US20180264190A1 - Air tolerant implantable piston pump - Google Patents

Abstract

An implantable infusion device includes a reservoir for housing an infusion medium and a drive mechanism having an inlet chamber, a piston and a piston channel. The inlet chamber is in fluid communication with the reservoir. The piston channel is in fluid communication with the inlet chamber, and has a distal end and a proximal end, the proximal end being closer to the inlet channel than the distal end. The piston is axially moveable within the piston channel to drive infusion medium out of the distal end of the piston channel. The clearance between the piston and the channel is sufficiently small to prevent undissolved gas in the inlet chamber from passing through the clearance. The inlet chamber may be sufficiently large to allow undissolved gas to accumulate without adversely affecting the performance of the infusion device.

Description

RELATED APPLICATION
• This is a continuation application of U.S. patent application Ser. No. 12/684,436, filed Jan. 8, 2010, now issued as U.S. Pat. No. 9,968,733 on May 15, 2018, which is a Continuation-In-Part application of U.S. application Ser. No. 12/334,985, filed on Dec. 15, 2008, published as US 2009/0118711 on May 7, 2009, which application is incorporated herein by reference in its entirety to the extent that it does not conflict with the disclosure presented herein.
FIELD
• The present disclosure relates generally to implantable infusion devices; in particular to implantable infusion devices employing piston drive mechanisms.
BACKGROUND
• Treatment of diseases and ailments of the body often benefit from short- or long-term infusion of therapeutic compositions. While such therapeutic compositions may be administered extracorporeally, e.g., via transcutaneous injection, many patients benefit from the consistent and repeatable dosage provided by an implantable infusion device. Such devices may employ a reservoir for storing an infusible therapeutic composition and a pumping mechanism coupled to the reservoir for discharging the infusible fluid through an outlet of the device. The discharge outlet is typically connected to flexible medical tubing, e.g., a catheter, leading to a targeted delivery site within the patient. The infusion device may further include electronics to control delivery of the therapeutic composition to the patient in accordance with a prescribed schedule.
• Implantable infusion devices are typically implanted subcutaneously, e.g., in the chest or abdominal cavity. The device reservoir may be accessible via a self-sealing, needle-penetrable septum. Such devices are typically implanted so that the septum is located generally directly beneath the skin. The septum provides a fluid passageway that permits the reservoir to be refilled periodically via a transcutaneous injection. Accordingly, the pump reservoir can be filled or refilled without requiring surgical removal from the patient's body, and further without requiring any other significant surgical procedure.
• During initial filling or refilling of the reservoir, gas bubbles or gas dissolved or entrained in the infusible therapeutic composition may be introduced into the reservoir. Formation or introduction of gas bubbles in the reservoir can potentially lead to problems with the pumping mechanism that can result in inaccurate delivery of the therapeutic composition or pump failure. For many infusion devices, it is recommended to vent or aspirate the reservoir prior to refilling to remove air trapped in the reservoir. In some case, it is also recommended to degas the therapeutic composition prior to introducing the composition into the reservoir. Such processes can be time consuming and may not be fully effective, due in part to faulty technique.
• While air bubbles can cause problems with many pumping mechanisms, with piston pumps air bubbles tend to cause inaccurate delivery of fluid due to the volume occupied by the air. Further many implantable infusion devices employing piston pumps include valves upstream or downstream of the piston. Air in the system may result in inoperability of the system due to inability to generate sufficient pressure to draw or force air through the valves or may require prolonged amounts of time to clear the air prior to resuming fully functional operation.
BRIEF SUMMARY
• The present disclosure describes, among other things, implantable infusion devices employing piston pumps that can tolerate air bubbles. Such devices continue to function despite incomplete aspiration of the reservoir or degassing, if such procedures are warranted.
