CN1261288A - 粘性、柔韧的水凝胶和含药涂层 - Google Patents

粘性、柔韧的水凝胶和含药涂层 Download PDF

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CN1261288A
CN1261288A CN98806544.4A CN98806544A CN1261288A CN 1261288 A CN1261288 A CN 1261288A CN 98806544 A CN98806544 A CN 98806544A CN 1261288 A CN1261288 A CN 1261288A
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polymer
coating
stabilization
copolymer
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理查德·J·惠特伯恩
张宪平
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Angiotech Biocoatings Corp
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    • A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
    • A61L29/14—Materials characterised by their function or physical properties, e.g. lubricating compositions
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    • A—HUMAN NECESSITIES
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    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
    • A61L29/08—Materials for coatings
    • A61L29/085—Macromolecular materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L31/16—Biologically active materials, e.g. therapeutic substances
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
    • A61L2300/606—Coatings
    • A61L2300/608—Coatings having two or more layers

Abstract

本发明的粘性涂层在粘合到医用装置表面的一层中包含一种稳定聚合物以及一种活性试剂(一种亲水性聚合物和/或一种生物活性剂)。本发明包括用于涂覆医用装置的涂层液体、涂覆该装置的方法、和有该涂层的装置。该稳定聚合物的选择要使该活性试剂包埋在涂层中,从而涂层具有高度的柔韧性,对多种底物具有改进了的粘合性。优选的稳定聚合物是可交联的丙烯酸聚合物和甲基丙烯酸聚合物、乙烯丙烯酸共聚物、苯乙烯丙烯酸共聚物、乙烯基乙酸酯聚合物和共聚物、乙烯基缩醛聚合物和共聚物、环氧树脂、三聚氰胺树脂、其他氨基树脂、酚聚合物及其共聚物、和它们的组合。

Description

粘性、柔韧的水凝胶和含药涂层
                         发明背景
本发明涉及用于医用装置的涂层，在该装置中活性试剂包埋在稳定聚合物中，该聚合物提供了改进的粘合性和柔韧性。该活性试剂可以是形成润滑水凝胶的亲水性聚合物、赋予生理功效的生物活性剂、或二者的组合，因而该涂层可以是水凝胶和/或含药涂层。
可用于医用装置的已知润滑涂层包括聚乙烯吡咯烷酮(PVP)、聚氨酯、丙烯酸酯聚合物、乙烯树脂、碳氟化合物、硅酮、橡胶、和某些组合的涂层。Whitbourne的美国专利5,001,009涉及含有PVP和纤维素酯聚合物的亲水性涂层。Whitbourne的美国专利5,525,348论述了基于纤维素酯的含药聚合物涂层。
用于可插入装置的已知水凝胶和含药涂层的缺点包括对惰性聚烯烃和金属表面的粘着性差、摩擦过大、持久性过低、使用方法困难或危险。对聚氨酯-PVP涂层来说，无法控制涂层的润滑程度和耐湿磨的程度，因此该涂层通常是不稳定的。PVP-纤维素酯涂层可能是脆性的，因此难以与某些底物粘合。当被置于含水环境中时，水凝胶能够吸收数倍于自身重量的水，导致水分渗透至涂层/底物界面，而使粘性丧失，这是一个严重的问题。
为了解决这些问题，用于医用装置的涂层需要一种改进的聚合物共混物，它可以形成水凝胶和/或含药涂层，干燥时粘合良好，耐湿磨，其柔韧性足以保持黏附在柔韧的装置上，使多种底物能提高粘性，并能够从化学稳定的和生物相容的溶剂中制备。
                         发明概述
本发明的粘性涂层包含稳定聚合物，其中包埋有一种活性试剂，该活性试剂是亲水性聚合物和/或生物活性剂，该涂层是柔韧的，并粘合在医用装置的表面上。本发明包括用于涂覆医用装置的涂层液、涂覆该装置的方法、和有涂层的装置。该涂层可以是经过涂层组分的单次涂覆或连续涂覆而形成的。
本发明满足了人们长期以来对较为柔韧、粘性的水凝胶和用于可插入医用装置的含药涂层的需要。在大量成熟的技术中，尽管前人在提供这种涂层上作了广泛努力，但都失败了，而本发明成功了。本发明不需要纤维素酯、聚氨酯、和其他现有技术中使用的涂层聚合物，但对湿磨仍具有良好的耐受性、并增强了的柔韧性和粘性。本发明的材料和方法是前所未知的或未曾提示过的，其优点也是以前未曾认识到的。
本发明包括涂在医用装置表面上的涂层，该涂层包含：(a)一种稳定聚合物，选自可交联的丙烯酸酯聚合物和甲基丙烯酸酯聚合物、乙烯丙烯酸共聚物、苯乙烯丙烯酸共聚物、乙酸乙烯酯聚合物和共聚物、乙烯基缩醛聚合物和共聚物、环氧树脂、三聚氰胺树脂、其他氨基树脂、酚聚合物、及其共聚物、和它们的组合；和(b)一种活性试剂，选自亲水性聚合物、生物活性剂、和它们的组合，所选择的亲水性聚合物要与该稳定聚合物相互作用，以形成润滑的水凝胶；该活性试剂被包埋在该稳定聚合物中，以使涂层在干燥和湿润情况下都黏附在表面上，即使表面发生弯曲也保持粘性。
优选地，该稳定聚合物是可交联的，该涂层包含一种用于该稳定聚合物的交联剂，例如环氧树脂、三聚氰胺树脂、其他氨基树脂、和酚醛树脂。该稳定聚合物可以选自羧基官能的丙烯酸酯聚合物、羟基官能的丙烯酸聚合物、胺官能的丙烯酸聚合物、羟甲基官能和酰胺官能的丙烯酸聚合物。它可以是可交联的丙烯酸，选自甲基丙烯酸甲酯、甲基丙烯酸丁酯、甲基丙烯酸异丁酯、甲基丙烯酸乙酯、丙烯酸甲酯、丙烯酸乙酯、丙烯酸、甲基丙烯酸、甲基丙烯酸苯乙烯酯、和丙烯酸苯乙烯酯、和它们的共聚物。
医用装置的表面优选包含的一种材料选自不锈钢、镍、金、铬、镍钛合金、铂、另一种金属、硅酮、聚乙烯、其他聚烯烃、聚酯、其他塑料、玻璃、聚氨酯、缩醛、聚酰胺和聚氯乙烯。
医用装置可以从用于侵入或类似操作的任何可插入的或部分可插入的装置中选择，例如针、导线、导管、外科器械、内窥镜检查用设备、丝线、移植片固定模、血管成形术气囊、伤口引流管、伤口敷料、动静脉分流器、胃肠管、尿道插入物、腹腔镜检查设备、小丸、和植入物。
生物活性剂优选地选自药剂、盐、渗透剂、和DNA。涂层中可以包含表面活性剂、着色剂、或增塑剂。
稳定聚合物可以集中在内层中，活性剂可以集中在外层中。在优选的实施方式中，涂层厚度小于50微米，活性剂是亲水性聚合物，涂层是水凝胶，可选地还含有生物活性剂。
该涂层能耐湿磨，当涂在难以涂覆的内表面、例如不锈钢上时，即使弯曲也保持粘性而不裂开。稳定聚合物的选择可以与底物中是否含有该稳定聚合物无关。
本发明的方法适用于在具有惰性表面的医用装置上涂层，方法是将包含稳定聚合物的涂料液体和包含活性试剂的涂料液体涂在表面上，干燥以除去液体，使活性试剂包埋在稳定聚合物中，涂层在干燥和湿润情况下都黏附在表面上，即使表面发生弯曲也保持粘性。单一的或多重涂料液体都可以含有稳定聚合物和一种或几种活性试剂。涂覆液体的方法可以是浸渍、喷涂、刷涂、或擦拭，或本领域已知的其他方法。在涂覆步骤之前，装置表面可以用等离子气体或其他电离处理法进行预处理，和/或可以涂覆一层预涂层。干燥方法一般包括将涂层加热到至少约50℃的步骤。
当医用装置表面包括本发明的稳定聚合物之一时，制备涂层的方法可以是涂上涂料液体，液体中包含能够侵蚀装置表面的溶剂和活性试剂，使该活性试剂包埋在表面聚合物中，涂层在干燥和湿润情况下都黏附在表面上，尽管医用装置发生弯曲也保持粘性。
按照本发明的试剂盒包含一种包含稳定聚合物的液体和一种包含活性试剂的液体，两种液体是同一种或分离的，稳定聚合物和活性试剂的选择要能在医用装置上形成粘性、柔韧的涂层，该涂层具有湿润的和干燥的粘性。如果液体是分离的，包含活性试剂的液体优选地还包含一种用于稳定聚合物的交联剂。该一种或几种液体可以是以溶剂为基础，该溶剂选自水、二甲苯、四氢呋喃、环己酮、乙醇、丁内酯、丁醇、三氯乙酸、苯甲醇、乙酸异丁酯、甲乙酮、石油溶剂150、甲苯、和丁基溶纤剂。稳定聚合物的液体可以是含水的可交联的丙烯酸分散液。
稳定聚合物优选为水不溶性聚合物，它与溶液中的亲水性聚合物或生物活性剂不发生明显反应，吸水性低，具有高度柔韧性，对多种底物具有改进的粘合性。可以用在本发明中的适当的商品包括丙烯酸类，例如ACRYLOID(Rohm & Haas)AT-63、AT-51、AT-81、WR-97；乙烯丙烯酸共聚物，例如PRIMACORTM(DOW)5989、5990；三聚氰胺树脂，例如CYMEL六甲氧基甲基三聚氰胺(CYTEC Industries)303、370、380；环氧树脂，例如EPON(Shell)1001；聚乙烯丁缩醛，例如BUTVAR B-79(Monsanto)。优选的丙烯酸稳定聚合物包括反应性基团、如羟基或羧基，能够与环氧树脂反应但不赋予聚合物以亲水性。
在一种实施方式中，本发明的涂层包括一种亲水性聚合物，例如水溶性聚烯烃，如具有极性侧基的亲水性乙烯基聚合物、具有亲水性酯化基团的聚丙烯酸酯或甲基丙烯酸酯、聚醚、聚乙二醇、或本领域已知的其他具有亲水性特征的聚合物。亲水性聚合物优选为PVP或PVP/乙酸乙烯酯，例如PVP/VA(GAF)E-335和E-635。稳定聚合物无需与亲水性聚合物反应，不过在本发明的某些实施方式中，使用了能与自身交联的稳定聚合物，从而形成交联的网络，把亲水性聚合物分子包埋在交联的网络中。在另一种实施方式中，除了稳定聚合物以外，涂层中还包含生物活性剂，用来代替亲水性聚合物或者还包含亲水性聚合物。生物活性剂可以是抗血栓形成剂、抗菌剂、抗癌剂、基因治疗剂、或其他药剂，其含量是在涂层所处条件下有效达到所需作用的量。这一般包括可归因于生物活性剂与稳定聚合物之间的相互作用的按时间释放作用。
从以下的详细说明，本发明所能够达到的进一步目的和优点将更加清楚。
                      发明的详细说明
在对实施例中所阐述的本发明优选的实施方式进行描述时，为了清楚起见，使用特定的术语。不过，本发明不打算仅限于所选择的特定术语，应当认为，每种特定的要素都包括所有技术上的等价物，它们以相似方式发挥作用，实现相似目的。
用于医用装置的水凝胶和含药涂层的化学结构和物理性质知之甚少，难以描绘。该领域中的研究都是依赖于针对具体的涂层组合物在有关条件下的性能而得出的经验性结论。因此，本发明涂层的特殊优点不能从现有技术中认识到。
本发明涂层是这样一种共混物，各组分在混合后不能彼此区别开来。这种涂层是一种复杂结构，可能具有一种物理形态或若干物理形态的组合。该涂层是这样一种材料，它在底物上形成薄的连续层，可以称之为膜。它可以是稳定聚合物和亲水性聚合物或生物活性剂、添加剂、和可能存在的残留溶剂共混在一起而形式的固体混合物。或者，该涂层可以是全固体溶液，是均匀分散于整个固体相的一种混合物，具有分子或离子水平上的同种性，或者涂层可以是溶解组分与混合组分的组合，例如聚合物涂层溶液与不溶性粒子混悬液的混合物。涂层可以是复合材料的形式，即具有由聚合物与其他成分的混合物或组合物所组成的一种结构，这些其他成分具有不同的形态和化学组成，并且基本上是彼此不溶的。可以称之为聚合物的基质，其中包埋有其他组分。涂层可以包含单独的层，是不连续的或被掺杂的，各自可以具有任意或若干这些形态。
因此，涂层的结构中掺杂了聚合物组分和其他涂层组分的分子，且分布均匀，属于固相混合物和溶液。在干燥过程中，聚合物估计可能变为缠结在一起，使水凝胶或稳定的基质具有延迟释放生物活性剂的所需特征。组分之间的关系是指活性试剂在稳定聚合物中的包埋，其结果是活性试剂不被增溶或从涂层中不被直接除去，像没有稳定聚合物一样，而且涂层充分黏附在底物上，足以经得起干燥处理和使用过程中遇到的湿润条件。
本发明的稳定聚合物是无毒的和生理学上可接受的。大多数适合的稳定聚合物可溶于有机溶剂，对水的亲和性较差，当与其他涂层组分涂在底物上时形成水不溶性涂层膜，在插入组织和从组织中除去的应用条件下，黏附在底物上或预涂在底物上。这种聚合物一般吸收小于约30％、优选为小于约10％自身重量的水。稳定聚合物的量和种类也必须适合于涂层在其因亲水性聚合物的水合作用而发生溶胀的过程中保持完整性。因此，该稳定聚合物稳定了亲水性聚合物和生物活性剂，并使它们包埋在被涂的表面。
亲水性组分是无毒的和生理学上可接受的。它可溶于有机溶剂，部分或全部可溶于水。它和其他涂层组分共同吸收和保持水分，湿润时溶胀，吸收至少相当于自身重量的水，优选为超过自身重量的五倍，最优选为超过自身重量的十倍，而形成在湿润时适度润滑的水凝胶。亲水性聚合物以及疏水性聚合物和水合剂的量和种类是易于选择的，以满足这些要求。这种亲水性聚合物是本领域所熟知的，普通技术人员能够容易地找到适当的亲水性聚合物，从一起形成水凝胶这个意义上来说，它们与稳定聚合物是相容的。
亲水性组分可以是本发明所引用的参考文献《聚合物科学与工程简明百科全书》Kroschwitz编(Wiley 1990)第458-59页中所论述的任意种类。诸如聚乙烯吡咯烷酮、聚乙二醇、聚氧乙烯、或聚乙烯醇等的聚合物是可接受的，单用或组合使用。适用的亲水性聚合物例子包括下列化合物的均聚物或共聚物：诸如具有极性侧基的乙烯基聚合物等的聚烯烃、N-乙烯基吡咯烷酮、N-乙烯基内酰胺、N-乙烯基丁内酯、N-乙烯基己内酰胺、苯乙烯磺酸钠单体、2-丙烯酰氨基-2-甲基丙烷磺酸、乙烯基磺酸钠、乙烯基吡啶、具有亲水性酯化基团的丙烯酸酯或甲基丙烯酸酯。其他亲水性聚合物包括聚醚、聚乙二醇、多糖、亲水性聚氨酯、聚羟基丙烯酸酯、聚甲基丙烯酸酯、和乙烯基化合物与羟基丙烯酸酯或丙烯酸的共聚物，只要存在适当的亲水性即可。其他例子包括葡聚糖、黄原胶、羟丙基纤维素、甲基纤维素、聚丙烯酰胺、和多肽。其他亲水性组分是本领域技术人员已知的。涂层中该组分的浓度和类型应足以吸收水分，并在湿润时变为润滑的，同时与稳定聚合物组分和(如果有的话)生物活性剂相容。
涂层中亲水性聚合物的浓度优选为该涂层或外底层的约10％至约98％、最优选为约70％至约90％。在多层涂层中，如果亲水性组分存在于顶层中，顶层中还可以可选地包括至多约10％或更多的疏水性聚合物。某些稳定聚合物的亲水性较小，这对疏水性聚合物上文所定义的某些稳定性质是有利的，某些疏水性聚合物具有较高的吸水性，因此或多或少量的特定组分都可以达到本发明目的。
可以涂上本发明的涂层的底物包括聚氨酯、聚氯乙烯、缩醛、聚乙烯、聚丙烯、聚酰胺、聚酯、硅酮、和金属，例如不锈钢、铂、金、镍、钛、镍-钛合金、铬、以及其他等等。本发明涂层的优点在不锈钢丝线、聚乙烯导管、和其他公知的难以涂覆的底物上表现的尤为明显。优选的装置包括针、导线、导管、外科器械、内窥镜检查用设备、丝线、移植片固定模、血管成形术气囊、伤口引流管、伤口敷料、动静脉分流器、胃肠管、尿道插入物、腹腔镜检查设备、小丸、和植入物。
优选的稳定聚合物是如本文所定义的和如普通技术人员可以理解的，例如根据《聚合物科学与工程简明百科全书》Kroschwitz编(Wiley1990)或《Kirk-Othmer化学技术简明百科全书》(Wiley 1985)有下列这些种类：
·丙烯酸类，例如丙烯酸和甲基丙烯酸及其酯的聚合物和共聚物，例如用于工业涂饰的ACRYLOID热塑性丙烯酸酯树脂，Rohm & Haas，Bulletin 82A37(1987)，特别是可与至少一种含有羧基、羟基、酰胺、或羟甲基的组分交联的丙烯酸类。下列具有所示官能团的ACRYLOID聚合物是优选的：AT-51(羟基)、AT-63(羟基)、AT-81(羧基)、和WR-97(羟基)。也可以使用可交联的丙烯酸乳液、例如RHOPLEX B-15J(Rohm &Haas)，和苯乙烯丙烯酸乳液、例如AROLON 820-W-49(Reichhold)。
·氨基树脂，特别是三氰聚胺，和衍生物，例如甲基化或丁基化的衍生物，包括六甲氧基甲基三氰聚胺(HMMM)。
·酚醛树脂。
·环氧树脂，特别是固化环氧聚合物，例如EPOTUF 38-505(Reichhold)，优选那些用聚酰胺固化者，例如EPOTUF 37-618(Reichhold)。
·乙烯基聚合物，特别是乙酸乙烯酯、乙烯基缩醛，例如聚乙烯丁缩醛，和乙烯乙酸乙烯酯共聚物。
其他适当的具有所要求的特征的聚合物对普通技术人员来说是很清楚的。聚合物优选地(但不是必需)含有反应性基团或反应点，例如羟基、一、二和叔胺、诸如羧基、酰胺的酸、或其他代表化学反应点的基团。在丙烯酸的情况下，这是指具有可交联的“官能度”。聚合物和化学反应点能够形成吸引力，例如氢键，朝向医用装置表面，也朝向亲水性聚合物和/或生物活性剂。这些键是非常强的，为涂层提供了所需的粘性和柔韧性，估计可以不需要共价、离子、或其他连接。
对金属等底物来说，具有反应性基团的聚合物是优选的。不过，使用缺乏这类基团的聚合物也是有效的，例如丙烯酸或苯乙烯共聚物。
反应性基团还能够反应形成交联的基质，或者有助于形成交联的基质。如果需要的话，可以加入交联剂，例如脲醛树脂、三氰聚胺、异氰酸酯、酚醛塑料、以及其他等等，以便与聚合物链上的化学反应点发生相互作用，使本发明的聚合物自身交联。或者，交联剂可以与稳定聚合物自身反应，形成交联的基质，使亲水性聚合物陷入其中，从而形成粘性、柔韧的涂层。交联确保了在涂上后面的层时溶剂不会过度侵蚀和降解聚合物层，因此可用于提高粘性。
本发明的涂层可以用缺乏反应点的聚合物制备，例如丙烯酸或苯乙烯聚合物或共聚物。同样，涂层可以不进行交联。不过，为了达到按照本发明的高度粘性和柔韧性，比起由具有反应点的聚合物制成的层和交联的层来，这类涂层可能需要更大的涂层厚度。例如，由具有反应性基团的聚合物制成的交联涂层可以厚约二至约十微米，相形之下，顶层为水凝胶层的丙烯酸苯乙烯共聚物涂层的总厚度约为30-40微米。
