Implantable drug-delivery devices, and apparatus and methods for filling the devices.

(54) Title: IMPLANTABLE DEVICES FOR THE SUPPLY OF DRUGS, AND APPARATUS AND METHODS FOR FILLING THE DEVICES.

(54) Title: IMPLANTABLE DRUG-DELIVERY DEVICES, AND APPARATUS AND METHODS FOR FILLING THE DEVICES.

(57) Summary

The present invention relates to a tool for recharging an implantable drug delivery pump, the tool comprising: first and second independent fluid channels; a fluid reservoir in fluid communication with the first fluid channel; first and second pumps each fluidly coupled to one of the fluid channels, where (i) the first pump is configured to apply positive pressure to the first fluid channel so that fluid is conducted from the fluid reservoir through the itself, and (ii) the second pump is configured to apply negative pressure to the second fluid channel; and means for coupling a loading port of the implantable drug delivery pump; wherein the coupling means comprise a needle insertable into the charging port and having a single lumen in fluid communication with the first and second fluid channels.

(57) Abstract

In various embodiments, a tool is employed in filling a drug-delivery device. The tool may inelude, for example, a needle (200) that is admitted through a fill port (152) of the drug-delivery device.

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PATENT TITLE NO. 339941

Institute

Mexican Property

Industrial

Owner (s): MINIPUMPS, LLC

Address: 30th Street 319, Manhattan Beach, California, 90266, USA

Name: IMPLANTABLE DEVICES FOR THE SUPPLY OF DRUGS, AND APPARATUS AND METHODS FOR FILLING THE DEVICES.

Classification: lnt.CI.8: A61M39 / 02; A61M5 / 142

Inventor (s): JASON SHIH; CHANGLIN PANG; FUKANG JIANG; SEAN CAFFEY; MARK

HUMAYUN; YU-CHONG TAI; RAYMOND PECK

REQUEST

Numbers International filing date:

MX / a / 2014/006352 May 8, 2009

Divisional Patent Number: 323308

PRIORITY

<td>I</td><td>Country:</td><td>Date:</td><td>Number:</td>

<td>i</td><td>, US &lt;'</td><td>May 8, 2008</td><td> 61/051,422</td>

<td></td><td>US</td><td>October 30, 2008</td><td> 61/197,817</td>

<td> 3</td><td>US</td><td>October 30, 2008</td><td> 61/197,752</td>

<td></td><td>US</td><td>November 3, 2008</td><td> 61/198,126</td>

<td colspan="2">Validity: Twenty years</td><td>i ...</td><td></td>

Expiration Date: May 8, 2029

The (reference attempt is made with Andamento in articles 1, V fraction V, 6 fraction III, and 59 of the Industrial Property Law

In accordance with article 23 of the Industrial Property Law, this patent has a non-extendable term of twenty years, paid from the filing date of the international application and will be subject to the payment of the fee to maintain the rights in force. i; -⁵

Whoever subscribes to this title does so based on the provisions of articles 6 fractions lll and 7 As 2 of the Public Law.^!!fidüStr¡ar'tD'Bñ'oOfficial of the federation (DOF :) 06/27/1991, amended on 08/02/1994, 10/25/1996, 12/26/1997, 05/17/1999, 26 / 01/2004, 06/16/2005, 01/25/2006, 06/05/2009, 06/01/2010, 06/18/2010, 06/28/2010, 01/27/2012, and 09/04 / 2012); Articles 1, 3 fraction V Clause a), 4 and 12 'fractions I and lll of the Regulations of the Mexican Institute of Industrial Property (DOF 12/14/1999, amended on 07/01/2002, 07/15/2004, 07/28/2004 and 09/07/2007); Articles 1, 3 ', 4, 5, section V, subsection a), 16 sections I and III and 30 of the Organic Statute of the Mexican Institute of Industrial Property (DOF) 12/27/1999, amended on 10/10/2002, 07/29/2004, 08/04/2004 and 09/13/2007); Γ, 3 'and 5 ° Subsection a) of the Agreement that delegates powers to the Deputy Directors General, Coordinator, Divisional Directors, Holders of the Regional Offices, Divisional Deputy Directors, Departmental Coordinators and other subordinates of the Mexican Institute of Industrial Property. (DOF 12/15/1999, amended on 02/04/2000, 07/29/2004, 08/04/2004 and 09/13/2007).

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2ON,

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IMPLANTABLE DEVICES FOR THE SUPPLY OF PHARMACES, AND APPARATUS AND METHODS FOR FILLING THE DEVICES

Cross Reference to Related Requests

This application claims priority for and the benefit of, and incorporates herein by reference in its entirety, US provisional patent applications numbers 61 / 051,422, which was filed on May 8, 2008; 61 / 197,752, which was filed on October 30, 2008; 61 / 197,817, which was filed on October 30, 2008; and 61 / 198,126, which was filed on November 3, 2008.

Technical Field of the Invention

In various embodiments, the invention relates to implantable drug delivery devices and apparatus and methods for filling such devices.