• In various embodiments, an implantable infusion device includes a reservoir for housing an infusion medium and a drive mechanism having an inlet chamber, a piston and a piston channel. The inlet chamber is in fluid communication with the reservoir. The piston channel is in fluid communication with the inlet chamber, and has a distal end and a proximal end, the proximal end being closer to the inlet chamber than the distal end. The piston is axially moveable within the piston channel to drive infusion medium out of the distal end of the piston channel. The clearance between the piston and the channel is sufficiently small to prevent undissolved gas in the inlet chamber from passing through the clearance. For example, the clearance between the piston and the channel may be sufficiently small such that the infusion medium is retained in the clearance between the piston and the channel via capillary action and surface tension effects prevent the passage of undissolved gas through the clearance. The device may be configured to provide any suitably small clearance, such as a clearance between about 3 micrometers and about 10 micrometers.
• The reservoir may be a positive pressure reservoir or a negative pressure reservoir, relative to ambient atmospheric pressure. For example, the reservoir, in some embodiments may be maintained at a pressure of, for example, greater than 5 psia, greater than 10 psia or between about 15 psia and 16 psia. Use of negative pressure reservoirs (e.g., abut 14 psia or less) presents special concerns, as the ability of a gas to dissolve in a solution, such as a fluid therapeutic composition, decreases as pressure decreases; thereby increasing the likelihood of air bubble formation within the reservoir and pumping mechanism. In such situations, it may be important to properly degas the therapeutic composition prior to delivering the composition to the reservoir. The ability to tolerate incomplete degassing would be desirable, as degassing procedures are time consuming and often suffer from improper technique.
• Positive pressure reservoirs can also present special concerns. For example, proper functioning of a valves downstream of the piston channel are important in infusion devices employing positive pressure reservoirs. If the valve fails or is of too low of a cracking pressure, therapeutic fluid may be inadvertently pushed through the device and into the patient. However, due to concerns with air bubbles, the cracking pressure of such valves has been kept low to ensure that the drive mechanism can generate sufficient pressure to move the air bubble past the valve if such air bubbles are present and to maintain low energy consumption of the drive mechanism.
• In various embodiments, regardless of whether the reservoir is a positive pressure or a negative pressure reservoir, the infusion devices described herein include a valve downstream, of the piston channel. The valve may have a cracking pressure that is between about 5 psi less than the reservoir pressure and about 5 psi more than the reservoir pressure. For example, the valve cracking pressure may be about the same as the reservoir pressure. If the reservoir pressure is between 15 and 19 psia, the valve cracking pressure may be 20 psia or greater to ensure that inadvertent or undesired administration of infusion medium is avoided. Similarly, infusion devices having negative pressure reservoirs (e.g. 14 psia or less) may also include a valve downstream of the piston channel to prevent undesired or inadvertent administration of a therapeutic fluid when subjected to lower atmospheric pressures, such as experienced at high elevations or on an airplane. With prior devices employing piston drive mechanisms, valves with high cracking pressures would not have been employed due to fear that if air were to pass through the channel, the drive mechanism could not compress the air sufficiently to overcome the cracking pressure, causing the pump to effectively fail. However, with devices as described herein where undissolved air cannot pass through the channel, the piston drive mechanism can readily infuse a fluid medium through the channel to overcome the cracking pressure, open the valve, and force fluid out of the device. Accordingly, the devices described herein can employ safety valves that might not have been possible or practicable with prior infusion devices employing piston drive mechanisms.
• The infusion device may also include a filter disposed between the inlet chamber and the reservoir, wherein the filter is configured to prevent microorganisms from entering the inlet chamber from the reservoir. Such a filter will generally and beneficially prevent undissolved gas from passing from the reservoir into the inlet chamber. However, gas dissolved in the infusion medium may pass through the hydrophilic filter, and over time, some of the dissolved or entrained gas will be freed or come out of solution and will form air bubbles in the inlet chamber. Such bubbles cannot pass through the filter into the reservoir and cannot be removed by aspiration when the reservoir is replenished with infusion medium. Accordingly, over time an increased volume of the inlet chamber may be occupied with air bubbles. For at least this reason, prior devices employing piston drive mechanism-avoided placement of a filter between the reservoir and the inlet chamber. Yet, it has been found, as described herein, that when the piston to channel clearance is sufficiently small to prevent undissolved free gas bubbles from passing through the clearance, 70% or more of the inlet chamber volume can be occupied by undissolved gas. Accordingly, infusion devices as described herein can include the beneficial effects of preventing contaminated infusion medium from reaching the inlet chamber and thus being delivered to the patient.
• One or more embodiments of the infusion devices described herein may provide one or more advantages relative to previously manufactured or described devices. For example and in addition to the advantages of including a microbial filter and a valve as described above, the devices described herein can tolerate a good deal of error associated with degassing and aspiration associated with a refill procedure, which can often be a source of concern for implantable devices employing a piston drive mechanism. These and other aspects and advantages will be apparent to one of skill in the art from the accompanying detailed description and drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
• Referring now to the drawings in which like reference numbers represent corresponding parts throughout:
• FIG. 1 is a block diagram illustrating some components of a representative infusion device.
• FIG. 2 is a block diagram illustrating some components of a representative drive mechanism.
• FIGS. 3A-B are schematic diagrams of cross sections illustrating some representative components of a drive mechanism.
• FIG. 4A is a schematic representative of selected components of an infusion device.
• FIG. 4B is a schematic close-up view of the area withincircle4B ofFIG. 4A.
• FIG. 5 is a schematic representative of selected components of an infusion device.
• FIG. 6A is a schematic representative of selected components of an infusion device.
• FIG. 6B is a schematic close-up view of the area withincircle6B ofFIG. 6A.
• The drawings are not necessarily to scale. Like numbers used in the figures refer to like components, steps and the like. However, it will be understood that the use of a number to refer to a component in a given figure is not intended to limit the component in another figure labeled with the same number. In addition, the use of different numbers to refer to components is not intended to indicate that the different numbered components cannot be the same or similar.
DETAILED DESCRIPTION
• In the following detailed description, reference is made to the accompanying drawings that form a part hereof, and in which are shown by way of illustration several specific embodiments of devices, systems and methods. It is to be understood that other embodiments are contemplated and may be made without departing from the scope of spirit of the present invention. The following detailed description, therefore, is not to be taken in a limiting sense.
• All scientific and technical terms used herein have meanings commonly used in the art unless otherwise specified. The definitions provided herein are to facilitate understanding of certain terms used frequently herein and are not meant to limit the scope of the present disclosure.
• As used in this specification and the appended claims, the singular forms “a”, “an”, and “the” encompass embodiments having plural referents, unless the content clearly dictates otherwise. As used in this specification and the appended claims, the term “or” is generally employed in its sense including “and/or” unless the content clearly dictates otherwise.
• As used herein, undissolved gas means gas not dissolved or entrained in an infusion medium. It will be understood that gas may transition from being dissolved or entrained in an infusion medium to being in a free undissolved state. When in a free and undissolved state and surrounded by infusion medium, the gas will tend to form bubbles. Gas and air are generally used herein interchangeably.
• As used herein, “about” means +/−10% of the enumerated numerical value that it precedes. For example, “about” may mean +/−5%, or +/−3% of the enumerated numerical value that it precedes.
• The present disclosure describes, among other things, implantable infusion devices employing piston pumps that can tolerate air bubbles. It has been found that piston pumps having a piston to bore clearance sufficiently small to prevent undissolved gas (i.e., gas not dissolved in infusion medium) from passing through a radial clearance channel formed between the piston and the bore. For example, it has been found that if the clearance is sufficiently small such that infusion medium flows through the clearance channel via capillary action, undissolved gas bubbles do not pass through the clearance channel. Further, it has been shown that placement of an antimicrobial filter, such as a 0.22 micron filter, between a reservoir and an inlet chamber for the piston drive mechanism can be tolerated. Previously, infusion devices employing piston pumps would not include such filters due to fear that they might trap air bubbles within the piston inlet chamber causing pump inaccuracy or malfunction. In addition, such a filter generally prevents removal of the air bubbles from of the inlet chamber via aspiration during refilling of the reservoir. However, as described herein, it has been discovered that a large amount of undissolved gas can be tolerated within the pump inlet chamber (e.g., 70% or more of the volume of the chamber) without any significant adverse consequences.
• Prior to describing details regarding piston pump infusion devices configured to tolerate air bubbles, a general discussion of representative infusion devices and drive mechanisms is provided with regard toFIGS. 1, 2, 3A and 3B. Additional details regarding configurations for tolerating air bubbles are provided in the discussion related toFIGS. 4A, 4B, 5, 6A and 6B.
• Referring toFIG. 1, a block diagram of some components of arepresentative infusion device10 is shown. The device includes ahousing12. Housing may be made of any suitable material, such as a rigid polymeric material or metallic material, such as titanium. Ifdevice10 is configured to be implanted in a patient, thehousing12 is preferably hermetically sealed. In the depicteddevice10, a fluid flow path includes aninlet18, areservoir13, afilter4, adrive mechanism20, and anoutlet16. The flow path may also include a one-way valve17 disposed between thedrive mechanism20 and theoutlet16, as depicted. Theinlet18 is fluidly coupled withreservoir13, in which infusion medium may be stored. Theinlet18 may include a port through thehousing12 to allow access to thereservoir18 or fluid path upstream of the reservoir. A septum may be disposed over the port to seal theinlet18. Thereservoir13 is fluidly coupled to thedrive mechanism20, which may draw infusion medium from thereservoir13. Thefilter4 is configured to prevent microorganisms that may be in the infusion medium stored in thereservoir13 from passing into thedrive mechanism20. Thedrive mechanism20 is fluidly coupled to theoutlet16 and forces fluid drawn from thereservoir12 out of thedevice12 via theoutlet16. The outlet may include a port to which a catheter may be operably coupled. Theinfusion device10 may include other components that are not shown inFIG. 1. For example, a one-way valve may be disposed between theinlet18 and thereservoir13 or between thereservoir13 and thedrive mechanism20.
• Representative examples ofreservoirs13 which may be employed in embodiments of infusion devices are described in U.S. Published Patent Application 2003/0050623, published Mar. 13, 2003, and entitled “Infusion Device and Reservoir for Same,” which is incorporated herein by reference in its entirety to the extent that it does not conflict with the present disclosure. However, further embodiments may employ other suitable reservoir configurations, including, but not limited to, those described in U.S. Pat. No. 5,514,103 and U.S. Pat. No. 5,176,644, each to Srisathapat et al, U.S. Pat. No. 5,167,633 to Mann et al., U.S. Pat. No. 4,697,622 to Swift and U.S. Pat. No. 4,573,994 to Fischell et al.
• In various embodiments, thereservoir13 is a positive pressure reservoir, which means the pressure in the reservoir is greater than atmospheric pressure, forcing out the fluid contents of thereservoir13 into thedrive mechanism20. A propulsion mechanism (not shown) may be operably coupled to thereservoir13 to drive fluid out of the reservoir. Any suitable propulsion mechanism may be employed. By way of example, thereservoir13 may be a bellows reservoir and the propulsion mechanism may contain a propellant chamber that contains a fluid whose vapor pressure is such that, under conditions of normal body temperature, pressure is exerted on the bellows to force liquid in thereservoir13 to enter thedrive mechanism20. Examples of such propulsion mechanisms are found in Medtronic Inc.'s SYNCHROMED and ISOMED implantable infusion devices. A mechanical spring may be readily substituted for the liquid propellant. Alternatively, thereservoir13 may be formed, at least in part, of an elastomeric or resilient material biased in an empty configuration that expands when filled and forces fluid to exitreservoir13 and enter thedrive mechanism20. Thus, the propulsion mechanism and reservoir may, in some embodiments, be the same component. Apositive pressure reservoir13 may be maintained at any suitable positive pressure by the propulsion mechanism or the elastic or resilient properties of thereservoir13. Typically, ambient atmospheric pressure about 14.2 psia. In some embodiments, thepositive pressure reservoir13 is maintained at a pressure of greater than or equal to 15 psia, between 15 psia and 19 psia, between about 15 and about 16 psia, or between about 15.2 psia and about 15.5 psia.
• In some embodiments, thereservoir13 is a negative pressure reservoir, which means the pressure in the reservoir is greater than atmospheric pressure. For example, thereservoir13 may be maintained at a pressure of less than or equal to 14 psia, less than or equal to 10 psia, or between 12 and 14 psia. In general, whether positive or negative pressure, thereservoir13 may be maintained at a pressure of greater than 0 psia, greater than 5 psia, or greater than 10 psia, or greater than 15 psia.
• Examples ofinlet structures18 that may be employed in embodiments ofinfusions devices10 described herein are described in U.S. Pat. No. 7,186,236 to Gibson et al., entitled “Infusion Device And Inlet For Same;” U.S. Pat. No. 5,514,103 and U.S. Pat. No. 5,176,644, each to Srisathapat et al; U.S. Pat. No. 5,167,633 to Mann et al.; U.S. Pat. No. 4,697,622 to Swift; and U.S. Pat. No. 4,573,994 to Fischell et al.
• Still referring toFIG. 1, theinfusion device10 includeselectronics19 and apower source5 disposed in thehousing12. Theelectronics19 are operably coupled to thepower source18 and are configured to control thedrive mechanism20. Thepower source18 may include a battery, such as a rechargeable battery.Electronics18 may include a processor for controlling thedrive mechanism20; memory for storing instructions, recording diagnostics, or the like; a telemetry module for wireless communication; a diagnostics module; or the like. Such modules and electronic components are well known to those of skill in the art and may be readily included and employed as desired.
• Referring now toFIGS. 2-3, representative components ofpiston drive mechanisms20 are shown. In the block diagram ofFIG. 2, thedrive mechanism20 includes aninlet27, anoutlet28, andpiston actuation mechanism21. Thepiston actuation mechanism21 is disposed in the flow path between theinlet27 and theoutlet28. Some representative components of apiston drive mechanism20 are shown in the schematic cross sectional views depicted inFIGS. 3A-B.
• Thedrive mechanism20 depicted inFIGS. 3A-B, includes andinlet27, anoutlet28, astationary portion320 forming achannel35, and an actuator having apiston44 and anarmature42. InFIG. 3A, thepiston44 is in the retracted position. InFIG. 3B, thepiston44 is in the forward position. In various embodiments, thestationary portion320 forming thechannel35 is integrally formed with a housing of the drive mechanism. Thechannel35 has aproximal end351, nearer theinlet27, and adistal end352, nearer theoutlet28. Thepiston44 is positioned in, and axially movable within, thechannel35 to drive infusion medium out of thedistal end352 of thechannel35. Aclearance410 is formed between thepiston44 and thechannel35. Preferably, theclearance410 is sufficiently small such that fluidic resistance between thepiston44 and thechannel35 causes a volume of infusion medium delivered during the forward portion of the pumping stroke to be greater than a volume of the infusion medium backflowing through thechannel35 during the retracting portion of the pumping stroke. As described in more detail below (e.g. with regard toFIGS. 5-6), theradial clearance410 is sufficiently small to prevent sufficiently small to prevent undissolved gas in theinlet chamber330 from passing through the radial clearance channel. The intended fluid flow path is indicated by arrows inFIGS. 3A-B. Thearmature42 is operably coupled to thepiston44. In various embodiments,piston44 is integrally formed witharmature42. Thearmature42 andpiston44 together form an actuator.
• As thepiston44 retracts (e.g., moves from the position shown inFIG. 3B to the position shown inFIG. 3A), infusion medium is drawn throughinlet27 to thepiston channel35. As thepiston35 is advanced, infusion medium is forced out of thechannel35 and out of theoutlet28. Electromagnetic energy causes thearmature42 to advance thepiston44 in thechannel35. A coil or solenoid may be disposed in thestationary member320 forming thechannel35 to provide such electromagnetic energy. A mechanical biasing member (not shown), such as a spring, or electromagnetic force may allow thepiston44 to retract.
• Thedrive mechanism20 or components thereof, such as thearmature42, may be formed or configured in any suitable manner. In various embodiments, the drive mechanism or components thereof are drive mechanisms or components described in U.S. Patent Application Publication No. 2007/0168008, entitled “Implantable Therapeutic Substance Delivery Device Having a Piston Pump with and Anti-Cavitation Valve”; U.S. Patent Application Publication No. 2006/0206099, entitled “Low Profile Inlet Valve for a Piston Pump Therapeutic Substance Delivery Device”; U.S. Pat. No. 6,997,921, entitled “Infusion device and driving mechanism for same”, or described in US Patent Application Publication No. 2009/0118711, published on May 7, 2009, entitled “Reduced-noise implantable infusion device”, which patents and application are hereby incorporated herein by reference in their respective entireties to the extent that they do not conflict with the present disclosure.
• Pistons and armatures as described herein may be made of any suitable material. For example, pistons or armatures may be formed from generally rigid, biocompatible and infusion medium compatible material, having a relatively high magnetic permeability such as, but not limited to, ferrous materials, ferritic stainless steel with high corrosion resistance, or the like. Pistons or armatures can also be fabricated with non-compatible materials and encased or plated in compatible materials. Pistons, armatures, or actuators may be molded, machined, or otherwise formed.
• Referring now toFIG. 4A, a schematic drawing of some components of a representative implantable infusion device are shown. The implantable infusion device includes an actuator having apiston44 for pumping fluid from theinlet chamber320 through achannel35. Aradial clearance410 between the piston and channel is sufficiently small to prevent undissolved gas from passing from theinlet chamber320 into thechannel35. Referring toFIG. 4B, which represents the area within the circle labeled4B inFIG. 4A, the average distance d from a point on the exterior of thepiston44 to a closest point on the wall of thechannel35 in theclearance410 is, in many embodiments, sufficiently small such that infusion media flows through theclearance410 while undissolved air is prevented from passing through the clearance due to surface tension effects. Thesmall clearance410 provides fluidic resistance to prevent backflow and capillary retention of liquid to prevent passage of undissolved gas. While not intending to be bound by theory, it is believed that the liquid wets the surfaces of theclearance410 and surface tension of the liquid prevents undissolved air from entering thechannel410. In some embodiments, the distance d between thepiston44 and thechannel35 is between 3 micrometers and 10 micrometers, such as about 6 micrometers. By having a sufficientlysmall clearance410, where undissolved air or gas cannot escape between thepiston44 and thechannel35, by-pass valves may be eliminated which have been previously proposed for dealing with potential transmission of air. Such by-pass valves may be complex and may only be partially effective in eliminating problems associated with passing air through the channel, such as inaccurate fluid delivery and pump malfunction.
• Still with reference toFIG. 4A, the device may include avalve17 in communication with and downstream of thechannel35. In various embodiments, thevalve17 has a cracking pressure that is within about +/−5 psi of the pressure of thereservoir13. In some embodiments, thevalve17 has a cracking pressure that is greater than the pressure of thereservoir13; e.g. 1, 2, 3, or 5 psi or more than the pressure of reservoir. Higher valve cracking pressures (whether within +/−5 psi or greater than the reservoir pressure) may result in improved overall safety of the infusion device by preventing inadvertent or undesired leakage of infusion medium from the device. For example, if thereservoir13 is a positive pressure reservoir and thepiston44 is in the retracted position relative to thechannel35, the positive pressure of thereservoir13 may force infusion medium through thechannel35 and out of the device outlet in the absence of thevalve17. With prior devices employing piston drive mechanisms, valves with such a high relative cracking pressure would not have been employed due to fear that if air were to pass through the channel, the drive mechanism could not pump enough fluid to compress the air and overcome the cracking pressure, causing the pump to effectively fail. However, with devices as described herein where undissolved air cannot pass through thechannel35, the piston drive mechanism can readily infuse a fluid medium through the channel to overcome the cracking pressure, open thevalve17, and force fluid out of the device. In various embodiments, thereservoir13 is a positive pressure reservoir maintained at between about 15 and 16 psia and thevalve17 has a cracking pressure of greater than 15 psi.
• In various embodiments, thevalve17 has a cracking pressure that is 2 psi or greater than thereservoir13 pressure minus the outlet pressure (ambient atmospheric pressure), when the difference is a positive number (i.e., the reservoir pressure is greater than ambient atmospheric pressure). As a patient with an implanted infusion device changes altitude, the pressure differential across thevalve17 changes. While the reservoir pressure remains fairly constant, the ambient pressure changes with altitude. If the valve cracking pressure is not sufficiently high to account for changes in altitude over a workable range, fluid from the reservoir may undesirably leak out of the device. For example, if the reservoir pressure is 15 psia and the ambient pressure is 10 psia, the pressure differential across the valve would be 5 psia. Accordingly, therapeutic fluid from the reservoir would leak across a valve having a cracking pressure of 5 psi or less in such a situation. To prevent such undesirable leakage, thevalve17 may have, in various embodiments, a cracking pressure that is 2 psi or greater than thereservoir13 pressure minus the outlet pressure over the range of use of the device. In some embodiments, thevalve17 has a cracking pressure that is 3 psi or greater or 5 psi or greater than thereservoir13 pressure minus the outlet pressure (ambient pressure) to further prevent undesired leakage.
• A table of atmospheric pressures at different altitudes is presented below:

• 	Altitude (relative to sea level)	Pressure (psia)

  	−1,500 feet	15.5
  	0 feet	14.7
  	8,000 feet*	10.9
  	10,000 feet	10.1
  	15,000 feet	8.3
  	*Most airplanes in flight are pressurized to the equivalent of 8,000 feet

• Thus, if a device is designed to safely operate at altitudes of 15,000 feet, the valve cracking pressure should be equal to or greater than: [2+(reservoir pressure)−8.3 psia], which equals: (reservoir pressure−6.3 psia), if the reservoir pressure is greater than 8.3 psia. In many situations, avalve17 having a cracking pressure of +/−5 psi of thereservoir13 pressure will have a cracking pressure that is 2 psi or greater than thereservoir13 pressure minus the outlet pressure over the range of use of the device.
• In embodiments, when the piston motion is stopped at the end of the forward stroke, the valve-facing end of thepiston44 is in close proximity to thevalve17, for example, spaced from the valve member by no more than about ten percent (10%) of the piston diameter.
• Still referring toFIG. 4A, the device also includes areservoir13 in fluid communication with aninlet chamber320 of a drive mechanism. Afilter4 is disposed in the flow path between thereservoir13 and theinlet chamber320. Thefilter4 is configured to prevent microorganisms that may be present in thereservoir13 from entering theinlet chamber320. Anysuitable filter4 may be employed. For example, a 0.22 micron filter is suitable for preventing microbes from passing fromreservoir13 intoinfusion chamber320. It may be desirable for thefilter4 to be hydrophilic to allow infusion medium to readily cross from thereservoir13 into theinfusion chamber320 through thefilter4. Examples of hydrophilic materials that may be used to form suitable filters include nylon and polyvinylidene fluoride. Ahydrophilic filter4 will generally and beneficially prevent undissolved gas from passing from thereservoir13 into theinlet chamber320. However, gas dissolved in the infusion medium may pass through thehydrophilic filter4. Over time, some of the dissolved or entrained gas will be freed or come out of solution and will form air bubbles in theinlet chamber320. Such bubbles cannot pass through thefilter4 into thereservoir13 and cannot be removed by aspiration when thereservoir13 is replenished with infusion medium. Accordingly, over time an increased volume of theinlet chamber320 may be occupied with air bubbles.
• Accordingly, it may be desirable for the volume of theinlet chamber320 to be sufficiently large to accommodate a significant volume of undissolved gas that may accumulate over the service life of the infusion device. It has been found that when the clearance distance d between thepiston44 and thechannel35 is sufficiently small to prevent undissolved air from passing through theclearance410, 70% or more of the volume of theinlet chamber320 can be occupied with undissolved gas and the pump continues to deliver accurate amounts of infusion medium. While not relevant to infusion accuracy, high volumes of undissolved gas in theinlet chamber320 can result in increased noise resulting from contact of thearmature42 with the stationary portion of the drive mechanism surrounding the proximal end of thechannel35. Armature designs configured to reduce noise, such as those described in US 2009/118711 (published on May 7, 2009, entitled REDUCED-NOISE IMPLANTABLE INFUSION DEVICE, which application is hereby incorporated herein by reference to the extent that it does not conflict with the present disclosure), may be employed. It should be noted that, while alarge inlet chamber320 volume may be desirable from the standpoint of providing for increased volumes of undissolved gas over the service life of the infusion device (e.g., longer service life would tend to result in larger volume), alarge inlet chamber320 volume may be undesirable for keeping the overall volume of the device small and because, in infusion devices employing bellows or collapsible reservoirs, infusion medium cannot be readily removed from thechamber320 when thereservoir13 is refilled due to the presence of thefilter4. Thus, larger chamber volumes may lead to increased volumes of stale infusion medium that can reside in thechamber320. Accordingly, the size of theinlet chamber320 should be balanced between the desire to maximize the volume of undissolved gas that the chamber can accommodate, the desire to reduce overall size of the device, and the desire to minimize the volume of stale drug that may remain in the chamber. In various embodiments, theinlet chamber320 has a volume of between about 100 microliters and about 300 microliters. Such a volume may be desirable in an infusion device having a reservoir volume of between about 20 milliliters to about 50 milliliters and a service life of about 8 to 10 years. For infusion devices having larger or smaller reservoir volumes or service lives, it may be desirable for the inlet chamber volume to be larger or smaller in light of the considerations discussed above.
• Some of the concepts described above with regard toFIG. 4A are further discussed below with regard toFIGS. 5-6, in which selected portions or components of the device shown inFIG. 4A are shown. InFIGS. 5-6, a portion of the device including thefilter4, theinlet chamber320, thepiston44 and thechannel35 is shown.Infusion medium500 and anair bubble600 are shown in thechamber320. InFIG. 5, thepiston44 is in the retracted position and inFIG. 6A, thepiston44 is approaching the forward position. As the armature andpiston44 approach the forward position, theair bubble600 is moved slightly away from thechannel35 and is displaced with infusion medium (see, e.g.,FIG. 6B, which a close-up view of the area identified bycircle6B inFIG. 6A), allowing the infusion medium to enter thechannel35 while preventing theair bubble600 or a portion thereof from entering thechannel35 due to the small clearance between thepiston44 and thechannel35. The liquid will wet theinlet chamber320 and move freely around the gas bubbles or gas pocket. The undissolved gas will not enter the clearance due to wetting effects of the walls of theclearance channel35 and surface tension of the liquid retained in the clearance via capillary action. As discussed above, theair bubble600 or undissolved gas may occupy 70% or more of the volume of theinlet chamber320 without adverse consequences of inaccurate fluid delivery when the clearance between thepiston44 and thechannel35 is sufficiently small to prevent the undissolved gas from entering thechannel35 from theinlet chamber320.
• Thus, embodiments of the AIR TOLERANT IMPLANTABLE PISTON PUMP are disclosed. One skilled in the art will appreciate that the present invention can be practiced with embodiments other than those disclosed. The disclosed embodiments are presented for purposes of illustration and not limitation, and the present invention is limited only by the claims that follow.

Claims (17)

1-23. (canceled)

24. An implantable infusion device, comprising:

a reservoir for housing an infusion medium;

a drive mechanism having an inlet chamber, a piston and a piston channel,

wherein the inlet chamber is in fluid communication with the reservoir,

wherein the piston channel is in fluid communication with the inlet chamber, the piston channel having a distal end and a proximal end, the proximal end being closer to the inlet channel than the distal end,

wherein the piston is axially moveable within the piston channel to drive infusion medium out of the distal end of the piston channel,

wherein the piston is positioned and moveable within the channel such that a clearance between the piston and the piston channel is sufficiently small to prevent undissolved gas in the inlet chamber from passing through the clearance;

a filter disposed between the inlet chamber and the reservoir, wherein the filter is hydrophilic and is configured to prevent microorganisms from entering the inlet chamber from the reservoir, wherein the filter is configured to allow dissolved gas to pass from the reservoir to the inlet chamber such that over time, the dissolved gas comes out of solution as undissolved gas in the inlet chamber, and wherein the filter is configured to prevent the undissolved gas from passing from the inlet chamber to the reservoir;

an outlet in fluid communication with the piston channel, the outlet being closer to the distal end of the piston channel than the proximal end of the piston channel; and

a valve in fluid communication with, and disposed between, the outlet and the piston channel.

25. The implantable infusion device ofclaim 24, wherein the clearance between the piston and the piston channel is sufficiently small such that the infusion medium is retained in the piston channel via capillary action.

26. The implantable infusion device ofclaim 24, wherein the average clearance between the piston and the piston channel is between 3 micrometers and 10 micrometers.

27. The implantable infusion device ofclaim 24, wherein the filter is configured to filter particles larger than 0.22 microns in diameter.

28. The implantable infusion device ofclaim 24, wherein the volume of the inlet chamber is between 100 microliters and 300 microliters.

29. The implantable infusion device ofclaim 24, wherein the reservoir is maintained at a pressure of greater than 5 psia.

30. The implantable infusion device ofclaim 24, wherein the reservoir is maintained at a pressure of greater than 10 psia.

31. The implantable infusion device ofclaim 24, wherein the reservoir is maintained at a pressure of between 15 psia and 16 psia.

32. The implantable infusion device ofclaim 24,

wherein the valve has a cracking pressure that is between 5 psi less than the pressure of the reservoir and 5 psi more than the pressure of the reservoir.

33. The implantable infusion device ofclaim 24, wherein the valve has a cracking pressure that is at least 2 psi greater than the difference of the reservoir pressure minus the outlet pressure at the lowest ambient atmospheric pressure that the device is designed to be subjected.

34. The implantable infusion device ofclaim 24, wherein the valve has a cracking pressure that is equal to or greater than the reservoir pressure minus 6.3 psia.

35. The implantable infusion device ofclaim 24, wherein the drive mechanism is capable of continued operation without undissolved gas exiting the distal portion of the piston channel when 70% of the volume of the inlet chamber is occupied by undissolved gas.

36. The implantable infusion device ofclaim 24, wherein the reservoir is maintained at a pressure of greater than 8 psia.

37. The implantable infusion device ofclaim 24, wherein the reservoir is maintained at a pressure of greater than 10 psia.

38. The implantable infusion device ofclaim 24, wherein the reservoir is maintained at a pressure of between 14 psia and 19 psia.

39. The implantable infusion device ofclaim 24, wherein the reservoir is maintained at a pressure of greater than 0 psia.

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