CN102753118B - 组织分离性脂肪酸粘连屏障 - Google Patents
组织分离性脂肪酸粘连屏障 Download PDFInfo
- Publication number
- CN102753118B CN102753118B CN201080047130.0A CN201080047130A CN102753118B CN 102753118 B CN102753118 B CN 102753118B CN 201080047130 A CN201080047130 A CN 201080047130A CN 102753118 B CN102753118 B CN 102753118B
- Authority
- CN
- China
- Prior art keywords
- fatty acid
- adhesion barrier
- film
- tissue
- adhesion
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Classifications
-
- 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
- A61L31/148—Materials at least partially resorbable by the body
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
-
- 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
-
- 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
- A61L31/08—Materials for coatings
- A61L31/10—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
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L31/145—Hydrogels or hydrocolloids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P41/00—Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/04—Hollow or tubular parts of organs, e.g. bladders, tracheae, bronchi or bile ducts
- A61F2/06—Blood vessels
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2250/00—Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
- A61F2250/0058—Additional features; Implant or prostheses properties not otherwise provided for
- A61F2250/0067—Means for introducing or releasing pharmaceutical products into the body
-
- 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
- A61L2420/00—Materials or methods for coatings medical devices
- A61L2420/02—Methods for coating medical devices
Abstract
本发明的示例性实施方式提供了具有抗粘连和组织固定性质的粘连屏障。所述粘连屏障由基于脂肪酸的膜形成。所述基于脂肪酸的膜可从脂肪酸衍生的生物材料形成。所述膜可涂有或可包含组织固定材料以产生所述粘连屏障。所述粘连屏障是身体耐受良好的、具有抗炎性质、良好地固定于组织、以及具有足以防止术后粘连的停留时间。
Description
相关申请
本申请要求在2009年10月19日提交的美国申请No.12/581,582的优先权和权益,所述美国申请是以下申请的部分继续申请:2005年9月28日提交的题为“屏障层(BarrierLayer)”的序号为11/237,420的美国专利申请;2005年9月28日提交的题为“独立膜和用于制造它的方法(AStand-AloneFilmandMethodsforMakingtheSame)”的序号为11/237,264的美国专利申请;2007年10月30日提交的题为“涂层的外科网(CoatedSurgicalMesh)”的序号为11/978,840的美国专利申请;和2009年3月10日提交的题为“基于脂肪酸的粒子(Fatty-AcidBasedParticles)”的序号为12/401,243的美国专利申请。上述专利申请的内容通过参考结合于此。
技术领域
本发明总体涉及组织分离性粘连屏障。
背景技术
在外科场景下,医用膜往往被用作物理性屏障以在手术介入或钝性剥离后将某些器官与相邻的组织和医疗装置分离开,从而有助于使手术后的粘连形成最小化。例如,麻省剑桥Genzyme公司(GenzymeCorporationofCambridge,MA)的产品SEPRAFTLM(由化学改性的糖构成的膜)在腹部或盆腔外科中用作植入性处理,用来降低在不同组织和器官与植入性医疗装置之间的术后粘连形成的发生率、范围和严重性,所述植入性医疗装置例如软组织支持膜和网、或不可吸收的材料和网的组合。
美国专利申请No.5,017,229中描述了医用膜的一个实例。该′229专利的膜从不溶于水的凝胶形成,所述凝胶包含透明质酸(“HA”)、聚阴离子多糖和活化剂的反应产物。该′229专利中描述的凝胶能提供成粘连预防型组合物的形式,例如适合于纳入注射器的膜或组合物。通过浇铸成片状形式、挤出、压缩、或允许脱水成平片,所述凝胶形成为膜。当用多糖修饰时,生物降解性膜形成了上面所描述的SEPRAFTLM粘连限制或粘连屏障产物,其可作为脱水的生物分解性单层片市售获得。
植入性医用膜可以在手术期间置于靶部位,例如两个组织之间。为了预防或限制术后粘连形成,膜应留在靶部位必需的一段时间。例如,一些资料来源已指出,屏障功能在手术后3天和10天之间是需要的(参见,Gere.S.DiZerega、AlanH.DeCherney的腹膜手术(PeritonealSurgery),由Springer出版,2000年,第21页)。为了实现该屏障功能,生物降解性膜应在靶部位保持在位,并且它应经过一段足够的时间被身体吸收,从而在粘连形成时提供术后屏障功能。
然而,常规的医用膜被再吸收入人体过快,以致在术后粘连形成典型发生的时间期间不能提供有效的屏障功能。例如,许多基于交联羧甲基纤维素(“CMC”)的膜可在7天内被体内吸收。
发明内容
如下面更详细地描述的,可提供用固定材料例如羧甲基纤维素(“CMC”)或Na-CMC构成的基于脂肪酸的膜例如由鱼油制成的膜以固定该膜并预防膜迁移。尽管CMC具有炎性特性以及CMC和Na-CMC具有快速再吸收特性,但该粘连屏障是身体耐受良好、非炎性的,不从靶部位迁移,并且不需要CMC的交联。本发明的粘连屏障有效地将再吸收延迟至可接受的植入后时限(例如大于7天)。基于脂肪酸的膜与固定材料例如CMC或Na-CMC的组合产生了意想不到的协同效应。具体地,在基于脂肪酸的膜存在下的非交联CMC不像在没有脂肪酸存在下的交联CMC那么快地被吸收入体内。因此,粘连屏障的固定性部分被吸收入体内的速率比其它基于CMC的膜慢得多,以致在可能形成粘连的时间段中提供了屏障功能。
在本发明的一些示例性实施方式中,所述粘连屏障是乳液形式。所述乳液可包含浸在乳液基质中的基于脂肪酸的粒子。基于脂肪酸的粒子可通过与低温液体联合的脂肪酸衍生的生物材料碎裂而形成。乳液基质可包含固定材料例如CMC与基于水的溶液例如(但不限于)水、盐水或乳酸林格氏液(Ringer′slactatesolution)的混合物。
本发明的示例性实施方式提供了粘连屏障和用于配制所述粘连屏障的方法。根据本发明的一个示例性实施方式,所述粘连屏障采取基于脂肪酸的膜组合物的形式。所述粘连屏障包含基于脂肪酸的膜和组织固定涂层,所述基于脂肪酸的膜源自交联的脂肪酸衍生的生物材料,所述组织固定涂层从包裹所述基于脂肪酸的膜的材料形成。所述组织固定涂层可通过本技术领域已知的任何方式施加。
根据本发明的方面,所述脂肪酸衍生的生物材料是ω-3脂肪酸。脂肪酸衍生的生物材料可以是交联的或可以不是交联的。脂肪酸衍生的生物材料可以含有至少一种脂质或ω-3脂肪酸;例如,脂肪酸衍生的生物材料可以是鱼油。鱼油可以进一步包含维生素E。
根据一个示例性实施方式,所述附着材料可以是聚阴离子多糖,例如羧甲基纤维素(CMC)。根据另一个示例性实施方式,所述附着材料包含CMC的盐,例如羧甲基纤维素钠(Na-CMC)。
根据本发明进一步的方面,所述脂肪酸衍生的生物材料可以减少与固定材料相关的炎症。在一些实施方式中,所述粘连屏障不从手术放置部位迁移,而在进一步的实施方式中,所述粘连屏障具有足以防止术后粘连的停留时间。
附图说明
根据以下结合附图的说明,能更完整地理解本发明的上述及其它方面、实施方式、目的、特征和优势。在附图中,各图中同样的参考字符通常是指同样的特征和结构部件。附图不一定按照比例,而是将重点放在绘出本发明的原理。
图1描绘了本发明一个示例性实施方式的粘连屏障。
图2是描绘了根据本发明一个示例性实施方式制造示例性粘连屏障的示例性方法的流程图。
图3描绘了本发明一个示例性实施方式的粘连屏障。
图4描绘了本发明一个示例性实施方式的粘连屏障。
图5描绘了本发明一个示例性实施方式的作为乳液产生的粘连屏障。
图6是描绘用于制造如图5所描绘的示例性粘连屏障的示例性方法的流程图。
详细说明
本发明的示例性方面和实施方式提供了从基于脂肪酸的膜或基于脂肪酸的粒子形成的粘连屏障。所述粘连屏障具有固定性质的材料诸如基于CMC的膜,还有意想不到的协同效应,其显著减慢了所述粘连屏障的组织固定部分被吸收的速率而无需CMC成分的交联。
常规的膜
在一些常规产品中,亲水性组织固定成分例如聚乙二醇、聚氧化乙烯、聚HEMA、聚N-乙烯基吡咯烷酮、聚丙烯酸、羧甲基纤维素(CMC)、脱乙酰壳多糖等被用来提供膜的固定。该固定能解决膜移动性或迁移的问题。然而,这些亲水性材料可以表现出明显的异物反应和炎症,这是不可取的特性(参见,例如欧洲专利申请EP20020080404)。
此外,制造这些常规的组织固定成分造成了另外的挑战。具体地,上面的组织固定成分必须通过官能性末端基团修饰或利用化学交联剂进行化学交联,以提供适当的机械完整性以供操作和在潮湿环境中的不溶性。使用化学交联剂例如戊二醛或氮丙啶类需要通过洗涤或浸泡去除过量的交联剂的附加步骤,因为这些化合物往往比所需的水凝胶材料的生物相容性低。这些附加步骤增加了制造过程的费用和难度。
如上所述,膜可以由聚阴离子多糖和透明质酸制成。用于制作′229专利中描述的膜的一种优选聚阴离子多糖是CMC。′229专利中的膜由HA和CMC(“HA/CMC”)形成。然而,已注意到,由于用来去除制备中产生的生物毒性材料的程序,制备这种类型的膜的方法是有问题的(参见,例如美国专利申请公布No.2003/0124087)。′087申请指出,在HA/CMC制备中的水合过程可以引起处理和操作困难。
HA/CMC的一种替代方案是羧甲基纤维素钠(“Na-CMC”)。虽然Na-CMC作为抗粘连剂是有效的,但难以将Na-CMC作为抗粘连屏障应用,因为它在体内吸收过快以致不能有效作为粘连屏障。基于CMC的膜快速吸收进入体内是有问题的,因为该膜在它发挥有效的粘连屏障作用之前被再吸收。例如,HA/CMC膜能在7天内被吸收,而如上所述,在术后3天和10天之间可能需要屏障功能,并且在一些情况下,需要长达8周的屏障功能。
此外,生产从CMC的盐例如Na-CMC制得的膜可能是困难的或有问题的。生产这些膜可能需要通过交联固定CMC或稳定化,因为Na和CMC在水性介质中容易解离,从而让CMC溶解。交联是用化学键化学连接两个以上分子的过程。CMC的交联能通过例如辐射CMC来完成(参见,例如Fei等,生物降解性纤维素衍生物的水凝胶.I.辐射诱导的CMC交联(HydragelofBiodegradableCelluloseDerivative.I.Radiation-InducedCrosslinkingofCMC),JournalofAppliedPolymerScience,vol.78,pp.278-283(2000))。
如果没有通过交联固定或稳定CMC,从固体到液体的转变显著降低了Na-CMC膜提供有效的屏障保护的能力。CMC交联导致另外的问题。未修饰的CMC的辐射诱导交联需要存在介质例如水以使大分子活动起来并允许装配。CMC的固相辐射导致材料因糖苷键断裂而降解。
交联的CMC膜还具有在体内快速、即7天内再吸收的局限性。此外,已知CMC膜引起炎症,并可能缺乏粘附性和亲和力(参见,例如′087申请,段落[0009]-[0013])。
示例性实施方式
与常规的粘连屏障相反,本发明实施方式提供的粘连屏障在靶部位停留足够的时间以提供屏障功能,不需要CMC成分是交联的,并且不引起显著的炎性应答。根据本发明的示例性实施方式,由脂肪酸衍生的生物材料构成的基于脂肪酸的膜或基于脂肪酸的粒子被用作分离组织的再吸收性粘连屏障材料。ω-3和ω-6脂肪酸是可以从例如鱼油中获得的脂肪酸的实例。ω-3脂肪酸包括二十碳五烯酸(EPA)、二十二碳六烯酸(DHA)、和α-亚麻酸(ALA)。
由脂肪酸衍生的生物材料构成的基于脂肪酸的屏障有效分离相邻的组织表面、是身体耐受良好的、并且不表现出其它再吸收性和永久性植入材料典型的炎性应答。尽管基于CMC的膜良好地粘附于组织,但基于CMC的膜容易在约7天内溶解于水性介质。
将基于脂肪酸的膜或粒子和本文中描述的固定材料组合,产生了具有固定和抗炎性质的有效的抗粘连屏障。另外,组合这两种类型的材料还产生了意想不到的协同结果——具体地,从CMC和基于脂肪酸的膜或基于脂肪酸的粒子的组合形成的粘连屏障,无需CMC的交联,就留在处理部位提供了超过7天并长达28天或更长的屏障功能。这提供了足够的停留时间以有效地提供术后屏障功能。
在描述本发明的方面之前,应指出的是,在本文中使用时,术语“生物相容性”是指与活组织相容(例如无毒或无害)。生物相容性化合物可以水解成随后被周围组织生物吸收的非炎性成分。生物相容性化合物在本文中也被称为“生物材料”。
膜包括通过压缩凝胶、或通过允许或导致凝胶脱水、或通过利用热和/或光以各种方式固化凝胶而形成的物质。此外,膜能根据本技术领域普通技术人员已知的方法化学形成。
除了膜以外,本发明的示例性实施方式还包括乳液。乳液是两种以上不混溶的液体的溶体。在一个示例性实施方式中,乳液由乳液基质与基于脂肪酸的粒子混合形成。基于脂肪酸的粒子可以源自基于脂肪酸的膜。
在本文中使用时,基于脂肪酸的材料意欲包含脂肪酸可以采取的任何材料形式,包括膜和粒子。
示例性膜实施方式
图1描绘了本发明一个实施方式的粘连屏障100。粘连屏障100包含基于脂肪酸的膜110。所述基于脂肪酸的膜110可通过本技术领域已知的任何方法形成。在一个实施方式中,交联的脂肪酸衍生的生物材料包含可以是天然的或源自合成来源的油,并用于形成基于脂肪酸的膜110。所述交联的脂肪酸衍生的生物材料能包含生物油,例如含有至少一种脂质或ω-3脂肪酸的油,包括鱼油。所述生物材料能进一步包含维生素E。
粘连屏障100还包含从固定材料形成的组织固定涂层120。在一个实施方式中,所述固定材料是聚阴离子多糖。在另一个实施方式中,所述固定材料包含羧甲基纤维素(CMC)。在又一个实施方式中,所述固定材料包含羧甲基纤维素钠(Na-CMC)。
图2是描绘用于制造粘连屏障100的示例性方法的流程图。在步骤210,通过本技术领域已知的一种方法制备基于脂肪酸的膜110。例如,如美国专利申请No.11/237,420中所描述的,鱼油可以被暴露于加热和/或UV辐射以形成交联的脂肪酸衍生的生物材料例如凝胶。所述凝胶可以被进一步压缩或脱水以形成膜。本技术领域的普通技术人员将理解,其它方法可以被用来形成基于脂肪酸的膜110,并且本发明绝不仅限于上面所参考的申请或专利中描述的具体方法。
所述油成分也可以被硬化,如′420申请中描述的以及其它已知的方法。硬化步骤能包括硬化或固化,例如通过引入UV光、热、或氧,化学固化、或其它固化或硬化方法。硬化或固化的目的是将更具液体稠度的油成分或油组合物转变成更为固体的膜,同时仍保持足够的柔性以在需要时允许膜弯曲和卷绕。
在一些实施方式中,油成分在涂层前接受表面处理,例如等离子体处理。
在步骤220,基于脂肪酸的膜110任选被切成适当的大小。所切得的基于脂肪酸的膜110的最终尺寸将取决于具体的应用。
在步骤230,制备组织固定材料的涂层溶液。根据本发明的一个示例性实施方式,所述涂层溶液由在水溶液例如去离子水或无菌注射用水(SWFI)中0.1%-5%(重量/体积)的取代度为0.65-0.85(但是低于0.65和高达理论限3的取代度也是可以接受的)的非交联高分子量Na-CMC构成。任选地,所述涂层溶液可以包含增塑剂,例如甘油、丙二醇、聚乙二醇、柠檬酸甘油三乙酸酯或甘油三乙酸酯。
在重量/体积浓度高于约5%时,所述溶液变成了固体样凝胶,这可能是难以使用的。通常,大多数浓度小于5%的溶液是实际可使用的,但应注意例如Na-CMC在膜表面上的质量荷载。如果Na-CMC过少,这将导致粘连屏障的组织固定不充分。Na-CMC浓度低可能需要多次施加涂层,以达到所需要的荷载。在一个实施方式中,使用了2%的重量/体积浓度。我们已发现,可用于在体内达到充分的组织固定的最低干荷载为1.0mg/cm2。
高分子量例如700,000的Na-CMC可用于组织固定材料。在脱乙酰壳多糖的单独评估中,本发明人已发现组织固定似乎随分子量提高。
基于实验观察结果,并且不受理论束缚,组织固定是由于涂层的吸水性引起的。由于吸水性随取代度增加而增加,取代度的所有实际范围在本发明中均可以接受。0.65-1.2之间的取代度是一个实际的并容易获得的范围。
在步骤240,利用任何标准的涂布方法例如浸涂、喷涂、刷涂、浇铸、或旋涂,将涂层溶液涂敷于基于脂肪酸的膜110。在步骤250,让涂层干燥适当的时间量,例如2-24小时。或者,可以使用设备通过各种已知的方法加速干燥,只要涂层溶液的温度不升得过高(引起水性或胶状涂层)即可。例如,膜可以被真空干燥。
作为用固定材料涂布基于脂肪酸的膜的备选方案,固定材料可以在它形成为膜以前被引入至最初的油或凝胶中。这种实施方式的粘连屏障的一个实例如图3所示。如图所示,粘连屏障300由基于脂肪酸的膜310形成。粘连屏障300进一步包含从固定材料例如Na-CMC形成的固定粒子320。这种实施方式可以通过例如压制粒子法形成,在压制粒子法中,形成了脂肪酸例如O3FA的粒子,并形成了固定材料的粒子。然后,这两种类型的粒子被混合在一起,并被压制形成粘连屏障。本技术领域的普通技术人员将理解用于将两种材料组合在一起形成混合的复合材料类型的其它方法。在与本文所讨论的材料相容的范围内,所有这样的方法均在本发明的考虑范围内。
图4描绘了本发明另一个备选的实施方式。在图4所描绘的粘连屏障中,粘连屏障400由基于脂肪酸的膜410形成。基于脂肪酸的膜410仅在一面上涂布了固定涂层420。这种粘连屏障可通过例如仅在基于脂肪酸的膜410的单个面上刷涂或喷涂固定涂层420而形成。根据本公开,对于本技术领域的普通技术人员而言,涂布基于脂肪酸的膜410的单个面的其它方式将是显而易见的。或者,可被涂布于基于脂肪酸的膜410的两个或更多个表面,但不完全包裹所述基于脂肪酸的膜。因此,能在基于脂肪酸的膜的一个或两个面上实现组织固定。
示例性乳液实施例
图5描绘了本发明另一个备选的实施方式。图5中描绘的粘连屏障500是基于脂肪酸的粒子510与乳液基质520例如CMC和水的混合物混合的乳液。
可以通过将交联的脂肪酸衍生的生物材料与低温液体联合,并碎裂该生物材料/低温液体组合物,使得形成脂肪酸粒子,来形成基于脂肪酸的粒子510。在一个实施方式中,所述交联的脂肪酸衍生的生物材料的来源是鱼油,例如已加热或暴露于UV辐射以交链鱼油的部分或全部脂肪酸的鱼油。
在一个实施方式中,将交联的脂肪酸衍生的生物材料与低温液体联合包括悬浮、浸没、和包裹所述交联的脂肪酸衍生的生物材料。在另一个实施方式中,所述低温液体包含液氮。所述交联的脂肪酸衍生的生物材料/低温液体组合物能利用研磨、剪切、冲击、震碎、制粒、粉碎、切碎、压碎、均化、超声、振动、和/或碾磨中的一种或多种进行碎裂。在碎裂前或粒子形成后,低温液体能通过蒸发基本上去除。
所述交联的脂肪酸衍生的生物材料能包含可以是天然的或源自合成来源的油。所述交联的脂肪酸衍生的生物材料能包含生物油,例如含有至少一种脂质或ω-3脂肪酸的油,例如鱼油。鱼油能进一步包含维生素E。如在本文中所描述的,鱼油被暴露于加热和/或UV辐射以形成交联的脂肪酸衍生的生物材料(例如凝胶)。在一个实施方式中,在与低温液体联合前,所述交联的材料是膜的形式。在另一个实施方式中,所述膜在与低温液体联合前进行粗研磨。
当交联的脂肪酸衍生的生物材料是膜的形式时,治疗剂能在粒子形成前、粒子形成期间、或粒子形成后被荷载至膜中。在又一个实施方式中,膜涂布有治疗剂/溶剂混合物。治疗剂能被溶解在溶剂例如甲醇或乙醇中,并且治疗剂/溶剂混合物能被涂敷于膜,例如通过浸渍或喷涂。
一旦制备后,基于脂肪酸的粒子510能被浸泡在溶解于溶剂例如己烷、异构烷烃(isopar)、水、乙醇、甲醇、二丙二醇二甲醚(proglyme)、二氯甲烷、乙腈、丙酮或MEK中的治疗剂中,并且溶剂能被基本上去除,从而形成与治疗剂缔合的脂肪酸粒子。
治疗剂能是一种或多种抗氧化剂、抗炎剂、抗凝剂、改变脂质代谢的药物、抗增殖剂、抗肿瘤剂、组织生长刺激剂、功能性蛋白/因子递送剂、抗感染剂、显像剂、麻醉剂、化疗剂、组织吸收促进剂、抗粘连剂、杀菌剂、止痛剂、抗菌剂、或其可药用的盐、酯、或前体药。在具体的实施方式中,治疗剂选自雷帕霉素、丁哌卡因、环孢霉素A(在本文中称为“CSA”)、ISA247(在本文中称为“247”)和利福平。
在一个实施方式中,基于脂肪酸的粒子510的平均粒度在约1微米至约50微米、例如1微米至约10微米的范围内。在另一个实施方式中,粒子具有约1-20μm(v,0.1)、21-40μm(v,0.5)、和41-150μm(v,0.9)的粒度分布。
乳液基质520是在混合时不与基于脂肪酸的粒子510结合的液体或基于水的溶液。在一个实施例中,乳液基质是CMC和水的混合物。其它适当的乳液基质包括但不仅限于盐溶液和乳酸林格氏液(Ringer′slactatesolution)。乳液基质可以包含组织附着材料。
图6是描绘用于产生图5的粘连屏障的示例性方法的流程图。在步骤610,制备乳液基质溶液。在一个实施例中,包含CMC和水的混合物(4.2%w/w)的乳液基质溶液利用Silverson均质器(8kRPM)进行制备,并让其在室温下溶胀过夜。
在步骤620,制备基于脂肪酸的膜粒子,如上所述。具体地,可以如下形成基于脂肪酸的粒子:(a)将交联的脂肪酸衍生的生物材料(例如交联的鱼油)和治疗剂组合以形成第一组合物;(b)在低温液体中浸没、包裹、或悬浮该组合物;(c)碎裂该组合物;和(d)任选去除分散介质。
分散介质可以包含不溶解治疗剂或交联的脂肪酸衍生的生物材料的溶剂。在又一个实施方式中,所述溶剂是己烷、异构烷烃(Isopar)、水、乙醇、甲醇、二丙二醇二甲醚(Proglyme)、二氯甲烷、乙腈、丙酮、MEK、液氮、和其它不完全溶解治疗剂的溶剂。在另一个实施方式中,所述交联的脂肪酸衍生的生物材料是膜的形式。在另一个实施方式中,所述膜在与治疗剂联合前进行粗研磨。
通过用磁力驱动的杆撞击起始材料,起始材料可以被碎裂成固体粒子。例如,SpexCertiprepCryomill(型号6750)能被用于将固体材料碎裂成粒子。该组合物能被放置在封闭的小瓶中,并且杆样撞击器被封入小瓶中。该小瓶被保持在低温下,并且杆通过磁体在小瓶中快速振荡。
在一个实施例中,鱼油被部分固化,然后浇铸成6密耳(0.006″)厚度的薄膜。所述薄膜被UV固化15分钟,在烘箱中在93℃热固化24小时,然后冷却24小时。固化的鱼油膜在液氮存在下用臼和杵研磨。薄膜粒子进一步用低温研磨器研磨8个循环。在8个循环的各个循环中,低温研磨器以速率15开2分钟,并关2分钟。所述粒子被储存在-20℃。
在步骤630,用脂肪酸将所述粒子均匀化以形成基于脂肪酸的溶体。在一个示例性实施方式中,利用Silerson均质器(8kRPM)将1克粒子与8克鱼油均匀化,直至所有粒子均匀地分散。
在步骤640,乳液基质与基于脂肪酸的溶体混合以形成乳液。在一个实施例中,利用Silverson均质器(8kRPM)将基于脂肪酸的溶体与31克4.2%的CMC凝胶(溶胀后)混合。
在步骤650,乳液被灭菌。例如,乳液可以用23kGy剂量的电子束灭菌。
按照步骤610-650,制备示例性乳液。所产生的乳液的粘度在50,000-75,000cP范围内。
在应用中,本发明的粘连屏障被施加于靶部位,例如手术部位。所述粘连屏障可以被施加在两个目的区域之间—例如组织、器官、网、或其它非吸收性材料之间。粘连屏障的固定性质致使粘连屏障固定于目的区域,使得屏障不从靶部位迁移。
手术后,手术切口被封合,并允许靶部位愈合。在不使用粘连屏障的正常情况下,将开始在目标区域之间形成粘连。例如,在手术后3至10天,可以在组织和器官之间形成纤维束。当靶部位存在粘连屏障时,所述粘连屏障预防粘连形成。因为所述粘连屏障充分固定于目标区域,以及因为所述粘连屏障被相对缓慢地吸收入体内,因此,在否则会形成粘连的时间中,所述粘连屏障保持在靶部位的位置。
在屏障功能不再需要后,粘连屏障被吸收入体内。
下面描述示例说明性的实施方式。
实施例1:实验台上的脱离力(BenchTopForceofDetachment)-非无菌样品
将取代度为0.65的2%(w/v)非交联高分子量Na-CMC(Sigma)在去离子水中构成的涂层溶液涂敷于15个1平方英寸的基于脂肪酸的膜,并使其干燥,以形成本发明实施方式的粘连屏障。所述粘连屏障被置于新宰杀的牛的肠上,所述肠在试验前在自来水中冲洗。试验前,所述粘连屏障被允许在组织上停留3分钟。使用Chatillon表测量在与粘连屏障和组织之间的粘连平面平行的方向上的脱离力。收集各个样品在Chatillon表上测得的最大的力。测量15个无涂层的基于脂肪酸的膜以供参考。无涂层的膜的平均脱离力为0.08磅。相比之下,形成本发明实施方式的粘连屏障的涂层膜的平均脱离力为0.54磅。
实施例2:脂肪酸-CMC膜使组织与组织的粘连最小化的体内结果
利用上面在实施例1中描述的方法产生本发明示例性实施方式的粘连屏障的试验样品。没有为了增加交联而修饰CMC,并且没有使用交联促进剂。试验样品被植入预防粘连的兔子侧壁模型。样品利用电子束以22.5kGy的剂量进行灭菌。盲肠被完全擦伤以产生斑点状出血,并切除3x5cm的腹膜切片。在未处理的动物中,该模型产生密集的粘连。4x6cm涂有CMC的O3FA膜被置于腹膜缺损处上,且涂层侧与侧壁直接接触。在植入后28天,处死兔子,并对粘连面积定级。