如实施例所示，即使在进行黏附和弯曲试验时，本发明涂层也极为持久耐用。这种增强了的粘性和柔韧性是令人惊奇的结果。本发明的涂层可以涂在医用装置或其他装置的表面上，具有足够的厚度和持久性，在涂层装置的整个使用寿命内均能保持涂层具有所需的质量。本发明涂层与活体组织不发生反应，在血液中也不会导致血栓形成。
本发明涂层可以是薄的，约2至100微米，优选为小于约50微米，并且是连贯的，形成连续的表面层。它们长期浸泡在含水液体中也不易被除去，并可粘着在多种底物上。
涂层可以用多种工艺进行涂覆，例如浸渍、灌注、倾注、喷涂、刷涂、擦拭、或其他本领域技术人员已知的方法。涂层溶液具有较低粘度，一般小于100CPS，还具有良好的延展性质。优选地将涂层在高温下烘烤，一般为50℃至100℃，以除去有机溶剂。对某些表面，例如聚乙烯，还可以用等离子气体或其他电离处理法进行处理，以提高与涂层的相互作用和对底物的粘性。
除了诸如聚氨酯、聚酯、苯乙烯丁二烯共聚物、聚偏二氯乙烯、聚碳酸酯、和聚氯乙烯等的稳定聚合物以外，优选地在涂层的内层中还可含有聚合物，以提高对装置表面的粘性。U.S.S.N.08/791440公开了“用于医用装置表面涂层的粘合层”，在此全面引用，以便进一步详细描述。与现有技术中这些聚合物中的几种聚合物涂层相反，这些附加的聚合物对达到本发明的这些优点并不是必需的。
制备本发明涂层的方法是利用稳定、无毒的溶液，在储藏和操作时仅需少加谨慎即可。涂覆本发明涂层的方法可以包括：制备第一种有机溶液，其含有约0.01％至约30％(w/w)稳定聚合物，优选为约0.2％至约10％；将该溶液涂在底物表面上；蒸发溶剂(优选在高温下)；然后制备第二种有机溶液，其含有约0.001％至约30％(w/w)活性试剂，优选为约0.5％至约20％；将其涂在处理过的底物表面上；以及在室温或高温下蒸发溶剂。
稳定聚合物溶液也可以含有约0.01％至约20％活性试剂，优选为约0.1％至约5％。该活性试剂溶液也可以含有约0.01％至约30％稳定聚合物，优选为约0.1％至约10％。或者，该稳定聚合物和活性试剂可以制成单一溶液，在一步中涂覆。
增塑剂可以包括在稳定聚合物中，浓度为约0.01％至约20％，优选为约0.1％至约10％(w/w)。增塑剂可以是樟脑、蓖麻油、邻苯二甲酸二辛酯、乙酰三丁基柠檬酸酯、二丁基癸二酸酯、癸二酸、烷基树脂、聚乙二醇、聚丙二醇、邻苯二甲酸二丁酯、或其他普遍已知的增塑剂，单用或组合使用。根据需要，增塑剂可以加入到亲水性聚合物溶液或稳定聚合物溶液中，以增强涂层的柔韧性，当所要涂覆的物体在使用过程中容易弯曲时，这样做是优选的。不过，按照本发明，缺乏这类附加增塑剂的涂层组合物也可达到适当的柔韧性。
用于稳定和使聚合物具有粘性的溶剂包括有机溶剂，例如酮、酯、甲苯、内酯、二甲基甲酰胺、卤代溶剂、四氢呋喃、二烷、胺、乙二醇丁基醚、乙酸烷基酯、乙腈、和其他普遍已知的有机溶剂。低毒的溶剂是优选的。溶剂中包括少量羟基、如醇，和水分，对本发明的涂层和方法没有明显有害的影响。用于亲水性聚合物的溶剂包括大部分上述溶剂以及醇、乙酸、和类似溶剂。可以选择一种溶剂系统，它能够将涂层的所有成分溶解在均匀的溶液中，在涂层中能起到助溶剂的作用，并且是无毒的。如果需要的话，可以选择一种溶剂与特定底物表面发生相互作用，以提高粘性。
在本发明的一种实施方式中，所要涂上涂层的物体具有包含稳定聚合物的聚合物表面，由于能将润滑的亲水性聚合物(或顶层)直接涂在物体的聚合物表面上，内层或基层就没有必要使用“活性”溶剂。在该实施方式中，术语“活性溶剂”被定义为助溶剂，它对于聚合物或包含聚合物表面的聚合物混合物、或在混合的聚合物底物情况下的至少一种或几种聚合物，以及对于涂层聚合物来说均为一种助溶剂。
本发明的亲水性含药涂层在被含水溶液或低级醇(分别例如体液或者乙醇或甲醇)润湿后是润滑性很高的，不过在干燥时它们基本上是不润滑的。因此，本发明涂层的植入物不保持光滑性，有利于操作和制备，但是植入时变得润滑，以保护患者。涂层的润滑性可以在极润滑至不润滑的范围内根据需要调节，通过调节亲水性聚合物与稳定聚合物的比例可以实现。
按照本发明的涂层可以涂在医用装置或其他装置的表面上，具有足够的厚度和持久性，在涂层装置的整个使用寿命内保持涂层具有所需的质量。本发明涂层与活体组织不发生反应，在血液中也不会导致血栓形成。
本发明的涂层用于诸如医用植入物等装置的表面上具有有利的特征。涂层可以是亲水性的，在含水环境中吸收水分并溶胀，成为水凝胶，因此涂层具有润滑性质，湿润时比干燥时光滑得更显著。
多种生理学上活性的试剂均可以加入到水凝胶涂层中。可能是为了改善通常在植入医用装置表面上所遇到的问题，而加入这类试剂。例如，可以向水凝胶系统中加入抗血栓形成剂，如肝素-季铵配合物。可以向水凝胶系统中加入抗微生物剂例如各种银化合物、季铵化合物如苯扎氯铵、苯酚衍生物如麝香草酚、和抗生素例如庆大霉素、诺氟沙星、和利福霉素。水凝胶涂层也可以用作药库，用于目标药物的释放。可以加入诸如DNA的物质或诸如merbarone或甲氨蝶呤的抗癌剂。
加入生物活性剂的方法可以是在进行涂层之前溶解或分散在涂层溶液中，或者浸渗在涂层中。银盐的分散方法可以是就地从可溶性原料组分中生成盐，或者利用本领域技术人员已知的方法分散不溶性组分。很多有机试剂可以直接溶解在涂层液体中。直接可溶于本发明溶剂中的试剂是例如merbarone、诺氟沙星的游离碱形式和庆大霉素。为了可溶于本发明的溶剂中，一般呈离子或通常可得到其盐形式的其他试剂通常必须转化为有机盐。例如，硫酸庆大霉素可以转化为月桂基硫酸盐，后者易溶于本发明的溶剂中。肝素钠通常转化为季铵化合物的盐，例如苯扎氯铵，该盐易溶于本发明的溶剂中。甲氨蝶呤钠可以转化为季铵化合物的盐，例如苯扎氯铵，该盐易溶于本发明的溶剂中。本领域技术人员将会想到其他适合于完成本发明的组合。
因为各组分可以是不同的，本发明的方法有利于控制润滑性、稳定性、溶胀、柔韧性、粘性、和抗湿磨能力。因此，涂层的这些特征可以针对不同底物和应用进行调节。因为本发明的溶液具有良好的储藏稳定性，并在数月或数年期间内保持基本上没有沉淀产生，该方法也有利于一次性制备多种涂层用溶液混合物，用来在以后涂覆底物。或者，亲水性和疏水性稳定聚合物、和其他组分甚至可以在单一的溶液中制备。
几乎所有的聚合物从溶液中沉积在涂覆物表面上，在溶剂被蒸发后，聚合物保持在涂覆的层中。可以选择蒸发的持续时间和温度，以使涂层稳定，并实现被涂表面与涂覆层之间的粘合。
优选地，在多层或多重的实施方式中，外层溶液含有一定量的“活性”溶剂(即助溶剂)用于外层成分以及内层成分。活性溶剂本身使外层溶液渗透进入内层，被认为是引起了两层组分在分子水平上进行混合。
人们认为，这种分子混合仅包含物理混合，而没有化学反应。无论如何，在一种优选的实施方式中，相对于外层的外表面而言，在涂层中的亲水性聚合物和稳定聚合物之间存在高度的分子间混合，特别是在多层涂层中，在涂层的内层和外层之间的界面上存在这种混合。在实际情况中，调节溶剂混合物的活性，使外层渗透进入内层的程度在有用的范围内。例如，如果外层溶剂混合物对内层的活性过高，那么渗透进入内层过多，外层在湿润时将不够润滑。相反，如果外层溶剂对内层的活性不足，那么外层渗透进入内层过少，涂层容易受湿磨作用从内层中除去。
在本发明的一种实施方式中，润滑的亲水层和/或稳定聚合物和/或生物活性剂直接涂在聚合物表面上，使用一种助溶剂作为活性溶剂，既用于溶解可塑性底物聚合物或聚合物混合物或在混合的聚合物底物情况下的至少一种或几种聚合物，也用于溶解涂层中的涂层聚合物。干燥后，顶层聚合物层被部分包埋在聚合物表面内。在两层系统的情况下，涂覆过程中所用的溶剂可能活性过高，使顶层渗透进入聚合物表面，并达到涂覆层似乎已被高度交联的程度。这样防止了顶层在被含水液体湿润时，变得足够溶胀和光滑。在生物活性剂的情况下，它可能暴露不足，不能提供生理作用。溶剂混合物也可能活性太低，使涂层不足以抵抗湿磨，而容易被除去。
可用在本发明中的活性溶剂可以是个别的溶剂或含有两种或多种溶剂的溶剂混合物。在溶剂混合物的情况下，混合物中的一种或几种溶剂可以是活性的，而混合物中的其他溶剂可以是无活性的。无论如何，溶剂或溶剂混合物都能溶解或至少分散亲水性涂层聚合物和/或生物活性剂。在活性试剂被分散而不是被溶解的情况下，会达到这样一种状态，在所有溶剂留在涂层之前，活性试剂进入溶液。在干燥阶段，活性试剂处在溶液中，此间溶剂也渗透了聚合物表面的底物聚合物。因此，在底物聚合物和水凝胶聚合物之间可能发生分子间混合。
可用在本发明中的活性溶剂例子包括丁内酯、醇、二甲基乙酰胺、和n-甲基-2-吡咯烷酮。这些溶剂和其他溶剂导致可塑性底物或内层发生不同程度的溶胀，情况可能如此。
在用主观方法试验时，本发明的水凝胶涂层在湿润时比湿润的涂有润滑脂玻璃更光滑，在干燥时不如干燥玻璃光滑。使水流过涂层，并在湿润时贴紧手指进行摩擦，测定发现，本发明涂层具有抗湿磨除去的作用。粘上胶带，剧烈地拉去胶带，然后湿润涂覆的底物，检查粘胶带的位置是否还保留有润滑的涂层，测定发现，本发明涂层在干燥时具有高度的粘性。当储藏在水中较长时间后，本发明涂层保持了粘性和一致性，既没有脱皮、溶解，也没有分裂。
底物、聚合物、和溶剂的适当组合对技术人员来说将是显而易见的。一般来说，提高稳定聚合物对水溶性聚合物的比例，将增加对湿摩的耐受性，减少润滑性。在高比例下，水凝胶是不润滑的，涂层甚至能够被制成疏水性的。在低比例下，水凝胶在水中溶胀更多，对湿摩擦的耐受性较低。水凝胶可能变为暂时的，或者容易洗掉。
可以控制稳定聚合物与亲水性聚合物和/或生物活性剂之间的相互作用，以促进分子缠结。例如，溶剂的选择起到重要作用。如果所选择的溶剂允许水凝胶层渗透进入底物层，则发生界面层上的分子缠结。这导致对湿摩的耐受性增加，润滑性降低。在实施本发明时，本领域的技术人员可以考虑这些因素。
底物和与之有效的稳定聚合物制剂的例子列在下面。按照本发明的教导，很多其他的组合对普通技术人员来说也将是显而易见的。
聚氨酯：羟基官能的丙烯酸酯聚合物；丙烯酸分散聚合物；苯乙烯丙烯酸共聚物；环氧加聚酰胺
聚乙烯：羧基官能和羟基官能的丙烯酸酯聚合物加三氰聚胺加环氧树脂
硅酮：羧基官能的丙烯酸酯聚合物加环氧树脂
聚氯乙烯：羟基官能的丙烯酸酯聚合物；聚乙烯丁缩醛加酚醛树脂
缩醛：乙烯乙酸乙烯酯共聚物；聚乙烯基乙酸酯共聚物
玻璃：乙烯丙烯酸共聚物加三聚氰胺树脂加丙烯酸酯聚合物加羟基官能的丙烯酸酯聚合物
不锈钢：环氧加聚酰胺，乙烯丙烯酸共聚物；具有羧基官能的丙烯酸酯聚合物加环氧树脂
下列实施例显示如何使用本发明。除非另有指示，所有的量均以克给出。
实施例1
聚氨酯管用浸渍法涂覆下列溶液，然后在85℃下干燥45分钟。PVP                                          0.289苯甲醇                                       1.563乙醇                                         2.801环己酮                                       5.347具有羟基官能的丙烯酸酯聚合物                 0.050二甲苯                                       0.050
结果：用小刀沿涂层割线，然后将涂层浸入水中，用手指剧烈摩擦切口，测试涂层的粘性。湿润摩擦试验后没有丧失粘性(即向后脱皮)。下面测试涂层的干燥粘性，在涂层上紧紧地压上Universal Tape 83436带(United Stationers Supply，Co.)，然后迅速地揭去带子。涂层没有被这项测试除去。样本在带子测试中没有表现出粘性丧失。涂层在湿润时具有良好的润滑性。
实施例2
经氧等离子体处理过的聚乙烯管用浸渍法涂覆下列溶液，然后在85℃下干燥45分钟。5％(w/w)乙烯丙烯酸共聚物的THF溶液                  15.0环己酮                                             4.0羟基官能的丙烯酸酯聚合物                           0.24三氰聚胺树脂                                       0.0680％(w/w)异氰酸酯聚合物的THF溶液                   0.32三氯乙酸                                           0.20
烘箱干燥后，样本用浸渍法涂覆下列溶液，然后在80℃下干燥1小时。THF                                                74.00二甲苯                                             0.25具有羧基官能的丙烯酸酯共聚物                       13.88环氧树脂                                           0.75石油溶剂150溶剂                                    9.73丁基溶纤剂                                         1.39
下面，样本用浸渍法涂覆下列水凝胶溶液，然后在80℃下干燥1小时。丁内酯                                             1.80二甲基乙酰胺                                       1.20乙醇                                               8.75PVP                                                0.25THF                                                0.60二甲苯                                             0.05环氧树脂                                           0.10聚酰胺树脂                                         0.05
结果：如实施例1的测试证明，涂层显示出良好的干燥粘性、良好的润滑性、和良好的湿摩耐受性。
实施例3(对照)
本实施例将本发明的改进涂层与USP5,331,027的PVP-纤维素酯涂层进行比较，结果显示本发明涂层的粘性较为优异。将硅酮管样本用氧等离子体处理。然后用浸渍法涂覆下列溶液，然后在80℃下干燥120分钟。具有羧基官能的丙烯酸共聚物                         5.0石油溶剂150溶剂                                    3.5丁基溶纤剂                                         0.5THF                                                27.75环氧树脂                                           0.56二甲苯                                             0.19
下面，样本A用浸渍法涂覆与实施例2所用相同的水凝胶溶液。样本B用浸渍法涂覆下列溶液，供对照(USP5,331,027的PVP-纤维素酯制剂的一个例子)，然后在80℃下干燥2小时。PVP                                                31.74乙醇                                               462.01丁内酯                                             103.75环己酮                                             12.82硝基纤维素                                         0.008
结果：如实施例1方法测试这两种涂层样本。涂有与实施例2相同的水凝胶的样本A显示出良好的湿润与干燥粘性和对湿润脱皮的耐受性，并且是润滑的。在相同的测试条件下，涂有PVP-纤维素酯水凝胶溶液的样本B没有干燥粘性，湿润脱皮测试也不成功，说明本发明涂层优于现有技术。
实施例4
用浸渍法将下列溶液涂在聚氨酯管上，然后在85℃下干燥45分钟。乙醇                                               1.88苯甲醇                                             3.36环己酮                                             6.42PVP                                                0.35二甲苯                                             0.10具有羟基官能的丙烯酸共聚物                         0.10
结果：如实施例1的测试证明，该例具有良好的湿润滑性、湿润粘性、对湿摩的耐受性、和干燥粘性。
实施例5
用浸渍法将下列溶液涂在聚氨酯管上，然后在85℃下干燥45分钟。乙醇                                               1.88苯甲醇                                             3.36环己酮                                             6.42PVP                                                0.35可交联的丙烯酸含水乳剂(46％固体)                   0.20
结果：如实施例1的测试证明，该样本具有良好的湿润与干燥粘性、良好的脱皮耐受性，并且是润滑的。
实施例6
PVC管样本用浸渍法涂覆下列溶液，然后在85℃下干燥45分钟。乙醇                                               1.88苯甲醇                                             3.36环己酮                                             6.42PVP                                                0.35二甲苯                                             0.10具有羟基官能的丙烯酸酯聚合物                       0.10
结果：如实施例1的测试证明，该样本具有良好的润滑性、湿润粘性、湿摩擦耐受性、和干燥粘性。
实施例7
