CN101977561A - 多糖标记物 - Google Patents

多糖标记物 Download PDF

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CN101977561A
CN101977561A CN2009801096723A CN200980109672A CN101977561A CN 101977561 A CN101977561 A CN 101977561A CN 2009801096723 A CN2009801096723 A CN 2009801096723A CN 200980109672 A CN200980109672 A CN 200980109672A CN 101977561 A CN101977561 A CN 101977561A
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polysaccharide
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M·L·琼斯
P·卢波克
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SenoRx Inc
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    • A—HUMAN NECESSITIES
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    • A61B90/00—Instruments, implements or accessories specially adapted for surgery or diagnosis and not covered by any of the groups A61B1/00 - A61B50/00, e.g. for luxation treatment or for protecting wound edges
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    • A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
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    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
    • A61B2017/00004—(bio)absorbable, (bio)resorbable, resorptive
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
    • A61B2017/00831—Material properties
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
    • A61B2017/00831—Material properties
    • A61B2017/00898—Material properties expandable upon contact with fluid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B90/00—Instruments, implements or accessories specially adapted for surgery or diagnosis and not covered by any of the groups A61B1/00 - A61B50/00, e.g. for luxation treatment or for protecting wound edges
    • A61B90/39—Markers, e.g. radio-opaque or breast lesions markers
    • A61B2090/3904—Markers, e.g. radio-opaque or breast lesions markers specially adapted for marking specified tissue
    • A61B2090/3908—Soft tissue, e.g. breast tissue
