CN103599588B - Showing the rapid expansion and contraction of an improved balloon catheter - Google Patents

Showing the rapid expansion and contraction of an improved balloon catheter Download PDF

Info

Publication number
CN103599588B
CN103599588B CN 201310453105 CN201310453105A CN103599588B CN 103599588 B CN103599588 B CN 103599588B CN 201310453105 CN201310453105 CN 201310453105 CN 201310453105 A CN201310453105 A CN 201310453105A CN 103599588 B CN103599588 B CN 103599588B
Authority
CN
Grant status
Grant
Patent type
Application number
CN 201310453105
Other languages
Chinese (zh)
Other versions
CN103599588A (en )
Inventor
K·J·埃伦赖希
J·马加纳
P·孔希尼
Original Assignee
雅培心脏血管系统股份有限公司
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Grant date

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00Catheters; Hollow probes
    • A61M25/10Balloon catheters
    • A61M25/1018Balloon inflating or inflation-control devices
    • A61M25/10181Means for forcing inflation fluid into the balloon
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00Catheters; Hollow probes
    • A61M25/10Balloon catheters
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00Catheters; Hollow probes
    • A61M25/10Balloon catheters
    • A61M25/1002Balloon catheters characterised by balloon shape
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00Catheters; Hollow probes
    • A61M25/10Balloon catheters
    • A61M25/1018Balloon inflating or inflation-control devices
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00Catheters; Hollow probes
    • A61M25/10Balloon catheters
    • A61M25/1018Balloon inflating or inflation-control devices
    • A61M25/10184Means for controlling or monitoring inflation or deflation
    • A61M25/10185Valves
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00Catheters; Hollow probes
    • A61M25/10Balloon catheters
    • A61M25/1018Balloon inflating or inflation-control devices
    • A61M25/10184Means for controlling or monitoring inflation or deflation
    • A61M25/10187Indicators for the level of inflation or deflation
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00Catheters; Hollow probes
    • A61M25/10Balloon catheters
    • A61M25/104Balloon catheters used for angioplasty
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00Catheters; Hollow probes
    • A61M25/0021Catheters; Hollow probes characterised by the form of the tubing
    • A61M25/0023Catheters; Hollow probes characterised by the form of the tubing by the form of the lumen, e.g. cross-section, variable diameter
    • A61M25/0026Multi-lumen catheters with stationary elements
    • A61M2025/004Multi-lumen catheters with stationary elements characterized by lumina being arranged circumferentially
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00Catheters; Hollow probes
    • A61M25/10Balloon catheters
    • A61M2025/1043Balloon catheters with special features or adapted for special applications
    • A61M2025/105Balloon catheters with special features or adapted for special applications having a balloon suitable for drug delivery, e.g. by using holes for delivery, drug coating or membranes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00Catheters; Hollow probes
    • A61M25/10Balloon catheters
    • A61M2025/1043Balloon catheters with special features or adapted for special applications
    • A61M2025/1075Balloon catheters with special features or adapted for special applications having a balloon composed of several layers, e.g. by coating or embedding
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00Catheters; Hollow probes
    • A61M25/10Balloon catheters
    • A61M2025/1043Balloon catheters with special features or adapted for special applications
    • A61M2025/1086Balloon catheters with special features or adapted for special applications having a special balloon surface topography, e.g. pores, protuberances, spikes or grooves
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00Catheters; Hollow probes
    • A61M25/0021Catheters; Hollow probes characterised by the form of the tubing
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00Catheters; Hollow probes
    • A61M25/0021Catheters; Hollow probes characterised by the form of the tubing
    • A61M25/0023Catheters; Hollow probes characterised by the form of the tubing by the form of the lumen, e.g. cross-section, variable diameter
    • A61M25/0026Multi-lumen catheters with stationary elements
    • A61M25/0032Multi-lumen catheters with stationary elements characterized by at least one unconventionally shaped lumen, e.g. polygons, ellipsoids, wedges or shapes comprising concave and convex parts
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00Catheters; Hollow probes
    • A61M25/10Balloon catheters
    • A61M25/1018Balloon inflating or inflation-control devices
    • A61M25/10184Means for controlling or monitoring inflation or deflation
    • A61M25/10185Valves
    • A61M25/10186One-way valves

Abstract

本发明涉及一种导管,其能够迅速膨胀和收缩,并且由单个人操作。 The present invention relates to a catheter, which is capable of rapid expansion and contraction, and is operated by a single person.

Description

呈现迅速膨胀和收缩的改进型球囊导管 Showing the rapid expansion and contraction of an improved balloon catheter

[0001] 本申请是名称为"呈现迅速膨胀和收缩的改进型球囊导管"、国际申请日为2011年4月29日、国际申请号为PCT/US2011/034621、国家申请号为201180028064.7的发明专利申请的分案申请。 [0001] This application is entitled "presents rapid expansion and contraction of an improved balloon catheter," the international filing date is April 29, 2011, International Application No. PCT / US2011 / 034621, the national invention application number of 201180028064.7 divisional patent filed.

[0002] 相关申请的交叉参考 [0002] CROSS-REFERENCE TO RELATED APPLICATIONS

[0003] 本申请是下列同时待审的美国专利申请的部分连续案:2010年4月30日提交的美国专利申请序列No. 12/771946; 2010年4月30日提交的美国专利申请序列No. 12/771968; 2010年4月30 日提交的PCT/US2010/033270 ; 2010年4月30 日提交的PCT/US2010/033276 ; 2011年2月23日提交的美国专利申请序列No. 13/032733;和2011年2月23日提交的美国专利申请序列No. 13/032743,每个上述申请中所披露的内容都由此通过引用并入此文中。 [0003] This application is part of the following while the continuous case pending US patent applications: US Patent April 30, 2010 filed application Ser. No. 12/771946; US Patent April 30, 2010, filed sequence No . 12/771968; PCT 2010 Nian 4 filed May 30 in / US2010 / 033270; PCT 2010 Nian 4 filed May 30 in / US2010 / 033276; US Patent February 23, 2011 application serial No. 13/032733 filed ; and US Patent February 23, 2011 filed application Ser. No. 13/032743, each of the above application, the disclosure of which are hereby incorporated by reference in this article.

技术领域 FIELD

[0004] 本发明涉及一种改进型球囊导管,其被构造用于使球囊迅速膨胀和收缩以用于血管成形术、后处理和其它医疗手术。 [0004] The present invention relates to an improved balloon catheter, which is designed to rapidly expand and contract the balloon for angioplasty, post-treatment and other medical procedures.

背景技术 Background technique

[0005] 血管成形术导管典型地用于执行PCTA。 [0005] Typically angioplasty catheter for performing PCTA. 传统的血管成形术导管还已知被改造或被构造成将治疗用制剂局部地递送到目标对象的脉管系统。 Conventional angioplasty catheter is also known to be adapted or configured to deliver a therapeutic target object vasculature formulations locally. 然而,对使用血管成形术导管所必需的预备不但耗时,而且难处理。 However, the necessary preparatory catheter angioplasty using time-consuming and difficult to handle. 为了使血管成形术导管上的球囊膨胀,不但需要时间准备球囊和导管本体,而且需要两个人来操作装置。 In order for the balloon angioplasty catheter expansion, not only it takes time to prepare the balloon and catheter body, and two people to operate the device. 使用传统血管成形术导管损失掉的时间有时对于需要医疗手术的患者而言会是生死攸关的问题。 Using conventional angioplasty catheter sometimes lost time for patients in need of medical surgery will be life and death issues. 因而,需要一种球囊导管,其主要可以被快速地使用并且可以容易被一个操作者迅速地管控。 Thus, a need for a balloon catheter, which can be primarily used quickly and easily can be quickly control an operator.

[0006] 所披露主题通过提供被构造成能够使球囊迅速膨胀和收缩且容易由一个操作者使用的导管系统而解决了上述需要。 [0006] The disclosed subject matter is configured by providing the balloon can be quickly and easily by the expansion and contraction of a conduit system used by the operator solves the above need.

发明内容 SUMMARY

[0007] 根据所披露主题的一个方面,提供了一种改进型导管。 [0007] In accordance with one aspect of the disclosed subject matter, there is provided an improved catheter. 所披露主题的导管在膨胀时间和收缩时间方面以及在递送有益制剂(诸如药物和其它治疗剂)方面呈现出超越传统球囊导管的改进。 The disclosed subject matter beyond the traditional catheters, and exhibit improved delivery balloon catheter beneficial agents (such as drugs and other therapeutic agents) in terms of the expansion and contraction time terms of time. 所披露主题的导管还可以提供一种用于执行后处理技术的独特的改进型设计。 The disclosed subject matter catheter can also provide a unique improved design techniques for post-execution processing.

[0008] 在一个实施例中,导管包括:球囊,其被布置在导管的远端端部附近;和导管轴,其限定出膨胀管腔和导丝管腔。 [0008] In one embodiment, the catheter comprising: a balloon, which is disposed in the vicinity of the distal end of the catheter; and a catheter shaft defining an inflation lumen and a guidewire lumen. 膨胀管腔在膨胀端口与球囊的内部之间提供流体连通,而导丝管腔适于滑动地接受从近端导丝端口向远端导丝端口延伸的导丝。 Inflation lumen providing fluid communication between the interior of the balloon inflation port, the guidewire lumen adapted to slidably accept the guide wire extending from the proximal guidewire port to a distal guidewire port. 导管设计能够在少于约四秒的时间内使球囊膨胀。 Inflating the balloon catheter design is possible in less than about four seconds. 在某些实施例中,导管能够在少于约一秒的时间内使球囊膨胀。 In certain embodiments, the catheter is capable of inflating the balloon in less than about one second. 在又一个实施例中,球囊可以在半秒的时间内膨胀。 In yet another embodiment, the balloon may be inflated within half a second time.

[0009]在另一个实施例中,导管轴还包括收缩管腔。 [0009] In another embodiment, the catheter shaft further comprising a lumen contraction. 收缩管腔与膨胀管腔分离,并独立于该膨胀管腔。 Isolated systolic lumen inflation lumen, the inflation lumen and independent. 收缩管腔在收缩部分与球囊的内部之间提供流体连通。 Shrinkage lumen providing fluid communication between the inner portion and the contraction of the balloon. 在一个实施例中,球囊的收缩可以在少于约五秒的时间内发生。 In one embodiment, the shrinkage of the balloon may occur in less than about five seconds. 在一个实施例中,导管可以使球囊在一秒那么快的时间内收缩。 In one embodiment, the balloon catheter may shrink in a second time so fast. 导管球囊能够膨胀和收缩达多次循环。 The catheter balloon to expand and contract of a plurality of cycles. 这尤其有助于执行后处理技术。 This is especially facilitate the implementation of post-processing techniques. [0010]在某些实施例中,导管可以递送有益制剂。 [0010] In certain embodiments, the catheter may deliver beneficial agents. 具体而言,导管可以适于包括递送管腔,用以递送一种或多种有益制剂。 Specifically, the catheter may include a delivery lumen adapted to deliver one or more beneficial agents. 在另一个实施例中,球囊可以包括带有益制剂的涂层。 In another embodiment, the balloon may include a coating with a useful formulation. 在一个实施例中,有益制剂是造影介质。 In one embodiment, the formulation is a useful contrast medium. 这样,导管与传统血管成形术导管相比使用更少的造影介质。 Thus, the conventional catheter angioplasty catheter compared to the use of contrast media less. 例如,导管比血管成形术导管使用少四十倍的造影剂。 For example, the vascular catheter used catheter less than four times the contrast agent is formed. 有益制剂也可以是药物或其它治疗剂。 Advantageous preparation may also be a drug or other therapeutic agents. 在这些情况下,已经发现导管使组织对有益制剂的吸收平均提高了至少四十倍。 Under these circumstances, it has been found that the absorbent tissue conduit beneficial formulation by an average of at least four times. 合适的有益制剂包括但不限于:钙蛋白酶抑制剂、pH稳定剂、或内皮素受体阻滞剂、紫杉醇、雷帕霉素或它们的类似物或衍生物。 Suitable benefit agents include but are not limited to: calpain inhibitors, pH stabilizers, or endothelin receptor blockers, paclitaxel, rapamycin, or analog or derivative thereof. 有益制剂可以处于诸如PVP、丙三醇或这二者的赋形剂中。 Excipients such beneficial agents may be in PVP, glycerol, or in both.

[0011]在某些实施例中,膨胀管腔、收缩管腔、导丝管腔和递送管腔可以并置以形成工字梁形聚合物腹板,该聚合物腹板与管腔的纵向轴线横向地对准。 [0011] In certain embodiments, the inflation lumen, the lumen contraction, delivery lumen and guidewire lumen may be juxtaposed to form a beam shaped polymer web, the longitudinal web and the polymer lumen laterally aligned with the axis. 工字梁构造提供了改进的强度和较小的轮廓,以便插入血管中并且穿过曲折的脉管系统。 I-beam construction provides improved strength and lower profile for insertion into a blood vessel and through the tortuous vasculature.

[0012] 根据本发明主题,披露了一种用于改进患者心脏功能的导管。 [0012] The subject of the present invention, discloses a catheter for improving cardiac function in a patient. 该导管包括:球囊, 其被布置在导管的远端端部附近;和导管轴,其限定出膨胀管腔和分离的收缩管腔。 The catheter comprising: a balloon, which is disposed in the vicinity of the distal end of the catheter; and a catheter shaft defining an inflation lumen and a separate lumen contraction. 膨胀管腔和收缩管腔提供了在膨胀端口和收缩端口与球囊的内部之间的独立的流体连通。 Expansion and contraction of the lumen of the lumen provides a separate fluid between the interior of the port expansion and contraction of the balloon communicates with the port. 已经发现导管将目标对象的射血分数(ejection fraction)提高到至少30%。 It has been found conduit ejection target object (ejection fraction) raised to at least 30%. 30%的射血分数可以维持超过7天,并且在某些实施例中维持超过28天。 Ejection fraction of 30% can be maintained more than 7 days, and in certain embodiments is maintained over 28 days.

[0013] 根据另一个方面,提供一种导管系统。 [0013] According to another aspect, there is provided a catheter system. 该导管系统包括:被布置在导管的远端端部附近的球囊,以及流体回路。 The catheter system comprising: a balloon disposed near the distal end of the catheter, and a fluid circuit. 该流体回路包括:容装膨胀流体的储器、膨胀管腔以及分离的收缩管腔。 The fluid circuit comprising: accommodating expansion of the fluid reservoir, and separate inflation lumen lumen shrinkage. 膨胀管腔和收缩管腔在膨胀端口和收缩端口与球囊的内部之间提供独立的流体连通。 An inflation lumen and a separate lumen contraction fluid communication between the interior of the port expansion and contraction of the balloon port. 控制电路还包括不可逆的装载装置以允许膨胀流体从储器流到膨胀管腔。 The control circuit further includes a loading device to allow irreversible flow of inflation fluid from the inflation lumen reservoir. 在一个实施例中,装载装置穿透储器以允许将膨胀流体释放到膨胀管腔中。 In one embodiment, the loading means penetrating the reservoir to allow inflation fluid is released into the inflation lumen. 膨胀流体优选地是气态物质。 Inflation fluid is preferably a gaseous material.

[0014] 在一个实施例中,导管包括指示器,用以指示球囊完全膨胀。 [0014] In one embodiment, the catheter comprises an indicator for indicating the balloon fully inflated. 指示器被布置球囊在与收缩管腔相关联的止回阀之间。 It is disposed between the indicator associated with the contraction of the balloon lumen valve. 因而,指示器对于指示球囊膨胀而言是防误操作的。 Thus, the indicator for indicating the inflation of the balloon is in terms of anti-misoperation.

[0015] 在某些实施例中,已经发现导管在目标对象发生缺血性事件之后有助于改善目标对象的梗塞尺寸和/或风险面积。 [0015] In certain embodiments, the catheter has been found to help improve the infarct size of the target object and / or area at risk after the occurrence of an ischemic event audience.

附图说明 BRIEF DESCRIPTION

[0016] 参照以下被简要地描述的附图提供了对本文所描述主题的各种方面、特征和实施例的详细说明。 BRIEF [0016] Referring briefly described hereinafter provide various aspects of the subject matter described herein, features, and detailed description of the embodiments. 附图是示意性的,不必按比例来描绘,并且某些组成部件和特征为了清楚起见被夸大。 The drawings are schematic and not necessarily drawn to scale, and some components and features being exaggerated for clarity. 附图示出了本发明主题的各种方面和特征,并且可以整个地或部分地示出本发明主题的一个或多个实施例或示例。 The drawings illustrate various aspects and features of the subject matter of the present invention, and may be wholly or partially shows a subject matter of the present invention, one or more embodiments or examples.

[0017] 图1A和图1B是根据所披露主题的示例性后处理技术的原理性视图; [0017] FIGS. 1A and FIG. 1B is a schematic view of exemplary post-processing techniques in accordance with the disclosed subject matter;

[0018] 图2和图3是根据所披露主题的一个实施例的系统的原理性视图; [0018] FIG. 2 and FIG. 3 is a schematic view of a system of an embodiment according to the disclosed subject matter;

[0019]图4A至图4C是根据所披露主题的实施例的导管轴的原理性示意图; [0019] FIGS. 4A to 4C are a schematic view showing the catheter shaft in accordance with an embodiment of the disclosed subject matter;

[0020]图5是根据所披露主题的有关医生/操作者关注力或注意力分配的对比的图形表示图; [0020] FIG. 5 is a graphical comparison of interest or attention allocation in accordance with the disclosed subject matter related to physician / operator diagram showing;

[0021] 图6是示出了根据所披露主题的关于对膨胀时间和收缩时间对比研究的结果的图表; [0021] FIG. 6 is a graph showing the results of comparative study on the time of expansion and contraction of the time in accordance with the disclosed subject matter;

[0022] 图7A和图7B是根据所披露主题的一个实施例的导管轴的横截面视图; [0022] FIGS. 7A and FIG. 7B is a cross-sectional view of a catheter shaft according to one embodiment of the disclosed subject matter;

[0023]图8A和图8B是根据所披露主题的球囊的实施例的透视图; [0023] FIGS. 8A and 8B are a perspective view of an embodiment in accordance with the disclosed subject matter of the balloon;

[0024]图8C和图8D是根据所披露主题的球囊的另一个实施例的透视图; [0024] FIGS. 8C and 8D are perspective views of another embodiment of the balloon embodiments disclosed subject matter;

[0025]图8E至图8F是根据所披露主题的球囊的另一个实施例的透视图,并且图8G是在图8E至图8F示出的根据所披露主题的球囊的所述实施例的端视图; [0025] FIGS. 8E-8F is a perspective view of the disclosed subject matter to another embodiment of the balloon, the 8F and FIG. 8G is shown in accordance with the disclosed subject matter to the balloon in FIG. 8E embodiment an end view;

[0026]图9A和图9B是根据所披露主题的手柄的某些实施例的横截面视图; [0026] FIGS. 9A and 9B are cross-sectional views of some embodiments of the disclosed subject matter in accordance with the handle;

[0027]图9C至图9R是根据所披露主题的手柄的各种实施例的透视图; [0027] FIG. 9C to FIG 9R is a perspective view of the disclosed subject matter in accordance with various embodiments of the handle;

[0028]图10是根据所披露主题的一个实施例的流体回路的分解图; [0028] FIG. 10 is an exploded view of a fluid circuit according to one embodiment of the disclosed subject matter;

[0029]图11A至图11C是根据所披露主题的脉冲阀的原理性示意图; [0029] FIGS. 11A to 11C is a pulsing valve of the disclosed subject matter shows a schematic view;

[0030] 图12是根据所披露主题的流体回路的侧视图; [0030] FIG. 12 is a side view of the fluid circuit of the disclosed subject matter;

[0031] 图13A至图13T是图12的流体回路的示例性组成部件的透视图; [0031] FIGS. 13A to 13T is a perspective view of an exemplary component parts of the fluid circuit of FIG. 12;

[0032] 图14A至图14C是方框图,示出了通过根据所披露主题的一个实施例的流体回路的膨胀流体流动; [0032] FIGS. 14A to 14C is a block diagram illustrating the flow of inflation fluid through the fluid circuit according to one embodiment of the disclosed subject matter;

[0033] 图15A至图15N是根据所披露主题的装载装置的某些实施例的侧视图; [0033] FIGS. 15A to 15N are side views of certain embodiments of the loading device in accordance with the disclosed subject matter;

[0034] 图16是根据所披露主题所采用的造影剂的对比的图形表示图; [0034] FIG. 16 is a diagram illustrating a comparison of the contrast agent used relating to the disclosed pattern;

[0035] 图17是根据所披露主题的、在再灌注循环中的一系列步骤的图形表示图,其描绘出了向球囊远端递送造影剂; [0035] FIG. 17 is a graphical view showing the disclosed subject matter, a series of steps in reperfusion cycle, depicting the delivery of contrast agent into the distal end of the balloon;

[0036]图18是根据所披露主题的一个实施例的协同式机械式后处理和局部有益制剂疗法的原理性示意图; [0036] FIG. 18 is a schematic illustration of a process and topical formulations useful in therapy according to the subject matter disclosed a collaborative mechanical embodiment;

[0037]图19是示出根据所披露主题的、对有益制剂在各种组织中的组织吸收的对比研究的结果的图表; [0037] FIG. 19 is a graph showing the results of comparative studies of the disclosed subject matter, tissue beneficial formulation in various tissues of absorption;

[0038]图20是示出根据所披露主题的、在后处理之后的有益制剂的血浆浓度的图表; [0038] FIG. 20 is a graph showing the plasma concentrations according to the disclosed subject matter, useful in the formulation after post-processing;

[0039] 图21是示出根据所披露主题的、对梗塞尺寸与风险面积比率的对比的图形表示图;和 [0039] FIG. 21 is a diagram illustrating in accordance with the disclosed subject matter, a diagram showing a graphical comparison of infarct size and area ratio of the risk; and

[0040] 图22是根据所披露主题的对射血分数的对比的图形表示图。 [0040] FIG. 22 shows a graphical comparison of the ejection fraction of the disclosed subject matter.

具体实施方式[0041 ] I ·导管概述 DETAILED DESCRIPTION [0041] I · catheter Overview

[0042]根据本主题,导管系统被构造成允许诸如球囊的可扩张构件非常迅速地膨胀和收缩,并且尤其允许该可扩张构件顺序地(例如间歇并重复地)膨胀和收缩。 [0042] According to the present subject matter, the system is configured to allow the catheter balloon expandable member such as a very rapid expansion and contraction, and in particular to allow the expandable member sequentially (e.g. intermittently and repeatedly) expansion and contraction. 在一些实施例中, 球囊的顺序膨胀和收缩通过单触式(single-touch)致动来实现。 In some embodiments, the order of the expansion and contraction of the balloon by actuating the one-touch (single-touch) is achieved. 本文所使用术语"单触式" 意思是使可扩张构件膨胀和收缩的致动可以由单个开关、单个按钮或其它单个致动点来实现。 As used herein, the term "one-touch" means that the expansion and contraction of the expandable member may be actuated by a single switch, a single button or other single point of activation is achieved. 就此而言,使用者简单地按压或者致动致动器使球囊膨胀,并且再次按压该致动器以致动球囊的收缩。 In this regard, the user simply presses the actuator or actuators balloon is inflated and again presses the actuator to actuate the contraction of the balloon. 因而,与总体上要求测量尺寸、预备和通过转动膨胀收缩器上的螺钉来膨胀的血管成形术导管不同,本发明系统的一个实施例能够使其在不需要准备的情况下迅速地使用。 Accordingly, the overall size requirements of measurement, and by turning the screw on the preliminary expansion and contraction of the expansion device to different catheters in angioplasty, an embodiment of the present invention, the system can be used so quickly without the need to prepare.

[0043]逐步的对此显示出,血管成形术球囊导管要求许多步骤来测量尺寸、预备、去除气泡和使用装置,然而根据本发明系统的实施例的导管系统要有效得多,从而提供了更短的手术时间并减小了患者的风险。 [0043] exhibit this gradual, angioplasty balloon catheters require many steps to measure the size, preparation, and use of the device to remove air bubbles, however, is much more effective catheter system according to an embodiment of the present invention system, thereby providing shorter operative time and reduces the risk of the patient. 因此,本文所描述的系统使得后处理步骤减少,并最终通过节省对存活而言是关键因素的时间而挽救了生命。 Thus, the system described herein after making processing steps to reduce and eventually through savings in terms of survival time is a critical factor and saved lives.

Figure CN103599588BD00071

[0045] 在没有从患者身体去除快速交换导管、将导丝上球囊导管引入以将有益制剂递送到球囊远端并然后再次替换快速交换球囊导管的额外步骤下,传统的快速交换血管成形术球囊导管没有措施将诸如药物的有益制剂递送到球囊导管本体的球囊远端。 [0045] In a rapid exchange catheter is not removed from the patient, the balloon catheter is introduced over the guidewire to the additional step useful formulation and delivered to the distal end of the balloon is then again replace a rapid exchange balloon catheter, the rapid exchange vascular conventional angioplasty balloon catheter without measures such as drug delivery of benefit agents to the distal end of the balloon of the balloon catheter body.

