CN111001077A - 用于以高压输注胶束的球囊导管系统 - Google Patents

用于以高压输注胶束的球囊导管系统 Download PDF

Info

Publication number
CN111001077A
CN111001077A CN201811473275.1A CN201811473275A CN111001077A CN 111001077 A CN111001077 A CN 111001077A CN 201811473275 A CN201811473275 A CN 201811473275A CN 111001077 A CN111001077 A CN 111001077A
Authority
CN
China
Prior art keywords
balloon
range
diameter
wall
catheter system
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN201811473275.1A
Other languages
English (en)
Inventor
W·R·鲍姆巴赫
D·R·舍曼
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Calibre Therapy Co Ltd
Caliber Therapeutics Inc
Original Assignee
Calibre Therapy Co Ltd
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
Application filed by Calibre Therapy Co Ltd filed Critical Calibre Therapy Co Ltd
Publication of CN111001077A publication Critical patent/CN111001077A/zh
Pending legal-status Critical Current

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES 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
    • A61M25/00—Catheters; Hollow probes
    • A61M25/10—Balloon catheters
    • A61M25/104—Balloon catheters used for angioplasty
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/337—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/436—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
    • A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
    • A61L29/14—Materials characterised by their function or physical properties, e.g. lubricating compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
    • A61L29/14—Materials characterised by their function or physical properties, e.g. lubricating compositions
    • A61L29/146—Porous materials, e.g. foams or sponges
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
    • A61L29/14—Materials characterised by their function or physical properties, e.g. lubricating compositions
    • A61L29/16—Biologically active materials, e.g. therapeutic substances
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES 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
    • A61M25/00—Catheters; Hollow probes
    • A61M25/10—Balloon catheters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES 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
    • A61M25/00—Catheters; Hollow probes
    • A61M25/10—Balloon catheters
    • A61M25/1018—Balloon inflating or inflation-control devices
    • A61M25/10181—Means for forcing inflation fluid into the balloon
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES 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
    • A61M25/00—Catheters; Hollow probes
    • A61M25/10—Balloon catheters
    • A61M25/1018—Balloon inflating or inflation-control devices
    • A61M25/10181—Means for forcing inflation fluid into the balloon
    • A61M25/10182—Injector syringes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES 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
    • A61M25/00—Catheters; Hollow probes
    • A61M25/10—Balloon catheters
    • A61M25/1018—Balloon inflating or inflation-control devices
    • A61M25/10184—Means for controlling or monitoring inflation or deflation
    • A61M25/10185—Valves
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
    • A61L2300/22—Lipids, fatty acids, e.g. prostaglandins, oils, fats, waxes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/416—Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/43—Hormones, e.g. dexamethasone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
    • A61L2300/62—Encapsulated active agents, e.g. emulsified droplets
    • A61L2300/624—Nanocapsules
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
    • A61L2300/62—Encapsulated active agents, e.g. emulsified droplets
    • A61L2300/626—Liposomes, micelles, vesicles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2400/00—Materials characterised by their function or physical properties
    • A61L2400/12—Nanosized materials, e.g. nanofibres, nanoparticles, nanowires, nanotubes; Nanostructured surfaces
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES 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
    • A61M25/00—Catheters; Hollow probes
    • A61M25/10—Balloon catheters
    • A61M25/1011—Multiple balloon catheters
    • A61M2025/1013—Multiple balloon catheters with concentrically mounted balloons, e.g. being independently inflatable
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES 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
    • A61M25/00—Catheters; Hollow probes
    • A61M25/10—Balloon catheters
    • A61M2025/1043—Balloon catheters with special features or adapted for special applications
    • A61M2025/105—Balloon 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES 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
    • A61M25/00—Catheters; Hollow probes
    • A61M25/10—Balloon catheters
    • A61M2025/1043—Balloon catheters with special features or adapted for special applications
    • A61M2025/1075—Balloon catheters with special features or adapted for special applications having a balloon composed of several layers, e.g. by coating or embedding
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES 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
    • A61M25/00—Catheters; Hollow probes
    • A61M25/10—Balloon catheters
    • A61M25/1018—Balloon inflating or inflation-control devices