4只兔子被保持作为无处理的对照组。5只兔子用粘连屏障进行处理。在这4只对照对象中,平均粘连面积为100%。在具有粘连屏障的实验对象中,平均粘连面积为8%。
如前所述,在该实施例中没有使用交联促进剂。已知电子束能降解以前的固体CMC膜,这将导致更快的体内吸收。然而,尽管使用了电子束灭菌,来自实施例2的结果显示,粘连屏障保持组织附着至少28天。
实施例3
经辐射暴露进行交联是一种能用于增加水性CMC组合物在体内的停留时间的方法。为了评估辐射暴露对干燥的CMC膜的效应,将取代度为0.7的2%(w/v)Na-CMC(Hercules)在SWFI中构成的溶液用SWFI以5∶2的溶液∶SWFI比率进行稀释。稀释溶液被倒入特氟龙(Teflon)涂布的孔板中,并允许在室温下干燥24小时,以形成薄的固体CMC膜。该膜被切成几个单独包装的正方形片。几片用10MeV电子束源以22.5kGy的剂量辐射。辐射和未辐射的样品被浸没在分别的铝盘的去离子水中,并对溶解性和结构的维持/丧失进行评估。如果CMC薄膜因辐射暴露而交联,则膜的水合会导致一些溶胀,且维持最初的正方形几何形状。相反,辐射和未辐射的膜两者均在约10分钟内溶胀并丧失结构,并且在30分钟时不再能检测到固体或凝胶,这表明在这两个样品中,CMC是完全活动性的(没有交联或以其它方式通过化学键固定)。盘中的CMC溶液被允许在环境温度下蒸发48小时,产生了均匀的薄的固体CMC膜,该膜与盘子底部的圆盘几何形状一致。暴露和未暴露过的CMC膜的完全和相等的溶解性是电子束暴露没有明显限制(即交联)CMC材料的活动性的证据。
为了进一步评估辐射交联在O3FA存在下对CMC的效应,利用上面在实施例1中描述的方法产生本发明示例性实施方式的粘连屏障的两个试验样品。粘连屏障1被暴露于剂量为22.5kGy的10MeV电子束源。粘连屏障2没有暴露于电子束辐射。粘连屏障被称重,并暴露于200mL去离子水中,在2、5、和69小时进行目测评估。然后,粘连屏障在25毫托下真空干燥2小时。测量结果和观察结果提供在下面表1中。
表1
作者在先前已测得,所使用的涂层方法产生的涂层质量密度为2.28+/-0.11mg/cm2(平均+/-1σ,n=12)。这两种粘连屏障均有质量损失(分别为2.17和2.14mg/cm2),这支持下面的结论:该涂层在DI水中完全溶解,并因此没有交联或以其它方式固定。目测观察结果支持这个结论。
在O3FA存在下的CMC需要5至69小时来完全溶解于DI水中,而只有CMC的膜在30分钟内完全溶解。O3FA的存在看起来减慢了CMC在DI水中的溶解。这与电子束辐射无关。
实施例4
制备取代度为0.7的2%(w/v)Na-CMC(Hercules)和1%甘油在SWFI中构成的涂层溶液。所述涂层溶液被涂敷于几个基于脂肪酸的膜,并使其干燥,以形成粘连屏障。所述粘连屏障表现出极好的操作性,因为涂层被良好地塑化。将粘连屏障利用电子束以22.5kGy的剂量进行灭菌,并植入兔子侧壁粘连模型。盲肠被完全擦伤以产生斑点状出血,并切除3x5cm的腹膜切片。涂有CMC的4x6cm的膜被置于腹膜缺损处上,且涂层侧与侧壁直接接触。在植入后28天,处死兔子,并对粘连面积定级。
4只兔子被保持作为无处理的对照组。5只兔子用粘连屏障进行处理。在这4只对照对象中,平均粘连面积为100%。在具有粘连屏障的实验对象中,平均粘连面积为8%。
结果显示,在这项研究中,添加增塑剂对包含O3FA-CMC膜的粘连屏障的功效没有影响,因为粘连屏障没有从处理部位迁移。这项研究的结果显示,塑化的粘附屏障具有至少28天的组织固定性。
实施例5:具有组织固定性脱乙酰壳多糖涂层的O3FA膜。
将4%(w/v)ChitoPharmS(MW=50,000-1,000,000,Cognis)在1%乙酸溶液中构成的涂层溶液利用截止分子量为3,500的Fisherbrand再生纤维素透析袋进行透析。最终涂层溶液的pH为6.27。该涂层被施加于几个4x6cm的O3FA膜,并在预防粘连的兔子侧壁模型中进行评估。样品利用电子束以22.5kGy的剂量进行灭菌。盲肠被完全擦伤以产生斑点状出血,并切除3x5cm的腹膜切片。在未处理的动物中,该模型产生密集的粘连。涂有脱乙酰壳多糖的4x6cm的膜被置于腹膜缺损处上,且涂层侧与侧壁直接接触。在植入后28天,处死兔子,并对粘连面积定级。结果显示于下表中。
实施例6:乳液
根据图6中描述的程序制备如图5所描绘的乳液形式的粘连屏障。乳液样品被储存4℃直至进行试验。
乳液的试验样品在兔子侧壁模型中进行检测以评估粘连预防。盲肠被完全擦伤以产生斑点状出血,并切除3x5cm的腹膜切片。在未处理的动物中,该模型产生密集的粘连。10mL乳液被施用于腹膜和侧壁的损伤处。在植入后28天,处死兔子,并对粘连面积定级。
结果显示,6只试验动物的3只没有粘连形成(面积=0%)。剩余确实形成粘连的3只粘连度仅为1,这表明粘连是轻微的并容易被剥离。粘连覆盖的平均面积是28.3%,并且平均粘连度得分为0.5。这些结果与对照、即未经处理的动物形成对比,详见下表。
组 | 描述 | n | 平均粘连面积(%) | 粘连度 |
1 | 对照,无处理 | 4 | 100 | 2.75 |
2 | 乳液 | 6 | 28.3 | 0.5 |
生物相容性和体内性能
从文献中关于油氧化的传统科学报告(J.Dubois等.JAOCS.1996,Vol.73,No.6.,pgs787-794.;H.Ohkawa等,分析生物化学(AnalyticalBiochemistry),1979,Vol.95,pgs351-358.;H.H.Draper,2000,Vol.29,No.11,pgs1071-1077)看来,本发明所描述的制作基于脂肪酸的生物材料的过程导致了一些意想不到的化学过程和特性。由于形成了被认为生物不相容的反应性副产物例如氢过氧化物和α-β不饱和醛,油固化程序历来就有油氧化的顾虑(H.C.Yeo等.酶学方法(MethodsinEnzymology).1999,Vol.300,pgs70-78.;S-S.Kim等.脂质(Lipids).1999,Vol.34,No.5,pgs489-496.)。然而,在控制体内的生化过程中,来自油和脂肪的脂肪酸的氧化是正常且重要的。例如,调节某些生化途径例如促进或减少炎症是由不同的脂质氧化产物控制的(V.N.Bochkov和N.Leitinger,J.MolMed.2003;Vol.81,pgs613-626)。另外,已知ω-3脂肪酸对人类健康是重要的,特别是EPA和DHA具有体内抗炎性质。然而,EPA和DHA本身没有抗炎性,而产生体内抗炎效应的是它们生化转化成的氧化副产物(V.N.Bochkov和N.Leitinger,2003;L.J.RobertsII等.生物化学杂志(TheJournalofBiologicalChemistry).1998;Vol.273,No.22,pgs13605-13612.)。因此,尽管有某些生物不相容的油氧化产物,但也有几个具有积极的体内生化性质的其它产物(V.N.Bochkov和N.Leitinger,2003;F.M.Sacks和H.Campos.JClinEndocrinolMetab.2006;Vol.91,No.2,pgs398-400;A.Mishra等.ArteriosclerThrombVascBiol.2004;pgs1621-1627.)。因此,通过选择适当的工艺条件,能利用油氧化化学产生并控制油衍生的交联的疏水性生物材料,其最终的化学状况将具有有利的体内生物性能。
本发明的制作油衍生的疏水性非聚合生物材料的过程产生的最终化学状况是:就材料化学和在体内被身体水解和吸收后产生的产物而言,是生物相容的、使粘连形成最小化、发挥组织分离屏障的作用、并且是非炎性的。这些性质是由于本发明实施方式中的脂肪酸衍生的生物材料一些独特特性引起的。
本发明的一个方面是,没有使用有毒的短链交联剂(例如戊二醛)来形成油衍生的生物材料并进而形成本发明的粘连屏障。以前在文献中已证明,短链交联剂能在生物降解性聚合物水解期间洗脱并引起局部组织炎症。产生油衍生的生物材料的过程不涉及交联剂,因为所述油利用油自氧化或光氧化化学固化成涂层。氧化过程导致形成羧基和羟基官能团,让油衍生的生物材料非常快地变得水合并变得光滑,这使得植入期间和植入后的摩擦损伤显著降低和/或消除。本发明实施方式中描述的制作油衍生的生物材料的方法使得涂层中存在的脂肪酸、甘油酯和其它脂质副产物的烷基链是无序的,这产生了柔性并有助于在植入时操作所述材料的涂层。
本发明材料的几个个体化学成分有助于在体内观察到的生物相容性和低乃至无的炎性应答。本发明示例性实施方式的一个方面是,本文中描述的产生用于形成粘连屏障的油衍生的生物材料的过程引起的有生物相容性担忧的氧化脂质副产物例如醛的量低乃至不能检测到。在如本发明示例性实施方式中描述的固化过程期间,这些产物几乎被完全反应或挥发。产生油衍生的生物材料的过程极大地保留了天然油的酯类甘油三酯,并形成生物相容的酯和/或内酯交联(K.Park等,1993;J.M.Andersen,1995)。
除了油衍生的生物材料帮助其生物相容性的一般化学性质以外,还有具有积极的生物学性质的特定化学成分。另一个方面是,在产生油衍生的生物材料时产生的脂肪酸化学与组织的脂肪酸化学类似。因此,当脂肪酸从粘附屏障中洗脱时,它们不被身体视为“异质的”,并且不引起炎性应答。事实上,文献中已显示,粘附屏障中存在的C14(肉豆蔻)和C16(棕榈)脂肪酸减少炎性细胞因子α-TNF产生。α-TNF的表达已被鉴定为疝修补术后负责在腹腔中“开启”炎症、其后能导致异常愈合和粘连形成的关键细胞因子之一(Y.C.Cheong等,2001)。α-TNF也是血管损伤和炎症中的一个重要细胞因子(D.E.Drachman和D.I.Simon,2005;S.E.Goldblum,1989),例如在支架展开期间造成的血管损伤。除了刚才指定的脂肪酸之外,还有另外已鉴定的具有抗炎性质的氧化脂肪酸。从本文所描述的脂肪酸衍生的生物材料中鉴定的另一个成分是δ-内酯(即六元环的环酯)。δ-内酯已被鉴定为具有抗肿瘤的性质(H.Tanaka等.生命科学(LifeSciences)2007;Vol.80,pgs1851-1855)。
本文中所鉴定的成分并不意味着在范围上限制本发明,因为起始油组成和/或工艺条件的变化往往能改变脂肪酸和/或氧化副产物状况,并且能根据脂肪酸衍生的生物材料的预期目的和施用部位的需要而调整。
总之,形成本文中描述的粘连屏障的脂肪酸衍生生物材料的生物相容性和所观察到的体内性能是由于植入和愈合期间脂肪酸在材料水解期间洗脱引起的,并且不仅因材料的脂肪酸组成与天然组织相似而有利于预防体内异物反应(即生物“隐形”涂层),而且从涂层中洗脱的特定脂肪酸和/或其它脂质氧化物成分有助于预防异物反应并减少或消除炎症,这导致患者的结果改善。另外,从形成基于脂肪酸的粘附屏障膜的脂肪酸衍生生物材料中洗脱的脂肪酸和甘油酯成分能被局部组织吸收并被细胞代谢,例如在三羧酸循环中(M.J.Campell,《生物化学:第二版》(Biochemistry:SecondEdition).1995,pgs366-389)。因此,本发明所描述的脂肪酸衍生的生物材料也是生物可吸收的。
使用粘连屏障的处理方法
一般而言,人类存在四种类型的软组织:上皮组织,例如皮肤以及血管和许多器官的内衬;结缔组织,例如肌腱、韧带、软骨、脂肪、血管、和骨骼;肌肉,例如骨骼肌(横纹肌)、心肌、或平滑肌;和神经组织,例如脑、脊髓和神经。本发明的粘附屏障能用于处理这些软组织区域的损伤。因此,在一个实施方式中,本发明的粘附屏障能用于促进软组织增殖以愈合伤口。此外,急性创伤后,作为愈合和康复过程的结果,软组织经历变化和调适。这种变化包括但不限于化生,这是指一种组织转变成对该组织而言非正常的形式;发育异常,这是指组织的异常发育;增生,这是指正常组织排列中的正常细胞的过度增殖;和萎缩,这是指由于细胞死亡和再吸收或细胞增殖减少引起的组织尺寸缩小。因此,本发明的脂肪酸衍生的生物材料能用于削弱或减轻由软组织中的急性创伤造成的或相关的至少一个症状。
根据本发明的一个示例性实施方式,如下所述,粘附屏障能用于预防组织粘连。组织粘连可以是例如钝性剥离的结果。钝性剥离通常能被描述为沿着天然的分裂线分离组织而未经切割完成的剥离。钝性剥离利用许多不同的钝性手术器械来执行,这是本技术领域普通技术人员能理解的。钝性剥离往往在心血管、肛肠、泌尿科、妇科、上消化道和整形外科应用等等中执行。
在钝性剥离将所需要的组织分离成分开的区域后,往往需要保持这些组织的分离。事实上,术后粘连能发生在几乎任何类型的手术后,导致严重的术后并发症。手术粘连的形成是一个复杂的炎性过程,其中作为手术创伤的结果,在体内正常保持分离的组织变成互相物理接触并相互粘附。
据信,当来自受损组织的出血和血浆蛋白渗漏在腹腔中沉积并形成所谓的纤维蛋白性渗出物时,粘连形成。使受伤组织恢复的纤维蛋白是粘性的,因此纤维蛋白性渗出物可以在腹部中与相邻的解剖结构粘附。创伤后的或持续的炎症加剧了该过程,因为纤维蛋白沉积是对局部炎症的一致宿主反应。在损伤后的最初几天,这种粘附似乎是可逆的,因为纤维蛋白性渗出物经受由纤溶因子、最显著的是组织型纤溶酶原激活物(t-PA)释放引起的酶促降解。t-PA与纤溶酶原激活物抑制剂之间有恒定的作用。手术创伤通常降低t-PA活性并增加纤溶酶原激活物抑制剂。当发生这种情况时,纤维蛋白性渗出物中的纤维蛋白被胶原代替。血管开始形成,这导致粘连的发展。一旦发生这种情况,粘连就被认为是不可逆的。因此,在创伤后最初几天期间的纤维蛋白沉积和降解之间的平衡对粘连的发展是至关重要的(HolmdahlL.Lancet1999;353:1456-57)。如果正常的纤溶活性能被维持或迅速恢复,纤维蛋白沉积物就被溶解,并能避免永久性粘连。粘连能表现为薄的组织片或厚的纤维束。
经常地,炎症应答也被体内异物例如植入的医疗装置触发。身体将该植入物视为异物,并且炎性应答是隔开异物的细胞反应。该炎症能导致对植入的装置形成粘连;因此,极少乃至不引起炎性应答的材料是所希望的。
因此,本发明的粘连屏障可被用作保持组织分离以避免形成粘连例如手术粘连的屏障。用于预防粘连的应用实例包括腹部手术、脊柱修复、矫形外科手术、肌腱和韧带的修复、妇科和盆腔手术、和神经修复的应用。该粘附屏障可以被施用在创伤部位上或包在组织或器官周围以限制粘连形成。可以利用将治疗剂添加至这些预防粘连应用所使用的脂肪酸衍生的生物材料,以获得附加的有利效应,例如缓解疼痛或使感染最小化。该粘连屏障的其它外科应用可以包括使用独立膜作为硬脑膜斑贴、支撑材料、内部伤口护理(如移植吻合部位)、和内部药物递送系统。该粘连屏障也可以被用于经皮、伤口愈合、和非手术领域的应用。该粘连屏障可被用于外部伤口护理,例如对烧伤或皮肤溃疡的处理。该粘连屏障可被用作清洁的、非渗透性的、非粘性的、非炎性的、抗炎敷料而没有任何治疗剂,或者粘连屏障可以与一种或多种治疗剂一起使用以获得附加的有利效应。当脂肪酸衍生的生物材料荷载或涂有一种或多种治疗剂时,粘连屏障也可以被用作经皮药物递送斑贴。
伤口愈合的过程涉及对损伤作出响应的组织修复,并且它包含许多不同的生物学过程,包括上皮的生长和分化、纤维组织的产生和作用、血管生成、和炎症。因此,粘连屏障提供了适合用于伤口愈合应用的极好的材料。
将基于脂肪酸的膜与组织固定材料组合产生了具有固定和抗炎性质的有效的粘连屏障。所产生的粘连屏障身体耐受良好、减少术后粘连、并且由于膜的固定性质而不从靶部位迁移。此外,与常规的基于CMC的膜相比,所述粘附屏障被吸收入体内相对缓慢,并因此在长达28天内减轻了粘连屏障和处理部位之间的组织粘连。这提供了足够的停留时间以有效提供术后屏障功能。此外,将基于脂肪酸的膜与组织固定材料组合可避免对交联组织固定材料的需求,从而减少制造膜的成本和复杂性。
由前面的说明书看来,本发明的许多修改和备选实施方式对于本技术领域的专业人员将是显而易见的。因此,本说明书被解释为仅是说明性的,并且目的是教导本技术领域的专业人员执行本发明的最佳方式。在不脱离本发明的精神下,结构细节能显著变化,并且保留落在权利要求范围内的所有修改的专属应用。本发明意欲仅被限制到权利要求和适用的法规所要求的程度。
本申请中引用的所有文献和类似的材料,包括专利、专利申请、文章、书籍、专著、论文和网页,不管这种文献和类似材料的格式如何,明确地以其全文通过参考引入于此。在一个或多个引入的文献和类似材料与本申请不同或矛盾的情况下,包括定义的术语、术语的使用、所描述的技术等在内,以本申请为准。
本文中使用的章节标题仅用作组织的目的,不应以任何方式解释为限制所描述的主题。
尽管本发明已结合各种实施方式和实施例进行描述,但本发明的教导意欲不限于这样的实施方式或实施例。相反,本发明包括各种备选方案、修改和等价物,这将是本技术领域的专业人员能理解的。
权利要求不应读作限于所描述的顺序或元素,除非规定了该效应。应当理解,在不脱离权利要求的范围下,形式和细节能作出各种变化。因此,要求保护落在权利要求书的范围和精神内的所有实施方式及其等价物。
Claims (39)
1.粘连屏障,其包含:
具有组织抗粘连特性的基于脂肪酸的材料;和
被置于所述基于脂肪酸的材料的表面上或周围的亲水性组织固定材料;
其中所述基于脂肪酸的材料包括通过酯键彼此交联的脂肪酸;
其中所述基于脂肪酸的材料是生物可吸收的;以及
其中所述基于脂肪酸的材料和所述组织固定材料形成所述粘连屏障,形成方式使得所述粘连屏障是非炎性的并且所述组织固定材料将所述粘连屏障在体内直接固定于组织历时大于10天的持续时间,
其中所述组织固定材料包含以下之一:羧甲基纤维素、羧甲基纤维素钠、聚乙二醇、聚氧化乙烯、聚HEMA、聚N-乙烯基吡咯烷酮、聚丙烯酸、脱乙酰壳多糖、和聚阴离子多糖。
2.权利要求1的粘连屏障,其中所述基于脂肪酸的材料源自交联的脂肪酸衍生的生物材料。
3.权利要求1的粘连屏障,其中所述基于脂肪酸的材料从鱼油产生。
4.权利要求1的粘连屏障,其中所述基于脂肪酸的材料是基于脂肪酸的膜,且所述组织固定材料被置于所述基于脂肪酸的膜的仅一个面上。
5.权利要求4的粘连屏障,其中所述基于脂肪酸的材料减轻在不存在所述基于脂肪酸的膜时与所述组织固定材料相关的炎症。
6.权利要求1的粘连屏障,其进一步包含向所述粘连屏障添加增塑剂。
7.权利要求6的粘连屏障,其中所述增塑剂包含以下之一:甘油、丙二醇、聚乙二醇、柠檬酸甘油三乙酸酯和甘油三乙酸酯。
8.粘连屏障,其包含:
源自脂肪酸衍生的生物材料的膜;和
遍及所述膜被布置的组织固定材料;
其中所述源自脂肪酸衍生的生物材料包括通过酯键彼此交联的脂肪酸;
其中所述膜和所述组织固定材料形成所述粘连屏障,形成方式使得所述粘连屏障是非炎性的并且所述组织固定材料将所述粘连屏障在体内直接固定于组织历时大于10天的持续时间,
其中所述组织固定材料包含以下之一:羧甲基纤维素、羧甲基纤维素钠、聚乙二醇、聚氧化乙烯、聚HEMA、聚N-乙烯基吡咯烷酮、聚丙烯酸、脱乙酰壳多糖、和聚阴离子多糖。
9.权利要求8的粘连屏障,其中所述组织固定材料包含包裹所述膜的组织固定涂层并将所述粘连屏障直接吸水性固定到组织。
10.权利要求8的粘连屏障,其中所述组织固定材料作为所述膜的一部分被提供并将所述粘连屏障直接吸水性固定到组织。
11.权利要求8的粘连屏障,其中所述膜是基于ω-3脂肪酸的膜。
12.权利要求8的粘连屏障,其中所述脂肪酸衍生的生物材料是交联的。
13.权利要求8的粘连屏障,其中所述脂肪酸衍生的生物材料包含鱼油。
14.权利要求8的粘连屏障,其中所述脂肪酸衍生的生物材料减轻在不存在所述源自脂肪酸衍生的生物材料的膜时与所述组织固定材料相关的炎症。
15.权利要求8的粘连屏障,其中所述粘连屏障具有足以防止术后粘连的停留时间。
16.权利要求8的粘连屏障,其进一步包含增塑剂。
17.权利要求16的粘连屏障,其中所述增塑剂包含以下之一:甘油、丙二醇、聚乙二醇、柠檬酸甘油三乙酸酯和甘油三乙酸酯。
18.用于制备由具有组织抗粘连特性的基于脂肪酸的膜和亲水性组织固定材料形成的粘连屏障的方法,形成方式使得所述粘连屏障是非炎性的并且所述组织固定材料将所述粘连屏障在体内直接固定于组织历时大于10天的持续时间,所述方法包括:
提供所述基于脂肪酸的膜,其中所述基于脂肪酸的膜包括通过酯键彼此交联的脂肪酸,以及其中所述基于脂肪酸的膜是生物可吸收的;
提供所述组织固定材料;和
将所述基于脂肪酸的膜与所述组织固定材料组合以形成所述粘连屏障,
其中所述组织固定材料包含以下之一:羧甲基纤维素、羧甲基纤维素钠、聚乙二醇、聚氧化乙烯、聚HEMA、聚N-乙烯基吡咯烷酮、聚丙烯酸、脱乙酰壳多糖、和聚阴离子多糖。
19.权利要求18的方法,其中所述基于脂肪酸的膜源自交联的脂肪酸衍生的生物材料。
20.权利要求18的方法,其中所述基于脂肪酸的膜从鱼油产生。
21.权利要求18的方法,其中所述基于脂肪酸的膜不从手术放置部位迁移。
22.权利要求18的方法,其中所述组织固定材料被置于所述基于脂肪酸的膜的仅一个面上以便将所述粘连屏障直接吸水性粘附于组织。
23.权利要求18的方法,其中所述组织固定材料在所述基于脂肪酸的膜的一个以上的面上包覆所述基于脂肪酸的膜以便将所述粘连屏障直接吸水性粘附于组织。
24.权利要求18的方法,其中所述组织固定材料遍及所述基于脂肪酸的膜被布置以便将所述粘连屏障直接吸水性粘附于组织。
25.权利要求18的方法,其中所述基于脂肪酸的膜减轻在不存在所述基于脂肪酸的膜时与所述组织固定材料相关的炎症。
26.权利要求18的方法,其进一步包括向所述组织固定材料添加增塑剂。
27.权利要求26的方法,其中所述增塑剂包含以下之一:甘油、丙二醇、聚乙二醇、柠檬酸甘油三乙酸酯和甘油三乙酸酯。
28.粘连屏障,其包含:
源自脂肪酸衍生的生物材料的基于脂肪酸的粒子,其中所述基于脂肪酸的粒子包括通过酯键彼此交联的脂肪酸;和
包含组织固定材料的乳液基质;
其中所述基于脂肪酸的粒子与所述乳液基质混合以形成所述粘连屏障,形成方式使得所述粘连屏障是非炎性的并且在体内直接附着于组织历时大于10天的持续时间,
其中所述组织固定材料包含以下之一:羧甲基纤维素、羧甲基纤维素钠、聚乙二醇、聚氧化乙烯、聚HEMA、聚N-乙烯基吡咯烷酮、聚丙烯酸、脱乙酰壳多糖、和聚阴离子多糖。
29.权利要求28的粘连屏障,其中所述基于脂肪酸的粒子在与所述乳液基质混合前被浸泡在治疗剂中。
30.权利要求28的粘连屏障,其中所述基于脂肪酸的粒子的平均粒度在1微米和50微米之间。
31.权利要求30的粘连屏障,其中所述基于脂肪酸的粒子的平均粒度在1微米和10微米之间。
32.权利要求28的粘连屏障,其中所述基于脂肪酸的粒子具有1-20μm的粒度分布。
33.权利要求28的粘连屏障,其中所述基于脂肪酸的粒子具有21-40μm的粒度分布。
34.权利要求28的粘连屏障,其中所述基于脂肪酸的粒子具有41-150μm的粒度分布。
35.权利要求28的粘连屏障,其中所述基于脂肪酸的粒子是基于ω-3脂肪酸的粒子。
36.权利要求28的粘连屏障,其中所述脂肪酸衍生的生物材料是交联的。
37.权利要求28的粘连屏障,其中所述脂肪酸衍生的生物材料包含鱼油。
38.权利要求1的粘连屏障,其中所述组织固定材料直接亲水性固定于所述组织。
39.权利要求28的粘连屏障,其中所述粘连屏障通过亲水性粘附直接附着于所述组织。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US12/581,582 | 2009-10-19 | ||
US12/581,582 US9278161B2 (en) | 2005-09-28 | 2009-10-19 | Tissue-separating fatty acid adhesion barrier |
PCT/US2010/052899 WO2011049833A1 (en) | 2009-10-19 | 2010-10-15 | Tissue-separating fatty acid adhesion barrier |
Publications (2)
Publication Number | Publication Date |
---|---|
CN102753118A CN102753118A (zh) | 2012-10-24 |
CN102753118B true CN102753118B (zh) | 2016-01-20 |
Family
ID=43900625
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201080047130.0A Expired - Fee Related CN102753118B (zh) | 2009-10-19 | 2010-10-15 | 组织分离性脂肪酸粘连屏障 |
Country Status (5)
Country | Link |
---|---|
US (3) | US9278161B2 (zh) |
EP (1) | EP2490618A4 (zh) |
JP (2) | JP5778159B2 (zh) |
CN (1) | CN102753118B (zh) |
WO (1) | WO2011049833A1 (zh) |
Families Citing this family (19)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9801982B2 (en) | 2004-09-28 | 2017-10-31 | Atrium Medical Corporation | Implantable barrier device |
WO2006036969A2 (en) | 2004-09-28 | 2006-04-06 | Atrium Medical Corporation | Formation of barrier layer |
WO2006036982A2 (en) | 2004-09-28 | 2006-04-06 | Atrium Medical Corporation | Drug delivery coating for use with a stent |
US9012506B2 (en) | 2004-09-28 | 2015-04-21 | Atrium Medical Corporation | Cross-linked fatty acid-based biomaterials |
US9000040B2 (en) | 2004-09-28 | 2015-04-07 | Atrium Medical Corporation | Cross-linked fatty acid-based biomaterials |
US8367099B2 (en) | 2004-09-28 | 2013-02-05 | Atrium Medical Corporation | Perforated fatty acid films |