PVC管用浸渍法涂覆下列溶液，然后在85℃下干燥30分钟。乙醇                                               1.88苯甲醇                                             3.36环己酮                                             6.42PVP                                                0.49二甲苯                                             0.15具有羟基官能的丙烯酸酯聚合物                       0.15
结果：如实施例1的测试证明，该样本具有良好的湿润与干燥粘性和湿润脱皮/摩擦耐受性，不易除去，并且是润滑的。
实施例8(对照)
本实施例将本发明涂层与USP5,331,027的PVP-纤维素酯涂层进行比较，结果显示本发明涂层的粘性较为优异。涂有脂族聚氨酯的Nitinol线(镍-钛合金)样本涂覆下列溶液的一种或另一种，然后在85℃下干燥1小时。
样本A：本发明工艺乙醇                                               1.88苯甲醇                                             3.36环己酮                                             6.42PVP                                                0.49二甲苯                                             0.15具有羟基官能的丙烯酸酯聚合物                       0.15
样本B：现有技术(即5331027)乙醇                                               1.88苯甲醇                                             3.36环己酮                                             6.42PVP                                                0.350.0625％硝基纤维素的环己酮溶液                     0.14
结果：按照本发明的样本A具有良好的湿润与干燥粘性、良好的光滑性和良好的湿摩耐受性。样本B的湿润粘性和湿摩耐受性较差(在湿润时整个涂层容易擦去)。这种对比证明，本发明优于现有技术。
实施例9
用浸渍法将下列溶液涂在缩醛表面上，空气干燥10分钟，再在85℃下用烘箱干燥30-60分钟。乙烯乙酸乙烯酯共聚物                               1.5THF                                                10.8环己酮                                             2.7
然后，用下列水凝胶溶液涂覆样本，空气干燥10分钟，再在85℃下用烘箱干燥30-60分钟。PVP                                                0.75乙醇                                               11.40苯甲醇                                             2.85
结果：该样本是润滑的，抗湿擦除，并具有良好的湿润与干燥粘性。
实施例10
重复实施例9，只是涂层用水凝胶溶液是由下列组成的：聚乙酸乙烯酯                                       4.0乙醇                                               12.8苯甲醇                                             3.2
结果：该样本是润滑的，抗湿擦除，并具有良好的湿润与干燥粘性。
实施例11
将下列涂层溶液刷涂在玻片上，然后在85℃下干燥30分钟。预涂层-  5％(w/w)乙烯丙烯酸共聚物的THF溶液         15.0
     环己酮                                    4.0
     羟基官能的丙烯酸酯共聚物                  0.24
     三氰聚胺树脂                              0.06
      80％(w/w)异氰酸酯                        0.32
      三氯乙酸                                 0.20
然后，涂以下列涂层溶液，然后在85℃下干燥60分钟。基本涂层- 30％(w/w)丙烯酸酯聚合物的甲苯溶液        9.9
      环己酮                                   8.8
      苯甲醇                                   4.8
      聚氨酯                                   0.86
      THF                                      7.74
      羟基官能的丙烯酸酯聚合物                 1.80
      三氰聚胺树脂                             0.45
      三氯乙酸                                 0.1
      二甲苯                                   1.76
      丁醇                                     0.49
然后，涂以实施例9的水凝胶，然后在85℃下用烘箱干燥30-60分钟。
结果：该样本具有良好的粘性和润滑性。
实施例12
将下列涂层溶液涂在聚氨酯管上，然后在85℃下干燥60分钟。乙醇                                               18.8苯甲醇                                             33.6环己酮                                             64.2PVP                                                3.5具有羧基官能的丙烯酸酯聚合物                       1.11石油溶剂150溶剂                                    0.78丁基溶纤剂                                         0.11THF                                                1.67环氧树脂                                           0.25二甲苯                                             0.08
结果：该样本是润滑的，抗湿磨，并具有良好的粘性。
实施例13
将下列溶液涂在聚氨酯管上，然后在85℃下干燥18小时。乙醇                                               1.8苯甲醇                                             3.36环己酮                                             6.42PVP                                                0.35苯乙烯丙烯酸共聚物                                 0.20水                                                 0.20
结果：该样本是润滑的，抗湿磨，并具有良好的粘性。
实施例14
将不锈钢线涂以下列预涂层溶液，然后在85℃下干燥60分钟。5％(w/w)乙烯丙烯酸共聚物的THF溶液                  15.0环氧树脂                                           0.17二甲苯                                             0.06THF                                                0.23
然后，将样本涂以下列溶液，然后在85℃下干燥1小时。环氧树脂                                           0.37聚酰胺树脂                                         0.18二甲苯                                             0.20THF                                                6.24PVP-乙酸乙烯酯共聚物                               0.25乙醇                                               0.25环己酮                                             1.00三十二烷基甲基肝素铵                               0.10
该样本设计成不润滑的。它具有良好的湿润和干燥粘性。
实施例15
将下列溶液用浸渍法涂在聚氨酯管上，然后在85℃下干燥60分钟。乙醇                                               1.88苯甲醇                                             3.36二甲基乙酰胺                                       4.00环己酮                                             6.42PVP                                                0.35Merbarone(非离子抗癌剂)                            0.07具有羟基官能的丙烯酸共聚物                         0.15二甲苯                                             0.15
结果：这种含药涂层样本具有良好的湿润与干燥粘性，并且抗湿磨。
实施例16
将下列溶液涂在5Fr.聚氨酯管上，然后在85℃下干燥20分钟。
溶液16A：甲苯                                               4.00二甲苯                                             0.15IPA                                                3.00羟基官能的丙烯酸共聚物                             0.15环己酮                                             1.0050％(w/w)PVP/VA的乙醇溶液                          0.50肝素苯甲烃铵                                       0.10
溶液16B：甲苯                                               7.00IPA                                                2.00环己酮                                             2.0050％(w/w)PVP/VA的乙醇溶液                          0.50具有羟基官能的丙烯酸酯聚合物                       0.20二甲苯                                             0.20
溶液16C：Gensolve 2004                                      7.0环己酮                                             1.0三十二烷基甲基肝素铵                               0.2050％(w/w)PVP/VA的乙醇溶液                          0.50羟基官能的丙烯酸共聚物                             0.20二甲苯                                             0.20
将溶液16A、16B和16C用浸渍法涂在聚氨酯管上，然后在85℃下干燥20分钟。接着，按照附在后面的凝固试验测试样本的抗凝固活性。
结果：当暴露在没有涂层的聚氨酯管中时，血浆在数分钟内凝固。而即使在实施例16的任意三种涂层样本中暴露过夜，血浆也不凝固。这证明了涂层具有较强的抗血栓形成活性。
实施例17
将不锈钢线(0.025”直径)用浸渍法涂以下列溶液，然后在85℃下干燥60分钟。5％(w/w)聚乙烯丙烯酸共聚物的THF溶液                10.0环氧树脂                                           0.113二甲苯                                             0.038THF                                                0.15环己酮                                             2.0
接着，不锈钢线用浸渍法涂覆与实施例16A相同的含羟基肝素涂层溶液，然后在85℃下干燥20分钟。然后，使用与实施例16所用相同的方法测试涂层样本的抗凝固活性。
结果：暴露在没有涂层的不锈钢中的血浆在数分钟内凝固。暴露在涂层样本中的血浆保持不凝固过夜，证明了涂层具有较强的抗血栓形成活性。
实施例18
制备下列溶液。二甲苯                                             0.60THF                                                34.52环氧树脂                                           0.90聚酰胺                                             0.48DNA                                                5.00PVP                                                3.10乙醇                                               22.05
然后，将多种抗微生物剂与8.0gm上述溶液混合。庆大霉素游离碱                                     0.08-溶解诺氟沙星游离碱                                     0.08-溶解利福霉素SV                                         0.09-溶解磺胺嘧啶银                                         0.08-分散
将每种溶液涂在5Fr聚氨酯管上，然后在85℃下干燥45分钟。然后，用对E.epi.的“抑制区”试验测试涂层样本的抗微生物活性。各自测试两份样本。结果：    抗微生物剂                               抑制区(cm)
      庆大霉素游离碱                           1.9/2.0
      诺氟沙星游离碱                           2.5/2.5
      利福霉素SV                               4.5/4.5
      磺胺嘧啶银                               0.7/0.7
这些结果证明，多种抗微生物剂都能加入到本发明的涂层中，同时表现出较强的抗微生物活性。预期其他类型的药剂也能加入到涂层中，并且能够在表面涂层范围内发挥出它们的活性。例如，可向涂层中加入药剂，来治疗癌症或再狭窄患者。
实施例19
将聚氨酯管涂以下列溶液，然后在85℃下干燥20分钟。Gensolve 2004                                      7环己酮                                             150％(w/w)PVP-乙酸乙烯酯共聚物的乙醇溶液            0.550％羟基官能的丙烯酸酯聚合物的二甲苯溶液           0.4硬脂基二甲基苄基肝素铵                             0.2
用实施例16的凝固试验测试样本。血浆即使暴露过夜也不凝固。
实施例20(对照)
制备下列溶液。
溶液20A：RS硝基纤维素                                       25.2甲苯                                               11.3乙酸丁酯                                           17.0乙酸乙酯                                           34.8邻苯二甲酸二丁酯                                   6.6樟脑                                               4.82-羟基-4-甲基二苯甲酮                              0.3
然后，制备下列溶液。20B是美国专利5,001,009技术的代表。