[0046] 另外,虽然导丝上球囊导管会能够堵塞血流并将物质递送到导管本体远端端部的远端,但是本文所实施的导管提供了优点。 [0046] Further, although the balloon catheter over the guidewire and will be capable of delivering a substance blockage of blood flow distal to the distal end of the catheter body, the catheter embodied herein provides advantages. 快速交换长度线材的使用是最普遍的。 Using the rapid exchange length wire is the most common. 本发明的导管能够在切换导丝不损失时间的情况下使用。 Catheter of the present invention can be used in case of switching the guidewire without losing time. 切换导丝(RX切换到0TW)耗费时间。 Switching guide wire (RX switch to 0TW) time-consuming. 本发明的导管装置允许操作者将导丝留在合适的位置中,而0TW导管设计需要医生更换并可能扰动到导丝的位置。 The catheter device according to the present invention allows the operator to leave the guide wire in place, whereas 0TW catheter design may require a doctor and replacement of the guidewire to the location of the disturbance. 因而,即使0TW导管能够将有益制剂递送到导管本体的远端,更换导丝也损失时间。 Accordingly, even if the catheter can be useful 0TW formulation is delivered to the distal end of the catheter body, the guide wire can replace loss of time. 本发明的导管系统可以在导丝上延伸,并且球囊可以在有益制剂被递送到血管的另一个其它区域的同时堵塞血管。 The catheter system according to the present invention may extend over the guidewire, and the balloon can be delivered to another vessel at a region other beneficial agents simultaneously occlude the vessel. 在一个实施例中,一种尺寸适合所有尺寸的球囊允许操作者将有益制剂递送到血管的位置。 In one embodiment, one size fits all sizes of the balloon allows the operator to deliver benefit agents to the location of the blood vessel. 而且,与血管符合球囊形状的情况截然相反,球囊符合血管形状的能力允许使导管一次用在多个尺寸的管腔中和多个位置中。 Further, the case of vascular compliance balloon shape diametrically opposed, the shape of the balloon comply with the ability to allow the vessel the catheter lumen once with multiple sizes and a plurality of positions. 在其它装置中, 如果操作者想要在血管成形术或后处理手术期间递送药物或其它化合物,则他或她将不得不获取不同尺寸的血管成形术球囊以将有益制剂递送到血管的不同位置中。 In other devices, if the operator wants to angioplasty or post treatment delivery of a drug or other compounds during surgery, he or she will have acquired angioplasty balloon different sizes of different beneficial agents to be delivered to a blood vessel location. 相反地,本文所描述的导管允许导管运动到其它位置。 Conversely, the catheter described herein allow the catheter is moved to another location. 因而,当导管用于递送诸如药物或其它治疗剂的有益制剂时,与传统快速交换球囊导管或导丝上血管成形术球囊导管相比,本文所描述实施例的关于减少使用导管所需要的步骤和手术程序数量的优点变得明显。 Thus, when the catheter is used to deliver beneficial agents such as drugs or other therapeutic agents, and on conventional rapid exchange balloon catheter or guide wire angioplasty balloon catheter compared to the embodiment described herein with respect to use of the catheter to reduce the required the number of steps of the surgical procedure and advantages will become apparent. 因而,当需要使用导管将有益制剂递送到球囊远端时,使用快速交换导管没有节约时间的优点。 Accordingly, when it is desired to use a catheter to deliver benefit agents to the distal end of the balloon, the advantages of using a rapid exchange catheter without time-saving. 至此,医生受限于使用没有与快速交换导管相同的节约时间优点的导丝上球囊导管。 Thus, the doctor is not limited to the use of a balloon catheter and a time-saving advantages of the same guidewire rapid exchange catheter. 因此,本发明系统借助在导管与快速交换导丝联接的同时通过导管递送治疗剂的能力而提供了快速交换球囊导管以及导丝上球囊导管的益处。 Accordingly, the present invention provides a system benefits rapid exchange balloon catheter and the balloon catheter guide wire by means of the ability to deliver therapeutic agents by the rapid catheter exchange conduit coupled to the guidewire.

[0047] 在传统血管成形术技术中,球囊的尺寸和直径必须与待扩大动脉的堵塞节段的尺寸和天然直径相匹配。 Match [0047] In the conventional angioplasty techniques, the balloon size and diameter must be enlarged and the size of the artery to be blocked natural diameter segment. 如果球囊的尺寸和直径小于天然的动脉,球囊血管成形术的结果不是最理想的,需要用更大尺寸的球囊进行第二次扩大。 If the balloon size and diameter is smaller than the native artery, balloon angioplasty result is suboptimal, requiring a second larger expanded balloon. 在某些情况下导致手术失败而会需要第二次单独的血管成形术手术程序或替换管手术(bypass surgery)。 In some cases lead to surgical failure and may require a second angioplasty procedure separate or alternative vascular surgery procedures (bypass surgery). 如果球囊相对于天然血管的堵塞节段过大,则动脉的内壁会从动脉的其余部分割开而完全堵塞血管,导致血液到心肌靶区域的流动总体终止。 If the balloon is too large with respect to a native blood vessel blockage section, the inner wall of the artery will be completely occlude the vessel, causing blood flow to the myocardium of the target area from the rest of the overall termination cut the artery. 该并发症会导致急性心肌梗塞和必要的紧急替换管手术。 The complications can lead to acute myocardial infarction and needed emergency surgery to replace the tube. 如果急性梗塞导致更大的梗塞,则可能导致死亡。 If acute infarction leads to greater infarction, it may result in death.

[0048] 如果患者在右冠状动脉系统系统或左冠状动脉系统中具有单个受阻部位,将为想要的扩张手术选择具有匹配直径和尺寸的单个球囊导管。 [0048] If a patient has a single site in a blocked right coronary artery or left coronary artery system system system, for selecting a desired surgical expansion matching diameter and size of a single balloon catheter. 当球囊在天然动脉或其它血管的堵塞节段内膨胀时,球囊应当在最大容许压力下维持初始预成形构造和直径。 When the balloon is inflated in the artery blockage or other segment of the native vessel, the balloon should maintain the original pre-shaped configuration and the diameter at the maximum allowable pressure. 在扩大单个受伤部位时,虽然有在初始不合适地选择了球囊导管使得必须要第二个球囊导管来成功完成手术程序的情况,但是选择合适大小的球囊导管是较简单的。 When expanding a single injury site, although there is inappropriate to choose a balloon catheter in the initial situation makes it necessary to be the second player to complete the surgical procedure balloon catheter successfully, but selecting the appropriate size of balloon catheter is relatively simple.

[0049] 然而,在多血管疾病中,球囊导管选择变得混乱和复杂。 [0049] However, in multi-vessel disease, balloon catheter selection becomes complicated and confusing. 例如,患者可能在左冠状动脉中具有三个受伤部位,这三个受伤部位各个都可以接近来成功实现球囊血管成形术。 For example, a patient may have three injured area in the left coronary artery, the three injured area can be close to each successful balloon angioplasty. 但是这些受伤部位可能处于尺寸不同的血管中。 But the injured area may be in a different size vessels. 借助传统球囊导管在尺寸不同的受伤部位中执行血管成形术并不是总会不可能,但这既麻烦又低效。 With conventional balloon catheter to perform an angioplasty is not always impossible in different sizes injured area, but this is cumbersome and inefficient. 对于每个受伤部位而言,匹配的球囊导管被交换并操纵到靶受伤部位中。 For each injured area, the matching balloon catheter is exchanged and manipulated into the target site of injury. 为此,三次连续的手术大致需要三倍的手术程序时间、三倍的造影剂量,和最少三个分离的球囊导管及其附属装置。 To this end, surgery generally requires three successive three times the surgical procedure time, three times the amount of contrast medium, and a balloon catheter and a minimum of three separate attachment.

[0050] 根据所描述主题的一个方面,提供了一种更有功效且更有效率的球囊导管系统。 [0050] According to an aspect of the subject matter described herein, there is provided a more efficient and more efficacy balloon catheter system. 在一个实施例中,球囊导管系统是预组装的装置,具有一种尺寸适合所有尺寸的球囊,该球囊被设计用于在各种不同血管(例如冠状血管、外周血管、脊柱血管、大脑血管)中使用,从而提供一种操作者不需要对球囊膨胀选择压力或体积的装置。 In one embodiment, a balloon catheter system is pre-assembled apparatus, having one size fits all sizes of the balloon, the balloon is designed for use in various vessels (e.g. coronary, peripheral, spinal vascular, cerebral blood vessels) in use, so that the operator need not provide a means of pressure or volume of the balloon inflation options. 因此,医生不需要浪费时间在对球囊定尺寸和制备所需的额外步骤上,而这些步骤正是传统血管成形术球囊导管所需要的。 Thus, the doctor does not need to waste time on the extra step and the balloon is sized to produce the desired, and these steps is the traditional angioplasty balloon catheter required. 因而,系统的一个实施例为医生提供一种轻松有效地使用导管的方式,所述导管被设计成使得球囊迅速地膨胀和收缩,从而不仅用于例如在缺血性事件之后减少或防止对器官或组织的再灌注损伤(诸如后处理),还用于操作者典型地使用传统血管成形术球囊导管的其它应用场合。 Thus, one embodiment of the system provide a way to easily and efficiently using a catheter for the physician, the balloon catheter is designed such that rapid expansion and contraction, thereby not only reducing or preventing, for example, after an ischemic event organ or tissue reperfusion injury (such as a post-treatment), the operator typically used for conventional angioplasty balloon catheter in other applications of the technique.

[0051] 当本发明的系统用于后处理应用场合时,系统可以用于(1)通过使球囊在血管中膨胀一定的时间量来停止对器官或组织的血液灌注;和(2)通过使球囊收缩另一段时间来允许对器官或组织的再灌注,顺序地重复膨胀(停止)和收缩(灌注);和可选地(3)将例如药物、造影剂、治疗用制剂等的有益制剂递送到球囊远端的区域。 [0051] When the system of the invention for post-processing applications, the system may be used (1) by inflating the balloon of a certain amount of time in a blood vessel to stop the blood perfusion of the organ or tissue; and (2) shrinking the balloon another period of time to allow reperfusion of the organ or tissue, are sequentially repeated expansion (stop) and contraction (perfusion); and, optionally, (3) such as a drug, a contrast agent, such as therapeutic preparations useful formulation delivered to the distal region of the balloon.

[0052] 球囊可以被构造成在可扩张构件扩张或膨胀期间堵塞血管,并且然后允许在可扩张构件紧缩或收缩期间恢复血流灌注。 [0052] The balloon may be configured during expansion of the expandable member to expand or occlude the vessel, and then allowed to recover during the perfusion of the expandable member contracts or shrinks. 堵塞的脉管系统可以包括如在逆行灌注中的静脉血管,或者如在再灌注中的动脉血管。 Vasculature blockage may include as in retrograde perfusion in the vein or artery as in reperfusion. 堵塞的血管可以来自冠状脉管系统、外周脉管系统、大脑脉管系统或其它脉管系统。 Obstructed blood vessel may be derived from the coronary vasculature, peripheral vasculature, cerebral vasculature, or other vasculature.

[0053]如在图1A和图1B的原理图中所示,在一个实施例中,通过从使导管球囊在受伤部位的近端膨胀和收缩一次或多次循环(每次循环从约10秒至60秒直到约三十分钟)来实现后处理。 [0053] As shown in the schematic diagram of FIGS. 1A and 1B, in one embodiment, by one or more cycles of the catheter from the proximal end of the expansion and contraction of the balloon injured area (from about 10 per cycle and 60 seconds up to about thirty minutes) post-treatment is achieved. 在一个示例中,球囊膨胀并维持约30秒,然后球囊收缩并维持约30秒(图1A)。 In one example, the balloon is inflated and maintained for about 30 seconds, and then shrinking the balloon and maintained for about 30 seconds (FIG. 1A). 在另一个实施例中,球囊膨胀并维持少于二十秒,然后球囊收缩并维持收缩状态约20秒至约2分钟。 In another embodiment, the balloon is inflated and maintained less than twenty seconds, and then shrinking the balloon collapsed state and maintained for about 20 seconds to about 2 minutes. 对执行后处理疗法必要时重复这些循环。 After these repeated cycles of therapy necessary to perform processing. 本文所使用的术语"循环"指的是一次完整的膨胀和收缩步骤。 As used herein, the term "cycle" refers to a complete expansion and contraction step. 例如,可扩张构件顺序地收缩和膨胀以允许血液灌注约10秒至约60秒或更久并停止灌注约10秒至约60秒或更久(例如,30分钟)用于一次或多次循环。 For example, the expandable member is sequentially contracted and expanded to allow blood perfusion from about 10 seconds to about 60 seconds or longer and perfusion is stopped about 10 seconds to about 60 seconds or longer (e.g., 30 minutes) for one or more cycles . 在某些实施例中,重复了约3次循环至约10次或更多次循环。 In certain embodiments, repeated about 10 times or more to about 3 cycles cycles. 然而,可以采用其它后处理方法,例如在Vinten-Johansen等人的美国专利公开No. 2004/0255956和2007/0160645中说明的后处理方法,这些专利所披露的内容通过引用并入此文中用于所有目的。 However, other post-processing method may be employed, for example, in U.S. Pat Vinten-Johansen et al., Discloses No. 2004/0255956 and 2007/0160645 post-processing method described in these patent disclosures are incorporated herein by reference for the all purposes. 然而,本文所披露导管系统不限于后处理手术或不限于防止或减少再灌注损伤。 However, the catheter system disclosed herein is not limited to post surgical treatment to prevent or reduce Any or reperfusion injury.

[0054] 在某些实施例中,球囊导管被设计成在不改变被植入支架尺寸的情况下在打支架的血管内膨胀。 [0054] In certain embodiments, the balloon catheter is designed to fight the stent expanded within the vessel without changing the size of the stent is implanted. 这样,可扩张构件是如下文所描述的顺应性球囊,所述顺应性球囊在球囊膨胀和收缩期间对被植入支架没有消极影响。 Thus, the expandable member is a compliant balloon as described below, the compliant balloon is no negative impact on the implanted stent balloon during expansion and contraction. 因而,根据一个实施例,可以在被植入支架的管腔内发生包括使球囊膨胀和收缩在内的医疗手术程序。 Thus, according to one embodiment, expansion and contraction of the balloon comprises medical procedures, including procedures may occur within the lumen of the implanted stent.

[0055] 当导管系统用于后处理时,如在图1A和图1B中所示,可以在给血管打支架之前或接在给血管打支架之后采用后处理技术。 [0055] When a catheter system for post-processing, as shown in FIGS. 1A and 1B, the vessel to be played before the stent or after contact with a blood vessel stent playing With processing techniques. 关于在打支架之前或之后的后处理,在此实施的系统的实施例被设计成使得对血管的后处理将不用移走被固定到血管壁上的血小板(plaque)。 Playing on the stent after treatment before or after, the embodiments of the embodiment is designed such that the system is fixed to the post-treatment vessels to the vessel wall without removing platelets (plaque). 关于在打支架之后的后处理,可以在支架的近端、支架的远端和/或支架的内部进行后处理。 Post treatment after beating the stent may be treated in the proximal end of the stent, the stent distal end and an inner and / or the stent is. 有利地,当在打支架的血管内采用后处理时,本文所实施的导管装置不改变展开的支架的形状或尺寸。 Advantageously, when the stent employed in the playing processing vessel, conduit means embodied herein without changing the shape or size of the expanded stent. 因此,本发明导管实施例可以用于在血管中放置支架之前或之后进行的后处理。 Thus, the catheter of the present invention may be used in embodiments of the post-processing prior to placement in a blood vessel or the stent after.

[0056] 如图2中所示,导管系统10总体上包括:具有纵长轴200的导管;可扩张构件300;和含有被容装在手柄中的控制系统1 〇〇〇的流体回路。 [0056] As shown in Figure 2 the catheter system 10 generally comprises: a catheter having a longitudinal axis 200; expandable member 300; containing control system is accommodated in the handle 1 〇〇〇 the fluid circuit.

[0057] 在一些实施例中,手柄100(图3)被不可移除地附装到导管系统,以便提供单个的一体式装置。 [0057] In some embodiments, the handle 100 (FIG. 3) is non-removably attached to the catheter system, in order to provide a single integral unit. 有利地,一体式装置被包装在即用(ready-to-use)的状态中。 Advantageously, the integrated device is packaged ready for use (ready-to-use) state. 换言之,装置可以是预组装单元,其准备好用于任何尺寸的血管,由此消除了如现有技术的装置所要求的对测量患者并选择合适尺寸球囊和导管的需要。 In other words, the device may be pre-assembled unit ready for any size of vessel, thereby eliminating the need for measurement of the patient and select the appropriate size of the balloon and catheter of the prior art apparatus as required. 在图3中示出了预组装单元的示例性实施例。 In FIG 3 illustrates an exemplary embodiment of a preassembled unit. 一旦将装置从所提供的任何包装移除并与膨胀流体源联接时,如在下文更加详细描述地,该装置准备好使用。 Once the device and coupled to a source of inflation fluid is removed from any package offered, as described in more detail hereinafter, the device is ready for use. 另外,在递送治疗剂的应用场合中,本发明主题的装置提供用于更加有效的手术程序,因为快速交换导丝可以在递送治疗剂期间保持留在导管管腔内。 Further, in applications where delivery of therapeutic agents, the device subject of the present invention provides a more efficient surgical procedure, because of the rapid exchange guidewire may remain held within the catheter lumen during delivery of therapeutic agents. 在某些实施例中,可扩张构件300被布置在导管的纵长轴的远端区段处。 In certain embodiments, the expandable member 300 is disposed at the distal end section of the longitudinal axis of the catheter.

[0058] 纵长轴200包括至少两个管腔,如在图4A至图4C更好地所见。 [0058] the longitudinal axis comprises at least two lumens 200, as better seen in FIG. 4C. 4A to FIG. 在一个实施例中,至少两个管腔包括膨胀管腔和分离的、专用的、独立的收缩管腔。 In one embodiment, the at least two lumens and an inflation lumen comprises a separate, dedicated, independent lumen contraction. 膨胀管腔和独立的收缩管腔与球囊300的内部部分流体连通,但总体上没有与彼此流体连通。 An inflation lumen and a separate inner part of the fluid lumen of the balloon 300 is contracted communication, but not in fluid communication with each other as a whole. 具体而言,任何加压流体(诸如二氧化碳、含有氦、氖的惰性气体之类)和加压液体(诸如盐水或造影剂之类)的膨胀流体经由膨胀管腔引入到球囊300中使球囊膨胀,并然后从球囊出来进入独立的收缩管腔。 Specifically, any pressurized fluid (such as carbon dioxide, helium containing inert gas is neon or the like) and pressurized liquid (such as saline or contrast agent or the like) of the expanded fluid is introduced into the balloon 300 via an inflation lumen manipulation ball the balloon inflated, and then out into the balloon separate from the lumen shrinkage. 膨胀流体通过流体回路的流动是单程的。 Inflation fluid flow through fluid circuit is one-way. 独立的收缩管腔允许球囊迅速收缩,并且如将在下文描述地在一个实施例中被构造用于文丘里辅助式收缩(Venturi-assisted deflation)〇 A balloon lumen discrete constriction allows rapid contraction, and as will be described hereinafter in one embodiment, is configured to assist the Venturi narrowing (Venturi-assisted deflation) square embodiment

[0059] 手柄100被布置在导管的近端端部处或在该端部附近,并容装流体回路的控制系统1000(图2和图3)。 [0059] The handle 100 is disposed in the control system at the proximal end of the catheter or in the vicinity of the end portion, and accommodating the fluid circuit 1000 (FIG. 2 and FIG. 3). 手柄100被构造用于使得医生能够轻松地借助在一些实施例中的一触式致动器101使可扩张构件300自动且顺序地膨胀和收缩。 Handle 100 is configured to enable a physician to easily make the expandable member by 101 In some embodiments, a touch of the actuator 300 to automatically and sequentially expand and contract. 这样,一触式致动器可以是开关、 按钮、杠杆或其它装置,其适于允许使用者当可扩张构件300在第一位置中或沿着第一方向被致动时使可扩张构件膨胀,并且当可扩张构件300在第二位置中或沿着第二方向被致动时使可扩张构件收缩。 Thus, one-touch actuator may be a switch, button, lever, or other means, which is adapted to allow a user to be expandable so that when the expandable member when the expandable member 300 in the first position or is actuated in a first direction , and the contraction of the expandable member when the expandable member 300 in the second position or is actuated in the second direction. 一触式致动器优点颇多。 A touch actuator lot of advantages. 它允许操作者通过轻松使用开关来容易地操纵导管装置,没有传统血管成形术导管的难处理且耗时的操作要求。 It allows an operator to easily manipulate the catheter by easily switching device, no conventional angioplasty catheter intractable requirements and time-consuming operation. 一个开关的致动加上步骤的减少以及实施后处理所需时间的相应减少,允许医生或其它干预者能够将他们的注意力和关注力更多集中在患者上,而不是如传统血管成形术导管所需的全神贯注于步骤和装置组成部件的排列。 The step of actuating a switch coupled to reduce the post-treatment, and a corresponding reduction in the time required to allow a physician or other interventions able to focus their attention and forces more concentrated on the patient, rather than as a conventional angioplasty concentrate conduit arranged in the desired steps and apparatus components.

[0060] 图5示出了对医生/干预者集中注意力要求的比较。 [0060] FIG. 5 shows a comparison of the doctor / intervener focus requirements. 本文所披露导管被表示为图5 中的"PUFF",其要求的手术步骤较少,并提供了带有触发操作的预组装装置使得医生/干预者将注意力更多地集中在患者上。 The catheter disclosed herein is expressed as in FIG. 5 "PUFF", which requires fewer steps surgery, pre-assembled and provided with means of triggering operation allows the physician / intervention will focus more on the patient. 此外,本发明所披露的设备可以由单个医生/干预者操作,而传统血管成形术装置则需要两个医生来操作。 Furthermore, the disclosed apparatus of the present invention may be operated by a single physician / intervener, traditional angioplasty apparatus is required to operate the two doctors.

[0061] 使可扩张构件300顺序地膨胀和收缩的一触式轻松操作可以通过使导管轴适应性地包括独立的膨胀管腔和分离的独立的收缩管腔来实现。 [0061] The expandable member 300 so that expansion and contraction are sequentially one-touch operation can easily be achieved by adaptively catheter shaft including an inflation lumen and a separate separate separate lumen contraction. 在一些实施例中,开关被构造成使得使用者不能让可扩张构件300过度膨胀。 In some embodiments, the switch is configured such that the user can not get over-expansion of the expandable member 300. 具体而言,系统可以包括脉冲阀,其在可扩张构件被完全膨胀时关闭通向可扩张构件的出口端口,由此防止过度膨胀。 Specifically, the system may include a pulse valve, which closes the outlet port leading to the expandable member when the expandable member is fully inflated, thereby preventing excessive expansion. 这样,当球囊被完全膨胀时,开关的进一步致动没有使球囊进一步膨胀,由此使系统"防误操作",并实现了使可扩张构件膨胀的再现性。 Thus, when the balloon is fully inflated, a further switch is not actuated to further expand the balloon, thereby making the system "misoperation", and realized that the reproducibility of the expandable member is expanded. 流体回路不需要电力或电子器件来实现球囊的膨胀或收缩、 对膨胀或收缩的致动或者膨胀流体通过回路的流动。 Fluid circuit does not require electric or electronic devices to achieve expansion or contraction of the balloon, expansion or contraction of the flow of fluid through actuating or expander circuit. 这样,当球囊完全膨胀时,开关的进一步致动没有使球囊进一步膨胀,由此使系统"防误操作",并实现了使可扩张构件膨胀的再现性。 Thus, when the balloon is fully inflated, a further switch is not actuated to further expand the balloon, thereby making the system "misoperation", and realized that the reproducibility of the expandable member is expanded.

[0062] 在一些实施例中,手柄100包括被布置在导管装置内的流体回路的控制系统1000。 [0062] In some embodiments, the handle 100 is disposed within the catheter includes a fluid circuit means a control system 1000. 控制系统1000被构造用于帮助调控贯穿导管系统的流体回路的膨胀流体,从而使可扩张构件300膨胀和收缩。 The control system 1000 is configured to help regulate the inflation fluid through a fluid circuit catheter system, such that the expandable member 300 can expand and contract. 在一些实施例中,如下文将描述地,流体回路并且尤其是独立的收缩管腔可以被构造用于诱发文丘里辅助式流动,从而使可扩张构件300迅速地收缩。 In some embodiments, as will be described, the fluid circuit and in particular a lumen discrete constriction can be configured to induce a venturi assisted flow so that the expandable member 300 may shrink rapidly.

[0063] Π .导管本体 [0063] Π. Catheter body

[0064]根据一个实施例,如图4A所示,导管包括大体上纵长的管状轴200,该轴具有处于流体连通的近端轴节段201和远端轴节段202。 [0064] According to one embodiment, as shown in FIG. 4A, the catheter comprising a generally elongated tubular shaft 200, the shaft having a proximal shaft section 201 in fluid communication with the distal end of shaft 202 and segments. 近端轴节段201和远端轴节段202可以由具有相同或相似硬度或硬度计硬度的材料形成,以便沿着导管本体提供均匀的挠性。 Proximal shaft segment 201 and a distal shaft segment 202 may be formed of a material having the same or similar hardness or durometer hardness, to provide a uniform flexibility along the catheter body. 备选地,近端轴节段和远端轴节段可以由挠性不同的材料形成,以便提供挠性沿长度变化的导管。 Alternatively, the proximal shaft segment and a distal shaft section may be formed of a flexible material different, so as to provide varying flexibility along the length of the catheter. 例如但非限制性地,近端轴节段可以由海波管形成,而远端轴可以由聚合物材料形成,以便提供沿着导管管状轴增大的挠性。 For example, but without limitation, the proximal shaft section may be formed by a hypotube, while the distal end of the shaft may be formed of a polymer material to provide increased flexibility along the catheter tubular shaft. 因而,近端轴节段和远端轴节段可以由相同的管形成,或备选地可以是两个分离的管,这两个分离的管被连接或焊接在一起以形成一体式管。 Thus, proximal shaft section and a distal shaft section may be formed of the same tube, or alternatively may be two separate tubes which are connected to two separate tubes or welded together to form a unitary tube. 导管可以包括一种或多种聚合物,或者具有不同硬度的聚合物混合物。 The catheter may include one or more polymers, or a mixture of polymers having different hardnesses.