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B90/00—Instruments, implements or accessories specially adapted for surgery or diagnosis and not covered by any of the groups A61B1/00 - A61B50/00, e.g. for luxation treatment or for protecting wound edges
    • A61B90/39—Markers, e.g. radio-opaque or breast lesions markers
    • A61B2090/3925—Markers, e.g. radio-opaque or breast lesions markers ultrasonic
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B90/00—Instruments, implements or accessories specially adapted for surgery or diagnosis and not covered by any of the groups A61B1/00 - A61B50/00, e.g. for luxation treatment or for protecting wound edges
    • A61B90/39—Markers, e.g. radio-opaque or breast lesions markers
    • A61B2090/3962—Markers, e.g. radio-opaque or breast lesions markers palpable
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B90/00—Instruments, implements or accessories specially adapted for surgery or diagnosis and not covered by any of the groups A61B1/00 - A61B50/00, e.g. for luxation treatment or for protecting wound edges
    • A61B90/39—Markers, e.g. radio-opaque or breast lesions markers
    • A61B2090/3987—Applicators for implanting markers
    • 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
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A61K9/0024—Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue

Abstract

所描述的标记物部件输送系统具有放置在输送管或套管内的多个标记物部件，所述多个标记物部件包含合适的如淀粉(例如玉米淀粉或马铃薯淀粉)的多糖和如甲基纤维素的黏料。这些标记物部件优选由粉末压制成形。所述系统优选具有至少一个由可生物吸收的材料形成的标记物部件，其中不透射线的元件附连到或结合到其中。具有不透射线的元件的标记物优选放置在由多糖形成的两个标记物部件之间的输送管内，并且优选由不同于多糖的可生物吸收的材料形成。

Description

多糖标记物
技术领域
本发明主要涉及远程可检测的体内标记物以及用于将这种标记物输送到患者体内期望位置的设备和方法。
背景技术
在诊断和治疗某些医学病症时，通常期望标记可疑的身体部位，用于随后的活体检查样本的获取、用于输送药物、射线或者用于其它治疗，从其获取活体检查样本或对其执行一些其它过程的部位的重新定位。如所知的，在癌症和其它恶性肿瘤的诊断中典型地采用通过活体检查获得组织样本以及随后的检查，以便确认怀疑的损害或肿瘤不是恶性的。从这些诊断测试和/或检查获得的信息经常用于制订适当的外科手术或其它疗程的治疗计划。
在许多情况中，要采样的可疑组织位于皮下部位，如在人的乳房内。为了最小化对患者身体的手术侵入，通常期望插入小的仪器(如活体检查针头)到身体中，用于提取获取检查样本，同时使用荧光透视、超声成像、X射线、磁共振成像(MRI)或任何其它适当形式的成像技术或触诊来成像过程。通过活体检查获取的组织样本的检查在乳癌的诊断和治疗中特别显著。在接下来的讨论中，尽管本发明也适于标记人的其它部分和其它哺乳动物身体，但是所描述的活体检查和治疗部分通常将是人的乳房。