Abstract

本发明提供一种用于以高压输注胶束的球囊导管系统。该系统包括带有药物洗脱球囊的导管，该药物洗脱球囊具有穿孔壁，该穿孔壁具有许多孔，该系统还包括水溶液中的纳米颗粒的储存器，该储存器布置在球囊内或与球囊流体连通。颗粒可以包括载有药物的胶束，其中胶束以通常40至250nm(0.040μm至0.250μm)的尺寸范围提供，并且球囊壁的孔被配置成允许胶束以最小的破坏通过。孔是圆锥形的，球囊壁的内侧处的孔的直径小于球囊壁的外侧处的孔的直径。

Description

用于以高压输注胶束的球囊导管系统
技术领域
下面描述的本发明涉及治疗血管疾病的领域，并且更具体地涉及用于治疗再狭窄的药物洗脱球囊的领域。
背景技术
我们的在先美国专利8,696,644，名称为用于将干燥药物输送囊泡输送到体内的 血管的球囊导管系统(Balloon Catheter Systems For Delivery of Dry Drug Delivery Vesicles To A Vessel In The Body)，描述了一种药物洗脱球囊导管系统，该药物洗脱球囊导管系统非常适合于将纳米颗粒的悬浮物，特别是载有雷帕霉素的胶束，输送到患者的血管以治疗各种血管疾病。
发明内容
下面描述的设备和方法提供了纳米颗粒的悬浮物通过药物洗脱球囊的壁的改进的给药。该系统包括带有药物洗脱球囊的导管，该药物洗脱球囊具有穿孔壁，该穿孔壁具有许多孔，该系统还包括水溶液中的纳米颗粒的储存器，该储存器布置在球囊内或与球囊流体连通。颗粒可以包括载有药物的胶束(micelles)，其中胶束以通常40至250nm(0.040μm至0.250μm)的尺寸范围提供，并且球囊壁的孔被配置成允许胶束以最小的破坏通过。孔是圆锥形的，球囊壁的内侧处的孔的直径小于球囊壁的外侧处的孔的直径。
附图说明
图1图示了球囊导管系统。
图2示出了球囊的横截面，图示了球囊中的孔的锥形形状。
具体实施方式
图1图示了球囊导管系统1，该球囊导管系统1包括球囊导管2、储存器5和增压器6；球囊导管2包括导管轴3，导管轴3在该导管轴的远端处具有多孔球囊4；储存器5包含纳米颗粒的悬浮物，特别是胶束，该纳米颗粒载有治疗剂；增压器6用于迫使胶束的悬浮物进入导管和球囊内，并通过球囊的壁。球囊壁是多孔的，具有多个孔7，该多个孔7布置在球囊的表面上并穿过球囊壁，从球囊的内部连通到球囊的外部。球囊适于引入患者的脉管系统内，被放置在冠状动脉、外周动脉中或脉管系统中的其他地方。储存器可以被附接到导管轴的近端，与从该轴的近端延伸到球囊内部的腔流体连通。储存器优选地包括注射器8，注射器8具有可滑动地布置在注射器内的活塞9以限定第一室10和第二室11，该第一室10包含纳米颗粒的悬浮物、与腔球囊导管轴4和球囊的内部空间流体连通，该第二室11包含增压流体并且与增压器6流体连通。可以提供旋塞阀或三通阀12以使第一室通气，或连接到储存的小瓶或新近重新构建的纳米颗粒的悬浮物，以用纳米颗粒的悬浮物填充第一室。
图2示出了球囊的横截面，图示了球囊中的孔的锥形形状。球囊4具有壁13，壁13有多个孔7。如图2中所示，该孔在纵向横截面中是大致圆锥形的(锥形横截面，沿着该孔从球囊壁的内表面到球囊壁的外表面的轴线)，并且在横向横截面中是大致圆形的。该孔具有在球囊壁的内表面处的第一直径14，和在球囊壁的外表面处的第二直径15，并且第一直径小于第二直径。在球囊的内表面处的第一直径优选地在3至8μm(微米或μ)的范围内。在球囊的外表面处的第二直径优选地在7至16μm的范围内(更优选地在7至12μm的范围内)，尽管大于第一直径。壁厚优选在15至28μm的范围内，优选约21μm厚。在适用于患者的冠状动脉的实施例中，球囊的圆柱形部分可以是10至25mm长，并且当加压时可膨胀至约2至5mm的直径。用于冠状动脉的孔的数量可以范围从100至400个孔，并且用于外周动脉的孔的数量可以范围从100至1000个孔，均匀地分布在球囊的圆柱形部分上，选择性地成行(5至15行)分散设置在球囊的周长周围。
胶束可以载有雷帕霉素或其他治疗剂，例如，雷帕霉素类似物、ABT-578、佐他莫司、依维莫司、优美莫司(biolimus A9)、地磷莫司(deforolimus)(也称为雷帕霉素-42(二甲基次磷酸酯)(ridaforolimus))、替西罗莫司(temsirolimus)、他克莫司、吡美莫司(pimcrolimus)、一氧化氮合酶、C3外酶、RhoA抑制剂、tubulusin、A3激动剂、CB2激动剂、17-AAG、Hsp90拮抗剂、酪氨酸磷酸化抑制剂(tyrphostins)、组织蛋白酶S抑制剂、紫杉醇、皮质类固醇、糖皮质激素、地塞米松、神经酰胺、二甲基鞘氨醇、醚连接的甘油二酯、醚连接的磷脂酸、二氢鞘氨醇(sphinganines)、雌激素、他克唑(taxol)、他克唑类似物(taxolanalogs)、放线菌素D、前列腺素、维生素A、普罗布考、巴马司他(Batimastat)、他汀类药物、曲匹地尔(Trapidil)、丝裂霉素C和细胞松弛素B。