Background of the Invention

Medical treatment often requires the administration of a therapeutic agent (eg medication, drugs, etc.) to a particular part of the patient. As patients live longer and with chronic conditions and / or a patient's body, they are diagnosed as needing of placing even more protein therapies, debilitating drugs, the likely result will be an increase in

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MEXICAN INSTITUTE, _, OF THE PROPERTY OF SMALL MOLECULES, AND OTHER TARGET-DENWBFRtee MEDICINES THROUGH THE BODY OF THE RISING Mgnnag DISEASES, HOWEVER, ARE DIFFICULT TO TREAT WITH CURRENTLY AVAILABLE THERAPIES AND / OR REQUIRE THE ADMINISTRATION OF DRUGS TO ANATOMICAL REGIONS which access is difficult to achieve.

A patient's eye is a prime example of a hard-to-reach anatomical region, and many vision-threatening diseases, including retinitis pigmentosa, age-related macular degeneration (AMD), diabetic retinopathy, and glaucoma, are difficult to deal with many of the therapies currently available. For example, oral medications can have systemic side effects; topical applications can cause itching and lead to poor patient compliance; injections generally require a medical visit, can be painful, and are at risk of infection; and sustained-release implants must commonly be removed after their supply has been depleted (and generally offer limited ability to change the dose in response to the clinical picture).

Another example is cancer, such as breast or meningiornas cancer, where large doses of highly toxic chemotherapies such as rapamycin, bevacizumab (eg AVASTIN), or irinotecan (CPT-11), commonly

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MEXICAN INSTITUTE OF PROPERTY

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administered to the patient intravenously¹?™⁵’’!¹# - which can result in numerous, undesired, side effects outside the target area. Yet another example is the administration of drugs to the knee, where drugs often have difficulty penetrating avascular cartilage tissue for diseases such as osteoarthritis.

Implantable drug delivery devices, which may have a refillable drug reservoir, a cannula to deliver the drug, etc., generally allow the controlled delivery of pharmaceutical solutions to a specific target. As the drug within the drug reservoir runs out, the physician can refill the reservoir with, for example, a syringe, while leaving the device implanted within the patient's body. This approach can minimize the surgical incision required for implantation and typically prevents future or repeated surgeries or invasive procedures.

A variety of challenges, however, are associated with rechargeable drug delivery devices. For example, while a charging port may be located on a surface of the device to facilitate post-implantation access, the fact that the device is installed within the patient's anatomy may make such access uncomfortable for the patient and a risk of hurt

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MEXICAN INSTITUTE

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INDUSTRIAL for the device. Such difficulties are especially troublesome if the device is manually recharged. When the drug reservoir is loaded using a manual syringe, for example, it is possible to generate high pressures in the syringe, particularly when small volumes are involved and the syringe plunger is of a small diameter. These high pressures can damage the device and / or cause an inadequate expulsion of the drug. Also, trying to refill the drug delivery device with a single-barrel manual syringe may require several cycles of needle insertion and removal as different fluids are removed and injected into the device. This can cause stress to the patient and doctor, and creates unnecessary wear on the charging port.

There is a need, therefore, for implantable devices for improved drug delivery, and apparatus and methods for charging such devices.

Summary of the Invention

In various embodiments, the present invention features apparatus and methods for emptying, rinsing, and filling, in situ, a drug reservoir from a drug delivery device implanted within a patient's body through one or more charging ports accessible by needle, self-sealing. The drug delivery device may be, for example, an implantable pump for

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MEXICAN INSTITUTE OF PROPERTY drug supply. The apparatus generally^INDit runs^_ features, and commonly in-veluemii pasus methods, that allow emptying, rinsing, and loading to occur in a way that minimizes the risk of damage to the pump, thereby maximizing its effective life time. For example, in one embodiment, a dedicated refilling instrument allows multiple fluids to be controlled and directed through a single drug delivery pump loading port and only with a single needle insert. In short, the recharging process can be automated so that pump components are protected from potential damage and ensure reliable and reproducible recharging.

In various modalities, the implantable pump charging port (s) contain (s) itself several features that, either alone or in combination, promote reliable and reproducible refilling of the implantable drug delivery pump. . For example, as described herein, the charging port or ports may (n) contain features that prevent the reverse flow of the drug from the drug reservoir through the charging port.

In general, in one aspect, embodiments of the invention feature an implantable drug delivery pump. The pump includes a drug reservoir and, in fluid communication with it, a charging port that includes an elastomeric plug. The shutter extends at least

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MEXICAN INSTITUTE OF FROP1EDAD

INDUSTRIAL partially through an opening in a loading port wall. The pump also includes means to improve the retention of the plug inside the opening (for example, grooves or cords, or other features that promote mechanical securing between parts, in the opening). In various embodiments, the pump also includes a parylene coating at or above the opening.

In general, in another aspect, embodiments of the invention present another implantable drug delivery pump. Again, this pump includes a drug reservoir and, in fluid communication with it, a charging port that includes an elastomeric plug that extends at least partially through an opening in one wall of the charging port. In addition, the pump also includes a check valve, which can be closed over the opening, to prevent reverse flow from the tank through the loading port. The check valve can include a pair of parylene flaps or a single parylene flap that can be closed over the opening.

In either pump, the wall through which the loading port opening is formed may be the same as a wall that surrounds, at least partially, the drug reservoir. Alternatively, tubing can be used to connect the opening of the loading port to the drug reservoir. In different modalities, the shutter is made of silicone. The charging port can include

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MEXICAN INSTITUTE OF PROPERTY a guide for the needle to guide a needle to it. Also, the charging port can tenex .... mia goowefevi'gr that is compatible only with needles that have a complementary geometry.