乳房的周期性体检和乳房X射线成像对于潜在的癌症损害的早期检查很重要。在乳房X射线成像中，乳房挤压在两块板之间，同时获取特殊的X射线图像。如果通过体检或乳房X射线成像发现乳房中的异常块，则可以使用超声来确定该块是否是固体肿瘤或填满液体的囊肿。固体块通常经历某些类型的组织活体检查以确定该块是否为癌。
如果固体块或损害大到可以触摸到，则可以通过多种技术从该块移除组织样本，该技术包括但不限于开放手术活体检查、已知为精细针头抽吸活体检查(FNAB)的技术以及特征是“真空辅助大核心活体检查设备”的仪器。
如果乳房的固体块小并且不可触摸(例如典型地通过乳房X射线成像发现的类型)，则通常使用真空辅助大核心活体检查过程。在执行乳房的立体定位活体检查时，患者躺在特殊的活体检查台上，并且她的乳房挤压在乳房X射线成像装置的各板之间，并且从两个不同的视点获取两个分离的X射线或数字视频视图。计算机计算损害的精确位置以及损害在乳房内的深度。此后，利用由计算机计算的坐标和深度信息编程机械立体装置，并且这种装置用于将活体检查针头精确地推进到小的损害中。该立体技术可以用于获得组织样本。通常从小的损害的周围位置获得至少五个分离的活体检查样本以及从损害的中心获得一个活体检查样本。
用于乳房的癌症损害的可用治疗选项包括各种程度的乳房切除术或乳房肿瘤切除术、放射治疗、化疗以及这些治疗的组合。然而，原始在乳房X射线成像中观察到的放射成像可见组织特征可能通过活体检查过程被移除、改变或屏蔽，并且可能治愈或随着活体检查而另外改变。为了在进行活体检查过程后的几天或几星期后外科医生或放射肿瘤学家将手术或放射治疗指引到乳房损害的精确位置，期望将活体检查部分标记物放置在患者体内以用作用于随后的损害部分的定位的路标。活体检查部分标记物可以是永久的标记物(例如在X射线检查下可见的金属标记物)或暂时的标记物(例如利用超声可检测的可生物再吸收的标记物)。尽管当前的射线成像类标记物可以在活体检查部位处持续，但是通常必须在随后的治疗或手术时执行另外的乳房X射线成像，以便定位之前的手术或活体检查的部位。此外，一旦使用乳房X射线成像定位了之前过程的部位，该部位通常必须利用定位线来标记，该定位线在进入之前过程的部分的端部具有钩。该钩用于关于之前过程的部位固定定位线的顶端，使得患者于是可以从乳房X射线成像装置的限制移开，并且执行随后的过程。然而，当患者从乳房X射线成像装置移开或者另外运送时，定位线的位置可能相对于之前过程的部分改变或偏移。这依次可能导致随后的治疗被误导到患者组织的不期望的部分。
作为对射线照相成像的替代或附属，超声成像(这里简写为“USI”)或可视化技术可以用于在手术或活体检查过程或随后过程期间成像感兴趣的部位处的感兴趣的组织。USI能够在过程期间提供可疑组织、周围组织和患者体内的活体检查仪器的精确定位和成像。这种成像便利可疑组织的准确和可控的移除或采样，以便最小化对周围健康组织的损伤。
例如，在乳房活体检查过程期间，活体检查设备通常利用USI成像，同时该设备被插入患者的乳房内并且被激活来移除可以乳房组织的样本。因为USI通常用于在随后的治疗期间成像组织，所以可能期望具有标记物，类似于上述射线照相标记物，其可以放置在患者体内在手术过程的部位处并使用USI可见。这种标记物允许执行随后的过程，而不需要传统的射线照相乳房X射线成像，如上所述，作为定位线偏移的结果，该传统的射线照相乳房X射线成像可能经历不准确，并且对患者来说是令人厌烦和不舒服的。
在患者体内放置标记物或多种标记物要求输送设备能够将标记物保持在设备内，直到该设备正确地位于乳房或其它身体位置内。因此，期望用于将标记物保留在标记物输送设备内同时允许在期望的体内位置处从设备放出的设备和方法。
除了标记功能外，还经常期望利用标记物部件提供治疗，如止血治疗等。
发明内容
本发明通常贯注于一种远程可成像标记物系统，其适于部署在患者体内的部位处，特别是如患者乳房中的活体检查部位处。该可成像标记物系统具有多个标记物部件，其包含足够量的多糖以提供止血特性，并且具有大约3500到大约200,000道尔顿的分子重量。包含标记物部件的多糖优选从干粉末压制成形为片形。多糖和黏料粉末应当具有大约10微米到大约200微米的微粒尺寸。多糖标记物在部署部位处的脱水血液的过程中快速吸收体液并与水化合，以便快速开始凝结。
多糖优选是淀粉(玉米淀粉或马铃薯淀粉)，但是各种可生物吸收的多糖是合适的，包括淀粉、糖原、纤维素、壳多糖、壳聚糖、右旋糖苷、果胶、葡聚糖、琼脂、藻酸盐和角叉菜。黏料优选是甲基纤维素，但是替代甲基纤维素或除了甲基纤维素之外，还可以采用多种黏料。其它合适的黏料包括羟乙基纤维素、聚乙二醇、聚乙烯醇、聚乙烯吡咯烷酮。
远程可成像标记物系统优选包括标记物主体，具有连接到其或并入其中的不透射线的元件，以便提供体内部位的长期标识。优选地，不透射线的元件由非磁材料形成，以避免对磁共振成像(MRI)的干扰。合适的非磁材料包括钛、铂、金、铱、钽、钨、银、铑、非磁不锈钢(316)等。不透射线的元件应当具有在远程成像时在体内部位处容易识别的形状。不透射线的元件应当具有大约0.5到大约5mm的最大直径，优选为大约1到大约3mm，以便确保远程标识，特别是利用MRI。具有不透射线的元件的标记物主体优选由可生物吸收的聚合物材料形成，如具有比多糖片(pallet)更长分解时间的聚乳酸聚羟基乙酸(polylactic-co-polyglycolic)，尽管也可以使用多糖片。
包含片的多糖将通常具有大约0.02英寸到大约0.1英寸(0.5-2.5mm)的横向尺寸，优选为大约0.035英寸到大约0.075英寸(0.9-1.9mm)，并且典型地为大约0.056英寸(1.4mm)。片将具有大约0.1英寸到大约0.4英寸(2.5-10mm)的长度，优选为大约0.15英寸到大约0.35英寸(3.8-8.9mm)。片提供足够的断裂强度以便利插入管状输送设备中以及从管状输送设备排出。标记物优选安排为在输送管内输送，并且标记物具有在由多糖形成的两个相邻标记物部件之间的不透射线的元件。如目前预期的，在输送管内，将存在远离具有不透射线的元件的标记物的两个多糖标记物部件和靠近具有不透射线的元件的标记物的两个多糖标记物部件。
体现本发明的特征的标记物部件可以通过合适的输送系统(如2003年5月23日提交的序列号10/444,770和2003年12月23日提交的序列号10/753,277的共同未审申请)容易地输送到期望的位置。标记物输送系统通常具有伸长的套管或管，其具有远端端口和近端端口以及在各端口之间延伸的内腔。标记物部件可滑动地放置在输送套管的内腔中，并且活塞可滑动地放置在输送套管的内腔中靠近标记物。活塞可从管内靠近标记物的初始位置移动到接近套管的远端中的排出开口的输送位置，以便将标记物部件推出排出开口进入目标组织部位。
在排出进入体内目标部位时，包含标记物的多个多糖在该部位快速地吸收体液，启动脱水过程并提供止血。具有不透射线的标记物元件的其它标记物部件允许通过远程USI进行短期检测(至少三个星期，优选至少四个星期但少于一年)，并且优选通过远程乳房X射线成像进行长期检测或通过不透射线的元件进行MRI标识。典型地，多糖主体在大约5秒到大约2分钟内就地溶解，并且在大约2-5天内酶降解。
标记物输送设备的套管可以构造成安装在活体检查设备(如
Figure BPA00001228826200051
(Johnson&Johnson销售)、SenoRx(本受让人)销售的SenoCor 360TM活体检查设备、SenoRx销售的EnCorTM活体检查设备)的引导套管和/或同轴针头引导内。输送套管还可以构造成安装到管状切削部件中，如SenoRx销售的EnCorTM活体检查系统中找到的，其是2004年8月3日提交的共同待审申请序列号10/911,106的主题。
一种适于输送通过管状切削器(例如EncorTM系统)的合适的输送系统是2004年8月3日提交的共同待审申请序列号10/911,106中描述的注射器型输送系统，具有管状轴，并且扩口引导在远端尖端上或与远端尖端集成，以便利与管状切割器的近端结合。另一种注射器型输送系统具有插入的远端尖端以防止体液与已经在输送系统的管状轴中的一个或多个标记物。这种流体灌输可以通过使得标记物吸收水或在输送套管的内腔中膨胀，延迟或限制排出输送套管的内腔中的标记物。具有插入尖端的输送系统在2003年5月23日提交的序列号10/444,770和2003年12月23日提交的序列号10/753,277的共同未审申请中描述，在此通过引用并入其全部内容。
各种治疗或诊断试剂也可以并入标记物主体中。并入的试剂可以包括例如用于控制疼痛的麻醉试剂、用于治疗残留瘤组织的化疗试剂或用于便利部位的随后视觉定位的着色试剂。抗生素、抗真菌试剂和抗病毒剂也可以并入标记物主体中。
在输送到体内部位时，通过超声成像(USI)可从部位处的周围组织容易地识别标记物。
包含体现本发明特征的标记物的多糖提供若干优点。多糖标记物主体快速溶解在部位处的体液中，以便即使在严重出血的情况下也在其中提供快速止血。此外，材料快速降解，因此在部位处没有长期刺激或炎症。
当与示例性附图结合时，本发明的这些和其它优点将从下面详细的实施例的描述中变得更明显。
附图说明
图1是体现本发明的特征的压制成形的标记物部件的平面图。
