CN102576385B - 具有自适应控制的电解药物输送泵 - Google Patents

具有自适应控制的电解药物输送泵 Download PDF

Info

Publication number
CN102576385B
CN102576385B CN201080046911.8A CN201080046911A CN102576385B CN 102576385 B CN102576385 B CN 102576385B CN 201080046911 A CN201080046911 A CN 201080046911A CN 102576385 B CN102576385 B CN 102576385B
Authority
CN
China
Prior art keywords
pump
medicine
medicine transportation
intubate
liquid
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Fee Related
Application number
CN201080046911.8A
Other languages
English (en)
Other versions
CN102576385A (zh
Inventor
J·什
J·布伦南
F·蒋
S·卡菲
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.)
MiniPumps LLC
Original Assignee
MiniPumps LLC
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 MiniPumps LLC filed Critical MiniPumps LLC
Publication of CN102576385A publication Critical patent/CN102576385A/zh
Application granted granted Critical
Publication of CN102576385B publication Critical patent/CN102576385B/zh
Expired - Fee Related legal-status Critical Current
Anticipated expiration legal-status Critical

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
    • A61M5/00Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/14Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
    • A61M5/142Pressure infusion, e.g. using pumps
    • GPHYSICS
    • G16INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16HHEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
    • G16H20/00ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance
    • G16H20/10ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance relating to drugs or medications, e.g. for ensuring correct administration to patients
    • G16H20/17ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance relating to drugs or medications, e.g. for ensuring correct administration to patients delivered via infusion or injection
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F9/00Methods or devices for treatment of the eyes; Devices for putting-in contact lenses; Devices to correct squinting; Apparatus to guide the blind; Protective devices for the eyes, carried on the body or in the hand
    • A61F9/0008Introducing ophthalmic products into the ocular cavity or retaining products therein
    • A61F9/0017Introducing ophthalmic products into the ocular cavity or retaining products therein implantable in, or in contact with, the eye, e.g. ocular inserts
    • 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
    • A61M5/00Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/14Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
    • A61M5/142Pressure infusion, e.g. using pumps
    • A61M5/14244Pressure infusion, e.g. using pumps adapted to be carried by the patient, e.g. portable on the body
    • A61M5/14276Pressure infusion, e.g. using pumps adapted to be carried by the patient, e.g. portable on the body specially adapted for implantation
    • 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
    • A61M5/00Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/14Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
    • A61M5/142Pressure infusion, e.g. using pumps
    • A61M5/145Pressure infusion, e.g. using pumps using pressurised reservoirs, e.g. pressurised by means of pistons
    • A61M5/14586Pressure infusion, e.g. using pumps using pressurised reservoirs, e.g. pressurised by means of pistons pressurised by means of a flexible diaphragm
    • A61M5/14593Pressure infusion, e.g. using pumps using pressurised reservoirs, e.g. pressurised by means of pistons pressurised by means of a flexible diaphragm the diaphragm being actuated by fluid pressure
    • 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
    • A61M5/00Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/14Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
    • A61M5/142Pressure infusion, e.g. using pumps
    • A61M5/145Pressure infusion, e.g. using pumps using pressurised reservoirs, e.g. pressurised by means of pistons
    • A61M5/148Pressure infusion, e.g. using pumps using pressurised reservoirs, e.g. pressurised by means of pistons flexible, e.g. independent bags
    • 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
    • A61M5/00Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/14Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
    • A61M5/168Means for controlling media flow to the body or for metering media to the body, e.g. drip meters, counters ; Monitoring media flow to the body
    • A61M5/16804Flow controllers
    • 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
    • A61M5/00Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/14Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
    • A61M5/168Means for controlling media flow to the body or for metering media to the body, e.g. drip meters, counters ; Monitoring media flow to the body
    • A61M5/16831Monitoring, detecting, signalling or eliminating infusion flow anomalies
    • 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
    • A61M5/00Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/14Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
    • A61M5/168Means for controlling media flow to the body or for metering media to the body, e.g. drip meters, counters ; Monitoring media flow to the body
    • A61M5/172Means for controlling media flow to the body or for metering media to the body, e.g. drip meters, counters ; Monitoring media flow to the body electrical or electronic
    • GPHYSICS
    • G16INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16HHEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
    • G16H10/00ICT specially adapted for the handling or processing of patient-related medical or healthcare data
    • 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
    • A61M5/00Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/14Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
    • A61M5/142Pressure infusion, e.g. using pumps
    • A61M2005/14204Pressure infusion, e.g. using pumps with gas-producing electrochemical cell
    • 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
    • A61M2205/00General characteristics of the apparatus
    • A61M2205/33Controlling, regulating or measuring
    • A61M2205/3331Pressure; Flow
    • 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
    • A61M2205/00General characteristics of the apparatus
    • A61M2205/33Controlling, regulating or measuring
    • A61M2205/3331Pressure; Flow
    • A61M2205/3334Measuring or controlling the flow rate
    • 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
    • A61M2205/00General characteristics of the apparatus
    • A61M2205/33Controlling, regulating or measuring
    • A61M2205/3368Temperature
    • 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
    • A61M2210/00Anatomical parts of the body
    • A61M2210/06Head
    • A61M2210/0612Eyes
    • 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
    • A61M2210/00Anatomical parts of the body
    • A61M2210/06Head
    • A61M2210/0693Brain, cerebrum
    • 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
    • A61M31/00Devices for introducing or retaining media, e.g. remedies, in cavities of the body
    • A61M31/002Devices for releasing a drug at a continuous and controlled rate for a prolonged period of time
    • 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
    • A61M5/00Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/14Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
    • A61M5/142Pressure infusion, e.g. using pumps
    • A61M5/14244Pressure infusion, e.g. using pumps adapted to be carried by the patient, e.g. portable on the body
    • 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
    • A61M5/00Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/14Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
    • A61M5/168Means for controlling media flow to the body or for metering media to the body, e.g. drip meters, counters ; Monitoring media flow to the body
    • A61M5/16831Monitoring, detecting, signalling or eliminating infusion flow anomalies
    • A61M5/16854Monitoring, detecting, signalling or eliminating infusion flow anomalies by monitoring line pressure

Landscapes

  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Biomedical Technology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Vascular Medicine (AREA)
  • Veterinary Medicine (AREA)
  • Hematology (AREA)
  • Anesthesiology (AREA)
  • Medical Informatics (AREA)
  • Epidemiology (AREA)
  • Primary Health Care (AREA)
  • Ophthalmology & Optometry (AREA)
  • Physics & Mathematics (AREA)
  • Fluid Mechanics (AREA)
  • Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Medicinal Chemistry (AREA)
  • Infusion, Injection, And Reservoir Apparatuses (AREA)