在上面描述的系统和方法中使用的纳米颗粒应具有大致在40至250nm范围内的直径，并且当包含由上述三嵌段共聚物(PLGA-PEG-PLGA)配制的胶束时在60至120nm的范围内，如由动态光散射技术确定。该尺寸将导致胶束有效渗透到动脉壁内与胶束内足够的空间以包封合适量的雷帕霉素或其他治疗物质的平衡。使用三嵌段聚合物如PLGA-PEG-PLGA将提供所需尺寸范围中的胶束。胶束直径与第一直径的比优选在0.08至1(近似1至12)到0.005至1(1至200)的范围内，更优选约1至20的范围内。除胶束外，能使用上面描述的系统和方法来输送其他小药物输送囊泡或输送血管，例如纳米颗粒和脂质体。
由增压器施加到储存器的压力可以是二到二十个大气压(203kPa到2027kPa)，并且增压器优选地操作以施加6到16个大气压(608kPa到1621kPa)，更优选地6到12个大气压(608kPa至1216kPa)。利用悬浮室中的悬浮胶束配方，以及如上确定大小和确定尺寸的孔洞，施加12个大气压(1216kPa)60秒将通过导管和球囊壁输送整个1ml的悬浮的胶束配方。压力可以在给药过程中变化，例如，通过施加6-8大气压(608kPa至811kPa)范围内的压力约20秒，并且将压力增加至12至18大气压(1216kPa至1823kPa)另外20至40秒(在给药过程中平均为12-14大气压(1216kPa至1418kPa))。可以调整参数以在10至120秒的过程中，优选地约20至60秒的过程中，流速为0.0033至0.0375ml/sec(优选在冠状动脉中)或0.0005至0.038ml/sec(优选在外周动脉中)，将0.2至0.75ml的悬浮物输送出球囊，以供周围血管壁吸收。每孔的流速优选在0.0001至0.00003毫升/秒/孔洞的范围内用于冠状动脉和在0.0001至0.00001毫升/秒/孔洞的范围内用于外周动脉。这些低流速有助于保持球囊膨胀，从而其持续对周围动脉施加开启力并维持与动脉壁的良好接触。优选地，输送的总体积为0.2ml至0.75ml。因此，通过控制设置在胶束储存室中的胶束配方中的药物或治疗剂的量，能一定程度确定地控制和预定实际输送的药物或治疗剂的剂量。例如，如果是希望将2mg的雷帕霉素输送到血管的患病部位，包含2或3mg的雷帕霉素的胶束储存器能被储存在胶束储存室中，利用流体重新构建胶束，以获得2mg/ml的浓度(即，如果胶束储存室包含2mg总雷帕霉素，则1ml)，将1ml的流体抽出到盘管悬浮室内，并迫使整个1ml通过导管和球囊进入血管壁。
可以控制平均颗粒尺寸与(在球囊壁的内表面处上的)总孔面积的比，以获得迫使血管顺应球囊以用于血管成形术所需的内部球囊压力、来自球囊的悬浮物的流速以促使悬浮的胶束进入周围血管壁内的吸收和避免血流中的悬浮物的损失的平衡。总孔面积可以在从约900至约30,000微米(942μm2(例如，在3微米平均直径的100个孔洞)至25,120μm2(在8微米平均直径的1000个孔洞))的范围。平均胶束粒径与内壁总孔面积在低侧上的在0.0000016比1和在大侧上的在0.0008比1范围中的非常小的比允许悬浮物在高压下被给药，足以用于血管成形术，同时提供通过孔的流动足以用载有的治疗剂治疗该区域。例如，利用5微米的平均孔直径(约20.7平方微米)和200总孔洞的配置，总孔面积为4142μm2(4.142百万平方纳米)，0.250μm(250nm)的颗粒直径，颗粒尺寸与内壁上的总孔面积的比会为0.00006比1。
在使用中，治疗患病血管的方法包括将球囊导管系统的球囊插入血管并迫使纳米颗粒的悬浮物进入球囊内并通过孔到血管壁，使用增压器以高压将压力施加到储存器，迫使纳米颗粒的悬浮物进入球囊，并通过球囊的壁。利用如图1和2中所示配置的孔和如上所述尺寸的纳米颗粒，纳米颗粒将从球囊的内部流到球囊的外部，而球囊本身被增压到足够压力，以对血液壁施加力，足以促进血管壁吸收纳米颗粒和/或进行血管成形术。
虽然已经参考研发它们的环境描述了设备和方法的优选实施例，但它们仅仅是对本发明原理的说明。各种实施例的要素可以被结合到每个其他种类中以获得那些要素与这种其他种类组合的益处，并且各种有益特征可以在实施例中单独使用或者彼此结合使用。在不脱离本发明的精神和所附权利要求的范围的情况下，可以设计出其他实施例和配置。