In general, in yet another aspect, embodiments of the invention feature an implantable drug delivery pump that includes a drug reservoir, a cannula to deliver fluid from the reservoir to a target site, an electrolyte chamber, an expandable diaphragm that separates the chamber and reservoir and providing a fluid barrier between them, and a plurality of charging ports to provide external access to at least one of the reservoir or chamber. For example, a first charging port can provide external access to the tank and a second charging port can provide external access to the chamber. Alternatively or additionally, at least two charging ports can each provide external access to the tank and / or at least two charging ports can each provide external access to the chamber.

In general, in yet another aspect, embodiments of the invention present a tool for refilling an implantable drug delivery pump, such as a pump as described above. The tool includes independent first and second fluid channels, a fluid reservoir in fluid communication with the first fluid channel, first and second pumps each coupled

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INDUSTRIAL

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fluidly to one of the fluid channels, and means for coupling an implantable pump loading port for drug delivery. The first pump can be configured to apply positive pressure to the first fluid channel so that fluid is conducted from the fluid reservoir through it, and the second pump can be configured to apply negative pressure to the second fluid channel. For this part, the means for coupling may be a needle that is configured for insertion into the charging port. The needle may have a lumen in fluid communication with the first and second fluid channels.

In various embodiments, the tool further includes a third independent fluid channel, a second fluid reservoir in fluid communication with it, and a third pump fluidly coupled to the third fluid channel. In such a case, the third pump can be configured to apply positive pressure to the third fluid channel so that it conducts fluid from the second fluid reservoir through it.

The tool may also include governing circuitry, which prevents fluid pressure at an outlet from the needle lumen from exceeding a predefined level. The first and second valves, in response to the governing circuitry, may also be included to control the flow of the fluid through the first and second fluid channels,

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respectively. Furthermore, the tool may include a bubble detector and / or a gas eliminator at least one of the first, second, or third fluid channel. The bubble detector may be, for example, an ultrasonic bubble detector, an optical bubble detector, a thermal bubble detector, or an electrical bubble detector.

In another embodiment, the needle displays first and second lumens through it. The first and second lumens can be fluidly isolated from each other. The first lumen can communicate with the first fluid channel, and the second lumen can communicate with the second fluid channel.

In general, in yet another aspect, embodiments of the invention present a method of filling an implantable drug delivery pump having a drug chamber. According to the method, a tool is provided first. The tool includes independent first and second fluid channels, and a fluid reservoir in fluid communication with the first fluid channel. The tool can be attached to an implantable pump delivery port for drug delivery, and then used to purge the drug chamber and subsequently pump fluid from the fluid reservoir into the drug chamber through the first fluid channel. without exceeding a maximum pressure in the drug chamber.

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INDUSTRIAL

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In various embodiments, the tool is coupled to the load port by means of a needle that has a lumen in fluid communication with the first and second fluid channels. The purge step may include pumping fluid from the fluid reservoir into the drug chamber through the needle and the first fluid channel, and then sucking fluid out of the drug chamber through the needle and second fluid channel. . In another embodiment, the tool further includes a third independent fluid channel and a second fluid reservoir in fluid communication with it, and the purge step involves pumping fluid from the second fluid reservoir into the drug chamber through the needle and the third fluid channel, and then suck the fluid from the drug chamber through the needle and the second fluid channel.

These and other objects, together with the advantages and characteristics of the embodiments of the present invention described herein, will be more apparent by reference to the following description, the accompanying drawings, and the claims. Furthermore, it is to be understood that the characteristics of the various modalities described herein are not mutually exclusive and may exist in various combinations and permutations, even though they have not been made explicit herein.

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MEXICAN INSTITUTE OF INDUSTRIAL PROPERTY

Brief Description of Drawings

In the drawings, similar reference characters generally refer to the same parts through different views. Also, the drawings are not necessarily to scale, the emphasis instead is generally placed on illustrating the principles of the invention. In the following description, various embodiments of the present invention are described with reference to the following drawings, in which:

Figure IA schematically illustrates, in cross section, an implantable drug delivery device according to an embodiment of the invention;

Figure IB schematically illustrates, in cross section, an implantable drug delivery device according to another embodiment of the invention;

Figure 2 schematically illustrates an implantable drug delivery device, having multiple charging ports, in accordance with yet another embodiment of the invention;

Figure 3A schematically illustrates, in cross section, the internal structure of a charging port according to an embodiment of the invention, as it is pierced by a recharging needle;

Figure 3B schematically illustrates, in cross section, the internal structure of a charging port that is piped to a drug reservoir of

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MEXICAN INSTITUTE OF INDUSTRIAL PROPERTY according to an embodiment of the invention, as the loading port is crossed by a recharging needle;

Figures 4A-4D schematically illustrate, in cross section, the internal structure of various charging ports according to further embodiments of the invention;

Figures 5A-5E schematically illustrate, in cross section, a process for making yet another variant of a charging port according to an embodiment of the invention;

Figures 6A-6D schematically illustrate, in cross section, the internal structure of various loading ports having needle stops according to embodiments of the invention;

Figure 7 schematically illustrates, in cross section, the internal structure of a loading port having a needle guide according to an embodiment of the invention.