US8312836B2 (en) | 2004-09-28 | 2012-11-20 | Atrium Medical Corporation | Method and apparatus for application of a fresh coating on a medical device |
EP1879632A2 (en) * | 2005-04-29 | 2008-01-23 | Atrium Medical Corporation | Drug delivery coating for use with a medical device and methods of treating vascular injury |
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 |
US8574627B2 (en) | 2006-11-06 | 2013-11-05 | Atrium Medical Corporation | Coated surgical mesh |
CA2626030A1 (en) | 2005-10-15 | 2007-04-26 | Atrium Medical Corporation | Hydrophobic cross-linked gels for bioabsorbable drug carrier coatings |
US9492596B2 (en) | 2006-11-06 | 2016-11-15 | Atrium Medical Corporation | Barrier layer with underlying medical device and one or more reinforcing support structures |
US20110038910A1 (en) | 2009-08-11 | 2011-02-17 | Atrium Medical Corporation | Anti-infective antimicrobial-containing biomaterials |
US10322213B2 (en) | 2010-07-16 | 2019-06-18 | Atrium Medical Corporation | Compositions and methods for altering the rate of hydrolysis of cured oil-based materials |
US9867880B2 (en) * | 2012-06-13 | 2018-01-16 | Atrium Medical Corporation | Cured oil-hydrogel biomaterial compositions for controlled drug delivery |
IN2013DE03528A (zh) | 2013-12-05 | 2015-06-12 | Colgate Palmolive Co | |
WO2015085151A1 (en) * | 2013-12-05 | 2015-06-11 | Colgate-Palmolive Company | Method of measuring viscosity of gums |
CN103750922B (zh) * | 2013-12-31 | 2016-07-13 | 金仕生物科技(常熟)有限公司 | 制备人工心脏瓣膜瓣叶的方法 |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5580923A (en) * | 1995-03-14 | 1996-12-03 | Collagen Corporation | Anti-adhesion films and compositions for medical use |
CN1633313A (zh) * | 2002-02-15 | 2005-06-29 | Cv医药有限公司 | 用于医用装置的聚合物涂层 |
CN1925881A (zh) * | 2004-02-28 | 2007-03-07 | 汉莫堤克科技公司 | 药物表面的生物相容性涂层、方法和用途 |
CN101094698A (zh) * | 2003-09-29 | 2007-12-26 | 汉莫堤克科技公司 | 医学表面的生物相容,生物稳定的涂层 |
Family Cites Families (518)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2735814A (en) * | 1956-02-21 | Die forging compound | ||
US2403458A (en) | 1946-07-09 | Solvent extraction of drying oils | ||
US1948959A (en) | 1934-02-27 | Coating material | ||
US2555976A (en) | 1951-06-05 | Oxidation of drying and semidkying | ||
US2368306A (en) | 1941-05-02 | 1945-01-30 | Stackpole Carbon Co | Method of treating electrodes |
US2986540A (en) | 1958-08-01 | 1961-05-30 | Stamford Rubber Supply Company | Organic plastic materials made from vulcanized oils and their preparation |
US3328259A (en) * | 1964-01-08 | 1967-06-27 | Parachem Corp | Dressing for a wound containing a hemostatic agent and method of treating a wound |
US3464413A (en) | 1967-05-26 | 1969-09-02 | United Merchants & Mfg | Medical bandages |
US3556294A (en) | 1968-11-25 | 1971-01-19 | Bard Inc C R | Catheter package with self-contained lubricant |
US3567820A (en) | 1969-04-09 | 1971-03-02 | George S Sperti | Compositions and treatment for the alleviation of diaper rash |
JPS4826844B1 (zh) | 1970-11-17 | 1973-08-16 | ||
JPS4950124A (zh) | 1972-09-27 | 1974-05-15 | ||
US3967728A (en) | 1973-03-02 | 1976-07-06 | International Paper Company | Catheter package |
US4185637A (en) | 1978-05-30 | 1980-01-29 | Ethicon, Inc. | Coating composition for sutures |
DE2828623C2 (de) | 1978-06-29 | 1983-11-17 | Kernforschungsanlage Jülich GmbH, 5170 Jülich | Mit radioaktivem Flour markierte C↓1↓↓6↓-bis C↓1↓↓8↓- Fettsäuren, ein Verfahren zu ihrer Herstellung sowie deren Verwendung |
DE2842938A1 (de) | 1978-10-02 | 1980-04-17 | Roehm Gmbh | Verfahren zum polymerisieren mittels uv-licht |
EP0011437B1 (en) | 1978-11-20 | 1983-06-22 | Imperial Chemical Industries Plc | A process for setting a product comprising electrostatically spun fibres, and products prepared according to this process |
US4447418A (en) | 1981-03-06 | 1984-05-08 | Maddoux Lilla A | Animal medicine |
US4557925A (en) | 1982-07-08 | 1985-12-10 | Ab Ferrosan | Membrane-coated sustained-release tablets and method |
SE8206744D0 (sv) | 1982-11-26 | 1982-11-26 | Fluidcarbon International Ab | Preparat for kontrollerad avgivning av substanser |
US4702252A (en) | 1983-10-13 | 1987-10-27 | Smiths Industries Public Limited Company | Catheters |
DE3339236A1 (de) | 1983-10-28 | 1985-05-09 | Bayer Ag | Arzneimittelzubereitung |
SU1297865A1 (ru) | 1984-05-04 | 1987-03-23 | Ленинградский Государственный Институт Усовершенствования Врачей Им.С.М.Кирова | Способ лечени больных хроническим неспецифическим звенным колитом |
SE456346B (sv) | 1984-07-23 | 1988-09-26 | Pharmacia Ab | Gel for att forhindra adhesion mellan kroppsvevnader och sett for dess framstellning |
US5176956A (en) | 1984-09-26 | 1993-01-05 | Medtronic, Inc. | Biomedical apparatus having fatty acid dimer derived skin compatible adhesive composition thereon |
US5411951A (en) | 1984-10-04 | 1995-05-02 | Monsanto Company | Prolonged release of biologically active somatotropin |
HU193951B (en) | 1985-03-11 | 1987-12-28 | Richter Gedeon Vegyeszet | Process for producing new sulfur-containing 5-substituted benzimidazol derivatives and pharmaceutical compositions containing them |
US4824436A (en) | 1985-04-09 | 1989-04-25 | Harvey Wolinsky | Method for the prevention of restenosis |
US4655221A (en) | 1985-05-06 | 1987-04-07 | American Cyanamid Company | Method of using a surgical repair mesh |
US4895724A (en) | 1985-06-07 | 1990-01-23 | Pfizer Inc. | Chitosan compositions for controlled and prolonged release of macromolecules |
JPS61291520A (ja) | 1985-06-19 | 1986-12-22 | Daigo Eiyou Kagaku Kk | エリスロマイシン脂肪乳剤 |
US4664114A (en) | 1985-08-12 | 1987-05-12 | Kamran Ghodsian | Dilator for cervical canal |
US4883667A (en) | 1985-08-16 | 1989-11-28 | Alza Corporation | Process for forming dispensing device |
JPS6274364A (ja) | 1985-09-27 | 1987-04-06 | 株式会社 ニツシヨ− | 医療用具 |
US4733665C2 (en) | 1985-11-07 | 2002-01-29 | Expandable Grafts Partnership | Expandable intraluminal graft and method and apparatus for implanting an expandable intraluminal graft |
US4847301A (en) | 1985-11-13 | 1989-07-11 | Pennwalt Corporation | Methods of use of α-(aminoalkyl)-arylacetic acid derivatives |
IN166447B (zh) | 1985-11-27 | 1990-05-12 | Ethicon Inc | |
US5061281A (en) | 1985-12-17 | 1991-10-29 | Allied-Signal Inc. | Bioresorbable polymers and implantation devices thereof |
US4769038A (en) | 1986-03-18 | 1988-09-06 | C. R. Bard, Inc. | Prostheses and techniques and repair of inguinal and femoral hernias |
DE3634016A1 (de) | 1986-04-17 | 1987-10-29 | Lohmann Gmbh & Co Kg | Flaechenfoermiges therapeutisches system, verfahren zu seiner herstellung und seine verwendung |
WO1987006463A1 (en) | 1986-05-02 | 1987-11-05 | Brigham And Women's Hospital | A composition having reduced nephrotoxicity comprising a fatty acid containing component and cyclosporine |
US5118493A (en) | 1986-05-02 | 1992-06-02 | Brigham And Women's Hospital | Composition having reduced nephrotoxocity comprising a fatty acid containing component and cyclosporine |
DE3622399A1 (de) | 1986-07-01 | 1988-02-04 | Eberhardt Schlueter | Selbsttaetige injektionsvorrichtung sowie ampulle oder patrone fuer eine injektionsvorrichtung |
US5371109A (en) | 1986-07-01 | 1994-12-06 | Drilletten Ab | Controlled release composition for a biologically active material dissolved or dispersed in an L2-phase |
US5071609A (en) | 1986-11-26 | 1991-12-10 | Baxter International Inc. | Process of manufacturing porous multi-expanded fluoropolymers |
US4911707A (en) | 1987-02-13 | 1990-03-27 | Ciba-Geigy Corporation | Monolithic user-activated transdermal therapeutic system |
IL81975A0 (en) | 1987-03-24 | 1987-10-20 | Haifa Chemicals Ltd | Method for the manufacture of slow-release fertilizers |
US6387379B1 (en) | 1987-04-10 | 2002-05-14 | University Of Florida | Biofunctional surface modified ocular implants, surgical instruments, medical devices, prostheses, contact lenses and the like |
US4894231A (en) | 1987-07-28 | 1990-01-16 | Biomeasure, Inc. | Therapeutic agent delivery system |
US4947840A (en) | 1987-08-21 | 1990-08-14 | Massachusetts Institute Of Technology | Biodegradable templates for the regeneration of tissues |
US4846844A (en) | 1987-08-31 | 1989-07-11 | Eli Lilly And Company | Antimicrobial coated implants |
US5705485A (en) * | 1987-09-18 | 1998-01-06 | Ethicon, Inc. | Gel formulations containing growth factors |
US5017229A (en) | 1990-06-25 | 1991-05-21 | Genzyme Corporation | Water insoluble derivatives of hyaluronic acid |
DE3734147C2 (de) | 1987-10-09 | 1998-10-29 | Braun Melsungen Ag | Isotone omega-3-fettsäurenhaltige Fettemulsion und ihre Verwendung |
JPH01175864A (ja) | 1987-12-29 | 1989-07-12 | Terumo Corp | 留置針およびその製法 |
US5254105A (en) | 1988-05-26 | 1993-10-19 | Haaga John R | Sheath for wound closure caused by a medical tubular device |
US4941308A (en) | 1988-07-25 | 1990-07-17 | Abbott Laboratories | Method of packaging for a sterilizable calibratable medical device |
JP2836878B2 (ja) | 1988-08-24 | 1998-12-14 | スリピアン,マービン,ジェイ | 生分解性高分子材料による管腔内封止 |
US4938763B1 (en) | 1988-10-03 | 1995-07-04 | Atrix Lab Inc | Biodegradable in-situ forming implants and method of producing the same |
US5087246A (en) | 1988-12-29 | 1992-02-11 | C. R. Bard, Inc. | Dilation catheter with fluted balloon |
US5041125A (en) | 1989-01-26 | 1991-08-20 | Cordis Corporation | Balloon catheter |
US4941877A (en) | 1989-01-26 | 1990-07-17 | Cordis Corporation | Balloon catheter |
US5087244A (en) | 1989-01-31 | 1992-02-11 | C. R. Bard, Inc. | Catheter and method for locally applying medication to the wall of a blood vessel or other body lumen |
DE3903056A1 (de) | 1989-02-02 | 1990-08-09 | Braun Melsungen Ag | Fettemulsion zur intraperitonealen applikation, ihre herstellung und anwendung |
US6146358A (en) | 1989-03-14 | 2000-11-14 | Cordis Corporation | Method and apparatus for delivery of therapeutic agent |
US4994033A (en) | 1989-05-25 | 1991-02-19 | Schneider (Usa) Inc. | Intravascular drug delivery dilatation catheter |
US5171148A (en) | 1989-06-30 | 1992-12-15 | Ethicon, Inc. | Dental inserts for treatment of periodontal disease |
FR2653338B1 (fr) * | 1989-10-23 | 1994-06-10 | Dow Corning Sa | Formulation pour des pansements a liberation prolongee de medicament et son utilisation. |
US5843089A (en) | 1990-12-28 | 1998-12-01 | Boston Scientific Corporation | Stent lining |
US5304121A (en) | 1990-12-28 | 1994-04-19 | Boston Scientific Corporation | Drug delivery system making use of a hydrogel polymer coating |
US5049132A (en) | 1990-01-08 | 1991-09-17 | Cordis Corporation | Balloon catheter for delivering therapeutic agents |
US5179174A (en) | 1990-04-23 | 1993-01-12 | C. R. Bard, Inc. | Flexible lubricious organic coatings |
US5199951A (en) | 1990-05-17 | 1993-04-06 | Wayne State University | Method of drug application in a transporting medium to an arterial wall injured during angioplasty |
US5202310A (en) | 1990-06-06 | 1993-04-13 | Levy Gary A | Cyclosporine metabolites |
US5499971A (en) | 1990-06-15 | 1996-03-19 | Cortrak Medical, Inc. | Method for iontophoretically delivering drug adjacent to a heart |
US5498238A (en) | 1990-06-15 | 1996-03-12 | Cortrak Medical, Inc. | Simultaneous angioplasty and phoretic drug delivery |
DE69110467T2 (de) | 1990-06-15 | 1996-02-01 | Cortrak Medical Inc | Vorrichtung zur abgabe von medikamenten. |
GB9018144D0 (en) | 1990-08-17 | 1990-10-03 | Unilever Plc | Polymerisation process |
US5102402A (en) | 1991-01-04 | 1992-04-07 | Medtronic, Inc. | Releasable coatings on balloon catheters |
WO1992013500A1 (en) | 1991-02-08 | 1992-08-20 | Surgical Innovations, Inc. | Method and apparatus for repair of inguinal hernias |