溶液20B：溶液20A                                            31.9环己酮                                             22.8苯甲醇                                             22.8乙酸乙酯                                           17.8铁蓝RS分散系(佩恩色)                               2.3棕色氧化物分散系(佩恩色)                           0.7TiO2分散系(佩恩色)                                1.6
溶液20C：这是本发明的代表。THF                                                67.5聚氨酯树脂                                         2.5环己酮                                             10.0聚乙烯丁缩醛                                       3.6酚醛树脂                                           2.8
然后，将溶液20B和20C刷涂在未经处理的平整的惰性聚乙烯表面上，然后在85℃下干燥60分钟。已知着色剂是不会影响到润滑性或粘性的。聚氨酯是这种类型涂层的可选成分，该涂层不必具有柔韧性。冷却至室温后，从惰性塑料表面上剥去涂层，以评价不损伤底物的柔韧性。即使如实施例2进行等离子体处理，这样的涂层也足以黏附大多数底物，或者预涂层适合于更大面积的涂覆。
结果：20B样本(现有技术)裂开并破碎成脆性小片。20C样本(本发明技术)平坦地剥下，并且是非常柔韧的。它可以大幅度弯曲，而不裂开或断裂。它保持为连续的有弹性的膜，可以伸展而不断开。剥离的涂层不裂开的柔韧性，预示具有涂覆底物所需的粘性和柔韧性。与剥离涂层的裂开相反，柔韧性预示涂层失败的可能性降低，尤其是涂在较小直径的底物和那些预计会受到大幅度弯曲的底物上。这证明了本发明的柔韧性优于常规涂层。
实施例21(对照)
制备下列溶液。
溶液21A：溶液20A                                            37.7环己酮                                             19.5苯甲醇                                             10.610％(w/w)聚氨酯树脂的THF溶液                       19.050％(w/w)羟基官能的丙烯酸酯聚合物                  10.00的二甲苯/丁醇(78/22)溶液三氯乙酸                                           0.17.5％(w/w)铁蓝分散系(佩恩色)                       1.032.0％(w/w)TiO2分散系(佩恩色)                      1.411％(w/w)棕色氧化物分散系(佩恩色)                  0.7
溶液21B：THF                                                74.0二甲苯                                             0.25具有羧基官能的丙烯酸酯聚合物                       13.88环氧树脂                                           0.75石油溶剂150溶剂                                    9.73丁基溶纤剂                                         1.39
将溶液用浸渍法涂在0.020英寸不锈钢线圈导向线的独立样本上，在85℃下干燥60分钟。测试两种导向线样本的方法是将它们紧紧地缠绕在1/4”心轴上，检查涂层的裂开情况。
结果：涂有21A溶液(现有技术)的导向线样本有裂开，裂缝之间的部分是直的。涂有本发明溶液的样本没有裂开，当绕着心轴弯曲时，具有平滑、连续的弧形。这证明了本发明工艺的柔韧性更高，说明与现有技术相比，提高了涂层底物的柔韧性，尤其是在较薄(即＜.050”直径)的装置上，设计要求是柔韧的，并且必须能够在使用过程中实现多重、较大幅度的弯曲。
实施例22
将下列溶液用浸渍法涂在PVC管上，然后空气干燥60分钟。
溶液22A：聚氨酯树脂                                         3.0甲基乙基酮                                         42.9N-甲基-2-吡咯烷酮                                  15.0THF                                                32.6酚醛树脂                                           5.1聚乙烯丁缩醛树脂                                   0.3丁醇                                               1.1
然后，将样本用浸渍法涂以下列溶液，然后在80℃下干燥1-2小时。
PVP                                            4.0
乙醇                                           34.5
苯甲醇                                         30.0
异丙醇                                         30.0
聚亚乙基二醇400                                1.5
样本具有良好的湿润滑性和良好的粘性。
本说明书中阐述和论述的实施方式仅仅是用来教给本领域的技术人员据发明人所知的实施和使用本发明的最佳方式。本说明书中的所有内容都不应当被认为是对本发明范围的限制。在不背离本发明的前提下，可对本发明的上述实施方式作修改和变化，而如上所指出的，这一点是可以被本领域技术人员所领会的。因此可以理解的是，在权利要求书及其等同替换的范围内，可以并非如具体所述的那样实施本发明。

Claims (29)

1.一种涂在医用装置表面上的涂层，该涂层包含：
(a)一种稳定聚合物，选自可交联的丙烯酸聚合物和甲基丙烯酸聚合物、乙烯丙烯酸共聚物、苯乙烯丙烯酸共聚物、乙酸乙烯酯聚合物和共聚物、乙烯基缩醛聚合物和共聚物、环氧树脂、三聚氰胺树脂、其他氨基树脂、酚醛聚合物、及它们的共聚物、和它们的组合；和
(b)一种活性试剂，选自亲水性聚合物、生物活性剂、和它们的组合，所选择的亲水性聚合物要与该稳定聚合物相互作用，以形成润滑的水凝胶，
该活性试剂被包埋在该稳定聚合物中，以使涂层在干燥和湿润情况下都黏附在表面上，即使表面发生弯曲也保持粘性而不裂开。
2.根据权利要求1的涂层，其中的稳定聚合物是可交联的，该涂层进一步包含一种用于该稳定聚合物的交联剂。
3.根据权利要求1的涂层，其中的交联剂选自环氧树脂、三聚氰胺树脂、其他氨基树脂、和酚醛树脂。
4.根据权利要求1的涂层，其中该稳定聚合物具有至少一种选自含有羧基、羟基、胺、或羟甲基官能团的丙烯酸组分。
5.根据权利要求1的涂层，其中该医用装置的表面包含的一种材料选自不锈钢、镍、金、铬、镍钛合金、铂、另一种金属、硅酮、聚乙烯、其他聚烯烃、聚酯、其他塑料、玻璃、聚氨酯、缩醛、聚酰胺和聚氯乙烯。
6.根据权利要求1的涂层，其中的医用装置选自针、导向线、导管、外科器械、内窥镜检查用设备、丝线、移植片固定模、血管成形术气囊、伤口引流管、伤口敷料、动静脉分流器、胃肠管、尿道插入物、腹腔镜检查设备、小丸、和植入物。
7.根据权利要求1的涂层，其中该稳定聚合物是一种可交联的丙烯酸酯，选自甲基丙烯酸甲酯、甲基丙烯酸丁酯、甲基丙烯酸异丁酯、甲基丙烯酸乙酯、丙烯酸甲酯、丙烯酸乙酯、丙烯酸、甲基丙烯酸、甲基丙烯酸苯乙烯酯、和丙烯酸苯乙烯酯、和它们的共聚物。
8.根据权利要求1的涂层，其中的生物活性剂选自药剂、盐、渗透剂、和低聚核苷酸。
9.根据权利要求1的涂层，进一步包含一种添加剂，选自表面活性剂、着色剂、和增塑剂。
10.根据权利要求1的涂层，其中的涂层包含内层和外层，它们具有不同比例的该稳定聚合物和该活性试剂。
11.根据权利要求1的涂层，其中的涂层厚度小于约50微米。
12.根据权利要求1的涂层，其中的活性试剂是一种亲水性聚合物，该涂层是一种水凝胶。
13.根据权利要求1的涂层，其中的活性试剂是一种生物活性剂。
14.根据权利要求12的涂层，其中的涂层包含一种生物活性剂。
15.根据权利要求1的涂层，其中的涂层涂覆在不锈钢上后，能抗湿磨，即使弯曲也保持粘性。
16.根据权利要求1的涂层，其中的稳定聚合物的选择与底物中是否含有该稳定聚合物无关。
17.一种涂覆具有惰性表面的医用装置的方法，该方法包括：
将包含一种稳定聚合物的涂层液体涂在表面上，该稳定聚合物选自可交联的丙烯酸聚合物和甲基丙烯酸聚合物、乙烯丙烯酸共聚物、苯乙烯丙烯酸共聚物、乙烯基乙酸酯聚合物和共聚物、乙烯基缩醛聚合物和共聚物、环氧树脂、三聚氰胺树脂、其他氨基树脂、酚醛聚合物、及它们的共聚物、和它们的组合，
涂覆包含一种活性试剂的涂层液体，该活性试剂选自亲水性聚合物、生物活性剂、和它们的组合，所选择的亲水性聚合物要与该稳定聚合物相互作用，以形成润滑的水凝胶，
干燥以除去液体，使该活性试剂包埋在该稳定聚合物中，该涂层在干燥和湿润情况下都黏附在表面上，即使表面发生弯曲也保持粘性。
18.根据权利要求17的涂层，其中单一的涂层液体既包含该稳定聚合物，也包含该活性试剂。
19.根据权利要求17的方法，其中该涂覆步骤包括浸渍、喷涂、刷涂、或擦拭。
20.根据权利要求17的方法，在涂覆步骤之前，进一步包括将该医用装置的表面用等离子气体或其他电离处理法进行预处理。
21.根据权利要求17的方法，其中的干燥包括将涂层加热到至少约50℃。
22.一种涂覆包含一种表面聚合物的医用装置的方法，该表面聚合物选自可交联的丙烯酸聚合物和甲基丙烯酸聚合物、乙烯丙烯酸共聚物、苯乙烯丙烯酸共聚物、乙烯基乙酸酯聚合物和共聚物、乙烯基缩醛聚合物和共聚物、环氧树脂、三聚氰胺树脂、其他氨基树脂、酚聚合物及其共聚物、和它们的组合；该方法的步骤包括涂覆一种涂层液体和一种活性试剂，该涂层液体包含一种能够侵蚀装置表面的溶剂，该活性试剂选自亲水性聚合物、生物活性剂、和它们的组合，所选择的亲水性聚合物要与该表面聚合物相互作用，以产生有润滑性的水凝胶，然后干燥涂层液体，使该活性试剂包埋在该表面聚合物中，该涂层在干燥和湿润情况下都黏附在表面上，即使该医用装置发生弯曲也保持粘性。
23.用于涂覆医用装置的试剂盒，该试剂盒包含：
一种含稳定聚合物的液体，该稳定聚合物选自可交联的丙烯酸酯聚合物和甲基丙烯酸聚合物、乙烯丙烯酸共聚物、苯乙烯丙烯酸共聚物、乙烯基乙酸酯聚合物和共聚物、乙烯基缩醛聚合物和共聚物、环氧树脂、三聚氰胺树脂、其他氨基树脂、酚醛聚合物、及它们的共聚物、和它们的组合；和
一种含活性试剂的液体，该活性试剂选自亲水性聚合物、生物活性剂、和它们的组合，所选择的亲水性聚合物要与该稳定聚合物相互作用以形成光滑的水凝胶，
这两种液体是同一液体或分离的，该稳定聚合物和该活性试剂的选择要能在医用装置上形成粘性、柔韧的涂层，该涂层具有湿润的和干燥的粘性。
24.权利要求23的试剂盒，其中的液体是分离的。
25.权利要求24的试剂盒，其中的包含活性试剂的液体进一步包含一种稳定聚合物。
26.权利要求24的试剂盒，其中的包含稳定聚合物的液体进一步包含一种活性试剂。
27.权利要求23的试剂盒，其中的一种或两种液体包含一种溶剂，该溶剂选自水、二甲苯、四氢呋喃、环己酮、乙醇、丁内酯、丁醇、三氯乙酸、苯甲醇、乙酸异丁酯、甲乙酮、石油溶剂150、甲苯、和丁基溶纤剂。
28.权利要求23的试剂盒，其中的稳定聚合物液体是一种含水的可交联的丙烯酸分散液。
29.权利要求23的试剂盒，包含一种液体，该液体包含一种用于该稳定聚合物的交联剂。
CN98806544.4A 1997-06-23 1998-06-22 粘性、柔韧的水凝胶和含药涂层 Pending CN1261288A (zh)

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Families Citing this family (303)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5811447A (en) 1993-01-28 1998-09-22 Neorx Corporation Therapeutic inhibitor of vascular smooth muscle cells
US6515009B1 (en) 1991-09-27 2003-02-04 Neorx Corporation Therapeutic inhibitor of vascular smooth muscle cells
US6099562A (en) * 1996-06-13 2000-08-08 Schneider (Usa) Inc. Drug coating with topcoat
US20020091433A1 (en) * 1995-04-19 2002-07-11 Ni Ding Drug release coated stent
US5674236A (en) * 1996-04-30 1997-10-07 Medtronic, Inc. Lancet for capillary puncture blood samples
US5997517A (en) 1997-01-27 1999-12-07 Sts Biopolymers, Inc. Bonding layers for medical device surface coatings
US6890546B2 (en) * 1998-09-24 2005-05-10 Abbott Laboratories Medical devices containing rapamycin analogs
EP1027074A1 (en) * 1997-10-28 2000-08-16 American Home Products Corporation Compositions and methods for delivery of genetic material
SE9704712D0 (sv) * 1997-12-17 1997-12-17 Astra Ab Medical device
US20020188037A1 (en) * 1999-04-15 2002-12-12 Chudzik Stephen J. Method and system for providing bioactive agent release coating
ATE219693T1 (de) * 1998-04-27 2002-07-15 Surmodics Inc Bioaktive wirkstoffe freisetzende beschichtungen
US6673053B2 (en) 1999-05-07 2004-01-06 Scimed Life Systems, Inc. Hydrophilic lubricity coating for medical devices comprising an antiblock agent
FR2796560A1 (fr) * 1999-07-21 2001-01-26 Inst Nat Sciences Appliq Procede de traitement d'un objet ou materiau, pour lui conferer une biocompatibilite, avec une faible adherence biologique
FR2796559B1 (fr) * 1999-07-21 2002-09-13 Inst Nat Sciences Appliq Procede de traitement d'un objet ou materiau, pour lui conferer une biocompatibilite, avec une faible adherence biologique
US7682647B2 (en) * 1999-09-03 2010-03-23 Advanced Cardiovascular Systems, Inc. Thermal treatment of a drug eluting implantable medical device
US20070032853A1 (en) * 2002-03-27 2007-02-08 Hossainy Syed F 40-O-(2-hydroxy)ethyl-rapamycin coated stent
US6790228B2 (en) * 1999-12-23 2004-09-14 Advanced Cardiovascular Systems, Inc. Coating for implantable devices and a method of forming the same
US7807211B2 (en) 1999-09-03 2010-10-05 Advanced Cardiovascular Systems, Inc. Thermal treatment of an implantable medical device
EP1104681A1 (en) * 1999-12-03 2001-06-06 Biomat B.V. Wire, tube or catheter with hydrophilic coating
US6908624B2 (en) * 1999-12-23 2005-06-21 Advanced Cardiovascular Systems, Inc. Coating for implantable devices and a method of forming the same
WO2001047572A2 (en) * 1999-12-29 2001-07-05 Advanced Cardiovascular Systems, Inc. Device and active component for inhibiting formation of thrombus-inflammatory cell matrix
AU2001253479A1 (en) * 2000-04-13 2001-10-30 Sts Biopolymers, Inc. Targeted therapeutic agent release devices and methods of making and using the same