Figure 8 schematically illustrates, in cross section, the internal structure of a loading port having a pair of flaps as a check valve in accordance with an embodiment of the invention, as the drug is led into it;

Figure 9 schematically illustrates, in cross section, the internal structure of a loading port having a single flap as a check valve.

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'' 1 %

MEXICAN INSTITUTE OF INDUSTRIAL PROPERTY according to an embodiment of the invention, as the drug is led to it;

Figure 10 schematically illustrates a tool for recharging an implantable drug delivery device in accordance with an embodiment of the invention;

Figure 11 schematically illustrates a tool, having a single lumen refill needle, inserted into a charging port of an implantable drug delivery device according to an embodiment of the invention;

Figure 12 schematically illustrates a tool, having a double lumen refill needle, inserted into a charging port of an implantable drug delivery device in accordance with one embodiment of the invention; and

Figure 13 schematically illustrates the tool of Figure 10 coupled to an input and deployment device in accordance with an embodiment of the invention.

Detailed description of the invention

In general, embodiments of the present invention are related to pumps for administration of implantable drugs into a patient's body, such as, for example, into the patient's eye or brain, and to apparatus and methods for recharging those pumps. In certain modalities, implantable pumps for delivery of

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IN «TITUTO WEX ^ CANO drugs combine small size and a tank ^^^ M / íár²Rechargeable. The small size minimizes the discomfort of the. pump to deliver drugs to the patient, while the refillable reservoir allows the pump to be recharged on site, rather than having to be replaced. As such, a fluid, such as a solution of a drug, can be supplied to the patient over long periods of time.

Modalities of the invention can be used in connection with various types of implantable drug delivery pumps. Figures IA and IB schematically illustrate two variations of an implantable drug delivery pump (100) (namely, an exemplary electrolyte pump (100)) implanted within a patient's eye (104). The pump 100 may, however, instead be implanted in other portions of a patient's body. For example, it can be implanted in the sub-arachnoid space of the brain to provide chemotherapy or to provide another type of treatment for the brain (for example, by administering to the brain parenchyma directly), or near a tumor in any part of the body of the brain. patient to provide chemotherapy, or in a pancreas that does not respond well to glucose to provide agents (eg, proteins, viral vectors, etc.) that will cause insulin release, or in the knee to provide drugs that will treat osteoarthritis and others

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cartilage diseases, or near^{THE A}i3 ^ sTRiXEOJ to provide vertebral medications for dpi &lt;~&gt; r a ..

anti-inflammatory, or in other places. As illustrated in Figures IA and IB, embodiments of the pump (100) may include two main components: a pair of chambers (108), (112) surrounded, at least in part, by a wall (115), and a cannula (120). As illustrated in FIG. IA, the wall 115 surrounding the chambers 108, 112 can include or consist of a separate film of parylene 116 and, on it, a separate protective shell 128 made of a relatively stiff biocompatible material (eg, medical grade polypropylene). Alternatively, as illustrated in Figure IB, the wall 115 may correspond only to the protective shell 128, which may be coated with parylene. The upper chamber 108 defines a drug reservoir that, when used to treat a patient, may contain the drug to be administered in liquid form. For its part, the lower chamber (112) can contain a liquid that, when subjected to electrolysis, emanates a gaseous product. For example, that liquid can be water, which can be electrolytically separated by an applied voltage, to generate hydrogen gas and oxygen gas. Alternatively, like other examples, the electrolyte liquid can be a saline solution (eg, NaCl and H2O) or a solution containing either

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MEXICAN INSTITUTE of i «opiety.

magnesium sulfate or sodium sulfate. In und ^ oaalidacT? the two chambers (108), (112) are s -— ρυι ΙΠΓ corrugated diaphragm (124). In other words, the diaphragm 124 provides a fluid barrier between the two 5 chambers 108, 112. Like the independent film 116, the diaphragm 124 can be constructed from, for example, parylene.

As illustrated in Figure IA, the independent film (116) can act as an outer barrier to the drug reservoir (108) and the protective shell (128) can provide a hard surface against which the film (116) exerts Pressure. In such a case, the armor (128) can be perforated to allow movement of the eye, brain, or other fluid body movement. Alternatively, as illustrated in Figure IB, the shield shell (128) can act as the external barrier to the drug reservoir (108) and be unperforated. In both modalities shown in Figures IA and IB, the protective shell (128) can prevent external pressure from being exerted on the drug reservoir (108). As illustrated in Figure IA, a lower portion (126) (by For example, a floor (126) of the shield shell (128) may include suture holes (130). Similarly, although not shown in any of Figures IA or IB, the cannula (12 0) may also include suture holes along its sides. Suture holes (130) can be used in

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suture (eg, anchor) the pump (100) to the patient's body. -As also illustrated in FIG. 1A, to provide power to the pump (100) and to allow data transmission therewith, a battery and control circuitry (132) may be integrated (eg, hermetically sealed) below chambers (108), (112) (for example, between a lower portion of the independent parylene film (116) of the drug reservoir (108) and the floor (12 6) of the protection shell (128)), and an induction coil (136) can be integrated into the shield shell (128) (eg, by injection molding). Figure IB more clearly illustrates an airtight case (135) for housing the conventional battery and control circuitry (132), but, for simplicity, does not show the components housed therein. The sealed case 135 may be made of biocompatible metals (eg, titanium) or metal alloys. The bottom of the airtight case (135) can be flat, or it can be concave to help the implantable pump (100) fit into the patient's eye (104).