US5458568A (en) | 1991-05-24 | 1995-10-17 | Cortrak Medical, Inc. | Porous balloon for selective dilatation and drug delivery |
DE4133694C2 (de) | 1991-10-11 | 1993-10-07 | Fresenius Ag | Verwendung einer Emulsion mit mehrfach ungesättigten Fettsären zur i.v.-Verabreichung zur Behandlung von Hauterkrankungen |
CA2380683C (en) | 1991-10-28 | 2006-08-08 | Advanced Cardiovascular Systems, Inc. | Expandable stents and method for making same |
JPH07503943A (ja) | 1991-10-29 | 1995-04-27 | クローバー コンソリデイテッド,リミテッド | 封入及び薬剤放出に有用な架橋性の多糖類、ポリカチオン及び脂質 |
US5206077A (en) | 1991-11-25 | 1993-04-27 | The Dow Chemical Company | Low vaporizable ethylenically unsaturated monomer emission vinyl ester and polyester resin compositions |
US5147374A (en) | 1991-12-05 | 1992-09-15 | Alfredo Fernandez | Prosthetic mesh patch for hernia repair |
US5683448A (en) | 1992-02-21 | 1997-11-04 | Boston Scientific Technology, Inc. | Intraluminal stent and graft |
SE9200541D0 (sv) | 1992-02-24 | 1992-02-24 | Kabi Pharmacia Ab | New usee of omega-3-fatty acids |
CA2117588C (en) | 1992-02-28 | 1998-08-25 | Jeffrey A. Hubbell | Photopolymerizable biodegradable hydrogels as tissue contacting materials and controlled-release carriers |
WO1993017635A1 (en) | 1992-03-04 | 1993-09-16 | C.R. Bard, Inc. | Composite prosthesis and method for limiting the incidence of postoperative adhesions |
ES2187506T3 (es) * | 1992-04-24 | 2003-06-16 | Chienna Bv | Dispositivos para la prevencion de adhesiones de tejidos. |
ATE155684T1 (de) | 1992-04-28 | 1997-08-15 | Fresenius Ag | Verwendung einer omega-3-fettsäuren enthaltenden emulsion zur herstellung eines parenteral zu verabreichenden arzneimittels zur behandlung von entzündlichen erkrankungen |
US5368566A (en) | 1992-04-29 | 1994-11-29 | Cardiovascular Dynamics, Inc. | Delivery and temporary stent catheter having a reinforced perfusion lumen |
US5637317A (en) | 1992-05-18 | 1997-06-10 | Dietl; Hans | Pharmaceutical preparation containing cyclosporin(s) for oral administration and process for producing same |
US5766246A (en) | 1992-05-20 | 1998-06-16 | C. R. Bard, Inc. | Implantable prosthesis and method and apparatus for loading and delivering an implantable prothesis |
US6312442B1 (en) | 1992-06-02 | 2001-11-06 | General Surgical Innovations, Inc. | Method for developing an anatomic space for laparoscopic hernia repair |
DE4222380A1 (de) | 1992-07-08 | 1994-01-13 | Ernst Peter Prof Dr M Strecker | In den Körper eines Patienten perkutan implantierbare Endoprothese |
US5283257A (en) | 1992-07-10 | 1994-02-01 | The Board Of Trustees Of The Leland Stanford Junior University | Method of treating hyperproliferative vascular disease |
US5879359A (en) | 1992-08-03 | 1999-03-09 | Fidia S.P.A. | Biodegradable guide channels comprised of esters of hyaluronic acid for use in tissue repair as surgical aids |
US5753343A (en) | 1992-08-04 | 1998-05-19 | Minnesota Mining And Manufacturing Company | Corrugated nonwoven webs of polymeric microfiber |
US5634899A (en) | 1993-08-20 | 1997-06-03 | Cortrak Medical, Inc. | Simultaneous cardiac pacing and local drug delivery method |
DE4236912A1 (de) | 1992-10-31 | 1994-05-05 | Huels Chemische Werke Ag | Vernetzte Ricinusöl-Derivate |
US5336178A (en) | 1992-11-02 | 1994-08-09 | Localmed, Inc. | Intravascular catheter with infusion array |
US5807306A (en) | 1992-11-09 | 1998-09-15 | Cortrak Medical, Inc. | Polymer matrix drug delivery apparatus |
DE4238994A1 (de) | 1992-11-19 | 1994-05-26 | Basf Ag | Aniline als Markierungsmittel für Mineralöle |
CA2114290C (en) | 1993-01-27 | 2006-01-10 | Nagabushanam Totakura | Post-surgical anti-adhesion device |
US6491938B2 (en) | 1993-05-13 | 2002-12-10 | Neorx Corporation | Therapeutic inhibitor of vascular smooth muscle cells |
US5279565A (en) | 1993-02-03 | 1994-01-18 | Localmed, Inc. | Intravascular treatment apparatus and method |
US5356432B1 (en) | 1993-02-05 | 1997-02-04 | Bard Inc C R | Implantable mesh prosthesis and method for repairing muscle or tissue wall defects |
US5267985A (en) | 1993-02-11 | 1993-12-07 | Trancell, Inc. | Drug delivery by multiple frequency phonophoresis |
US5368602A (en) | 1993-02-11 | 1994-11-29 | De La Torre; Roger A. | Surgical mesh with semi-rigid border members |
US5433996A (en) | 1993-02-18 | 1995-07-18 | W. L. Gore & Associates, Inc. | Laminated patch tissue repair sheet material |
DE4306850C1 (de) | 1993-03-01 | 1994-08-18 | Ethicon Gmbh | Implantat, insbesondere zum Verschluß von Trokareinstichstellen |
US6015844A (en) | 1993-03-22 | 2000-01-18 | Johnson & Johnson Medical, Inc. | Composite surgical material |
GB2280850B (en) | 1993-07-28 | 1997-07-30 | Johnson & Johnson Medical | Absorbable composite materials for use in the treatment of periodontal disease |
US5985307A (en) | 1993-04-14 | 1999-11-16 | Emory University | Device and method for non-occlusive localized drug delivery |
DE4313402A1 (de) | 1993-04-23 | 1994-10-27 | Hexal Pharma Gmbh | Transdermale Wirkstoffzubereitung |
US5464650A (en) | 1993-04-26 | 1995-11-07 | Medtronic, Inc. | Intravascular stent and method |
US5380328A (en) | 1993-08-09 | 1995-01-10 | Timesh, Inc. | Composite perforated implant structures |
WO1995005083A1 (en) | 1993-08-13 | 1995-02-23 | Smith & Nephew Richards Inc | Microporous polymeric foams and microtextured surfaces |
EP0746362B1 (en) | 1993-08-23 | 2002-01-16 | Boston Scientific Corporation | Improved balloon catheter |
US5746745A (en) | 1993-08-23 | 1998-05-05 | Boston Scientific Corporation | Balloon catheter |
FR2710161B1 (fr) | 1993-09-13 | 1995-11-24 | Suisse Electronique Microtech | Réseau miniature d'obturateurs de lumière. |
FR2709947B1 (fr) | 1993-09-13 | 1995-11-10 | Bard Sa Laboratoires | Filet prothétique galbé et son procédé de fabrication. |
WO1996014895A1 (en) | 1994-11-14 | 1996-05-23 | Scimed Life Systems, Inc. | Catheter balloon with retraction coating |
US5411988A (en) | 1993-10-27 | 1995-05-02 | Bockow; Barry I. | Compositions and methods for inhibiting inflammation and adhesion formation |
US5403283A (en) | 1993-10-28 | 1995-04-04 | Luther Medical Products, Inc. | Percutaneous port catheter assembly and method of use |
US5468242A (en) | 1993-11-19 | 1995-11-21 | Leibinger Gmbh | Form-fitting mesh implant |
JP3185906B2 (ja) | 1993-11-26 | 2001-07-11 | ニプロ株式会社 | 心房中隔欠損の補綴材 |
AU681231B2 (en) | 1993-12-29 | 1997-08-21 | Intarcia Therapeutics, Inc. | Methods and compositions for the treatment of a host with a cellular proliferative disease |
JPH09509081A (ja) | 1994-02-17 | 1997-09-16 | ダブリュ.エル.ゴア アンド アソシエイツ,インコーポレイティド | 切削可能なptfe移植材料 |
US6228383B1 (en) | 1994-03-03 | 2001-05-08 | Gs Development Ab | Use of fatty acid esters as bioadhesive substances |
US5558071A (en) | 1994-03-07 | 1996-09-24 | Combustion Electromagnetics, Inc. | Ignition system power converter and controller |
ATE180971T1 (de) | 1994-03-30 | 1999-06-15 | Gs Dev Ab | Verwendung von fettsäureester als bioklebstoffe |
US5456666A (en) | 1994-04-26 | 1995-10-10 | Boston Scientific Corp | Medical balloon folding into predetermined shapes and method |
US5760081A (en) | 1994-05-10 | 1998-06-02 | The General Hospital Corporation | Omega 3 fatty acids in the prevention of ventricular fibrillation |
US5549901A (en) | 1994-05-20 | 1996-08-27 | Novavax, Inc. | Antimicrobial oil-in-water emulsions |
US5547677A (en) | 1994-05-20 | 1996-08-20 | Novavax, Inc. | Antimicrobial oil-in-water emulsions |
US5629077A (en) | 1994-06-27 | 1997-05-13 | Advanced Cardiovascular Systems, Inc. | Biodegradable mesh and film stent |
US5857998A (en) | 1994-06-30 | 1999-01-12 | Boston Scientific Corporation | Stent and therapeutic delivery system |
US5458572A (en) | 1994-07-01 | 1995-10-17 | Boston Scientific Corp. | Catheter with balloon folding into predetermined configurations and method of manufacture |
US5716614A (en) | 1994-08-05 | 1998-02-10 | Molecular/Structural Biotechnologies, Inc. | Method for delivering active agents to mammalian brains in a complex with eicosapentaenoic acid or docosahexaenoic acid-conjugated polycationic carrier |
US5514092A (en) | 1994-08-08 | 1996-05-07 | Schneider (Usa) Inc. | Drug delivery and dilatation-drug delivery catheters in a rapid exchange configuration |
JPH0865685A (ja) | 1994-08-23 | 1996-03-08 | Nec Corp | 動きベクトル検出回路 |
US5931165A (en) | 1994-09-06 | 1999-08-03 | Fusion Medical Technologies, Inc. | Films having improved characteristics and methods for their preparation and use |
US5591230A (en) | 1994-09-07 | 1997-01-07 | Global Therapeutics, Inc. | Radially expandable stent |
US5891108A (en) | 1994-09-12 | 1999-04-06 | Cordis Corporation | Drug delivery stent |
SE518619C2 (sv) | 1994-12-09 | 2002-10-29 | Gs Dev Ab | Komposition för reglerad frisättning innehållande monokaproin |
DE4432708A1 (de) | 1994-09-14 | 1996-03-21 | Hoechst Ag | Modifizierte Gallensäuren, Verfahren zu ihrer Herstellung und ihre Verwendung |
US5509899A (en) | 1994-09-22 | 1996-04-23 | Boston Scientific Corp. | Medical device with lubricious coating |
US6176863B1 (en) | 1994-09-29 | 2001-01-23 | Bard Asdi Inc. | Hernia mesh patch with I-shaped filament |
US5634931A (en) * | 1994-09-29 | 1997-06-03 | Surgical Sense, Inc. | Hernia mesh patches and methods of their use |
US5637113A (en) | 1994-12-13 | 1997-06-10 | Advanced Cardiovascular Systems, Inc. | Polymer film for wrapping a stent structure |
US6004549A (en) | 1994-12-14 | 1999-12-21 | Schering Corporation | Crystalline protein controlled release compositions |
US6262109B1 (en) | 1995-12-22 | 2001-07-17 | Henkel Corporation | Methods of preventing and/or treating high serum levels of cholesterol and/or lipids |
US5569198A (en) | 1995-01-23 | 1996-10-29 | Cortrak Medical Inc. | Microporous catheter |
US5749845A (en) | 1995-01-25 | 1998-05-12 | Iotek, Inc. | Delivering an agent to an organ |
US5629021A (en) | 1995-01-31 | 1997-05-13 | Novavax, Inc. | Micellar nanoparticles |
US6231600B1 (en) | 1995-02-22 | 2001-05-15 | Scimed Life Systems, Inc. | Stents with hybrid coating for medical devices |
US5496832A (en) | 1995-03-09 | 1996-03-05 | American Home Products Corporation | Method of treating cardiac inflammatory disease |
KR19980702961A (ko) | 1995-03-17 | 1998-09-05 | 나까도미 히로다까 | 재조합 인간 면역 결핍 바이러스 생산 세포주 |
US5900245A (en) | 1996-03-22 | 1999-05-04 | Focal, Inc. | Compliant tissue sealants |
US5605696A (en) | 1995-03-30 | 1997-02-25 | Advanced Cardiovascular Systems, Inc. | Drug loaded polymeric material and method of manufacture |
US5837313A (en) | 1995-04-19 | 1998-11-17 | Schneider (Usa) Inc | Drug release stent coating process |
MY118354A (en) | 1995-05-01 | 2004-10-30 | Scarista Ltd | 1,3-propane diol derivatives as bioactive compounds |
KR100400620B1 (ko) | 1995-06-09 | 2004-02-18 | 노파르티스 아게 | 라파마이신유도체 |
FR2735015B1 (fr) | 1995-06-12 | 1998-02-13 | Microval | Prothese interne sous forme d'un support textile ou autre et son appareil d'insertion par voie coelioscopique |
SE504582C2 (sv) | 1995-07-06 | 1997-03-10 | Gs Dev Ab | Cyklosporinkomposition baserad på en L2-fas |
RU2125887C1 (ru) | 1995-08-25 | 1999-02-10 | Владивостокский государственный медицинский университет | Способ приготовления липосомального интерферона |
CN1301139C (zh) | 1995-08-29 | 2007-02-21 | 菲迪亚高级生物聚合物公司 | 包括透明质酸衍生物的用于预防手术后粘连的生物材料 |
GB9602638D0 (en) | 1995-09-07 | 1996-04-10 | Croda Int Plc | Triglyceride drying oil derivatives |
US5868704A (en) | 1995-09-18 | 1999-02-09 | W. L. Gore & Associates, Inc. | Balloon catheter device |
AU702030B2 (en) | 1995-10-12 | 1999-02-11 | Gs Development Ab | A pharmaceutical composition for administration of an active substance to or through a skin or mucosal surface |