US7682648B1 (en) 2000-05-31 2010-03-23 Advanced Cardiovascular Systems, Inc. Methods for forming polymeric coatings on stents
US6451373B1 (en) * 2000-08-04 2002-09-17 Advanced Cardiovascular Systems, Inc. Method of forming a therapeutic coating onto a surface of an implantable prosthesis
ATE547080T1 (de) 2000-08-30 2012-03-15 Univ Johns Hopkins Vorrichtungen zur intraokularen arzneimittelabgabe
DE60128817T2 (de) * 2000-09-12 2008-02-07 Union Carbide Chemicals & Plastics Technology Corp., Danbury Polymerische mischungen enthaltend ethylenoxid-copolymere
JP2002095736A (ja) * 2000-09-22 2002-04-02 Unitika Ltd 体内挿入医療用具及びその製造方法
JP2002095734A (ja) * 2000-09-22 2002-04-02 Unitika Ltd 潤滑性を有する医療用具及びその製造方法
US6953560B1 (en) 2000-09-28 2005-10-11 Advanced Cardiovascular Systems, Inc. Barriers for polymer-coated implantable medical devices and methods for making the same
US20050226993A1 (en) * 2000-10-03 2005-10-13 Nawrocki Jesse G Medical devices having durable and lubricious polymeric coating
US7807210B1 (en) 2000-10-31 2010-10-05 Advanced Cardiovascular Systems, Inc. Hemocompatible polymers on hydrophobic porous polymers
EP1347794A2 (en) * 2000-11-27 2003-10-01 Medtronic, Inc. Stents and methods for preparing stents from wires having hydrogel coating layers thereon
US6591970B2 (en) 2000-12-13 2003-07-15 Ecolab Inc. Water-activatable conveyor lubricant and method for transporting articles on a conveyor system
US6824559B2 (en) * 2000-12-22 2004-11-30 Advanced Cardiovascular Systems, Inc. Ethylene-carboxyl copolymers as drug delivery matrices
GB0100761D0 (en) 2001-01-11 2001-02-21 Biocompatibles Ltd Drug delivery from stents
US6630460B2 (en) * 2001-02-09 2003-10-07 Medtronic, Inc. Heparin compositions and methods of making and using the same
US7771468B2 (en) * 2001-03-16 2010-08-10 Angiotech Biocoatings Corp. Medicated stent having multi-layer polymer coating
DE10114247A1 (de) * 2001-03-22 2002-10-10 Heraeus Kulzer Gmbh & Co Kg Antibiotikum-/Antibiotika-Polymer-Kombination
US6780424B2 (en) * 2001-03-30 2004-08-24 Charles David Claude Controlled morphologies in polymer drug for release of drugs from polymer films
US20020146385A1 (en) * 2001-04-10 2002-10-10 Lin Tung Liang Ionic antimicrobial coating
US6764505B1 (en) 2001-04-12 2004-07-20 Advanced Cardiovascular Systems, Inc. Variable surface area stent
US6712845B2 (en) * 2001-04-24 2004-03-30 Advanced Cardiovascular Systems, Inc. Coating for a stent and a method of forming the same
US6656506B1 (en) * 2001-05-09 2003-12-02 Advanced Cardiovascular Systems, Inc. Microparticle coated medical device
US7862495B2 (en) 2001-05-31 2011-01-04 Advanced Cardiovascular Systems, Inc. Radiation or drug delivery source with activity gradient to minimize edge effects
US6743462B1 (en) 2001-05-31 2004-06-01 Advanced Cardiovascular Systems, Inc. Apparatus and method for coating implantable devices
GB0113697D0 (en) 2001-06-06 2001-07-25 Smith & Nephew Fixation devices for tissue repair
US7175873B1 (en) 2001-06-27 2007-02-13 Advanced Cardiovascular Systems, Inc. Rate limiting barriers for implantable devices and methods for fabrication thereof
US7247313B2 (en) * 2001-06-27 2007-07-24 Advanced Cardiovascular Systems, Inc. Polyacrylates coatings for implantable medical devices
US8741378B1 (en) 2001-06-27 2014-06-03 Advanced Cardiovascular Systems, Inc. Methods of coating an implantable device
US6695920B1 (en) 2001-06-27 2004-02-24 Advanced Cardiovascular Systems, Inc. Mandrel for supporting a stent and a method of using the mandrel to coat a stent
US6656216B1 (en) 2001-06-29 2003-12-02 Advanced Cardiovascular Systems, Inc. Composite stent with regioselective material
US7682669B1 (en) 2001-07-30 2010-03-23 Advanced Cardiovascular Systems, Inc. Methods for covalently immobilizing anti-thrombogenic material into a coating on a medical device
US8303651B1 (en) 2001-09-07 2012-11-06 Advanced Cardiovascular Systems, Inc. Polymeric coating for reducing the rate of release of a therapeutic substance from a stent
US7989018B2 (en) 2001-09-17 2011-08-02 Advanced Cardiovascular Systems, Inc. Fluid treatment of a polymeric coating on an implantable medical device
US7285304B1 (en) 2003-06-25 2007-10-23 Advanced Cardiovascular Systems, Inc. Fluid treatment of a polymeric coating on an implantable medical device
US7223282B1 (en) 2001-09-27 2007-05-29 Advanced Cardiovascular Systems, Inc. Remote activation of an implantable device
US6709514B1 (en) * 2001-12-28 2004-03-23 Advanced Cardiovascular Systems, Inc. Rotary coating apparatus for coating implantable medical devices
US20030216758A1 (en) * 2001-12-28 2003-11-20 Angiotech Pharmaceuticals, Inc. Coated surgical patches
US7481799B2 (en) * 2002-01-03 2009-01-27 Oxira Medical Inc. Delivery source of oxygen
US8142412B2 (en) * 2002-01-03 2012-03-27 Oxira Medical Inc. Method and apparatus for delivering oxygen and/or other gases to tissue
US20090326508A1 (en) * 2008-01-09 2009-12-31 Michael Braun Method and apparatus for delivering oxygen and/or other gases and/or pharmacological agents to tissue
US6716200B2 (en) 2002-01-18 2004-04-06 C.R. Bard, Inc. Antimicrobial urine collection system and methods of manufacturing the same
US8685427B2 (en) * 2002-07-31 2014-04-01 Boston Scientific Scimed, Inc. Controlled drug delivery
US7919075B1 (en) 2002-03-20 2011-04-05 Advanced Cardiovascular Systems, Inc. Coatings for implantable medical devices
US7041308B2 (en) * 2002-04-18 2006-05-09 Poly-Med, Inc. Drug-polymer coated stents with segmented homochain copolyesters
US8313760B2 (en) 2002-05-24 2012-11-20 Angiotech International Ag Compositions and methods for coating medical implants
PT1509256E (pt) * 2002-05-24 2009-10-15 Angiotech Int Ag Composições e métodos de revestimento de implantes médicos
US7097850B2 (en) * 2002-06-18 2006-08-29 Surmodics, Inc. Bioactive agent release coating and controlled humidity method
US7918382B2 (en) * 2002-06-18 2011-04-05 Zimmer Technology, Inc. Method for attaching a porous metal layer to a metal substrate
US6945448B2 (en) * 2002-06-18 2005-09-20 Zimmer Technology, Inc. Method for attaching a porous metal layer to a metal substrate
US7056523B1 (en) 2002-06-21 2006-06-06 Advanced Cardiovascular Systems, Inc. Implantable medical devices incorporating chemically conjugated polymers and oligomers of L-arginine
US7217426B1 (en) 2002-06-21 2007-05-15 Advanced Cardiovascular Systems, Inc. Coatings containing polycationic peptides for cardiovascular therapy
US8506617B1 (en) 2002-06-21 2013-08-13 Advanced Cardiovascular Systems, Inc. Micronized peptide coated stent
US7794743B2 (en) 2002-06-21 2010-09-14 Advanced Cardiovascular Systems, Inc. Polycationic peptide coatings and methods of making the same
US7033602B1 (en) 2002-06-21 2006-04-25 Advanced Cardiovascular Systems, Inc. Polycationic peptide coatings and methods of coating implantable medical devices
US7622146B2 (en) * 2002-07-18 2009-11-24 Advanced Cardiovascular Systems, Inc. Rate limiting barriers for implantable devices and methods for fabrication thereof
DE60316579T2 (de) * 2002-08-13 2008-07-03 Medtronic, Inc., Minneapolis System zur abgabe von wirkstoffen mit einem hydrophoben cellulose-derivat
WO2004014449A1 (en) * 2002-08-13 2004-02-19 Medtronic, Inc. Active agent delivery system including a polyurethane, medical device, and method
US20040039437A1 (en) * 2002-08-13 2004-02-26 Medtronic, Inc. Medical device exhibiting improved adhesion between polymeric coating and substrate
US20040086569A1 (en) * 2002-08-13 2004-05-06 Medtronic, Inc. Active agent delivery systems, medical devices, and methods
WO2004014448A1 (en) * 2002-08-13 2004-02-19 Medtronic, Inc. Active agent delivery system including a hydrophilic polymer, medical device, and method
CA2494186A1 (en) * 2002-08-13 2004-02-19 Medtronic, Inc. Active agent delivery system including a poly(ethylene-co-(meth)acrylate), medical device, and method
DE10242476B4 (de) * 2002-09-11 2006-10-26 Heraeus Kulzer Gmbh Antibiotikum-/Antibiotika-Polymer-Kombination
MXPA05003238A (es) * 2002-09-26 2005-09-12 Endovascular Devices Inc Aparato y metodo para administrar mitomicina a traves de un dispositivo medico implantable biocompatible de elucion.