In one embodiment, the induction coil 136 allows wireless communication (eg, radio frequency) with an external device ( eg, a portable device). The portable device can be used to send wireless signals to the control circuitry

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INSTITUTO MEXICANO DE LA l'ROPJEDAD (132) in order to program, reprogram, operate, calibrate or otherwise configure the pump (ί-ΘΟ): - ~ In this mode, the control circuitry (132) communicates electrically with electrolysis electrodes (134) in the electrolyte chamber (112) by means of metal interconnections (pathways) (138) passing through a lower portion of the electrolyte reservoir (112). Electrolysis electrodes 134 are made of, for example, platinum, gold, and / or other metals. As will be described later, the control circuitry (132) controls the pumping action of the pump (100), including the closed-loop control process described below.

In one embodiment, as illustrated in FIG. IA, the cannula (120) connects the drug chamber (108) to a check valve (140) inserted at the site of administration. Alternatively, or additionally, as illustrated in Figure IB, the check valve (140) may be integral with, and located at, a proximal end of the cannula (120) (i.e., at the end closest to the drug deposit (108)). One or more flow sensors (144) to monitor drug flow - and thus allow measurement of drug volume - through cannula (120) may be associated with one or more of a proximal, medial, or distal portion of the cannula (120). Optionally, as illustrated in Figure IA, a pressure sensor (148) can also be integrated at one end

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INSTITUTO MEXICANO OE INDUSTRIAL PROPERTY distal of the cannula (120) (that is, at the end furthest from the drug reservoir (108)) to measure the pressure at the site of administration (for example, the intravitreal chamber, the capsule of the shoulder, knee capsule, cerebral ventricles, spinal canal, etc.). In one embodiment, the pressure sensor (148) provides feedback to the control circuitry (132) such that the drug flow can be measured by a closed-loop control process. For example, increased pressure in the drug target region can cause a decrease in drug flow from the pump (100).

As illustrated in Figure 1A, the cannula (120) can be an extension of the independent parylene film (116). Alternatively, as illustrated in figure

IB, the cannula (120) can be a separate component coupled to the protection shell (128). For example, a proximal end of the cannula (120) can be inserted through a fluid connection port formed in the shield shell (128) and attached therein by means of, for example, a biocompatible epoxy glue (150 ). A silicone sleeve (154) can be placed around a portion of the cannula (120) (see figure IB), but this is optional (see figure 1A).

In one embodiment, as illustrated in FIG. 1A, a charging port 152 is assembled with the drug reservoir

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INSTITUTO MEXICANO DE LA ΓΜ HEDAD (108) and it is sealed with a sealant (eg eif ^ íS¹) * '*' biocompatible epoxy resin) (156) a ~ —Ía—— independent (116) and the protective shell (128). In another embodiment, as illustrated in Figure IB, a hole may be formed through the protection shell (128) and the loading port (152) presented therein. In yet another embodiment, the loading port 152 can be formed in another part of the pump 100 and connected to the drug reservoir 108 through tubing. For example, the loading port (152) can be molded from biocompatible materials, coupled to a corresponding notch in the airtight case (135), and connected to the drug reservoir (108) through the tubing. In one embodiment, the tubing is inserted through a fluid connection port formed in a wall surrounding the drug reservoir (108) and is bonded thereto by means of a biocompatible epoxy glue. In either case, as described below, the charging port 152 is in fluid communication with the drug reservoir 108 and allows an operator of the pump 100 (eg, a physician) to refill the reservoir of drug (108) in situ (eg, while the pump (100) is implanted within the eye of the patient (104)). In general, the drug reservoir (108) can be refilled by inserting a refill needle into and through the charging port (152).

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In various embodiments, the main pump parts 100 (i.e., the pair of chambers 108, 112 and cannula 120) are suitable for monolithic micro-fabrication and integration using multiple parylene layer processes . The charging port 152, the protection shell 128, and other components can be assembled with the pump 100 after the microfabrication steps.

In operation, when current is supplied to the electrolysis electrodes 134, the electrolyte emanates gas, expanding the corrugated diaphragm 124 (i.e., moving the diaphragm upward in Figures IA and IB) and forcing the liquid ( ie, the drug) to be led out of the drug reservoir (108), through the cannula (120), and out of its distal end to the target site of administration. The corrugations and other kinks in the expandable diaphragm (124) allow a high degree of expansion, without sacrificing volume within the drug reservoir (108) when the diaphragm (124) relaxes. When the current is stopped, the electrolyte gas condenses back to its liquid state, and the diaphragm (124) recovers its efficient corrugations in space.