Claims (27)

1.一种球囊导管系统，其特征在于，包括：
导管，其包括导管轴，该导管轴具有远端和近端，该导管轴有布置在该近端上的球囊，所述球囊具有球囊壁，该球囊壁具有连通该球囊壁的多个孔；
储存器，其包含纳米颗粒悬浮物的溶液；
增压器，其是可操作的以迫使纳米颗粒悬浮物通过该导管并且通过该球囊壁；
其中该孔沿着该孔的穿过该球囊壁的长轴线具有锥形横截面。
2.如权利要求1所述的球囊导管系统，其特征在于，
该孔在该球囊的内表面处具有在3至8μm的范围内的第一直径，并且在该球囊的外表面处具有在7至16μm的范围内的第二直径。
3.如权利要求1所述的球囊导管系统，其特征在于，
该孔在该球囊的内表面处具有在3至8μm的范围内的第一直径，并且在该球囊的外表面处具有在7至16μm的范围内的第二直径；和
该悬浮物中的该纳米颗粒具有在40至250nm的范围内的直径。
4.如权利要求1所述的球囊导管系统，其特征在于，
该孔在该球囊的内表面处具有在3至8μm的范围内的第一直径，并且在该球囊的外表面处具有在7至16μm的范围内的第二直径；和
该悬浮物中的该纳米颗粒具有在60至120nm的范围内的直径。
5.如权利要求3或4所述的球囊导管系统，其特征在于，
该纳米颗粒包括载有治疗剂的胶束。
6.如权利要求3或4所述的球囊导管系统，其特征在于，
胶束直径与该第一直径的比在约0.08至1(1至12)到约0.005至1(1至200)的范围内。
7.如权利要求3或4所述的球囊导管系统，其特征在于，
胶束直径与该第一直径的比为约1至20。
8.如权利要求3或4所述的球囊导管系统，其特征在于，
该增压器是可操作的以向该储存器施加6至16个大气压。
9.如权利要求3或4所述的球囊导管系统，其特征在于，
该增压器是可操作的以向该储存器施加6至12个大气压。
10.如权利要求5所述的球囊导管系统，其特征在于，
该增压器是可操作的以在第一时段施加6至8个大气压，并且随后在第二时段施加12-14个大气压。
11.如权利要求3或4所述的球囊导管系统，其特征在于，
纳米颗粒的平均直径与该球囊壁的内表面上的总孔面积的比在0.0000016至1到0.0008至1的范围内。
12.一种球囊导管系统，其特征在于，包括：
导管，其包括导管轴，该导管轴具有远端和近端，该导管轴有布置在该近端上的球囊，所述球囊具有球囊壁，该球囊壁具有连通该球囊壁的多个孔；
储存器，其包含纳米颗粒悬浮物的溶液；
增压器，其是可操作的以迫使纳米颗粒悬浮物通过该导管并且通过该球囊壁；
其中该纳米颗粒的平均直径与该球囊壁的内表面上的总孔面积的比在0.0000016至1到0.0008至1的范围内。
13.如权利要求12所述的球囊导管系统，其特征在于，
该纳米颗粒的平均尺寸在40至250nm的范围内；和
该球囊壁的内表面上的总孔面积在900至30,000微米的范围内。
14.如权利要求11所述的球囊导管系统，其特征在于，
该纳米颗粒的平均尺寸在40至250nm的范围内；和
该孔在该球囊的内壁上具有3至8μm的平均尺寸；和
孔的数量在100至1000的范围内。
15.如权利要求12所述的球囊导管系统，其特征在于，
该纳米颗粒包括载有治疗剂的胶束。
16.如权利要求12至15中任一项所述的球囊导管系统，其特征在于，
该纳米颗粒载有治疗剂，并且所述治疗剂包括下面中的至少一种：雷帕霉素或雷帕霉素类似物、ABT-578、佐他莫司、依维莫司、优美莫司、地磷莫司、替西罗莫司、他克莫司、吡美莫司、一氧化氮合酶、C3外酶、RhoA抑制剂、tubulusin、A3激动剂、CB2激动剂、17-AAG、Hsp90拮抗剂、酪氨酸磷酸化抑制剂、组织蛋白酶S抑制剂、紫杉醇、皮质类固醇、糖皮质激素、地塞米松、神经酰胺、二甲基鞘氨醇、醚连接的甘油二酯、醚连接的磷脂酸、二氢鞘氨醇、雌激素、他克唑、他克唑类似物、放线菌素D、前列腺素、维生素A、普罗布考、巴马司他。