US7087263B2 (en) * 2002-10-09 2006-08-08 Advanced Cardiovascular Systems, Inc. Rare limiting barriers for implantable medical devices
US7041088B2 (en) * 2002-10-11 2006-05-09 Ethicon, Inc. Medical devices having durable and lubricious polymeric coating
AU2003291311A1 (en) * 2002-11-07 2004-06-03 Carbon Medical Technologies, Inc. Biocompatible medical device coatings
US7169178B1 (en) 2002-11-12 2007-01-30 Advanced Cardiovascular Systems, Inc. Stent with drug coating
US7022372B1 (en) 2002-11-12 2006-04-04 Advanced Cardiovascular Systems, Inc. Compositions for coating implantable medical devices
US6982004B1 (en) * 2002-11-26 2006-01-03 Advanced Cardiovascular Systems, Inc. Electrostatic loading of drugs on implantable medical devices
US7758880B2 (en) * 2002-12-11 2010-07-20 Advanced Cardiovascular Systems, Inc. Biocompatible polyacrylate compositions for medical applications
US7776926B1 (en) 2002-12-11 2010-08-17 Advanced Cardiovascular Systems, Inc. Biocompatible coating for implantable medical devices
US7074276B1 (en) 2002-12-12 2006-07-11 Advanced Cardiovascular Systems, Inc. Clamp mandrel fixture and a method of using the same to minimize coating defects
US20060002968A1 (en) 2004-06-30 2006-01-05 Gordon Stewart Anti-proliferative and anti-inflammatory agent combination for treatment of vascular disorders
US7758881B2 (en) 2004-06-30 2010-07-20 Advanced Cardiovascular Systems, Inc. Anti-proliferative and anti-inflammatory agent combination for treatment of vascular disorders with an implantable medical device
US8435550B2 (en) 2002-12-16 2013-05-07 Abbot Cardiovascular Systems Inc. Anti-proliferative and anti-inflammatory agent combination for treatment of vascular disorders with an implantable medical device
US6926919B1 (en) * 2003-02-26 2005-08-09 Advanced Cardiovascular Systems, Inc. Method for fabricating a coating for a medical device
US7563483B2 (en) 2003-02-26 2009-07-21 Advanced Cardiovascular Systems Inc. Methods for fabricating a coating for implantable medical devices
US8313759B2 (en) * 2003-03-06 2012-11-20 Boston Scientific Scimed, Inc. Implantable or insertable medical devices containing miscible polymer blends for controlled delivery of a therapeutic agent
KR20060003872A (ko) 2003-04-04 2006-01-11 티슈메드 리미티드 조직-부착성 제형물
IES20030294A2 (en) * 2003-04-17 2004-10-20 Medtronic Vascular Connaught Coating for biomedical devices
US8791171B2 (en) 2003-05-01 2014-07-29 Abbott Cardiovascular Systems Inc. Biodegradable coatings for implantable medical devices
CA2524271C (en) 2003-05-02 2012-09-04 Surmodics, Inc. Controlled release bioactive agent delivery device
US8246974B2 (en) 2003-05-02 2012-08-21 Surmodics, Inc. Medical devices and methods for producing the same
US7279174B2 (en) * 2003-05-08 2007-10-09 Advanced Cardiovascular Systems, Inc. Stent coatings comprising hydrophilic additives
US20050118344A1 (en) 2003-12-01 2005-06-02 Pacetti Stephen D. Temperature controlled crimping
US7056591B1 (en) * 2003-07-30 2006-06-06 Advanced Cardiovascular Systems, Inc. Hydrophobic biologically absorbable coatings for drug delivery devices and methods for fabricating the same
US9114199B2 (en) * 2003-07-31 2015-08-25 Boston Scientific Scimed, Inc. Implantable or insertable medical devices containing acrylic copolymer for controlled delivery of therapeutic agent
US7785512B1 (en) 2003-07-31 2010-08-31 Advanced Cardiovascular Systems, Inc. Method and system of controlled temperature mixing and molding of polymers with active agents for implantable medical devices
US7431959B1 (en) 2003-07-31 2008-10-07 Advanced Cardiovascular Systems Inc. Method and system for irradiation of a drug eluting implantable medical device
US7645474B1 (en) 2003-07-31 2010-01-12 Advanced Cardiovascular Systems, Inc. Method and system of purifying polymers for use with implantable medical devices
US20050064005A1 (en) * 2003-08-13 2005-03-24 Dinh Thomas Q. Active agent delivery systems including a miscible polymer blend, medical devices, and methods
EP1660145A2 (en) * 2003-08-13 2006-05-31 Medtronic, Inc. Active agent delivery systems, including a single layer of a miscible polymer blend, medical devices and methods
WO2005018696A1 (en) * 2003-08-19 2005-03-03 Polybiomed Limited Polymeric drug release system for medical devices
DE10339557A1 (de) * 2003-08-26 2005-04-07 Heraeus Kulzer Gmbh Zahnfüllungsmaterial
US7441513B1 (en) 2003-09-26 2008-10-28 Advanced Cardiovascular Systems, Inc. Plasma-generated coating apparatus for medical devices and a method of coating deposition
US7198675B2 (en) 2003-09-30 2007-04-03 Advanced Cardiovascular Systems Stent mandrel fixture and method for selectively coating surfaces of a stent
US7318932B2 (en) * 2003-09-30 2008-01-15 Advanced Cardiovascular Systems, Inc. Coatings for drug delivery devices comprising hydrolitically stable adducts of poly(ethylene-co-vinyl alcohol) and methods for fabricating the same
DK1675908T3 (da) * 2003-10-07 2009-04-20 Coloplast As Sammensætning der er nyttig som et adhæsiv samt anvendelse af en sådan sammensætning
US7704544B2 (en) * 2003-10-07 2010-04-27 Advanced Cardiovascular Systems, Inc. System and method for coating a tubular implantable medical device
US20050090905A1 (en) * 2003-10-23 2005-04-28 Hawkins Michael E. Porous implant with a dried, lubricious when wet, in vivo absorbable coating
US7329413B1 (en) 2003-11-06 2008-02-12 Advanced Cardiovascular Systems, Inc. Coatings for drug delivery devices having gradient of hydration and methods for fabricating thereof
US7261946B2 (en) 2003-11-14 2007-08-28 Advanced Cardiovascular Systems, Inc. Block copolymers of acrylates and methacrylates with fluoroalkenes
US9114198B2 (en) 2003-11-19 2015-08-25 Advanced Cardiovascular Systems, Inc. Biologically beneficial coatings for implantable devices containing fluorinated polymers and methods for fabricating the same
WO2006053007A2 (en) * 2004-11-09 2006-05-18 Angiotech Biocoatings Corp. Antimicrobial needle coating for extended infusion
CA2536188A1 (en) * 2003-11-20 2005-06-09 Angiotech International Ag Electrical devices and anti-scarring agents
US8192752B2 (en) 2003-11-21 2012-06-05 Advanced Cardiovascular Systems, Inc. Coatings for implantable devices including biologically erodable polyesters and methods for fabricating the same
US7560492B1 (en) * 2003-11-25 2009-07-14 Advanced Cardiovascular Systems, Inc. Polysulfone block copolymers as drug-eluting coating material
US7807722B2 (en) * 2003-11-26 2010-10-05 Advanced Cardiovascular Systems, Inc. Biobeneficial coating compositions and methods of making and using thereof
US7435788B2 (en) 2003-12-19 2008-10-14 Advanced Cardiovascular Systems, Inc. Biobeneficial polyamide/polyethylene glycol polymers for use with drug eluting stents
US8309112B2 (en) * 2003-12-24 2012-11-13 Advanced Cardiovascular Systems, Inc. Coatings for implantable medical devices comprising hydrophilic substances and methods for fabricating the same
US7959659B2 (en) 2004-01-02 2011-06-14 Advanced Cardiovascular Systems, Inc. High-density lipoprotein coated medical devices
WO2005065526A1 (ja) 2004-01-07 2005-07-21 Olympus Corporation カプセル型医療装置、医療用カプセル筐体とその製造方法
US20050272153A1 (en) 2004-01-27 2005-12-08 Zou Xuenong Bone tissue engineering by ex vivo stem cells ongrowth into three-dimensional trabecular metal
US8685431B2 (en) 2004-03-16 2014-04-01 Advanced Cardiovascular Systems, Inc. Biologically absorbable coatings for implantable devices based on copolymers having ester bonds and methods for fabricating the same
US8551512B2 (en) 2004-03-22 2013-10-08 Advanced Cardiovascular Systems, Inc. Polyethylene glycol/poly(butylene terephthalate) copolymer coated devices including EVEROLIMUS
US20050208093A1 (en) 2004-03-22 2005-09-22 Thierry Glauser Phosphoryl choline coating compositions
US8778014B1 (en) 2004-03-31 2014-07-15 Advanced Cardiovascular Systems, Inc. Coatings for preventing balloon damage to polymer coated stents
WO2005099787A1 (en) * 2004-04-06 2005-10-27 Surmodics, Inc. Coating compositions for bioactive agents
US9498563B2 (en) * 2004-04-23 2016-11-22 Boston Scientific Scimed, Inc. Medical articles having therapeutic-agent-containing regions formed from coalesced polymer particles
US7820732B2 (en) 2004-04-30 2010-10-26 Advanced Cardiovascular Systems, Inc. Methods for modulating thermal and mechanical properties of coatings on implantable devices
WO2005104845A1 (en) * 2004-04-30 2005-11-10 Coloplast A/S A hydrophilic coating of a water-swellable hydrophilic matrix and an anti-microbial polymer
US8293890B2 (en) 2004-04-30 2012-10-23 Advanced Cardiovascular Systems, Inc. Hyaluronic acid based copolymers
US9561309B2 (en) 2004-05-27 2017-02-07 Advanced Cardiovascular Systems, Inc. Antifouling heparin coatings
US7563780B1 (en) 2004-06-18 2009-07-21 Advanced Cardiovascular Systems, Inc. Heparin prodrugs and drug delivery stents formed therefrom
US20050287184A1 (en) 2004-06-29 2005-12-29 Hossainy Syed F A Drug-delivery stent formulations for restenosis and vulnerable plaque
WO2006002628A1 (en) * 2004-06-30 2006-01-12 Coloplast A/S A hydrophilic, water-swellable, cross-linked matrix having incorporated therein an anti-microbial polymer
US7635510B2 (en) * 2004-07-07 2009-12-22 Boston Scientific Scimed, Inc. High performance balloon catheter/component
JP3992698B2 (ja) * 2004-07-20 2007-10-17 電気化学工業株式会社 ポリビニルアセタール樹脂組成物、シート及び合わせガラス
US7494665B1 (en) 2004-07-30 2009-02-24 Advanced Cardiovascular Systems, Inc. Polymers containing siloxane monomers
US8357391B2 (en) 2004-07-30 2013-01-22 Advanced Cardiovascular Systems, Inc. Coatings for implantable devices comprising poly (hydroxy-alkanoates) and diacid linkages
KR20070051297A (ko) 2004-08-03 2007-05-17 티슈메드 리미티드 조직-접착성 물질
US7648727B2 (en) 2004-08-26 2010-01-19 Advanced Cardiovascular Systems, Inc. Methods for manufacturing a coated stent-balloon assembly
US7244443B2 (en) 2004-08-31 2007-07-17 Advanced Cardiovascular Systems, Inc. Polymers of fluorinated monomers and hydrophilic monomers
US7229471B2 (en) 2004-09-10 2007-06-12 Advanced Cardiovascular Systems, Inc. Compositions containing fast-leaching plasticizers for improved performance of medical devices
US8110211B2 (en) 2004-09-22 2012-02-07 Advanced Cardiovascular Systems, Inc. Medicated coatings for implantable medical devices including polyacrylates
US9011831B2 (en) * 2004-09-30 2015-04-21 Advanced Cardiovascular Systems, Inc. Methacrylate copolymers for medical devices
US8603634B2 (en) 2004-10-27 2013-12-10 Abbott Cardiovascular Systems Inc. End-capped poly(ester amide) copolymers
US7390497B2 (en) 2004-10-29 2008-06-24 Advanced Cardiovascular Systems, Inc. Poly(ester amide) filler blends for modulation of coating properties
US7588642B1 (en) 2004-11-29 2009-09-15 Advanced Cardiovascular Systems, Inc. Abluminal stent coating apparatus and method using a brush assembly
US8609123B2 (en) 2004-11-29 2013-12-17 Advanced Cardiovascular Systems, Inc. Derivatized poly(ester amide) as a biobeneficial coating
US7892592B1 (en) 2004-11-30 2011-02-22 Advanced Cardiovascular Systems, Inc. Coating abluminal surfaces of stents and other implantable medical devices
US7604818B2 (en) 2004-12-22 2009-10-20 Advanced Cardiovascular Systems, Inc. Polymers of fluorinated monomers and hydrocarbon monomers
US7419504B2 (en) 2004-12-27 2008-09-02 Advanced Cardiovascular Systems, Inc. Poly(ester amide) block copolymers
US8007775B2 (en) 2004-12-30 2011-08-30 Advanced Cardiovascular Systems, Inc. Polymers containing poly(hydroxyalkanoates) and agents for use with medical articles and methods of fabricating the same
AU2005100176A4 (en) * 2005-03-01 2005-04-07 Gym Tv Pty Ltd Garbage bin clip
US9381279B2 (en) 2005-03-24 2016-07-05 Abbott Cardiovascular Systems Inc. Implantable devices formed on non-fouling methacrylate or acrylate polymers
US7700659B2 (en) * 2005-03-24 2010-04-20 Advanced Cardiovascular Systems, Inc. Implantable devices formed of non-fouling methacrylate or acrylate polymers
US7790216B2 (en) * 2005-04-19 2010-09-07 Zimmer Technology, Inc. Method for producing a zirconia-layered orthopedic implant component
US7795467B1 (en) 2005-04-26 2010-09-14 Advanced Cardiovascular Systems, Inc. Bioabsorbable, biobeneficial polyurethanes for use in medical devices
US8778375B2 (en) 2005-04-29 2014-07-15 Advanced Cardiovascular Systems, Inc. Amorphous poly(D,L-lactide) coating
CN101687385A (zh) * 2005-05-12 2010-03-31 佐治亚科技研究公司 包覆的金属氧化物纳米颗粒及其制备方法
US20060282166A1 (en) * 2005-06-09 2006-12-14 Sdgi Holdings, Inc. Compliant porous coating