In some embodiments, referring to Figure 2, the implantable pump (100) includes a plurality of loading ports (152). For example, pump (100) may include a first unique charging port (152A) that provides access

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<img file="MX339941B_D0026.tif" />

external to the drug reservoir (108) and a second unique charging port (152B) that provides external access to the electrolyte chamber (112). In this way, any of. cameras 108, 112 can be recharged when depleted (eg, as detected by control circuitry 132). Alternatively, the pump 100 may include (i) two or more charging ports 152A providing external access to the drug reservoir 108 and none or a single charging port 152B providing external access to the chamber. electrolyte (112), or (ii) two or more charging ports (152B) providing external access to the electrolyte chamber (112) and a single charging port (152a) (or no charging port) providing external access to the drug depot (108), or (iii) two or more charging ports (152A) providing external access to the drug reservoir (108) and two or more charging ports (152B) providing external access to the electrolyte chamber (112). In one embodiment, multiple charging ports 152 for a single chamber 108, 112 facilitate emptying, rinsing, and / or refilling by recharging chamber 108, 112 (eg, removing trapped air). , etc.), with one charging port receiving new fluid while existing fluid is leaving another charging port. The multiple charging ports 152A, 152B can be integrated with the pump 100 as described above (eg, formed through the protection shell 128); coupled

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INSTITUTE ς to the pump (100) in another place and connected. to the^ECd) ®pB®i-to drug (108) or the electrolyte chamber (112J, in any case, through pipe, etc.).

Figure 3A schematically illustrates the internal structure of a charging port (152), in accordance with an embodiment of the invention, as punctured by a refill needle (200). The charging port (152) is illustrated in Figure 3A being in fluid communication with the drug reservoir (108). However, as described above, the charging port (152) may instead be in fluid communication with the electrolyte chamber (112). Furthermore, instead of being in direct contact with the drug reservoir (108) or the electrolyte chamber (112), the charging port can be connected to it through intermediate pipe (202), as illustrated in the figure 3B. Consequently, it will be understood by a person with ordinary knowledge in the art that the following

<td>description</td><td>of</td><td>the</td><td>different</td><td>modalities</td><td>of the</td><td>port</td><td>of</td>

<td>cargo (152)</td><td>AND</td><td colspan="2">of the various</td><td>modalities</td><td>of</td><td>recharge</td><td>the</td>

<td>deposit of</td><td colspan="2">drug</td><td colspan="2">(108) using the port</td><td>of</td><td colspan="2">cargo (152)</td>

it also applies in the same way for a charging port (152) that is in fluid communication with the electrolyte chamber (112) (either directly or through the use of intermediate pipe (202)) and for methods to recharge the electrolyte (112) using the charging port (152).

<img file="MX339941B_D0028.tif" />

IMPI

As illustrated in Figures 3A and 3B, one embodiment of the charging port (152) includes an eiaéTóIllér'lCU shutter (204) that is molded into a hollow structure (208) defined by a charging port wall (224) (152). Where the loading port 152 is in fluid communication with the drug reservoir 108 without the use of the pipe 202 (Figure 3A), the hollow structure 208 may in fact be an opening spanning the thickness of the armor of protection (128) and / or the independent film (116). As shown in Figures 3A and 3B, the elastomeric plug (204) can extend at least partially through the opening (208). In one embodiment, the diameter and thickness of the elastomeric plug (204) is generally less than 3 mm.

The elastomeric plug (204) can be, for example, a silicone plug (204) (as indicated in Figures 3A and 3B). More generally, however, the obturator 204 may be made of any material (eg, soft plastic) that can be pierced with a needle 200 and is capable of resealing itself after the needle is removed. (200) . Furthermore, the self-sealing material of the obturator (204) may be capable of supporting multiple needle piercings (200), and may be biocompatible. In addition to silicone, the materials from which the plug can be made include, but are not limited to, polydimethylsiloxane (PDMS), Parylene C, Parylene HT, Polycarbonates, Copolymers

IMPI

MEXICAN INSTITUTE DSLA I'ROEIECAD polyolef inas, polyurethanes, acrylic copolymers^N&lt;5 ¥ íi £ rilo7 of polyvinyl chloride; - · ami daS7

<img file="MX339941B_D0029.tif" />

Polysulfones, Polystyrenes, Polyvinylfluorides, Polyvinyl Alcohols, Polyvinyl Esters, Polyvinyl Butyrate, Polyvinyl Acetate, Polyvinylidene Chlorides, Polyvinylurethane Polyurethane Polyurethane Polyurethane Polyurethane Polyurethane Polyurethane Polyurethane Polystyrene polyvinyl acetate, nylon, cellulose, gelatin, and porous rubber.

In one embodiment, to form the silicone plug (204), uncured silicone rubber is injected directly into the hollow structure (208) and cured in place. The self-sealing properties of silicone rubber allow the needle (200) to be inserted into and removed from the charging port (152) without causing permanent leakage.

The charging port (152) illustrated in Figures 3A and 3B includes a smooth internal surface opening (208). In some embodiments, however, the charging port (152) further includes means for improving the retention of the shutter (204) within the opening (208). For example, as shown in the loading port (152) illustrated in Figure 4A, filaments, grooves, or other features (212) that facilitate mechanical securing may be carved or molded within the walls (224) that define the opening. (208) to keep the shutter (204) secure

IMPI

INSTÍTVTC W-XiCAA'O SiNDUSTínía on site. These features (212) increase the area of

<img file="MX339941B_D0030.tif" />

sealing surface and also mechanically anchor the shutter (204) in place.