17.如权利要求5所述的球囊导管系统，其特征在于，
该治疗剂包括下面中的至少一种：雷帕霉素或雷帕霉素类似物、ABT-578、佐他莫司、依维莫司、优美莫司、地磷莫司、替西罗莫司、他克莫司、吡美莫司、一氧化氮合酶、C3外酶、RhoA抑制剂、tubulusin、A3激动剂、CB2激动剂、17-AAG、Hsp90拮抗剂、酪氨酸磷酸化抑制剂、组织蛋白酶S抑制剂、紫杉醇、皮质类固醇、糖皮质激素、地塞米松、神经酰胺、二甲基鞘氨醇、醚连接的甘油二酯、醚连接的磷脂酸、二氢鞘氨醇、雌激素、他克唑、他克唑类似物、放线菌素D、前列腺素、维生素A、普罗布考、巴马司他。
18.一种治疗患者的患病血管的方法，其特征在于，所述方法包括：
将球囊导管系统的球囊插入血管内，其中所述球囊包括球囊壁，该球囊壁具有连通该球囊壁的多个孔，并且所述孔沿着该孔从该球囊壁的内表面穿过该球囊壁的外表面的轴线具有锥形横截面；
迫使纳米颗粒悬浮物进入该球囊并通过该孔至血管壁。
19.如权利要求18所述的方法，其特征在于，
该孔在该球囊的内表面处具有在3至8μm的范围内的第一直径，并且在该球囊的外表面处具有在7至16μm的范围内的第二直径。
20.如权利要求19所述的方法，其特征在于，
该悬浮物中的该纳米颗粒具有在40至250nm的范围内的直径。
21.如权利要求19所述的方法，其特征在于，
该悬浮物中的该纳米颗粒具有在60至120nm的范围内的直径。
22.如权利要求20或21所述的方法，其特征在于，
该纳米颗粒包括载有治疗剂的胶束。
23.如权利要求22所述的方法，其特征在于，
迫使纳米颗粒悬浮物进入该球囊内的步骤包括在6至16个大气压范围内的压力下，更优选地在6至12个大气压范围内的压力下，迫使纳米颗粒悬浮物进入该球囊内。
24.如权利要求22所述的方法，其特征在于，
迫使该纳米颗粒悬浮物进入该球囊内的步骤包括在第一时段在6至8个大气压范围内的压力下，和随后在第二时段在12至14个大气压范围内的压力下，迫使该纳米颗粒悬浮物进入该球囊内。
25.如权利要求18所述的方法，其特征在于，
实现迫使纳米颗粒悬浮物进入该球囊并通过该孔至血管壁的步骤，以提供该悬浮物离开该球囊的0.0005至0.038ml/sec的流速。
26.如权利要求18所述的方法，其特征在于，
实现迫使纳米颗粒悬浮物进入该球囊并通过该孔至血管壁的步骤，以提供该悬浮物离开该球囊的0.0033至0.0375ml/sec的流速。
27.如权利要求22所述的方法，其特征在于，
该治疗剂包括下面中的至少一种：雷帕霉素或雷帕霉素类似物、ABT-578、佐他莫司、依维莫司、优美莫司、地磷莫司、替西罗莫司、他克莫司、吡美莫司、一氧化氮合酶、C3外酶、RhoA抑制剂、tubulusin、A3激动剂、CB2激动剂、17-AAG、Hsp90拮抗剂、酪氨酸磷酸化抑制剂、组织蛋白酶S抑制剂、紫杉醇、皮质类固醇、糖皮质激素、地塞米松、神经酰胺、二甲基鞘氨醇、醚连接的甘油二酯、醚连接的磷脂酸、二氢鞘氨醇、雌激素、他克唑、他克唑类似物、放线菌素D、前列腺素、维生素A、普罗布考、巴马司他。
CN201811473275.1A 2018-10-04 2018-12-04 用于以高压输注胶束的球囊导管系统 Pending CN111001077A (zh)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201862741421P 2018-10-04 2018-10-04
US62/741,421 2018-10-04