[0065]如图4B中所示,在一个实施例中,纵长轴200包括独立的膨胀管腔203,其被构造用于提供膨胀流体至可扩张构件300的通道或流动,所述可扩张构件被布置在导管轴的远端端部202处或在该端部附近。 As shown in FIG. 4B [0065], In one embodiment, the longitudinal axis 200 includes a separate inflation lumen 203, which is configured to provide inflation fluid to the expandable member 300 or flow passage, the expandable the distal end member 202 is disposed in the catheter shaft or in the vicinity of the end portion. 纵长轴200还可以包括独立的收缩管腔204以提供第二流体流动通道,从而在收缩期间使膨胀流体从可扩张构件300流出。 The longitudinal axis 200 may further comprise a separate lumen 204 to provide a contraction of the second fluid flow passage, so that during the inflation fluid flows from the contraction of the expandable member 300. 这样,在后处理技术期间,可以有效且迅速地进行可扩张构件300的顺序膨胀和收缩以及随之发生的血液流动停止和开始。 Thus, during post-processing techniques can be effectively and rapidly sequence the expandable member 300 expands and contracts and consequent blood flow stops and starts. 例如,在系统的一个实施例中,可以在五秒或更短时间内、优选地在一秒或更短时间内、 最优选地在1/15秒或更短时间内使可扩张构件300膨胀。 For example, in one embodiment of the system may be in five seconds or less, preferably one second or less, most preferably 1/15 second or less so that expansion of the expandable member 300 . 另外,可以在五秒或更短时间内、 优选地在三秒或更短时间内、最优选地在1/4秒或更短时间内使可扩张构件收缩。 Further, in five seconds or less, preferably in three seconds or less, most preferably 1/4 seconds or less so that the expandable member contracts. 使可扩张构件迅速膨胀和收缩为后处理技术提供了使用传统血管成形术导管所不能得到的优点。 So that the expandable member expands and contracts rapidly provides the advantage of using conventional angioplasty catheter can not be obtained for the post-processing techniques. 如图6中所示,进行了对比研究来比较传统血管成形术导管和本发明导管系统的膨胀时间和收缩时间。 As shown in FIG. 6, a comparative study to compare conventional angioplasty time expansion and contraction of time the catheter and system of the present invention. 如图表中所示,血管成形术导管需要近乎五秒(4.81秒)来膨胀,而本发明主题的导管系统仅需要半秒。 As shown in the graph, the angioplasty catheter requires approximately five seconds (4.81 seconds) to the expansion, the catheter system of the subject invention requires only half a second. 因而,本发明导管膨胀起来比血管成形术导管快了近乎十倍。 Thus, the catheter of the present invention is inflated catheter almost ten times faster than angioplasty. 当对比血管成形术导管和本发明主题的导管二者所需要的收缩时间时,结果是类似的。 Contraction time when both the catheter and the angioplasty catheter contrast subject of the present invention is required, results are similar. 血管成形术导管需要约7秒(6.81秒)来收缩,而PUFF导管在一秒内收缩。 Angioplasty catheter takes about 7 seconds (6.81 seconds) to shrink, and shrink within a second conduit PUFF. 因此,对于八次循环后处理技术而言,血管成形术导管需要超过93秒(每个膨胀/收缩循环为11.65秒)来完成,而PUFF 导管设计仅在12秒(每个膨胀/收缩循环为1.5秒)内完成循环。 Thus, after eight cycles for the processing, the angioplasty catheter requires more than 93 seconds (per expansion / contraction cycle is 11.65 seconds) to complete, while PUFF catheter design only 12 seconds (per expansion / contraction cycle of cycle is completed within 1.5 seconds). 本文所描述的导管系统呈现出迅速有效的膨胀和收缩循环,并可以优化后处理。 The catheter system described herein exhibit rapid and effective expansion and contraction cycles, and post-treatment can be optimized.

[0066] 纵长轴200可以形成多种形状,例如,在一个实施例中,所述轴可以具有如图4B中所示的管状构造。 [0066] The longitudinal axis 200 may be formed in various shapes, for example, in one embodiment, the shaft may have a tubular configuration as shown in FIG 4B. 然而,可以采用本技术领域中已知的其它形状,例如椭圆形。 However, other shapes may be employed known in the art, such as elliptical.

[0067]例如,除了膨胀管腔和收缩管腔以外,纵长轴200还可以包括导丝管腔205。 [0067] For example, in addition to expansion and contraction of the lumen than the lumen, the longitudinal axis 200 may further include a guidewire lumen 205. 具体而言,导丝管腔205可以被构造成从纵长轴200的远端端部处的尖端400延伸到纵长轴200的更近端的位置,从而提供导丝上导管(over-the-wire catheter)。 Specifically, the guidewire lumen 205 can be configured to extend from the distal end 200 of the tip end portion of the longitudinal axis 400 at a position more proximal to the longitudinal axis 200, so as to provide a catheter over the guidewire (over-the -wire catheter). 或者,纵长轴200可以被形成为具有凹口(未示出),该凹口布置在纵长轴200的远端端部202与近端端部201之间的位置处,以便提供迅速交换导管。 Alternatively, the longitudinal axis 200 may be formed to have a recess (not shown), the recess longitudinal axis is disposed at a distal end 200 and proximal portion 202 between the position 201, to provide rapid exchange catheter.

[0068]根据另一个实施例,纵长轴200还可以包括药物递送管腔206-一例如药物注入管腔,其被构造用于局部地递送例如如上文所描述那些的有用制剂或其它制剂。 [0068] According to another embodiment, the longitudinal axis 200 may further comprise a drug delivery lumen 206- e.g. a drug infusion lumen, which is configured to be delivered locally, for example, those described above as useful formulation or other formulations described. 在一个实施例中,有用制剂被局部地递送到发生缺血性事件的区域。 In one embodiment, a useful formulation is delivered locally to a region of ischemic events. 在其它实施例中,导管没有药物递送管腔,取而代之地,在导管轴上布置了涂覆有药物的球囊以用于局部地递送有用制剂。 In other embodiments, a drug delivery catheter without a lumen, instead, the catheter shaft is arranged with a drug coated balloon for delivery of beneficial agents locally. [0069]在一些实施例中,纵长轴200包括四个分离并独立的管腔(例如,膨胀管腔203、收缩管腔204、导丝管腔205和药物递送管腔206)。 [0069] In some embodiments, the longitudinal axis 200 and comprises four separate independent lumen (e.g., inflation lumen 203, shrink the lumen 204, guidewire lumen 205, and a drug delivery lumen 206). 然而,可以采用其它构造。 However, other configurations may be employed. 在一些实施例中, 管腔的直径具有不同的尺寸。 In some embodiments, the diameter of the lumen having different sizes. 例如,在一些实施例中,收缩管腔直径尺寸大约是膨胀管腔直径尺寸的两倍。 For example, in some embodiments, the lumen diameter shrinkage is approximately twice the diameter of the inflation lumen. 在一个实施例中,如图4C中所示,膨胀管腔的直径203d约为0.100mm,收缩管腔的直径204d约为0.200mm,导丝管腔的直径205d约为0.400mm,并且膨胀管腔的直径206d 约为0.300_。 In one embodiment, as shown in FIG. 4C, the inflation lumen diameter of about 0.100 mm 203d, 204d shrinkage lumen diameter of about 0.200mm, the diameter of the guide wire lumen 205d is about 0.400 mm, and the expansion pipe the diameter cavity approximately 0.300_ 206d. 因此,每个管腔都可以构造成根据期望具有不同尺寸的直径。 Thus, each lumen can be configured as desired sizes having different diameters.

[0070] 在一些实施例中,如图7A和图7B中所示,纵长轴200可以通过单次挤压而形成有多个管腔,例如如上文所描述的四个管腔。 [0070] In some embodiments, as shown in FIG. 7A and 7B, the longitudinal axis 200 may be formed with a plurality of lumens, e.g. four lumens as described above by a single pressing. 如进一步示出地,四个管腔可以在挤压过程中被取向,使得留在管腔之间的、被挤压的聚合物腹板208形成"工字梁"横截面。 As further shown, the four lumens may be oriented in the extrusion process, so that left between lumen, extruded polymer web 208 is formed a cross-sectional "beams." 工字梁构造使得强度增加以有助于导管追踪通过脉管系统而无需轴上的多个单独的管和/或编织部,在一些实施例中,工形梁构造可以被制成为具有与编织轴相等的强度和比编织导管轴更小的轮廓。 I-beam construction increases the strength such that the catheter to aid in tracking multiple individual tubes and / or the braided portion through the vasculature without the shaft, in some embodiments, the I-shaped beam configuration may be made with the knitting axis intensity ratio equal braided catheter shaft and smaller profile. 因此,图7B中绘出的工字梁构造允许导管总体上更小,并允许导管本体内有多个专用管腔。 Thus, the configuration of beams depicted in FIG. 7B allows a smaller overall catheter body allow the catheter and a plurality of dedicated lumens.

[0071] 工字梁构造提供了用于抵抗在聚合物腹板208的平面中的弯曲和剪切的有效形式。 [0071] I-beam construction provides an effective form to resist bending and shear in the plane of the polymer in the web 208. 这样,多个管腔203、204、205、206被构造为借助被布置在这些管腔之间的聚合物腹板208被物理上彼此间隔开的独立管腔。 Thus, a plurality of lumens 203,204,205,206 by means of independent lumen is configured to be disposed between the lumens polymer web 208 is physically spaced apart from each other. 工字梁形状的优点在于,导管轴在导管沿着特定方向被拉动时更能抵抗弯曲。 Beam shape word advantage that the catheter shaft when the catheter is pulled more resistant to bending in a particular direction.

[0072] 在一些实施例中,尺寸不同的管腔在挤压过程中被布置或取向以形成图案,使得尺寸最大的管腔205邻近尺寸较小的管腔203、管腔204、管腔206中的每个管腔(如图4B和图4C中所示),从而被设置在管腔203、管腔204和管腔205之间的聚合物腹板208形成工字梁图案(如图7A和图7B中所示)。 [0072] In some embodiments, the lumen of different sizes are disposed or oriented in the extrusion process to form a pattern, such that the maximum dimension of the lumen 205 adjacent the smaller size of the lumen 203, lumen 204, lumen 206 each of the lumen (shown in Figure 4B and FIG. 4C), so as to be disposed in the lumen 203, the polymer web 205 between lumen 204 and lumen 208 forming an I-beam pattern (FIG. 7A and FIG. 7B). 在一些实施例中,被挤压的聚合物腹板208的厚度基本上等同于轴的弯曲力矩。 In some embodiments, the thickness of the polymer web 208 is pressed substantially equivalent bending moment to the shaft. 当力矩被施加到结构元件上时存在于该结构元件中的弯曲力矩使元件弯曲。 When a torque is applied to the structural elements present in the bending moments of the structural elements of the element is bent. 力矩和转矩总体上被测定为力与距离的乘积,所以它们具有单位牛•米(N · m),或英尺镑力(ft-lbf)。 The torque and the torque to be measured is generally the product of force and distance, they have a unit N • m (N · m), or a pound force feet (ft-lbf). 这样,被认为的是,纵长轴200将相等地抵抗弯曲,而不管对导管轴的弯曲方向如何。 Thus, to be considered that the longitudinal axis 200 will resist bending equally, regardless of the direction of bending of the catheter shaft. 还被认为的是,没有这些特征的导管轴将依据血管内部的取向弯曲到不同的程度。 Also considered that none of these features will be based on the orientation of the catheter shaft is bent inside the vessel to different degrees. [0073] 纵长轴200还可以包括远端尖端400(图4A),其具有与导管本体的远端端部202邻接或重叠的近端端部。 [0073] the longitudinal axis 200 may further include a distal tip 400 (FIG. 4A), having a proximal end and a distal end portion of the catheter body 202 adjacent to or overlapping. 在一个实施例中,导管尖端400包括一个或多个管腔。 In one embodiment, the catheter tip 400 comprises one or more lumens. 例如,在一个实施例中,尖端400可以包括与纵长轴200的导丝管腔205对准的第一管腔以及与注入管腔206 对准的第二管腔。 For example, in one embodiment, the tip 400 may include a guidewire lumen with a longitudinal axis 200 of the first lumen 205 is aligned with the injection lumen and a second lumen 206 aligned. 导丝管腔205与通过被布置在导管轴的远端端部202处的导管尖端400的管腔对准。 Aligned with the guidewire lumen 205 through the lumen 202 at the distal end of the catheter shaft is disposed in the catheter tip 400. 这些对准的管腔允许导管跨接在导丝上。 These alignment across allow the catheter lumen over the guidewire. 此外,一旦导丝被适当地插入,导丝可以被移除,并且流体可以经管腔通过。 Further, once the guidewire is properly inserted, the guide wire may be removed and the fluid can be administered through the chamber.

[0074]在一个实施例中,尖端400可以由比导管材料更软的材料形成,使得尖端具有足够的裂断强度来抵抗插入期间的压曲(buckling),却又具有足够的挠性从而在没有导丝的情况下当尖端在身体中经受轴向或径向载荷时发生变形。 [0074] In one embodiment, the tip 400 may be formed of a softer material than the catheter material, so that the tip has sufficient column strength to resist buckling (buckling) during insertion, but flexible enough so as not when the case is deformed when the tip of the guidewire is subjected to an axial or radial loads in the body. 导管纵长轴200被构造成使得导丝在外科手术程序期间能够在管腔205内通过并纵向地平移。 The longitudinal axis of the catheter 200 is configured such that the guidewire through during a surgical procedure within the lumen 205 and longitudinally translate.

[0075]纵长轴200可以由各种材料制造,所述材料包括金属、塑料和复合材料。 [0075] the longitudinal axis 200 may be fabricated from a variety of materials, the material including metals, plastics and composites. 在一个实施例中,近端轴201被制造为金属管,例如为不锈钢海波管,并且可以涂覆有诸如PTFE的聚合物材料。 In one embodiment, the proximal end of shaft 201 is made as a metal pipe, for example, stainless steel hypotube and may be coated with a polymeric material such as PTFE. 金属管也可以利用一层或多层塑性材料通过一种或多种工艺加以覆盖,所述工艺包括共同挤压、浸渍、热收缩、以及静电和热涂覆。 Metal tube may also use one or more layers of plastic material to be covered by one or more processes, the process comprising co-extrusion, dipping, thermal shrinkage, and thermal and electrostatic coating. 在另一个实施例中,纵长轴200被制造为塑料管。 In another embodiment, the longitudinal axis 200 is made as a plastic tube. 适于用在导管管中的材料包括但不限于:聚氨酯(PU),例如Tecoflex、 Pellethene、Bionate、corethane、Elasteon及其混合物;聚乙稀(PE),例如PET、PBT、PVDF、 Teflon、ETFE及其混合物;聚烯烃,例如HDPE、PE、LDPE、LLDPE、聚丙烯及其混合物;聚酰亚胺;聚酰胺;所有级别的尼龙,例如尼龙11、尼龙12、尼龙6,6、尼龙6、尼龙7,11、尼龙11,12、 及其混合物;嵌段共聚物;PEBA类型聚合物,例如ELY、PEBAX、Ubes ta及其混合物、以及生物可降解的聚合物。 Suitable for use in the catheter tube materials include, but are not limited to: a polyurethane (PU), e.g. Tecoflex, Pellethene, Bionate, corethane, Elasteon and mixtures thereof; polyethylene (PE), e.g. PET, PBT, PVDF, Teflon, ETFE and mixtures thereof; polyolefins, e.g. HDPE, PE, LDPE, LLDPE, polypropylene, and mixtures thereof; polyimides; polyamides; all levels nylon, such as nylon 11, nylon 12, nylon 6,6, nylon 6, nylon 7,11, nylon 11,12, and mixtures thereof; block copolymer; PEBAs types of polymers, e.g. ELY, PEBAX, Ubes ta and mixtures thereof, and biodegradable polymer.

[0076]合适材料还包括上述材料的混合物以及任何复合材料,如这些材料的双层、三层、 多层。 [0076] Suitable materials also include mixtures of the above as well as any composite materials, these materials such as bilayer, trilayer, multilayer. 例如,导管轴可以由管制造,该管包括由尼龙制成的外层和由诸如聚乙烯或PTFE的润滑材料制成的内层。 For example, the catheter shaft may be manufactured from a tube, the tube comprising an inner layer and an outer layer made of a lubricious material such as polyethylene or PTFE is made of nylon. 也可以在导管轴的层内或层之间包含有金属编织物或非金属编织物。 May be within the layer of the catheter shaft comprises a metal or non-metal braid or braid between the layers. [0077]导管尖端400可以被构造用于在纵长轴200与壁之间(纵长轴200在外科手术期间可以抵着该壁推动)提供无损伤接触。 [0077] The catheter tip 400 may be configured between the longitudinal axis 200 of the wall (the longitudinal axis 200 during a surgical procedure can be pushed against the wall) to provide a contact without damage. 导管尖端可以构造为软尖端,该软尖端在一些实施例中可以由软套管组成,软套管被固定在远端端部202上并且延伸超过该端部,或者备选地, 软套管被固定在纵长轴200的管腔上并且延伸超过该管腔。 The catheter tip may be configured as a soft tip, the soft tip In some embodiments, the sleeve may be composed of a soft, flexible sleeve is fixed to the distal end portion 202 and extends beyond the end portion, or alternatively, the soft cannula It is fixed to the longitudinal axis 200 and a lumen extending beyond the lumen. 典型地,软尖端通过焊接工艺固定,但是在本发明的范围内还包括其它的固定技术,例如粘接。 Typically, the soft tip is fixed by a welding process, but within the scope of the present invention further comprises other fixing techniques, such as adhesive. 用于套管的合适材料可以选自适于制造纵长轴200的任何材料。 Suitable materials for the sleeve may be made of any material selected from the longitudinal axis 200 is adapted. 套管可以由比纵长轴200更软的材料制造,并且可以由与可扩张构件300相同的材料形成或由不同材料形成,例如,由参照纵长轴200所描述材料的材料或者组合中的任一种形成。 The sleeve may be a softer material than the longitudinal axis 200, and may be expandable by a member 300 formed of the same material or formed of different materials, for example, any of the materials described with reference to the longitudinal major axis 200 of material or combination A method of forming. 在一个实施例中,制造套管的材料的基本组成与可扩张构件300材料或纵长管200材料相同,但是制造套管的材料的肖氏硬度计硬度低于可扩张构件300材料或纵长管200材料。 In one embodiment, the basic composition and the expandable sleeve member material 300 manufactured material or longitudinal tube 200 is the same material, but the manufacturing materials of the sleeve is less than the Shore durometer hardness of the expandable member 300 or elongated material 200 tube material. 在另一个实施例中,套管可以由PEBAX55D聚合物和PEBAX63D 聚合物的混合物制造。 Embodiment, the sleeve may be manufactured from a mixture of polymer and PEBAX63D PEBAX55D In another embodiment the polymer. 本领域的技术人员将认识到,套管可以由根据上文所描述材料的各种其它材料制造,例如由聚氨酯、聚乙烯、聚烯烃、聚酰亚胺、聚酰胺(如尼龙)、嵌段共聚物或者这些材料的混合物、合成物或由这些材料的双层或多层来制造。 Those skilled in the art will recognize, the sleeve may be formed from a variety of other materials according to the above-described materials, for example polyurethane, polyethylene, polyolefins, polyimides, polyamides (such as nylon), block copolymer, or mixtures of these materials, or composite materials produced from these two or more layers.

[0078] m·可扩张构件 [0078] m · expandable member

[0079] 根据本发明的一个实施例,可扩张构件300是聚合物球囊。 [0079] According to one embodiment of the present invention, the expandable balloon member 300 is a polymer. 优选地,球囊300是顺应性球囊。 Preferably, the balloon 300 is a compliant balloon. 与被构造用于提供新的圆形敞开管腔的典型血管成形术球囊不同,本实施例的聚合物球囊300应当具有足够的顺应性,以便与血管的解剖结构吻合。 Typical blood vessels are configured to provide a new open circular lumen balloon angioplasty different polymeric balloon embodiment 300 should be sufficiently compliant so as to coincide with the vascular anatomy. 这样,球囊300可以堵塞具有从约2mm至约30mm的直径的血管,根据应用场合是用于冠状血管、大脑血管或外周血管的情况而定。 Thus, the balloon 300 can be blocked from the vessel having a diameter of about 2mm to about 30mm, depending on the application are the coronary vessels, cerebral vascular or peripheral vascular for the case may be. 在一个实施例中,对于冠状血管或大脑血管应用场合而言,球囊可以在约0.5atm至2atm的压力下堵塞具有从约2mm至约4.5mm的直径的血管。 In one embodiment, for coronary or cerebral vascular applications, the balloon may have a blockage in the blood vessel diameter from about 4.5mm to about 2mm at a pressure of from about 0.5atm to 2atm. 对于外周血管应用场合而言,球囊可以堵塞具有从约4mm至约30mm的直径的血管,或人体的任何管腔孔口(此处的流体流动堵塞会是治疗性的)。 For peripheral applications, the balloon may have a vascular blockage from a diameter of from about 4mm to about 30mm or any body lumen aperture (here fluid flow blockage can be therapeutic).

[0080] 在一个实施例中,球囊是"一种尺寸符合所有尺寸"的球囊。 [0080] In one embodiment, the balloon is "one size meets all size" balloon. 具体而言,球囊必须由顺应性聚合物材料形成。 Specifically, the balloon must be formed of a compliant polymer material. 例如但非限制性地,顺应性球囊300当在尺寸狭窄的血管内膨胀时可以拉长,而当在较大或较宽的血管内膨胀时可以具有球形形状。 For example, but not limitation, a compliant balloon 300, when inflated within the dimensions can be elongated narrow blood vessels, and when larger or wider expanded within the blood vessel may have a spherical shape. 因而,球囊能够与血管吻合。 Thus, the balloon can coincide with the vessel. 因此,医生不需要在进行后处理之前测量患者的动脉以使球囊300的大小适合患者。 Thus, physicians need not measured prior to performing the treatment of patients after arterial balloon 300 so that the size appropriate for the patient.

[0081 ]在一个实施例中,球囊300被安装至导管的纵长轴200。 [0081] In one embodiment, the balloon 300 is mounted to the catheter longitudinal axis 200. 球囊300包括中空的内部部分,该内部部分限定出膨胀通道,膨胀通道纵向地延伸穿过该内部部分,以便从纵长轴200 的膨胀管腔203接收膨胀流体。 The balloon 300 includes a hollow interior portion, the inner portion defining an inflation channel, the expansion channel extending longitudinally through the inner portion to receive inflation fluid from the longitudinal axis 203,200 of the inflation lumen. 在一个实施例中,球囊300的近端部分可以被构造成在球囊300的近端端部和远端端部处径向向内地渐缩。 In one embodiment, the proximal portion of the balloon 300 may be configured to taper inwardly in the radial direction of the balloon proximal end 300 and a distal end. 球囊300的近端端部和远端端部的尺寸被设定,以便安装和密封到纵长轴200的相应部分,而球囊的内部部分被构造成用于从未扩张的第一状态选择性地膨胀到扩张的第二状态。 Size proximal end and a distal end portion of the balloon 300 is set, for mounting and sealing to a respective portion of the longitudinal axis 200, while the inner portion of the balloon is configured for a first state to the unexpanded selectively expands to a second expanded state. 因此,扩张状态中的球囊300的横向横截面尺寸显著地大于球囊的近端端部和远端端部的向内渐缩端部部分的横向横截面尺寸。 Inwardly proximal end and a distal end portion and therefore, the transverse cross-sectional dimension of the balloon 300 in the expanded state of the balloon is significantly greater than the transverse cross-sectional dimension of the tapered end portion.

[0082]当球囊300被安装至纵长轴200时,纵长轴200的膨胀管腔203与球囊300的膨胀通道处于流体连通。 [0082] 300 when the balloon 200 is mounted to the longitudinal axis, the longitudinal axis 203 of the balloon inflation lumen 200 of the inflatable channel 300 in fluid communication. 因此,通过如下文所描述地操作在导管系统的近端端部处的一触式控制系统,可扩张构件300的内部部分可以从第一状态选择性地膨胀到膨胀的第二状态。 Thus, as described below by operation of a touch control system at the proximal end of the catheter system, the interior portion of the expandable member 300 may be selectively expanded from a first state to a second expanded state.

[0083]纵长轴200的远端轴202延伸通过球囊300的膨胀通道,其中导管的远端端部终止于球囊300的远端端部的远端处。 [0083] The distal end of the shaft 202 longitudinal axis 200 extending through balloon inflation channel 300, wherein the distal end of the catheter terminates in a distal end of the distal end portion 300 of the balloon. 如在图4A中最好地示出,远端轴202纵向地延伸通过球囊300的内部部分,并限定出导丝管腔205的远端部分,其中导丝管腔205的远端部分终止于纵长轴200的远端端部处的远端端口处。 As best shown in FIG. 4A, the distal end of the shaft 202 extending longitudinally through the interior of the balloon portion 300, and defines a distal portion of the guide wire lumen 205, wherein the distal end portion of guidewire lumen 205 terminates to the longitudinal axis at a distal port at the distal end portion 200. 因此,导丝(未示出)可以延伸通过纵长轴200的导丝管腔205,并且通过导管远端端部的远端端口出来。 Thus, the guide wire (not shown) may extend through the guidewire lumen 205 longitudinal axis 200, and out through the distal port of the distal end of the catheter. 这种通道使得导管能够沿着可以被策略地布置在血管中的导丝前进。 Such a channel so that the catheter can be advanced along the guidewire may be strategically disposed in the blood vessel.

[0084] 球囊300可以形成各种形状,如图8A和8B中所示。 [0084] The balloon 300 may be formed in various shapes, 8A and 8B. 如图所示,球囊300的形状可以是球形、柱形、或多边形。 As illustrated, the shape of the balloon 300 may be spherical, cylindrical, or polygonal. 可以选择如将在本技术领域中已知的各种聚合物来形成球囊300。 You may be selected as known in the art the balloon 300 is formed of various polymers. 然而,球囊材料应当具有足够的顺应性,使得球囊300可以与血管的形状吻合。 However, the balloon material should have sufficient compliance such that the balloon 300 can match the shape of the blood vessel.