US5736152A (en) | 1995-10-27 | 1998-04-07 | Atrix Laboratories, Inc. | Non-polymeric sustained release delivery system |
US5714360A (en) | 1995-11-03 | 1998-02-03 | Bsi Corporation | Photoactivatable water soluble cross-linking agents containing an onium group |
US5612074A (en) | 1995-12-21 | 1997-03-18 | Leach; Robin L. | Nutrient fortified food bar |
US6132765A (en) | 1996-04-12 | 2000-10-17 | Uroteq Inc. | Drug delivery via therapeutic hydrogels |
US5817343A (en) * | 1996-05-14 | 1998-10-06 | Alkermes, Inc. | Method for fabricating polymer-based controlled-release devices |
US6764509B2 (en) | 1996-09-06 | 2004-07-20 | Carbomedics Inc. | Prosthetic heart valve with surface modification |
DE19637082A1 (de) | 1996-09-12 | 1998-03-19 | Boehringer Mannheim Gmbh | Schnellzerfallende Pellets |
WO1998012274A1 (en) | 1996-09-23 | 1998-03-26 | Chandrashekar Pathak | Methods and devices for preparing protein concentrates |
TR199900786T2 (xx) | 1996-10-11 | 1999-07-21 | Scotia Holdings Plc | Eykoza penta enoik asit ve/veya stearidonik asit i�eren farmas�tik terkipler. |
FR2754705B1 (fr) | 1996-10-18 | 1998-12-18 | Cogent Sarl | Prothese anatomique pour la reparation de hernies par voie laparoscopique ou ouverte |
WO1998018338A1 (en) | 1996-10-25 | 1998-05-07 | Mccormick & Company, Inc. | Fat-coated encapsulation compositions and method for preparing the same |
ZA9710342B (en) | 1996-11-25 | 1998-06-10 | Alza Corp | Directional drug delivery stent and method of use. |
US5843919A (en) | 1996-11-25 | 1998-12-01 | Burger; John A. | Composition and method for the treatment of arthritis |
SE511313C2 (sv) | 1997-01-13 | 1999-09-06 | Gs Dev Ab | Komposition med reglerad frisättning innefattande fettsyraester av diacylglycerol |
IL121320A (en) | 1997-02-23 | 2000-12-06 | Ibr Ltd | Extracts from cells or tissue of organisms which are capable of entering dormancy for inhibition of proliferation of target cells or tissue |
US6152944A (en) | 1997-03-05 | 2000-11-28 | Scimed Life Systems, Inc. | Catheter with removable balloon protector and stent delivery system with removable stent protector |
WO1998046588A2 (en) | 1997-04-11 | 1998-10-22 | Neorx Corporation | Compounds and therapies for the prevention of vascular and non-vascular pathologies |
US5843172A (en) | 1997-04-15 | 1998-12-01 | Advanced Cardiovascular Systems, Inc. | Porous medicated stent |
US10028851B2 (en) | 1997-04-15 | 2018-07-24 | Advanced Cardiovascular Systems, Inc. | Coatings for controlling erosion of a substrate of an implantable medical device |
US6273913B1 (en) | 1997-04-18 | 2001-08-14 | Cordis Corporation | Modified stent useful for delivery of drugs along stent strut |
US6120539A (en) | 1997-05-01 | 2000-09-19 | C. R. Bard Inc. | Prosthetic repair fabric |
US6630151B1 (en) | 1997-05-27 | 2003-10-07 | Baker Hughes Incorporated | Method of increasing viscosity of oil-based compositions and compositions resulting therefrom |
DE69816759T2 (de) | 1997-05-29 | 2004-04-22 | K.U. Leuven Research & Development | Entfernung von trans-ungesättigte fettsäure enthaltenden verbindungen durch selektive adsorption mit zeolithen |
WO1999001111A1 (en) | 1997-07-02 | 1999-01-14 | Euro-Celtique, S.A. | Stabilized sustained release tramadol formulations |
US6500174B1 (en) | 1997-07-08 | 2002-12-31 | Atrionix, Inc. | Circumferential ablation device assembly and methods of use and manufacture providing an ablative circumferential band along an expandable member |
US5824082A (en) | 1997-07-14 | 1998-10-20 | Brown; Roderick B. | Patch for endoscopic repair of hernias |
US5897911A (en) | 1997-08-11 | 1999-04-27 | Advanced Cardiovascular Systems, Inc. | Polymer-coated stent structure |
JP3292481B2 (ja) | 1997-08-15 | 2002-06-17 | ユニチカ株式会社 | マンノース含有飼料及びその製造方法 |
US5854382A (en) | 1997-08-18 | 1998-12-29 | Meadox Medicals, Inc. | Bioresorbable compositions for implantable prostheses |
US6884429B2 (en) | 1997-09-05 | 2005-04-26 | Isotechnika International Inc. | Medical devices incorporating deuterated rapamycin for controlled delivery thereof |
US6281175B1 (en) | 1997-09-23 | 2001-08-28 | Scimed Life Systems, Inc. | Medical emulsion for lubrication and delivery of drugs |
US6013055A (en) | 1997-11-13 | 2000-01-11 | Boston Scientific Corporation | Catheter balloon having selected folding characteristics |
US6083950A (en) | 1997-11-13 | 2000-07-04 | Ranbaxy Laboratories Limited | 1-(4-arylpiperazin-1-yl)-ω-[n-(α,ω-dicarboximido)]-alka nes useful as uro-selective α1-adrenoceptor blockers |
ID26335A (id) | 1997-11-17 | 2000-12-14 | Lipogenic Inc | Metoda untuk mencegah restenosis dengan menggunakan tokotrienol |
AU743098B2 (en) | 1997-12-10 | 2002-01-17 | Cyclosporine Therapeutics Limited | Pharmaceutical compositions containing an omega-3 fatty acid oil |
US6187335B1 (en) | 1997-12-31 | 2001-02-13 | Orasomal Technologies, Inc. | Polymerizable fatty acids, phospholipids and polymerized liposomes therefrom |
US6541116B2 (en) | 1998-01-30 | 2003-04-01 | Advanced Cardiovascular Systems, Inc. | Superoxide dismutase or superoxide dismutase mimic coating for an intracorporeal medical device |
US6221425B1 (en) | 1998-01-30 | 2001-04-24 | Advanced Cardiovascular Systems, Inc. | Lubricious hydrophilic coating for an intracorporeal medical device |
US20020002154A1 (en) | 1998-02-11 | 2002-01-03 | Pol-Henri Guivarc'h | Method and composition for treatment of inflammatory conditions |
US6033380A (en) | 1998-02-13 | 2000-03-07 | Cordis Corporation | Six-pleated catheter balloon and device for forming same |
US6033436A (en) | 1998-02-17 | 2000-03-07 | Md3, Inc. | Expandable stent |
DE69910183T2 (de) | 1998-03-11 | 2004-06-03 | Grelan Pharmaceutical Co., Ltd., Hamura | Darmlösliche sprudelnde zusammensetzungen |
US6465525B1 (en) | 1998-03-18 | 2002-10-15 | Surmodics, Inc. | Latent reactive blood compatible agents |
DE19916086B4 (de) | 1998-04-11 | 2004-11-11 | Inflow Dynamics Inc. | Implantierbare Prothese, insbesondere Gefäßprothese (Stent) |
US6364856B1 (en) | 1998-04-14 | 2002-04-02 | Boston Scientific Corporation | Medical device with sponge coating for controlled drug release |
US6206916B1 (en) | 1998-04-15 | 2001-03-27 | Joseph G. Furst | Coated intraluminal graft |
US20030040790A1 (en) | 1998-04-15 | 2003-02-27 | Furst Joseph G. | Stent coating |
AUPP335598A0 (en) | 1998-05-06 | 1998-05-28 | Bose Nominees Pty Ltd | Laparoscopic hernia repair |
US6056970A (en) * | 1998-05-07 | 2000-05-02 | Genzyme Corporation | Compositions comprising hemostatic compounds and bioabsorbable polymers |
US6010776A (en) | 1998-05-19 | 2000-01-04 | 3M Innovative Properties Company | Microporous materials containing cross-linked oil |
US6197357B1 (en) | 1998-05-28 | 2001-03-06 | University Of Massachusetts | Refined vegetable oils and extracts thereof |
DE69913342T2 (de) | 1998-06-03 | 2004-10-28 | Blue Medical Devices B.V. | Stents mit diamantartiger beschichtung |
US6254634B1 (en) | 1998-06-10 | 2001-07-03 | Surmodics, Inc. | Coating compositions |
JP2000064047A (ja) | 1998-06-26 | 2000-02-29 | James A Mclaughlin | ダイヤモンド様炭素(dlc)又は他の真空蒸着被膜を基体に被覆する装置及び方法 |
US6369039B1 (en) | 1998-06-30 | 2002-04-09 | Scimed Life Sytems, Inc. | High efficiency local drug delivery |
US6669735B1 (en) | 1998-07-31 | 2003-12-30 | Davol, Inc. | Prosthesis for surgical treatment of hernia |
KR20010072816A (ko) | 1998-08-20 | 2001-07-31 | 쿡 인코포레이티드 | 피복된 삽입용 의료 장치 |
CA2338788A1 (en) | 1998-09-02 | 2000-03-09 | Scimed Life Systems, Inc. | Drug delivery device for stent |
US6740122B1 (en) | 1998-09-11 | 2004-05-25 | C. R. Bard, Inc. | Preformed curved prosthesis that is adapted to the external iliac vessels |
US6723133B1 (en) | 1998-09-11 | 2004-04-20 | C. R. Bard, Inc. | Performed curved prosthesis having a reduced incidence of developing wrinkles or folds |
US6093792A (en) | 1998-09-16 | 2000-07-25 | University Of Massachusetts | Bioresorbable copolymers |
US6048332A (en) | 1998-10-09 | 2000-04-11 | Ave Connaught | Dimpled porous infusion balloon |
WO2000025752A1 (en) | 1998-11-02 | 2000-05-11 | Church, Marla, J. | Multiparticulate modified release composition |
US6211315B1 (en) | 1998-11-12 | 2001-04-03 | Iowa State University Research Foundation, Inc. | Lewis acid-catalyzed polymerization of biological oils and resulting polymeric materials |
US6463323B1 (en) | 1998-11-12 | 2002-10-08 | Em Vascular, Inc. | Electrically mediated angiogenesis |
BR9916636A (pt) | 1998-12-31 | 2001-09-18 | Angiotech Pharm Inc | Enxertos de stent com revestimentos bioativos |
DE19900054A1 (de) | 1999-01-04 | 2000-07-06 | Hans Dietl | Taxane enthaltende stabile und sterile Emulsion und Verfahren zu ihrer Herstellung |
US6040330A (en) | 1999-01-08 | 2000-03-21 | Bionumerik Pharmaceuticals, Inc. | Pharmaceutical formulations of taxanes |
US7238711B1 (en) | 1999-03-17 | 2007-07-03 | Cambridge University Technical Services Ltd. | Compounds and methods to inhibit or augment an inflammatory response |
ES2209813T3 (es) | 1999-01-25 | 2004-07-01 | Ecosynthetix Inc. | Nanoparticulas de biopolimeros. |
US6955661B1 (en) | 1999-01-25 | 2005-10-18 | Atrium Medical Corporation | Expandable fluoropolymer device for delivery of therapeutic agents and method of making |
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 |
US7637886B2 (en) | 1999-01-25 | 2009-12-29 | Atrium Medical Corporation | Expandable fluoropolymer device and method of making |
US6326072B1 (en) | 1999-01-29 | 2001-12-04 | 3M Innovative Properties Company | Release liner incorporating syndiotactic vinyl aromatic polymer |
SE9900465D0 (sv) | 1999-02-12 | 1999-02-12 | Astra Ab | Storage package |
US6248363B1 (en) | 1999-11-23 | 2001-06-19 | Lipocine, Inc. | Solid carriers for improved delivery of active ingredients in pharmaceutical compositions |
US6761903B2 (en) | 1999-06-30 | 2004-07-13 | Lipocine, Inc. | Clear oil-containing pharmaceutical compositions containing a therapeutic agent |
WO2000051662A1 (en) | 1999-03-04 | 2000-09-08 | Tepha, Inc. | Bioabsorbable, biocompatible polymers for tissue engineering |
CN1167462C (zh) | 1999-03-09 | 2004-09-22 | 杭州华东医药集团生物工程研究所有限公司 | 一种含环孢素的药物组合物 |
US6364903B2 (en) | 1999-03-19 | 2002-04-02 | Meadox Medicals, Inc. | Polymer coated stent |
JP3030364B1 (ja) | 1999-03-24 | 2000-04-10 | 農林水産省食品総合研究所長 | 単分散固体脂質マイクロスフィアの製造方法 |
US6287316B1 (en) | 1999-03-26 | 2001-09-11 | Ethicon, Inc. | Knitted surgical mesh |
US6224579B1 (en) | 1999-03-31 | 2001-05-01 | The Trustees Of Columbia University In The City Of New York | Triclosan and silver compound containing medical devices |
US6730349B2 (en) | 1999-04-19 | 2004-05-04 | Scimed Life Systems, Inc. | Mechanical and acoustical suspension coating of medical implants |
US6368658B1 (en) | 1999-04-19 | 2002-04-09 | Scimed Life Systems, Inc. | Coating medical devices using air suspension |
US6607598B2 (en) | 1999-04-19 | 2003-08-19 | Scimed Life Systems, Inc. | Device for protecting medical devices during a coating process |
US6258124B1 (en) | 1999-05-10 | 2001-07-10 | C. R. Bard, Inc. | Prosthetic repair fabric |
US6632822B1 (en) | 1999-05-14 | 2003-10-14 | The Australian National University | Compounds and therapeutic methods |
US6610035B2 (en) | 1999-05-21 | 2003-08-26 | Scimed Life Systems, Inc. | Hydrophilic lubricity coating for medical devices comprising a hybrid top coat |
US6673843B2 (en) | 1999-06-30 | 2004-01-06 | Emory University | Curcumin and curcuminoid inhibition of angiogenesis |
JP4421699B2 (ja) | 1999-06-30 | 2010-02-24 | 大洋薬品工業株式会社 | 静脈注射可能なプロスタグランジン脂肪乳剤 |
ES2223583T3 (es) | 1999-07-28 | 2005-03-01 | United States Surgical Corporation | Barrera antiadherente de acido hialuronico. |
US6762203B2 (en) * | 1999-08-03 | 2004-07-13 | Kao Corporation | Oil composition |
US20020015970A1 (en) | 1999-08-11 | 2002-02-07 | Richard Murray | Novel methods of diagnosis of angiogenesis, compositions, and methods of screening for angiogenesis modulators |
US20030224071A1 (en) | 1999-08-20 | 2003-12-04 | Howard Murad | Pharmaceutical compositions and methods for managing connective tissue ailments |
US6159531A (en) | 1999-08-30 | 2000-12-12 | Cardiovasc, Inc. | Coating having biological activity and medical implant having surface carrying the same and method |
US6713119B2 (en) | 1999-09-03 | 2004-03-30 | Advanced Cardiovascular Systems, Inc. | Biocompatible coating for a prosthesis and a method of forming the same |
US6503556B2 (en) | 2000-12-28 | 2003-01-07 | Advanced Cardiovascular Systems, Inc. | Methods of forming a coating for a prosthesis |
US6497833B1 (en) | 1999-09-30 | 2002-12-24 | Amad Tayebi | Colored laminate and a method for coloring the surface of a membrane |
US6203551B1 (en) | 1999-10-04 | 2001-03-20 | Advanced Cardiovascular Systems, Inc. | Chamber for applying therapeutic substances to an implant device |
US6468354B2 (en) | 1999-10-05 | 2002-10-22 | Taiwan Semiconductor Manufacturing Co., Ltd | Semiconductor wafer support |
WO2001024866A1 (en) | 1999-10-06 | 2001-04-12 | The Penn State Research Foundation | System and device for preventing restenosis in body vessels |
US6577895B1 (en) | 1999-10-13 | 2003-06-10 | Biocardia, Inc. | Pulmonary vein arrhythmia diagnostic device and method for use |
JP2001120582A (ja) | 1999-10-22 | 2001-05-08 | Gunze Ltd | 人工心臓弁およびその作製方法 |
US6828346B2 (en) | 1999-10-25 | 2004-12-07 | Supergen, Inc. | Methods for administration of paclitaxel |
DE60016455T2 (de) * | 1999-12-17 | 2005-12-15 | Genzyme Corp., Cambridge | Chirurgische prothese |
US7066912B2 (en) | 1999-12-17 | 2006-06-27 | Astra Tech Ab | Catheter wetting apparatus |
US6355063B1 (en) | 2000-01-20 | 2002-03-12 | Impra, Inc. | Expanded PTFE drug delivery graft |
US6953593B2 (en) | 2000-02-01 | 2005-10-11 | Lipoprotein Technologies, Inc. | Sustained-release microencapsulated delivery system |
US6447835B1 (en) | 2000-02-15 | 2002-09-10 | Scimed Life Systems, Inc. | Method of coating polymeric tubes used in medical devices |
EP1259230A2 (en) | 2000-02-18 | 2002-11-27 | Cv Therapeutics, Inc. | Partial fatty acid oxidation inhibitors in the treatment of congestive heart failure |
IL134830A0 (en) | 2000-03-01 | 2001-05-20 | Chay 13 Medical Res Group N V | Peptides and immunostimulatory and anti-bacterial pharmaceutical compositions containing them |
DE10010072A1 (de) | 2000-03-02 | 2001-09-06 | Rheinchemie Rheinau Gmbh | Biozid-Batche auf Basis vernetzter Öle, Verfahren zu ihrer Gerstellung und ihre Verwendung in thermoplastischen Formmassen |
EP1132058A1 (en) | 2000-03-06 | 2001-09-12 | Advanced Laser Applications Holding S.A. | Intravascular prothesis |
US20030009213A1 (en) | 2000-03-13 | 2003-01-09 | Jun Yang | Stent having cover with drug delivery capability |
KR20030009389A (ko) | 2000-03-14 | 2003-01-29 | 브루카드 괴케 | 유문동-유문-십이지장 운동성에 대한 글루카곤 유사펩티드-1 (7-36)의 효과 |
US9314339B2 (en) | 2000-03-27 | 2016-04-19 | Formae, Inc. | Implants for replacing cartilage, with negatively-charged hydrogel surfaces and flexible matrix reinforcement |
US20020022052A1 (en) | 2000-04-06 | 2002-02-21 | Dransfield Charles William | Transdermal delivery system |
SE520688C2 (sv) | 2000-04-11 | 2003-08-12 | Bone Support Ab | Ett injicerbart ersättningsmaterial för benmineral |
US7875283B2 (en) | 2000-04-13 | 2011-01-25 | Advanced Cardiovascular Systems, Inc. | Biodegradable polymers for use with implantable medical devices |
US6527801B1 (en) | 2000-04-13 | 2003-03-04 | Advanced Cardiovascular Systems, Inc. | Biodegradable drug delivery material for stent |
WO2001079315A1 (en) * | 2000-04-18 | 2001-10-25 | Clemson University | Polylactide/dextran graft co-polymers for biomaterial and tissue engineering applications |
FR2807936B1 (fr) | 2000-04-20 | 2002-08-02 | Sofradim Production | Renfort de paroi abdominale pour le traitement des hernies inguinales par voie anterieure sans tension |
FR2808437B1 (fr) | 2000-05-05 | 2002-10-25 | Cousin Biotech | Prothese de reparation herniaire |
US6544224B1 (en) | 2000-05-05 | 2003-04-08 | Advanced Cardiovascular Systems, Inc. | Lobed balloon catheter and method of use |
US6776796B2 (en) | 2000-05-12 | 2004-08-17 | Cordis Corportation | Antiinflammatory drug and delivery device |
US7419678B2 (en) | 2000-05-12 | 2008-09-02 | Cordis Corporation | Coated medical devices for the prevention and treatment of vascular disease |
US6902522B1 (en) | 2000-06-12 | 2005-06-07 | Acorn Cardiovascular, Inc. | Cardiac disease treatment and device |
US6730016B1 (en) | 2000-06-12 | 2004-05-04 | Acorn Cardiovascular, Inc. | Cardiac disease treatment and device |
US6670355B2 (en) | 2000-06-16 | 2003-12-30 | Wyeth | Method of treating cardiovascular disease |
KR100392501B1 (ko) * | 2000-06-28 | 2003-07-22 | 동국제약 주식회사 | 다중 에멀젼법에 의한 서방출성 미립구의 제조방법 |
WO2002008333A1 (fr) | 2000-07-25 | 2002-01-31 | Mitsui Chemicals, Inc. | Composition durcissable et utilisations correspondantes |
US6610006B1 (en) | 2000-07-25 | 2003-08-26 | C. R. Bard, Inc. | Implantable prosthesis |
DE60133744T2 (de) | 2000-07-28 | 2009-05-14 | Anika Therapeutics, Inc., Woburn | Bioabsorbierbare kompositmaterialien aus derivatisierter hyaluronsäure |
DE10036832C1 (de) | 2000-07-28 | 2001-12-13 | Schott Glas | Verfahren und Vorrichtung zum Aufbringen einer hitzefixierten Gleitmittelschicht auf die Innenwandung von zylindrischen Behältern für medizinische Zwecke |
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 |
EP1318852A2 (en) | 2000-09-11 | 2003-06-18 | Solutions for Vascular Intervention, Inc. | Method and device to do arteriographies and angiographies with a balloon without injecting contrast media in the vessel lumen |
US7404819B1 (en) | 2000-09-14 | 2008-07-29 | C.R. Bard, Inc. | Implantable prosthesis |
US6610068B1 (en) | 2000-09-22 | 2003-08-26 | Scimed Life Systems, Inc. | Non-flush over-the-wire catheter devices |
US20020111590A1 (en) | 2000-09-29 | 2002-08-15 | Davila Luis A. | Medical devices, drug coatings and methods for maintaining the drug coatings thereon |
US7261735B2 (en) | 2001-05-07 | 2007-08-28 | Cordis Corporation | Local drug delivery devices and methods for maintaining the drug coatings thereon |
ATA16992000A (de) | 2000-10-05 | 2001-12-15 | Michael Dr Koncar | Verfahren zur herstellung von fettsäurealkylestern |
US6485752B1 (en) | 2000-10-23 | 2002-11-26 | Otto Torbjorn Hansen | Composition and method for alleviating joint pain and stiffness |
US6794485B2 (en) | 2000-10-27 | 2004-09-21 | Poly-Med, Inc. | Amorphous polymeric polyaxial initiators and compliant crystalline copolymers therefrom |
US20020161168A1 (en) | 2000-10-27 | 2002-10-31 | Shalaby Shalaby W. | Amorphous polymeric polyaxial initiators and compliant crystalline copolymers therefrom |
JP4583756B2 (ja) | 2000-10-31 | 2010-11-17 | クック インコーポレイテッド | 医療器具 |
US20040241211A9 (en) | 2000-11-06 | 2004-12-02 | Fischell Robert E. | Devices and methods for reducing scar tissue formation |
US20040018228A1 (en) | 2000-11-06 | 2004-01-29 | Afmedica, Inc. | Compositions and methods for reducing scar tissue formation |
US6534693B2 (en) | 2000-11-06 | 2003-03-18 | Afmedica, Inc. | Surgically implanted devices having reduced scar tissue formation |
US20050084514A1 (en) | 2000-11-06 | 2005-04-21 | Afmedica, Inc. | Combination drug therapy for reducing scar tissue formation |
US7749539B2 (en) | 2000-11-30 | 2010-07-06 | Efrat Biopolymers Ltd. | Polymeric formulations for drug delivery |
US20020084178A1 (en) | 2000-12-19 | 2002-07-04 | Nicast Corporation Ltd. | Method and apparatus for manufacturing polymer fiber shells via electrospinning |
US6599323B2 (en) | 2000-12-21 | 2003-07-29 | Ethicon, Inc. | Reinforced tissue implants and methods of manufacture and use |
CA2365376C (en) | 2000-12-21 | 2006-03-28 | Ethicon, Inc. | Use of reinforced foam implants with enhanced integrity for soft tissue repair and regeneration |
US6852330B2 (en) | 2000-12-21 | 2005-02-08 | Depuy Mitek, Inc. | Reinforced foam implants with enhanced integrity for soft tissue repair and regeneration |
US6471980B2 (en) | 2000-12-22 | 2002-10-29 | Avantec Vascular Corporation | Intravascular delivery of mycophenolic acid |
US20020082679A1 (en) | 2000-12-22 | 2002-06-27 | Avantec Vascular Corporation | Delivery or therapeutic capable agents |
CN1360951A (zh) | 2000-12-28 | 2002-07-31 | 微创医疗器械(上海)有限公司 | 一种具有防再狭窄涂层的血管支架 |
CA2342641C (en) | 2000-12-29 | 2009-03-03 | Ethicon, Inc. | Hernia repair prosthesis and method |
US6544223B1 (en) | 2001-01-05 | 2003-04-08 | Advanced Cardiovascular Systems, Inc. | Balloon catheter for delivering therapeutic agents |
US20020120333A1 (en) | 2001-01-31 | 2002-08-29 | Keogh James R. | Method for coating medical device surfaces |
US20020103494A1 (en) | 2001-01-31 | 2002-08-01 | Pacey John Allen | Percutaneous cannula delvery system for hernia patch |
US6783542B2 (en) | 2001-02-22 | 2004-08-31 | Scimed Life Systems, Inc | Crimpable balloon/stent protector |
US6479683B1 (en) | 2001-03-06 | 2002-11-12 | Ag Processing Inc | Process for conjugating fatty acid esters |
US7771468B2 (en) | 2001-03-16 | 2010-08-10 | Angiotech Biocoatings Corp. | Medicated stent having multi-layer polymer coating |
EP1581121B1 (en) | 2001-03-26 | 2011-05-25 | Tyco Healthcare Group LP | Oil coated sutures |
DE10115740A1 (de) | 2001-03-26 | 2002-10-02 | Ulrich Speck | Zubereitung für die Restenoseprophylaxe |
US7056339B2 (en) | 2001-04-20 | 2006-06-06 | The Board Of Trustees Of The Leland Stanford Junior University | Drug delivery platform |
US20020192352A1 (en) | 2001-04-24 | 2002-12-19 | Mccormick & Company, Inc. | Fat encapsulation compositions and method of preparing the same |
US20020159468A1 (en) | 2001-04-27 | 2002-10-31 | Foster Michael S. | Method and system for administrative ports in a routing device |
US7244853B2 (en) | 2001-05-09 | 2007-07-17 | President And Fellows Of Harvard College | Dioxanes and uses thereof |
US6685956B2 (en) | 2001-05-16 | 2004-02-03 | The Research Foundation At State University Of New York | Biodegradable and/or bioabsorbable fibrous articles and methods for using the articles for medical applications |
AU2002310325A1 (en) | 2001-06-08 | 2002-12-23 | Baylor College Of Medicine | Use of ozone for the prevention of infection caused by medical devices |
US7201940B1 (en) | 2001-06-12 | 2007-04-10 | Advanced Cardiovascular Systems, Inc. | Method and apparatus for thermal spray processing of medical devices |
WO2002102428A1 (fr) | 2001-06-15 | 2002-12-27 | Gunze Limited | Materiau inhibiteur de synechie |
US6565659B1 (en) | 2001-06-28 | 2003-05-20 | Advanced Cardiovascular Systems, Inc. | Stent mounting assembly and a method of using the same to coat a stent |
US6787179B2 (en) | 2001-06-29 | 2004-09-07 | Ethicon, Inc. | Sterilization of bioactive coatings |
US7030127B2 (en) | 2001-06-29 | 2006-04-18 | Ethicon, Inc. | Composition and medical devices utilizing bioabsorbable polymeric waxes |
US7034037B2 (en) | 2001-06-29 | 2006-04-25 | Ethicon, Inc. | Compositions and medical devices utilizing bioabsorbable polymeric waxes and rapamycin |
US6682771B2 (en) | 2001-07-02 | 2004-01-27 | Scimed Life Systems, Inc. | Coating dispensing system and method using a solenoid head for coating medical devices |
WO2003004001A1 (en) | 2001-07-06 | 2003-01-16 | Lifecycle Pharma A/S | Controlled agglomeration |
EP1273314A1 (en) | 2001-07-06 | 2003-01-08 | Terumo Kabushiki Kaisha | Stent |
US6444318B1 (en) | 2001-07-17 | 2002-09-03 | Surmodics, Inc. | Self assembling monolayer compositions |
US6913626B2 (en) | 2001-08-14 | 2005-07-05 | Mcghan Jim J. | Medical implant having bioabsorbable textured surface |
US6585997B2 (en) | 2001-08-16 | 2003-07-01 | Access Pharmaceuticals, Inc. | Mucoadhesive erodible drug delivery device for controlled administration of pharmaceuticals and other active compounds |
US20040137066A1 (en) | 2001-11-26 | 2004-07-15 | Swaminathan Jayaraman | Rationally designed therapeutic intravascular implant coating |
US20070238697A1 (en) | 2001-08-29 | 2007-10-11 | University Of British Columbia | Pharmaceutical compositions and methods relating to fucans |
US6641611B2 (en) | 2001-11-26 | 2003-11-04 | Swaminathan Jayaraman | Therapeutic coating for an intravascular implant |
IN2014DN10834A (zh) | 2001-09-17 | 2015-09-04 | Psivida Inc | |
US6753071B1 (en) | 2001-09-27 | 2004-06-22 | Advanced Cardiovascular Systems, Inc. | Rate-reducing membrane for release of an agent |
US20030065345A1 (en) | 2001-09-28 | 2003-04-03 | Kevin Weadock | Anastomosis devices and methods for treating anastomotic sites |
US20030064965A1 (en) | 2001-10-02 | 2003-04-03 | Jacob Richter | Method of delivering drugs to a tissue using drug-coated medical devices |
US20030077310A1 (en) | 2001-10-22 | 2003-04-24 | Chandrashekhar Pathak | Stent coatings containing HMG-CoA reductase inhibitors |
CA2465517C (en) | 2001-10-31 | 2011-08-23 | Edwards Lifesciences Corporation | Drug eluting radially expandable tubular stented grafts |
WO2003041756A1 (en) | 2001-11-08 | 2003-05-22 | Dsb Invest Holding Sa | Endoluminal devices coated with latrunculin to prevent ingrowth of cells |
CA2466432A1 (en) | 2001-11-08 | 2003-05-15 | Atrium Medical Corporation | Intraluminal device with a coating containing a therapeutic agent |
JP2003171301A (ja) | 2001-11-09 | 2003-06-20 | Mahidol Univ | 歯周炎治療における補助剤としてのカルメグゲル |
EP1461093B1 (en) | 2001-11-30 | 2007-10-03 | Universite Laval | Milk protein biofilm and uses thereof |
US6663880B1 (en) | 2001-11-30 | 2003-12-16 | Advanced Cardiovascular Systems, Inc. | Permeabilizing reagents to increase drug delivery and a method of local delivery |
AU2002241676B2 (en) | 2001-12-21 | 2008-10-23 | Nfocus Neuromedical, Inc. | Composite stent with polymeric covering and bioactive coating |
US20030124087A1 (en) * | 2001-12-26 | 2003-07-03 | Amitie Co. Ltd. | Anti-adhesion barrier |
US6790213B2 (en) | 2002-01-07 | 2004-09-14 | C.R. Bard, Inc. | Implantable prosthesis |
IL162734A0 (en) | 2002-02-01 | 2005-11-20 | Ariad Gene Therapeutics Inc | Phosphorus-containing compounds & uses thereof |
US6887270B2 (en) | 2002-02-08 | 2005-05-03 | Boston Scientific Scimed, Inc. | Implantable or insertable medical device resistant to microbial growth and biofilm formation |
EP1474291A4 (en) | 2002-02-13 | 2010-05-26 | Rf & Son Inc | NEW LAMINATES FOR THE MANUFACTURE OF A HIGH-WET, POROUS, STERILIZABLE PACKAGING |
EP1487377B1 (en) | 2002-03-01 | 2012-08-15 | Ethicon, Inc. | Apparatus for treating pelvic organ prolapses in female patients |
US6755868B2 (en) | 2002-03-22 | 2004-06-29 | Ethicon, Inc. | Hernia repair device |
US20030204168A1 (en) | 2002-04-30 | 2003-10-30 | Gjalt Bosma | Coated vascular devices |
SE0201330D0 (sv) | 2002-04-30 | 2002-04-30 | Astra Tech Ab | Catheter assembly |
US7048962B2 (en) | 2002-05-02 | 2006-05-23 | Labcoat, Ltd. | Stent coating device |
US6645547B1 (en) | 2002-05-02 | 2003-11-11 | Labcoat Ltd. | Stent coating device |
US20030207907A1 (en) | 2002-05-03 | 2003-11-06 | Iversen Patrick L. | Delivery of microparticle-conjugated drugs for inhibition of stenosis |
US7011688B2 (en) | 2002-05-10 | 2006-03-14 | C.R. Bard, Inc. | Prosthetic repair fabric |
EP1505931A1 (en) | 2002-05-20 | 2005-02-16 | Orbus Medical Technologies, Inc. | Drug eluting implantable medical device |
EP1511442B1 (en) | 2002-06-12 | 2010-01-06 | Boston Scientific Limited | Medical slings |
EP1539032A2 (en) | 2002-07-02 | 2005-06-15 | Polycord, Inc. | Polymerized and modified rapamycins and their use in coating medical prostheses |
US6767405B2 (en) | 2002-07-10 | 2004-07-27 | Carmeda Ab | Apparatus and process for coating articles |
DK1521603T3 (da) | 2002-07-12 | 2011-04-18 | Cook Inc | Coated medicinsk anordning |
ES2295647T3 (es) | 2002-07-15 | 2008-04-16 | Alcon, Inc. | Composiciones de implante farmaceuticas lipofilas, no polimeras, para uso intraocular. |
US7101381B2 (en) | 2002-08-02 | 2006-09-05 | C.R. Bard, Inc. | Implantable prosthesis |
EP1550477B1 (en) | 2002-08-23 | 2015-11-04 | National Cerebral and Cardiovascular Center | Stent and process for producing the same |
US7732535B2 (en) | 2002-09-05 | 2010-06-08 | Advanced Cardiovascular Systems, Inc. | Coating for controlled release of drugs from implantable medical devices |
US6875231B2 (en) | 2002-09-11 | 2005-04-05 | 3F Therapeutics, Inc. | Percutaneously deliverable heart valve |
US20040058008A1 (en) | 2002-09-20 | 2004-03-25 | Tarcha Peter J. | Microparticles having serum as a dispersing agent and process for their preparation and use |
DE10244847A1 (de) | 2002-09-20 | 2004-04-01 | Ulrich Prof. Dr. Speck | Medizinische Vorrichtung zur Arzneimittelabgabe |
US6966916B2 (en) | 2002-09-26 | 2005-11-22 | Kumar Sarbjeet S | Device and method for surgical repair of abdominal wall hernias |
CN1684725A (zh) | 2002-09-26 | 2005-10-19 | 血管技术国际股份公司 | 血管周包裹物 |
US6991096B2 (en) | 2002-09-27 | 2006-01-31 | Medtronic Minimed, Inc. | Packaging system |
US7112209B2 (en) | 2002-10-07 | 2006-09-26 | Sofradim Production | Anatomical wall reinforcement for the treatment of an inguinal hernia |
US9211259B2 (en) | 2002-11-29 | 2015-12-15 | Foamix Pharmaceuticals Ltd. | Antibiotic kit and composition and uses thereof |
US20050095267A1 (en) | 2002-12-04 | 2005-05-05 | Todd Campbell | Nanoparticle-based controlled release polymer coatings for medical implants |
US20040153125A1 (en) | 2002-12-13 | 2004-08-05 | Mark Roby | Antimicrobial fatty acid containing suture coating |
US6899729B1 (en) | 2002-12-18 | 2005-05-31 | Advanced Cardiovascular Systems, Inc. | Stent for treating vulnerable plaque |
US7152611B2 (en) | 2002-12-30 | 2006-12-26 | International Tape Partners, Llc | Coated multifilament dental devices overcoated with imbedded particulate |
EP1596755B1 (en) | 2003-01-16 | 2016-10-12 | Massachusetts General Hospital | Methods for making oxidation resistant polymeric material |
US6919100B2 (en) | 2003-01-22 | 2005-07-19 | Cordis Corporation | Method for coating medical devices |
US20040224003A1 (en) | 2003-02-07 | 2004-11-11 | Schultz Robert K. | Drug formulations for coating medical devices |
US20040167572A1 (en) | 2003-02-20 | 2004-08-26 | Roth Noah M. | Coated medical devices |
CA2513443A1 (en) | 2003-02-26 | 2004-09-10 | Medivas, Llc | Bioactive stents and methods for use thereof |
US7077910B2 (en) | 2003-04-07 | 2006-07-18 | Surmodics, Inc. | Linear rail coating apparatus and method |
US7972616B2 (en) | 2003-04-17 | 2011-07-05 | Nanosys, Inc. | Medical device applications of nanostructured surfaces |
DE10318803B4 (de) | 2003-04-17 | 2005-07-28 | Translumina Gmbh | Vorrichtung zum Aufbringen von Wirkstoffen auf Oberflächen von medizinischen Implantaten, insbesondere Stents |
US20040230176A1 (en) | 2003-04-23 | 2004-11-18 | Medtronic Vascular, Inc. | System for treating a vascular condition that inhibits restenosis at stent ends |
DE10323676A1 (de) | 2003-05-15 | 2004-12-02 | Aesculap Ag & Co. Kg | Implantat mit antibiotischer Langzeitwirkung |
US20040236278A1 (en) | 2003-05-22 | 2004-11-25 | Atrium Medical Corp. | Therapeutic agent delivery |
US8021418B2 (en) | 2003-06-19 | 2011-09-20 | Boston Scientific Scimed, Inc. | Sandwiched radiopaque marker on covered stent |
WO2005007019A2 (en) | 2003-07-07 | 2005-01-27 | Ethicon, Inc. | Implantable surgical mesh having a lubricious coating |
US20050025804A1 (en) * | 2003-07-28 | 2005-02-03 | Adam Heller | Reduction of adverse inflammation |
RU2360646C2 (ru) | 2003-08-14 | 2009-07-10 | Блу Медикел Дивайсиз Б.В. | Эндолюминальный протез, содержащий лечебное средство |
CN1220528C (zh) | 2003-08-19 | 2005-09-28 | 大连永兴医用材料有限公司 | 羧甲基壳聚糖/羧甲基纤维素防手术粘连膜及其制备方法 |
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 |
US8021331B2 (en) | 2003-09-15 | 2011-09-20 | Atrium Medical Corporation | Method of coating a folded medical device |
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 |
US6996952B2 (en) | 2003-09-30 | 2006-02-14 | Codman & Shurtleff, Inc. | Method for improving stability and effectivity of a drug-device combination product |
GB0326180D0 (en) | 2003-11-11 | 2003-12-17 | Leuven K U Res & Dev | Biocompatible coating of medical devices |
EP1682012A4 (en) | 2003-11-13 | 2008-09-24 | Alza Corp | COMPOSITION AND APPARATUS FOR TRANSDERMAL DELIVERY |
US20050208095A1 (en) | 2003-11-20 | 2005-09-22 | Angiotech International Ag | Polymer compositions and methods for their use |
US20050112170A1 (en) | 2003-11-20 | 2005-05-26 | Hossainy Syed F. | Coatings for implantable devices comprising polymers of lactic acid and methods for fabricating the same |
CA2536242A1 (en) | 2003-11-20 | 2005-06-09 | Angiotech International Ag | Implantable sensors and implantable pumps and anti-scarring agents |
US20050113849A1 (en) | 2003-11-26 | 2005-05-26 | Nicholas Popadiuk | Prosthetic repair device |
US7316822B2 (en) | 2003-11-26 | 2008-01-08 | Ethicon, Inc. | Conformable tissue repair implant capable of injection delivery |
JP2007513147A (ja) | 2003-12-04 | 2007-05-24 | ファイザー・プロダクツ・インク | 押し出し機を使用して、好ましくはポロキサマーとグリセリドを含有する多粒子結晶性医薬組成物を製造するための噴霧凝結方法 |
US8747881B2 (en) | 2003-12-19 | 2014-06-10 | Cordis Corporation | Intraluminal medical devices in combination with therapeutic agents |
DE10361667A1 (de) | 2003-12-30 | 2005-07-28 | Omega For Life Gmbh | Neuartige Fettpulver |
US7323178B1 (en) | 2004-01-16 | 2008-01-29 | The Ohio Department Of Agriculture | Method of identification of equine herpes virus type 1 causing neurological disease, method of producing a vaccine against neurological disease caused by equine herpes virus type 1, and vaccine against neurological disease caused by equine herpes virus type 1 |
US7303758B2 (en) | 2004-01-20 | 2007-12-04 | Cordis Corporation | Local vascular delivery of mycophenolic acid in combination with rapamycin to prevent restenosis following vascular injury |
US20050268573A1 (en) | 2004-01-20 | 2005-12-08 | Avantec Vascular Corporation | Package of sensitive articles |
US20050159809A1 (en) | 2004-01-21 | 2005-07-21 | Medtronic Vascular, Inc. | Implantable medical devices for treating or preventing restenosis |
US7211108B2 (en) | 2004-01-23 | 2007-05-01 | Icon Medical Corp. | Vascular grafts with amphiphilic block copolymer coatings |
US7806924B2 (en) | 2004-02-18 | 2010-10-05 | Cordis Corporation | Implantable structures for local vascular delivery of cladribine in combination with rapamycin for restenosis |
US7775965B2 (en) | 2004-03-09 | 2010-08-17 | The Board Of Regents Of The University Of Oklahoma | Decellularized grafts from umbilical cord vessels and process for preparing and using same |
US8075910B2 (en) | 2004-05-20 | 2011-12-13 | Pbm Pharmaceuticals, Inc. | Oral compositions comprising edible oils and vitamins and/or minerals and methods for making oral compositions |
EP1769021B1 (en) | 2004-05-25 | 2009-08-12 | NOVAMONT S.p.A. | Use of perforated biodegradable films and sanitary products obtained therefrom |
WO2005115341A2 (en) | 2004-05-27 | 2005-12-08 | Advanced Bionutrition Corporation | Microparticles for oral delivery |
US20060020031A1 (en) | 2004-07-26 | 2006-01-26 | Roger Berlin | Compositions containing policosanol and omega-3 fatty acids and their pharmaceutical uses |
BRPI0513967A (pt) | 2004-07-30 | 2008-05-20 | Acrymed Inc | composições de prata antimicrobianas |
US7311980B1 (en) | 2004-08-02 | 2007-12-25 | Advanced Cardiovascular Systems, Inc. | Polyactive/polylactic acid coatings for an implantable device |
CA2575943A1 (en) * | 2004-08-03 | 2006-02-09 | Tissuemed Limited | Tissue-adhesive materials |
US20070292478A1 (en) | 2004-08-30 | 2007-12-20 | Popowski Youri | Medical Implant Provided with Inhibitors of Atp Synthesis |
US20060058737A1 (en) | 2004-09-16 | 2006-03-16 | Herweck Steve A | Catheter treatment stylet |
US20060058881A1 (en) | 2004-09-16 | 2006-03-16 | Trieu Hai H | Intervertebral disc nucleus implants and methods |
US8298290B2 (en) | 2004-09-20 | 2012-10-30 | Davol, Inc. | Implantable prosthesis for soft tissue repair |
FR2875396B1 (fr) | 2004-09-20 | 2007-03-02 | Microval Sa | Ensemble prothetique pour le renforcement des tissus dans le traitement des hernies inguinales |
US20090011116A1 (en) | 2004-09-28 | 2009-01-08 | Atrium Medical Corporation | Reducing template with coating receptacle containing a medical device to be coated |
US8312836B2 (en) | 2004-09-28 | 2012-11-20 | Atrium Medical Corporation | Method and apparatus for application of a fresh coating on a medical device |
US20060083768A1 (en) | 2004-09-28 | 2006-04-20 | Atrium Medical Corporation | Method of thickening a coating using a drug |
US8367099B2 (en) | 2004-09-28 | 2013-02-05 | Atrium Medical Corporation | Perforated fatty acid films |
US9801982B2 (en) | 2004-09-28 | 2017-10-31 | Atrium Medical Corporation | Implantable barrier device |
US9012506B2 (en) | 2004-09-28 | 2015-04-21 | Atrium Medical Corporation | Cross-linked fatty acid-based biomaterials |
WO2006036982A2 (en) | 2004-09-28 | 2006-04-06 | Atrium Medical Corporation | Drug delivery coating for use with a stent |
WO2006036969A2 (en) | 2004-09-28 | 2006-04-06 | Atrium Medical Corporation | Formation of barrier layer |
US9000040B2 (en) * | 2004-09-28 | 2015-04-07 | Atrium Medical Corporation | Cross-linked fatty acid-based biomaterials |
JP2006109377A (ja) * | 2004-10-08 | 2006-04-20 | Rohm Co Ltd | イメージセンサ、及び画像処理装置 |
US20060093643A1 (en) | 2004-11-04 | 2006-05-04 | Stenzel Eric B | Medical device for delivering therapeutic agents over different time periods |
US7727554B2 (en) | 2004-12-21 | 2010-06-01 | Board Of Regents Of The University Of Nebraska By And Behalf Of The University Of Nebraska Medical Center | Sustained-release nanoparticle compositions and methods for using the same |
TWI244270B (en) | 2005-01-17 | 2005-11-21 | Novatek Microelectronics Corp | Digital-to-analog converter |
WO2006102374A2 (en) | 2005-03-22 | 2006-09-28 | Tyco Healthcare Group Lp | Bioactive wide-weave mesh |
US8747882B2 (en) | 2005-04-21 | 2014-06-10 | Astra Tech Ab | Catheter assembly with bactericidal effect |
US8414907B2 (en) | 2005-04-28 | 2013-04-09 | Warsaw Orthopedic, Inc. | Coatings on medical implants to guide soft tissue healing |
US9180229B2 (en) | 2005-05-19 | 2015-11-10 | Ethicon, Inc. | Antimicrobial polymer compositions and the use thereof |
KR101430767B1 (ko) | 2005-07-18 | 2014-08-19 | 유니버시티 오브 메사츄세츠 로웰 | 나노에멀젼 조성물 및 이의 제조 및 사용 방법 |
US9278161B2 (en) * | 2005-09-28 | 2016-03-08 | Atrium Medical Corporation | Tissue-separating fatty acid adhesion barrier |
US8574627B2 (en) | 2006-11-06 | 2013-11-05 | Atrium Medical Corporation | Coated surgical mesh |
US9427423B2 (en) | 2009-03-10 | 2016-08-30 | Atrium Medical Corporation | Fatty-acid based particles |
US7691946B2 (en) | 2005-09-30 | 2010-04-06 | The United States Of America As Represented By The Secretary Of Agriculture | Soy-based thermosensitive hydrogels for controlled release systems |
WO2007047028A1 (en) | 2005-10-14 | 2007-04-26 | Atrium Medical Corporation | Packaging and sterilization of medical devices |
CA2626030A1 (en) | 2005-10-15 | 2007-04-26 | Atrium Medical Corporation | Hydrophobic cross-linked gels for bioabsorbable drug carrier coatings |
WO2007050565A2 (en) | 2005-10-25 | 2007-05-03 | Baylor College Of Medicine | Incorporation of antimicrobial combinations onto devices to reduce infection |
US10029034B2 (en) | 2005-12-15 | 2018-07-24 | CARDINAL HEALTH SWITZERLAND 515 GmbH | Drug-eluting articles with improved drug release profiles |
ATE510535T1 (de) | 2006-01-05 | 2011-06-15 | Lifecycle Pharma As | Zerfallende befüllbare tabletten |
MX2008010126A (es) | 2006-02-08 | 2010-02-22 | Tyrx Pharma Inc | Protesis de malla temporalmente rigidizadas. |
JP4878178B2 (ja) | 2006-02-28 | 2012-02-15 | 株式会社日立製作所 | データ処理方法および装置並びにその処理プログラム |
US8784886B2 (en) | 2006-03-09 | 2014-07-22 | GlaxoSmithKline, LLC | Coating capsules with active pharmaceutical ingredients |
FR2898486B1 (fr) | 2006-03-14 | 2008-06-27 | Cie De Rech En Composants Impl | Plaque implantable et son procede de fabrication |
CN101448474A (zh) * | 2006-04-12 | 2009-06-03 | 麻省理工学院 | 抑制粘连的组合物和方法 |
FR2901467B1 (fr) | 2006-05-24 | 2008-08-15 | Aspide Medical Soc Par Actions | Prothese anatomique pour le traitement des hernies, telles que hernies inguinales et crurales et autres |
US20070280986A1 (en) | 2006-06-01 | 2007-12-06 | Carlos Gil | Intra-operative coating of implants |
US20070299538A1 (en) | 2006-06-26 | 2007-12-27 | Roeber Peter J | Ease of use tissue repair patch |
US7892593B2 (en) | 2006-06-27 | 2011-02-22 | Ingo Werner Scheer | Process for coating a substrate |
WO2008016664A2 (en) | 2006-08-02 | 2008-02-07 | University Of Massachusetts Lowell | Compositions and methods for treating cancer with dacarbazine nanoemulsions |
KR101272976B1 (ko) | 2006-09-19 | 2013-06-10 | (주)아모레퍼시픽 | 경구용 피복 조성물 |
CN104774275A (zh) | 2006-09-25 | 2015-07-15 | 阿彻-丹尼尔斯-米德兰德公司 | 超吸收性的经表面处理的羧烷基化多糖及其制备方法 |
US9289279B2 (en) | 2006-10-06 | 2016-03-22 | Promethean Surgical Devices, Llc | Apparatus and method for limiting surgical adhesions |
US9492596B2 (en) | 2006-11-06 | 2016-11-15 | Atrium Medical Corporation | Barrier layer with underlying medical device and one or more reinforcing support structures |
JP5518288B2 (ja) | 2006-11-30 | 2014-06-11 | 有限会社ナイセム | 癒着阻止用医用材料 |
US8906502B2 (en) | 2006-12-29 | 2014-12-09 | Ccp Composites Us Llc | Organic powder useful as the replacement of mineral filler in composites |
US20080207756A1 (en) | 2007-02-27 | 2008-08-28 | Atrium Medical Corporation | Bio-absorbable oil suspension |
US20130084243A1 (en) | 2010-01-27 | 2013-04-04 | Liliane Goetsch | Igf-1r specific antibodies useful in the detection and diagnosis of cellular proliferative disorders |
US20090036996A1 (en) * | 2007-08-03 | 2009-02-05 | Roeber Peter J | Knit PTFE Articles and Mesh |
WO2009039373A1 (en) | 2007-09-19 | 2009-03-26 | Ethicon, Inc. | Naturally contoured, preformed, three dimensional mesh device for breast implant support |
WO2009048929A1 (en) | 2007-10-08 | 2009-04-16 | Lux Biosciences, Inc. | Ophthalmic compositions comprising calcineurin inhibitors or mtor inhibitors |
CA2702183A1 (en) | 2007-10-10 | 2009-04-16 | Miv Therapeutics Inc. | Lipid coatings for implantable medical devices |
JP2011507665A (ja) * | 2007-12-31 | 2011-03-10 | アクラレント インコーポレイテッド | 粘膜組織包帯剤及び使用方法 |
WO2009091900A1 (en) | 2008-01-15 | 2009-07-23 | Research Foundation Of The City University Of New York | A green approach in metal nanoparticle-embedded antimicrobial coatings from vegetable oils and oil-based materials |
FR2929835B1 (fr) | 2008-04-11 | 2010-06-11 | Sofradim Production | Attache chirurgicale pour la fixation d'une prothese herniaire |
US20090270999A1 (en) | 2008-04-24 | 2009-10-29 | Brown Roderick B | Patch for endoscopic repair of hernias |
CA2735899A1 (en) | 2008-09-25 | 2010-04-01 | Cephalon, Inc. | Liquid formulations of bendamustine |
US20100318108A1 (en) | 2009-02-02 | 2010-12-16 | Biomerix Corporation | Composite mesh devices and methods for soft tissue repair |
US20110028412A1 (en) | 2009-08-03 | 2011-02-03 | Cappellos, Inc. | Herbal enhanced analgesic formulations |
US20110045050A1 (en) | 2009-08-24 | 2011-02-24 | Atrium Medical Corporation | Nanoemulsion formulations for direct delivery |
US20110144667A1 (en) | 2009-09-08 | 2011-06-16 | Anthony Richard Horton | Hernia patch |
US8435307B2 (en) | 2010-05-20 | 2013-05-07 | Ces Advancements, Llc | Reinforcement device with dissolvable layer and its use |
US10322213B2 (en) | 2010-07-16 | 2019-06-18 | Atrium Medical Corporation | Compositions and methods for altering the rate of hydrolysis of cured oil-based materials |
WO2012064705A1 (en) | 2010-11-10 | 2012-05-18 | Agrium Advanced Technologies | Cross-linked modified waxes for controlled release fertilizers |
KR101428145B1 (ko) | 2011-11-24 | 2014-08-08 | (주)아모레퍼시픽 | 수불용성 겔 조성물 및 그 제조방법 |
-
2009
- 2009-10-19 US US12/581,582 patent/US9278161B2/en not_active Expired - Fee Related
-
2010
- 2010-10-15 CN CN201080047130.0A patent/CN102753118B/zh not_active Expired - Fee Related
- 2010-10-15 WO PCT/US2010/052899 patent/WO2011049833A1/en active Application Filing
- 2010-10-15 EP EP10825447.5A patent/EP2490618A4/en not_active Withdrawn
- 2010-10-15 JP JP2012534404A patent/JP5778159B2/ja not_active Expired - Fee Related
-
2015
- 2015-07-08 JP JP2015136955A patent/JP6096844B2/ja not_active Expired - Fee Related
-
2016
- 2016-01-20 US US15/001,585 patent/US9844611B2/en not_active Expired - Fee Related
-
2017
- 2017-11-17 US US15/817,018 patent/US11083823B2/en active Active
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5580923A (en) * | 1995-03-14 | 1996-12-03 | Collagen Corporation | Anti-adhesion films and compositions for medical use |
CN1633313A (zh) * | 2002-02-15 | 2005-06-29 | Cv医药有限公司 | 用于医用装置的聚合物涂层 |
CN101094698A (zh) * | 2003-09-29 | 2007-12-26 | 汉莫堤克科技公司 | 医学表面的生物相容,生物稳定的涂层 |
CN1925881A (zh) * | 2004-02-28 | 2007-03-07 | 汉莫堤克科技公司 | 药物表面的生物相容性涂层、方法和用途 |
Also Published As
Publication number | Publication date |
---|---|
EP2490618A4 (en) | 2014-05-07 |
CN102753118A (zh) | 2012-10-24 |
US11083823B2 (en) | 2021-08-10 |
JP5778159B2 (ja) | 2015-09-16 |
EP2490618A1 (en) | 2012-08-29 |
US20160206789A1 (en) | 2016-07-21 |
JP2013508033A (ja) | 2013-03-07 |
US20100183697A1 (en) | 2010-07-22 |
US20180133376A1 (en) | 2018-05-17 |
JP2015198983A (ja) | 2015-11-12 |
US9844611B2 (en) | 2017-12-19 |
WO2011049833A1 (en) | 2011-04-28 |
US9278161B2 (en) | 2016-03-08 |
JP6096844B2 (ja) | 2017-03-15 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN102753118B (zh) | 组织分离性脂肪酸粘连屏障 | |
US10159742B2 (en) | Hydrogel compositions | |
DE60108258T2 (de) | Selbstklebende, hydratierbare matrix für therapeutische anwendungen | |
JP5963208B2 (ja) | 再生組織足場 | |
EP2384189B1 (en) | Enhanced carriers for the delivery of microparticles to bodily tissues and fluids | |
US20140056982A1 (en) | Enhanced Carriers For The Delivery of Microparticles To Bodily Tissues And Fluids | |
Yang et al. | Characteristics and biocompatibility of a biodegradable genipin‐cross‐linked gelatin/β‐tricalcium phosphate reinforced nerve guide conduit | |
Eldeeb et al. | 3D nanocomposite alginate hydrogel loaded with pitavastatin nanovesicles as a functional wound dressing with controlled drug release; preparation, in-vitro and in-vivo evaluation | |
US20100015226A1 (en) | Bioresorbable hydrogel | |
Warner et al. | Fabrication of biodegradable foams for deep tissue negative pressure treatments | |
Arslan et al. | The effect of alginate scaffolds on bone healing in defects formed with drilling model in rat femur diaphysis |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
CF01 | Termination of patent right due to non-payment of annual fee | ||
CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20160120 Termination date: 20211015 |