Publications (1)

Publication Number Publication Date
CN111001077A true CN111001077A (zh) 2020-04-14

Family

ID=69250248

Family Applications (2)

Application Number Title Priority Date Filing Date
CN201811473275.1A Pending CN111001077A (zh) 2018-10-04 2018-12-04 用于以高压输注胶束的球囊导管系统
CN201822023030.0U Active CN209967376U (zh) 2018-10-04 2018-12-04 用于以高压输注胶束的球囊导管系统

Family Applications After (1)

Application Number Title Priority Date Filing Date
CN201822023030.0U Active CN209967376U (zh) 2018-10-04 2018-12-04 用于以高压输注胶束的球囊导管系统

Country Status (5)

Country Link
US (1) US20210386979A1 (zh)
EP (1) EP3860700A4 (zh)
JP (1) JP2022508608A (zh)
CN (2) CN111001077A (zh)
WO (1) WO2020072280A1 (zh)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111001077A (zh) * 2018-10-04 2020-04-14 口径疗法有限责任公司 用于以高压输注胶束的球囊导管系统

Citations (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996034967A1 (en) * 1995-05-04 1996-11-07 Board Of Trustees Of The Leland Stanford Junior University, The Office Of Technology Licensing Apparatus and method for delivering a nucleotide into cell nuclei
US6210392B1 (en) * 1999-01-15 2001-04-03 Interventional Technologies, Inc. Method for treating a wall of a blood vessel
JP3403233B2 (ja) * 1994-01-20 2003-05-06 テルモ株式会社 バルーンカテーテル
US20100010470A1 (en) * 2008-07-11 2010-01-14 Paragon Intellectual Properties, Llc Nanotube-Reinforced Balloons For Delivering Therapeutic Agents Within Or Beyond The Wall of Blood Vessels, And Methods Of Making And Using Same
WO2012156914A2 (en) * 2011-05-15 2012-11-22 By-Pass, Inc. Microporous balloon catheter, delivery system, and methods of manufacture and use
CN202589701U (zh) * 2012-04-25 2012-12-12 中国人民解放军第四军医大学 电控活塞式药物注射器
WO2011082367A8 (en) * 2009-12-30 2013-07-11 Caliber Therapeutics, Inc. Balloon catheter systems for delivery of dry drug delivery vesicles to a vessel in the body
CN105492047A (zh) * 2013-07-10 2016-04-13 拜耳医疗保健股份有限公司 用于活塞和注射器接口的真空系统
WO2017100767A1 (en) * 2015-12-10 2017-06-15 Endoperfusion Solutions, Llc Methods and formulations for treating vascular disease
US9730726B2 (en) * 2011-10-07 2017-08-15 W. L. Gore & Associates, Inc. Balloon assemblies having controllably variable topographies
CN108159535A (zh) * 2017-12-29 2018-06-15 成都三木行新能源科技有限公司 一种用于麻醉的注射器
CN209967376U (zh) * 2018-10-04 2020-01-21 口径疗法有限公司 用于以高压输注胶束的球囊导管系统