Abstract

基于泵状况的变化控制药物输送泵的致动。

Description

具有自适应控制的电解药物输送泵
相关申请的交叉引用
本发明要求2009年8月18日提交的美国临时专利申请No.61/234,742的优先权和权益,通过引用把其全部内容合并于此。
技术领域
在各个实施例中,本发明涉及药物输送泵。特别地,本发明的实施例涉及药物输送泵,该药物输送泵的致动可为动态且自适应控制的。
背景技术
药物治疗通常需要把治疗剂(例如药剂、药物等)给药至患者身体的特定部位。随着患者寿命延长并被诊断出患有慢性病和/或无力症,可能的结果将是更需要把更多蛋白药品、小分子药物和其他药剂置入遍及患者整个身体中的靶区。然而,一些疾病难以用当前可用的疗法治疗和/或需要把药物给药至难以触及的解剖区域。
患者眼睛是难以触及的解剖区域的最好例子,而且,许多危及视力的疾病难以用目前存在的许多疗法治疗,这些疾病包括色素性视网膜炎、老年性黄斑病变(AMD)、糖尿病视网膜病变和青光眼。例如,口服药物会具有系统性副作用;局部用药会引起刺痛并引起病人不良适应性;注射通常需要去医院,而且会引起痛苦,并有感染的风险;以及,持续释放药物的植入物在药物耗尽后必须取出来(以及通常,适应临床症状而改变剂量的能力有限)。
另一个例子是癌症,诸如乳腺癌或者脑膜瘤,其通常通过静脉注射向患者给药大剂量的高毒性化学治疗药物,如雷帕霉素、贝伐单抗(例如AVASTIN)或者伊立替康(CPT-11),这会致使在靶区以外出现很多不期望的副作用。还一个例子是药物输送至膝盖,在膝盖处,药物难以穿过无血管的软骨组织来治疗如骨关节炎的疾病。
可植入药物输送装置(例如,药物输送泵)通常允许把药品溶液有控制地输送到指定靶区,该可植入药物输送装置可以具有可重复填充的药物储存器、用于输送药物的插管、止回阀等。当药物储存器中的药物耗尽时,医生能够用例如注射器重新填充储存器而保留抑制在患者体内的装置。这种方法可以使植入所需的外科切口最小,通常避免了以后或重复性的介入性外科手术或过程。
可植入药物输送泵,特别是在眼科应用中,通常利用被动药物输送机制(例如,在手指按在药物储存器上时把药物泵出)。这些传统的、被动驱动的药物输送泵的一个局限在于它们不能动态地响应泵内的变化(例如,故障、阻塞等)或响应药物输送靶区内的变化(例如,增高的压力、泵插管的挠度、引起插管周围压力的炎症等)。具备能够响应这些变化的能力不仅能够改善泵的治疗价值,而且改善了安全性。
主动药物输送泵,特别是反馈驱动泵,代表了超越被动驱动泵的实质性改进。通常,这些反馈驱动泵是电动机械泵。它们通常使用控制器单元,其接收来自监测目标治疗区的传感器的输入,以及作为响应,引导药物或治疗剂的释放以实现期望的结果。因此在每个剂量周期内释放的药物量主要由靶区的现状决定,并确定为依据靶区状况的许可可变。
然而,药物治疗方案可能需要药物在固定时间间隔以固定量给药而不管药物输送靶区的变化条件。由于通过现有闭环反馈驱动系统产生的剂量水平高度依赖于治疗区域的参数并因此容易波动,它们不足以在周期性间隔上输送固定的药物剂量。例如,靶区的状况变化,诸如阻塞或其他的生化或生理事件,会导致输送至靶区的可变水平的药物。因此,有维持目标剂量水平而不管这些变化的反馈驱动泵的需求。
此外,虽然基于靶区状况的反馈在许多治疗应用中是重要的,而在药物给药中的失误也会由泵自身内的状况变化引起。传统的泵通常不考虑这些变化,这同样会导致可变的释放药物量。因此,同样有动态响应泵自身内的状况变化的药物输送系统的需求,以例如在周期性时间间隔上连续地释放固定的药物剂量。
发明内容
在各个实施例中,本发明的特征是外用的或可植入的药物输送泵,其包括动态、自适应控制系统。该控制系统可操作该泵以使得在固定时间间隔上基本将固定量的药物或治疗剂释放至目标治疗区域。在某些实施例中,控制系统持续地监测(直接或间接地)泵内部的状况,其对泵激励的程度和持续时间有影响,并因此影响释放药物量。如这里所使用的,术语“基本”指的是±10%(例如,按重量或体积),以及某些实施例中为±5%。
在一个实施例中,药物输送泵是电化学激励泵,如电解驱动泵。对比于电动机械泵,电化学激励泵提供了针对药物输送系统的多个优势。例如,它们通常少有活动部件,这使得它们小且便携,以及这使得它们比电动机械泵不易发生机械故障。特别地是,电化学激励泵适合于需要小的泵尺寸的环境,诸如眼科环境。如这里进一步描述,电解驱动泵通常使用电极以产生电化学活性气体,其可变地加压包含于隔离腔中的药物从而以可控制方式分配药物。分配的药物量取决于由泵致动器可变产生的气体压力,而这又依赖于经过电极的电流。由于这些电解驱动泵内的内在可变性(例如,气体体积和/或电解质的量会在每个泵循环之间变化),这里描述的自适应控制设计能够具有重要的优势,这将在下文进一步说明。
一般而言,在一个方面,本发明的实施例的特征在于药物输送泵,其包括药物储存器、用于从储存器引导液体至目标位置的插管、用于推动来自储存器的液体穿过插管的泵致动器、以及用于控制致动器的电路。特别地,该电路控制致动器以i)初始地输送随时间(例如,在周期性时间间隔上或通过连续注射)基本固定的液体剂量至目标部位,和ii)补偿泵的状况变化以维持或恢复随时间(例如,在周期性时间间隔上或通过连续注射)基本固定的液体剂量至目标部位的输送。
一般而言,在另一方面,本发明的实施例的特征在于一种将从药物输送泵输送药物至患者的方法,该药物输送泵包括药物储存器和泵致动器,该致动器用于推动液体从储存器进入患者体内。该方法包括建立药物储存器和患者(即,目标部位)之间的流体连通,以及包括控制泵致动器。特别地是,控制该致动器以i)初始地从药物储存器输送随时间(例如,在周期性时间间隔上或通过连续注射)基本固定的液体剂量至患者,和ii)补偿泵的状况变化以维持或恢复随时间(例如,在周期性时间间隔上或通过连续注射)基本固定的液体剂量至患者的输送。
在各个实施例中,控制电路包括存储器,其用于存储在先前输送事件时候(例如,每个输送时间间隔时候)的泵的状况。此外,药物输送泵还包括流量传感器,用于测量通过插管并进入患者的流体流速,以及电路可以至少部分地基于流速分析控制泵致动器。电路还可以基于已存储的先前剂量时的泵的状况和/或致动器的实时数据控制致动器。
如前所述,药物输送泵可以是电解驱动泵。更特别地,泵致动器可以包括电解腔、隔开电解腔和药物储存器并提供了它们之间流体屏障的可膨胀隔膜、以及引起在电解腔内放出气体的电解电极。气体的放出扩张了隔膜从而推动流体从药物储存器进入插管。在各个实施例中,通过改变供给电极的激励电流来调节隔膜的膨胀。在其他实施例中,通过改变电极的激励持续时间来调节隔膜的膨胀。如这里所描述的,可通过恒定电流或时变电流波形驱动电解电极。
一般而言,在还一方面,本发明的实施例的特征在于药物输送泵,其包括药物储存器、电解腔、电解电极、隔开电解腔和药物储存器并提供了它们之间流体屏障的可膨胀隔膜、用于从药物储存器引导流体至目标部位的插管、以及基于目标部位的状况(例如,目标部位上一个或多个生化参数的变化、目标部位上的电活性的变化、和/或目标部位上压力的变化)用于调节隔膜扩张的电路。该泵还包括传感器用于探测这些状况。对它们来说,可以激励电解电极以引起气体在电解腔内放出,这使得隔膜扩张从而推动流体从药物储存器进入插管。
通过参考下面的说明书、附图以及权利要求会使这里公开的本发明的这些及其他目的以及益处和特征更加显而易见。此外,应该理解,即使在这里没有明确,这里所述的各个实施例的特征不是互斥的,而是可以各种组合和互换存在。
附图说明
附图中,相似的参考数字通常指不同视图中的相同部件。以及,附图不必是按比例的,而重点通常在于说明本发明的原理。在下面说明中,参考下面附图描述本发明的各个实施例,其中
图1示意性地以截面视图示出了根据本发明的一个实施例的可植入药物输送泵;
图2示意性地以截面视图示出了根据本发明的另一个实施例的可植入药物输送泵;
图3是根据本发明的一个实施例的药物输送泵的框图;
图4是表示如何使图1-3所描述的每个药物输送泵适应泵内的变化状况从而输送目标剂量水平的示例;
图5A示出了没有反馈控制操作的泵的示例性流量和激励曲线图;
图5B示出了随着泵的效率降低在一个更长的时期激励泵致动器的泵的示例性流量和激励曲线图;
图5C示出了随着泵的效率降低增加泵的激励电流的泵的示例性流量和激励曲线图;
图6是患者眼睛截面图,其示意了根据本发明的一个实施例的药物输送泵植入患者眼睛中。
具体实施方式
总地来说,本发明的实施例是关于外用或可植入的药物输送泵(不管它们是否是可重复使用以及可重新填充的泵、一次性泵等),该药物输送泵的致动是动态且自适应控制的。例如,实施例的药物输送泵可以是可植入患者体内的,如患者眼中或脑中。在某些实施例中,可植入药物输送泵结合了小尺寸且可重新填充的药物储存器。该小尺寸最小化了药物输送泵对患者的不适感,而该重新填充储存器允许泵在原处重新填充而不用替换。这样,液体,如药物溶剂,能够在一段较长时间内供给至患者。
A.示例性药物输送泵
本发明的实施例可结合各种类型的药物输送泵来使用,而不管它们是否是外用泵或可植入患者体内的泵。图1和2示意性地说明了植入患者眼睛104中的示例性可植入药物输送泵100(即,示例性电解或电解驱动泵100)的两个变型。然而泵100可以替换为植入患者身体的其他部位中。例如,它可以植入到大脑的蛛网膜下腔空间以向大脑提供化学治疗或提供另一种类型的治疗(例如,通过对直接对大脑软组织给药);植入到患者身体任何部位处的肿瘤附近以提供化学治疗;植入到对葡萄糖代谢不好的胰腺中以提供触发胰岛素释放的药剂(例如蛋白质、病毒载体等);在患者体外而使插管置于皮下或腹腔中以输送胰岛素;植入膝盖中以提供治疗骨关节炎或其他软骨疾病的药物;植入到靠近脊柱以提供止痛药或消炎药;或植入到其他地方。
如图1和2所示,泵100的实施例包括两个主要组件:一对腔108、112,其至少部分地由壁115包绕;以及插管120。如图1所示,包绕腔108、112的壁115包括或由以下组成:独立的聚对二甲苯薄膜116;以及在其之上的隔离保护壳128,其由相对刚性的生物相容性材料(例如,医学级的聚丙烯)制成。可替代地,如图2所示,壁115可仅仅对应于保护壳128,其涂敷有聚对二甲苯。
上腔108限定了药物储存器,其在用于治疗患者时可以含有以液体形式给药的药物。对于下腔112来说,下腔112包括液体,其在该液体被电解时,产生气态产物。例如,该液体可以是水,其可由所施加电压电解分离为氢气和氧气。可替代地,作为其他示例,该电解液可以是盐溶液(即,H2O中的NaCl)或者是含有硫酸镁或硫酸钠的溶液。在一个实施例中,两个腔108、112由褶皱隔膜124隔开。换言之,隔膜124提供了两个腔108、112之间的流体屏障。类似于独立薄膜116,隔膜124可由例如聚对二甲苯构成。如图1所示,独立薄膜116作为对药物储存器108的外部屏障,保护壳128提供了抵住薄膜116施力的硬表面。在这种情况下,外壳128带有孔以允许眼睛、大脑或其他体液流动。可替代地,如图2所示,保护壳128可以自身作为针对药物储存器108的外部屏障,且无孔。在图1和2所描述的两个实施例中,保护壳128能够阻止施加在药物储存器108上的外部压力。如图1所示,保护壳128的底部126(即,底板126)可以包括缝合孔130。类似的,尽管未在图1或2中示出,插管120也可以沿其侧面包括缝合孔。缝合孔130可用来在患者体内将泵100缝合(即,锚固)在适当位置。
同样如图1所示,为了给泵100供能并能在其间进行数据传送,可在腔108、112下(即,介于药物储存器108的独立聚对二甲苯薄膜116的底部和保护壳128的底板126之间)(例如,密封地)嵌入电池和控制电路132,并且把感应线圈136集成在保护壳128内(例如,通过注入成型)。图2更清楚的示意了用于容纳电池和常规控制电路132的密封外罩135,但为了简化起见,没有描述容纳于其中的组件。密封外罩135由生物相容性材料(例如,钛)或金属合金制成。密封外罩135的底部是平的,或者可以是凹面的以帮助可植入泵100安装在患者眼睛104上。
在一个实施例中,感应线圈136允许与外部装置(例如,手持机)无线(例如,射频)通信。手持机可以用来发送无线信号至控制电路132以编程、重新编程、操作、校准或者是配置泵100的其他操作。在一个实施例中,控制电路132通过跨越电解储存器112底部的金属互连件(通路)138与电解腔112内的电解电极134电通信。电解电极134可由例如铂、金、和/或其他金属制成。如下文进一步描述的,控制电路132控制泵100的抽吸作用,其包括下文描述的闭环控制过程。
在一个实施例中,如图1所示,插管120将药物储存器108连接到插在给药部位的止回阀140。止回阀140可以是单向止回阀,其阻止任何液体回流进入药物储存器108。可替代的,或另外的,如图2所示,止回阀140可以集成并定位在插管120的近端(即,处于最接近药物储存器108的一端)。然而,更一般而言,止回阀140可以定位在沿插管120的任何位置。此外,一个或多个用于监测药物流量、以及进而能够测量通过插管120的已输送药物体积和/或药物流速的流量传感器144可以结合在插管120的近端、中间或远端部分中的一个或多个。任选的,如图1所示,一个或多个目标部位传感器148也可以集成在插管120的远端(即,在离药物储存器108最远的一端)以测量给药部位(例如,玻璃体腔、肩关节囊、膝关节囊、脑室、椎管等)上的一个或多个参数。例如,可利用目标部位传感器148来感测目标部位处生物或生化参数的变化(例如,特定分析物浓度的变化、存在或不存在特定生化标记,等)、目标部位处电活动的变化(其可以例如由生理变化而引起)、以及目标部位处压力的变化中的一个或多个。在一个实施例中,目标部位传感器148提供反馈(即,实时测量)至控制电路132从而通过闭环控制过程测量药物流量。例如,药物靶区内增大的压力可以证明来自泵100的药物流量的减少。
如图1所示,插管120可以是独立聚对二甲苯薄膜116的延伸。可替代的,如图2所示,插管120可以是连接至保护壳128的独立组件(例如,聚对二甲苯组件)。例如,可以穿过形成在保护壳128中的流体连通口插入插管120的近端,并通过例如生物相容性环氧树脂胶150与之粘结。硅树脂套154可以围绕插管120的一部分设置(参加图2),但这是可选的(参见图1)。
在一个实施例中,如图1所示,药物储存器108装配有填充口152且该填充口由密封剂(例如,生物相容性环氧树脂)156密封至独立薄膜116和保护壳128。在又一实施例中,如图2所示,可以形成通过保护壳128的孔,并把填充口152置于孔中。在另一个实施例中,填充口152可形成在泵100上其他位置处并通过管子连接到药物储存器108。例如,填充口152可以用生物相容性材料模制而成,耦合到密封罩135上的配合凹口上,并通过管子连接到药物储存器108。在一个实施例中,管子通过在围绕药物储存器108的壁上形成的流体连通口插入,并通过生物相容性环氧树脂胶与之粘结。在任一种情况下,填充口152和药物储存器108流体连通,并允许泵100的操作者(例如医生)在原处(例如,在泵100植入在患者眼睛104中时)重新填充药物储存器108。一般来说,可以通过把再填充针插入并穿过填充口152而重新填充药物储存器108。
在各个实施例中,泵100的主要部件(即,一对腔108、112和插管120)可采用多层聚对二甲苯工艺进行单片微加工和集成。可在微加工步骤之后,为泵100装配填充口152、保护壳128以及其他组件。
工作时,当向电解电极134提供电流时,电解质产生气体,使褶皱隔膜124膨胀(即,在图1和2中向上方移动隔膜124),并迫使液体(例如,药物)流出药物储存器108进入和通过插管120,并流出其远端以到达给药的目标部位。可膨胀隔膜124中的褶皱或其他折叠允许大程度的膨胀,而不会在隔膜124松弛时牺牲药物储存器108内的容积。当停止电流时,电解气体凝结回液态,并且隔膜124恢复到其节省空间的褶皱状态。
B.基于内部泵的状况的自适应控制
一般而言,电解驱动泵100对提供给电解电极134的给定输入电流的响应依赖于药物储存器108内剩余的液体量。例如,如果药物储存器108接近排空,在开始增加压力和起动抽吸作用前需要更多的电流以引起药物储存器108至其“充满”配置。另一方面,如果药物储存器108完全充满,在药物输送开始前只需要非常小的电流。类似的,电解驱动泵100对给定输入电流的响应还依赖于电解腔112内的气/液比。特别地,药物储存器108充满药物时(例如,当电解腔112以低气/液比工作时)与药物储存器108接近排空时(例如,当电解腔112以高气/液比工作时)相比,泵100的响应将会非常不同。此外,其他因素能够引起电解驱动泵100的响应以随时间变化,这些其他因素包括,例如,电解电极134的降解、电解腔112内电解质浓度的变化、止回阀140的流动特性的变化、以及由于组织生长或一些其他机制而在插管120出口处形成的限制。
由于这些因素,电解泵100是内在可变的。因此,根据该变化的自适应控制能够使泵100具有很大的优势。例如,如下文进一步说明的,通过分析先前剂量来确定泵100如何响应给定输入电流,能够获得针对当前剂量的最佳设置(例如,提供最精确和最少剂量的设置)。这在剂量体积相比于药物储存器108的容积较小时显得特别有利。在这种情况下,泵100的状态参数(例如,药物储存器108中剩余的药物体积、电解腔112内的液/气比、电极134的状况、止回阀140的特性等)从一个剂量到紧接下来的剂量是几乎相同的,因此,先前剂量是对当前剂量的极好预测。
图3是药物输送泵200的框图,其更加详细地描述了控制电路132。药物输送泵200可以是任何类型的外用或内用泵,其具有推动液体从药物储存器108进入并通过插管120的致动器204。例如,药物输送泵200可以是电解驱动泵,并参照上述图1和2所描述的,泵致动器204可以包括电解腔112、可膨胀隔膜124、以及电解电极134。对于控制电路132来说,控制电路132包括计算机存储器208,用于存储泵200的一个或多个状况;以及自适应控制器212,用于基于泵200状况的变化控制泵致动器204。可选地,控制电路132还可以包括一个或多个模块来将从流量传感器144接收到的原始数据转化为有意义的值(例如,转化为以NL/min表示的流速)和/或将从泵致动器204接收到的类似原始数据转化为有意义的值。可替代地,由该模块(或该多个模块)执行的功能可替换为由自适应控制器212执行。
计算机存储器208可作为任意类型的易失性或非易失性(例如,闪存)存储器实现,而自适应控制器212和/或上文描述的模块可作为能够提供这里描述的功能的任意的软件程序、硬件装置、或它们的组合来实现。例如,自适应控制器212和/或上文描述模块的每个可以是专用集成电路(ASIC)或现场可编程门阵列(FPGA)。可替代地,自适应控制器212可以使用能够用任何适合的编程语言或多种编程语言(例如,C++、,C#、Java、VisualBasic、LISP、BASIC、PERL等)来编程的通用微处理器(例如由Intel公司提供的任意的PENTIUM微处理器)来实现。本领域技术人员能够较容易地实现这些合适的控制编程而无需过多的实验。
在一个特定实施例中,如下面所描述的,编程控制电路132以周期性时间间隔从药物储存器108输送固定剂量的药物至目标部位,并配置控制电路132,把在每一个时间间隔上的泵200的状况存储在计算机存储器208中。在每个给药间隔上(或在其他周期性间隔上)可存储的一些示例性而非限制性的泵200的内部状况包括:通过电解电极134的电流、电解电极134的跨电压、或电解电极134的电阻;用于驱动电解电极134的总电荷;通过插管120的最大药物流速;通过插管120的药物流动方式的任何变化;泵200达到通过插管120的药物的特定流速所需要的激励时间;流动药物从特定流速缓降至零流速所需要的时间;泵200的初始激励和通过插管120的药物的初始流动之间的时间延迟;泵致动器204的效率(其在电解驱动泵200的情形中,可由泵送通过致动器204的电荷量和由此生成的气体量之间的比值定义);药物储存器108的内部压力;泵200经历的加速度;特别涉及流量传感器144结构体系的流量传感器参数(例如,在流量传感器144是电阻式温度探测器时,可能需要存储传感器和发热元件的电阻);以及泵致动器204、药物储存器108、和/或插管120的物理尺寸,它们可能由于阻塞、结疤或其他生化/生理事件而改变。
在一个实施例中,这些参数通过使用物理传感器直接或间接地测量,诸如,流量传感器144,药物储存器108或插管120内的压力传感器,加速计、陀螺仪、高度计,接近电解电极134的传感器(例如,用来测量电解电极134的电阻、通过其中的电流、和/或电解电极134处的电压或跨电压),或散布在泵200中的任意其他传感器。在其他实施例中,这些参数通过使用已知关系来确定。例如,通过插管120的药物流速可以通过在插管120中使用的压力传感器并利用压力和流速之间的已知线性关系来确定。在另一实施例中,这些参数中的大部分可通过分析用于驱动泵致动器204的电波形和/或通过分析由流量传感器144感测的流动曲线来确定。
在所有的情形中,如下文所描述的,控制电路132的自适应控制器212能够接收并处理参数数据并补偿泵200的任何状况变化,从而调节其操作以维持目标剂量水平。该“自补偿”可以通过存储上文所述的在输送先前剂量时的泵200状态的参数数据并通过考虑实时参数值来确定在进行下一剂量事件时用于电解电极134的最佳激励电流和/或其激励持续时间来实现。例如,如图3所示,自适应控制器212可以接收、分析并处理来自先前剂量的存储参数、来自泵致动器204的实时数据以及来自流量传感器144的实时数据(例如,流速数据),从而确定并引导恰当的输出信号至泵致动器204(即,为了以恰当方式驱动泵200)。针对初始给药,或在上述数据不可用的情形时(例如,由于泵200的复位动作),自适应控制器212可以利用一组预定参考的参数值。这些参考值可以具体为所使用的具体电解电极134的特性、所使用的电解溶液的类型、和/或电解致动器204、药物储存器108和插管120的物理尺寸。
在操作电解驱动泵200的一个模式中,使用恒定电流在可变量时间上驱动电解电极134。在该模式中,该恒定电流使通过插管120的药物流速单调上升直至关闭电流,此时,泵200中剩余压力引起流速的缓慢衰退直至流速为零。在针对该操作模式的功能性示例中,在每个给药间隔上将以下三个参数存储在计算机存储器208中:为驱动泵200而提供给电解电极134的电流(I);通过插管120的最大药物流速(Fmax);以及在泵致动器204停用(V关闭)后,由泵200基于剩余压力输送的液体(即,药物)的体积。该存储的信息然后用在将来剂量中以改善给药速度和精确性。例如,可以基于先前剂量数据调节用于驱动将来剂量的电流(例如,如果最大流速太小则增加,以及最大流速太高则降低),从而保持每个剂量的持续时间、并保持每个剂量所输送的药物体积相对地恒定。在一个实施例中,这通过如下所述的线性方式来实现:
I当前=F最佳/F最大,先前×I先前
其中I当前是在目前剂量期间要供给电解电极134的电流,F最佳是通过插管120的期望最大药物流速,F最大,先前是在先前剂量期间通过插管120的最大药物流速,以及I先前在先前剂量期间供给电解电极134的电流。
作为另一示例,泵致动器204的关闭时间可以替换为可调节的,或可额外调节的(例如,如果在泵致动器204停用后所输送的药物体积低于期望的则延迟关闭时间,以及如果在泵致动器204停用后所输送的药物体积高于期望的,则提早关闭时间)以保持所输送的药物体积保持相对恒定。这里也可以使用线性近似来实现,其中泵致动器204在满足如下条件后立即停用:
V累积+F/F最大,先前×V关闭,先前=V目标
其中V累积是目前为止当前剂量所输送的总药物体积,F是通过插管120的实时药物流速;F最大,先前是先前剂量通过插管120的最大药物流速,V关闭, 先前是先前剂量在泵致动器204关闭后所输送的药物体积,以及V目标是将要输送的药物的目标体积。在该方式中,自适应控制器212不断地调节激励泵200的方式并计算出泵200特性上的系统性、非随机的变化。
当泵200是电解驱动泵时,对启动通过插管120的药物流动并随后达到特定流速所需的电流量以及当电解电极134不再施加电流后从药物储存器108输送的液体量的确定和控制是特别有利的。特别地,第一个参数是重要的,这是因为通过插管120的药物流动并之后达到特定流速所需的电流量取决于药物储存器108中剩余的液体多少。使用过低的电流在能量上并不经济,这是由于即使插管120中没有或有非常低的药物流过,所有系统也都将要运转。另一方面,使用过高的电流将导致药物流速过冲至不安全水平。第二个参数同样是重要的,这是因为在泵200关闭后所输送的药物体积主要取决于电解腔112中的气/液比。针对泵200时间周期中后期使用的剂量(例如,其中泵200以电解腔112内高气/液比运转),在泵200完全停止前有太多的气体需要排出。但针对前期的剂量,情况却相反。
本领域普通技术人员应该理解的是,除了上面给出的两个示例,自适应控制器212可以在控制泵致动器204时,以及最终在从药物储存器108配给药物时,识别和分析泵200内部状况上的许多其他变化。例如,可能会期望泵200能使在一段指定时间内(t最优)的每个剂量达到最佳流速(F最优),然后让剩余的剂量维持该流速。实现这种情况的一种方式是通过使用恒定电流(I开始)驱动泵200的电解电极134以起动每个剂量,直到达到最佳流速(F最优),此时得到来自流量传感器144的反馈并使用算法(例如,比例-积分-微分(“PID”)算法或其他算法)调节供给电解电极134的电流,从而让剩余剂量维持最佳流速(F最优)。换言之,可以使用时变电流波形来驱动泵200。在一个实施例中,为了在一段指定时间内(t最优)达到最佳流速(F最优),逐个剂量地调节起动电流(I开始)。以类似于之前的方式,这可以通过使用线性近似(然而,本领域普通技术人员应该理解的是,也可以对此处获得的任何参数应用非线性近似)来实现。更具体而言,当前剂量的起动电流(I开始,当前)能够通过使用先前剂量的起动电流(I开始, 先前)和在先前剂量流速达到最佳流速(F最优)花费的时间(t先前)来计算,如下所示:
I开始,当前=t先前/t最优×I开始,先前
现参照图4,示例性图表300示意了上述对药物剂量水平自适应控制的效果。在该示例中,在每个释放事件期间待输送的目标剂量水平是200纳升(nL)。事件1对应基于参照参数值计算的180nL初始给药剂量。然后,自适应控制器212针对泵200参数(例如,如上所述的,可增加提供给电解电极134的电流量和/或其激励时间以增加输送给目标部位的药物体积)计算合理的调节值,直到在事件2上达到200nL的目标输送。如所示意的,在事件1和事件2之间可以存在因自适应控制器212过度补偿且泵200输送了多于目标剂量的剂量(例如,205nL)的时间点304。在这种情况下,自适应控制器212改进其针对泵200参数的调节值(例如,可降低提供给电解电极134的电流量和/或其激励时间以降低输送给目标部位的药物体积),直到实际达到了在事件2上的200nL的目标输送。
继续图4的图标300所描述的示例,由于泵200的一个或多个参数的变化,事件3中的剂量于是下降至190nL。能够变化并导致所输送药物剂量的这种降低(即,导致泵200效率的降低)的泵200自身内的示例性状况包括:电解电极134的降解(例如,冲蚀或腐蚀)、电解腔112的溶液中电解质浓度的减少、和/或一般的机械或化学损耗。作为响应,自适应控制器212随后如上所述的进行补偿以使得泵200在事件4上释放准确的药物量。因此,泵200动态地作用于泵200状况的变化。
图5A描绘了在没有控制电路132提供的反馈控制(例如,针对应用开环控制系统的泵)下的泵200操作时的示例性流量曲线400和激励曲线404。如图所示,尽管激励电流保持相同(在图5A中针对前期和后期剂量的激励曲线404重叠),但由于泵送效率降低,后期输送的药物量减少。
图5B描绘了在由控制电路132提供的反馈控制下泵200操作时的示例性流量曲线408和激励曲线412。特别地,图5B示出了针对后期剂量如何增加泵送时间以补偿减少的泵200的效率。更具体地,针对后期剂量,泵200以相同电流激励更长的时间,从而成功输送了目标剂量。
图5C同样描绘了在由控制电路132提供的反馈控制下泵200操作的示例性流量曲线416和激励曲线420。特别地,图5C示出了如何通过提高后期剂量的激励电流以保持前期和后期剂量的给药时间恒定,同时仍能补偿减少的泵200的效率。前期和后期剂量的流量曲线416重叠,说明在这两个剂量期间输送了相同药物量。
C.基于目标部位状况的自适应控制
在其他实施例中,再次参照图1至图3,自适应控制器212同样能够接收来自监测药物输送治疗区域的目标部位传感器148的信息,并随后在某些时间周期改变目标剂量。更特别地,如果治疗区域的变化(例如,症状的恶化或改善、生物或生化参数的变化、电活动变化、压力变化等)需要更高或更低剂量水平或需要在剂量频率上变化,自适应控制器212能够控制泵致动器204以调节剂量并将其维持在新水平直到需要另一改变。换言之,自适应控制器212可以激励泵200以达到期望结果,诸如具体生理状态或生化参数的规律。如之前的,由目标传感器148感测的参数(例如,压力、温度等)可以存储在计算机存储器208中用于后期使用(例如,用于对比以确定待输送药物的合理剂量)。
作为示例,假设泵200每分钟输送200nL的初始目标剂量。在一段时间后,由于治疗区域的变化或给药体系的变化,剂量需要减少至150nL。则自适应控制器212可以操作泵致动器204以使得每30分钟输送150nL药物,直到由于治疗区域上发生另一变化或由泵200使用者发出了指令,或是其他情况。
有利地是,这种灵活性便于泵200能应用于更广泛的治疗方案,这些治疗方案可能要求在一段相当长的时期内会有不同剂量或不同剂量频率的交叠。
可选地,自适应控制器212可以编程以响应泵200自身状况的变化以及同时响应目标治疗区域状况的变化。换言之,自适应控制器212可以接受来自泵200内部传感器或其他装置以及来自目标治疗传感器148的数据,分析这两组数据,并控制泵致动器204以计算这两组数据。可替代地,在另一个实施例中,如果该确定性的参数是泵200自身的而不是治疗区域的,则自适应控制器212可以编程以例如基于因生理变化或结疤而在靶区内形成的阻塞来制止起动动作。
D.动态、自适应控制药物输送泵的示例性应用
图6示意性说明了根据本发明一个实施例的植入到患者眼睛中的药物输送泵100、200。如图所示,泵100、200置于眼结膜上,以及从中插入插管120的远端进入眼睛后房。这样,插管120的远端(以及,因此,药物储存器108)与患者流体连通。之后药物输送泵100、200将治疗液体通过插管120和止回阀140给药至眼睛后房,其中止回阀140如前文所述用于阻止液体回流。特别地,通过使用自适应控制器212和其他控制电路132以上文所述的任意方式(例如,基于泵自身状况变化和/或基于目标部位状况)来控制泵致动器204,从而从药物储存器108输送一个或多个液体剂量穿过插管120并进入患者眼睛。
在其他实施例中,泵100、200用于给药液体至眼睛前房,其与后房由晶状体隔开。然而,更一般的是,可应用如前所提及的泵100、200来给药液体至患者身体的任何部位。
作为另外示例,泵100、200可以是粘附于身体的电解驱动泵,用于药物注入至患者皮下组织。例如,泵100、200可以在三到七天内连续地输送胰岛素至患者身体。尽管患者可能需要重新计算他或她的胰岛素输送(例如,随时间增加或减少基本速率),以及编程泵100、200以在饭后提供间歇性大剂量峰值的胰岛素。因此,该示例中的泵100、200能够调节电解以增加或减少胰岛素流量,从而随时间来精确地输送准确的液体体积。此外,在一段较长时间上的药物输送,如三天,会使泵100、200经受新的环境状况。例如,患者可能驾车从低海拔到高海拔高度或者在密闭飞机里飞行。泵100、200能够使用两个环境信号(例如,高度计、压力变化、流速变换等)来调节药物流量并确保准确的药物输送。
作为又一个示例,泵100、200可以使用来自加速计或陀螺仪的输入来感测患者位置。例如,泵100、200能够感测患者在之前7天晚10点至早6点的时间(由于,例如,患者在睡觉)是平卧的。在这种情况下,泵100、200则可以识别患者的睡眠时间(即,从感测到患者处于平卧位置)或REM睡眠周期,随后使用该信息来注入不同的药物体积(或在指定时间的药物),从而来适应最佳状况。例如,可以在睡眠时间调节泵100、200的流速至由医生预定的量(例如,通常最好的是在REM睡眠周期期间注入一些青光眼药物至患者眼内从而使药物更好地遍布在整个眼中,而一些用于视网膜的诸如抗-VEGF药物会作用一个月的时间,因此应该平静地注入玻璃体内;此外,应当在睡眠期间以较低基础速率注入胰岛素或注入更少的止痛药物)用于注入。与理解患者何时在睡眠形成对比,泵100、200还可以识别患者何时在运动或患者何时不是仰卧的,并相应地调节药物注入(例如,调节到医生预编程的针对在某些动作期间的注入)。
有利的是,能够将这里描述的控制电路132用于特性不相同的泵,这或是由于使用者选择的偏爱或是由于在制造过程中产生的变化。例如,使用的电极或电解液的类型决定了电解驱动泵的性能。然而控制电路132具有足够的鲁棒性和通用性以适应以各种参数值操作的泵。作为另一示例,流量传感器元件的电阻的制造加工偏差可以通过控制电路132的自适应性质得到调节。更具体而言,由加工偏差引起的流量传感器元件的电阻不匹配会导致产生偏移,对此控制电路132能够补偿。
可选地,控制电路132还可以通过监测某些关键的泵参数来增强泵100、200的安全性以及效能。例如,可以针对每个参数或针对对应于具体泵状态的一些总参数组合来限定允许范围,在此允许范围泵100、200持续正常运转。如果单个参数或一些总参数组合没有落入这些预定范围,则将在泵100、200内触发动作,诸如关闭或给使用者发出需要做出响应的报警。例如,泵100、200可以通过光照、声音、震动或打击来报警患者。在一个实施例中,编程以在患者移动时产生报警从而最大可能性的使患者接收到报警,以及还有在患者睡眠时避免报警来保存电池能量。
在一个特定示例中,控制电路132能够响应并预知流量传感器144的故障。其中,例如,流量传感器144包括一组发热器和电阻温度探测器,由于使用中经历的热应力,这些元件中的一个可能会在不确定数量的剂量后开始发生故障。控制电路132能够周期性的(例如,逐个剂量地)监测到发热元件的电阻,并探测电阻的变化,其能够指示开始故障或完全故障(诸如开路)。包括传感器和致动器的利用电阻或电容元件的其他泵组件也可以类似的由控制电路132监测以保证正常的功能运转。
描述了本发明的某些实施例后,对本领域普通技术人员显而易见的是可以使用包括此处公开概念的其他实施例而不背离本发明的精神和范围。例如,尽管已经主要描述了自适应控制器212和其他控制电路132结合电解驱动泵使用,而这仅是示意性的。本领域普通技术人员应该容易的意识和理解到自适应控制器212和其他控制电路132还可以应用到其他类型的药物输送泵中,诸如基于如电渗透、机械激励、或压力驱动机制的那些药物输送泵。因此,所述实施例在各方面应理解为仅是示例性的而不是限制性的。

Claims (11)

1.一种药物输送泵,包括:
药物储存器;
插管,其用于将液体从储存器引导至目标部位;
泵致动器,其用于推动来自储存器的液体穿过插管,所述泵致动器包括电解腔和电解电极,以引起在电解腔内放出气体从而增大药物储存器的压力,使得液体从药物储存器进入插管;以及
电路,其用于控制泵致动器以i)初始地在固定的时间间隔下输送基本固定的液体剂量至目标部位,和ii)补偿药物输送泵的状况变化以维持或恢复基本固定的液体剂量的输送,对于每个剂量配置所述电路以至少部分地基于当电流被供给时所达到的最大流速或在电流不再被供给之后通过剩余压力输送的液体的量,控制供给到电解电极的激励电流的量和电极的激励持续时间,以便补偿所述最大流速以及所述通过剩余压力输送的液体的量的变化。
2.权利要求1所述的药物输送泵,其中所述电路包括存储器,其用于存储先前输送事件时药物输送泵的状况。
3.权利要求1所述的药物输送泵,还包括流量传感器,其用于测量通过插管的液体的流速。
4.权利要求3所述的药物输送泵,其中所述电路至少部分地基于所述流速的分析控制泵致动器。
5.权利要求4所述的药物输送泵,其中所述电路还基于所存储的先前剂量时药物输送泵的状况控制泵致动器。
6.权利要求4所述的药物输送泵,其中所述电路还基于来自泵致动器的实时数据控制泵致动器。
7.权利要求1所述的药物输送泵,其中所述泵致动器还包括
可膨胀隔膜,其隔开所述电解腔和所述储存器并提供它们之间的流体屏障,使得在电解质内放出气体扩张所述隔膜,从而加压所述储存器。
8.权利要求7所述的药物输送泵,其中所述可膨胀隔膜通过改变供给电极的所述激励电流来调节。
9.权利要求7所述的药物输送泵,其中所述可膨胀隔膜通过改变电极的所述激励持续时间来调节。
10.权利要求1所述的药物输送泵,其中所述电解电极通过恒定电流来驱动。
11.权利要求1所述的药物输送泵,其中所述电解电极通过时变电流波形来驱动。
CN201080046911.8A 2009-08-18 2010-08-18 具有自适应控制的电解药物输送泵 Expired - Fee Related CN102576385B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US23474209P 2009-08-18 2009-08-18
US61/234,742 2009-08-18
PCT/US2010/045897 WO2011022484A1 (en) 2009-08-18 2010-08-18 Electrolytic drug-delivery pump with adaptive control

Publications (2)

Publication Number Publication Date
CN102576385A CN102576385A (zh) 2012-07-11
CN102576385B true CN102576385B (zh) 2016-02-24

Family

ID=43127347

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201080046911.8A Expired - Fee Related CN102576385B (zh) 2009-08-18 2010-08-18 具有自适应控制的电解药物输送泵

Country Status (9)

Country Link
US (2) US9199035B2 (zh)
EP (1) EP2467797B1 (zh)
JP (1) JP5758388B2 (zh)
KR (1) KR101697388B1 (zh)
CN (1) CN102576385B (zh)
AU (1) AU2010284216B2 (zh)
CA (1) CA2771584A1 (zh)
MX (1) MX2012002063A (zh)
WO (1) WO2011022484A1 (zh)