Furthermore, where the plug (204) is made of a polymer (for example, silicone) that is capable of leaching or absorbing drugs that come into contact with it, the charging port (152) may be coated with a biocompatible polymer (for eg, parylene) so that less drug is exposed to the polymer. Coating (216) also helps minimize the possibility of leakage at the shutter / bracket interface. The parylene coating (216) can be applied before, after, or both before and after the formation of the shutter (204) so ​​that the parylene coating (216) is applied in, on, or both in and on top of the opening (208), respectively. For example, the refill port (152) shown in Figure 4B features a silicone plug (204) molded within the smooth inner surface opening (208) having a single parylene coating (216) within the opening ( 208), The charging port (152) shown in Figure 4C features a silicone plug (204) molded within a smooth internal surface opening (208) having a single parylene coating (216) above (and only partially within) of opening (208), and charging port (152) shown in Figure 4D have a silicone plug (204) molded within a

IMPI

MEXICAN INSTITUTE OF INDUSTRIAL PROPERTY smooth internal surface opening (208) that has a double parylene coating (216) (both inside¹ as above opening (208)).

In yet another embodiment, the parylene coating (216) can be applied inside the opening (208) and over a lower portion thereof, but not over an upper portion of the opening (208). Such a structure for the charging port (152) is illustrated in Figure 5E, while Figures 5A-5D schematically illustrate the steps in an example process for making the structure shown in Figure 5E. In greater detail, referring first to Figure 5A, a parylene coating (216) is first applied to the opening (208) of the loading port (152), and then the shutter (204) is formed therein. Then, as illustrated in Figure 5B, the top surface of the charging port (152) is masked by applying an additional segment (226) of silicone to it. Subsequently, a second parylene coating (216) can be applied (Figure 5C) and the additional silicone segment (226) is removed from the charging port (152) (Figure 5D), leaving the structure shown in Figure 5E. Advantageously, the use of the silicone segment (226) prevents the second parylene coating (216) from covering the upper surface of the opening (208). One reason why such a structure is desirable is that it prevents the second parylene coating (216) from being pulled in.

<img file="MX339941B_D0031.tif" />

MEXICAN INSTITUTE OF THE FIRST INDUSTRY!

<img file="MX339941B_D0032.tif" />

. . , INDUSTRIAL of the obturator (204) during insertion of the needle (200) 7 Dragging the parylene coating (216) dSIltl'U ÚGl · · obturator (204) can, for example, damage the charging port (152) and cause fluid leakage from it.

Referring now to Figures 6A-6D, in some cases it is desirable to have a stop on the needle (220) positioned within the loading port (152). As illustrated, the stop (220) can extend at least partially into the opening (208). The stop (220) 10 may be integrally formed with the wall (224) of the charging port (152) or it may be a separately manufactured part, which is secured to the wall (224) by, for example, gluing the stop (220 ) to the wall (224) with an epoxy resin or other suitable adhesive. In this way, the progress of the recharging needle (200) within the charging port (152) stops when a tip of the needle (200) makes contact with the stop (220). This prevents the needle (200) from being inserted too far into the pump (100), which could cause damage to it.

The stop (220) can take the form of a mechanical plate (for example, as illustrated in Figures 6A and 6D), a filter (for example, as illustrated in Figure 6C), an inflection (for example, as illustrated in Figure 6B) or any number of other structures whose shape is suitable to carry out the functions of a stop (220) described herein. Furthermore, as illustrated in Figures 6A and

<img file="MX339941B_D0033.tif" />

6D, the top surface of the stop (220) can be flat. Alternatively, the top surface of the stop (220) may have a cup or concave shape. In this way, the stop (220) can also help prevent the reload needle (200) from contacting, and possibly penetrating, one of the side walls (224) that define the opening (208).

The loading port (152) and the needle stop (220) thereof can also be designed so that only certain needles (200) can be used to access the drug reservoir (108). In other words, the charging port 152 can be designed to have a geometry that is compatible only with needles 200 having a complementary geometry. For example, as illustrated in Figure 6D, a needle exit hole (200) only coincides with an access channel (228) when the needle (200) is fully inserted into the stop of the needle (220). And, as illustrated in Figures 6A-6C, the needle exit hole (200) only coincides with an area of ​​the opening (208) not occupied by the shutter (204) when the needle (200) is fully inserted at the needle stop (220).

In general, the stop (220) of the charging port (152) can be constructed of any relatively rigid and mechanically robust material, or combinations of materials, that have / have the mechanical strength required to perform the functions of the stop (220) described in the

<img file="MX339941B_D0034.tif" />

IMPIí

MEXICAN INSTITUTE OF FROflEDAD

INDUSTRIAL present. For example, the stop (220) may be constructed of a metal, a hard plastic (eg, fully crosslinked or reinforced), a composite material, or a combination thereof. More specific examples of materials for the bumper (220) include a thick layer of PDMS, polyimide, polypropylene, polyaryl ether ketone (PEER), polycarbonate, acetyl film (eg, acetyl copolymer), plastic polyoxymethylene ( for example, DERLIN), gold, stainless steel, nickel, and / or chrome. The stop (220) may (but not necessarily) be biocompatible.