Patent Citations (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP3403233B2 (ja) * 1994-01-20 2003-05-06 テルモ株式会社 バルーンカテーテル
WO1996034967A1 (en) * 1995-05-04 1996-11-07 Board Of Trustees Of The Leland Stanford Junior University, The Office Of Technology Licensing Apparatus and method for delivering a nucleotide into cell nuclei
US6210392B1 (en) * 1999-01-15 2001-04-03 Interventional Technologies, Inc. Method for treating a wall of a blood vessel
US20100010470A1 (en) * 2008-07-11 2010-01-14 Paragon Intellectual Properties, Llc Nanotube-Reinforced Balloons For Delivering Therapeutic Agents Within Or Beyond The Wall of Blood Vessels, And Methods Of Making And Using Same
WO2011082367A8 (en) * 2009-12-30 2013-07-11 Caliber Therapeutics, Inc. Balloon catheter systems for delivery of dry drug delivery vesicles to a vessel in the body
WO2012156914A2 (en) * 2011-05-15 2012-11-22 By-Pass, Inc. Microporous balloon catheter, delivery system, and methods of manufacture and use
US9730726B2 (en) * 2011-10-07 2017-08-15 W. L. Gore & Associates, Inc. Balloon assemblies having controllably variable topographies
CN202589701U (zh) * 2012-04-25 2012-12-12 中国人民解放军第四军医大学 电控活塞式药物注射器
CN105492047A (zh) * 2013-07-10 2016-04-13 拜耳医疗保健股份有限公司 用于活塞和注射器接口的真空系统
WO2017100767A1 (en) * 2015-12-10 2017-06-15 Endoperfusion Solutions, Llc Methods and formulations for treating vascular disease
CN108159535A (zh) * 2017-12-29 2018-06-15 成都三木行新能源科技有限公司 一种用于麻醉的注射器
CN209967376U (zh) * 2018-10-04 2020-01-21 口径疗法有限公司 用于以高压输注胶束的球囊导管系统

Also Published As

Publication number Publication date
EP3860700A1 (en) 2021-08-11
CN209967376U (zh) 2020-01-21
US20210386979A1 (en) 2021-12-16
JP2022508608A (ja) 2022-01-19
WO2020072280A1 (en) 2020-04-09
EP3860700A4 (en) 2022-06-29

Similar Documents

Publication Publication Date Title
US20230191090A1 (en) Balloon Catheter Systems for Delivery of Dry Drug Delivery Vesicles to a Vessel in the Body
CA2499053C (en) Medical devices coated for dispensing medicaments by pressing the device against a tissue surface
JP2006504463A (ja) 薬剤放出用拡張性ポーションを備えた装置
JP2010535074A (ja) 改善された薬剤被覆医療製品，その製造及び使用方法
CN209967376U (zh) 用于以高压输注胶束的球囊导管系统
US10098650B2 (en) Systems and methods for treating atherosclerotic plaque
JP3631777B2 (ja) 薬剤投与カテーテル
US9242005B1 (en) Pro-healing agent formulation compositions, methods and treatments
US20120136367A1 (en) Multi-segment protective sheath for expandable medical devices
AU2020281081B2 (en) Balloon catheter systems for delivery of dry drug delivery vesicles to a vessel in the body
CN213609294U (zh) 血管导流的药物球囊扩张导管
US20200316350A1 (en) Inflatable Balloon Over Catheter With Bypass Passageway
US20100217227A1 (en) Method and apparatus for delivering oxygen and/or other gases and/or pharmacological agents to tissue and medical wire for use within the body
WO2012162668A1 (en) Method and apparatus for delivering oxygen and/or other gases and/or pharmacological agents to tissue, and medical wire for use within the body
WO2010042945A1 (en) Method and apparatus for delivering oxygen and/or other gases and/or pharmacological agents to tissue and medical wire for use within the body
NZ538900A (en) Medical device for dispensing medicaments

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination