. The results show that the lubricating surface coating effectively inhibits bacterial adhesion. Only a small amount of bacteria adheres to the surface of the catheter, and the underlying coating has a bactericidal function, so the adhesion The bacterial morphology of the broken down to dead bacteria, indicating that the catheter surface coating of the embodiment group is an anti-killing binding surface.
以上所述仅是本发明的优选实施方式，应当指出，对于本技术领域的普通技术人员来说，在不脱离本发明原理的前提下，还可以做出若干改进和润饰，这些改进和润饰也应视为本发明的保护范围。The above is only a preferred embodiment of the present invention, it should be pointed out that, for those of ordinary skill in the art, without departing from the principle of the present invention, some improvements and modifications can also be made, and these improvements and modifications can also be made. It should be regarded as the protection scope of the present invention.
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