[0085] 在一个实施例中,球囊300可以由诸如ΤΕ€ΟΤΪΙΑΝΕ:®(Ώιθηιιθ(ϋε8)的聚氨酯材料形成。TEGOTHAJME®,是热塑性芳香族聚醚型聚氨酯,其由亚甲基二异氰酸酯(MDI)、聚四亚甲基醚二醇(PTMEG)和1,4丁二醇扩链剂合成。TECOTHΑΝΈ®.等级1065D目前是优选的,其具有65D的肖氏硬度计硬度、约为300%的断裂伸长率和约lOOOOpsi 的高屈服拉伸强度。然而,可以使用其它适当的等级,包括TE€OTHAIVI:®1〇75D,其具有约D 7 5的肖氏硬度。其它适当的顺应性聚合物材料包括:ENG AGE® (DU Ρ ο nt D 0 W Elastomers(乙稀α-稀经聚合物)和EXACT® (Exxon Chemical),二者都是热塑性聚合物;弹性体硅胶;和乳胶。 [0085] In one embodiment, the balloon 300 may be formed such ΤΕ € ΟΤΪΙΑΝΕ: forming .TEGOTHAJME® ® (Ώιθηιιθ (ϋε8) polyurethane material is a thermoplastic aromatic polyether polyurethane which methylene diisocyanate ( MDI), polytetramethylene ether glycol (of PTMEG) and 1,4 butanediol chain extender synthesis .TECOTHΑΝΈ®. grade 1065D is presently preferred, having a Shore durometer of 65D, is about 300% high tensile strength at yield elongation at break of about lOOOOpsi However, other suitable grades, including TE € OTHAIVI: ®1〇75D, having a Shore hardness of about D 7 5 other suitable polymeric compliance. materials include: ENG AGE® (DU Ρ ο nt D 0 W elastomers (ethylene α- polymer-lean) and EXACT® (Exxon Chemical), both of which are thermoplastic polymers; silicone elastomers; and latex.

[0086] 顺应性材料可以是交联的或非交联的。 [0086] compliant material may be cross-linked or non-crosslinked. 当前优选的聚氨酯球囊材料不是交联的。 The current preferred polyurethane balloon material is not crosslinked. 通过将球囊顺应性材料交联可以控制膨胀球囊的最终尺寸。 By compliant material, the balloon can be controlled inflation of the balloon crosslinked final size.

[0087] 可以使用包括热处理和电子束曝光在内的传统交联技术。 [0087] using conventional crosslinking techniques including electron beam exposure and a heat treatment including a. 在交联、初始加压、扩张和预收缩后,球囊将由此响应于给定的膨胀压力以受控方式扩张至可再现的直径。 In the crosslinking, the initial pressure, after pre-expansion and contraction, whereby the balloon in response to the inflation pressure of a given diameter expands to reproduce in a controlled manner.

[0088]在一个实施例中,球囊300由诸如硅酮-聚氨酯共聚物的低拉伸定型聚合物形成。 [0088] In one embodiment, the balloon 300 such as silicone - polyurethane copolymer formed of low tensile styling polymers. 优选地,硅酮-聚氨酯是醚聚氨酯,并且尤其是脂肪族醚聚氨酯,例如PURSIL AL575A和PURSIL AL10(Polymer Technology Group)和ELAST-E0N3_70A(Elastomedics),它们是娃酮聚醚聚氨酯共聚物,并且尤其是脂肪族醚聚氨酯硅氧烷共聚物。 Preferably, the silicone - polyurethane is a polyurethane ether, an aliphatic ethers and in particular polyurethanes, e.g. PURSIL AL575A and PURSIL AL10 (Polymer Technology Group), and ELAST-E0N3_70A (Elastomedics), which is one polyether polyurethane copolymer baby, and in particular It is an aliphatic ether urethane siloxane copolymer.

[0089]在备选实施例中,低拉伸定型聚合物是双烯聚合物。 [0089] In an alternative embodiment, a low tensile styling polymers are diene polymers. 可以使用各种适当的双烯聚合物,例如但不限于异戊二烯,例如AB和ΑΒΑ聚(苯乙烯-嵌段-异戊二烯)、氯丁橡胶、AB和ΑΒΑ聚(苯乙烯-嵌段-丁二烯),例如苯乙烯丁二烯苯乙烯(SBS)和苯乙烯丁二烯橡胶(SBR) 及1,4-聚丁二烯。 May use various suitable diene polymers, such as, but not limited to isoprene, e.g. ΑΒΑ AB and poly (styrene - block - isoprene), chloroprene rubber, ΑΒΑ AB and poly (styrene - block - butadiene), such as styrene butadiene styrene (SBS) and styrene butadiene rubber (SBR) and 1,4-polybutadiene. 双烯聚合物可以是异戊二烯,其包括异戊二烯共聚物和异戊二烯嵌段共聚物,例如聚(苯乙烯-嵌段-异戊二烯)。 Diene can be isoprene polymer comprising isoprene copolymers and isoprene block copolymers, such as poly (styrene - block - isoprene). 当前优选的异戊二烯是苯乙烯-异戊二烯-苯乙烯嵌段共聚物,例如可从Kraton Inc获得的Kratonll61K。 Presently preferred is isoprene styrene - isoprene - styrene block copolymer, e.g. Kratonll61K available from Kraton Inc. 然而,可以使用各种适当的异戊二稀,包括可从Apex Medical获得的HT200、可从Kraton获得的Kraton R310及可从Dupont Elastomers获得的异戊二稀(即2-甲基-1,3-丁二稀)。 However, various suitable isoprene, including HT200 available from Apex Medical, available from Kraton Kraton R310 and isoprene, available from Dupont Elastomers (i.e., 2-methyl-1,3 - butadiene). 本发明中有用的氯丁橡胶等级包括可从Apex Medical获得的HT501和可从Dupont Elastomers获得的氯丁橡胶(即聚氯丁二稀),包括可从Dupont Elastomers获得的氯丁橡胶G型、W型、T型和A型。 Useful in the invention include polychloroprene levels HT501 available from Apex Medical and neoprene (i.e., polychloroprene butadiene), include neoprene-type G, available from Dupont Elastomers available from Dupont Elastomers, W type, T type and A type.

[0090] 在一个实施例中,聚合物材料是顺应性材料,例如但不限于:聚酰胺/聚醚嵌段共聚物(通常称为PEBA或聚醚-嵌段-酰胺)。 [0090] In one embodiment, the polymeric material is a compliant material, such as, but not limited to: polyamide / polyether block copolymers (PEBA or commonly referred to as polyether - block - amide). 优选地,嵌段共聚物的聚酰胺和聚醚节段可以通过酰胺或酯链联接。 Preferably, the polyether and the polyamide segments of the block copolymer may be coupled through an amide or ester linkage. 聚酰胺嵌段可以选自本技术领域中已知的各种脂肪族或芳香族聚酰胺。 The polyamide blocks may be selected from a variety of known art aliphatic or aromatic polyamide. 优选地,聚酰胺是脂肪族的。 Preferably, the aliphatic polyamides. 一些非限制性示例包括尼龙12、尼龙11、尼龙9、尼龙6、尼龙6/12、尼龙6/11、尼龙6/9和尼龙6/6。 Some non-limiting examples include nylon 12, nylon 11, nylon 9, nylon 6, nylon 6/12, nylon 6/11, nylon 6/9 and nylon 6/6. 优选地,聚酰胺是尼龙12。 Preferably, the polyamide is nylon 12. 聚醚嵌段可以选自本技术领域中已知的各种聚醚。 Polyether block may be selected from various known in the art polyethers. 聚醚节段的一些非限制性示例包括聚(四甲撑二醇)、四亚甲基醚、聚乙二醇、聚丙二醇、聚(五甲基醚)和聚(六甲基醚)。 Some non-limiting examples of the polyether segment include poly (tetramethylene glycol), polytetramethylene ether glycol, polyethylene glycol, polypropylene glycol, poly (pentamethyl ether) and poly (ether Rokko). 也可以使用可从市场上获得的PEBA材料,例如由Arkema(法国)供应的PEBAX®材料。 You can also use PEBA materials available on the market, such as PEBAX® material Arkema (France) supply. 用于从聚酰胺/聚醚嵌段共聚物形成球囊的各种技术是在本技术领域中已知的。 Various techniques for forming a balloon from a polyamide / polyether block copolymers are known in the art. 在Wang的美国专利No. 6406457中披露了一个这种示例,该专利所披露的内容通过引用并入此文中。 One such example is disclosed in Wang, U.S. Patent No. 6406457, the disclosure of which patent is incorporated by reference in this text.

[0091] 在另一个实施例中,球囊材料由聚酰胺形成。 [0091] embodiment, the balloon is formed from a polyamide material in another embodiment. 优选地,聚酰胺具有相当的拉伸强度,甚至在折叠和打开之后也能防止形成针孔(pin-holing),并且总体上具有耐刮伤性,例如在Pinchuk的美国专利No. 6500148中披露的那些聚酰胺,该专利所披露的内容通过引用并入此文中。 Preferably, the polyamide having a considerable tensile strength, even after folding and opening can be prevented the formation of pinholes (pin-holing), scratch resistance and has a generally, for example, disclosed in U.S. Patent No. 6500148 Pinchuk in those polyamides, disclosure of this patent is incorporated by reference in this context. 适用于球囊的聚酰胺材料的一些非限制性示例包括尼龙12、尼龙11、尼龙9、尼龙69和尼龙66。 Some non-limiting examples of suitable balloon materials include polyamides nylon 12, nylon 11, nylon 9, nylon 69 and nylon 66. 优选地,聚酰胺是尼龙12。 Preferably, the polyamide is nylon 12. 在又一个实施例中,球囊300由若干不同的层构成,每个层都是不同的聚酰胺或者聚酰胺/聚醚嵌段共聚物。 In yet another embodiment, the balloon 300 consists of several different layers, each layer is different polyamides or polyamide / polyether block copolymers.

[0092] 在另一个实施例中,球囊300被设计成具有用于膨胀的最小体积和与血管壁的最小接触。 [0092] embodiment, the balloon 300 is designed to have a minimum volume for expansion and minimal contact with the vessel wall in another embodiment. 如图8C中所示,球囊可以具有球茎状构造。 As shown in FIG 8C, the balloon may have a bulbous configuration. 如图所示,球囊可以经由球囊肩部与导管轴相关联。 As illustrated, the balloon via a balloon catheter and associated shaft shoulder. 球囊的锥形部到球囊直径最大点并且可以是渐变的和/或陡峭的以最小化与血管壁的接触。 The tapered portion of the balloon to the maximum spot diameter of the balloon and may be graded and / or steep to minimize contact with the vessel wall. 另外,球囊优选地由高度顺应性的材料形成,例如但不限于具有45至50的硬度计硬度的PEBAX®、硅酮或其它具有高度顺应性的热塑性弹性体。 Further, the balloon is preferably formed from a highly compliant material such as but not limited to PEBAX® having a durometer hardness of 45 to 50, silicone, or other thermoplastic elastomers having high degree of compliance. 在某些实施例中,球囊具有可变的最大直径,该最大直径可以通过改变用于使球囊膨胀的膨胀流体的体积而加以控制。 In certain embodiments, the balloon has a maximum diameter variable by changing the diameter of the maximum volume of inflation fluid for inflating the balloon to be controlled. 例如,最大直径可以通过控制膨胀流体的引入而在约2mm与5mm之间变化。 For example, the maximum diameter may vary between about 2mm and 5mm by controlling the introduction of inflation fluid. 膨胀和收缩速率还可以被优化。 The rate of expansion and contraction may also be optimized. 由于球囊的形状被设定成是基本上非柱形的形式,球囊将具有与典型半顺应性或非顺应性球形球囊相比较少的内部体积来达到相同的最大直径。 Due to the shape of the balloon is set to be substantially non-cylindrical form, the balloon having an internal volume compared to the typical semi-compliant or non-compliant balloon-spherical less to achieve the same maximum diameter. 减小的内部体积可以导致更快的膨胀和收缩速率。 A reduced internal volume can result in a faster rate of expansion and contraction. 在一个实施例中,球囊肩部可以在与导管轴结合之前被倒置。 In one embodiment, the balloon shoulder may be inverted before combining with the catheter shaft. 在该方面中,锥形部的坡度被最大化,这进一步减小了球囊在膨胀时与血管壁的接触长度。 In this aspect, the slope of the tapered portion is maximized, which further reduces the length of the balloon when inflated in contact with the vessel wall.

[0093] 在另一个实施例中,球囊包括沿着其弯曲形状的多个螺旋部。 [0093] embodiment, the balloon comprises a plurality of coil portions along the curved shape in other embodiments. 这些螺旋部被设置用于将球囊在初始更好地折叠,并在被插入目标对象血管中期间更好地沿着导引导管追踪。 These coil portions are provided for folding the balloon in the initial better and better tracking along the guide catheter during vessel is inserted into the target object. 在一个实施例中,球囊在鼓起或成形时没有螺旋部。 In one embodiment, when the balloon portion does not bulge or spiral shaped. 可以通过将球囊的一侧紧固(例如, 焊接)到导管轴再扭转球囊材料以形成螺旋形状并在保持扭转构造的同时将球囊的相对一侧固定(例如,焊接)到导管轴来形成螺旋。 You can secure one side of the balloon (e.g., welded) to the balloon catheter shaft material and then twisted to form a spiral shape and structure while maintaining the torsion of the opposite side of the balloon is fixed (e.g., welded) to the catheter shaft to form a spiral. 然而,顺应性球囊典型地在初始膨胀之后失去其形状,通过以上述方式扭转顺应性球囊可以甚至在球囊初始膨胀之后也维持螺旋形状。 However, compliant balloons typically lose their initial shape after expansion, even after the initial expansion of the balloon is maintained in a spiral shape by twisting the above-described manner compliant balloon. 球囊被构造成在收缩期间沿着凹槽再折叠,这使再折叠的球囊具有较小的轮廓。 The balloon is then folded along the groove configured during contraction, so that in the folded balloon which has a lower profile.

[0094] 在又一个实施例中,如图8E至图8G中所示,球囊可以是带有凹坑的球囊(fluted catheter)300〃'。 [0094] In yet another embodiment, as shown in Fig. 8E to 8G, the balloon may be a balloon with pits (fluted catheter) 300〃 '. 在图8E中示出带有凹坑的球囊的透视图。 In FIG. 8E shows a perspective view of the balloon with pits. 球囊包括沿着球囊表面在轴向方向上的纵向凹槽。 The balloon comprises a longitudinal groove along the balloon surface in the axial direction. 凹槽产生出带有凹坑的球囊表面和褶皱部,球囊由于凹槽的区域所提供的硬度差而沿着该褶皱部再折叠。 Generating groove portion and fold the balloon surface with a pit, since the hardness difference balloon region of the recess being provided along the pleated portion refolding. 在一个实施例中,凹槽沿着球囊表面的最大直径布置。 In one embodiment, the maximum diameter of the recess arranged along the balloon surface. 在一个实施例中,球囊包括沿着球囊表面的最大直径的多个凹槽。 In one embodiment, the maximum diameter of the balloon comprises a plurality of grooves along the balloon surface. 褶皱包括横向于球囊周向轴线成形的纵向凹槽,如在图8F中所示。 Fold transversely to the longitudinal groove comprises a balloon shaped circumferential axis, as shown in FIG. 8F. 球囊可以具有第一锥形部和沿着相反方向的第二锥形部(例如,近端锥形部和远端锥形部)。 The balloon may have a first tapered portion and a second tapered portion (e.g., proximal and distal tapered portions tapered portion) in the opposite direction. 第一锥形部和第二锥形部在球囊表面的最大直径处相交。 A first tapered portion and a second tapered portion intersects the surface of the largest diameter of the balloon. 在一个实施例中,纵向凹槽沿着球囊的第一锥形部和第二锥形部布置。 In one embodiment, the longitudinal groove disposed along the first tapered portion of the balloon and a second tapered portion. 凹槽的形状可以充分地变化。 Shape of the grooves can vary substantially. 例如,凹槽可以具有基本上"U"形或"V"形的形状、圆形形状或其它形状,所述形状提供改变的硬度以促进球囊的有效再折叠。 For example, the groove may have substantially a "U" or "V" shape, a circular shape or other shapes which provide an altered stiffness to facilitate efficient refolding of the balloon.

[0095] 根据一些实施例,球囊300可以由单个聚合物层构成,或者备选地可以是多层化球囊,例如在1811丨(^的美国专利如.5478320、1^〇«3的美国专利如.5879369或1^6的美国专利No. 6620127中描述的那些,这些专利所披露的内容通过引用并入此文中。 [0095] According to some embodiments, the balloon 300 may be constituted by a single polymeric layer, or alternatively may be a multilayered balloon, for example, in U.S. Patent No. 1811 Shu (^ ^ square as .5478320,1 «3 those disclosed in U.S. Patent No. 6,620,127 are described as 1 ^ 6 or .5879369 U.S. Patent No. disclosed in the incorporated herein by reference.

[0096] IV.手柄和流体回路 [0096] IV. Handles fluid circuit and

[0097] 如上文所描述地,导管系统包括手柄100,该手柄大体上布置在导管的近端端部处或在该端部附近。 [0097] As described above, the catheter system 100 includes a handle, the handle is generally disposed near the proximal end of the catheter or at the end portion. 手柄的尺寸和形状被设定成能够被舒适地接纳在医师手中。 The size and shape of the handle is set to be comfortably received in the hands of the physician. 手柄100可以包括具有各种形状和构造的外壳,如图9C至图9R中所示。 A housing having a handle 100 may comprise a variety of shapes and configurations, as shown in FIG. 9C to FIG. 9R. 在一个实施例中,手柄100被不可移除地附装到导管,从而系统成为需要在使用之前组装的一体式装置。 In one embodiment, the handle 100 is non-removably attached to the catheter, so that the system need to be integrated device assembled prior to use. 换言之,导管系统可以在"即用"的状态下售卖,这与上文所描述的传统血管成形术导管不同。 In other words, the catheter system can be sold at a "ready to use" state, which is described above with conventional vascular angioplasty different catheters.

[0098] 流体回路大体上包括:沿着导管轴200布置的膨胀管腔和独立的收缩管腔;布置在手柄100中的控制系统;和多个阀,用以控制和调节膨胀流体通过导管系统的脉动的和/或调控的流动。 [0098] generally fluid circuit comprising: a catheter shaft 200 is arranged along the inflation lumen and a separate lumen contraction; catheter system and a plurality of valves to control and regulate the expansion of the fluid through; the control system is arranged in the handle 100 flow pulsation and / or regulated. 流体是"闭合的"流体回路,因此该回路的组成部件不暴露于大气。 Fluid is a "closed" fluid circuit, so the circuit component parts are not exposed to the atmosphere. 结果,膨胀流体在被包含在流体回路中时降至大气压力。 As a result, inflation fluid is reduced to atmospheric pressure when contained in the fluid circuit.

[0099]在一些实施例中,纵长轴200包括入口端口和出口端口。 [0099] In some embodiments, the longitudinal axis 200 includes an inlet port and an outlet port. 入口端口由来自作为流体回路控制系统1000-部分的第一储器的膨胀流体流加压。 The inlet port from the fluid circuit as a first control fluid expansion reservoir is pressurized stream 1000- portion. 膨胀流体流动通过纵长轴200的膨胀管腔203,经由入口端口进入可扩张构件300的内部部分。 The flow of inflation fluid through inflation lumen 200 of the longitudinal axis 203, via the inlet port into the interior portion of the expandable member 300. 膨胀流体进入可扩张构件300 内部的流动使得可扩张构件膨胀并在被放置在血管中时堵塞血管中的血流。 Expansion fluid flow into the interior of the expandable member 300 such that the expandable member may be expanded and blocked blood flow in the vessel when placed in a blood vessel. 布置在纵长轴200上的出口端口通过提供开口来帮助可扩张构件300收缩,所述开口用于使膨胀流体在收缩期间从可扩张构件300流到收缩管腔204。 Arranged on the longitudinal axis 200 of the outlet port by providing an opening to help contraction of the expandable member 300, an opening for the inflation fluid from the contraction during the contraction flow lumen 300 of the expandable member 204.

[0100]出口端口被构造用于帮助在收缩管腔204中的文丘里辅助式流动,以便使可扩张构件300收缩。 [0100] outlet port is configured to assist the venturi-type flow in the retracted auxiliary lumen 204, so that the contraction of the expandable member 300. 例如,膨胀管腔203和收缩管腔204二者可以在可扩张构件300内敞开。 For example, both the inflation lumen 203 and lumen 204 may be open at shrinking the expandable member 300. 膨胀流体可以从膨胀管腔203通过可扩张构件300进入收缩管腔204中。 203 may be inflation fluid from an inflation lumen by the expandable member 300 into the lumen 204 of shrinkage. 膨胀管腔203和收缩管腔204由一系列单向止回阀连接起来。 An inflation lumen 203 and lumen 204 are connected by a series of contraction-way check valve up. 在一个实施例中,膨胀压力导致收缩止回阀保持关闭。 In one embodiment, the expansion pressure causes the shrinkage of the check valve remains closed. 在止回阀和脉冲阀的后侧(back side)上累积的压力(图10; 117、112和109)产生文丘里效应以促进迅速收缩。 Accumulated on the rear side of the check valve and the pulse valve (back side) Pressure (FIG. 10; 117,112 and 109) to produce a venturi effect to promote rapid contraction. 当致动器被操纵到收缩位置时,在收缩止回阀的后侧上的压力被移除。 When the actuator is operated to the retracted position, the pressure on the rear side of the check valve is removed contraction. 因此止回阀打开,可扩张构件300可以收缩。 Thus check valve opens, the expandable member 300 may shrink. 膨胀压力的迅速耗尽产生文丘里效应,即,膨胀压力的迅速耗尽使球囊压力下降(draw down),并一道拉动膨胀流体通过收缩管腔到装置手柄中的排放口。 The rapid depletion of the inflation pressure to produce a venturi effect, i.e., the rapid depletion of the inflation pressure the balloon pressure drop (draw down), and an inflation fluid lumen to pull the vent means in the handle by shrinking. 排放口不对大气敞开。 Discharge mouth does not open to the atmosphere. 在流体回路中在收缩管腔与手柄中的排放口之间定位有阀。 In the fluid circuit between the retracted handle lumen positioned in the vent valve. 当膨胀流体在文丘里效应下被拉动时,涌动的膨胀流体的压力打开阀,从而收缩流体可以排放进入手柄中。 When inflation fluid is pulled in the Venturi effect, the fluid pressure of the expansion valve is opened surging, so that contraction of the fluid may be discharged into the handle. 当收缩流体从流体回路排尽时,阀关闭以保持流体回路关闭。 When contracting fluid drained from the fluid circuit, the valve is closed to maintain the closed fluid circuit. 因而,可扩张构件在小于一秒的时间内收缩,并且在一些实施例中,可扩张构件在少于1/4秒的时间内收缩。 Thus, the expandable member contracts in less than one second, and in some embodiments, the expandable member contracts in less than 1/4 seconds.

[0101] 根据本发明的另一个方面,可以经由如上文所描述的触发器或按钮控制球囊膨胀和收缩。 [0101] According to another aspect of the present invention, the balloon can be controlled via the expansion and contraction of the trigger or button as hereinbefore described. 这样做的优点在于,其允许球囊迅速地膨胀和收缩,并允许例如在用于后处理应用时更短的再灌注循环时间。 This has the advantage that it allows rapid expansion and contraction of the balloon, for example, and allows shorter cycle times during reperfusion for post-processing applications. 图11示出用于在此实施和所描述的导管系统(称为"PUFF")和传统血管成形术导管装置(称为"AngioPC")的膨胀时间和收缩时间的对比。 11 shows a catheter system in this embodiment and as described for (referred to as "PUFF") catheter apparatus (referred to as "AngioPC") and comparison time expansion and contraction time of conventional angioplasty. 如图所示,本发明的导管系统与传统的血管成形术导管相比以超量的速度膨胀和收缩。 As shown, the catheter system of the present invention as compared with the conventional angioplasty catheter at excess speed expansion and contraction. 与可以以约0.50秒的速度膨胀的本发明导管装置相比,成形术导管的膨胀是约4.84秒。 Compared with the catheter device of the present invention at about 0.50 seconds can be expanded, inflated angioplasty catheter is approximately 4.84 seconds. 收缩结果示出血管成形术导管用了至少6.81秒来收缩,而本发明的导管可以在约1.0秒内收缩。 The results are shown shrinkage angioplasty catheter with at least 6.81 seconds to the shrinkage, and shrinkage of the catheter of the present invention may be in about 1.0 second.

[0102] 在一个实施例中,如图12中所示,控制系统1000包括致动器107,其能够在手指轻击下致动可扩张构件300的膨胀和收缩。 [0102] In one embodiment, shown in Figure 12, the control system 1000 includes an actuator 107, which can be actuated expansion and contraction of expandable member 300 at the tap of the finger. 致动器107可以被致动使球囊顺序地膨胀和收缩以用于后处理应用场合或其它应用场合。 The actuator 107 may be actuated sequentially balloon to expand and contract for post-processing application or other applications. 已经发现,一段时间的缺血或中断血流(例如但不限于在STEMI或其它梗塞期间)之后迅速打开动脉会导致再灌注损伤。 It has been found, or interruption of blood flow in ischemic period of time (such as, but not limited to, during, or other STEMI infarction) to quickly open the artery after reperfusion injury can result. 一种减少再灌注损伤的方法是在从STEMI或其它阻塞重新打开初始流动之后即刻在梗塞的动脉中顺序地开始和停止血流多次循环。 A method for reducing reperfusion injury is in the order of start and stop blood from multiple cycles of STEMI or other obstruction reopened after the initial flow in the immediate infarct artery. 本发明为医生提供的系统被设计成实现迅速有效且可再现的后处理。 The system of the present invention is to provide physicians are designed to achieve rapid and reproducible efficient workup. 包括控制系统1000的流体回路110被设计用于允许在不需要其它输入或电子器件的情况下由单个致动器107来操作系统,其被称为"一触式"。 Fluid circuit 110 includes a control system 1000 is designed to allow input in the case where no additional electronics or the actuator 107 is operated by a single system, which is called "one-touch." 致动器107可以被构造成包括用于使可扩张构件300膨胀的第一位置或方向和用于使可扩张构件300收缩的第二位置或方向。 The actuator 107 may be configured to include a first position for expandable member 300 or the direction of expansion and a second position or orientation of the expandable member 300 is contracted. 例如, 致动器107可以是按钮(图9F)、开关(图9A)或杠杆(图9B),其具有用于致动球囊膨胀的瞬时方向和用于致动球囊收缩的可制动方向。 For example, the actuator may be a button 107 (FIG. 9F), the switch (FIG. 9A) or a lever (FIG. 9B), having the instantaneous direction for actuating the balloon inflation and contraction of the balloon for actuating the brake can be direction. 通过将医生相互作用限制于仅一个开关、按钮或杠杆,可以根据后处理的时间要求提供在可扩张构件300的膨胀和收缩方面的再现性。 By the physician to limit the interaction merely a switch, button or lever, may require post-processing time in the reproducibility of the expandable member 300 expands and contracts aspects. 因此,流体回路设计和一触式致动为后处理提供了使用轻松性和高度再现性。 Thus, fluid circuit design and a touch actuator provides the use of high reproducibility and ease of post-treatment. 另外,在此实施的装置允许管理后处理的医生关注监控器或其它设备仪器,这与在使用期间必须关注装置的情况截然相反。 Further, in this embodiment of the apparatus allows a medical management processing or other concern monitoring equipment and the equipment must be concerned with the case that during use of the device opposite.

[0103] 在一个实施例中,膨胀流体从储器101释放到控制通向球囊300的流体压力的调节器或单压力止回阀。 [0103] In one embodiment, expansion fluid 101 is released from the reservoir to the actuator to control the fluid pressure or a single balloon 300 of the check valve. 由于流体回路不对大气敞开,被调节的膨胀流体没有被下调到大气压力。 Since the fluid circuit does not open to the atmosphere, the inflation fluid is not regulated down to atmospheric pressure. 被调节的膨胀流体通过入口管线106流到致动器107(例如开关),该致动器控制膨胀流体通过止回阀流到脉冲阀113并继而流到球囊115。 Regulated inflation fluid flows through the inlet line 106 of the actuator 107 (e.g. switch), the actuator control inflation fluid flows through check valve 113 and then flows to the pulse 115 of the balloon.

[0104] 脉冲阀113允许膨胀流体在阀内以指定的时间段从入口端口流到出口端口。 [0104] valve 113 to allow inflation fluid pulse at a specified time period from the inlet port to the outlet port in the valve. 如将在下文描述地,可以例如通过设定脉冲阀内的入口端口、出口端口和相对弹簧压力的大小来指定时间。 As will be described below, for example, may be specified by setting the time within a pulse valve inlet port, outlet port and the magnitude of the relative spring pressure. 如在图11A至图11C中最好示出地,在一个实施例中,脉冲阀113包括被布置在柱形本体1400内的内壁1401。 As best shown in FIGS. 11A to 11C, in one embodiment, the impulse valve 113 includes an inner wall 1401 is disposed within the cylindrical body 1400. 柱形本体1400具有第一端部1410和相对的第二端部1411。 Cylindrical body portion 1400 having a first end 1410 and an opposite second end portion 1411. 具有入口端口1406和出口端口1407的内壁1401被布置在第一端部1410与第二端部1411之间的本体1400内。 An inner wall having an inlet port and an outlet port 1406 1407 1401 1400 is disposed within the body between the first end portion 1410 and the second end portion 1411. 优选地,入口端口1406大于出口端口1407,以便使膨胀流体通过入口端口流入在第二端部1411与内壁1401之间的柱形本体中的速率快于通过出口端口1407流到在第一壁1410与内壁1401之间的柱形本体的速率。 Preferably, the inlet port 1406 is greater than the outlet port 1407, so that the expansion rate of the fluid flowing into the port between the second end of the cylindrical body portion and the inner wall 1411 through inlet 1401 through outlet port 1407 to the faster flow of the first wall 1410 and the rate between the inner wall of the cylindrical body 1401. 因此,与离开出口端口1407的膨胀流体量相对比的进入入口端口1406中的膨胀流体量使得流体压力在第二壁1411与内壁1401之间累积。 Thus, the amount of fluid exiting the expander outlet port 1407 into the expansion ratio of the relative amount of fluid inlet port 1406 so that fluid pressure buildup between the second wall 1411 and inner wall 1401. 结果,如图11B中所示,当累积的压力推动内壁时,累积的压力对内壁施加作用力,并最终克服弹簧1402的强度而导致弹簧压缩。 As a result, as shown in FIG. 11B, when the accumulated pressure pushes the inner wall, the accumulated pressure is applied to force the inner wall, and eventually overcome the strength of the spring 1402 caused by compression of the spring. 内壁1401接触被布置在柱形本体1400内的止动构件1405。 A stopper member in contact with the inner wall 1401 is disposed within the cylindrical body 1400. 1405. 在一些实施例中,止动件被设置在柱形本体的内表面上。 In some embodiments, the stopper member is disposed on the inner surface of the cylindrical body. 该止动件被布置在出口端口115的近端,该出口端口导向到例如球囊300 (未示出)的可扩张构件的路径。 The stop member is disposed at the proximal end 115 of the outlet port, the outlet port into the guide path may, for example, a balloon expandable member 300 (not shown). 如图11C中所示,内壁1401接触止动件1405,变得与通向球囊300的出口端口115轴向地对准。 As shown in FIG 11C, the inner wall 1401 contacts the stopper 1405, the outlet port 115 become axially aligned with the leads 300 of the balloon. 当内壁1401 与出口端口115轴向地对准时,由端口提供的通路被阻断,使得没有膨胀流体能够行进到可扩张构件300。 When the inner wall 1401 with the outlet port 115 is axially aligned passage provided by the port is blocked, so that no fluid is able to travel to the expansion of the expandable member 300. 因此,脉冲阀113提供一种"防误操作"的致动器。 Therefore, the pulse valve 113 to provide a "misoperation" actuator. 具体而言,医生即使继续按压致动器让可扩张构件300膨胀,却不能进一步使可扩张构件膨胀,因为出口115被内壁1401阻断。 Specifically, even if the doctor continues to press the actuator 300 so that the expandable member expands, but not further expandable member is expanded, since the outlet 115 is blocked by the inner wall 1401. 因而,即使采取另外的尝试来膨胀,在更多膨胀流体能够通过系统之前,也必须先将该系统断电。 Thus, additional attempts to take even expansion possible by the system before, the system must be powered down in more inflation fluid. 因而,系统可以安全地控制进入可扩张构件的流体量。 Thus, the system can safely control the amount of fluid into the expandable member. 膨胀流体可以是本 Expanding fluid may be present

技术领域中已知的各种流体。 Art known various fluids. 例如,膨胀流体可以是气体流体或液体流体。 For example, inflation fluid may be a gas fluid or liquid fluid. 处于说明性目的,膨胀流体可以是二氧化碳或盐水。 In the illustrative purposes, the inflating fluid may be carbon dioxide or saline.

[0105] 在另一个实施例中,流体回路包括可扩张构件的文丘里辅助式收缩。 [0105] embodiment, the fluid circuit comprises an expandable member venturi assisted contraction in another. 这样,产生出真空以使来自可扩张构件的膨胀流体迅速地收缩。 Thus, a vacuum is generated so that the expansion of the fluid from the expandable member is contracted rapidly. 具体而言,当收缩由医生致动时,脉冲阀被断电,脉冲阀内的流体逸出从而释放止回阀后侧上的压力,这产生了文丘里效应,使得球囊收缩的时间缩短。 Specifically, when actuated by the contraction of the doctor, the pulse valve is de-energized, fluid escapes the pulse valve to release the pressure on the rear side of the check valve, which produces the Venturi effect, such that the contraction of the balloon is shortened . 在一些实施例中,可扩张构件在少于约5秒的时间内收缩,优选地在少于约3秒的时间内收缩,更优选地在少于1秒的时间内收缩。 In some embodiments, the expandable member contracts in less than about 5 seconds, preferably less than about 3 shrink in the seconds, more preferably less than 1 shrinks in seconds.

[0106] 如本文所描述地,如图12所示的控制回路1000包括流体回路110,该流体回路大体上包括管线1〇6(图10)和多个止回阀,用以调控膨胀流体通过流体回路并最终到纵长轴200 膨胀管腔的流动,纵长轴的膨胀管腔与流体回路110和可扩张构件300流体连通,并且通过独立的收缩管腔返回。 [0106] As described herein, the control circuit 1000 shown in Figure 12 includes a fluid circuit 110, which generally comprises a line 1〇6 fluid circuit (FIG. 10) and a plurality of check valves for the regulation of inflation fluid through fluid circuit 200 and ultimately to the longitudinal major axis of the expansion of the flow lumen, the longitudinal axis 300 of the fluid inflation lumen 110 and the fluid circuit and the expandable member in communication, and returns through a separate lumen contraction. 图10中示出了流体回路的一个实施例的分解图。 10 shows an exploded view of one embodiment of a fluid circuit. 容装在手柄100中的流体回路110可以包括以下组成部件:用于提供高压膨胀流体的第一储器101,例如但不限于BestWhip(LG)(Genuine Innovations,Part2042或4130)(图13A);用于可控制地导流第一储器101的穿透机构103,例如柳叶刀组件,诸如SA00102、SA00068、SA00101 SMM235008-21N、MM235008-llN(Genuine Innovations)(图13B至图13F);用于控制从膨胀流体到可扩张构件300的压力的压力调节器104(例如分别为MAR-l(Clippard)或SA00196(Genuine Innovations),图13G至图13H)。 Accommodated in the handle 100 of the fluid circuit 110 may include the following components: means for providing a first high pressure expansion of the fluid reservoir 101, e.g., but not limited BestWhip (LG) (Genuine Innovations, Part2042 or 4130) (FIG. 13A); a first deflector for controllably reservoir penetration mechanism 101 103, for example, the lancet assembly, such as SA00102, SA00068, SA00101 SMM235008-21N, MM235008-llN (Genuine Innovations) (FIGS. 13B-13F); with to control the pressure in the expandable member 300 is expanded from the fluid pressure regulator 104 (e.g., respectively MAR-l (Clippard) or SA00196 (Genuine Innovations), FIG. 13G to 13H). 备选地,可以使用单压力止回阀或不变压力调节器,例如, Qosina-P/Nll582或"Lee Chek"Part Number CCPI2510014S,(图1:3P);用以将压力调节器104连接到管状构件106的连接器105(未示出),例如,UT0-2-PKG(Clippard)(图131);用于控制膨胀流体从第一储器101进入可扩张构件300中的流动的致动器107,例如主开关,诸如FBV-3DMF(Clippard)(图13K);用于将管状构件106从压力调节器104连接到致动器107的连接器108,例如,CT2-PKG(C1 ippard)(图13J);用于对膨胀流体分流的分流器109,例如,UT0-2002-PKG(Clippard)(图13L);连接器111,例如CT2-PKG(Clippard)(图13M),该连接器用于将分流器109通过管状构件112连接到脉冲阀113,例如PV-1 (Clippard)(图13N),从而将一定体积的膨胀流体的受控脉冲递送到可扩张构件300;连接器114,例如转动连接器,诸如UT0-2-PKG(Clippard)(图130),该连接器用以将脉冲阀113连接到单向止回阀115(例如, C Alternatively, a single constant pressure valve or a pressure regulator, e.g., Qosina-P / Nll582 or "Lee Chek" Part Number CCPI2510014S, (FIG. 1: 3P); for the pressure regulator 104 is connected to the the tubular member 106 of connector 105 (not shown), e.g., UT0-2-PKG (Clippard) (FIG. 131); means for controlling the expansion of the first fluid from the reservoir 101 to flow into the expandable member 300 may be actuated 107, such as a main switch, such as FBV-3DMF (Clippard) (FIG. 13K); for the tubular member 106 from the pressure regulator 104 is connected to the connector 107 of actuator 108, e.g., CT2-PKG (C1 ippard) (FIG. 13J); shunt for inflation fluid diverter 109, e.g., UT0-2002-PKG (Clippard) (FIG. 13L); connector 111, e.g. CT2-PKG (Clippard) (FIG. 13M), the connector according to the diverter 109 is connected to the tubular member 112 through the pulsing valve 113, for example PV-1 (Clippard) (FIG. 13N), whereby a controlled expansion of the fluid pulses delivered into a volume of the expandable member 300; a connector 114, e.g. rotary connection, such as a UT0-2-PKG (Clippard) (FIG. 130), which is connected to a pulse valve 113 is connected to the one-way valve 115 (e.g., C CPI2510000S(Lee Company)或Qosina-P/N11582(图13P)),该单向止回阀允许膨胀流体流到可扩张构件,并确保膨胀流体的流动方向仅是单向的,即从脉冲阀113到纵长轴200的膨胀管腔203;分流器116,例如UT0-2002-PKG(Clippard)(图13R),其通过管状构件117连接到分流器109,其中分流器109将来自收缩管腔204的软管连接到压力指示器118;压力指示器118,例如IND-1-WH(Clippard)(图13S),其用于示出收缩管腔204中的压力以确保可扩张构件200被膨胀;双软管倒钩119(未示出),例如C22-PKG(Clippard)(图13Q),用于将止回阀120连接到通向导管的软管;以及止回阀120,例如CCPI12510000S(Lee Company)(图13T), 用以确保膨胀流体从在导管脉冲阀上的出口管腔到入口管腔203的流动方向。 CPI2510000S (Lee Company) or Qosina-P / N11582 (FIG. 13P)), the check valve allows the inflation fluid to flow expandable member, and to ensure that the flow direction of the inflation fluid is only unidirectional, i.e., from the pulse valve 113 to the longitudinal axis of the inflation lumen 200 203; splitter 116, e.g. UT0-2002-PKG (Clippard) (FIG. 13R), which is connected to the diverter 117 through the tubular member 109, wherein the diverter 109 from the lumen 204 shrink the hose is connected to a pressure indicator 118; 118 pressure indicator, e.g. IND-1-WH (Clippard) (FIG. 13S), for illustrating the systolic pressure in the lumen 204 to ensure that the expandable member 200 is expanded; double hose barb 119 (not shown), for example C22-PKG (Clippard) (FIG. 13Q), for connecting a hose leading to the catheter check valve 120; and a check valve 120, e.g. CCPI12510000S (Lee Company) (FIG. 13T), to ensure expansion of the fluid lumen of the catheter from the pulsing valve outlet to the inlet flow direction of the lumen 203. 如所示出地, 流体回路不需要电子器件来操作。 As shown, the fluid circuit does not need to operate the electronic device.

[0107] 如图14A的方框图中所示,在操作中,膨胀流体(在该示例中为二氧化碳)通过穿透机构103从第一储器101中的存储状态流出来。 [0107] As shown in a block diagram in FIG. 14A, in operation, the expansion fluid (carbon dioxide in this example) from the storage state by the first reservoir 101 penetration mechanism 103 to flow out. 膨胀流体流入主阀或致动器开关中。 Fluid flows into the main expansion valve or actuator switch. 在一些实施例中,膨胀流体的流动被停止进出主阀。 In some embodiments, inflation fluid flowing out of the main valve is stopped. 如图14B中所示,流体回路可以被构造用于允许膨胀流体穿过阀流入第二止回阀中。 As shown in FIG. 14B, the fluid circuit may be configured to allow fluid to pass through the expansion valve flows into the second check valve. 在一些实施例中,允许气体流动约0.1秒。 In some embodiments, the gas is allowed to flow for about 0.1 seconds. 经该段时间后,第二阀可以被构造用于不再允许膨胀流体流动。 After this period of time, the second valve may not be configured to permit flow of inflation fluid. 止回阀允许膨胀流体流入球囊中却不从球囊流出。 The check valve allows flow into the balloon inflation fluid does not flow out from the balloon. 第三止回阀允许膨胀流体从球囊流出但不流入球囊。 Third check valve allows the inflation fluid flows from the balloon but does not flow into the balloon. 当膨胀流体(例如二氧化碳气体)流到膨胀止回阀时,膨胀流体具有较高的压力,所以系统此时被锁定(膨胀)。 When the inflation fluid (e.g. carbon dioxide gas) flows to the expansion valve, the expansion fluid with a higher pressure, the system is locked at this time (expanded). 另外,如图14C中所示,第二阀内部的压力耗尽,由此产生如上文提及的文丘里力,随着所有气体从主阀的顶部排出将球囊拉动到收缩位置中。 Further, as shown in FIG. 14C, the internal pressure of the second valve is exhausted, thereby creating a venturi forces As mentioned above, all the gas discharged as the balloon is pulled to a retracted position from the top of the main valve. 此时,主阀不允许气体流入。 In this case, it does not allow gas to flow into the main valve. 因此,流体回路允许使用者以迅速连续的轻松方式使可扩张构件顺序地膨胀和收缩。 Thus, the fluid circuit allowing a user to easily rapid continuous manner sequentially expandable member expands and contracts. 手柄还可以包括脉冲阀,用以将流动以受时间控制或受体积控制的方式递送到球囊300。 The handle may further include a pulse valve for controlling the flow in a time-controlled manner or by volume delivered to balloon 300. 在该方面中,第二管状构件可以包括单向止回阀,用以将被脉冲阀递送的二氧化碳锁定在可扩张构件300中。 In this aspect, the second tubular member may comprise a one-way valve, pulse valve for carbon dioxide will be delivered in locking the expandable member 300.

[0108] V.指示器 [0108] V. Indicator

[0109] 在一些实施例中收缩管腔包括指示器一一例如但不限于压力监测器一一来确保球囊膨胀。 [0109] In some embodiments, contraction of the lumen comprises an indicator, for example, but not limited to eleven pressure monitor eleven to ensure the balloon is inflated. 在一些实施例中,压力监测器被布置在球囊与收缩止回阀之间以确保球囊膨胀。 In some embodiments, a pressure monitor is arranged between the balloon and the balloon is inflated to ensure contraction check valve. 例如,如果导管被纽结不能允许膨胀,则指示器将不指示已膨胀。 For example, if the catheter is inflated not allow kinking, the indicator will indicate not expanded. 另外,如果导管在球囊处有泄漏,则指示器将不指示已膨胀。 Further, if there is a leak in the balloon of the catheter, the indicator will indicate not expanded. 因此,指示器是球囊膨胀的真实测试。 Therefore, the balloon inflation indicator is the true test.

[0110]在一个实施例中,指示器118(图9A、9B、9C和图10)或压力标识器布置在系统的近端端部处。 [0110] In one embodiment, the indicator 118 (FIG. 9A, 9B, 9C, and FIG. 10) or a pressure marker disposed at the proximal end of the system. 在一个实施例中,指示器118包括与系统的收缩管腔相关联的突出构件。 In one embodiment, the indicator 118 includes a projecting member associated with the contraction of the lumen system. 在一些实施例中,指示器118被构造成当在系统的收缩管腔中感测到压力时至少部分地延伸通过手柄100。 In some embodiments, the indicator 118 is configured in a collapsed lumen when the system pressure is sensed at least partially extends through the handle 100. 这样,指示器取向可以为医生提示可扩张构件的状态。 Thus, the orientation indicator status prompt may be a physician expandable member. 换言之,当指示器由于例如压力迫使按钮延伸而从手柄外壳100伸出并且被医生可见时,医生会意识到膨胀流体在可扩张构件中的事实。 In other words, since, for example, when the indicator button pressure forces extend and protrude from the handle housing 100 visible when the doctor, the doctor will appreciate the fact that the fluid expands the expandable member. 相反地,不从手柄1〇〇伸出的指示器告知使用者可扩张构件没有完全膨胀。 Conversely, the user does not inform the expandable member may be expanded from the indicator of the handle is not fully extended 1〇〇. 由于指示器与在系统的近端端部处的收缩管腔相关联(例如相联接),指示器只有在来自膨胀流体的压力已经流过膨胀管腔与可扩张构件流体连通并通过收缩管腔返回到系统的近端区段为止才能指示或延伸。 Since the indicator lumen and the proximal end of the contraction of the system associated with (e.g., coupled), the indicator only has the pressure from the expansion of the fluid flowing through the inflation lumen in fluid communication with the expandable member and by contracting the lumen the system returns to the proximal section extending up to or indicated. 因而,除非可扩张构件在导管系统的远端区段处膨胀,不然指示器118不会指示压力。 Accordingly, unless the expandable member expands in the distal section of the catheter system, or the indicator 118 does not indicate pressure. 有利地,指示器是球囊内部真实压力的指示。 Advantageously, the indicator is an indication of the actual pressure inside the balloon. 相反地,与收缩管腔不直接流体连通的指示器将不会真实地指示球囊是膨胀状态还是收缩状态。 Conversely, the pointer is not in direct fluid communication with the lumen contraction will not be truly indicative of the balloon is expanded or shrunk.

[0111] VI.装载装置 [0111] VI. Loading device

[0112] 在一个实施例中,如在图9A和图9B的剖视图中所示,并且最好地参见图10,流体回路110的控制系统1000大体上包括第一储器101 (例如容器或罐),其具有已存储的膨胀流体。 [0112], as shown in one embodiment in cross-sectional view of FIGS. 9A and 9B, and the best (e.g. vessel or tank 10, the fluid circuit 110 of the control system 1000 generally includes a first reservoir 101 ), which it has been stored in the expanding fluid. 第一储器101可以被选择(基于尺寸),使得具有特殊尺寸的特定球囊膨胀和收缩。 The first reservoir 101 may be selected (based on size), such that expansion and contraction of the balloon has a particular special size. 因此, 所选储器尺寸可以防止再使用和/或促进安全性,尤其是当膨胀流体为加压气体(例如二氧化碳)时。 Thus, the selected size of the reservoir can be prevented from re-use and / or improved safety, especially when the inflating fluid is a pressurized gas (e.g. carbon dioxide).

[0113] 在一些实施例中,装载装置114(图15A)被布置在第一储器的近端,并且被构造用于将装置装载。 [0113] In some embodiments, the loading device 114 (FIG. 15A) is disposed at the proximal end of the first reservoir, and means for loading being configured. 装载装置可以是不可逆的。 The loading device may be irreversible. 在该方面中,"不可逆"意味着一旦本发明的装置被装载,则不能被解除装载。 In this aspect, "irreversible" means that when the apparatus of the invention is loaded, the loading can not be released. 在使用之前,装载装置114由医生致动以穿透含有膨胀流体的储器110。 Prior to use, the loading device 114 by the physician to penetrate the actuating fluid reservoir 110 containing expanded. 例如如图15A和图15B中所示地,当装载装置114被下推时,第一储器101被向前推, 并且位于手柄外壳112上的棘轮与突出部116啮合,从而防止装载装置114返回到其原始位置。 For example, as shown in 15A and 15B, when the loading apparatus 114 is pushed down, a first reservoir 101 is pushed forward, the engagement of the ratchet and is positioned on the handle housing 112 and the protruding portion 116, thereby preventing the loading device 114 returns to its original position. 系统被装载,由此允许流体从第一储器101中的开口流动。 The system is loaded, thereby allowing fluid to flow from the first opening 101 of the reservoir.

[0114] 图15C至图15N中示出了装载装置114的其它实施例。 [0114] FIG. 15C to FIG. 15N shows a further embodiment of the loading device 114. 例如,在图15C和图15D中,装载装置114由按钮114a和楔形物114b形成,按钮和楔形物被定位成使得施加在按钮114a上的向下作用力导致楔形物114b沿着垂直方向运动,由此通过释放存储在储器101中的膨胀流体使第一储器101向前运动到装载位置中。 For example, in FIG. 15C and FIG. 15D, the loading apparatus 114 buttons 114a and 114b is formed by the wedge, the wedge and button are positioned such that the downward force exerted on the button 114a causes the wedge 114b moves in a vertical direction, thus by releasing the inflation fluid stored in the reservoir 101 in the first reservoir 101 is moved to the loading position forward. 突出部116再次与位于手柄外壳112上的棘轮啮合,从而防止按钮114a和楔形物114b二者返回到其原始位置。 Re-engaging projection 116 located on the handle housing ratchet 112, thereby preventing the wedge both buttons 114a and 114b is returned to its original position.

[0115] 在图15E至图15J中示出了杠杆型安全装置114。 [0115] In FIGS. 15E through 15J illustrated in FIG lever-type safety device 114. 如图所示,医生必须将杠杆从第一位置运动到第二位置,以便使第一储器101前进到其装载位置中。 As shown, the physician must lever from the first position to the second position to the first reservoir 101 is advanced to its loading position. 杠杆装载装置114的初始位置和终止位置仅仅取决于系统的制造要求。 The initial loading lever 114 and end positions depends only on the manufacturing requirements of the system. 在一些实施例中,位于手柄外壳112-侧上的棘轮与杠杆装载装置114的两侧啮合,由此防止杠杆装载装置114返回到其原始位置。 In some embodiments, located on the side of handle housing 112- ratchet engagement with the lever 114 of the loading means on both sides, thereby preventing the loading apparatus 114 returns the lever to its original position.

[0116] 也可以根据本发明的一些实施例使用如图15K至15L中所示的拉片型装载装置114。 [0116] According to some embodiments may use the present invention, the pull tab type shown in FIG. 15K 15L to the loading apparatus 114 shown in FIG. 在这些实施例中,拉片型装载装置114可以由拉片114c和弹簧机构114d形成。 In these embodiments, the pull tab loading apparatus type 114 may be formed of spring mechanism and the tab 114c 114d. 弹簧被偏压在收缩的状态中,直到拉片被移除为止。 The spring is biased in the contracted state until the tab is removed so far. 通过从手柄100移除拉片114c允许弹簧机构114d 伸长,弹簧施加作用力推动或允许第一储器101接合导流装置(诸如柳叶刀),从而将装置装载。 By removing the tab from the handle allows the spring means 100 114c 114d extended, the spring exerts a force to push or to allow the first guide means engaging the reservoir 101 (such as a lancet), so that the loading means.