Families Citing this family (43)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2493921T3 (es) 2006-03-14 2014-09-12 University Of Southern California Dispositivo MEMS para la administración de agentes terapéuticos
MX2010006840A (es) 2007-12-20 2010-08-12 Univ Southern California Aparato y métodos para suministrar agentes terapeuticos.
MX2010007382A (es) 2008-01-03 2010-12-20 Univ Southern California Dispositivos implantables para suministro de farmacos, y aparato y metodos para recargar los dispositivos.
WO2009137777A2 (en) 2008-05-08 2009-11-12 Replenish Pumps, Llc Implantable drug-delivery devices, and apparatus and methods for filling the devices
ES2534864T3 (es) 2008-05-08 2015-04-29 Minipumps, Llc Bombas implantables y cánulas para las mismas
US8231609B2 (en) 2008-05-08 2012-07-31 Minipumps, Llc Drug-delivery pumps and methods of manufacture
US9333297B2 (en) * 2008-05-08 2016-05-10 Minipumps, Llc Drug-delivery pump with intelligent control
CN102576385B (zh) 2009-08-18 2016-02-24 迷你泵有限责任公司 具有自适应控制的电解药物输送泵
CN103108665A (zh) * 2010-04-20 2013-05-15 迷你泵有限责任公司 电解驱动药物泵装置
US9603997B2 (en) 2011-03-14 2017-03-28 Minipumps, Llc Implantable drug pumps and refill devices therefor
US9919099B2 (en) 2011-03-14 2018-03-20 Minipumps, Llc Implantable drug pumps and refill devices therefor
US20120234433A1 (en) * 2011-03-14 2012-09-20 Jason Shih Instrument and methods for filling an implanted drug pump
US10286146B2 (en) 2011-03-14 2019-05-14 Minipumps, Llc Implantable drug pumps and refill devices therefor
CN103501837B (zh) 2011-06-23 2016-01-13 生物技术公司 用于医疗泵的通风容器
EP2540261A1 (en) * 2011-06-30 2013-01-02 Sanofi-Aventis Deutschland GmbH Intraocular medicament delivery device
EP2760504B1 (en) * 2011-09-30 2020-07-22 MiniPumps, LLC Implantable drug pumps and refill devices therefor
EP2780055A2 (en) * 2011-11-18 2014-09-24 Minipumps, LLC Accurate flow control in drug pump devices
CN103127579B (zh) * 2011-11-21 2017-06-16 上海泽生科技开发股份有限公司 便携式注射泵的驱动系统
US20130338635A1 (en) * 2012-06-15 2013-12-19 Animas Corporation Pressure independent delivery method for portable infusion pump
US9199044B2 (en) 2012-08-06 2015-12-01 Elwha Llc Devices and methods for wearable injection guides
US20140088554A1 (en) * 2012-09-24 2014-03-27 Po-Ying Li Drug-delivery pump with intelligent control
US9629963B2 (en) 2012-10-30 2017-04-25 Elwha Llc Systems and methods for generating an injection guide
US10046119B2 (en) 2012-10-30 2018-08-14 Elwha Llc Systems and methods for generating an injection guide
DE102012025143A1 (de) * 2012-11-07 2014-05-08 Heraeus Medical Gmbh Verfahren zur Wirkstofffreisetzung und Wirkstofffreisetzungssysteme
EP2964289A4 (en) * 2013-03-05 2016-11-23 Insuline Medical Ltd DEVICE, SYSTEM AND METHOD OF SUBCUTANEOUS DRUG DELIVERY
CA2913148C (en) 2013-05-23 2021-06-15 Turnpoint Medical Devices, Inc. Pneumatically coupled fluid control system and process with air detection and elimination
AU2014281685A1 (en) * 2013-06-17 2016-01-21 Minipumps, Llc Vented implantable drug-delivery device
CA2915985A1 (en) * 2013-06-25 2014-12-31 Andrew Dunn Electrolysis recombination control mask and method of manufacture thereof
WO2015021031A1 (en) 2013-08-05 2015-02-12 Cam Med Llc Conformable patch pump
EP3240591A4 (en) * 2014-12-30 2018-09-05 MiniPumps, LLC Implantable electrolytic diaphragm pumps
US11285307B2 (en) * 2016-02-19 2022-03-29 University Of Florida Research Foundation, Incorporated Drug delivery integrated circuit (IC) and system
TWI762521B (zh) * 2016-10-17 2022-05-01 潔霺生醫科技股份有限公司 微遞送裝置
EP3534991A1 (en) * 2016-11-01 2019-09-11 Sanofi-Aventis Deutschland GmbH Volume measuring arrangement
EP3318226B1 (de) * 2016-11-03 2021-01-06 This AG Saubere venturi aspiration
US11278665B2 (en) 2016-11-22 2022-03-22 Eitan Medical Ltd. Method for delivering a therapeutic substance
US20190054234A1 (en) * 2017-08-17 2019-02-21 Qualcomm Incorporated Electronic control of drug administration via hypodermic needle devices
CN107811748A (zh) * 2017-09-18 2018-03-20 歌尔股份有限公司 电子设备滴加眼药水的方法、头戴设备以及存储介质
EP3744368A1 (en) 2018-10-05 2020-12-02 Sorrel Medical Ltd. Triggering sequence
EP3653183B8 (en) * 2018-11-14 2022-01-19 Industrial Technology Research Institute Eye wearing device
CN113164033A (zh) * 2018-12-04 2021-07-23 奥尔托特洛菲克斯有限公司 用于治疗骨关节炎的制剂
CN110367927B (zh) * 2019-08-01 2022-04-08 中山大学 青光眼眼压连续检测系统及其检测方法
US11000647B2 (en) * 2019-10-04 2021-05-11 Arnold Chase Controller based on lifestyle event detection
US11698285B2 (en) 2020-01-02 2023-07-11 Kyndryl, Inc. Monitoring dispensation of a substance

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4886514A (en) * 1985-05-02 1989-12-12 Ivac Corporation Electrochemically driven drug dispenser
AU8997891A (en) * 1990-12-31 1992-07-02 S.I. Scientific Innovations Ltd. Liquid delivery device particularly useful for delivering drugs
CN1321096A (zh) * 1999-09-17 2001-11-07 巴克斯特国际公司 具有稳定流体流动的流体分送器
WO2001089607A2 (en) * 2000-05-23 2001-11-29 Elan Pharma International Limited Gas driven drug delivery device
CN101125086A (zh) * 2006-08-18 2008-02-20 刘胜 闭环自动控制胰岛素注射系统
CN101365505A (zh) * 2006-01-06 2009-02-11 诺沃-诺迪斯克有限公司 使用收缩式储存器的药物输送设备
WO2009086112A2 (en) * 2007-12-20 2009-07-09 University Of Southern California Apparatus and methods for delivering therapeutic agents