图2是图1所示的标记物部件的端视图。
图3是多个标记物布置在输送管(未示出)内时的透视图。
图4是具有体现本发明的特征的多个标记物部件的标记物输送组件的局部剖视透视图。
图5是沿着图4中所示的线5-5截取的横向剖视图。
具体实施方式
图1和2图示了体现本发明特征的压制成形的标记物部件10，该标记物部件10由多糖粉末和甲基纤维素粉末的混合物形成。压制成形的标记物部件10具有足够的多糖粉末，以便在体内部位与血液形成接触时快速形成血栓。典型地，标记物部件10将具有65％(重量百分比)的多糖和35％(重量百分比)的甲基纤维素。标记物部件10优选通过以下形成：以适当的量混合多糖粉末(玉米淀粉或马铃薯淀粉)和甲基纤维素粉末，将混合的粉末放入压片模具中，然后使得压片模具中的粉末经历大约6到60ksi(典型地大约12ksi)的压力。
一种合适的多糖材料是U.S.P.Topical Starch。可替代地，也可以使用可从美国明尼苏达州明尼阿波利斯市Medafor，Inc.公司获得的HemadermTM。这种产品至少部分地在美国专利No.6,060,461中进行了描述。
标记物部件10可以以各种形状和尺寸形成，但是通常标记物部件的长度至少是最大横向尺寸的长度的两倍，优选是五倍。标记物部件10应当具有足够的断裂强度，以允许它被推入输送管中而没有显著损坏。在一些示例中，标记物部件可以部分地或完全地覆盖有可生物吸收的聚合物材料(诸如聚乳酸、聚羟基乙酸及其共聚物)，以便控制标记物部件的材料的分解。
在图4A-4B中示出一种合适的标记物输送系统15，该标记物输送系统15包括具有内腔17的输送管或套管16、远端部分18以及具有手柄20的近端部分19。可释放的远端插塞21和压制成形的标记物10被示出是放置在内腔17中。由不同于多糖的可生物吸收的材料形成的、具有不透射线的元件的标记物主体22放置在至少两个压制成形的标记物主体10之间。活塞23可滑动地布置在内腔17中，并且在近端25上设置有头部24，该头部24构造成允许操作者按压活塞进一步进入内腔中，并且将可释放的插塞21以及标记物部件10和标记物主体22推出输送套管16的远端27中的排出端口或开口26。套管手柄20允许操作者在按压活塞23以排出可释放的插塞21以及标记物部件10和标记物主体22的同时保持套管稳定。
优选由聚乙二醇形成的可释放插塞21基本上可以填满排出开口26，如图4A所示，或者至少占据或阻断排出开口的一部分。插塞21的暴露面优选设置有倾斜构造。可释放插塞21构造成在内腔17中足够紧(例如压装配)，以防止其无意的释放，这可能允许标记物10太早从输送套管16中排出，但是当活塞23被按压深入输送套管16的内腔17中时，活塞必须容易释放。可以使用黏料或(多个)机械元件来将可释放插塞21保持在内腔17中的位置，以闭塞排出开口26。合适的黏料包括基于聚亚安酯或聚丙烯酸的黏料、基于聚羟基甲基丙烯酸的黏料、血纤维蛋白胶(例如TissealTM)、胶原质黏料或其混合物。在共同待审申请序列号10/174,401中描述了用于紧固可释放插塞21的合适的机械部件。输送套管16的远端26设置有斜坡27，其将排出的插塞21和标记物部件10引出侧面端口28进入目标部位。远端尖端29可以形成为锥形，用于输送通过引导管(未示出)。
输送套管16可以设置有用作视觉路标的标记30，以帮助操作者精确地将套管16的远端部分18放置在患者体内的期望位置中，用于排出标记物10。
输送套管10的外部优选构造为装配在引导套管内，确定该引导套管的尺寸以接受
Figure BPA00001228826200081
EnCorTM、
Figure BPA00001228826200082
或活体检查设备。典型地，插塞21和标记物部件10将具有由内腔17的尺寸确定的直径，并且典型地为大约0.02英寸(0.5mm)到大约0.5英寸(12mm)，优选地为大约0.04英寸(1mm)到大约0.3英寸(8mm)。插塞21可以具有稍大的横向尺寸以提供紧密装配。
当标记物部件10接触体腔(如乳房肿瘤切除术或活体检查部位)内的体液时，黏料溶解，并且多糖从部位处的血液和其它流体中汲取水分，并且凝固级联开始在部位处形成血栓，导致止血。
尽管在此已经在乳房活体检查部位的环境中描述和图示了本发明的一种或多种特定形式，但是将明显的是，除了其中已经移除组织的人类乳房外，具有本发明的特征的设备和方法可以在各种位置和各种应用中找到用途。此外，可以进行各种修改而不偏离本发明的精神和范围。例如，尽管在此多糖主体主要描述为压制成形的主体，但是多糖材料可以封装在可生物吸收的主体中或是其它形式。因此，意图不在于将本发明限制于图示的特定实施例。因此，意图在于本发明在现有技术允许的情况下由随后的权利要求的范围定义的尽可能宽，并且如果需要则考虑说明书。此外，本领域技术任一将意识到，一个实施例中所示的特征可以在其它实施例中使用。片形或其它标记物部件以及输送系统的额外细节可以在2004年1月7日提交的序列号10/753,694和2004年10月27日提交的序列号10/976,138的共同待审申请中找到。
当在下面的权利要求中使用时，如“元件”、“部件”、“设备”、“片段”、“部分”、“步骤”、“部件”和类似重要的词的术语不应解释为调用35U.S.C.§112(6)的规定，除非下面的权利要求明确使用跟随特定功能而没有具体结构的术语“部件”，或明确使用跟随特定功能而没有具体动作的术语“步骤”。上面引用的所有专利和专利申请在此通过引用并入其全部内容。

Claims (18)

1.一种远程可成像标记物系统，包括管状输送部件和多个标记物部件，所述多个标记物部件包括量足够呈现止血特性的可生物吸收的多糖以及黏料，并且所述多个标记物部件放置在管状输送部件的内腔中。
2.如权利要求1所述的可成像标记物系统，其中所述标记物部件是大约10％到大约90％(重量百分比)的生物可吸收多糖。
3.如权利要求2所述的可成像标记物系统，其中所述标记物部件由选自由以下物质组成的组中的多糖形成：淀粉、糖原、纤维素、壳多糖、壳聚糖、右旋糖苷、果胶、葡聚糖、琼脂、藻酸盐和角叉菜。
4.如权利要求2所述的可成像标记物系统，其中所述标记物部件由玉米淀粉或马铃薯淀粉形成。
5.如权利要求3所述的可成像标记物系统，其中所述标记物部件是大约10％到大约90％(重量百分比)的黏料。
6.如权利要求1所述的可成像标记物系统，其中所述标记物部件由选自由以下物质组成的组中的黏料形成：甲基纤维素、羟乙基纤维素、聚乙二醇、聚乙烯醇、聚乙烯吡咯烷酮。
7.如权利要求1所述的可成像标记物系统，其中所述标记物部件由包括甲基纤维素的黏料形成。
8.如权利要求1所述的可成像标记物系统，其中所述标记物部件压制成形为期望的形状。
9.如权利要求8所述的可成像标记物系统，其中压制成形的标记物部件由具有小于0.01英寸的微粒尺寸的粉末形成。
10.如权利要求9所述的可成像标记物系统，其中所述粉末具有大约10微米到大约200微米的微粒尺寸。
11.如权利要求8所述的可成像标记物系统，其中压制成形的标记物部件具有大约0.02英寸到大约0.1英寸的横向尺寸。
12.如权利要求8所述的可成像标记物系统，其中压制成形的标记物部件具有大约0.035英寸到大约0.075英寸的短的横向尺寸。
13.如权利要求8所述的可成像标记物系统，其中压制成形的标记物部件具有大约0.1英寸到大约0.4英寸的长度。
14.如权利要求8所述的可成像标记物系统，其中压制成形的标记物部件具有大约0.15英寸到大约0.35英寸的长度。
15.如权利要求1所述的可成像标记物系统，其中管状输送部件具有放置在其内腔中的由生物可吸收材料形成的标记物主体以及不透射线的标记物元件。
16.如权利要求15所述的可成像标记物系统，其中具有不透射线的标记物元件的标记物主体放置在由多糖形成的两个标记物部件之间。
17.如权利要求16所述的可成像标记物系统，其中存在两个远离具有不透射线的标记物元件的标记物主体的、由多糖形成的标记物部件。
18.如权利要求16所述的可成像标记物系统，其中存在两个靠近具有不透射线的标记物元件的标记物主体的、由多糖形成的标记物部件。
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CN113423369B (zh) * 2019-02-15 2023-08-18 巴德股份有限公司 止血活检道制品

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US20090030309A1 (en) 2009-01-29
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CA2715743A1 (en) 2009-08-27
US20090216118A1 (en) 2009-08-27
AU2009215896A1 (en) 2009-08-27
US9149341B2 (en) 2015-10-06
US20120078092A1 (en) 2012-03-29
AU2009215896B2 (en) 2013-09-12
US20120116215A1 (en) 2012-05-10
JP2011516408A (ja) 2011-05-26

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