[0117] 在其它实施例中,装载装置114可以是螺钉型装载装置,如在图15M至图15N中所示。 [0117] In other embodiments, the loading device 114 may be a screw-type loading device, as shown in FIGS. 15M to 15N shown in FIG. 如图所示,位于装载装置114上的螺纹114e接合外壳112中的开口。 As shown, the threaded 114e on the loading device 114 in the housing 112 engages the opening. 沿着适当方向转动装载装置114导致装载装置114向前前进,并且导致第一储器101前进到其装载位置中。 Rotation of the loading apparatus 114 appropriate direction causes the load device 114 advances forward, and results in the first reservoir 101 is advanced to its loading position. 在一些实施例中,装载装置114可以包含有锁定机构(未示出),其防止第一储器101被解除装载和/ 或沿着错误方向转动。 In some embodiments, the loading device 114 may include a locking mechanism (not shown), which prevents the reservoir 101 is released first loading and / or rotated in the wrong direction.

[0118] 如所描述地,装载装置114通过使第一储器101与穿透构件103(图9A、图10)接合而将第一储器101装载,使得储器被导流或穿透以释放容纳在储器外壳内的膨胀流体。 [0118] As described, the loading device 114 to load 101 through the first penetrating member 101 and the reservoir 103 (FIG. 9A, 10) engages a first reservoir, such that the reservoir is penetrated to flow or releasing inflation fluid housed within the reservoir housing. 流出的膨胀流体进入流体回路并最后流到在导管本体的远端段处的可扩张构件,并经由独立的收缩管腔从球囊流出。 Inflation fluid flowing into the fluid circuit and finally flows to the expandable member at the distal section of the catheter body, and flows out from the balloon via an independent lumen shrinkage.

[0119] W.有益制剂的局部施用 [0119] W. topical administration of beneficial agents

[0120] 如上文所描述地,在此实施的导管可以包括用于递送有益制剂的注入管腔206。 [0120] As described above, the catheter in this embodiment may be used to deliver beneficial agents include injection lumen 206. 注入管腔206可以被构造成在后处理技术之前、期间或之后将药物或其它治疗剂局部地施用到发生缺血性事件的区域。 Injection lumen 206 may be configured to post-processing techniques before, during, or after a drug or other therapeutic agent is administered topically to an area of ​​ischemic events. 在该方面中,所提供的医疗可以将有效量的有益制剂局部地施用,从而缓解已经经受或正在经受缺血的组织或器官的再灌注损伤。 In this aspect, the medical may be provided an effective amount of beneficial agents administered topically to relieve reperfusion injury has been subjected to or is being subjected to ischemic tissues or organs.

[0121] 因此,按照本发明的一个方面,提供了一种用于缓解缺血性事件之后组织梗塞方法。 [0121] Thus, according to one aspect of the present invention, there is provided a tissue after an ischemic event for mitigation method infarction. 在一个实施例中,该方法使球囊在血管内膨胀,以便在第一时间段至少部分地堵塞血管。 In one embodiment, the method of inflating the balloon within the blood vessel to occlude the vessel in a first time period at least partially. 第一时间段可以是约五秒或更少一直到五分钟的时间、十秒或更少一直到五分钟的时间、十五秒或更少一直到五分钟的时间、二十秒或更少一直到五分钟的时间、三十秒或更少一直到五分钟的时间。 The first time period may be up to about five seconds or less, five minutes, ten seconds or less up to five minutes, fifteen seconds or less up to five minutes, twenty seconds or less until five minutes thirty seconds or less up to five minutes. 然后,球囊在血管内收缩,使得允许在第二时间段至少部分地再灌注血流。 Then, contraction of the balloon within the blood vessel, so as to allow a second time period at least partially reperfusion of blood flow. 第二时间段可以长于或短于第一时间段。 The second period may be longer or shorter than the first time period. 为了说明的目的,第二时间段可以是五秒或更少一直到五分钟的时间、十秒或更少一直到五分钟的时间、十五秒或更少一直到五分钟的时间、二十秒或更少一直到五分钟的时间、三十秒或更少一直到五分钟的时间、四十秒或更少一直到五分钟的时间、五十秒或更少一直到五分钟的时间。 For illustrative purposes, the second time for five seconds or less may be up to five minutes, ten seconds or less up to five minutes, fifteen seconds or less up to five minutes twenty seconds or less up to five minutes thirty seconds or less up to five minutes, forty seconds or less up to five minutes, fifty seconds or less up to five minutes. 在允许至少部分地再灌注之后,球囊可以至少部分地膨胀以在第三时间段堵塞血管,并然后使球囊收缩以允许再次至少部分地再灌注。 After allowing at least partially reperfusion, the balloon can be inflated to at least partially occlude the vessel at the third time period, and then shrink the balloon at least partially again allow reperfusion. 这些步骤可以以顺序的方式重复,有益制剂也可以在膨胀步骤期间、 在收缩步骤期间或在两个步骤期间被局部地递送给缺血区域。 These steps may be repeated in a sequential manner, the formulation may be useful during the expansion step, during the shrinking step or is locally delivered to the ischemic area during step two. 在一个实施例中,仅在再灌注步骤期间施用有益制剂。 In one embodiment, the administration of beneficial agents only during reperfusion procedures. 在另一个实施例中,每30秒递送有益制剂以至八次后处理循环。 In another embodiment, the delivery formulation as well as every 30 seconds after eight beneficial treatment cycle. 照这样,循环指的是膨胀步骤(堵塞)及随后的收缩步骤(再灌注)。 In this manner, the cycle refers to the expansion step (clogging) and subsequent contraction step (reperfusion).

[0122] 根据目前所披露主题的另一方面,本发明的设备和方法大幅度地减少在后处理期间所需要的造影剂量。 [0122] According to another aspect of the presently disclosed subject matter, apparatus and method of the present invention to significantly reduce the dose of contrast during post-processing required. 虽然造影剂通常是使用安全的,但是施用各种造影介质可以导致多种身体状况。 Although the use of contrast agents is generally safe, but the application of various contrast media can cause a variety of physical conditions. 反应可以从轻微到严重,有时会导致死亡。 The reaction can range from mild to severe, sometimes leading to death. 发展严重反应的风险因素包括强烈过敏、支气管哮喘、心脏病和β受体阻滞剂使用。 Risk factors for the development of a severe reaction include strong allergies, bronchial asthma, heart disease and β-blocker use. 因此,减少造影剂的使用量有利于缓解患者不良反应的风险。 Therefore, to reduce the amount of contrast agent will help alleviate the risk of adverse reactions in patients. 例如,减少造影剂的使用对于糖尿病患者以及具有并发症的其它人群是优选的。 For example, reducing the use of contrast agents for diabetes and a complication of other populations are preferred.

[0123] 如图16中所示,由"PUFF"图表所表示的本发明再灌注系统使用了0.37ml的造影剂来确认八次循环的后处理堵塞和再灌注,而由"AngioPC"所表示的传统血管成形术技术使用了7.75ml的造影剂。 [0123] As shown in FIG. 16, the present invention consists of "PUFF" reperfusion chart showing system uses a contrast agent to confirm 0.37ml eight cycle process clogging and reperfusion, and is represented by "AngioPC" conventional angioplasty techniques using 7.75ml of a contrast agent. 因此,传统的血管成形术导管所需的造影剂几乎是本文所实施和所描述的导管装置的二十一倍。 Thus, the conventional angioplasty catheter is almost required twenty double contrast agent conduit means and the embodiments described herein. 因而,本发明的设备和方法充分地减少造影剂暴露。 Thus, the method and apparatus of the present invention to sufficiently reduce the contrast agent is exposed. 如以上对于递送治疗剂所描述地,造影剂可以通过导管的管腔递送到被定位在球囊远端的出口或端口。 As described above for delivery of therapeutic agents as described, the contrast agent may be delivered to an outlet positioned at the distal end of the balloon through the lumen of the catheter or port. 图17所描绘的一系列图像展示了造影剂被部署在球囊300远端的端口250处的再灌注循环(箭头"A"指示流动方向)。 FIG 17 depicts a series of images showing reperfusion cycle the contrast agent is deployed in the distal end of the balloon 300 at the port 250 (the arrow "A" indicates the direction of flow). 由于出口被布置在球囊的远端,可以首先使球囊膨胀以堵塞血流,然后可以递送造影剂。 Since the outlet is disposed at the distal end of the balloon, inflating the balloon to first be blocked blood flow, then the contrast agent may be delivered. 在血流被堵塞的情况下,造影剂不会被稀释或被迫向下游。 In the case where the blood flow is blocked, the contrast agent is not diluted or forced downstream. 结果, 本发明在需要较少造影剂的同时提供了较好的控制和可见度。 As a result, the present invention requires less contrast agents while providing good visibility and control.

[0124] 在球囊远端定位递送端口可以增强治疗剂递送和被患者吸收的功效。 [0124] positioned at the distal end of the balloon can enhance the delivery of therapeutic agent delivery port, and is absorbed by the patient's efficacy. 虽然在图16 中描绘出单个端口250,但是根据期望可以包括额外的端口。 Although a single port 250 depicted in FIG. 16, as desired but may include additional ports. 另外,造影剂和治疗剂可以根据期望设置在在球囊远端具有分离的出口的分离的管腔中。 In addition, contrast agents and therapeutic agents as desired may be provided with separate outlet separated at the distal end of the balloon lumen. 在另一个实施例中,目前所描述主题的导管轴可以包括分离的管腔来递送与有益制剂分离的造影剂。 In another embodiment, the presently described subject matter may include a separate catheter shaft lumen to deliver the separate formulations useful contrast agents. 管腔可以根据期望被布置在球囊的近端或远端,从而可以将造影剂和/或有益制剂递送到球囊的近端或远端。 Lumen may be disposed as desired in a proximal or distal end of the balloon, so that the contrast agent and / or beneficial agents may be delivered to the proximal or distal end of the balloon.

[0125] 珊.使用导管的示例性应用 [0125] Shan. Exemplary application using a catheter

[0126] 在此实施并描述的导管可以用于各种应用场合,包括局部药物递送、后处理和血管成形术。 [0126] In this embodiment, the catheter may be described and used for various applications, including topical drug delivery, and post-angioplasty treatment. 在一个这样的应用场合中,提供了一种用于协同地缓解在已经受到缺血性事件的哺乳动物中的再灌注损伤的方法。 In one such application, there is provided a method for synergistically to alleviate reperfusion injury in mammals has been ischemic events in the. 该方法大体上包括在缺血性事件之后在后处理期间将有益制剂局部地递送到血管。 The method generally comprises, after an ischemic event during the post-treatment benefit agents delivered locally to a blood vessel. 缺血性事件的起因可以是在哺乳动物的各种不同脉管系统或微脉管系统中的阻塞。 Cause of ischemic events can be blocked in a variety of different vascular system or micro vascular system of a mammal. 例如,特定脉管系统可以包括冠状系统的脉管系统、脊柱系统的脉管系统、外周系统的脉管系统或大脑系统的脉管系统。 For example, a particular system may include the coronary vasculature system, vascular system, vascular system of the spine system, the outer periphery of the vasculature system or cerebral vasculature system. 该方法可以例如用于缓解休克之后的大脑损伤、心脏病发作之后的冠脉损伤、栓塞之后的脊柱或外周损伤,或其它包括供血不足和缺氧在内的疾病。 This method can be used to relieve brain damage such as after the shock, coronary artery damage after a heart attack, spinal or peripheral injury after embolization, or other diseases, including insufficiency and hypoxia, including.

[0127] 如图1A中所示,示出了后处理方法的一个实施例。 [0127] As shown in FIG 1A, there is shown a post-processing method according to one embodiment. 以下实施并描述的球囊导管装置通过血管引入到在受伤部位近端或靠近受伤部位的位置。 It means balloon catheter and the following description of embodiments of the injured area is introduced to a position at or near the proximal end of the injured area by a vessel. 球囊暂时膨胀以将通过血管的血液停止灌注一定量的时间,随后暂时收缩一定量的时间以允许血液通过血管再灌注一段时间。 The balloon is inflated to temporarily stop the blood vessels by perfusion certain amount of time, then an amount of temporary shrinkage of time to allow the blood through the vascular reperfusion period. 例如,后处理手术程序可以在给血管打支架之前实施,例如如图1A中所示。 For example, post-processing may be carried out prior to a surgical procedure to hit a blood vessel stent, as shown in FIG. 1A. 如图1B中所示,后处理可以在打支架之前和打支架之后执行。 As shown in FIG. 1B, and post processing may be performed before the stent after beating play stent. 在后处理在打支架之后执行的情况下, 球囊优选地在支架近端膨胀和收缩,即使球囊可以在支架的管腔内顺序地膨胀和收缩。 In the latter case the processing performed after playing the stent, preferably the stent proximal balloon expands and contracts, even if the balloon may be inflated sequentially within the lumen of the stent and contraction. 为了不意性目的,后处理方法也在Vinten-Johansen的美国专利公开No · 2004/0255956和2007/0160645中得以描述,这些专利所披露的内容通过参考包含于此以用于所有目的。 For purposes intended, after treatment Vinten-Johansen also disclosed in U.S. Patent No · 2004/0255956 and 2007/0160645 been described in, the disclosures of these patents are incorporated herein by reference for all purposes.

[0128] 机械式后处理在再灌注时提供了将一种或多种有益制剂递送到缺血性血管和递送到在缺血下游的组织或器官(诸如心肌)的独特机会。 [0128] After the mechanical processing provides a unique opportunity to deliver one or more beneficial agents to be delivered to the ischemic vascular and ischemic tissue or organ in the downstream (such as the myocardium) during reperfusion. 有益制剂可以在膨胀(堵塞)或收缩(不堵塞)或二者的后处理循环期间被直接地递送到血管。 Advantageous formulations may be expanded (blocked) or contraction (no clogging) or during the post-treatment cycle two is directly delivered into a blood vessel. 这样,如果经静脉施用,则有益制剂可以以高于可能的浓度施用。 Thus, if intravenously administered, the formulations can be administered in a useful concentration may be higher. 另外,在没有暂时堵塞的情况下,有浓度的有益制剂在后处理期间递送时在血管中的停留时间大于在由传统冠脉导管递送时的停留时间。 Further, in the temporary absence of clogging, when the concentration of beneficial agents delivered during the residence time in the post treatment vessel is greater than the residence time when delivered by conventional coronary catheter.

[0129] 在一个实施例中,如图18中所示,后处理手术程序可以包括数次30秒循环的球囊膨胀和收缩,从而实现交替的数次30秒循环的血液流动和不流动。 [0129] In one embodiment, as shown in FIG. 18, post-processing may comprise several surgical procedures 30 seconds balloon inflation and deflation cycles in order to achieve several alternating cycles of 30 seconds blood flow and no flow. 另外,后处理方法和装置可以包括在不流动循环期间局部地递送有益制剂,如图所示。 Further, the processing method and apparatus may include a local delivery of beneficial agents not flow during the cycle, as shown in FIG. 在某些实施例中,可以对于一次或多次不流动循环局部地施用有益制剂。 In certain embodiments, it may not be repeatedly administered topically flow cycle for one or more beneficial agents. 如图18中所示,该方法的一个实施例包括,在缺血之后在数次堵塞或不流动循环的每个时期期间局部地递送有益制剂。 As shown in FIG. 18, one embodiment includes, after the ischemia locally deliver beneficial agents blocked several times during each period or cycle of the process flow. 然而,可以在后处理的膨胀阶段和收缩阶段二者期间递送有益制剂。 However, beneficial agents may be delivered both during the expansion phase of post-processing and contraction phase. 在该方面中,递送的有益制剂将在膨胀循环期间留滞而在收缩循环期间流动。 In this aspect, the delivery of beneficial agents will flow during deflation cycles the lag during an expansion cycle. 有益制剂在后处理期间的局部递送协同地缓解了再灌注损伤。 Advantageous formulations topical delivery during post-treatment synergistically alleviated reperfusion injury.

[0130] 在此应预料到,可以在后处理期间局部地递送各种有益制剂,从而协同地缓解缺血之后在哺乳动物中的再灌注损伤。 [0130] In should be expected to be locally during the delivery of various beneficial agents, whereby synergistic alleviate reperfusion injury after ischemia in a mammal. 已经发现,有益制剂在后处理期间的局部递送显著地增加了有益制剂在哺乳动物组织中的吸收。 It has been found useful in the topical formulation during the delivery of post-treatment significantly increased the absorption of beneficial agents in a mammal tissue. 认为的是,在后处理手术程序的膨胀阶段,估算出的后处理组织浓度是C ' =(A/V)*K ' *Co*Exp-(k+k ')*t ' ; 0〈t〈t ' =膨胀时间。 That is, after expansion stage of the processing of a surgical procedure, tissue treatment after the estimated concentration C '= (A / V) * K' * Co * Exp- (k + k ') * t'; 0 <t <t '= inflation time. 在收缩阶段, 估算出的后处理组织浓度被认为是C〃=(A/V)*K ' *C ' *Exp-(k '/R)*t 〃-(A/V)C ' *Exp-(k 7 R)*( tx/V)。 In the contraction phase, the estimated post-treatment tissue concentration is considered C〃 = (A / V) * K '* C' * Exp- (k '/ R) * t 〃- (A / V) C' * Exp - (k 7 R) * (tx / V). 相反地,没有后处理的常规冠脉内手术被认为是C=(A/V)*K ' C ' *Exp-(k ' *x/V/ R)f(tx/V)。 In contrast, no post-treatment in a conventional coronary surgery is considered to be C = (A / V) * K 'C' * Exp- (k '* x / V / R) f (tx / V). 因此,由于膨胀-收缩的后处理循环,组织的有益制剂浓度更大。 Accordingly, since the expansion - more beneficial agents after contraction processing loop, the tissue concentration.

[0131] 在此使用的"有益制剂"包括促进健康、恢复或诊断的任何制剂。 [0131] As used herein, "beneficial agents" includes any preparation to promote health, recovery or diagnosis. 例如,有益制剂可以是药物、蛋白质或造影剂。 For example, beneficial agents may be a drug, a protein, or a contrast agent. 合适的有益制剂包括钙蛋白酶抑制剂、内皮素受体阻滞剂、 pH稳定剂、类糜蛋白酶抑制剂、氧和氧混合物、抗血栓剂、蛋白质、包括血管生成因子的载体或细胞、以及生物材料。 Suitable benefit agents include calpain inhibitors, endothelin receptor blockers, pH stabilizers, chymase inhibitors, a mixture of oxygen and oxygen, antithrombotic agents, proteins, vectors comprising angiogenic factors or cells, and organisms material. 有益制剂的其它示例包括硝化甘油、肾上腺素、利多卡因、肝磷脂、 水蛭素和ReoPro™。 Other examples of beneficial agents include nitroglycerin, epinephrine, lidocaine, heparin, hirudin and ReoPro ™. 然而,正如本领域中所认识到地,可以采用其它药物或有益制剂。 However, as is recognized in the art, other drugs or beneficial agents may be employed.

[0132] 钙蛋白酶抑制剂的非限制性示例包括ABT-099、A-965431、A705253、A-705239、或外消旋物及其混合物。 [0132] Non-limiting examples of calpain inhibitors include ABT-099, A-965431, A705253, A-705239, racemates, or mixtures thereof. 在W098/25899、W098/25883、W09954305、W099/54310、W099/61423、 TO00/78933、W02008/080969、W02009/083581,美国公开No .2006/0205671 和2008/0097385 中披露了钙蛋白酶抑制剂的其它示例,这些专利每个所披露的内容都通过参考包含于此。 In W098 / 25899, W098 / 25883, W09954305, W099 / 54310, W099 / 61423, TO00 / 78933, W02008 / 080969, W02009 / 083581, U.S. Publication No .2006 / 0205671 and 2008/0097385 disclose the calpain inhibitor other examples, each of these patent disclosures are incorporated herein by reference. 在动脉堵塞的患者中进行再灌注处理使得钙流入心肌细胞中,刺激依赖钙的酶钙蛋白酶。 Of reperfusion process such that calcium influx into cardiac myocytes, calcium-dependent stimulation of the enzyme calpain in a patient's arterial blockage. 钙蛋白酶的激活随后导致细胞骨架蛋白(即胞衬蛋白)降解,从而增加了膜脆性。 Subsequently leads to the activation of calpain cytoskeletal proteins (i.e. fodrin) degradation, thereby increasing the brittleness of the film. 膜脆性与流体到缺血性细胞中的注入组合在一起可以导致细胞肿胀和死亡。 Injecting the fluid into the film brittle compositions in ischemic cell together may result in cell swelling and death.

[0133] 在一个实施例中,有益制剂是钙蛋白酶抑制剂、地塞米松和腺苷的混合物。 [0133] In one embodiment, the formulation is advantageous calpain inhibitor, dexamethasone and a mixture of adenosine. 在另一个实施例中,该方法包括将钙蛋白酶抑制剂在后处理期间的局部递送与腺苷的持续释放结合起来。 In another embodiment, the method includes a calpain inhibitor in sustained release local delivery of adenosine during post-processing combined. 例如,可以在血管中部署洗脱腺苷或其类似物的支架。 For example, adenosine-eluting stent may be deployed in a blood vessel or the like. 在某些实施例中,支架可以被设计成洗脱腺苷超过一天至三天的一段时间以减少微脉管阻塞。 In certain embodiments, the stent may be designed to be eluted more than one day to three days adenosine period of time to reduce microvascular obstruction. 在其它实施例中,支架洗脱腺苷或其类似物长达七天或更长的一段时间以防止支架血栓形成。 In other embodiments, adenosine eluting stent or analogs period up to seven days or longer to prevent stent thrombosis. 因而,本发明包括多个方法来减小或缓解微脉管阻塞和支架血栓形成。 Accordingly, the present invention comprises a plurality of ways to reduce or ameliorating microvascular occlusion and stent thrombosis. "支架血栓形成"指的是动脉损伤和暴露的血栓形成材料,这有时是由于放置支架引起的。 "Stent thrombosis" refers to arterial damage and expose thrombogenic material, which is sometimes caused due to the placement of the stent.

[0134] 合适的内皮素受体阻滞剂包括ET-A和/或ET-B受体阻滞剂,例如,Astrasentan (ABT-627;A-147627),ABT-546(A-216546)及其外消旋物。 [0134] Suitable endothelin receptor blockers include ET-A and / or ET-B receptor blocker, e.g., Astrasentan (ABT-627; A-147627), ABT-546 (A-216546) and racemates. 在冠状动脉堵塞的患者中的再灌注典型地导致对促进远端脉管系统的血管收缩和/或血管痉挛的因子的释放。 In patients with coronary artery blockage of reperfusion and typically result in the release of factors promoting vasoconstriction distal vasculature and / or vasospasm. 一些因子包括内皮素、血清素、5-羟色胺、血栓素和组胺。 Some factors include endothelin, serotonin, serotonin, thromboxane, and histamine. 造成的血管收缩可以导致微脉管阻塞(即没有回流),所述微脉管阻塞可以持续了数天至数周并且已经发现是心室重构的前兆。 May lead to vasoconstriction resulting microvascular obstruction (i.e., no reflux), the microvascular occlusion can be continued for several days to several weeks and has been found to be a precursor of ventricular remodeling. 例如, 认为的是,没有回流的心肌容量与患者发展左心室重构(增大的舒张期容量)的可能性直接相关,而左心室重构可以导致心力衰竭。 For example, he believed that without reflux in patients with cardiac capacity and the possibility of (increased diastolic volume) is directly related to the development of left ventricular remodeling, and left ventricular remodeling can lead to heart failure. 在一个实施例中,方法包括通过局部递送内皮素受体阻滞剂来缓解心室重构。 In one embodiment, the method includes ventricular remodeling to relieve local delivery by an endothelin receptor antagonist. 另外,可以在再灌注时间期间局部地递送内皮素受体阻滞剂以缓解微脉管阻塞和/或减小梗塞面积。 Furthermore, it can be locally delivered endothelin receptor blockers during reperfusion time to alleviate microvascular occlusion and / or reducing infarct size. 内皮素受体阻滞剂可以在堵塞时期期间在堵塞的球囊下游被局部地递送、在堵塞时期期间和在回流时期期间在注入导管下游注入、选择性地递送给通过心动周期供给再灌注的组织或器官的动脉、选择性地递送给在心脏舒张期间供给再灌注的组织的动脉以便递送给心内膜。 Endothelin receptor antagonist can be delivered locally during the plugging of downstream occlusion balloon period, and during the period of clogging during injection conduit downstream of the reflux period injection is selectively delivered to the cardiac cycle is supplied by reperfusion arterial tissue or organ, to selectively delivered to arterial tissue reperfusion supplied during diastole for delivery to the endocardium. 如果期望将有益制剂到缺血性心肌的递送最大化,则有益制剂的系统性递送可以通过冠脉递送补充,或有益制剂的冠脉递送可以通过静脉内递送补充。 If it is desired to maximize the delivery of benefit agents to the ischemic myocardium, the delivery of the beneficial systemic formulations can be delivered by coronary supplemented, or beneficial agents may be delivered coronary delivery by intravenous supplement.

[0135] 在该方法的又一个方面中,脉管组织的pH可以在缺血性事件之后被稳定以优化组织活力。 [0135] In yet another aspect of the method, pH vascular tissue can be stabilized in order to optimize tissue viability after the ischemic event. 这样,期望的是在后处理期间局部地递送pH稳定剂。 Thus, it is desirable during the process locally deliver a pH stabilizer. 这样,可以弥补缺血性再灌注治疗常见的对血管的急剧变化,并且可以减小再灌注损伤和梗塞面积。 In this way, we can make up for ischemic reperfusion therapy common dramatic changes to blood vessels and can reduce infarct size and reperfusion injury. 在一个实施例中,pH 稳定剂被递送到血管或血管壁。 In one embodiment, pH stabilizing agent is delivered into the vessel or vessel wall. 在再灌注之后,递送的pH稳定剂可以行进到受伤组织中并且控制氧通过血液递送到组织中的速率。 After reperfusion, pH stabilizers may be delivered to the injured tissue and travel control the rate of oxygen delivery to the tissue by blood. 由于,氧合作用及组织内的pH变化可以被调控并且进行更长一段时间。 Since, oxygenation and changes in tissue pH can be regulated, and for a longer period of time.

[0136] 允许组织逐渐地实现体内平衡缓解了组织细胞上的应力并使组织活力优化。 [0136] allows to achieve gradual tissue homeostasis relieve stress on the tissue cells and tissue viability optimization. 应认识到,调控可以通过各种原因实现。 It should be recognized that the regulation can be achieved by a variety of reasons. 例如,治疗剂可以通过取代靶组织内的容量来减小递送氧的速率并且因此防止被氧化的血液(至少部分地)进入组织中。 For example, the therapeutic agent may be reduced by the rate of oxygen delivery capacity in the target tissue and thus prevent substituted oxidized blood (at least partially) into the tissue. 或者,有益制剂可以与血液中存在的氧相互作用以产生化学副产品,所述化学副产品可以进入组织和救缓其中的pH。 Alternatively, the beneficial agents may interact with the oxygen present in the blood to produce chemical by-products, by-products of the chemical into the tissue and can save buffer pH therein. pH稳定剂例如包括碳酸钠和柠檬酸的混合物,其产生作为副产品的二氧化碳、一氧化氮、以及一氧化氮和二氧化碳的混合物。 pH stabilizers include, for example mixture of sodium carbonate and citric acid, which is produced as a by-product carbon dioxide, nitric oxide, and a mixture of carbon dioxide and nitric oxide. 它们每个都具有减小pH的效果并且可以控制组织内的pH变化的速率。 They each have the effect of reducing the pH can be controlled and the rate of pH change within the tissue. 合适的pH稳定剂包括但不限于:碳酸钠和柠檬酸;一氧化氮;一氧化氮和二氧化碳,它们全部都减小梗塞的血管内的pH。 Suitable pH stabilizers include, but are not limited to: sodium carbonate and citric acid; nitric oxide; nitric oxide and carbon dioxide, all of which are within the reduced pH of infarction. 在一个实施例中,膨胀流体和有益制剂可以是一氧化氮。 In one embodiment, expansion fluid formulations may be advantageous, and nitric oxide. 因此,灌注球囊可以经由作为介质的一氧化氮来膨胀。 Thus, nitric oxide perfusion balloon may be inflated via a medium.

[0137] 在一个实施例中,有益制剂可以是腺苷和腺苷类似物。 [0137] In one embodiment, the formulation may be advantageous adenosine and adenosine analogs. 合适的腺苷类似物包括:腺苷A1 兴奋剂j|^nCVT-510、BN-063、CPA(N6-cyclopentyladenosine),CCPA(lchloroN6-cyclopentyladenosine);和腺苷A2兴奋剂,例如CGS21680、NECA N-ethylcaroxamide adenosine、2HE-NECA、APEC(2[2-aminoethylaminocarbonylethylphenylethylamino]-5 'N ethylcarboxamindoadenosine。腺苷可以从洗脱支架施用以实现有益制剂的持续释放。在一个实施例中,洗脱支架可以洗脱腺苷七天到约两个月至三个月。这样,腺苷或其兴奋剂的持续释放可以缓解器官狭窄、支架血栓形成或微脉管阻塞(MV0)。 Suitable adenosine analogues comprising: adenosine A1 agonists j | ^ nCVT-510, BN-063, CPA (N6-cyclopentyladenosine), CCPA (lchloroN6-cyclopentyladenosine); and adenosine A2 agonists, such as CGS21680, NECA N -ethylcaroxamide adenosine, 2HE-NECA, APEC (2 [2-aminoethylaminocarbonylethylphenylethylamino] -5 'N ethylcarboxamindoadenosine. adenosine can be administered to achieve a sustained release of beneficial agents from eluting stent. in one embodiment, can be eluted eluting stents adenosine seven days to about two to three months. Thus, a sustained release of adenosine agonists may relieve or stenosis, stent thrombosis or microvascular obstruction (MVO).

[0138] 在一个实施例中,方法包括:将持续释放的腺苷施用;在围手术程序期间(peri-procedually)灌注钙蛋白酶抑制剂;和对缺血性血管进行机械式后处理,从而实现协同的或额加的改善以减少再灌注治疗期间的梗塞尺寸。 [0138] In one embodiment, the method includes: administering the sustained release adenosine; during the perioperative procedures (peri-procedually) perfusion calpain inhibitor; and ischemic blood vessel after mechanical treatment, in order to achieve synergistic amount plus improvements or to reduce infarct size during reperfusion therapy.

[0139] 在又一个方面中,有益制剂包括类糜蛋白酶抑制剂。 [0139] In yet another aspect, the beneficial agents comprising chymase inhibitors. 以下提供类糜蛋白酶抑制剂的某些非限制性示例。 Some non-limiting examples are provided below chymase inhibitors.

Figure CN103599588BD00241

[0142]在一个实施例中,有益制剂是氧、一氧化氮和氧、或活性〇2和氧。 [0142] In one embodiment, the beneficial agents is oxygen, nitric oxide and oxygen, or oxygen and reactive 〇2. 在该方面中,该方法包括在被布置在血管内的球囊顺序膨胀和收缩期间将氧循环递送到血管和/或梗塞部位。 In this aspect, the method comprises sequentially arranged during balloon within the blood vessel expansion and contraction cycles deliver oxygen to the blood vessel and / or infarction site. 例如,循环加压的〇2可以递送到左主冠状动脉、左心室、左心室壁、右心房通道。 For example, the cycle may be delivered to the pressurized 〇2 left main coronary artery, left ventricle, left ventricular wall, right atrial channel. 在某些实施例中,可以使用人造〇2载体,例如富含〇2的全氟化碳流体。 In certain embodiments, the carrier may be an artificial 〇2, e.g. rich in 〇2 perfluorocarbon fluid. 在另一个实施例中,人造〇2载体的循环灌注可以被引入冠状脉管床。 In another embodiment, the artificial circulation support 〇2 perfusion beds may be introduced into the coronary vasculature. 左主动脉处的正压力与静脉侧处的负压力结合将引入富含〇2的瞬时流动环路。 Positive pressure in conjunction with the negative pressure side at the vein of the left aorta introducing enriched 〇2 instantaneous flow loop. 在某些实施例中,加压的〇2可以通过导管的专用管腔经由纳米气泡被局部地递送到动脉。 In certain embodiments, the pressurized 〇2 dedicated lumen of the catheter can be delivered to the artery through the nano bubble locally. 在该方面中,导管可以包括抽吸接触和加压的释放喷嘴。 In this aspect, the catheter may comprise contacting a suction nozzle and a pressure release. 在循环中在分配加压〇2的同时通过抽吸可以紧紧地保持接触面积。 In the cycle in the pressurized dispensing 〇2 while tightly holding the contact area by suction. 循环的〇2可以被递送以诱导梗塞修复、增强成纤维细胞生长和/或血管生成。 〇2 cycle may be delivered to induce infarct repair, augmentation fibroblast growth and / or angiogenesis.

[0143] 在一个实施例中,有益制剂包括锌螯合剂。 [0143] In one embodiment, the beneficial agents include zinc chelator. 锌螯合剂可以用于增强灌注的生物材料凝胶体就地交联和凝胶化。 Biomaterial gel zinc chelating agents may be used to enhance perfusion in situ crosslinking and gelling. 在另一个实施例中,锌螯合剂是生物材料的侧基。 In another embodiment, the zinc chelator is a side group of biological material.

[0144] 在另一个方面中,生物材料(例如polaxamers、pluronics、PEG_PLLA和PEG-PLGA二嵌段或三嵌段共聚物)可以被施用以屏蔽受体,从而防止Zn 2+损坏梗塞面积。 [0144] In another aspect, the biological material (e.g. polaxamers, pluronics, PEG_PLLA, and PEG-PLGA diblock or triblock copolymer) may be administered to shield the receptor, thereby preventing damage to infarct size Zn 2+.

[0145] 其它有益制剂可以包括但不限于:存在基质细胞衍生因子(SDF-1)的供体小板、胰高血糖素样肽l(GLP-l)、博来霉素和/或四环素。 [0145] Other beneficial agents may include but are not limited to: the presence of stromal cell derived factor (SDF-1) donor platelets, glucagon-like peptide-l (GLP-l), bleomycin and / or tetracycline. 在该方面中,血小板可以从供体获得。 In this aspect, the platelets can be obtained from the donor. 血小板可以在存在SDF-1的情况下被电穿孔以增加血小板SDF-1含量。 Platelets can be electroporated in the presence of SDF-1 in the case of SDF-1 to increase the platelet content. 可以通过将经处理的血小板局部地递送到供给梗塞的心肌的冠状动脉中来治疗已经受到心肌梗塞的目标对象。 The target object can be treated by the myocardial infarction has been delivered to the infarcted myocardium supplied by coronary locally treated platelets.

[0146] 在一个实施例中,血小板可以借助细胞因子(例如可溶性kit配体、促血小板生成素)激活。 [0146] In one embodiment, the platelet (e.g. soluble kit ligand, thrombopoietin) can be activated by cytokines. 在不固持任何理论的情况下认为的是,经处理的血小板将梆缚到梗塞区域内的受损伤动脉的表面或将聚集以在在梗塞区域中形成微脉管阻塞。 Without any theory holding that is to bang the treated platelets to a surface of the injured artery tied in the region of the infarct or the aggregated micro-vascular obstructions formed in the infarct region. 在梗塞区域内的血小板激活将刺激祖细胞恢复和截存,所述祖细胞将替换心肌细胞和/或促进梗塞区域的血管再生,改善心肌功能并且减小心力衰竭的可能性。 Platelet activation in the infarcted area to stimulate the recovery of progenitor cells and sequestration, and the progenitor cells to replace the possibility of cardiomyocytes / or promote revascularization of the infarcted region, improve cardiac function and reduced heart failure.

[0147] 在一个实施例中,有益制剂是生物材料,当生物材料在机械式后处理期间释放时可以增加在脉管系统中的停留时间。 [0147] In one embodiment, the formulation is beneficial biological material, when the biological material is released during the mechanical treatment after can increase the residence time in the vasculature. 该停留时间的增加可以增强从梗塞诱导受伤部位下游进入血管中的质量运输性能,并增加在相邻组织中的生物材料吸收。 This increases the residence time may enhance the induction into the wound site downstream of the mass transport properties from the blood vessel infarction, and increased biological material in the adjacent tissue absorption. 生物材料吸收效力的增加将增强心肌重构的衰减。 Increase the effectiveness of biological material to absorb the increased cardiac remodeling attenuation. 术语"心肌重构"指的是心室经历消极的几何和/或结构变化, 通常随后是心肌梗塞。 The term "cardiac remodeling" refers to the negative experience ventricular geometry and / or structural changes, usually followed by myocardial infarction. 典型地,该重构包括梗塞的扩大和健康心室区段的扩张,期导致壁应力增大。 Typically, the infarct remodeling involves the expansion of the expansion and ventricular health sector, of leading to increased wall stress.

[0148] 例如可以通过增大与血液相容性聚合物的增大赋形剂粘度而提高有益制剂的停留时间。 [0148] For example excipients may increase the viscosity of the blood compatibility of the polymer and increase the residence time by increasing the beneficial agents. 合适的血液相容性聚合物包括透明质酸、聚乙烯吡咯烷酮(PVP)、泊咯沙姆、普朗尼克、海藻酸钠、聚谷氨酸、聚丙烯酸(PAA)、聚乙二醇(PEG)、聚氧化乙烯、PEG反应凝胶、EDTA-共辄聚丙烯酸、丝弹性蛋白(如同蛋白质聚合物)、聚(NIPAAM)-PAA共聚物、白蛋白和聚(乙烯醇)PVA。 Suitable polymers include hemocompatible hyaluronic acid, polyvinylpyrrolidone (PVP), poloxamers, pluronics, sodium alginate, polyglutamic acid, polyacrylic acid (PAA), polyethylene glycol (PEG ), polyoxyethylene, PEG gel reaction, EDTA-co Noir polyacrylic, silk elastin (as the protein polymer), poly (NIPAAM) -PAA copolymer, albumin, and poly (vinyl alcohol) PVA.

[0149] 可以采用各种用于局部递送有益制剂的方法。 [0149] The method may be employed topical delivery for a variety of beneficial agents. 定量供给方法、配方设计方法和递送方法可以被设计成将特定功能或效果作为目标。 Dosing method, the formulation design and method of delivery methods may be designed to target a specific function or effect. 在该方面中,设计选择会影响局部药物代谢动力学(例如,C max、T1/2、AUC等等)、血液试剂流入组织的速率、微循环阻塞、血管接触面积和血管接触接近性以及作用力。 In this aspect, the design choice will affect local drug pharmacokinetics (e.g., C max, T1 / 2, AUC and the like), the rate of blood flow into the reagent tissue, microvascular obstruction, vessel contact area and the proximity of the contact and the role of vascular force. 例如,可以选择参数(例如有益制剂选择、给药方案、配方设计、球囊膨胀/收缩算法、球囊形状、球囊表面、球囊材料和递送顺序)来实现期望的结果。 For example, the parameters may be selected (e.g. selected beneficial agents, the dosing regimen, formulation, balloon inflation / deflation algorithm, the shape of the balloon, the surface of the balloon, and the balloon material delivery order) to achieve the desired results.

[0150] 球囊形状参数 [0150] balloon shape parameter

[0151] 例如,球囊形状可以被设计成避免在膨胀期间与血管壁接触。 [0151] For example, the balloon shape may be designed to avoid contact with the vessel walls during expansion. 这样,局部递送的有益制剂可以在球囊的表面与血管壁之间流动,从而血液试剂流入心肌的速率将得以控制。 Thus, local delivery of beneficial agents may be between the surface of the balloon and the vessel wall flow, whereby the rate of blood flow into the myocardium agent will be controlled. 形状的效果包括:(1)使堵塞期间的接触最小化,和(2)以允许流动(渗漏或蠕动)但不灌注的方式调控流速。 Effect of the shape include: (1) contacting period to minimize clogging, and (2) to allow flow (peristaltic or leakage) without perfusion flow rate regulated manner. 在一个实施例中,球囊形状参数包括球囊具有较大的曲率程度,即低的面积对容量的比率,例如但不限于球形球囊。 In one embodiment, the balloon includes a balloon shape parameters having a large degree of curvature, i.e., the ratio of the area of ​​low capacity, for example, but not limited to spherical balloon. 球囊表面可以包括凝胶涂层、表面活性剂涂层,或被涂覆以实现期望的设计参数(例如血管接触和抵靠血管壁的增大的作用力)。 The balloon surface may include a gel coating, surfactant coating, or coated to achieve desired design parameters (e.g. vessel contact against the vessel wall and increased force). 在该方面中,可以选择涂覆有凝胶的球囊表面以设计提供在递送有益制剂期间抵靠血管壁的更大接触。 In this aspect, the gel coated may be selected to balloon designed to provide greater surface contact with the beneficial agents during delivery against the vessel wall.

[0152] 算法参数 [0152] algorithm parameters

[0153] 膨胀收缩算法例如可以选自包括锯齿状、斜锯齿状、整流正弦波在内的算法。 [0153] Algorithm for the expansion and contraction may be selected from, for example, serrated, jagged diagonal, including algorithms rectified sine wave. 定剂量率例如在机械式后处理的膨胀循环和收缩循环二者期间可以恒定不变、单调递增或单调递减。 Dosing rate can be constant, for example, during the expansion and contraction cycle in the cycle both the mechanical processing, monotonic increasing or decreasing monotonically. 在一个实施例中对流速加以控制,例如流速中断、逐渐地增加、逐渐地中断、然后逐渐地增加。 In one embodiment of the controlled flow, such as flow rate interruption is gradually increased, gradually break, and then gradually increase.

[0154] 有益制剂赋形剂 [0154] Advantageous excipients

[0155] 有益制剂配方设计可以是含有缓冲剂的盐水赋形剂,或可替代地,赋形剂可以包括粘度改进剂、悬浮液、脂质体、胶束、纳米粒子、微球体、或生物材料。 [0155] Advantageous formulations Formulation excipients may be a buffer containing salt, or alternatively, the excipients may include viscosity modifiers, suspensions, liposomes, micelles, nanoparticles, microspheres, or biological material.

[0156] 有益制剂的递送可以通过各种方法实现,例如在再灌注装置中的注入管腔、涂覆球囊、针头球囊、灌注球囊。 [0156] deliver beneficial agents may be achieved by various methods, for example, reperfusion injection lumen device, the coated balloon, the balloon needle, the perfusion balloon. 在一个实施例中,再灌注装置被设计有管腔,所述管腔适于将有益制剂局部地递送到血管中的梗塞或受伤部位的远端。 In one embodiment, the reperfusion apparatus is designed with a lumen distal end adapted to locally deliver benefit agents into the blood vessel of the infarct or wound site.

[0157] 功效研究 [0157] Efficacy Study

[0158] 对猪的冠状动脉中的在诱发90分钟缺血之后的经皮缺血后处理的急性效果进行了评价。 [0158] The evaluation was induced 90 minutes after the percutaneous treatment of ischemic acute ischemic coronary effects in swine. 选择非动脉粥样硬化猪模型,这是因为猪的动脉和人的动脉具有相关类似的解剖结构,FDA以及Schwartz等人的"用于外周应用场合的药物-洗脱支架的临床前评价:来自Expert Consensus Group,Circulation,2004; 110:2498-2505的推荐"也推荐将猪模型用于临床前研究。 Non-selected porcine model of atherosclerosis, since porcine and human arteries associated with similar arterial anatomy, the FDA and Schwartz, et al., "Medicament for peripheral applications - the preclinical evaluation eluting stents: from Expert Consensus Group, Circulation, 2004; 110: 2498-2505 recommendation "is also recommended in a porcine model for preclinical studies. 动物具有以下模型描述: Animal model has the following description:

Figure CN103599588BD00261

[0160] 在研究中,动物接受了抗血小板治疗以防止或减少血栓形成事件的发生。 [0160] In the study, the animals received the anti-platelet therapy to prevent or reduce the occurrence of thrombotic events. 至少在进行干预的三天前让动物每日接受口服乙酰水杨酸(325mg)和氯吡格雷(初始剂量300mg并且随后75mg)。 At least three days before carrying out the intervention of the animals received daily oral administration of acetylsalicylic acid (325mg) and clopidogrel (300mg initial dose and then 75mg). 在手术之前,用咪达唑仑0.4mg/kg肌肉注射使动物镇静并在1分钟至5分钟之后用氯胺酮20mg/kg和阿托品0.04mg/kg肌肉注射施用。 Prior to surgery, with midazolam 0.4mg / kg intramuscular injection the animals were killed and after 1-5 minutes with ketamine 20mg / kg and Atropine 0.04mg / kg administered intramuscularly. 在浅麻醉诱导时,动物被插管并且用机械通风支持。 When shallow induction of anesthesia, intubation and the animal is supported by mechanical ventilation. 通过IV连续/间歇行注入异丙酸4mg/kg/h和芬酞尼0.004mg/kg/h(在5%葡萄糖溶液中)实现麻醉。 By IV continuous / intermittent injection line isopropylate 4mg / kg / h and fentanyl 0.004mg / kg / h of anesthesia (5% glucose solution). 以每15分钟0. lmg/kg的剂量施用咪达唑仑。 Every 15 minutes at 0. lmg / kg dose administered midazolam. 根据需要仅以较低量施用异氟烷来维持手术的麻醉。 The only required lower amounts administered isoflurane anesthesia is maintained.

[0161] 在麻醉诱导之后,通过腹股沟皮肤切口接近左或右股动脉。 [0161] After the induction of anesthesia, inguinal skin incision near the left or right femoral artery. 丁哌卡因被肌肉注射施用以管理手术期间的疼痛。 Bupivacaine is administered intramuscularly in the management of pain during surgery. 导引导管被放置在鞘中并且在透视引导下前进到左冠状动脉口中。 Guide catheter is placed in the sheath and advanced to the mouth of the left coronary artery under fluoroscopic guidance. 冠脉导丝通过引导导管插入并且前进到冠状动脉左前降支(LAD)中。 Coronary guide catheter is inserted through the guide wire and advanced to the left anterior descending coronary artery (LAD) in. 球囊沿着导丝前进,直到球囊到达LAD的第二对角分支的远端为止。 Advancing the balloon over the guidewire, until the distal end of the second diagonal branch of LAD until it reaches the balloon. 将球囊膨胀到具有足以完全堵塞冠状动脉的压力(1:1:1尺寸比)。 The balloon is inflated to have a pressure sufficient to completely block the coronary artery (1: 1: 1 ratio). 使用血管造影术来检验LAD被完全堵塞住。 Use angiography to examine the LAD was completely blocked live. 使球囊膨胀90分钟并且对动物在两个小时的再灌注时期进行观察。 Inflating the balloon 90 minutes and the animals were observed during the two hours of reperfusion.

[0162] 在完成再灌注即后,使用本文所描述系统的实施例执行后处理。 [0162] After completion of reperfusion i.e., using the embodiment of the system described herein performs post-processing described herein. 通过使球囊导管在导丝上通过引导导管前进到部署位置而将装置引入冠状动脉中。 The device into the coronary artery by the balloon catheter over the guidewire advances through the guide catheter to the deployment position. 部署一触式致动器开关,并且使球囊持续膨胀30 ± 3秒。 Deploying a touch switch actuator, and continued expansion of the balloon 30 ± 3 seconds. 在膨胀时期之后,球囊收缩,并且通过造影剂注射确定血管开放(ΊΊΜΙ流动评价)。 After expansion period, the balloon is contracted, and the injection is determined patency (ΊΊΜΙ flow Evaluation) contrast agent. 在30 ± 3秒的膨胀期间,施用lmg/kg剂量的钙蛋白酶抑制剂。 During expansion 30 ± 3 seconds, administered lmg / kg dose of calpain inhibitors. 在球囊收缩了30±3秒之后,球囊膨胀另一个30秒的循环。 After the contraction of the balloon 30 ± 3 seconds balloon inflation cycle for another 30 seconds. 上述循环被重复,直到完成八次回合的30秒膨胀/收缩为止。 The above cycle is repeated until 30 seconds to complete the second leg of the eight expansion / contraction so far. 此后,移除递送装置。 Thereafter, the delivery device is removed.

[0163] 参照图19,在后处理期间钙蛋白酶抑制剂的局部递送导致梗塞组织处的有益制剂组织吸收比骨骼肌肉处和健康组织处的有益制剂吸收增加平均四十倍。 [0163] Referring to FIG 19, during post-processing of the local delivery of calpain inhibitors useful formulation results in infarcted tissue at the tissue absorption than the beneficial agents and skeletal muscle tissue health at four times the average increase in absorbance. 梗塞心肌中的有益制剂浓度是24 · 411 yg/gm,骨骼肌肉中的有益制剂浓度是0 · 174yg/gm,健康心肌中的有益制剂浓度是〇. 457yg/gm。 The concentration of beneficial agents in infarcted myocardium is 24 · 411 yg / gm, the concentration of beneficial agents skeletal muscle is 0 · 174yg / gm, the concentration of beneficial agents healthy myocardium is square. 457yg / gm. 应认识到,有益制剂停留时间的增加和远端停滞产生了对流,从本文所描述方法导致了显著更高的有益制剂吸收。 It should be appreciated that increasing the residence time and the distal end of the stagnation of beneficial agents produce convection methods described herein resulted from significantly higher absorption of beneficial agents.

Figure CN103599588BD00271

[0165] [0165]

Figure CN103599588BD00281

[0166] 以上的表1是示出在目标对象的梗塞组织/健康组织中检测到的钙蛋白酶抑制剂的浓度yg/gm的表格。 [0166] The above Table 1 is a table showing the density detection of the target object in the infarcted tissue / healthy tissue calpain inhibitor yg / gm of. 这些结果令人惊奇地示出了在骨骼肌肉、梗塞组织和健康组织中钙蛋白酶抑制剂的吸收增加了超过144倍(猪11),并且甚至最低结果仍然增加了4.5倍(猪42)。 These results surprisingly shows an absorption calpain inhibitors in skeletal muscle, infarcted tissue, and healthy tissue, it increased more than 144-fold (11 pigs), and even the lowest result is still increased by 4.5-fold (42 pigs).

[0167] 图20示出在后处理手术期间,在局部递送到血管之后,在时间15分钟、30分钟、60 分钟、90分钟和120分钟检测到的血浆浓度的图表。 [0167] FIG. 20 shows the operation during post-processing, after local delivery into a blood vessel, at time 15 minutes, 30 minutes, 60 minutes, graph the plasma concentration detected 90 and 120 minutes. 如图所示,甚至在手术之后的两个小时, 血浆中钙蛋白酶抑制剂的浓度保持在0. 〇356μg/ml水平。 As shown, even after two hours of operation, a calpain inhibitor concentration in plasma is maintained at 0. 〇356μg / ml level. 以下的表格2是在时间5分钟、10分钟、15分钟、30分钟、60分钟、90分钟和120分钟在猪体内检测到血浆的钙蛋白酶抑制剂的浓度μg/ml的表格。 The following Table 2 is a time of 5 minutes, 10 minutes, 15 minutes, 30 minutes, 60 minutes, 90 minutes and 120 minutes to form detected in pigs calpain inhibitor concentration in plasma μg / ml of. 如图所示,有益制剂的平均浓度随着时间减小,但是仍然保持明显的浓度, 在10分钟时为0.615ug/ml,在15分钟时为0.318ug/ml,在30分钟时为0.145ug/ml,在60分钟时为0.069ug/ml,在90分钟时为0.0469ug/ml,和在120分钟时为0.0356ug/ml。 As shown, the average concentration of beneficial agents decreases over time, but still maintaining significant concentration at 10 minutes was 0.615ug / ml, at 15 min was 0.318ug / ml, at 30 minutes 0.145ug / ml, at 60 minutes of 0.069ug / ml, for 90 minutes at 0.0469ug / ml, and was 0.0356ug / ml at 120 minutes.