US7823533B2 (en) 2005-06-30 2010-11-02 Advanced Cardiovascular Systems, Inc. Stent fixture and method for reducing coating defects
US8021676B2 (en) 2005-07-08 2011-09-20 Advanced Cardiovascular Systems, Inc. Functionalized chemically inert polymers for coatings
US7785647B2 (en) 2005-07-25 2010-08-31 Advanced Cardiovascular Systems, Inc. Methods of providing antioxidants to a drug containing product
US7735449B1 (en) 2005-07-28 2010-06-15 Advanced Cardiovascular Systems, Inc. Stent fixture having rounded support structures and method for use thereof
US8663673B2 (en) 2005-07-29 2014-03-04 Surmodics, Inc. Devices, articles, coatings, and methods for controlled active agent release or hemocompatibility
DE102005054106A1 (de) * 2005-11-12 2007-05-16 Fresenius Medical Care De Gmbh Verfahren zum Beschichten von Oberflächen mit Hydrogelen und mit Hydrogelbeschichtungen versehene Polymersubstrate
US7976891B1 (en) 2005-12-16 2011-07-12 Advanced Cardiovascular Systems, Inc. Abluminal stent coating apparatus and method of using focused acoustic energy
US7867547B2 (en) 2005-12-19 2011-01-11 Advanced Cardiovascular Systems, Inc. Selectively coating luminal surfaces of stents
US20070156230A1 (en) 2006-01-04 2007-07-05 Dugan Stephen R Stents with radiopaque markers
US20070179618A1 (en) * 2006-01-31 2007-08-02 Sdgi Holdings, Inc. Intervertebral prosthetic disc
US20070179615A1 (en) * 2006-01-31 2007-08-02 Sdgi Holdings, Inc. Intervertebral prosthetic disc
EP1979015A2 (en) * 2006-01-31 2008-10-15 Angiotech BioCoatings, Corp. Lubricious coatings
EP1979016B1 (en) 2006-02-01 2015-07-01 Hollister Incorporated Methods of applying a hydrophilic coating to a substrate, and substrates having a hydrophilic coating
CA2640629A1 (en) 2006-02-03 2007-08-09 Tissuemed Limited Tissue-adhesive materials
US20070196428A1 (en) 2006-02-17 2007-08-23 Thierry Glauser Nitric oxide generating medical devices
US7713637B2 (en) 2006-03-03 2010-05-11 Advanced Cardiovascular Systems, Inc. Coating containing PEGylated hyaluronic acid and a PEGylated non-hyaluronic acid polymer
US8858855B2 (en) 2006-04-20 2014-10-14 Boston Scientific Scimed, Inc. High pressure balloon
US8069814B2 (en) 2006-05-04 2011-12-06 Advanced Cardiovascular Systems, Inc. Stent support devices
US7985441B1 (en) 2006-05-04 2011-07-26 Yiwen Tang Purification of polymers for coating applications
US8304012B2 (en) 2006-05-04 2012-11-06 Advanced Cardiovascular Systems, Inc. Method for drying a stent
US7943221B2 (en) * 2006-05-22 2011-05-17 Boston Scientific Scimed, Inc. Hinged compliance fiber braid balloon
US20130325107A1 (en) 2006-05-26 2013-12-05 Abbott Cardiovascular Systems Inc. Stents With Radiopaque Markers
US7775178B2 (en) 2006-05-26 2010-08-17 Advanced Cardiovascular Systems, Inc. Stent coating apparatus and method
US8568764B2 (en) 2006-05-31 2013-10-29 Advanced Cardiovascular Systems, Inc. Methods of forming coating layers for medical devices utilizing flash vaporization
US9561351B2 (en) 2006-05-31 2017-02-07 Advanced Cardiovascular Systems, Inc. Drug delivery spiral coil construct
US8703167B2 (en) 2006-06-05 2014-04-22 Advanced Cardiovascular Systems, Inc. Coatings for implantable medical devices for controlled release of a hydrophilic drug and a hydrophobic drug
US8778376B2 (en) 2006-06-09 2014-07-15 Advanced Cardiovascular Systems, Inc. Copolymer comprising elastin pentapeptide block and hydrophilic block, and medical device and method of treating
US8603530B2 (en) 2006-06-14 2013-12-10 Abbott Cardiovascular Systems Inc. Nanoshell therapy
US8114150B2 (en) 2006-06-14 2012-02-14 Advanced Cardiovascular Systems, Inc. RGD peptide attached to bioabsorbable stents
US20080095918A1 (en) * 2006-06-14 2008-04-24 Kleiner Lothar W Coating construct with enhanced interfacial compatibility
US8048448B2 (en) 2006-06-15 2011-11-01 Abbott Cardiovascular Systems Inc. Nanoshells for drug delivery
US8535372B1 (en) 2006-06-16 2013-09-17 Abbott Cardiovascular Systems Inc. Bioabsorbable stent with prohealing layer
US8246973B2 (en) 2006-06-21 2012-08-21 Advanced Cardiovascular Systems, Inc. Freeze-thaw method for modifying stent coating
US8017237B2 (en) 2006-06-23 2011-09-13 Abbott Cardiovascular Systems, Inc. Nanoshells on polymers
US8128688B2 (en) 2006-06-27 2012-03-06 Abbott Cardiovascular Systems Inc. Carbon coating on an implantable device
US8956640B2 (en) * 2006-06-29 2015-02-17 Advanced Cardiovascular Systems, Inc. Block copolymers including a methoxyethyl methacrylate midblock
US20080008736A1 (en) * 2006-07-06 2008-01-10 Thierry Glauser Random copolymers of methacrylates and acrylates
US8685421B2 (en) * 2006-07-07 2014-04-01 Surmodics, Inc. Beaded wound spacer device
US9028859B2 (en) 2006-07-07 2015-05-12 Advanced Cardiovascular Systems, Inc. Phase-separated block copolymer coatings for implantable medical devices
US7823263B2 (en) 2006-07-11 2010-11-02 Abbott Cardiovascular Systems Inc. Method of removing stent islands from a stent
US8685430B1 (en) 2006-07-14 2014-04-01 Abbott Cardiovascular Systems Inc. Tailored aliphatic polyesters for stent coatings
US8952123B1 (en) 2006-08-02 2015-02-10 Abbott Cardiovascular Systems Inc. Dioxanone-based copolymers for implantable devices
US8703169B1 (en) 2006-08-15 2014-04-22 Abbott Cardiovascular Systems Inc. Implantable device having a coating comprising carrageenan and a biostable polymer
US20080064800A1 (en) * 2006-09-08 2008-03-13 Bruce Edward Wade Poly(vinyl butyral) Dispersions Comprising a Non-Ionic Surfactant
US8405069B2 (en) * 2006-11-10 2013-03-26 Georgia Tech Research Corporation Printable thin-film transistors with high dielectric constant gate insulators and methods for producing same
US20080118541A1 (en) * 2006-11-21 2008-05-22 Abbott Laboratories Use of a terpolymer of tetrafluoroethylene, hexafluoropropylene, and vinylidene fluoride in drug eluting coatings on medical devices
WO2008064058A2 (en) * 2006-11-21 2008-05-29 Abbott Laboratories Use of a terpolymer of tetrafluoroethylene, hexafluoropropylene, and vinylidene fluoride in drug eluting coatings
US7713541B1 (en) * 2006-11-21 2010-05-11 Abbott Cardiovascular Systems Inc. Zwitterionic terpolymers, method of making and use on medical devices
US8597673B2 (en) 2006-12-13 2013-12-03 Advanced Cardiovascular Systems, Inc. Coating of fast absorption or dissolution
US8017141B2 (en) * 2006-12-15 2011-09-13 Advanced Cardiovascular Systems, Inc. Coatings of acrylamide-based copolymers
US20080175882A1 (en) * 2007-01-23 2008-07-24 Trollsas Mikael O Polymers of aliphatic thioester
US20080286332A1 (en) 2007-05-14 2008-11-20 Pacetti Stephen D Implantable medical devices with a topcoat layer of phosphoryl choline acrylate polymer for reduced thrombosis, and improved mechanical properties
US8147769B1 (en) 2007-05-16 2012-04-03 Abbott Cardiovascular Systems Inc. Stent and delivery system with reduced chemical degradation
US9056155B1 (en) 2007-05-29 2015-06-16 Abbott Cardiovascular Systems Inc. Coatings having an elastic primer layer
US10155881B2 (en) * 2007-05-30 2018-12-18 Abbott Cardiovascular Systems Inc. Substituted polycaprolactone for coating
US8133553B2 (en) 2007-06-18 2012-03-13 Zimmer, Inc. Process for forming a ceramic layer
US9737638B2 (en) * 2007-06-20 2017-08-22 Abbott Cardiovascular Systems, Inc. Polyester amide copolymers having free carboxylic acid pendant groups
US8109904B1 (en) 2007-06-25 2012-02-07 Abbott Cardiovascular Systems Inc. Drug delivery medical devices
US7927621B2 (en) * 2007-06-25 2011-04-19 Abbott Cardiovascular Systems Inc. Thioester-ester-amide copolymers
US8048441B2 (en) 2007-06-25 2011-11-01 Abbott Cardiovascular Systems, Inc. Nanobead releasing medical devices
US7901452B2 (en) 2007-06-27 2011-03-08 Abbott Cardiovascular Systems Inc. Method to fabricate a stent having selected morphology to reduce restenosis
US7955381B1 (en) 2007-06-29 2011-06-07 Advanced Cardiovascular Systems, Inc. Polymer-bioceramic composite implantable medical device with different types of bioceramic particles
US20090004243A1 (en) 2007-06-29 2009-01-01 Pacetti Stephen D Biodegradable triblock copolymers for implantable devices
US20090041923A1 (en) * 2007-08-06 2009-02-12 Abbott Cardiovascular Systems Inc. Medical device having a lubricious coating with a hydrophilic compound in an interlocking network
US8790345B2 (en) * 2007-08-21 2014-07-29 Zimmer, Inc. Titanium alloy with oxidized zirconium for a prosthetic implant
US9814553B1 (en) 2007-10-10 2017-11-14 Abbott Cardiovascular Systems Inc. Bioabsorbable semi-crystalline polymer for controlling release of drug from a coating
US20090104241A1 (en) * 2007-10-23 2009-04-23 Pacetti Stephen D Random amorphous terpolymer containing lactide and glycolide
US20090306120A1 (en) * 2007-10-23 2009-12-10 Florencia Lim Terpolymers containing lactide and glycolide
US8642062B2 (en) 2007-10-31 2014-02-04 Abbott Cardiovascular Systems Inc. Implantable device having a slow dissolving polymer
US20090110713A1 (en) * 2007-10-31 2009-04-30 Florencia Lim Biodegradable polymeric materials providing controlled release of hydrophobic drugs from implantable devices
US8216600B2 (en) * 2007-11-14 2012-07-10 Cordis Corporation Polymeric materials for medical devices
US8128983B2 (en) * 2008-04-11 2012-03-06 Abbott Cardiovascular Systems Inc. Coating comprising poly(ethylene glycol)-poly(lactide-glycolide-caprolactone) interpenetrating network
US8916188B2 (en) * 2008-04-18 2014-12-23 Abbott Cardiovascular Systems Inc. Block copolymer comprising at least one polyester block and a poly (ethylene glycol) block
US20090285873A1 (en) * 2008-04-18 2009-11-19 Abbott Cardiovascular Systems Inc. Implantable medical devices and coatings therefor comprising block copolymers of poly(ethylene glycol) and a poly(lactide-glycolide)
US20090297584A1 (en) * 2008-04-18 2009-12-03 Florencia Lim Biosoluble coating with linear over time mass loss
US8697113B2 (en) * 2008-05-21 2014-04-15 Abbott Cardiovascular Systems Inc. Coating comprising a terpolymer comprising caprolactone and glycolide
US20090318863A1 (en) 2008-06-18 2009-12-24 Boston Scientific Scimed, Inc. Functional Balloon With Built in Lubricity or Drug Delivery System
US8257722B2 (en) 2008-09-15 2012-09-04 Cv Ingenuity Corp. Local delivery of water-soluble or water-insoluble therapeutic agents to the surface of body lumens
US8128951B2 (en) 2008-09-15 2012-03-06 Cv Ingenuity Corp. Local delivery of water-soluble or water-insoluble therapeutic agents to the surface of body lumens
US8114429B2 (en) 2008-09-15 2012-02-14 Cv Ingenuity Corp. Local delivery of water-soluble or water-insoluble therapeutic agents to the surface of body lumens
US9198968B2 (en) * 2008-09-15 2015-12-01 The Spectranetics Corporation Local delivery of water-soluble or water-insoluble therapeutic agents to the surface of body lumens
US8882678B2 (en) * 2009-03-13 2014-11-11 Atrium Medical Corporation Pleural drainage system and method of use
US8697110B2 (en) * 2009-05-14 2014-04-15 Abbott Cardiovascular Systems Inc. Polymers comprising amorphous terpolymers and semicrystalline blocks
GB2470940A (en) 2009-06-10 2010-12-15 Systagenix Wound Man Ip Co Bv Vacuum wound dressing with hydrogel layer
EP2335745B1 (de) * 2009-12-21 2017-11-22 Biotronik VI Patent AG Implantat mit Beschichtung
US8568471B2 (en) 2010-01-30 2013-10-29 Abbott Cardiovascular Systems Inc. Crush recoverable polymer scaffolds
US8808353B2 (en) 2010-01-30 2014-08-19 Abbott Cardiovascular Systems Inc. Crush recoverable polymer scaffolds having a low crossing profile
US20110244254A1 (en) * 2010-03-30 2011-10-06 Zhiqiang Song Anticorrosion coatings with reactive polyelectrolyte complex system
US8685433B2 (en) 2010-03-31 2014-04-01 Abbott Cardiovascular Systems Inc. Absorbable coating for implantable device
EP2583699B1 (en) * 2010-06-16 2019-01-23 Terumo Kabushiki Kaisha Method for producing medical device
WO2012123273A1 (en) 2011-03-11 2012-09-20 Basf Se Antimicrobial coating
US9457132B2 (en) 2011-06-28 2016-10-04 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Controlled covalent attachment of bioactive bacteriophage for regulating biofilm development
US8726483B2 (en) 2011-07-29 2014-05-20 Abbott Cardiovascular Systems Inc. Methods for uniform crimping and deployment of a polymer scaffold
US9352119B2 (en) 2012-05-15 2016-05-31 Becton, Dickinson And Company Blood control IV catheter with antimicrobial properties
MX351261B (es) 2012-06-01 2017-10-06 Surmodics Inc Aparato y método para recubrir catéteres con globo.