Family Cites Families (312)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2445477A (en) * 1945-03-12 1948-07-20 Marvin L Folkman Ampoule
US3175558A (en) * 1962-03-14 1965-03-30 James C Caillonette Thermal therapeutic pack
US3731681A (en) * 1970-05-18 1973-05-08 Univ Minnesota Implantable indusion pump
FR2091189A5 (zh) 1970-05-18 1972-01-14 Regents University Minne
US3760805A (en) * 1971-01-13 1973-09-25 Alza Corp Osmotic dispenser with collapsible supply container
BE792363A (fr) 1971-12-06 1973-06-06 Mpl Inc Dispensateur de liquide et procede et appareil pour le remplir
CH557178A (de) 1972-08-10 1974-12-31 Siemens Ag Geraet fuer die zufuehrung von medikamenten.
US3916899A (en) * 1973-04-25 1975-11-04 Alza Corp Osmotic dispensing device with maximum and minimum sizes for the passageway
US3977404A (en) * 1975-09-08 1976-08-31 Alza Corporation Osmotic device having microporous reservoir
DE2626348C3 (de) * 1976-06-11 1980-01-31 Siemens Ag, 1000 Berlin Und 8000 Muenchen Implantierbare Dosiereinrichtung
DE2626294C3 (de) * 1976-06-11 1980-01-10 Siemens Ag, 1000 Berlin Und 8000 Muenchen Implantierbare Dosiereinrichtung
US4164560A (en) * 1977-01-05 1979-08-14 Folkman Moses J Systems for the controlled release of macromolecules
US4180375A (en) * 1977-01-21 1979-12-25 Altex Scientific, Inc. Liquid chromatography pump
US4150673A (en) * 1977-02-03 1979-04-24 Pharmachem Corporation Coded entry system for blood bag
US4203441A (en) * 1978-12-18 1980-05-20 Alza Corporation Osmotically triggered device with gas generating means
US4237881A (en) * 1978-12-26 1980-12-09 Anatros Corporation Device for the intravenous or enteric infusion of liquids into the human body at a predetermined constant rate
DE2906830C2 (de) * 1979-02-22 1981-07-16 B. Braun Melsungen Ag, 3508 Melsungen Gerät für Dauerinfusionen
US4373527B1 (en) * 1979-04-27 1995-06-27 Univ Johns Hopkins Implantable programmable medication infusion system
US4525165A (en) 1979-04-27 1985-06-25 The Johns Hopkins University Fluid handling system for medication infusion system
US4553973A (en) * 1982-07-12 1985-11-19 Alza Corporation Process for preparing osmotic device
US4888176A (en) * 1984-05-21 1989-12-19 Massachusetts Institute Of Technology Controlled drug delivery high molecular weight polyanhydrides
US4708716A (en) 1983-08-18 1987-11-24 Drug Delivery Systems Inc. Transdermal drug applicator
US4543088A (en) * 1983-11-07 1985-09-24 American Hospital Supply Corporation Self-sealing subcutaneous injection site
US4692145A (en) 1984-10-15 1987-09-08 American Hospital Supply Corporation Power system for infusion pumps
US4687423A (en) 1985-06-07 1987-08-18 Ivac Corporation Electrochemically-driven pulsatile drug dispenser
EP0461680A3 (en) 1985-06-10 1992-02-26 Drug Delivery Systems Inc. Programmable control and mounting system for transdermal drug applicator
US4738657A (en) * 1985-09-30 1988-04-19 Mcghan Medical Corporation Self-sealing injection reservoir
NO165378C (no) 1985-11-22 1991-02-06 Ellingsen O & Co Medikamentavgivende innretning for implantering i menneskekroppen.
US4781675A (en) * 1985-11-27 1988-11-01 White Thomas C Infusion cannula
US4959217A (en) * 1986-05-22 1990-09-25 Syntex (U.S.A.) Inc. Delayed/sustained release of macromolecules
CA1311686C (en) 1986-06-25 1992-12-22 John Weldon Shell Controlled release bioerodible drug delivery system
US4781695A (en) * 1986-07-11 1988-11-01 Dalton Michael J Implantable fluid dispenser
US4751926A (en) * 1986-09-12 1988-06-21 Dow Corning Wright Corporation Instrument for subcutaneous insertion of an injection reservoir
US5989579A (en) * 1986-10-02 1999-11-23 Escalon Medical Corp. Ocular insert with anchoring protrusions
US5147647A (en) * 1986-10-02 1992-09-15 Sohrab Darougar Ocular insert for the fornix
CA1283827C (en) 1986-12-18 1991-05-07 Giorgio Cirelli Appliance for injection of liquid formulations
GB8701731D0 (en) 1987-01-27 1987-03-04 Patcentre Benelux Nv Sa Pumps
US4902278A (en) 1987-02-18 1990-02-20 Ivac Corporation Fluid delivery micropump
US4760837A (en) * 1987-02-19 1988-08-02 Inamed Development Company Apparatus for verifying the position of needle tip within the injection reservoir of an implantable medical device
EP0315656B1 (de) 1987-05-18 1993-07-07 Disetronic Ag Infusionsgerät
US4838887A (en) * 1987-12-15 1989-06-13 Shiley Infusaid Inc. Programmable valve pump
US4853224A (en) * 1987-12-22 1989-08-01 Visionex Biodegradable ocular implants
US5066276A (en) 1988-06-21 1991-11-19 Alcon Laboratories, Inc. Method and apparatus for injecting viscous fluid into the eye to lift pre-retinal and post-retinal membrane with linear pressure control
DD274863A1 (de) 1988-08-12 1990-01-03 Komb Medizin Und Labor Technik Sicherheitsventil fuer minimale durchflussmengen, insbesondere fuer implantierbare infusionspumpen
US5062834A (en) 1989-02-24 1991-11-05 Product Development (S.G.Z.) Ltd Device for dispensing a liquid particularly useful for delivering medicaments at a predetermined rate
FR2649617A1 (fr) * 1989-07-12 1991-01-18 Veprol Dispositif de delivrance d'un principe actif pharmacologique par pompage electrolytique
US5164188A (en) * 1989-11-22 1992-11-17 Visionex, Inc. Biodegradable ocular implants
US5067491A (en) 1989-12-08 1991-11-26 Becton, Dickinson And Company Barrier coating on blood contacting devices
US5207227A (en) * 1990-03-02 1993-05-04 Powers Alexandros D Multiprobes with thermal diffusion flow monitor
US5213568A (en) 1990-03-30 1993-05-25 Medtronic Inc. Activity controlled electrotransport drug delivery device
US5135498A (en) 1990-04-02 1992-08-04 Kam Robert J Controlled release infusion device
US5318540A (en) 1990-04-02 1994-06-07 Pharmetrix Corporation Controlled release infusion device
US5476445A (en) * 1990-05-31 1995-12-19 Iovision, Inc. Glaucoma implant with a temporary flow restricting seal
US5178604A (en) * 1990-05-31 1993-01-12 Iovision, Inc. Glaucoma implant
US5242406A (en) 1990-10-19 1993-09-07 Sil Medics Ltd. Liquid delivery device particularly useful for delivering drugs
US5090963A (en) 1990-10-19 1992-02-25 Product Development (Z.G.S.) Ltd. Electrochemically driven metering medicament dispenser
US5108372A (en) * 1990-12-12 1992-04-28 Houston Advanced Research Center Intravenous fluid temperature regulation method and apparatus
US5527288A (en) 1990-12-13 1996-06-18 Elan Medical Technologies Limited Intradermal drug delivery device and method for intradermal delivery of drugs
US5163909A (en) 1991-01-28 1992-11-17 Alan E. Jordan Medical fluid delivery system
US5279607A (en) 1991-05-30 1994-01-18 The State University Of New York Telemetry capsule and process
US5425716A (en) 1991-08-09 1995-06-20 Atom Kabushiki Kaisha Infusion apparatus
US5171213A (en) * 1991-08-14 1992-12-15 Price Jr Francis W Technique for fistulization of the eye and an eye filtration prosthesis useful therefor
EP0746356B1 (en) 1991-10-24 2000-05-17 Insutech, Incorporated Gas pressure driven infusion system by hydrogel electrolysis
US5462739A (en) * 1991-11-21 1995-10-31 Yeda Research And Development Co., Ltd. Microdelivery device and method for enhanced drug administration to the eye
US5629008A (en) 1992-06-02 1997-05-13 C.R. Bard, Inc. Method and device for long-term delivery of drugs
US5407441A (en) * 1992-06-04 1995-04-18 Greenbaum; Scott Ophthalmologic cannula
WO1993025841A1 (de) 1992-06-15 1993-12-23 Max Wyssmann Vorrichtung zur gezielten, steuerbaren abgabe einer flüssigkeit oder einer viskosen masse
US5318557A (en) 1992-07-13 1994-06-07 Elan Medical Technologies Limited Medication administering device
IE930532A1 (en) * 1993-07-19 1995-01-25 Elan Med Tech Liquid material dispenser and valve
US5676651A (en) 1992-08-06 1997-10-14 Electric Boat Corporation Surgically implantable pump arrangement and method for pumping body fluids
US5242408A (en) 1992-09-23 1993-09-07 Becton, Dickinson And Company Method and apparatus for determining pressure and detecting occlusions in a syringe pump
US5252192A (en) * 1992-10-19 1993-10-12 Hughes Aircraft Company Electrolytic pump
CA2083555A1 (en) 1992-11-23 1994-05-24 David H. Laing Portable infusion device
US5290240A (en) 1993-02-03 1994-03-01 Pharmetrix Corporation Electrochemical controlled dispensing assembly and method for selective and controlled delivery of a dispensing fluid
US5474527A (en) 1993-03-29 1995-12-12 Bettinger; David S. Positive displacement transdermal system
US5398851A (en) 1993-08-06 1995-03-21 River Medical, Inc. Liquid delivery device
US5458095A (en) 1993-09-15 1995-10-17 Energy Reductions Systems, Inc. Air pump-assisted hydrogen/oxygen fuel cell for use with internal combustion engine
DE4333736A1 (de) 1993-10-04 1995-04-06 Anschuetz & Co Gmbh Infusionspumpe
DE69431994T2 (de) 1993-10-04 2003-10-30 Res Int Inc Mikro-bearbeitetes fluidbehandlungsvorrichtung mit filter und regelventiler
US5443505A (en) * 1993-11-15 1995-08-22 Oculex Pharmaceuticals, Inc. Biocompatible ocular implants
US5505697A (en) 1994-01-14 1996-04-09 Mckinnon, Jr.; Charles N. Electrically powered jet injector
CA2189000C (en) 1994-05-16 2002-08-13 Mitsuo Nakamura Process and diastereomeric salts useful for the optical resolution of racemic .alpha.-[4-(1,1-dimethylethyl)phenyl]-4-(hydroxydiphenylmethyl)-1-piperidinebutanol and derivative compounds
US5472436A (en) * 1994-07-26 1995-12-05 Fremstad; Daria A. Ocular appliance for delivering medication
JPH0858897A (ja) 1994-08-12 1996-03-05 Japan Storage Battery Co Ltd 流体供給装置
DE4436540C2 (de) 1994-10-13 1997-03-06 Fresenius Ag Sperrvorrichtung für eine Vorrichtung zum Zuführen eines flüssigen Medikaments unter Druck
IE72524B1 (en) * 1994-11-04 1997-04-23 Elan Med Tech Analyte-controlled liquid delivery device and analyte monitor
PT788351E (pt) * 1994-11-10 2003-06-30 Univ Kentucky Res Foundation T Dispositivo implantavel recarregavel de libertacaocontrolada para administrar medicamentos direc tamente numa porcao interna do corpo
US5725493A (en) * 1994-12-12 1998-03-10 Avery; Robert Logan Intravitreal medicine delivery
US5788682A (en) * 1995-04-28 1998-08-04 Maget; Henri J.R. Apparatus and method for controlling oxygen concentration in the vicinity of a wound
IL113723A (en) * 1995-05-14 2002-11-10 Optonol Ltd Intraocular implant
WO1996041159A1 (en) 1995-06-07 1996-12-19 Ceramatec, Inc. Gas amplifier
US5616219A (en) 1995-06-13 1997-04-01 Patterson; James A. System and method for electrolysis and heating of water
US5707499A (en) 1995-10-06 1998-01-13 Ceramatec, Inc. Storage-stable, fluid dispensing device using a hydrogen gas generator
CA2243649C (en) * 1996-02-15 2009-08-04 J. Paul Santerre Bioresponsive pharmacologically-active polymers and articles made therefrom
US5904144A (en) * 1996-03-22 1999-05-18 Cytotherapeutics, Inc. Method for treating ophthalmic diseases
US6904318B2 (en) 2000-09-26 2005-06-07 Medtronic, Inc. Method and system for monitoring and controlling systemic and pulmonary circulation during a medical procedure
US5798114A (en) 1996-04-30 1998-08-25 Medtronic Incorporated Refillable body powered drug delivery techniques
US5785688A (en) 1996-05-07 1998-07-28 Ceramatec, Inc. Fluid delivery apparatus and method
ITFI960154A1 (it) 1996-06-27 1997-12-29 Giglio Mauro Del Metodo e sistema per la terapia delle aritmie ipercinetiche atriali
US5713857A (en) 1996-06-28 1998-02-03 Becton Dickinson France, S.A. Sequential stopper
US6544193B2 (en) 1996-09-04 2003-04-08 Marcio Marc Abreu Noninvasive measurement of chemical substances
US5711987A (en) * 1996-10-04 1998-01-27 Dow Corning Corporation Electronic coatings
US5725017A (en) * 1997-01-27 1998-03-10 Medtronic, Inc. In-line pressure check valve for drug-delivery systems
US5782799A (en) 1997-02-07 1998-07-21 Sarcos, Inc. Method for automatic dosing of drugs
US6416510B1 (en) 1997-03-13 2002-07-09 Biocardia, Inc. Drug delivery catheters that attach to tissue and methods for their use
US5993374A (en) 1997-06-17 1999-11-30 Radiance Medical Systems, Inc. Microcapsules for site-specific delivery
MY125849A (en) 1997-07-25 2006-08-30 Alza Corp Osmotic delivery system, osmotic delivery system semipermeable body assembly, and method for controlling delivery rate of beneficial agents from osmotic delivery systems
US5951538A (en) 1997-08-07 1999-09-14 Ceramatec, Inc. Gas generating device for delivering beneficial agents to a body cavity
AU9739898A (en) 1997-08-20 1999-03-08 Westonbridge International Limited Micro pump comprising an inlet control member for its self-priming
US6527744B1 (en) 1997-08-27 2003-03-04 Science Incorporated Fluid delivery device with light activated energy source
WO1999017749A1 (en) 1997-10-02 1999-04-15 Iep Group, Inc. A micromachined valve for fluid applications
US6345502B1 (en) 1997-11-12 2002-02-12 California Institute Of Technology Micromachined parylene membrane valve and pump
US7780623B2 (en) 1998-01-29 2010-08-24 Soltanpour David P Implantable pump apparatuses
US6589198B1 (en) 1998-01-29 2003-07-08 David Soltanpour Implantable micro-pump assembly
US6203523B1 (en) 1998-02-02 2001-03-20 Medtronic Inc Implantable drug infusion device having a flow regulator
US6048328A (en) 1998-02-02 2000-04-11 Medtronic, Inc. Implantable drug infusion device having an improved valve
US7070577B1 (en) 1998-02-02 2006-07-04 Medtronic, Inc Drive circuit having improved energy efficiency for implantable beneficial agent infusion or delivery device
US6370970B1 (en) 1998-03-18 2002-04-16 Satoshi Hosokawa Cargo handling machine including force control
US5993414A (en) 1998-04-23 1999-11-30 Medtronic, Inc. Implantable device
AU7785998A (en) 1998-06-04 1999-12-20 Elan Corporation, Plc Gas driven drug delivery device
DE69906523T2 (de) 1998-06-18 2004-02-19 Medical Research Group, Inc., Sylmar Medizinische Infusionsvorrichtung mit einem eine kontrollierte Nachgiebigkeit aufweisenden Element
US6697694B2 (en) 1998-08-26 2004-02-24 Electronic Materials, L.L.C. Apparatus and method for creating flexible circuits
US6254586B1 (en) 1998-09-25 2001-07-03 Minimed Inc. Method and kit for supplying a fluid to a subcutaneous placement site
US7766873B2 (en) 1998-10-29 2010-08-03 Medtronic Minimed, Inc. Method and apparatus for detecting occlusions in an ambulatory infusion pump
AU1710300A (en) 1998-10-29 2000-05-22 University Of Iowa Research Foundation, The Therapeutics and diagnostics for ocular abnormalities
EP1144890A2 (en) 1998-11-16 2001-10-17 California Institute of Technology Parylene micro check valve and fabrication method thereof
CA2358296A1 (en) 1999-01-05 2000-07-13 Anthony P. Adamis Targeted transscleral controlled release drug delivery to the retina and choroid
US6390797B1 (en) 1999-02-05 2002-05-21 The Dial Corporation Apparatus for manufacturing multicolored soap bars
US6281192B1 (en) * 1999-03-01 2001-08-28 Vista Scientific Llc Mucin containing ophthalmic preparations
US6835194B2 (en) 1999-03-18 2004-12-28 Durect Corporation Implantable devices and methods for treatment of pain by delivery of fentanyl and fentanyl congeners
US6458102B1 (en) 1999-05-28 2002-10-01 Medtronic Minimed, Inc. External gas powered programmable infusion device
EP1183059A1 (en) 1999-06-08 2002-03-06 Medical Research Group, Inc. Method and apparatus for infusing liquids using a chemical reaction in an implanted infusion device
US6852097B1 (en) 1999-06-24 2005-02-08 Fulton, Iii Richard E. Mechanically active infusion catheter
EP2309130B1 (en) 1999-06-28 2016-08-10 California Institute of Technology Microfabricated elastomeric valve and pump systems
US6899137B2 (en) 1999-06-28 2005-05-31 California Institute Of Technology Microfabricated elastomeric valve and pump systems
US7033603B2 (en) * 1999-08-06 2006-04-25 Board Of Regents The University Of Texas Drug releasing biodegradable fiber for delivery of therapeutics
US6471689B1 (en) 1999-08-16 2002-10-29 Thomas Jefferson University Implantable drug delivery catheter system with capillary interface
DE60018582T2 (de) 1999-08-18 2006-01-19 Microchips, Inc., Bedford Thermisch aktivierbarer microchip als abgabevorrichtung für chemikalien
US6416777B1 (en) * 1999-10-21 2002-07-09 Alcon Universal Ltd. Ophthalmic drug delivery device
US7758521B2 (en) 1999-10-29 2010-07-20 Medtronic, Inc. Methods and systems for accessing the pericardial space
US6264971B1 (en) * 1999-11-04 2001-07-24 Btg International Limited Ocular insert
US6520930B2 (en) 1999-11-24 2003-02-18 Medrad, Inc. Injectors, injector systems and injector control
US6589205B1 (en) 1999-12-17 2003-07-08 Advanced Bionica Corporation Externally-controllable constant-flow medication delivery system
WO2001056634A1 (en) 2000-02-03 2001-08-09 Medtronic, Inc. Variable infusion rate catheter
WO2001058506A2 (en) 2000-02-10 2001-08-16 Power Paper Ltd. Drug delivery device and method
AU2001241641A1 (en) 2000-03-08 2001-09-17 Rosemount, Inc. Piston position measuring device
US6375972B1 (en) * 2000-04-26 2002-04-23 Control Delivery Systems, Inc. Sustained release drug delivery devices, methods of use, and methods of manufacturing thereof
US20040175410A1 (en) 2000-04-26 2004-09-09 Control Delivery Systems, Inc. Sustained release device and method for ocular delivery of carbonic anhydrase inhibitors
US20040208910A1 (en) 2000-04-26 2004-10-21 Control Delivery Systems, Inc. Sustained release device and method for ocular delivery of adrenergic agents
US7860583B2 (en) 2004-08-25 2010-12-28 Carefusion 303, Inc. System and method for dynamically adjusting patient therapy
ATE547080T1 (de) * 2000-08-30 2012-03-15 Univ Johns Hopkins Vorrichtungen zur intraokularen arzneimittelabgabe
CA2423717A1 (en) 2000-10-04 2002-04-11 Insulet Corporation Data collection assembly for patient infusion system
ATE352333T1 (de) 2000-11-09 2007-02-15 Insulet Corp Gerät zur transkutanen abgabe von medikamenten
IL156367A0 (en) * 2000-12-14 2004-01-04 Control Delivery Sys Inc Implantable refillable and ported controlled release drug delivery device
JP4248238B2 (ja) 2001-01-08 2009-04-02 プレジデント・アンド・フェローズ・オブ・ハーバード・カレッジ マイクロ流体システム用の弁およびポンプならびにマイクロ流体システムを作製するための方法
JP4657577B2 (ja) 2001-01-09 2011-03-23 マイクロチップス・インコーポレーテッド 眼への適用および他への適用のための可撓性マイクロチップデバイス