[0168] 表2 [0168] TABLE 2

Figure CN103599588BD00291

[0170] [0170]

Figure CN103599588BD00301

[0171] 图21示出在试验的三个不同样本集之间的梗塞尺寸/风险面积比率的对比:(1) "Control"组,其中不执行后处理;(2)"Angi 〇PC"组,其中使用传统的血管成形术导管执行后处理;和(3)"PUFF"组,使用在本文所实施并描述的"PUFF"再灌注系统执行后处理手术。 [0171] FIG. 21 shows a comparison of infarct size in the three different sets of samples between test / risk area ratio: (1) "Control" group, wherein the post-processing is not performed; (2) "Angi 〇PC" group , using a conventional angioplasty catheter after performing process; and (3) "PUFF" group, used in the embodiments herein described and "PUFF" reperfusion processing system to perform surgery. 该图表示出对于每个组而言在七天和二十八天时的梗塞尺寸相对于风险面积(即在梗塞的下游)的比率。 The graph shows seven days for each group and infarct size at day twenty-eight risk relative to the area (i.e., downstream infarction) ratio. 风险面积通过T2w-ST IR确定,T2w-ST IR是已知用于确定心脏内的水量(水肿) 的方法。 Area at risk is determined by T2w-ST IR, T2w-ST IR methods are known in water (edema) in the heart for determining.

[0172] 如图所示,使用传统的血管成形术导管和"PUFF"系统二者的后处理在七天和在二十八天提供了明显超过"Control"组(即不执行后处理)的优点。 [0172] As shown, using conventional angioplasty advantages over seven days and provided a significant "Control" group (i.e., post-processing is not performed) for 48 days in the second conduit and both "PUFF" after treatment system . " Control"组示出梗塞尺寸/风险面积的比率在7天时是约70%和在28天时是约58%,而AngioPC组示出梗塞尺寸/风险面积的比率在7天时约45%、在28天时是40%,而PUFF组示出梗塞尺寸/风险面积的比在7天时约53%和在28天时是38%。 "Control" group shows the ratio of infarct size / risk area at day 7 was about 70% and at 28 days was about 58%, while AngioPC group shows the ratio of infarct size / risk area at day 7 to about 45%, at 28 day was 40%, while the ratio shown PUFF group infarct size / risk area of ​​about 53% at 7 days and at 28 days was 38%. 因此,与使用传统的血管成形术导管的后处理相比,随着时间,使用PUFF系统的后处理改进了对再灌注损伤的缓解和减少。 Thus, using conventional angioplasty catheter post-treatment compared with the time, the system used PUFF aftertreatment improves the ease of reduction and reperfusion injury.

[0173] 除了改进的梗塞尺寸/风险面积之外,使用PUFF系统的后处理手术还体现出超过不进行后处理的情况和使用传统的血管成形术导管的后处理的改进的射血分数。 [0173] In addition to improved infarct size / area at risk, the use of surgical PUFF aftertreatment system reflects the situation after further processing is not exceeded, and ejection fraction using the improved conventional vascular treatment catheter is formed. "射血分数"指的是在每次心搏下从充满的心室栗送出来的血液百分比。 "Ejection fraction" means at every heartbeat Li sent out from the blood filled ventricle percentage. 在收缩之前即刻的心室内血液体量已知为舒张末期容量。 Indoor blood body cardiac contraction immediately before is known as end-diastolic volume. 在收缩结束时的左心室中的血液容量是收缩末期容量。 The volume of blood in the left ventricle at the end of the contraction is the systolic volume. 舒张末期容量和收缩末期容量之间的差是心搏容量或每次心搏射出的血液容量。 The difference between end-diastolic volume and end-systolic volume or capacity of cardiac blood volume ejected per beat. 因此,射血分数是心搏容量除以舒张末期容量。 Therefore, cardiac ejection fraction is divided by the capacity of end-diastolic volume. 正常的LV射血分数是55%至70%。 Normal LV ejection fraction is 55-70%.

[0174] 图22是示出与不执行后处理的"Control"组相比在缺血性事件和由传统的血管成形术导管和PUFF再灌注导管执行的后处理之后射血分数的对比研究结果的图表。 [0174] FIG. 22 is a diagram illustrating a result of ischemic events compared with the comparison process is not executed after the "Control" group and after ejection fraction by a conventional angioplasty catheter and the treatment catheter PUFF reperfusion studies performed chart. 如图表中所示,在七天之后,根据使用本发明再灌注系统(即"PUFF")的后处理治疗后的目标对象展示出与"Control"组和"AngioPC"组二者相比改进的射血分数。 Improved compared to both the audience as shown in the graph show, after seven days, according to the present invention using the system of reperfusion (i.e. "PUFF") post-treatment after the treatment with the "Control" group and "AngioPC" group shot ejection fraction. 在该方面中,与其它另外两个组相比,7天之后的射血分数更接近于55%至70%的正常射血分数。 In this aspect, compared to the other two other groups, 7 days after the ejection fraction is closer to 55-70% of normal ejection fraction. 此外,在28天时取得的射血分数测量时,这种改进与"AngioPC"组相比得以维持并确实增加。 Further, when the ejection fraction measurements taken at 28 days, with this improvement "AngioPC" group compared maintained and does increase. 在没有固持任何理论的情况下认为的是,血管成形术导管会破坏脉管壁而导致射血分数随着时间减小,但是"PUFF"组令人惊异地展示出射血分数随着时间增大。 In the absence of any theory holding that is, angioplasty catheter will destroy the vessel wall caused by ejection fraction decreases over time, but the "PUFF" group exhibit surprisingly ejection fraction increases with time .

[0175] 应当理解的是,本文所描述主题并不限于所描述特定实施例,并因此当然可以变化。 [0175] It should be appreciated that the subject matter described herein is not limited to the particular embodiments described herein, and thus of course, vary. 还应当理解的是,由于本发明主题的范围仅受所附权利要求书的限制,本文所使用术语仅用于描述特定实施例而非限制性的。 It should also be appreciated that, since the scope of the subject matter of the present invention is limited only by the appended claims, the terms used herein is for describing particular embodiments only and not limiting. 当提供了数值的范围时,应当理解的是,该范围的上限值与下限值之间的每个中间值以及在所提及范围内的任何其它被提及的数值或中间值被包含在所披露主题内。 When a range of values ​​is provided, it is understood that each intervening value between the upper limit and lower limit of that range and any other intermediate mentioned value or values ​​within the mentioned range are contained within the disclosed subject matter. 虽然已经参照示例性实施例详细地说描述和指明本发明,但本领域的技术人员将理解,可以在没有脱离所披露实施例的精神的情况下进行各种改变,修改, 置换和删除。 Although it has been said with reference to the exemplary embodiments described and specified in the present invention in detail, those skilled in the art will appreciate that in the embodiments without departing from the spirit of the disclosed embodiments various changes, modifications, substitutions and deletions. 因此,要求保护的本发明将包括在以下权利要求书的范围内的等同内容。 Accordingly, the claimed invention includes the equivalents within the scope of the following claims.

Claims (18)

  1. 1. 一种导管系统,包括: 导管轴(200)和被布置在所述导管轴上的球囊(300),其中,所述导管系统能够由一个人操作,从而在少于四秒的时间内致动所述球囊的膨胀,所述导管轴包括沿着导管轴布置的膨胀管腔(203)和独立的收缩管腔(204); 手柄(100 ),该手柄能够用手携带并包括: 储器(101 ),该储器被布置在所述手柄中,用以向所述导管轴和所述球囊供给流体, 致动器(107),该致动器适于当在第一位置或方向中被致动时允许所述球囊膨胀;以及一系列阀(115),其用于控制和调节膨胀流体通过所述导管系统的脉动的和/或调控的流动, 布置在所述手柄中的控制系统; 流体回路,该流体回路包括所述膨胀管腔、所述独立的收缩管腔、所述控制系统和所述一系列阀, 其中,流体通过所述流体回路的流动是单向的。 A catheter system, comprising: a catheter shaft (200) and is disposed in the balloon catheter shaft (300), wherein said catheter system can be operated by one person, so that less than four seconds actuating the expansion of said balloon, said catheter shaft comprises a catheter shaft disposed along the inflation lumen (203) and an independent shrinkage lumen (204); a handle (100), the handle can be carried by hand and comprises : reservoir (101), which reservoir is arranged in the handle for the catheter shaft to the balloon and the fluid supply, the actuator (107), when the actuator is adapted in a first position or direction is permitted upon expansion of the balloon actuated; and a series of valves (115), for controlling and adjusting the inflation fluid through a pulsation of the catheter system and / or flow control, disposed in the the control system in the handle; fluid circuit, the fluid circuit comprising the inflation lumen, the contraction of separate lumen, and the series of the control valve system, wherein the flow of fluid through said fluid circuit is a single direction.
  2. 2. 根据权利要求1所述的导管系统,其中,所述导管系统能够在少于一秒的时间内使所述球囊膨胀。 2. The catheter system according to claim 1, wherein the system enables the balloon catheter inflated in less than one second.
  3. 3. 根据权利要求1所述的导管系统,其中,所述流体回路还包括文丘里辅助式收缩,其中,所述导管系统能够在少于五秒的时间内使所述球囊收缩。 The catheter system according to claim 1, wherein said fluid circuit further comprises a venturi assisted contraction, wherein said balloon catheter system capable of shrinkage in less than five seconds.
  4. 4. 根据权利要求1所述的导管系统,其中,所述导管系统能够在一秒的时间内使所述球囊收缩。 The catheter system according to claim 1, wherein said balloon catheter system capable of the contraction in the time of one second.
  5. 5. 根据权利要求1所述的导管系统,其中,所述导管轴包括独立的管腔(206),用以递送一种或更多种有益制剂。 The catheter system according to claim 1, wherein said catheter shaft comprises a separate lumen (206), to deliver one or more beneficial agents.
  6. 6. 根据权利要求1所述的导管系统,其中,所述导管轴包括从所述导管轴的近端区段和远端区段延伸的三个独立的管腔(203,204和205),并且其中,所述管腔并置以形成工字梁状聚合物腹板(208),所述工字梁状聚合物腹板与所述管腔的纵向轴线横向地对准。 6. The catheter system according to claim 1, wherein said catheter shaft comprises three separate lumens (203, 204 and 205) extending from a proximal section and a distal section of the catheter shaft, and wherein , the lumen juxtaposed to form a polymer-beam web (208), the I-beam-like polymer web transversely aligned with the longitudinal axis of the lumen.
  7. 7. 根据权利要求1所述的导管系统,其中,所述球囊是顺应性球囊。 7. The catheter system according to claim 1, wherein the balloon is a compliant balloon.
  8. 8. 根据权利要求7所述的导管系统,其中,所述球囊具有足够的顺应性,以便在引入血管中时适应所述血管的形状。 8. The catheter system of claim 7, wherein the balloon has sufficient compliance to accommodate the shape of the blood vessel when introduced into the blood vessel.
  9. 9. 根据权利要求1所述的导管系统,其中,所述球囊是螺旋形的或是形成有凹坑。 9. The catheter system according to claim 1, wherein the balloon is formed with a helical or pits.
  10. 10. -种导管系统,包括: 导管轴(200)和被布置在所述导管轴上的球囊(300), 容装有膨胀流体的储器(101), 所述导管轴限定出膨胀管腔(203)和独立的收缩管腔(204)、以及入口端口和出口端口,所述膨胀管腔和所述收缩管腔通过一系列单向止回阀(115)连接,在膨胀端口和收缩端口与所述球囊的内部之间提供单向的、独立的流体连通,以及致动器(107),该致动器适于当在第一位置或方向中被致动时允许所述球囊膨胀;以及不可逆的装载装置(114),用以允许膨胀流体从所述储器流到所述膨胀管腔。 10. - species catheter system, comprising: a catheter shaft (200) and a balloon disposed on the catheter shaft (300), receiving a reservoir containing expansion fluid (101), said catheter shaft defining an inflation tube chamber (203) and an independent shrinkage lumen (204), and the inlet and outlet ports, the contraction of the lumen and an inflation lumen through a series of one way check valve (115) is connected to the port expansion and contraction providing unidirectional port and between the interior of the balloon, independent fluid communication, and an actuator (107), adapted to allow the actuator when the ball is actuated in a first direction or position balloon expansion; irreversible and loading means (114), to allow the inflation fluid to flow from the lumen of the expansion reservoir.
  11. 11. 根据权利要求10所述的导管系统,其中,所述装载装置适于穿透所述储器以允许将膨胀流体释放到所述膨胀管腔中。 11. The catheter system of claim 10, wherein said loading means adapted to penetrate said reservoir to permit the inflation fluid is released to the expanded lumen.
  12. 12. 根据权利要求11所述的导管系统,其中,所述膨胀流体是气态物质。 12. The catheter system of claim 11, wherein the expansion fluid is a gaseous substance.
  13. 13. 根据权利要求10所述的导管系统,其中,所述导管轴包括压力指示器(118),该指示器被布置在所述球囊和与所述收缩管腔相关联的止回阀之间。 13. The catheter system according to claim 10, wherein said catheter shaft comprises a pressure indicator (118), the indicator being disposed on the balloon and associated with the contraction of the lumen of a check valve between.
  14. 14. 根据权利要求10所述的导管系统,其中,所述导管轴包括独立的管腔(206),用以递送有益制剂来改善缺血性事件之后在目标对象中的梗塞尺寸。 14. A catheter system according to claim 10, wherein said catheter shaft comprises a separate lumen (206) for delivering beneficial agents to improve the infarct size after ischemic event in the target object.
  15. 15. -种用于实施缺血后处理的系统,包括: 导管(200),该导管包括至少一个能扩张构件(300),所述导管被构造成用于各种血管尺寸,所述导管被构造成接收具有预定尺寸的导丝,并且所述导管具有沿着所述导管布置的膨胀管腔(203)以及独立的收缩管腔(204); 手柄(100),该手柄具有整个位于所述手柄中的、用于容装膨胀流体的储器(101);所述储器与所述导管联接,所述至少一个能扩张构件被布置成与所述储器流体连通,并能够经由膨胀管腔(203)通过膨胀流体膨胀一段时间和能够经由独立的收缩管腔(204)收缩,其中,所述至少一个能扩张构件的顺序膨胀和收缩由单触式致动来实现。 15. - seed treatment for post-ischemic embodiment of the system, comprising: a catheter (200), the conduit comprises at least one expansion member (300), the catheter is configured for a variety of vessel size, the catheter is configured to receive a guidewire having a predetermined size, and the catheter having an inflation lumen along said conduit arrangement (203) and an independent shrinkage lumen (204); a handle (100), the handle having positioned the entire the handle, for containing inflation fluid reservoir (101); said reservoir and said conduit coupling said at least one expansion member is arranged to be in fluid communication with the reservoir, and can be inflated via a tube chamber (203) is expanded by inflation fluid for a time and via an independent shrinkage collapsible lumen (204), wherein the at least one order of expansion and contraction of the expansion member is realized by one-touch actuation.
  16. 16. 根据权利要求15所述的系统,该系统被构造成在进行后处理的同时递送治疗用制剂。 16. The system according to claim 15, the system is configured to process after performing the simultaneous delivery of therapeutic agents.
  17. 17. 根据权利要求16所述的系统,其中,所述导管被构造成在递送治疗用制剂的同时接收快速交换导丝。 17. The system according to claim 16, wherein the conduit is configured to deliver therapeutic agents at the same time receiving a rapid exchange guidewire.
  18. 18. 根据权利要求15所述的系统,其中,所述能扩张构件被构造成具有足够的顺应性以使得所述能扩张构件能够吻合血管形状。 18. The system according to claim 15, wherein said expansion member is configured to have sufficient compliance such that the expansion member can be vascularized shape.
CN 201310453105 2010-04-30 2011-04-29 Showing the rapid expansion and contraction of an improved balloon catheter CN103599588B (en)

Priority Applications (14)

Application Number Priority Date Filing Date Title
USPCT/US2010/033270 2010-04-30
US12/771,968 2010-04-30
US12771968 US8821438B2 (en) 2010-04-30 2010-04-30 Catheter system having a fluid circuit
PCT/US2010/033276 WO2011136815A1 (en) 2010-04-30 2010-04-30 Catheter system having a fluid circuit
USPCT/US2010/033276 2010-04-30
US12771946 US9155869B2 (en) 2010-04-30 2010-04-30 Catheter having inflation and deflation lumen useful for preventing or reducing reperfusion injury
US12/771,946 2010-04-30
PCT/US2010/033270 WO2011136813A1 (en) 2010-04-30 2010-04-30 Catheter having inflation and deflation lumen useful for preventing or reducing reperfusion injury
US13032743 US8366659B2 (en) 2010-04-30 2011-02-23 Reperfusion balloon inflation device
US13032733 US8540669B2 (en) 2010-04-30 2011-02-23 Catheter system providing step reduction for postconditioning
US13/032,733 2011-02-23
US13/032,743 2011-02-23
CN201180028064.72011.04.29 2011-04-29
CN 201180028064 CN102939126B (en) 2010-04-30 2011-04-29 Showing the rapid expansion and contraction of an improved balloon catheter

Publications (2)

Publication Number Publication Date
CN103599588A true CN103599588A (en) 2014-02-26
CN103599588B true CN103599588B (en) 2017-04-26

Family

ID=44147604

Family Applications (2)

Application Number Title Priority Date Filing Date
CN 201310453105 CN103599588B (en) 2010-04-30 2011-04-29 Showing the rapid expansion and contraction of an improved balloon catheter
CN 201180028064 CN102939126B (en) 2010-04-30 2011-04-29 Showing the rapid expansion and contraction of an improved balloon catheter

Family Applications After (1)

Application Number Title Priority Date Filing Date
CN 201180028064 CN102939126B (en) 2010-04-30 2011-04-29 Showing the rapid expansion and contraction of an improved balloon catheter

Country Status (4)

Country Link
EP (1) EP2563446A1 (en)
CN (2) CN103599588B (en)
GB (2) GB2493120B (en)
WO (1) WO2011137372A9 (en)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9289319B2 (en) 2012-05-14 2016-03-22 Abbott Cardiovascular Systems Inc. Flow regulation valve for controlling inflation rate of a balloon deploying a scaffold
US20150080747A1 (en) * 2013-06-28 2015-03-19 Cardiovascular Systems, Inc. Devices, systems and methods for locally measuring biological conduit and/or lesion compliance, opposition force and inner diameter of a biological conduit

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3960007A (en) * 1974-09-27 1976-06-01 Swensen Eugene T Ultrasonic standing wave sensor
US5085249A (en) * 1990-06-01 1992-02-04 Centrix, Inc. Valve for a vascular dilating device

Family Cites Families (37)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3190291A (en) * 1962-10-08 1965-06-22 Frederic E B Foley Self-inflating bag catheter
US3274311A (en) 1963-04-25 1966-09-20 Reynolds Metals Co Method of molding alumina
US3273311A (en) 1964-08-12 1966-09-20 Gary G Henry Animal halter
US3378011A (en) * 1965-06-23 1968-04-16 John P. Vitello Self-inflating catheter with means to prevent leakage of inflation fluid
US3860007A (en) * 1973-02-20 1975-01-14 Kendall & Co Catheter with safety deflation means
US4740203A (en) * 1986-06-05 1988-04-26 Thomas J. Fogarty Refillable injection device
US5304197A (en) 1988-10-04 1994-04-19 Cordis Corporation Balloons for medical devices and fabrication thereof
US5087246A (en) * 1988-12-29 1992-02-11 C. R. Bard, Inc. Dilation catheter with fluted balloon
US5478320A (en) 1989-11-29 1995-12-26 Cordis Corporation Puncture resistant balloon catheter and method of manufacturing
US5484411A (en) * 1994-01-14 1996-01-16 Cordis Corporation Spiral shaped perfusion balloon and method of use and manufacture
US6406457B1 (en) 1994-03-02 2002-06-18 Scimed Life Systems, Inc. Block copolymer elastomer catheter balloons
US5695468A (en) * 1994-09-16 1997-12-09 Scimed Life Systems, Inc. Balloon catheter with improved pressure source
US5647847A (en) * 1994-09-16 1997-07-15 Scimed Life Systems, Inc. Balloon catheter with improved pressure source
EP1611917B1 (en) 1995-10-11 2016-04-27 Terumo Kabushiki Kaisha Catheter balloon and balloon catheter
US20020077564A1 (en) * 1996-07-29 2002-06-20 Farallon Medsystems, Inc. Thermography catheter
DE19650975A1 (en) 1996-12-09 1998-06-10 Basf Ag New heterocyclic substituted benzamides and their use
CN1245486A (en) 1996-12-11 2000-02-23 Basf公司 Ketobenzamides as calpain inhibitors
JP4621351B2 (en) 1998-04-20 2011-01-26 アボット ゲゼルシャフト ミット ベシュレンクテル ハフツング ウント コンパニー コマンディトゲゼルシャフトAbbott GmbH & Co. KG Heterocyclic substituted amides as calpain inhibitors
CA2328396C (en) 1998-04-20 2009-02-10 Basf Aktiengesellschaft New substituted amides, their production and their use
US6482832B1 (en) 1998-05-25 2002-11-19 Abbott Laboratories Heterocyclically substituted amides, their production and their use
DE19928021A1 (en) 1999-06-18 2000-12-21 Basf Ag New nucleic acid encoding testis-specific calpain-11, useful for identifying specific inhibitors for treatment of fertility disorders
US6620127B2 (en) 1999-12-01 2003-09-16 Advanced Cardiovascular Systems, Inc. Medical device balloon
US7163504B1 (en) * 2000-02-16 2007-01-16 Advanced Cardiovascular Systems, Inc. Multi-lumen fluted balloon radiation centering catheter
US6436090B1 (en) * 2000-12-21 2002-08-20 Advanced Cardiovascular Systems, Inc. Multi lumen catheter shaft
US20030014071A1 (en) * 2001-07-14 2003-01-16 Reynolds Timothy C. Inflation device and methods of use
US20070160645A1 (en) 2001-10-25 2007-07-12 Jakob Vinten-Johansen PostConditioning System And Method For The Reduction Of Ischemic-Reperfusion Injury In The Heart And Other Organs
EP1471849A4 (en) 2001-12-21 2011-01-05 Univ Emory Post-conditioning for the reduction of ischemic-reperfusion injury in the heart and other organs
US7641668B2 (en) * 2003-05-16 2010-01-05 Scimed Life Systems, Inc. Fluid delivery system and related methods of use
WO2005003150A3 (en) 2003-07-02 2005-10-13 Univ Emory Compositions and methods for use of a protease inhibitor and adenosine for preventing organ ischemia and reperfusion injury
WO2006069170A3 (en) 2004-12-22 2007-01-04 Univ Emory Therapeutic adjuncts to enhance the organ protective effects of postconditioning
US8221348B2 (en) * 2005-07-07 2012-07-17 St. Jude Medical, Cardiology Division, Inc. Embolic protection device and methods of use
EP2439205B1 (en) 2006-12-29 2015-03-11 AbbVie Deutschland GmbH & Co KG Carboxamide compounds and their use as calpain inhibitors
WO2009083581A1 (en) 2007-12-28 2009-07-09 Abbott Gmbh & Co. Kg Carboxamide compounds and their use as calpain inhibitors
WO2008117257A3 (en) * 2007-03-27 2009-02-05 Intratech Medical Ltd Spiral balloon catheter
WO2008132892A1 (en) 2007-04-17 2008-11-06 Kyocera Corporation Band-pass filter, and radio communication module and radio communication device using the filter
FR2922095B1 (en) * 2007-10-16 2010-09-03 Cie Euro Etude Rech Paroscopie The inflation device of a surgical implant
JP5195144B2 (en) 2008-08-07 2013-05-08 株式会社デンソー Electromagnetic switch

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3960007A (en) * 1974-09-27 1976-06-01 Swensen Eugene T Ultrasonic standing wave sensor
US5085249A (en) * 1990-06-01 1992-02-04 Centrix, Inc. Valve for a vascular dilating device

Also Published As

Publication number Publication date Type
CN102939126A (en) 2013-02-20 application
GB2493120A (en) 2013-01-23 application
CN102939126B (en) 2015-09-16 grant
EP2563446A1 (en) 2013-03-06 application
CN103599588A (en) 2014-02-26 application
GB2505572A8 (en) 2014-06-11 application
GB201219332D0 (en) 2012-12-12 grant
GB201315742D0 (en) 2013-10-16 grant
WO2011137372A1 (en) 2011-11-03 application
WO2011137372A9 (en) 2011-12-22 application
GB2505572A (en) 2014-03-05 application
GB2493120B (en) 2014-04-09 grant
GB2505572B (en) 2014-08-06 grant

Similar Documents

Publication Publication Date Title
US7250041B2 (en) Retrograde pressure regulated infusion
US20060167437A1 (en) Method and apparatus for intra aortic substance delivery to a branch vessel
US20130053792A1 (en) Expandable catheter system for vessel wall injection and muscle and nerve fiber ablation
US7364566B2 (en) Method and apparatus for intra-aortic substance delivery to a branch vessel
US7104981B2 (en) Apparatus and method for inserting an intra-aorta catheter through a delivery sheath
US20020016564A1 (en) Embolization protection sytem for vascular procedures
US6623448B2 (en) Steerable drug delivery device
US6692459B2 (en) Anti-occlusion catheter
US7108684B2 (en) Drug delivery balloon catheter
US7077836B2 (en) Methods and apparatus for sclerosing the wall of a varicose vein
US6706013B1 (en) Variable length drug delivery catheter
US7232432B2 (en) Particle-removing medical device and method
US7131986B2 (en) Catheter having exchangeable balloon
US20030216693A1 (en) Tortuous path injection device and method
US20110060275A1 (en) Drug Eluting Balloon
US20030045860A1 (en) Methods for minimally invasive, localized delivery of sclerotherapeutic agents
US6893421B1 (en) Catheter shaft assembly
US20090209909A1 (en) Percutaneous single-phase surgical procedure for creating a pneumostoma to treat chronic obstructive pulmonary disease
US5817046A (en) Apparatus and method for isolated pelvic perfusion
US7241273B2 (en) Intra-aortic renal delivery catheter
US6613017B1 (en) Controlled depth injection device and method
US20050043678A1 (en) Medical device with drug delivery member
US20040015150A1 (en) Method and apparatus for emboli containment
US6685672B1 (en) Multi-balloon drug delivery catheter for angiogenesis
US20060200191A1 (en) Method and apparatuses for treating an intravascular occlusion

Legal Events

Date Code Title Description
C06 Publication
GR01