US9827401B2 (en) 2012-06-01 2017-11-28 Surmodics, Inc. Apparatus and methods for coating medical devices
US9956385B2 (en) 2012-06-28 2018-05-01 The Spectranetics Corporation Post-processing of a medical device to control morphology and mechanical properties
CN102973986A (zh) * 2012-07-19 2013-03-20 黄斌 一种超滑抗菌医用导管涂层液
US9579486B2 (en) 2012-08-22 2017-02-28 Becton, Dickinson And Company Blood control IV catheter with antimicrobial properties
JP6298468B2 (ja) 2012-10-16 2018-03-20 サーモディクス，インコーポレイテッド 創傷充填デバイスおよび方法
US9750928B2 (en) 2013-02-13 2017-09-05 Becton, Dickinson And Company Blood control IV catheter with stationary septum activator
US9695323B2 (en) 2013-02-13 2017-07-04 Becton, Dickinson And Company UV curable solventless antimicrobial compositions
US9750927B2 (en) 2013-03-11 2017-09-05 Becton, Dickinson And Company Blood control catheter with antimicrobial needle lube
US9327095B2 (en) 2013-03-11 2016-05-03 Becton, Dickinson And Company Blood control catheter with antimicrobial needle lube
US10525171B2 (en) 2014-01-24 2020-01-07 The Spectranetics Corporation Coatings for medical devices
US9622891B2 (en) 2014-04-17 2017-04-18 Abbott Cardiovascular Systems Inc. Coatings for braided medical devices and methods of forming same
US10376686B2 (en) 2014-04-23 2019-08-13 Becton, Dickinson And Company Antimicrobial caps for medical connectors
US9675793B2 (en) 2014-04-23 2017-06-13 Becton, Dickinson And Company Catheter tubing with extraluminal antimicrobial coating
US9789279B2 (en) 2014-04-23 2017-10-17 Becton, Dickinson And Company Antimicrobial obturator for use with vascular access devices
US9381280B2 (en) 2014-06-13 2016-07-05 Abbott Cardiovascular Systems Inc. Plasticizers for a biodegradable scaffolding and methods of forming same
US10232088B2 (en) 2014-07-08 2019-03-19 Becton, Dickinson And Company Antimicrobial coating forming kink resistant feature on a vascular access device
US10201457B2 (en) 2014-08-01 2019-02-12 Surmodics, Inc. Wound packing device with nanotextured surface
US9999527B2 (en) 2015-02-11 2018-06-19 Abbott Cardiovascular Systems Inc. Scaffolds having radiopaque markers
JP6456196B2 (ja) * 2015-03-10 2019-01-23 テルモ株式会社 抗血栓性接着用組成物、ならびに該抗血栓性接着用組成物を利用した医療用具およびその製造方法
CN107949403A (zh) 2015-04-16 2018-04-20 好利司泰公司 亲水性涂层及其形成方法
US9700443B2 (en) 2015-06-12 2017-07-11 Abbott Cardiovascular Systems Inc. Methods for attaching a radiopaque marker to a scaffold
US10493244B2 (en) 2015-10-28 2019-12-03 Becton, Dickinson And Company Extension tubing strain relief
EP3442642A1 (en) 2016-04-12 2019-02-20 Boston Scientific Scimed, Inc. Medical balloon
EP3445424B1 (en) 2016-04-22 2023-08-23 Eli Lilly and Company Infusion set with components comprising a polymeric sorbent to reduce the concentration of m-cresol in insulin
US11596948B2 (en) 2016-11-17 2023-03-07 Enicor Gmbh Coated articles for blood coagulation testing and methods of preparing the same
US10849629B2 (en) 2016-12-13 2020-12-01 Boston Scientific Scimed, Inc. Medical balloon
EP3615099B1 (en) 2017-04-25 2023-03-01 Boston Scientific Scimed, Inc. Medical balloon
AU2018261179B2 (en) 2017-05-04 2023-02-09 Hollister Incorporated Lubricious hydrophilic coatings and methods of forming the same
EP3638330B1 (en) * 2017-05-30 2021-08-25 SuSoS AG Device having a switchable wet-dry lubricating coating
JP6850370B2 (ja) * 2018-01-30 2021-03-31 富士フイルム株式会社 超音波プローブ、超音波プローブ用樹脂組成物、樹脂組成物の超音波プローブのシース材料としての使用、及び超音波プローブの製造方法
WO2020112816A1 (en) 2018-11-29 2020-06-04 Surmodics, Inc. Apparatus and methods for coating medical devices
KR102232226B1 (ko) * 2019-05-02 2021-03-25 포항공과대학교 산학협력단 윤활층과 탄력층을 포함하는 인공혈관 모델 및 이의 제조방법
US11819590B2 (en) 2019-05-13 2023-11-21 Surmodics, Inc. Apparatus and methods for coating medical devices
US11738188B2 (en) 2020-06-08 2023-08-29 Covidien Lp Connection of intravascular interventional elements and elongate manipulation members
CN112142925B (zh) * 2020-10-13 2023-07-28 稳健平安医疗科技(湖南)有限公司 一种亲水性自润滑聚合物改性剂、合成方法及其应用

Family Cites Families (33)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3695921A (en) * 1970-09-09 1972-10-03 Nat Patent Dev Corp Method of coating a catheter
US4055682A (en) * 1971-11-19 1977-10-25 High Voltage Engineering Corporation Catheter and the method of making
US3939049A (en) * 1974-04-10 1976-02-17 The United States Of America As Represented By The United States Energy Research And Development Administration Process for radiation grafting hydrogels onto organic polymeric substrates
US4100309A (en) * 1977-08-08 1978-07-11 Biosearch Medical Products, Inc. Coated substrate having a low coefficient of friction hydrophilic coating and a method of making the same
SE448544B (sv) * 1979-12-05 1987-03-02 Kendall & Co Vattenabsorberande komposition och anvendning derav som berare for ett lekemedel
US4373009A (en) * 1981-05-18 1983-02-08 International Silicone Corporation Method of forming a hydrophilic coating on a substrate
US4459318A (en) * 1981-11-09 1984-07-10 American Hospital Supply Corporation Method for forming a self-lubricating fill tube
US4773901A (en) * 1981-12-31 1988-09-27 C. R. Bard, Inc. Catheter with selectively rigidified portion
SE430696B (sv) * 1982-04-22 1983-12-05 Astra Meditec Ab Forfarande for framstellning av en hydrofil beleggning samt en enligt forfarandet framstelld medicinsk artikel
US4769013A (en) * 1982-09-13 1988-09-06 Hydromer, Inc. Bio-effecting medical material and device
US4589873A (en) * 1984-05-29 1986-05-20 Becton, Dickinson And Company Method of applying a hydrophilic coating to a polymeric substrate and articles prepared thereby
EP0166998B1 (en) * 1984-06-04 1991-05-08 TERUMO KABUSHIKI KAISHA trading as TERUMO CORPORATION Medical instrument and method for making
US4883699A (en) * 1984-09-21 1989-11-28 Menlo Care, Inc. Polymeric article having high tensile energy to break when hydrated
US4678660A (en) * 1984-12-07 1987-07-07 Deseret Medical, Inc. Thermoplastic polyurethane anticoagulant alloy coating
US4835003A (en) * 1985-04-17 1989-05-30 Baxter International Inc. Medical tubing with water-activated lubricating coating
US4642267A (en) * 1985-05-06 1987-02-10 Hydromer, Inc. Hydrophilic polymer blend
SE8504501D0 (sv) * 1985-09-30 1985-09-30 Astra Meditec Ab Method of forming an improved hydrophilic coating on a polymer surface
US4781703A (en) * 1985-10-17 1988-11-01 Menlo Care, Inc. Catheter assembly
US5001009A (en) * 1987-09-02 1991-03-19 Sterilization Technical Services, Inc. Lubricious hydrophilic composite coated on substrates
US4867174A (en) * 1987-11-18 1989-09-19 Baxter Travenol Laboratories, Inc. Guidewire for medical use
US5019096A (en) * 1988-02-11 1991-05-28 Trustees Of Columbia University In The City Of New York Infection-resistant compositions, medical devices and surfaces and methods for preparing and using same
US4884579A (en) * 1988-04-18 1989-12-05 Target Therapeutics Catheter guide wire
US4847324A (en) * 1988-04-25 1989-07-11 Hydromer, Inc. Hydrophilic polyvinylbutyral alloys
US4950257A (en) * 1988-09-15 1990-08-21 Mallinckrodt, Inc. Catheter introducer with flexible tip
US5041100A (en) * 1989-04-28 1991-08-20 Cordis Corporation Catheter and hydrophilic, friction-reducing coating thereon
JP2540211B2 (ja) * 1989-07-10 1996-10-02 テルモ株式会社 ガイドワイヤ―
US5525348A (en) * 1989-11-02 1996-06-11 Sts Biopolymers, Inc. Coating compositions comprising pharmaceutical agents
US5084315A (en) * 1990-02-01 1992-01-28 Becton, Dickinson And Company Lubricious coatings, medical articles containing same and method for their preparation
US5443907A (en) * 1991-06-18 1995-08-22 Scimed Life Systems, Inc. Coating for medical insertion guides
DK172393B1 (da) * 1992-06-10 1998-05-18 Maersk Medical As Fremgangsmåde til fremstilling af en genstand med friktionsnedsættende overfladebelægning, belægningsmateriale til anvendelse ved fremstilling af en sådan genstand samt anvendelse af en osmolalitetsforøgende forbindelse i opslæmmet eller emulgeret form i belægningsmaterialet
US5824048A (en) * 1993-04-26 1998-10-20 Medtronic, Inc. Method for delivering a therapeutic substance to a body lumen
US5620738A (en) * 1995-06-07 1997-04-15 Union Carbide Chemicals & Plastics Technology Corporation Non-reactive lubicious coating process
US5756145A (en) * 1995-11-08 1998-05-26 Baylor College Of Medicine Durable, Resilient and effective antimicrobial coating for medical devices and method of coating therefor

Cited By (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN100462107C (zh) * 2005-09-14 2009-02-18 浙江大学 一种水溶性多羟基多臂聚氧乙烯凝胶涂层的制备方法
CN102272244B (zh) * 2008-12-01 2014-08-27 贝克顿·迪金森公司 抗微生物溶剂涂料组合物
CN102271826A (zh) * 2008-12-01 2011-12-07 贝克顿·迪金森公司 对医疗器材施涂抗微生物涂料的系统和方法
CN102166377A (zh) * 2011-01-05 2011-08-31 北京泰杰伟业科技有限公司 医用导管润滑亲水涂层的组合物、制备方法与使用方法
CN103374843A (zh) * 2012-04-27 2013-10-30 福懋兴业股份有限公司 具色彩深浅预定图案的合成纤维织物和其制造方法
CN103374843B (zh) * 2012-04-27 2015-10-28 福懋兴业股份有限公司 具色彩深浅预定图案的合成纤维织物和其制造方法
CN107028641B (zh) * 2013-01-09 2020-04-21 柯惠有限合伙公司 用于血管内介入的装置
CN107028641A (zh) * 2013-01-09 2017-08-11 柯惠有限合伙公司 用于血管内介入的装置
CN103721916A (zh) * 2013-12-11 2014-04-16 甘肃大禹节水集团股份有限公司 一种交联聚乙烯涂层修饰的聚氯乙烯管材的生产方法
CN103721916B (zh) * 2013-12-11 2015-02-11 甘肃大禹节水集团股份有限公司 一种交联聚乙烯涂层修饰的聚氯乙烯管材的生产方法
CN103948975B (zh) * 2014-05-19 2015-09-23 上海赢生医疗科技有限公司 一种靶向药物释放介入类医疗器械及其制备方法
CN103948975A (zh) * 2014-05-19 2014-07-30 上海赢生医疗科技有限公司 一种靶向药物释放介入类医疗器械及其制备方法
CN104857572A (zh) * 2014-12-05 2015-08-26 美昕医疗器械（上海）有限公司 在惰性高分子材料表面制备亲水润滑涂层的方法及其医疗器械
CN104857572B (zh) * 2014-12-05 2018-07-17 美昕医疗器械（上海）有限公司 在惰性高分子材料表面制备亲水润滑涂层的方法及其医疗器械
CN108837262A (zh) * 2018-06-22 2018-11-20 江南大学附属医院 一种具有抗菌功能的支气管导管
CN113164656A (zh) * 2018-11-16 2021-07-23 心脏起搏器股份公司 润滑硅树脂
US11485925B2 (en) 2018-11-16 2022-11-01 Cardiac Pacemakers, Inc. Lubricous silicone
CN110713608A (zh) * 2019-09-17 2020-01-21 长春工业大学 一种核苷酸驱动的粘韧水凝胶的制备方法
CN111729130A (zh) * 2020-08-06 2020-10-02 四川大学 一种生物抗污性能优异的人工晶状体涂层及其制备方法
CN111729130B (zh) * 2020-08-06 2021-07-20 四川大学 一种生物抗污性能优异的人工晶状体涂层及其制备方法

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