US6602241B2 (en) 2001-01-17 2003-08-05 Transvascular, Inc. Methods and apparatus for acute or chronic delivery of substances or apparatus to extravascular treatment sites
US6520477B2 (en) * 2001-02-01 2003-02-18 William Trimmer Micro pump
US7181287B2 (en) * 2001-02-13 2007-02-20 Second Sight Medical Products, Inc. Implantable drug delivery device
US6620151B2 (en) 2001-03-01 2003-09-16 Advanced Neuromodulation Systems, Inc. Non-constant pressure infusion pump
US6713081B2 (en) * 2001-03-15 2004-03-30 The United States Of America As Represented By The Department Of Health And Human Services Ocular therapeutic agent delivery devices and methods for making and using such devices
US20070106557A1 (en) 2001-04-12 2007-05-10 Kivin Varghese Advertisements with Compensation for Attention
US7083593B2 (en) 2001-04-18 2006-08-01 Advanced Bionics Corporation Programmable implantable pump with accessory reservoirs and multiple independent lumen catheter
EP1387671A1 (en) * 2001-05-03 2004-02-11 MASSACHUSETTS EYE & EAR INFIRMARY Implantable drug delivery device and use thereof
US6491684B1 (en) 2001-05-22 2002-12-10 Durect Corporation Fluid delivery device having a water generating electrochemical/chemical pump and associated method
US6973718B2 (en) * 2001-05-30 2005-12-13 Microchips, Inc. Methods for conformal coating and sealing microchip reservoir devices
EP2316394B1 (en) * 2001-06-12 2016-11-23 The Johns Hopkins University Reservoir device for intraocular drug delivery
US6955670B2 (en) 2001-06-15 2005-10-18 Martin Francis J Nanopump system
EP1409040A4 (en) 2001-06-27 2009-08-12 Durect Corp CATHETER FOR ADMINISTRATION OF MINIMALLY INVASIVE DRUGS
PT1409065E (pt) 2001-07-23 2007-03-30 Alcon Inc Dispositivo de administração de fármacos oftálmicos
JP2005501602A (ja) * 2001-08-29 2005-01-20 カルバーリョ、リカルド エイ.ピー. デ 治療薬を組織に一方向送達するための封鎖可能な移殖型装置
US6723077B2 (en) 2001-09-28 2004-04-20 Hewlett-Packard Development Company, L.P. Cutaneous administration system
US7429258B2 (en) 2001-10-26 2008-09-30 Massachusetts Institute Of Technology Microneedle transport device
US7048963B2 (en) * 2001-11-30 2006-05-23 Cambridge Polymers Group, Inc. Layered aligned polymer structures and methods of making same
KR100507593B1 (ko) 2002-02-08 2005-08-10 주식회사 이화양행 액체공급장치
AUPS081502A0 (en) 2002-02-28 2002-03-21 Cochlear Limited Connector for drug delivery system
JP2003299732A (ja) 2002-04-12 2003-10-21 Terumo Corp 薬液注入装置および薬液容器
US6960192B1 (en) 2002-04-23 2005-11-01 Insulet Corporation Transcutaneous fluid delivery system
US7458965B2 (en) 2002-05-01 2008-12-02 Microlin, Llc Fluid delivery device having an electrochemical pump with an ion-exchange membrane and associated method
US7896867B2 (en) * 2002-05-01 2011-03-01 Microlin, Llc Fluid delivery device having an electrochemical pump with an ion-exchange membrane and associated method
US7470267B2 (en) 2002-05-01 2008-12-30 Microlin, Llc Fluid delivery device having an electrochemical pump with an anionic exchange membrane and associated method
AU2003217531A1 (en) * 2002-05-02 2003-11-17 Massachusetts Eye And Ear Infirmary Ocular drug delivery systems and use thereof
US20040124085A1 (en) 2002-06-26 2004-07-01 California Institute Of Technology Microfluidic devices and methods with electrochemically actuated sample processing
US7517440B2 (en) 2002-07-17 2009-04-14 Eksigent Technologies Llc Electrokinetic delivery systems, devices and methods
CN1678277B (zh) 2002-07-29 2010-05-05 艾克里麦德公司 治疗皮肤病的方法和组合物
US7225683B2 (en) 2002-07-31 2007-06-05 Sandia National Laboratories Composition pulse time-of-flight mass flow sensor
EP1741457A1 (en) 2002-08-09 2007-01-10 Ottawa Health Research Institute Ocular implant
US7534241B2 (en) 2002-09-23 2009-05-19 Microchips, Inc. Micro-reservoir osmotic release systems and microtube array device
KR100966536B1 (ko) 2002-09-24 2010-06-29 산요 덴키 가부시키가이샤 네트워크를 이용하는 조합기기 선정시스템
EP1403519A1 (en) 2002-09-27 2004-03-31 Novo Nordisk A/S Membrane pump with stretchable pump membrane
US20040068224A1 (en) 2002-10-02 2004-04-08 Couvillon Lucien Alfred Electroactive polymer actuated medication infusion pumps
AU2003284055A1 (en) 2002-10-09 2004-05-04 The Board Of Trustees Of The University Of Illinois Microfluidic systems and components
US6932458B2 (en) 2002-11-25 2005-08-23 Ricoh Printing Systems America, Inc. Obtaining high frequency performance by controlling chamber pressure
US6932584B2 (en) 2002-12-26 2005-08-23 Medtronic Minimed, Inc. Infusion device and driving mechanism and process for same with actuator for multiple infusion uses
US20040143221A1 (en) * 2002-12-27 2004-07-22 Shadduck John H. Biomedical implant for sustained agent release
US20040188648A1 (en) 2003-01-15 2004-09-30 California Institute Of Technology Integrated surface-machined micro flow controller method and apparatus
WO2004066871A2 (en) 2003-01-24 2004-08-12 Doheny Retina Institute Reservoirs with subretinal cannula for subretinal drug delivery
IL154243A0 (en) 2003-02-02 2003-09-17 Silex Projectors Ltd Stable infusion device
WO2004073551A2 (en) 2003-02-18 2004-09-02 Massachusetts Eye And Ear Infirmary Transscleral drug delivery device and related methods
US7627817B2 (en) 2003-02-21 2009-12-01 Motionpoint Corporation Analyzing web site for translation
JP2006519070A (ja) 2003-02-27 2006-08-24 バクスター・インターナショナル・インコーポレイテッド 注射器のためのピストンアセンブリ
US20040199130A1 (en) * 2003-04-03 2004-10-07 Chornenky Victor I. Apparatus and method for treatment of macular degeneration
ATE357939T1 (de) 2003-07-08 2007-04-15 Novo Nordisk As Tragbares medikamentenabgabegerät mit einer eingekapselten nadel
US7367968B2 (en) 2003-09-05 2008-05-06 Codman & Shurtleff, Inc. Implantable pump with adjustable flow rate
US7361155B2 (en) * 2003-09-16 2008-04-22 Therafuse, Inc. Compensating liquid delivery system and method
US7470266B2 (en) 2003-09-16 2008-12-30 I-Flow Corporation Fluid medication delivery device
US20050076242A1 (en) 2003-10-01 2005-04-07 Rolf Breuer Wireless access management and control for personal computing devices
NZ546265A (en) 2003-10-02 2010-03-26 Ams Res Corp Fluid reservoirs for penile implant devices that prevent blocking of the fluid reservoir outlet during use
WO2005046769A2 (en) 2003-11-12 2005-05-26 Vidacare Corporation Reusable intraosseous device and method for accessing bone marrow in the sternum
WO2005069969A2 (en) 2004-01-21 2005-08-04 University Of Utah Research Foundation Mutant sodium channel nav1.7 and methods related thereto
US20050187515A1 (en) * 2004-02-19 2005-08-25 Advanced Neuromodulation Systems, Inc. Reduced size programmable drug pump
US7503903B2 (en) * 2004-02-20 2009-03-17 Fluidnet Corporation Automated fluid flow control system
US20080102119A1 (en) 2006-11-01 2008-05-01 Medtronic, Inc. Osmotic pump apparatus and associated methods
US7276050B2 (en) * 2004-03-02 2007-10-02 Alan Franklin Trans-scleral drug delivery method and apparatus
US8313308B2 (en) 2004-03-26 2012-11-20 Hospira, Inc. Medical infusion pump with closed loop stroke feedback system and method
US20060009727A1 (en) 2004-04-08 2006-01-12 Chf Solutions Inc. Method and apparatus for an extracorporeal control of blood glucose
US20060079839A1 (en) 2004-06-29 2006-04-13 Becton, Dickinson And Company Single-use syringe
KR100696472B1 (ko) 2004-07-15 2007-03-19 삼성에스디아이 주식회사 증착 마스크, 이를 이용한 유기 전계 발광 소자의 제조방법
AU2005269599A1 (en) 2004-07-26 2006-02-09 Clarity Corporation Implantable device having reservoir with controlled release of medication and method of manufacturing the same
DE102004036358B4 (de) 2004-07-27 2016-11-03 Giesecke & Devrient Gmbh Dosiervorrichtung
US7537590B2 (en) 2004-07-30 2009-05-26 Microchips, Inc. Multi-reservoir device for transdermal drug delivery and sensing
EP1791643B1 (en) 2004-09-01 2009-03-11 Microchips, Inc. Multi-cap reservoir devices for controlled release or exposure of reservoir contents
WO2006024929A2 (en) 2004-09-03 2006-03-09 Atul Kumar An electromagnetically controlled tissue cavity distending system
US8187441B2 (en) 2004-10-19 2012-05-29 Evans Christine E Electrochemical pump
US7637897B2 (en) 2004-10-25 2009-12-29 Codman Neuro Sciences Sarl Implantable pump with integrated refill detection
US20080009801A1 (en) 2004-12-02 2008-01-10 Nickel Janice H Method for dispensing material into a drug delivery device
US7837644B2 (en) 2004-12-03 2010-11-23 Innfocus, Llc Glaucoma implant device
US9259175B2 (en) 2006-10-23 2016-02-16 Abbott Diabetes Care, Inc. Flexible patch for fluid delivery and monitoring body analytes
DE102005000799A1 (de) 2005-01-05 2006-07-13 Roche Diagnostics Gmbh Fluidische Struktur und Verfahren zum Erzeugen einer fluidischen Struktur
WO2006075016A1 (en) 2005-01-17 2006-07-20 Novo Nordisk A/S Fluide delivery device with integrated monitoring of physiological characteristics
US20090306633A1 (en) 2005-01-18 2009-12-10 Koninklijke Philips Electronics, N.V. Electronically controlled capsule
WO2006077529A2 (en) 2005-01-18 2006-07-27 Koninklijke Philips Electronics, N.V. System for controlling traversal of an ingested capsule
EP1688085A1 (en) 2005-02-02 2006-08-09 Disetronic Licensing AG Ambulatory medical device and method of communication between medical devices
WO2006087655A1 (en) 2005-02-21 2006-08-24 Koninklijke Philips Electronics N.V. Micro-fluidic systems based on actuator elements
US7699833B2 (en) 2005-05-06 2010-04-20 Moberg Sheldon B Pump assembly and method for infusion device
US20080097291A1 (en) 2006-08-23 2008-04-24 Hanson Ian B Infusion pumps and methods and delivery devices and methods with same
US7637892B2 (en) * 2005-05-10 2009-12-29 Palyon Medical (Bvi) Limited Variable flow infusion pump system
US8114055B2 (en) * 2005-05-10 2012-02-14 Palyon Medical (Bvi) Limited Implantable pump with infinitely variable resistor
US20060258994A1 (en) * 2005-05-12 2006-11-16 Avery Robert L Implantable delivery device for administering pharmacological agents to an internal portion of a body
CA2607918A1 (en) 2005-05-18 2006-11-23 Kolo Technologies, Inc. Micro-electro-mechanical transducers
WO2006127905A2 (en) 2005-05-24 2006-11-30 Chrono Therapeutics, Inc. Portable drug delivery device
US20070021735A1 (en) * 2005-07-15 2007-01-25 Sai Bhavaraju Dual membrane electro-osmotic fluid delivery device
WO2007014040A1 (en) 2005-07-22 2007-02-01 Medtronic, Inc. Miniature pump for drug delivery
US20090227855A1 (en) 2005-08-16 2009-09-10 Medtronic Minimed, Inc. Controller device for an infusion pump
US20070060870A1 (en) 2005-08-16 2007-03-15 Tolle Mike Charles V Controller device for an infusion pump
CA2622573A1 (en) 2005-09-16 2007-03-29 (Osi) Eyetech, Inc. Ophthalmic syringe
WO2007035654A2 (en) 2005-09-19 2007-03-29 Lifescan, Inc. Systems and methods for detecting a partition position in an infusion pump
WO2007035666A2 (en) 2005-09-19 2007-03-29 Lifescan, Inc. Electrokinetic infusion pump system
US8168584B2 (en) 2005-10-08 2012-05-01 Potentia Pharmaceuticals, Inc. Methods of treating age-related macular degeneration by compstatin and analogs thereof
US7416084B2 (en) 2005-10-13 2008-08-26 Wst International (Holdings) Limited Apparatus for piercing garbage bags and collecting nonrigid, elongate objects and powder
US7935104B2 (en) 2005-11-07 2011-05-03 Medingo, Ltd. Systems and methods for sustained medical infusion and devices related thereto
EP1960018A1 (en) 2005-12-08 2008-08-27 Novo Nordisk A/S Medical system comprising a sensor device
US7763034B2 (en) 2006-01-24 2010-07-27 Medtronic, Inc. Transobturator lead implantation for pelvic floor stimulation
EP1993633B1 (en) * 2006-02-09 2016-11-09 Deka Products Limited Partnership Pumping fluid delivery systems and methods using force application assembly
ES2493921T3 (es) 2006-03-14 2014-09-12 University Of Southern California Dispositivo MEMS para la administración de agentes terapéuticos
MX2008012103A (es) 2006-03-24 2008-12-17 Univ Utah Res Found Medicion del espesor de peliculas dielectricas en superficies.
WO2007114912A2 (en) 2006-03-30 2007-10-11 Wayne State University Check valve diaphragm micropump
CN103393483B (zh) 2006-03-31 2016-08-24 玛提治疗有限公司 用于鼻泪系统的药物释放方法、结构及组合物
US8323267B2 (en) * 2006-04-27 2012-12-04 Medtronic, Inc. Infusion device with active and passive check valves
JP2009535083A (ja) 2006-04-28 2009-10-01 コーニンクレッカ フィリップス エレクトロニクス エヌ ヴィ 少なくとも1つの気体放出材料を有するマイクロポンプ
US8100871B2 (en) 2006-04-28 2012-01-24 Medtronic, Inc. Implantable therapeutic substance delivery system with catheter access port control and method of use
US8491547B2 (en) * 2006-04-28 2013-07-23 Medtronic, Inc. Septum monitoring system and method for an implantable therapeutic substance delivery device
US20070255125A1 (en) 2006-04-28 2007-11-01 Moberg Sheldon B Monitor devices for networked fluid infusion systems
EP2029195A2 (en) 2006-05-30 2009-03-04 Yossi Gross Implantable pump for drug delivery to treat erectile dysfunction
WO2008008845A2 (en) 2006-07-11 2008-01-17 Microchips, Inc. Multi-reservoir pump device for dialysis, biosensing, or delivery of substances
JP4374584B2 (ja) 2006-07-28 2009-12-02 Smc株式会社 位置検出センサ
US20080039768A1 (en) 2006-08-10 2008-02-14 Medtronic, Inc. Implantable devices with photocatalytic surfaces for treating hydrocephalus
US8905999B2 (en) 2006-09-01 2014-12-09 Cardiac Pacemakers, Inc. Method and apparatus for endolymphatic drug delivery
CN101547719A (zh) 2006-09-29 2009-09-30 皇家飞利浦电子股份有限公司 多喷嘴经过皮的药物传送系统
CN101534711B (zh) 2006-10-31 2012-11-14 皇家飞利浦电子股份有限公司 用于在胃肠道中释放药物的可吞吃的多喷嘴给药设备的设计
CA2668184A1 (en) 2006-10-31 2008-05-08 Chrono Therapeutics, Inc. Transdermal delivery techniques for drugs, nutraceuticals and other active substances
US20100101670A1 (en) 2006-11-03 2010-04-29 Mcgill University Electrical microvalve and method of manufacturing thereof
UY30883A1 (es) 2007-01-31 2008-05-31 Alcon Res Tapones punctales y metodos de liberacion de agentes terapeuticos
US20100292557A1 (en) * 2007-03-19 2010-11-18 Benny Pesach Method and device for substance measurement
US8251960B2 (en) 2007-03-24 2012-08-28 The Alfred E. Mann Foundation For Scientific Research Valves, valved fluid transfer devices and ambulatory infusion devices including the same
US8226602B2 (en) 2007-03-30 2012-07-24 Reshape Medical, Inc. Intragastric balloon system and therapeutic processes and products
US20080269714A1 (en) 2007-04-25 2008-10-30 Medtronic Minimed, Inc. Closed loop/semi-closed loop therapy modification system
EP2155289A2 (en) 2007-05-11 2010-02-24 Medingo Ltd. A positive displacement pump
EP2170447B8 (en) 2007-06-13 2017-08-30 Maquet Critical Care AB A safety system for a breathing apparatus for delivering an anesthetic agent
US8932250B2 (en) 2007-06-15 2015-01-13 Animas Corporation Systems and methods to pair a medical device and a remote controller for such medical device
JP2010534530A (ja) * 2007-07-26 2010-11-11 エントラ ファーマシューティカルズ,インコーポレイテッド 薬物を供給するためのシステム及び方法
CN101951975B (zh) 2007-09-17 2013-06-19 萨蒂什·桑达尔 高精度输注泵
ES2788003T3 (es) 2007-10-01 2020-10-20 Hoffmann La Roche Adaptador de cartucho para su uso en un sistema de infusión
EP2204202A1 (en) 2007-10-10 2010-07-07 Olympus Corporation Medicinal solution dispenser
EP2195048B1 (en) 2007-10-11 2018-12-12 Roche Diabetes Care GmbH Carrier for an infusion system
DE102007055636A1 (de) 2007-11-21 2009-05-28 Robert Bosch Gmbh Medikamenten-Dosiervorrichtung zum Verabreichen eines flüssigen Medikaments
US8409133B2 (en) 2007-12-18 2013-04-02 Insuline Medical Ltd. Drug delivery device with sensor for closed-loop operation
MX2010007382A (es) * 2008-01-03 2010-12-20 Univ Southern California Dispositivos implantables para suministro de farmacos, y aparato y metodos para recargar los dispositivos.
US20090205399A1 (en) 2008-02-15 2009-08-20 Bayer Healthcare, Llc Auto-calibrating test sensors
US8425595B2 (en) 2008-03-12 2013-04-23 Visiogen, Inc. Method for inserting an intraocular lens
US7847276B2 (en) 2008-03-14 2010-12-07 Fluidnet Corporation Impulse analysis for flow sensor-based fluid control system
US20090259176A1 (en) 2008-04-09 2009-10-15 Los Gatos Research, Inc. Transdermal patch system
ES2534864T3 (es) * 2008-05-08 2015-04-29 Minipumps, Llc Bombas implantables y cánulas para las mismas
US9333297B2 (en) 2008-05-08 2016-05-10 Minipumps, Llc Drug-delivery pump with intelligent control
US8231609B2 (en) * 2008-05-08 2012-07-31 Minipumps, Llc Drug-delivery pumps and methods of manufacture
WO2009137777A2 (en) * 2008-05-08 2009-11-12 Replenish Pumps, Llc Implantable drug-delivery devices, and apparatus and methods for filling the devices
US20090281528A1 (en) 2008-05-12 2009-11-12 Medtronic, Inc. Osmotic pump apparatus and associated methods
US8579885B2 (en) 2009-02-20 2013-11-12 University Of Southern California MEMS electrochemical bellows actuator
WO2010119409A1 (en) 2009-04-17 2010-10-21 Sensile Pat Ag Medical device for glucose monitoring or regulation
EP2932994B1 (en) 2009-07-30 2017-11-08 Tandem Diabetes Care, Inc. New o-ring seal, and delivery mechanism and portable infusion pump system related thereto
CN102576385B (zh) 2009-08-18 2016-02-24 迷你泵有限责任公司 具有自适应控制的电解药物输送泵
US8317698B2 (en) 2009-08-31 2012-11-27 Hospira, Inc. Method of monitoring an automated point-of-care fluid testing system
WO2011028997A1 (en) 2009-09-04 2011-03-10 Minipumps Llc Adhesive skin patch with pump for subcutaneous drug delivery
CN103108665A (zh) 2010-04-20 2013-05-15 迷你泵有限责任公司 电解驱动药物泵装置
US20130184640A1 (en) 2010-04-20 2013-07-18 Minipumps, Llc Accurate flow control in drug pump devices
WO2012012406A1 (en) 2010-07-19 2012-01-26 Minipumps, Llc Catheter drug pump
US8397577B2 (en) 2011-03-06 2013-03-19 Alexander Henry Slocum, Sr. Rolling diaphragm pressure sensor
US9162023B2 (en) 2011-05-05 2015-10-20 Carefusion 303, Inc. Automated pressure limit setting method and apparatus
US8939930B2 (en) 2011-11-18 2015-01-27 Minipumps, Llc Accurate flow control in drug pump devices
EP2780055A2 (en) 2011-11-18 2014-09-24 Minipumps, LLC Accurate flow control in drug pump devices
US20140088554A1 (en) 2012-09-24 2014-03-27 Po-Ying Li Drug-delivery pump with intelligent control
US20140088508A1 (en) 2012-09-24 2014-03-27 Patrick Ryan Drug-delivery devices with integrated needle-insertion mechanism

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4886514A (en) * 1985-05-02 1989-12-12 Ivac Corporation Electrochemically driven drug dispenser
AU8997891A (en) * 1990-12-31 1992-07-02 S.I. Scientific Innovations Ltd. Liquid delivery device particularly useful for delivering drugs
CN1321096A (zh) * 1999-09-17 2001-11-07 巴克斯特国际公司 具有稳定流体流动的流体分送器
WO2001089607A2 (en) * 2000-05-23 2001-11-29 Elan Pharma International Limited Gas driven drug delivery device
CN101365505A (zh) * 2006-01-06 2009-02-11 诺沃-诺迪斯克有限公司 使用收缩式储存器的药物输送设备
CN101125086A (zh) * 2006-08-18 2008-02-20 刘胜 闭环自动控制胰岛素注射系统
WO2009086112A2 (en) * 2007-12-20 2009-07-09 University Of Southern California Apparatus and methods for delivering therapeutic agents

Also Published As

Publication number Publication date
WO2011022484A1 (en) 2011-02-24
US9199035B2 (en) 2015-12-01
CN102576385A (zh) 2012-07-11
EP2467797B1 (en) 2017-07-19
JP2013502279A (ja) 2013-01-24
KR101697388B1 (ko) 2017-01-17
EP2467797A1 (en) 2012-06-27
US9283322B2 (en) 2016-03-15
US20140074058A1 (en) 2014-03-13
JP5758388B2 (ja) 2015-08-05
AU2010284216B2 (en) 2015-10-15
MX2012002063A (es) 2012-08-01
US20110202032A1 (en) 2011-08-18
KR20120068867A (ko) 2012-06-27
AU2010284216A1 (en) 2012-03-15
CA2771584A1 (en) 2011-02-24

Similar Documents

Publication Publication Date Title
CN102576385B (zh) 具有自适应控制的电解药物输送泵
US9381299B2 (en) Implantable drug delivery devices
US7415384B2 (en) Therapy management techniques for an implantable medical device
Meng et al. MEMS-enabled implantable drug infusion pumps for laboratory animal research, preclinical, and clinical applications
US9764121B2 (en) Drug delivery apparatus
US7505869B2 (en) Non-conformance monitoring and control techniques for an implantable medical device
US7054782B2 (en) Non-conformance monitoring and control techniques for an implantable medical device
US20020087113A1 (en) Drug management techniques for an implantable medical device
US20020087116A1 (en) Patient scheduling techniques for an implantable medical device
US9314572B2 (en) Controlling drug delivery transitions
JP2005507757A (ja) 輸液ポンプ

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C14 Grant of patent or utility model
GR01 Patent grant
CF01 Termination of patent right due to non-payment of annual fee
CF01 Termination of patent right due to non-payment of annual fee

Granted publication date: 20160224

Termination date: 20210818