CN1899614B - 预防再狭窄的制剂 - Google Patents

预防再狭窄的制剂 Download PDF

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CN1899614B
CN1899614B CN2006100998225A CN200610099822A CN1899614B CN 1899614 B CN1899614 B CN 1899614B CN 2006100998225 A CN2006100998225 A CN 2006100998225A CN 200610099822 A CN200610099822 A CN 200610099822A CN 1899614 B CN1899614 B CN 1899614B
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乌尔里希·施佩克
布鲁诺·施勒
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Abstract

本发明涉及一种用于预防再狭窄的制剂。已知用于预防再狭窄的制剂尚不能在受损血管壁区域达到足够的活性剂浓度,原因是较高的剂量会引起不需要的副作用。本发明是加入至少一个亲脂性抗增生剂的制剂,其在丁醇和水之间的分配比为≥0.5。该亲脂性活性剂以足够的量被血管壁快速吸收。该制剂可为一种可以穿透毛细血管的液体,并且可含有造影剂,以便在通常需要进行造影放射照相的同时,不需要附加任何努力地将该活性剂转运至血管壁中。该制剂还可以包被于导管上。

Description

预防再狭窄的制剂
本申请是于2005年12月29日提交的申请号为200510135799.6,发明名称为“预防再狭窄的制剂”的分案申请。
本发明涉及一种预防再狭窄的制剂及其包被于血管造影术导管上的应用。
血管狭窄是发病和死亡的主要原因。在许多情况下,使用可膨胀的气囊导管可以将直径至少约达2mm的较大血管的局部狭窄或闭塞扩张恢复至其原始腔的大小。因使用很高的压力,可导致增厚的血管壁发生破裂,被挤压移位至周围组织中。在进行某些这样的操作中,植入管状穿孔的金属支架(斯滕特固定模)以保持血管开放。用此方法处理的血管壁经常在几周和几个月内出现厚度增加,类似于形成疤痕。结果,由于动脉硬化的进展,这些血管不久将再次狭窄(再狭窄)。再狭窄是一个严重的医学难题并造成医疗费用升高。
临床上被证实的预防再狭窄的方法是在手术后立即用高剂量x光(体外放射源或者管腔内放置的放射性同位素)对相关的血管壁区域进行辐射。
辐射主要的缺点是运用治疗性放射剂量时需要必要的安全措施。虽然在实验室和临床实践中试验了许多其他预防早期再狭窄的方法,但是至今仍无任何重要突破[Bult H.《再狭窄:药理学的一个挑战(Achallenge for pharmacology)》,Tips 21274-279,2000]。目前只有使用释放药物的斯滕特固定模才获得良好的效果。为了此方法的有效性,必须植入斯滕特固定模,而无斯滕特固定模植入的单独的血管扩张不可能预防再狭窄。
已经描述到有很多抑制有丝分裂、血管壁反应性增厚和再狭窄的药物。重要的作用原理是抑制血小板聚集、酶的抑制、有丝分裂的抑制、细胞生长抑制和类皮质激素。在体外和部分动物试验中取得了令人满意的结果,但是尚未在临床试验中得到证实。主要的解释是在相关的管壁区域中达不到足够的活性药物浓度。因为副作用限制了较高剂量的应用,口服和静脉内给药特别符合这种情况。作为替代方法,尝试使用特殊的导管给药,其中这些导管或者通过紧挨气囊的小孔将药物溶液直接推入血管壁中,或者阻断血管区域血液的供给排放,并使该管壁区域吸收接受所述药物溶液一段时间[Herdeg,C.,M.Oberhoff,D.I.Siegel-Axel,A.Baumbach,A.Blattner.A.Küttner,S.
Figure S06199822520060721D000021
K.R.Karsch:紫杉酚:预防再狭窄的化学疗法?体外和体内实验研究(Paclitaxel:Ein Chemotherapeutikumzur Restenoseprophylaxe?Experimentelle Untersuchungen inVitro und in Vivo).Z Kardiol 89 390-397,2000]。通过从包被的斯滕特固定模中缓慢释放活性剂可以使先前扩张的血管区域经较长一段时间有效地暴露于药物中。所有这些方法都仍然难以使需要治疗的血管区域足够长时间地暴露于足够的活性剂浓度之下。亲水性活性剂会很快从组织中冲掉[Baumbach,A.,C.Herdeg,M.Kluge,M.Oberhoff,M.Lerch,K.K.Haase,C.Wolter,S.K.R.Karsch:《局部药物的传递:压力、物质特性和斯滕特固定模对药物转移进入动脉壁的影响(Local drug delivery:Impact of pressure,substance characteristics,and stenting on drug transfer intothe arterial wall)》。Cathet Cardiovasc Intervent 47 102-106,1999]。由于采用导管侵入性进入,重复给药是不可能的。亲脂性的活性剂不能在血管相容的水性介质中充分溶解,或者在溶液中保持为微胞或脂质体;这些微胞或脂质体只能被组织缓慢吸收。特殊导管可在一段时间内中断血流给药,或在高压下将活性剂溶液压入血管壁,这首先造成额外的组织损害,并增强了反应性增生。包被的、释放药物的斯滕特固定模难以以恒定的质量制备,由于其重量轻和丝织形状,只能含有极少量的活性剂,并不适于对斯滕特固定模周围几毫米处有再狭窄危险的重要血管区域进行近端和远端的治疗。如果先前已植入斯滕特固定模,其管腔内出现狭窄,可以通过给气囊导管的扩张去除狭窄。将第二个斯滕特固定模植入第一个斯滕特固定模的血管腔中以预防扩张造成的管壁增生是不可取的,因此,对于这种情况,没有任何预防再狭窄的有效方法。上述情况同样适用于当血管成形术后没有需要植入斯滕特固定模的指征时,或在没有明显的腔狭窄而出现血管增生时,这样既不需要血管扩张,也不需要植入斯滕特固定模。某些这样的血管壁改变可导致突发性的、大多为血栓形成的栓塞。在这种情况下,也需要一种不依赖斯滕特固定模植入而抑制血管壁病理性变化的方法。
目前在实验研究规模中获得某些成功的活性剂是肝素和水蛭素衍生物、前列腺环素、类皮质激素、雷帕霉素、秋水仙素和紫杉酚。
在多数情况下,将这些活性剂应用于斯滕特固定模;只要是使用溶液,均为含乙醇或Cremophor(聚二醇化物的商品名)添加剂的水溶液或者水溶性很差的紫杉酚(4,10β-二乙酰氧基-13α-((2R,3S)-3-苯甲酰氨基-2-羟基-3-苯基丙酰氧基)-2α-苯甲酰氧基-5β,20-环氧-1,7β-二羟基-11-紫杉烯-9-酮)(紫杉烯=taxen)水溶液,使用Cremophor[聚(氧乙烯)-35-蓖麻油]会形成微胞,而使用乙醇可以大大避免微胞的形成。
已经有报道关于添加了有或无造影剂的在水性细胞抑制剂溶液中含较大颗粒的悬浮液或乳液,用于直接注射入肿瘤供血的血管。这些制剂用于闭塞肿瘤的血管,并同时进行细胞抑制的治疗。闭塞血管恰好是本发明的目的。
本发明的任务在于提供局部治疗潜在高增生组织的组合物,其使用方便,而且对患者没有损害。
根据现有技术的状况,本发明对此难题的解决,是通过在丁醇和水之间的分配比为≥0.5的含有至少一个抗增生的活性剂的制剂,加入到提高动脉和静脉显影的组合物中,或者包被导管而实现的。
由此本发明提供用于肠胃外、局部治疗过度增生性组织的制剂,其特别是在紧急治疗期间用于抑制病理性血管壁变化,用于预防再狭窄和用于局部肿瘤治疗,而无额外的血管壁损害或血流限制/栓塞;其含有亲脂的,抗过度增生的活性剂,并且其不含形成微胞的、延缓其快速和足量地被管壁吸收的物质,其中有机溶剂含量低于10%或经干燥除去,且活性剂在丁醇/水体系中具有分配比为≥0.5和/或结合细胞成分。
本发明的原理是基于以下惊人的观察:只要不被增溶剂封闭在向外亲水的微胞中,足够浓缩的溶液、凝胶或其他基质中的活性剂会被血管壁足量而快速地吸收。当活性剂是亲脂性的(丁醇与水性缓冲液(pH 7)的分配比≥0.5,优选≥1,特别优选≥5,或者辛醇与水性缓冲液(pH 7)的分配比≥1,优选≥10,特别优选≥50),或可逆地(>10%、优选>50%、特别优选>80%)和/或不可逆地与细胞成分(例如紫杉酚、普罗布考(4,4’-(亚异丙基二硫)双(2,6-二-叔丁基苯酚))、卟啉衍生物)结合时,在血管扩张和视需要斯滕特固定模植入期间给药时,药物在相关血管区域中的留滞时间足以产生治疗作用。通过阻止和减轻血管损伤所致的初期反应性增生,可以在数月中防止的血管壁的急剧增厚。令人惊奇的是,本发明的制剂证明不需要使被治疗的组织较长时间的暴露,或者不需要在额外损伤血管壁下直接渗入。
在血管成形术和斯滕特固定模植入期间,多次重复地将造影剂选择性地注入相关血管以确定狭窄的位置、程度和形态,以确定扩张导管的准确位置,评价扩张的成功与否,以及可选择性地植入一个适宜强度和长度的斯滕特固定模。通过将活性剂或其适于此目的的制剂加入用于诊断的造影剂中,则在每次注射造影剂的同时就将该活性剂传递至血管壁上,不需要作别的努力或对血管造成损伤。在此治疗的是用以诊断显影的整个血管区域,包括狭窄前的区域和其远端的区域。主要优点是:经扩张的狭窄和选择性斯滕特固定模植入部位的前后临界区域,均不会排除在治疗之外。
如果不需要或不希望注射造影剂,同样可以使用在其他的水性载体中的亲脂性活性剂溶液。条件是这些溶液所含活性剂的浓度高于其在水性介质中的饱和浓度。可以通过添加不产生或极少产生微胞的有机溶剂(例如乙醇和DMSO)达到此目的,和/或通过在不利于储存和给药条件(例如加热,与浓缩活性剂溶液的有机溶剂混合)下溶解这些活性剂,而形成足够稳定的过饱和溶液而达到此目的。
在某些情况下,水溶性低的亲脂性活性剂在造影剂溶液中的溶解性或过饱和溶液的稳定性得到惊人提高。造影剂所致的另一个令人惊奇的作用是增强了活性剂的管壁粘附性和血吸收性,以及在敏感的血管区域对某些极度系统毒性的物质具有良好的局部耐受性。
即使活性剂与造影剂不相容,或活性剂在造影剂中不能足够溶解,还可以通过诊断导管将该活性剂溶液直接注入或注射入相应的血管中。在此优选相近于通过导管使用造影剂给血管显影的容积[Elke M:造影剂在应用辐射学的诊断中(Kontrastmittel in derradiologischen Diagnostik),113-119页,第3版,Georg ThiemeVerlag Stuttgart New York,1992]。
造影剂是血管耐受的溶液、悬浮液或乳液,其可以用于增强X光照片、超声波检测、光学成像或磁共振成像中血管或血流的显像。这些造影剂包括例如Visipaque 320(碘克沙醇)、Ultravist 370(碘普胺)、Omnipaque 350(碘海醇)或Solutrast 370(碘帕醇)或Magnevist(马根维显,钆-DPTA)或Gadovist 1M(钆布醇,Gd-DO3A-butrol)。
作为活性剂考虑所有用于抑制细胞生长、细胞增殖和增生性增殖的适宜物质,只要它们符合上述关于亲脂性和/或与组织成分结合的条件。由于一些活性剂不具有足够的亲脂性或者结合能力,也可以使用它们的药物活性衍生物或药物活性剂的前体,这样它们直到组织中才释放真正的活性剂。优选的是类紫杉(Taxoide)的细胞抑制剂,例如紫杉酚和多西他赛((2R,3S)-N-(叔丁氧基羰基)-2-羟基-3-苯基-β-丙氨酸-(4-乙酰氧基-2α-苯甲酰氧基-5β,20-环氧-1,7β,10β-三羟基-9-氧代-11-紫杉酚-13α-基-酯),或者作为强亲脂性物质的实例是大环内酯类抗肿瘤药(Epothilone)。这些是亲脂性且不溶于水的,以致可优选例如NicollaouKC,Riemer C,Kerr MA,Rideout D,Wrasidlo W.在《紫杉醇的设计、合成和生物活性(Design,synthesis and biological activityof protaxols)》,《自然(Nature)》,1993;364:464-466或USP 457,674,《Novel Taxoids》中描述的较亲水的衍生物,只要它们的分子量不超过大约10KD。
其他可用的活性剂选自类皮质激素、有丝分裂抑制剂例如秋水仙碱、抗生素例如阿奇霉素或罗红霉素(Gupta等,1998)或抗氧化剂例如普罗布考,以及肝素和水蛭素衍生物或前列腺环素。另外,免疫抑制剂例如雷帕霉素也可用作活性剂。
其他亲水性细胞抑制剂的亲脂性衍生物的实例可见于Brunner H,Schellerer K-M,Treittinger B.的《作为有效的细胞抑制剂和射线损害抗肿瘤剂的铂(II)络合物中血卟啉型配体的合成和体外实验(Synthesis and in Vitro testing of hematoporphyrin type ligandsin platinum(II)complexes as potent cytostatic and phototoxicantitumor agents)》Inorganica Chimica Acta,1997;264:67-79,形式为铂络合物与卟啉的轭合物。
本发明含有细胞抑制剂作为活性剂的制剂,也适于治疗肿瘤疾病。用于局部治疗是有利的,将患者的紧张度降至最低。
除了亲脂性物质外,对血管壁,特别是对发生病理变化的血管壁,具有特异亲和力的活性剂或结合底物的活性剂也是适宜的。这些物质对血管壁具有特异亲和力,在数分钟内不会被血流冲走。已经知道静脉内给药后低浓度磁铁矿沉积在动脉硬化改变的血管壁中(SchmitzSA等,Watanabe可遗传高脂血兔动脉粥样硬化斑的超顺磁性氧化铁增强的MRI(Superparamagnetic iron oxide-enhanced MRI ofatherosclerotic plaques in Watanabe hereditable hyperlipidemicrabbits),Invest Radiol,2000;35:460-471)。但是,令人惊奇的是这些磁铁矿在短时间流过用气囊扩张的血管后,可以达到治疗的足够浓度。为了使这些磁铁矿可用于治疗,必须用药物将它们包被,这些药物例如为Lübbe AS,Bergemann C,Huhnt W,Fricke T,RiessH,Brock JW,Huhn D.在《用磁性药物定位的临床前试验:耐受性和效力(Preclinical Experiences with magnetic drug targeting:Tolerance and efficacy)》(Cancer Research,1996;56:4694-4701)中所述的药物。
将活性剂尽可能多地溶解在未稀释的造影剂中。也可将它们制备为独立的溶液,在使用前用造影剂对它们进行稀释。在此活性剂溶液和造影剂溶液的混合比应当不大于2∶1,优选小于1∶1,特别优选小于0.2∶1。该活性剂应当溶解于耐受性好的水性介质或可以与水混合的介质中。而且,还可以使用具有良好耐受性(至少在用造影剂溶液或另一种水性介质稀释后)的有机溶剂,例如乙醇、DMSO、DMF等。制备的注射溶液将尽可能用高份额的水(>90体积%,优选>95体积%,特别优选≥99体积%)。
每种活性剂的浓度范围根据它们不借助微胞形成剂(例如Cremophor的情况下)在生理耐受的溶剂中的溶解性,以及此活性剂的有效性和耐受性而定。浓度的上限通常通过给药的体积(例如100-200ml,用于多次注射入冠状动脉)和系统最大耐受剂量(例如对于紫杉酚约为100mg/m2体表面积)确定。优选地且因为局部给药和局部作用,足量的有效剂量为最大系统耐受剂量的1/10或更少。
可将其他有效物质例如凝结抑制剂、血小板聚集抑制剂、酶抑制剂、钙离子的络合物形成剂等加入此制剂中。这些物质不必符合所述亲脂性、与组织成分结合或分子量的条件,这是因为其作用也可以是急性血管内的;上面关于浓度和剂量段落中所述的内容适用于此,是因为重点集中在制剂流经的血管区域的局部作用上。
抗增生性活性剂的另一种给药方式是通过用于扩张血管的具有引起血管扩张的可膨胀的气囊导管进行给药。气囊可以用活性剂包被。气囊挤压在血管壁上以扩张血管。这为活性剂转运至血管壁提供了机会。如果将此气囊用于扩张斯滕特固定模,也可以将气囊和斯滕特固定模之间的活性剂释放出来,原因是造成了斯滕特固定模的金属支柱相的移动。与血管扩张或斯滕特固定模植入的原有方法相比,这些活性剂给药的方案对医生来说,不需要附加的步骤。
如果活性剂包被扩张血管的导管部分,则可使用下列的方法:将活性剂溶于不腐蚀导管的溶剂中,将相应的导管部分浸泡在该溶液中,将导管从溶液中取出,并干燥。可以将血管耐受的基质或凝胶形成辅剂加入活性剂溶液中,例如药物学上可用的脂质体或聚合物。可在多个步骤中进行包被,其中含有活性剂和不含活性剂的层可交替包被。选择各层溶剂的方法应当是后面的包被层不会将先前的包被层溶解。
本发明所提供的制剂中还可含有不形成微胞的增溶剂。优选所述抗过度增生的活性剂或携带该活性剂的组分与血管壁具有特异亲和力。
本发明还提供根据本发明的制剂在制备药物中的用途,所述药物用于预防再狭窄、抑制病理性管壁变化和用于局部肿瘤治疗,所述药物在血管造影术操作中或治疗措施中借助在管腔中的导管将所述抗过度增生的活性剂以立即生物供给的形式传送到组织中,而无需额外地中断血流或额外地损伤管壁。
下面的实施例进一步解释本发明:
实施例
实施例1a:一次性直接向动脉给药的溶液
将80mg 7-(2”,3”-二羟丙基氧羰基)-紫杉酚溶于5ml二甲亚砜,并用5ml 5%葡萄糖溶液稀释。将此溶液或其一部分缓慢地注入先前已经扩张的动脉中。
实施例1b:含抑制内膜增生的添加剂的X光造影剂
将一份1a中所述溶液加入99份市售的X光造影剂Visipaque 320中,并立即充分混合。该溶液在血管扩张前和后以惯用的方式用于血管造影术。
实施例2a:用于造影剂添加剂的溶液
将200mg 7-(2”,3”-二羟丙基氧羰基)-紫杉酚溶于10ml纯乙醇(=溶液A);可将0.35ml该溶液加入100ml造影剂中。
实施例2b:用于预防再狭窄的X光造影剂
100ml Ultravist 370(Schering AG,柏林;活性剂碘普胺,相当于370mg碘/ml)含有0.35体积%的乙醇和7mg 7-(2”,3”-二羟丙基氧羰基)-紫杉酚。通过将7-(2”,3”-二羟丙基氧羰基)-紫杉酚首先溶于乙醇,然后在不间断搅拌下,将其加入造影剂而制备该溶液。
实施例2c:用于预防再狭窄的X光造影剂
加入10IU低分子肝素按照实施例2b制备。
实施例2d:抑制再狭窄的灌注溶液
将实施例2a中所述的3.5ml溶液A与46.5ml乙醇混合,并在快速振荡下,加至1000ml温(~50℃)5%葡萄糖溶液或等渗电解质溶液中。就象造影剂那样,通过导管将该溶液注入将要治疗的血管中;但是,灌输的速度与给入造影剂相比,可以减慢。
实施例3a:用于抑制内膜增生的X光造影剂
将100ml Ultravist 370(参见实施例2b)与0.4体积%乙醇和14.4mg 7-(2”,3”-二羟丙基氧羰基)-紫杉酚混合。按照实施例2b所述制备此制剂。
实施例4a:用于抑制细胞生长的X光造影剂
100ml Solutrast 370(Byk-Gulden,Konstanz;活性剂碘普胺,相当于370mg碘/ml),含有1.0体积%的乙醇和8.2mg紫杉酚/ml。制备该制剂,首先在稍微加热下将紫杉酚溶于纯乙醇,溶解后快速加入造影剂,并用力搅拌。
实施例4b:用于抑制内膜增生的X光造影剂
实施例4a的制剂,添加5IU肝素和5mmol/l柠檬酸缓冲液(pH7.0)。
实施例5a:作为造影剂或灌注溶液的添加剂的溶液
将20mg(±)-反-1,2-二氨基环己烷{7,12-双[1-(1,4,7,10,13,16-六氧十七烷基)-乙基]-3,8,13,17-四甲基卟啉-2,18-二丙酸}铂(II)溶于10ml二甲亚砜(=溶液B)。
实施例5b:含抑制细胞生长添加剂的X光造影剂
在快速搅拌下,将1ml溶液B加入100ml Ultravist 370(参见实施例2b)。该溶液适于注入动脉或注射入活或死的组织中或体腔中。它可以产生最初分布的良好控制,并引起长期持续的细胞抑制作用。
实施例5c:含抑制细胞生长添加剂的磁共振断层照像术的造影剂
将1ml溶液B加入10ml 50毫摩尔马根维显(=Gadopentetat)溶液。通过10倍稀释Magnevist[一种市售制剂(Schering AG,Berlin)]制备50毫摩尔马根维显溶液。该溶液可以例如渗入致命的肿瘤或经过乙醇、加热或冷冻处理后的肿瘤。在磁共振断层照相术中该溶液的分布得到很好的显现。溶液本身支持在直接浸润区域及其邻近区域毫无遗漏地消灭肿瘤。
实施例6:实施例2b中所述制剂的体内效力
在麻醉下,将8头猪中每头猪的两条冠状动脉扩张,并植入斯滕特固定模(精细穿孔的金属管)。动脉的反应是壁增厚,它导致动脉原始管腔的狭窄。四头猪给予常规X光造影剂(Ultravist 370),以使动脉显影和检查斯滕特固定模的植入,四头猪给予实施例2b的制剂。处理后两个试验组的血管具有相同的宽度(内径3.4±0.2mm和3.5±0.2mm)。处理四周后,接受常规照影剂的动物的动脉内径狭窄了1.9±0.8mm,而接受了实施例2b溶液处理的动物的动脉直径仅仅减少了0.9±0.6mm。此差异具有统计学意义(p=0.01)。尽管在冠状动脉注射后以及ECG和血压测定的同时,加入高浓度的具有相当毒性的细胞抑制剂,实施例2b未稀释的溶液仍是可耐受的,而且没有副作用。
实施例7a:包被导管
在无菌的条件下,将为血管扩张而设计的气囊导管带有气囊的远端区域浸入实施例2a的乙醇溶液(=溶液A)中约5分钟,然后取出并在室温下干燥2小时。然后可以扩张血管常规的方法使用该气囊导管。或者,在干燥后,将斯滕特固定模装置在气囊区域。
实施例7b:
步骤类似实施例7a,不同的是将100mg药用蓖麻油加入溶液A中。实施例8a:在造影剂或生理NaCl溶液中的溶解性
将7.6mg紫杉酚溶于0.5mg乙醇,并在室温下,将其加入50mlUltravist-370(含有768mg碘普胺/ml,比重约1.4g/ml)中。混合后获得没有任何浑浊的澄清溶液,该溶液在几天内保持稳定。在显微镜下确定该溶液中没有任何颗粒。
将4.2mg紫杉酚溶于0.5ml乙醇中,并在室温下,将其加入50ml0.9%NaCl溶液中。混合后制剂立刻变得混浊;2小时后溶液表面出现大多数颗粒。使用显微镜可以发现有大量的细颗粒聚集。
评价:紫杉酚在造影剂中的溶解性令人惊奇的高。造影剂溶液含有0.7ml水/ml的溶液混合物,即与在NaCl溶液中的相比,在造影剂中对于紫杉酚有较少的溶剂可应用。尽管如此,紫杉酚在造影剂中溶解得好于在NaCl溶液中。
实施例8b:磁铁矿作为抗增生剂的载体
将75mg紫杉酚溶于5ml乙醇。将紫杉酚溶液加入50ml降解葡聚糖包被的胶态磁铁矿的含水制剂(浓度为Fe2+/3+0.5摩尔,例如SH U555C,柏林Schering AG的测试制剂)并快速相互混合。磁铁颗粒吸附紫杉酚,并在静脉内或动脉内注射后,将其转运至具有动脉硬化和脑肿瘤的动脉壁中。剂量随磁铁矿的使用而变化,大约50μmol Fe/kg体重。

Claims (15)

1.包含至少一种抗增生剂的制剂用于制造阻止或减轻由于在血管扩张和可能的斯滕特固定模的植入后的血管损伤所致的初期反应性增生的产品的导管的用途,所述抗增生剂在丁醇和水之间的分配比为≥0.5,所述制剂直接施加至导管上并干燥。
2.根据权利要求1的用途,所述导管用于使待治疗的组织短时间暴露于所述抗增生剂。
3.根据权利要求1或2的用途,所述导管用于局部治疗。
4.根据权利要求1或2的用途,其特征在于,所述抗增生剂不被增溶剂封闭在向外亲水的微胞中。
5.根据权利要求1或2的用途,其特征在于,所述制剂包含所述抗增生剂连同用于增强动脉和/或静脉显影的活性剂。
6.根据权利要求1或2的用途,其特征在于,所述抗增生剂为细胞生长抑制剂、类皮质激素、前列腺环素、抗氧化剂、抗生素、细胞增殖抑制剂或免疫抑制剂。
7.根据权利要求1或2的用途,其特征在于,所述抗增生剂为类紫杉。
8.根据权利要求1或2的用途,其特征在于,所述抗增生剂为紫杉醇、多西他塞、普罗布考、卟啉衍生物或大环内酯类抗肿瘤药。
9.根据权利要求5的用途,其特征在于,所述用于增强动脉和/或静脉显影的活性剂由血管可耐受并且适用于X光照相、超声波检测、光成像或磁共振成像用以增强血管或血流显像的溶液、悬浮液或乳液组成。
10.根据权利要求5的用途,其特征在于,所述用于增强动脉和/或静脉显影的活性剂为X光造影剂。
11.根据权利要求5的用途,其特征在于,所述用于增强动脉和/或静脉显影的活性剂为碘克沙醇(Visipaque)、钆-DTPA(马根维显)、轧布醇(Gadovist)、碘普胺(Ultravist)、碘海醇(Omnipaque)或碘帕醇(Solutrast)。
12.根据权利要求1或2的用途,其特征在于,所述制剂还包含凝结抑制剂和/或血小板聚集抑制剂和/或酶抑制剂和/或钙螯合剂。
13.根据权利要求1或2的用途,其特征在于,至少10%的所述抗增生剂可逆或不可逆地与组织结合。
14.根据权利要求1或2的用途,其特征在于,所述抗增生剂或携带该抗增生剂的组分与血管壁具有特异亲和力。
15.根据权利要求1或2的用途,其用于防止再狭窄。
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Families Citing this family (101)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6774278B1 (en) 1995-06-07 2004-08-10 Cook Incorporated Coated implantable medical device
US7947015B2 (en) 1999-01-25 2011-05-24 Atrium Medical Corporation Application of a therapeutic substance to a tissue location using an expandable medical device
US6955661B1 (en) 1999-01-25 2005-10-18 Atrium Medical Corporation Expandable fluoropolymer device for delivery of therapeutic agents and method of making
DE10115740A1 (de) * 2001-03-26 2002-10-02 Ulrich Speck Zubereitung für die Restenoseprophylaxe
ATE495769T1 (de) 2002-07-12 2011-02-15 Cook Inc Beschichtete medizinische vorrichtung
DE10244847A1 (de) 2002-09-20 2004-04-01 Ulrich Prof. Dr. Speck Medizinische Vorrichtung zur Arzneimittelabgabe
US8021331B2 (en) 2003-09-15 2011-09-20 Atrium Medical Corporation Method of coating a folded medical device
JP2007505658A (ja) 2003-09-15 2007-03-15 アトリウム メディカル コーポレーション 拡張可能医療用具を用いた治療物質の組織部位への塗布
US20050113687A1 (en) * 2003-09-15 2005-05-26 Atrium Medical Corporation Application of a therapeutic substance to a tissue location using a porous medical device
US9278015B2 (en) * 2003-10-16 2016-03-08 Minvasys Catheter system for stenting and drug treatment of bifurcated vessels
US8431145B2 (en) * 2004-03-19 2013-04-30 Abbott Laboratories Multiple drug delivery from a balloon and a prosthesis
US20070027523A1 (en) * 2004-03-19 2007-02-01 Toner John L Method of treating vascular disease at a bifurcated vessel using coated balloon
US7989490B2 (en) * 2004-06-02 2011-08-02 Cordis Corporation Injectable formulations of taxanes for cad treatment
US9012506B2 (en) 2004-09-28 2015-04-21 Atrium Medical Corporation Cross-linked fatty acid-based biomaterials
WO2006037080A2 (en) 2004-09-28 2006-04-06 Atrium Medical Corporation Uv cured gel and method of making
US9000040B2 (en) 2004-09-28 2015-04-07 Atrium Medical Corporation Cross-linked fatty acid-based biomaterials
US10076641B2 (en) 2005-05-11 2018-09-18 The Spectranetics Corporation Methods and systems for delivering substances into luminal walls
US9427423B2 (en) 2009-03-10 2016-08-30 Atrium Medical Corporation Fatty-acid based particles
US9278161B2 (en) 2005-09-28 2016-03-08 Atrium Medical Corporation Tissue-separating fatty acid adhesion barrier
US20080243068A1 (en) * 2005-12-29 2008-10-02 Kamal Ramzipoor Methods and apparatus for treatment of venous insufficiency
US7919108B2 (en) * 2006-03-10 2011-04-05 Cook Incorporated Taxane coatings for implantable medical devices
DE102006028232A1 (de) * 2006-06-20 2007-12-27 Bayer Technology Services Gmbh Vorrichtung und Verfahren zur Berechnung und Bereitstellung einer Medikamentendosis
US8414910B2 (en) 2006-11-20 2013-04-09 Lutonix, Inc. Drug releasing coatings for medical devices
US8425459B2 (en) 2006-11-20 2013-04-23 Lutonix, Inc. Medical device rapid drug releasing coatings comprising a therapeutic agent and a contrast agent
US8414525B2 (en) 2006-11-20 2013-04-09 Lutonix, Inc. Drug releasing coatings for medical devices
US9700704B2 (en) 2006-11-20 2017-07-11 Lutonix, Inc. Drug releasing coatings for balloon catheters
US9737640B2 (en) 2006-11-20 2017-08-22 Lutonix, Inc. Drug releasing coatings for medical devices
US8414909B2 (en) 2006-11-20 2013-04-09 Lutonix, Inc. Drug releasing coatings for medical devices
US8998846B2 (en) 2006-11-20 2015-04-07 Lutonix, Inc. Drug releasing coatings for balloon catheters
US8414526B2 (en) 2006-11-20 2013-04-09 Lutonix, Inc. Medical device rapid drug releasing coatings comprising oils, fatty acids, and/or lipids
US20080276935A1 (en) 2006-11-20 2008-11-13 Lixiao Wang Treatment of asthma and chronic obstructive pulmonary disease with anti-proliferate and anti-inflammatory drugs
US20080140002A1 (en) * 2006-12-06 2008-06-12 Kamal Ramzipoor System for delivery of biologically active substances with actuating three dimensional surface
KR20120106880A (ko) 2007-01-21 2012-09-26 헤모텍 아게 체강의 협착 치료 및 급성 재협착 예방을 위한 의료 제품
JP2008305262A (ja) * 2007-06-08 2008-12-18 Konica Minolta Business Technologies Inc サーバ及びシンクライアント環境でのプリンタ紹介方法
US9192697B2 (en) 2007-07-03 2015-11-24 Hemoteq Ag Balloon catheter for treating stenosis of body passages and for preventing threatening restenosis
DE102007036685A1 (de) 2007-08-03 2009-02-05 Innora Gmbh Verbesserte arzneimittelbeschichtete Medizinprodukte deren Herstellung und Verwendung
DE102007040868A1 (de) 2007-08-29 2009-04-16 Innora Gmbh Ballonkatheter mit Schutz vor Auffaltung
EP2191853B1 (en) 2007-09-28 2015-07-29 Terumo Kabushiki Kaisha In-vivo indwelling matter
WO2009065078A1 (en) * 2007-11-14 2009-05-22 Pathway Medical Technologies, Inc. Delivery and administration of compositions using interventional catheters
EP2789362B1 (en) 2007-11-21 2018-04-18 Invatec S.p.A. Balloon for the treatment of stenosis
DE102008008926A1 (de) * 2008-02-13 2009-08-20 Biotronik Vi Patent Ag System zum Einbringen einer intraluminalen Endoprothese und Verfahren zur Herstellung eines derartigen Systems
DE102008008925A1 (de) * 2008-02-13 2009-08-20 Biotronik Vi Patent Ag Katheter, System zum Einbringen einer intraluminalen Endoprothese sowie Verfahren zur Herstellung derselben
WO2009135125A2 (en) 2008-05-01 2009-11-05 Bayer Schering Pharma Ag Catheter balloon drug adherence techniques and methods
EP2296722B2 (de) 2008-05-31 2022-01-12 Lothar Sellin Medizinische einrichtung und verfahren zu ihrer herstellung
WO2010024898A2 (en) 2008-08-29 2010-03-04 Lutonix, Inc. Methods and apparatuses for coating balloon catheters
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
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
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
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
US8500687B2 (en) 2008-09-25 2013-08-06 Abbott Cardiovascular Systems Inc. Stent delivery system having a fibrous matrix covering with improved stent retention
US8226603B2 (en) 2008-09-25 2012-07-24 Abbott Cardiovascular Systems Inc. Expandable member having a covering formed of a fibrous matrix for intraluminal drug delivery
US8049061B2 (en) 2008-09-25 2011-11-01 Abbott Cardiovascular Systems, Inc. Expandable member formed of a fibrous matrix having hydrogel polymer for intraluminal drug delivery
US8076529B2 (en) 2008-09-26 2011-12-13 Abbott Cardiovascular Systems, Inc. Expandable member formed of a fibrous matrix for intraluminal drug delivery
WO2010080575A2 (en) 2008-12-18 2010-07-15 Michal Konstantino Method and apparatus for transport of substances into body tissue
IT1394522B1 (it) 2009-01-09 2012-07-05 Invatec Technology Ct Gmbh Dispositivo medicale con rilascio di farmaco
US20100261662A1 (en) * 2009-04-09 2010-10-14 Endologix, Inc. Utilization of mural thrombus for local drug delivery into vascular tissue
WO2010120620A1 (en) 2009-04-13 2010-10-21 Cook Incorporated Coated balloon catheter
CA2765258A1 (en) 2009-06-17 2010-12-23 Hans-Georg Neumann Method and device for coating catheters or balloon catheters
WO2011005421A2 (en) 2009-07-10 2011-01-13 Boston Scientific Scimed, Inc. Use of nanocrystals for a drug delivery balloon
EP2453938B1 (en) 2009-07-17 2015-08-19 Boston Scientific Scimed, Inc. Nucleation of drug delivery balloons to provide improved crystal size and density
US20110038910A1 (en) 2009-08-11 2011-02-17 Atrium Medical Corporation Anti-infective antimicrobial-containing biomaterials
CN102470196A (zh) 2009-08-27 2012-05-23 泰尔茂株式会社 药物输送用医疗器具
US8951595B2 (en) 2009-12-11 2015-02-10 Abbott Cardiovascular Systems Inc. Coatings with tunable molecular architecture for drug-coated balloon
US8480620B2 (en) 2009-12-11 2013-07-09 Abbott Cardiovascular Systems Inc. Coatings with tunable solubility profile for drug-coated balloon
CA2784689A1 (en) 2009-12-18 2011-06-23 Interface Biologics, Inc. Local delivery of drugs from self assembled coatings
EP2380604A1 (en) 2010-04-19 2011-10-26 InnoRa Gmbh Improved coating formulations for scoring or cutting balloon catheters
EP2380605A1 (en) 2010-04-19 2011-10-26 InnoRa Gmbh Improved formulations for drug-coated medical devices
DE102010023105A1 (de) * 2010-06-04 2011-12-08 Bayer Schering Pharma Aktiengesellschaft Gadobutrolherstellung im Eintopfverfahren mittels DMF-acetal und N-Methylimidazol
EP2593141B1 (en) 2010-07-16 2018-07-04 Atrium Medical Corporation Composition and methods for altering the rate of hydrolysis of cured oil-based materials
WO2012031236A1 (en) 2010-09-02 2012-03-08 Boston Scientific Scimed, Inc. Coating process for drug delivery balloons using heat-induced rewrap memory
EP2646066B1 (de) 2010-12-04 2018-03-14 Aachen Scientific International PTE. LTD. Beschichtung und beschichtungsverfahren für den ballon eines ballonkatheters sowie ballonkatheter mit beschichtetem ballon
DE102011000340A1 (de) 2010-12-04 2012-06-06 Alexander Rübben Beschichtung und Beschichtungsverfahren für den Ballon eines Ballonkatheters sowie Ballonkatheter mit beschichtetem Ballon
EP2654874B1 (en) 2010-12-21 2018-04-11 Invatec Technology Center GMBH Drug eluting balloon for the treatment of stenosis and method for manufacturing the balloon
US8669360B2 (en) 2011-08-05 2014-03-11 Boston Scientific Scimed, Inc. Methods of converting amorphous drug substance into crystalline form
WO2013028208A1 (en) 2011-08-25 2013-02-28 Boston Scientific Scimed, Inc. Medical device with crystalline drug coating
WO2013079476A1 (de) 2011-11-30 2013-06-06 Bayer Materialscience Ag Arzneimittelbeschichtetes medizinisches gerät und verfahren zu dessen herstellung
WO2013091722A1 (en) 2011-12-23 2013-06-27 Innora Gmbh Drug-coated medical devices
EP3219335B1 (en) 2012-03-27 2018-12-19 Terumo Kabushiki Kaisha Coating composition and medical device
WO2013146376A1 (ja) 2012-03-27 2013-10-03 テルモ株式会社 コーティング組成物および医療機器
AU2013270798B2 (en) 2012-06-08 2017-09-07 Biotronik Ag Rapamycin 40-O-cyclic hydrocarbon esters, compositions and methods
US9867880B2 (en) 2012-06-13 2018-01-16 Atrium Medical Corporation Cured oil-hydrogel biomaterial compositions for controlled drug delivery
US9956385B2 (en) 2012-06-28 2018-05-01 The Spectranetics Corporation Post-processing of a medical device to control morphology and mechanical properties
WO2014011805A1 (en) * 2012-07-10 2014-01-16 Bayer Pharma Aktiengesellschaft Catheter with drug coating
US10850076B2 (en) 2012-10-26 2020-12-01 Urotronic, Inc. Balloon catheters for body lumens
US10898700B2 (en) 2012-10-26 2021-01-26 Urotronic, Inc. Balloon catheters for body lumens
WO2016172343A1 (en) 2015-04-24 2016-10-27 Urotronic, Inc. Drug coated balloon catheters for nonvascular strictures
US10881839B2 (en) 2012-10-26 2021-01-05 Urotronic, Inc. Drug-coated balloon catheters for body lumens
US11504450B2 (en) 2012-10-26 2022-11-22 Urotronic, Inc. Drug-coated balloon catheters for body lumens
US10806830B2 (en) 2012-10-26 2020-10-20 Urotronic, Inc. Drug-coated balloon catheters for body lumens
CN111166942A (zh) 2012-10-26 2020-05-19 优敦力公司 用于非血管狭窄的药物涂层球囊导管
DE102013104029A1 (de) 2013-04-22 2014-10-23 Innora Gmbh Ballonkatheter
US20150190618A1 (en) 2014-01-09 2015-07-09 Medtronic Vascular, Inc. Balloon Catheter With Elastomeric Sheath and Methods
US10525171B2 (en) 2014-01-24 2020-01-07 The Spectranetics Corporation Coatings for medical devices
US9180226B1 (en) 2014-08-07 2015-11-10 Cook Medical Technologies Llc Compositions and devices incorporating water-insoluble therapeutic agents and methods of the use thereof
US9655998B2 (en) 2014-08-07 2017-05-23 Cook Medical Technologies Llc Encapsulated drug compositions and methods of use thereof
US11241520B2 (en) 2014-08-07 2022-02-08 Cook Medical Technologies Llc Compositions and devices incorporating water-insoluble therapeutic agents and methods of the use thereof
US9675734B2 (en) 2014-08-29 2017-06-13 Invatec S.P.A. Medical balloon coated with therapeutic agent, carboxylic acid, and salt thereof
US11904072B2 (en) 2015-04-24 2024-02-20 Urotronic, Inc. Drug coated balloon catheters for nonvascular strictures
TWI586391B (zh) * 2016-06-23 2017-06-11 何中庸 一種氣囊管裝置與運作方法
CN108543165B (zh) * 2018-02-27 2021-06-18 宁波胜杰康生物科技有限公司 一种基于载体的肌功能辅助装置
WO2019222843A1 (en) 2018-05-22 2019-11-28 Interface Biologics, Inc. Compositions and methods for delivering drugs to a vessel wall

Family Cites Families (316)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US554181A (en) * 1896-02-04 Robert frederick hall
US2624642A (en) * 1950-05-24 1953-01-06 Symington Gould Corp Journal box lid
US4101984A (en) * 1975-05-09 1978-07-25 Macgregor David C Cardiovascular prosthetic devices and implants with porous systems
US4247352A (en) * 1976-11-29 1981-01-27 North American Philips Corporation Method of bonding crystal layers to insulating substrates
DE2721752C2 (de) 1977-05-13 1983-12-29 Siemens AG, 1000 Berlin und 8000 München In einen menschlichen oder tierischen Körper implantierbares Gerät zur Infusion einer medizinischen Flüssigkeit
DE2909439A1 (de) * 1979-03-08 1980-09-18 Schering Ag Neue nichtionische roentgenkontrastmittel
US4479795A (en) 1979-06-29 1984-10-30 The Procter & Gamble Company Antimicrobial polymer compositions
US4343788A (en) 1979-06-29 1982-08-10 The Procter & Gamble Company Antimicrobial polymer compositions
US4305926A (en) 1979-09-13 1981-12-15 Johannes Everse Immobilization of Streptokinase
US4476590A (en) 1980-03-27 1984-10-16 National Research Development Corporation Antimicrobial surgical implants
JPS5881601A (ja) * 1981-11-11 1983-05-17 毛利 正巳 ずれ落ちないガ−タ付靴下
US4502159A (en) 1982-08-12 1985-03-05 Shiley Incorporated Tubular prostheses prepared from pericardial tissue
US4769013A (en) 1982-09-13 1988-09-06 Hydromer, Inc. Bio-effecting medical material and device
FR2540128B1 (fr) 1983-01-27 1986-02-21 Rhone Poulenc Spec Chim Compositions organopolysiloxaniques contenant des polyacyloxysilanes et durcissant tres rapidement en elastomeres en presence d'accelerateur du type hydroxyde metallique
US4573476A (en) * 1983-11-14 1986-03-04 Ruiz Oscar F Angiographic catheter
US5108424A (en) * 1984-01-30 1992-04-28 Meadox Medicals, Inc. Collagen-impregnated dacron graft
US5197977A (en) * 1984-01-30 1993-03-30 Meadox Medicals, Inc. Drug delivery collagen-impregnated synthetic vascular graft
US5456663A (en) 1984-05-25 1995-10-10 Lemelson; Jerome H. Drugs and methods for treating diseases
US4879135A (en) 1984-07-23 1989-11-07 University Of Medicine And Dentistry Of New Jersey Drug bonded prosthesis and process for producing same
GB8422876D0 (en) 1984-09-11 1984-10-17 Secr Defence Silicon implant devices
US4677143A (en) 1984-10-01 1987-06-30 Baxter Travenol Laboratories, Inc. Antimicrobial compositions
US4677413A (en) * 1984-11-20 1987-06-30 Vishay Intertechnology, Inc. Precision power resistor with very low temperature coefficient of resistance
WO1986007541A1 (en) 1985-06-19 1986-12-31 Yasushi Zyo Composition which can impart antithrombotic ability and medical apparatus to be in contact with blood
JPH0663145B2 (ja) 1985-09-11 1994-08-17 豊和工業株式会社 紡機におけるスライバ−供給方法および装置
US4733665C2 (en) 1985-11-07 2002-01-29 Expandable Grafts Partnership Expandable intraluminal graft and method and apparatus for implanting an expandable intraluminal graft
US4917686A (en) * 1985-12-16 1990-04-17 Colorado Biomedical, Inc. Antimicrobial device and method
US6051405A (en) * 1986-09-24 2000-04-18 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Constructs encoding recombinant antibody-toxin fusion proteins
US5059211A (en) * 1987-06-25 1991-10-22 Duke University Absorbable vascular stent
US4909799A (en) * 1987-09-18 1990-03-20 Olav Thulesius Methods for preventing thrombosis; and surgical implant having reduced platelet deposition characteristics
US5098977A (en) * 1987-09-23 1992-03-24 Board Of Regents, The University Of Texas System Methods and compositions for providing articles having improved biocompatability characteristics
US4886062A (en) 1987-10-19 1989-12-12 Medtronic, Inc. Intravascular radially expandable stent and method of implant
US5019601A (en) * 1987-12-29 1991-05-28 Cuno, Incorporated Elastomeric composition containing therapeutic agents and articles manufactured therefrom
JP2561853B2 (ja) 1988-01-28 1996-12-11 株式会社ジェイ・エム・エス 形状記憶性を有する成形体及びその使用方法
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
US5157049A (en) 1988-03-07 1992-10-20 The United States Of America As Represented By The Department Of Health & Human Services Method of treating cancers sensitive to treatment with water soluble derivatives of taxol
US4950256A (en) 1988-04-07 1990-08-21 Luther Medical Products, Inc. Non-thrombogenic intravascular time release catheter
US4994047A (en) * 1988-05-06 1991-02-19 Menlo Care, Inc. Multi-layer cannula structure
US5770198A (en) * 1988-05-18 1998-06-23 The Research Foundation Of The State Of New York Platelet-specific chimeric 7E3 immunoglobulin
US5182317A (en) * 1988-06-08 1993-01-26 Cardiopulmonics, Inc. Multifunctional thrombo-resistant coatings and methods of manufacture
US5019393A (en) * 1988-08-03 1991-05-28 New England Deaconess Hospital Corporation Biocompatible substance with thromboresistance
US5019090A (en) 1988-09-01 1991-05-28 Corvita Corporation Radially expandable endoprosthesis and the like
US5053048A (en) 1988-09-22 1991-10-01 Cordis Corporation Thromboresistant coating
US5298255A (en) * 1988-10-28 1994-03-29 Terumo Kabushiki Kaisha Antithrombic medical material, artificial internal organ, and method for production of antithrombic medical material
US4925668A (en) * 1989-01-18 1990-05-15 Becton, Dickinson And Company Anti-infective and lubricious medical articles and method for their preparation
US5165952A (en) 1989-01-18 1992-11-24 Becton, Dickinson And Company Anti-infective and antithrombogenic medical articles and method for their preparation
US6146358A (en) 1989-03-14 2000-11-14 Cordis Corporation Method and apparatus for delivery of therapeutic agent
US5004461A (en) * 1989-03-23 1991-04-02 Wilson Joseph E Methods for rendering plastics thromboresistant and product
JPH03505744A (ja) 1989-04-28 1991-12-12 シラキューズ ユニバーシティ サイトカラシン組成物および治療法
US5051257A (en) 1989-05-09 1991-09-24 Pietronigro Dennis D Antineoplastic solution and method for treating neoplasms
WO1990013332A1 (en) 1989-05-11 1990-11-15 Cedars-Sinai Medical Center Stent with sustained drug delivery
US4997643A (en) * 1989-07-12 1991-03-05 Union Carbide Chemicals And Plastics Company Inc. Polymeric salt delivery systems
US5232685A (en) * 1989-11-03 1993-08-03 Schering Aktiengesellschaft Nonionic x-ray contrast medium with high iodine content
US5067491A (en) 1989-12-08 1991-11-26 Becton, Dickinson And Company Barrier coating on blood contacting devices
US5059166A (en) 1989-12-11 1991-10-22 Medical Innovative Technologies R & D Limited Partnership Intra-arterial stent with the capability to inhibit intimal hyperplasia
US5674192A (en) 1990-12-28 1997-10-07 Boston Scientific Corporation Drug delivery
US5304121A (en) * 1990-12-28 1994-04-19 Boston Scientific Corporation Drug delivery system making use of a hydrogel polymer coating
US5135516A (en) 1989-12-15 1992-08-04 Boston Scientific Corporation Lubricious antithrombogenic catheters, guidewires and coatings
ATE120377T1 (de) 1990-02-08 1995-04-15 Howmedica Aufblasbarer dilatator.
CA2049973C (en) 1990-02-28 2002-12-24 Rodney G. Wolff Intralumenal drug eluting prosthesis
WO1991017724A1 (en) 1990-05-17 1991-11-28 Harbor Medical Devices, Inc. Medical device polymer
US5166143A (en) * 1990-05-31 1992-11-24 E. R. Squibb & Sons, Inc. Method for preventing onset of restenosis after angioplasty employing an ace inhibitor
US5407683A (en) * 1990-06-01 1995-04-18 Research Corporation Technologies, Inc. Pharmaceutical solutions and emulsions containing taxol
US5320634A (en) 1990-07-03 1994-06-14 Interventional Technologies, Inc. Balloon catheter with seated cutting edges
US5112457A (en) * 1990-07-23 1992-05-12 Case Western Reserve University Process for producing hydroxylated plasma-polymerized films and the use of the films for enhancing the compatiblity of biomedical implants
US5455040A (en) 1990-07-26 1995-10-03 Case Western Reserve University Anticoagulant plasma polymer-modified substrate
US5163952A (en) 1990-09-14 1992-11-17 Michael Froix Expandable polymeric stent with memory and delivery apparatus and method
US5222971A (en) * 1990-10-09 1993-06-29 Scimed Life Systems, Inc. Temporary stent and methods for use and manufacture
US5244654A (en) 1990-11-08 1993-09-14 Cordis Corporation Radiofrequency plasma biocompatibility treatment of inside surfaces of medical tubing and the like
CA2098984C (en) 1990-12-28 2002-03-05 Ronald Sahatjian Drug delivery system
US6524274B1 (en) 1990-12-28 2003-02-25 Scimed Life Systems, Inc. Triggered release hydrogel drug delivery system
US5102402A (en) 1991-01-04 1992-04-07 Medtronic, Inc. Releasable coatings on balloon catheters
US5893840A (en) * 1991-01-04 1999-04-13 Medtronic, Inc. Releasable microcapsules on balloon catheters
US5324261A (en) 1991-01-04 1994-06-28 Medtronic, Inc. Drug delivery balloon catheter with line of weakness
WO1992012717A2 (en) 1991-01-15 1992-08-06 A composition containing a tetracycline and use for inhibiting angiogenesis
US5762638A (en) * 1991-02-27 1998-06-09 Shikani; Alain H. Anti-infective and anti-inflammatory releasing systems for medical devices
US5344411A (en) 1991-02-27 1994-09-06 Leonard Bloom Method and device for inhibiting HIV, hepatitis B and other viruses and germs when using a catheter in a medical environment
US5171217A (en) 1991-02-28 1992-12-15 Indiana University Foundation Method for delivery of smooth muscle cell inhibitors
DE4115950A1 (de) 1991-05-16 1992-11-19 Herberts Gmbh Fluessige gemische von photoinitiatoren, verfahren zu deren herstellung und deren verwendung
NL9101159A (nl) 1991-07-03 1993-02-01 Industrial Res Bv Vormvast te maken uitzetbare ring, cylinder of huls.
US5356433A (en) 1991-08-13 1994-10-18 Cordis Corporation Biocompatible metal surfaces
SE9102778D0 (sv) 1991-09-25 1991-09-25 Siemens Elema Ab Implanterbar medicinsk anordning
US6515009B1 (en) 1991-09-27 2003-02-04 Neorx Corporation Therapeutic inhibitor of vascular smooth muscle cells
US5500013A (en) * 1991-10-04 1996-03-19 Scimed Life Systems, Inc. Biodegradable drug delivery vascular stent
WO1993006792A1 (en) 1991-10-04 1993-04-15 Scimed Life Systems, Inc. Biodegradable drug delivery vascular stent
US5464450A (en) 1991-10-04 1995-11-07 Scimed Lifesystems Inc. Biodegradable drug delivery vascular stent
DE4135193C1 (zh) 1991-10-22 1993-03-11 Schering Ag Berlin Und Bergkamen, 1000 Berlin, De
JP3093375B2 (ja) 1991-11-01 2000-10-03 株式会社東海メディカルプロダクツ 抗血栓性物質の固定化方法
US5264220A (en) 1991-11-12 1993-11-23 Long David M Jr Method of extending the vascular dwell-time of particulate therapeutic and particulate diagnostic agents
US5302397A (en) 1991-11-19 1994-04-12 Amsden Brian G Polymer-based drug delivery system
US5270047A (en) * 1991-11-21 1993-12-14 Kauffman Raymond F Local delivery of dipyridamole for the treatment of proliferative diseases
WO1993011120A1 (en) 1991-11-27 1993-06-10 Zynaxis Technologies, Incorporated Compounds, compositions and methods for binding bio-affecting substances to surface membranes of bio-particles
JPH07502274A (ja) 1991-12-10 1995-03-09 ラシユ−プレスビタリアン−セントルークス・メデイカル・センター 多薬剤耐性を低下させる方法および組成物
CA2086642C (en) 1992-01-09 2004-06-15 Randall E. Morris Method of treating hyperproliferative vascular disease
US5176626A (en) * 1992-01-15 1993-01-05 Wilson-Cook Medical, Inc. Indwelling stent
US5605896A (en) * 1992-02-25 1997-02-25 Recordati S.A., Chemical And Pharmaceutical Company Bicyclic heterocyclic derivatives having α1 adrenergic and 5HT1A activities
US5217493A (en) * 1992-03-11 1993-06-08 Board Of Regents, The University Of Texas System Antibacterial coated medical implants
US5282823A (en) * 1992-03-19 1994-02-01 Medtronic, Inc. Intravascular radially expandable stent
US5599352A (en) 1992-03-19 1997-02-04 Medtronic, Inc. Method of making a drug eluting stent
US5571166A (en) 1992-03-19 1996-11-05 Medtronic, Inc. Method of making an intraluminal stent
US5288711A (en) * 1992-04-28 1994-02-22 American Home Products Corporation Method of treating hyperproliferative vascular disease
US5383927A (en) * 1992-05-07 1995-01-24 Intervascular Inc. Non-thromogenic vascular prosthesis
US5629008A (en) * 1992-06-02 1997-05-13 C.R. Bard, Inc. Method and device for long-term delivery of drugs
US5383928A (en) * 1992-06-10 1995-01-24 Emory University Stent sheath for local drug delivery
DE4222380A1 (de) 1992-07-08 1994-01-13 Ernst Peter Prof Dr M Strecker In den Körper eines Patienten perkutan implantierbare Endoprothese
DE4225553C1 (de) 1992-08-03 1994-05-11 Michael Dr Rudolf Ballonkatheter
EP0752885B1 (en) 1992-09-25 2003-07-09 Neorx Corporation Therapeutic inhibitor of vascular smooth muscle cells
US5336178A (en) 1992-11-02 1994-08-09 Localmed, Inc. Intravascular catheter with infusion array
US5449382A (en) 1992-11-04 1995-09-12 Dayton; Michael P. Minimally invasive bioactivated endoprosthesis for vessel repair
US5578075B1 (en) 1992-11-04 2000-02-08 Daynke Res Inc Minimally invasive bioactivated endoprosthesis for vessel repair
AU5553894A (en) * 1992-11-27 1994-06-22 F.H. Faulding & Co. Limited Injectable taxol composition
US5342348A (en) 1992-12-04 1994-08-30 Kaplan Aaron V Method and device for treating and enlarging body lumens
US5443458A (en) 1992-12-22 1995-08-22 Advanced Cardiovascular Systems, Inc. Multilayered biodegradable stent and method of manufacture
EP0604022A1 (en) 1992-12-22 1994-06-29 Advanced Cardiovascular Systems, Inc. Multilayered biodegradable stent and method for its manufacture
US5419760A (en) * 1993-01-08 1995-05-30 Pdt Systems, Inc. Medicament dispensing stent for prevention of restenosis of a blood vessel
US5229172A (en) * 1993-01-19 1993-07-20 Medtronic, Inc. Modification of polymeric surface by graft polymerization
US6491938B2 (en) 1993-05-13 2002-12-10 Neorx Corporation Therapeutic inhibitor of vascular smooth muscle cells
EP2298310A3 (en) 1993-01-28 2011-04-06 Boston Scientific Limited Therapeutic inhibitors of vascular smooth muscle cells
US5981568A (en) 1993-01-28 1999-11-09 Neorx Corporation Therapeutic inhibitor of vascular smooth muscle cells
US5916596A (en) 1993-02-22 1999-06-29 Vivorx Pharmaceuticals, Inc. Protein stabilized pharmacologically active agents, methods for the preparation thereof and methods for the use thereof
US5976534A (en) * 1993-02-25 1999-11-02 Zymogenetics, Inc. Inhibition of intimal hyperplasia using antibodies to PDGF receptors and heparin
US5534288A (en) * 1993-03-23 1996-07-09 United States Surgical Corporation Infection-resistant surgical devices and methods of making them
US5607463A (en) * 1993-03-30 1997-03-04 Medtronic, Inc. Intravascular medical device
WO1994023787A1 (en) 1993-04-22 1994-10-27 Rammler David H Sampling balloon catheter
US5464650A (en) * 1993-04-26 1995-11-07 Medtronic, Inc. Intravascular stent and method
SE9301422D0 (sv) 1993-04-28 1993-04-28 Kabi Pharmacia Ab Method and means for inhibiting posterior capsule opacification
US5531715A (en) 1993-05-12 1996-07-02 Target Therapeutics, Inc. Lubricious catheters
ATE401911T1 (de) 1993-05-13 2008-08-15 Poniard Pharmaceuticals Inc Ein inhibitor für glatte gefässmuskelzellen für therapeutische nutzung
ATE502664T1 (de) 1993-07-19 2011-04-15 Angiotech Pharm Inc Herstellungsmethode eines stents mit anti- angiogener zusammensetzung
US5994341A (en) * 1993-07-19 1999-11-30 Angiogenesis Technologies, Inc. Anti-angiogenic Compositions and methods for the treatment of arthritis
US20030203976A1 (en) * 1993-07-19 2003-10-30 William L. Hunter Anti-angiogenic compositions and methods of use
EP0711158B2 (en) 1993-07-29 2008-07-23 THE GOVERNMENT OF THE UNITED STATES OF AMERICA, as represented by THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES Method of treating atherosclerosis or restenosis using microtubule stabilizing agent
US5567495A (en) 1993-08-06 1996-10-22 The Trustees Of Columbia University In The City Of New York Infection resistant medical devices
US5746745A (en) 1993-08-23 1998-05-05 Boston Scientific Corporation Balloon catheter
JP3694524B2 (ja) 1993-08-23 2005-09-14 ボストン サイエンティフィック コーポレイション 改良形バルーンカテーテル
US5380299A (en) * 1993-08-30 1995-01-10 Med Institute, Inc. Thrombolytic treated intravascular medical device
TW406020B (en) * 1993-09-29 2000-09-21 Bristol Myers Squibb Co Stabilized pharmaceutical composition and its method for preparation and stabilizing solvent
US5531716A (en) * 1993-09-29 1996-07-02 Hercules Incorporated Medical devices subject to triggered disintegration
DE4334272C2 (de) 1993-10-07 1996-07-18 Stemberger Axel Dr Beschichtung für Biomaterial und seine Verwendung
US5457113A (en) 1993-10-15 1995-10-10 Eli Lilly And Company Methods for inhibiting vascular smooth muscle cell proliferation and restinosis
US5454886A (en) 1993-11-18 1995-10-03 Westaim Technologies Inc. Process of activating anti-microbial materials
DE4341478C2 (de) 1993-12-02 1998-10-08 Max Delbrueck Centrum Mittel zur Antitumortherapie
ATE354377T1 (de) 1993-12-02 2007-03-15 Max Delbrueck Centrum Antitumormittel, enthaltend ein zytostatikum und ein kontrastmittel
US5397307A (en) 1993-12-07 1995-03-14 Schneider (Usa) Inc. Drug delivery PTCA catheter and method for drug delivery
WO1995020362A1 (en) 1994-01-26 1995-08-03 Reiley Mark A Improved inflatable device for use in surgical protocol relating to fixation of bone
DE4408768C1 (de) 1994-03-15 1995-05-04 Siemens Ag Verfahren zur Filterung einer digitalen Wertefolge mit verbessertem Rauschverhalten und Schaltungsanordnung zur Durchführung des Verfahrens
US5510330A (en) * 1994-03-25 1996-04-23 Boehringer Mannheim Gmbh Combinations of thrombolytically active proteins and non-heparin anticoagulants, and uses thereof.
DE4412055C1 (de) 1994-04-07 1995-05-18 Siemens Ag CMOS-Abschlußwiderstandsschaltung
US5554181A (en) 1994-05-04 1996-09-10 Regents Of The University Of Minnesota Stent
JP3631777B2 (ja) 1994-06-03 2005-03-23 テルモ株式会社 薬剤投与カテーテル
US5824644A (en) * 1994-07-07 1998-10-20 G. D. Searle & Co. Method of attenuating arterial stenosis
US6123715A (en) * 1994-07-08 2000-09-26 Amplatz; Curtis Method of forming medical devices; intravascular occlusion devices
US5649977A (en) * 1994-09-22 1997-07-22 Advanced Cardiovascular Systems, Inc. Metal reinforced polymer stent
US5733327A (en) * 1994-10-17 1998-03-31 Igaki; Keiji Stent for liberating drug
US5643580A (en) * 1994-10-17 1997-07-01 Surface Genesis, Inc. Biocompatible coating, medical device using the same and methods
GB9423419D0 (en) * 1994-11-19 1995-01-11 Andaris Ltd Preparation of hollow microcapsules
US5626562A (en) 1994-11-28 1997-05-06 Devices For Vascular Intervention Drug delivery catheter
DE4446694A1 (de) 1994-12-09 1996-06-13 Schering Ag Verwendung von Zusätzen zu Kontrastmitteln zur Verbesserung der Bildgebung
CA2163837C (en) 1994-12-13 1999-07-20 Robert K. Perrone Crystalline paclitaxel hydrates
US5599576A (en) * 1995-02-06 1997-02-04 Surface Solutions Laboratories, Inc. Medical apparatus with scratch-resistant coating and method of making same
DE19505155A1 (de) 1995-02-16 1996-08-22 Magna Zippex Autotechnik Gmbh Verfahren zum Herstellen eines Auskleidungsteiles aus Kunststoff und ein insbesonders nach diesem Verfahren hergestelltes Auskleidungsteil
US6558798B2 (en) * 1995-02-22 2003-05-06 Scimed Life Systems, Inc. Hydrophilic coating and substrates coated therewith having enhanced durability and lubricity
US5681846A (en) 1995-03-17 1997-10-28 Board Of Regents, The University Of Texas System Extended stability formulations for paclitaxel
US5605696A (en) 1995-03-30 1997-02-25 Advanced Cardiovascular Systems, Inc. Drug loaded polymeric material and method of manufacture
DE19514104C2 (de) 1995-04-13 1997-05-28 Behringwerke Ag Beschichtung für in den Blutstrom oder in das Gewebe des menschlichen Körpers einbringbares Biomaterial
US5624704A (en) * 1995-04-24 1997-04-29 Baylor College Of Medicine Antimicrobial impregnated catheters and other medical implants and method for impregnating catheters and other medical implants with an antimicrobial agent
IL113926A (en) 1995-05-31 2000-06-01 Korenstein Rafi Contrast medium with improved patient's tolerance thereto and its use
US5820607A (en) 1995-06-05 1998-10-13 Board Of Regents, University Of Texas Systems Multipurpose anti-microbial silastic sheath system for the prevention of device-related infections
CA2178541C (en) * 1995-06-07 2009-11-24 Neal E. Fearnot Implantable medical device
US7550005B2 (en) * 1995-06-07 2009-06-23 Cook Incorporated Coated implantable medical device
US7611533B2 (en) * 1995-06-07 2009-11-03 Cook Incorporated Coated implantable medical device
US5609629A (en) 1995-06-07 1997-03-11 Med Institute, Inc. Coated implantable medical device
US5772640A (en) * 1996-01-05 1998-06-30 The Trustees Of Columbia University Of The City Of New York Triclosan-containing medical devices
US6774278B1 (en) 1995-06-07 2004-08-10 Cook Incorporated Coated implantable medical device
AU701806B2 (en) 1995-06-29 1999-02-04 Macrochem Corporation Lipophilic and amphiphilic film-forming polymer compositions, and use thereof in topical agents delivery system and method of delivering agents to the skin
US5607475A (en) * 1995-08-22 1997-03-04 Medtronic, Inc. Biocompatible medical article and method
ES2153984T3 (es) 1995-11-08 2001-03-16 Scimed Life Systems Inc Procedimiento de formacion de balon mediante estrechamiento por estirado en frio.
US5792158A (en) 1995-11-15 1998-08-11 Lary; Banning Gray University dilator with expandable incisor
AU2150497A (en) 1996-01-25 1997-08-20 Schering Aktiengesellschaft Improved concentrated injection and infusion solutions for intravenous adminis tration
US6264642B1 (en) 1996-02-29 2001-07-24 Kimberly-Clark Worldwide, Inc. Elasticized laminate, liquid impermeable backsheet for a disposable absorbent article
EP0932399B1 (en) 1996-03-12 2006-01-04 PG-TXL Company, L.P. Water soluble paclitaxel prodrugs
US6441025B2 (en) * 1996-03-12 2002-08-27 Pg-Txl Company, L.P. Water soluble paclitaxel derivatives
US6071285A (en) 1996-03-25 2000-06-06 Lashinski; Robert D. Rapid exchange folded balloon catheter and stent delivery system
AU2821597A (en) 1996-05-03 1997-11-26 Emed Corporation Combined coronary stent deployment and local delivery of an agent
DK0906129T3 (da) 1996-06-04 2002-12-02 Cook Inc Implanterbar medicinsk anordning
US20040068241A1 (en) * 1996-06-04 2004-04-08 Fischer Frank J. Implantable medical device
DE69722720T2 (de) * 1996-07-24 2004-05-13 Cordis Corp., Miami Lakes Ballonkatheter und Methode zur Anwendung
US5797887A (en) * 1996-08-27 1998-08-25 Novovasc Llc Medical device with a surface adapted for exposure to a blood stream which is coated with a polymer containing a nitrosyl-containing organo-metallic compound which releases nitric oxide from the coating to mediate platelet aggregation
CA2209366C (en) 1996-09-13 2004-11-02 Interventional Technologies, Inc. Incisor-dilator with tapered balloon
US5954740A (en) 1996-09-23 1999-09-21 Boston Scientific Corporation Catheter balloon having raised radial segments
US5978698A (en) * 1996-10-08 1999-11-02 Merck & Co., Inc. Angioplasty procedure using nonionic contrast media
IT1294967B1 (it) 1996-10-09 1999-04-23 Ist Farmacoterapico It Spa Composizione immunogenica da tlp
DE69738406T2 (de) * 1996-10-21 2008-12-04 Ge Healthcare As Verbesserungen in oder an Kontrastmitteln
US5893867A (en) * 1996-11-06 1999-04-13 Percusurge, Inc. Stent positioning apparatus and method
US6515016B2 (en) * 1996-12-02 2003-02-04 Angiotech Pharmaceuticals, Inc. Composition and methods of paclitaxel for treating psoriasis
US6495579B1 (en) 1996-12-02 2002-12-17 Angiotech Pharmaceuticals, Inc. Method for treating multiple sclerosis
US6071616A (en) 1996-12-05 2000-06-06 Texas Instruments Incorporated Opaque low reflecting coating aperture on glass
US5980972A (en) 1996-12-20 1999-11-09 Schneider (Usa) Inc Method of applying drug-release coatings
US5871692A (en) 1997-01-14 1999-02-16 Steris Corporation Method and apparatus for cleaning, decontaminating, and sterilizing catheters
US5868719A (en) 1997-01-15 1999-02-09 Boston Scientific Corporation Drug delivery balloon catheter device
US6491619B1 (en) 1997-01-31 2002-12-10 Endologix, Inc Radiation delivery catheters and dosimetry methods
WO1998036784A1 (en) 1997-02-20 1998-08-27 Cook Incorporated Coated implantable medical device
BR9808109A (pt) 1997-03-31 2000-03-08 Neorx Corp Inibidor terapêutico de células vasculares da musculatura lisa
US6240616B1 (en) * 1997-04-15 2001-06-05 Advanced Cardiovascular Systems, Inc. Method of manufacturing a medicated porous metal prosthesis
US6273913B1 (en) 1997-04-18 2001-08-14 Cordis Corporation Modified stent useful for delivery of drugs along stent strut
GB9708240D0 (en) * 1997-04-23 1997-06-11 Nycomed Imaging As Improvements in or relating to contrast agents
DE19718339A1 (de) * 1997-04-30 1998-11-12 Schering Ag Polymer beschichtete Stents, Verfahren zu ihrer Herstellung und ihre Verwendung zur Restenoseprophylaxe
US6221467B1 (en) * 1997-06-03 2001-04-24 Scimed Life Systems, Inc. Coating gradient for lubricious coatings on balloon catheters
DE19724796A1 (de) * 1997-06-06 1998-12-10 Max Delbrueck Centrum Mittel zur Antitumortherapie
JPH1112160A (ja) 1997-06-19 1999-01-19 Nippon Schering Kk 水溶性抗腫瘍薬含有エマルジョン型製剤およびキット
US6171232B1 (en) * 1997-06-26 2001-01-09 Cordis Corporation Method for targeting in vivo nitric oxide release
US6214333B1 (en) * 1997-07-08 2001-04-10 Texas Heart Institute Vasoprotective recombinant adenovirus vector containing a human TFPI gene
CA2298543A1 (en) 1997-08-13 1999-02-25 James Barry Loading and release of water-insoluble drugs
US6306166B1 (en) 1997-08-13 2001-10-23 Scimed Life Systems, Inc. Loading and release of water-insoluble drugs
US6248100B1 (en) * 1997-08-14 2001-06-19 Scimed Life Systems, Inc. Drainage catheter delivery system
US5921952A (en) * 1997-08-14 1999-07-13 Boston Scientific Corporation Drainage catheter delivery system
KR20010023028A (ko) 1997-08-20 2001-03-26 맥슨 시스템스 아이엔시. (런던) 엘티디. 전자식 디렉토리의 저장된 엔트리 위치지정 방법 및 통신 장치
WO1999012577A1 (en) 1997-09-05 1999-03-18 Nycomed Imaging As Polymer particles made of polyvinyl alcohol and comprising a contrast agent for chemoembolization
US6284333B1 (en) 1997-09-10 2001-09-04 Scimed Life Systems, Inc. Medical devices made from polymer blends containing low melting temperature liquid crystal polymers
US5917772A (en) * 1997-09-16 1999-06-29 Micron Technology, Inc. Data input circuit for eliminating idle cycles in a memory device
WO1999013916A2 (en) 1997-09-18 1999-03-25 Nycomed Imaging As Methods and compositions for medical imaging
US7445792B2 (en) 2003-03-10 2008-11-04 Abbott Laboratories Medical device having a hydration inhibitor
US6890546B2 (en) 1998-09-24 2005-05-10 Abbott Laboratories Medical devices containing rapamycin analogs
US6309420B1 (en) * 1997-10-14 2001-10-30 Parallax Medical, Inc. Enhanced visibility materials for implantation in hard tissue
NZ504019A (en) * 1997-10-15 2003-06-30 Sherwood Serv Ag Lubricant coating for medical devices comprising C1-C12 alkyl benzene, C1-C12 alkylester, polymer, and isocyanate-terminated prepolymer; and a method for the preparation of this lubricant composition
US6273908B1 (en) 1997-10-24 2001-08-14 Robert Ndondo-Lay Stents
EP0996461B1 (en) 1997-10-31 2005-01-12 Walter Reed Army Institute of Research Use of a complement activation inhibitor in the manufacture of a medicament for inhibiting side effects of pharmaceutical compositions containing amphiphilic vehicles or drug carrier molecules
CA2310232A1 (en) 1997-11-17 1999-05-27 Ronald H. Lane Methods for preventing restenosis using tocotrienols
US6485514B1 (en) 1997-12-12 2002-11-26 Supergen, Inc. Local delivery of therapeutic agents
US6123923A (en) * 1997-12-18 2000-09-26 Imarx Pharmaceutical Corp. Optoacoustic contrast agents and methods for their use
US6203487B1 (en) * 1997-12-31 2001-03-20 Thomas Jefferson University Use of magnetic particles in the focal delivery of cells
CN1224622A (zh) 1998-01-24 1999-08-04 张尚权 肿瘤靶向造影剂
US6221425B1 (en) 1998-01-30 2001-04-24 Advanced Cardiovascular Systems, Inc. Lubricious hydrophilic coating for an intracorporeal medical device
GB9802745D0 (en) * 1998-02-09 1998-04-08 Pharmacia & Upjohn Spa Benzyloxy prodigiosine compounds
US6623521B2 (en) * 1998-02-17 2003-09-23 Md3, Inc. Expandable stent with sliding and locking radial elements
US5997162A (en) 1998-03-13 1999-12-07 Osram Sylvania Inc. Horizontal HID vehicle headlamp with magnetic deflection
US6306151B1 (en) 1998-03-31 2001-10-23 Interventional Technologies Inc. Balloon with reciprocating stent incisor
US6364856B1 (en) * 1998-04-14 2002-04-02 Boston Scientific Corporation Medical device with sponge coating for controlled drug release
US6296655B1 (en) 1998-04-27 2001-10-02 Advanced Cardiovascular Systems, Inc. Catheter balloon with biased multiple wings
EP1555036B1 (en) 1998-04-27 2010-05-05 Surmodics Inc. Bioactive agent release coating
WO1999058120A1 (en) * 1998-05-08 1999-11-18 Rolf Berge USE OF NON-β-OXIDIZABLE FATTY ACID ANALOGUES FOR TREATMENT OF SYNDROME-X CONDITIONS
WO1999059556A1 (en) 1998-05-15 1999-11-25 Nasa/Johnson Space Center Externally triggered microcapsules
WO2000000238A1 (en) 1998-06-26 2000-01-06 Quanam Medical Corporation Topoisomerase inhibitors for prevention of restenosis
US6203812B1 (en) 1998-06-29 2001-03-20 Hydromer, Inc. Hydrophilic polymer blends used to prevent cow skin infections
US6369039B1 (en) 1998-06-30 2002-04-09 Scimed Life Sytems, Inc. High efficiency local drug delivery
CA2362338A1 (en) 1998-07-30 2000-02-10 Human Rt. Pharmaceutically acceptable composition comprising an aqueous solution of paclitaxel and albumin
US6547760B1 (en) * 1998-08-06 2003-04-15 Cardeon Corporation Aortic catheter with porous aortic arch balloon and methods for selective aortic perfusion
US6013092A (en) * 1998-08-18 2000-01-11 Baxter International Inc. Folding of catheter-mounted balloons to facilitate non-rotational radial expansion of intraluminal devices
WO2000010622A1 (en) * 1998-08-20 2000-03-02 Cook Incorporated Coated implantable medical device
AU5687199A (en) 1998-08-24 2000-03-14 Global Vascular Concepts, Inc. Use of anti-angiogenic agents for inhibiting vessel wall injury
US6335029B1 (en) * 1998-08-28 2002-01-01 Scimed Life Systems, Inc. Polymeric coatings for controlled delivery of active agents
US5922754A (en) * 1998-10-02 1999-07-13 Abbott Laboratories Pharmaceutical compositions containing paclitaxel
AU2343700A (en) 1998-10-30 2000-05-22 Certco Inc Incorporating shared randomness into distributed cryptography
US6017948A (en) * 1998-10-30 2000-01-25 Supergen, Inc. Water-miscible pharmaceutical compositions
US6120533A (en) 1998-11-13 2000-09-19 Isostent, Inc. Stent delivery system for a radioisotope stent
CA2353606A1 (en) * 1998-12-03 2000-06-08 Boston Scientific Limited Stent having drug crystals thereon
US6040330A (en) * 1999-01-08 2000-03-21 Bionumerik Pharmaceuticals, Inc. Pharmaceutical formulations of taxanes
US7780628B1 (en) 1999-01-11 2010-08-24 Angiodynamics, Inc. Apparatus and methods for treating congestive heart disease
EP1148898A1 (en) 1999-01-28 2001-10-31 Union Carbide Chemicals & Plastics Technology Corporation Lubricious medical devices
US6419692B1 (en) * 1999-02-03 2002-07-16 Scimed Life Systems, Inc. Surface protection method for stents and balloon catheters for drug delivery
WO2000047197A2 (en) 1999-02-12 2000-08-17 Quanam Medical Corporation Alkylating agents for treatment of cellular proliferation
US6191619B1 (en) * 1999-08-24 2001-02-20 Analog Devices, Inc. Translators and methods for converting differential signals to single-ended signals
US6790228B2 (en) * 1999-12-23 2004-09-14 Advanced Cardiovascular Systems, Inc. Coating for implantable devices and a method of forming the same
US6503954B1 (en) * 2000-03-31 2003-01-07 Advanced Cardiovascular Systems, Inc. Biocompatible carrier containing actinomycin D and a method of forming the same
US6706892B1 (en) * 1999-09-07 2004-03-16 Conjuchem, Inc. Pulmonary delivery for bioconjugation
US6203551B1 (en) * 1999-10-04 2001-03-20 Advanced Cardiovascular Systems, Inc. Chamber for applying therapeutic substances to an implant device
US6682545B1 (en) 1999-10-06 2004-01-27 The Penn State Research Foundation System and device for preventing restenosis in body vessels
DE60037264D1 (de) 1999-10-06 2008-01-10 Penn State Res Found System und vorrichtung zur vermeidung von restenose in körpergefässen
JP4613406B2 (ja) 1999-11-05 2011-01-19 株式会社デンソー 受光素子、距離測定装置及び距離・画像測定装置
US6616591B1 (en) * 1999-12-08 2003-09-09 Scimed Life Systems, Inc. Radioactive compositions and methods of use thereof
US6254921B1 (en) 1999-12-08 2001-07-03 Surmodics, Inc. Coating process and apparatus
US6719774B1 (en) 1999-12-23 2004-04-13 Advanced Cardiovascular Systems, Inc. Method for forming low profile balloon and low profile balloon for use with a catheter
US6355058B1 (en) * 1999-12-30 2002-03-12 Advanced Cardiovascular Systems, Inc. Stent with radiopaque coating consisting of particles in a binder
AU2623201A (en) 1999-12-30 2001-07-16 Kam W Leong Controlled delivery of therapeutic agents by insertable medical devices
JP2003520210A (ja) 2000-01-05 2003-07-02 イマレックス セラピューティクス, インコーポレイテッド 低い水溶性を有する薬物の送達のための薬学的処方物
US6575888B2 (en) 2000-01-25 2003-06-10 Biosurface Engineering Technologies, Inc. Bioabsorbable brachytherapy device
ATE460951T1 (de) 2000-01-25 2010-04-15 Edwards Lifesciences Corp Freisetzungssysteme zur behandlung von restenose und anastomotischer intimaler hyperplasie
JP4626005B2 (ja) * 2000-01-27 2011-02-02 東洋紡績株式会社 血液適合性組成物およびそれを被覆した医療用具
WO2001076525A2 (en) 2000-04-10 2001-10-18 Advanced Cardiovascular Systems, Inc. Selectively coated stent delivery system and method of manufacture thereof
US6599448B1 (en) * 2000-05-10 2003-07-29 Hydromer, Inc. Radio-opaque polymeric compositions
US6585765B1 (en) 2000-06-29 2003-07-01 Advanced Cardiovascular Systems, Inc. Implantable device having substances impregnated therein and a method of impregnating the same
TWI257307B (en) * 2000-07-12 2006-07-01 Orthologic Corp Pharmaceutical composition for cardiac tissue repair
US6918927B2 (en) 2000-10-31 2005-07-19 Cook Incorporated Coated implantable medical device
US6635082B1 (en) * 2000-12-29 2003-10-21 Advanced Cardiovascular Systems Inc. Radiopaque stent
US6544223B1 (en) * 2001-01-05 2003-04-08 Advanced Cardiovascular Systems, Inc. Balloon catheter for delivering therapeutic agents
US7179251B2 (en) * 2001-01-17 2007-02-20 Boston Scientific Scimed, Inc. Therapeutic delivery balloon
US20020119178A1 (en) 2001-02-23 2002-08-29 Luc Levesque Drug eluting device for treating vascular diseases
DE10115740A1 (de) 2001-03-26 2002-10-02 Ulrich Speck Zubereitung für die Restenoseprophylaxe
FR2823118B1 (fr) * 2001-04-04 2004-03-19 Lavipharm Lab Inc Nouvelle composition filmogene a usage topique et son utilisation pour la delivrance d'agents actifs
TWI288654B (en) * 2001-05-17 2007-10-21 Ind Tech Res Inst Process for the purification of water-soluble non-ionic contrast agents
EP1412014A4 (en) 2001-06-14 2005-06-15 Cook Inc ENDOVASCULAR FILTER
WO2003022264A1 (en) * 2001-09-13 2003-03-20 Korea Institute Of Science And Technology Paclitaxel mixed composition and water-in-oil type emulsion formulation for chemoembolization and preparation method thereof
CA2458828A1 (en) * 2001-09-24 2003-05-01 James J. Barry Optimized dosing for drug coated stents
US20030143189A1 (en) 2001-11-14 2003-07-31 Askill Ian N Therapy for topical diseases
WO2003048166A1 (en) 2001-12-03 2003-06-12 Universitätsklinikum Charite Der Humboldt-Universität Zu Berlin Technologie Transferstelle Podophyllotoxins as antiproliferative agents
ATE495769T1 (de) 2002-07-12 2011-02-15 Cook Inc Beschichtete medizinische vorrichtung
EP2263709A1 (en) 2002-09-06 2010-12-22 Abbott Laboratories Medical device having hydration inhibitor
DE10244847A1 (de) 2002-09-20 2004-04-01 Ulrich Prof. Dr. Speck Medizinische Vorrichtung zur Arzneimittelabgabe
US7060051B2 (en) * 2002-09-24 2006-06-13 Scimed Life Systems, Inc. Multi-balloon catheter with hydrogel coating
CA2444781A1 (en) 2002-10-17 2004-04-17 Rolf C. Hagen Inc. Topical gel matrix
US7491234B2 (en) * 2002-12-03 2009-02-17 Boston Scientific Scimed, Inc. Medical devices for delivery of therapeutic agents
US20040224003A1 (en) 2003-02-07 2004-11-11 Schultz Robert K. Drug formulations for coating medical devices
JP2005301328A (ja) * 2003-07-10 2005-10-27 Finalabo Co Ltd 株式信用取引における顧客口座内全建玉について一律に実行する個別建玉ごとの指定率での損切り機能付き建玉管理システム、顧客口座内全株式について一律に実行する個別株式ごとの指定率での損切り機能付き所有株式管理システム、株式信用取引における顧客口座内全建玉について一律に実行する個別建玉ごとの指定の保証金維持率による損切り機能付き建玉管理システム
US20050063926A1 (en) * 2003-09-23 2005-03-24 Bathina Harinath B. Film-forming compositions for protecting animal skin
ATE534424T1 (de) 2004-03-19 2011-12-15 Abbott Lab Mehrfache arzneiabgabe aus einem ballon und eine prothese
US7704545B2 (en) 2004-05-12 2010-04-27 Medtronic Vascular, Inc. Drug-polymer coated stent
US20060029720A1 (en) 2004-08-03 2006-02-09 Anastasia Panos Methods and apparatus for injection coating a medical device
US20070128118A1 (en) * 2005-12-05 2007-06-07 Nitto Denko Corporation Polyglutamate-amino acid conjugates and methods
US7919108B2 (en) 2006-03-10 2011-04-05 Cook Incorporated Taxane coatings for implantable medical devices
JP4892289B2 (ja) * 2006-07-07 2012-03-07 株式会社日立製作所 複数のストレージ装置を含むストレージシステム
US20080012034A1 (en) 2006-07-17 2008-01-17 3M Innovative Properties Company Led package with converging extractor
US8414526B2 (en) 2006-11-20 2013-04-09 Lutonix, Inc. Medical device rapid drug releasing coatings comprising oils, fatty acids, and/or lipids
US8425459B2 (en) 2006-11-20 2013-04-23 Lutonix, Inc. Medical device rapid drug releasing coatings comprising a therapeutic agent and a contrast agent
US8414909B2 (en) 2006-11-20 2013-04-09 Lutonix, Inc. Drug releasing coatings for medical devices
US8414525B2 (en) 2006-11-20 2013-04-09 Lutonix, Inc. Drug releasing coatings for medical devices
EP2241342A3 (en) 2006-11-20 2011-01-12 Lutonix, Inc. Drug releasing coatings for medical devices
DE102007003184A1 (de) 2007-01-22 2008-07-24 Orlowski, Michael, Dr. Verfahren zur Beladung von strukturierten Oberflächen

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
Chu LI,ET AL.Synthesis,Biodistribution and Imaging PropertiesofIndium-111-DTPA-Paclitaxel in Mice BearingMammaryTumors.The Journal of Nucleal Medicine38 7.1997,38(7),第1042页右栏倒数第1、2段.
Chu LI,ET AL.Synthesis,Biodistribution and Imaging PropertiesofIndium-111-DTPA-Paclitaxel in Mice BearingMammaryTumors.The Journal of Nucleal Medicine38 7.1997,38(7),第1042页右栏倒数第1、2段. *

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