Because the charging port 152 can be of a relatively small size, it may be desirable, in some embodiments, for the charging port 152 to also include a needle guide to ensure that the needle 200 is inserts substantially straight into the charging port (152). While there is some margin for error, too great an entry angle can cause the needle 200 to hit the support structure for the charging port 152 (i.e. the wall 224), and fail to penetrate the elastomeric plug (204). As illustrated in Figure 7, the needle guide (232) may be tapered, or it may be in another shape. In addition, the needle guide (232) may be integrally formed with the charging port (152), or it may be removable and placed on top of the

ΙΜΡΙ

MEXICAN INSTITUTE OF LA FROKEPAO loading port (152), and mechanically or magnetically secured to it, just before the procedure du * itítdi'yar

<img file="MX339941B_D0035.tif" />

In another embodiment, the implantable drug delivery pump (100) also includes a check valve, for example, within the drug reservoir (108) or within the intermediate line (202) and can be closed over the opening (208 ), to prevent backflow from the tank (108) through the loading port (152). The check valve can also rectify the drug flow from the needle (200) to the drug reservoir (108) and reduce the possibility of leakage. In one embodiment, the check valve is opened as the liquid is pushed into the drug reservoir (108), and then closed.

Two exemplary check valve designs are shown in Figures 8 and 9. The illustrated check valves (300) include one (Figure 9) or two (Figure 8) flaps (304A), (304B) of a biocompatible polymer, such as parylene. The flap (s) (304A), (304B) can be attached to the bottom wall surface of the charging port (224) using, for example, an adhesive, thermal bonding, ultrasonic bonding, laser welding, etc. As illustrated in Figure 8, the flaps 304A, 304B are separated (or a single flap 304 is displaced from the opening 208, as illustrated in Figure 9), as the liquid is injected into the drug chamber

<img file="MX339941B_D0036.tif" />

MEXICAN INSTITUTE OF PROPERTY

INDUSTRIAL

<img file="MX339941B_D0037.tif" />

(108) from the refill needle (200). After withdrawing the needle (200), the pressure exerted on the flap (s) (304A), (304B) by the injected liquid will keep the check valve (300) closed on the opening (208), thus preventing any liquid backflow through the charging port (152). While in Figures 8 and 9 the charging ports (152) show a design with an uncoated smooth internal surface opening (208), it will be understood by someone with ordinary skill in the art that the charging ports (152) can in fact having any of the aforementioned configurations (for example, having threaded or grooved side walls, having parylene coating, etc.).

Modalities of the invention also facilitate loading and recharging of the drug reservoir (108) of the implantable drug delivery device (100) described above. Through the loading port 152 of the pump 100, any remaining liquid can be removed, the reservoir of drug 108 washed, and the new drug injected. Consequently, embodiments of the invention may have an external tool that interfaces with the implantable drug delivery pump (100) to facilitate automated refilling of the drug reservoir (108). Charging or recharging of the drug reservoir (108) can occur while the pump (100) is implanted inside the patient's body (for example, inside the eye ifj-yggSTT.TTU.— · -

<img file="MX339941B_D0038.tif" />

IMPI

INSTITUTO MEXICANO of the patient (104)) and may involve procddi ^ l ^ a &amp; os emptying, washing, and loading or recharging the chamber of drugs (108). As described below, these processes can be performed using a tool that features either a single lumen needle or a double lumen needle.

A tool for interacting and recharging a drug reservoir (108) as described herein can have two, three, or more independent fluid channels. For example, the tool 400 shown in FIG. 10 includes three independent fluid channels 404, 408, 412. The first channel (404) is in fluid communication with a first pump (416) that manipulates the drug (420). The second channel (408) is in fluid communication with a second pump (424) that manipulates a rinse solution (428). The third channel (412) uses vacuum suction (432) to remove or aspirate debris from the fluid (436) from the drug reservoir (108). Liquid flow through the three channels 404, 408, 412 can be effected using standard mechanical pumping technologies (eg, gear, diaphragm, peristaltic, syringe, etc.). Flows can also be pneumatically controlled through the application of pressure or vacuum to the individual channels 404, 408, 412. As illustrated in Figure 10, these three fluid channels 404, 408, 412 can be interfaced with a valve or flow change system 440 and ultimately terminate at the needle.

<img file="MX339941B_D0039.tif" />

(200), which is used to pierce the elastomeric plug (204) of the loading port (152T''V ..... t'é'ñ'éT accessed the drug tank (108).

Furthermore, in one embodiment, one, more, or all of the channels 404, 408, 412 include a bubble detector 442 and / or an in-line gas eliminator 446. Each of the detector (442) and the gas eliminator (446) may be located upstream of the valve system (440), as shown in Figure 10. Alternatively, one or both of the detector (442) and the gas eliminator (446) may in fact be located downstream of the valve system (440). As such, the order in which the various components of the tool 400 are shown in Figure 10 to be placed is not limiting.

In one embodiment, the bubble detector 442 serves to detect gas in its respective channel 404, 408, 412. The presence of gas within the drug reservoir (108) could cause the pump (100) to malfunction. Advantageously, by detecting by means of a bubble detector (442) a gas bubble in one of the channels (404), (408), (412), the detector (442) can indicate (for example, to the governing circuitry (444) ), described later) the presence of said gas. Charging / refilling of the drug reservoir (108) can then be stopped, the needle (200) removed from the charging port (152), and the tool (400) purged to remove any and all gas.

<img file="MX339941B_D0040.tif" />

INSTITUTO MEXICANO K &lt;* «-% £ DE LAPROPlcOAD« 'Industrial ^ ** -. * ZA bubble detector (442) can be implemented through a variety of means, including GOT— ~ per'ó ño ”limited to, ultrasonic, optical, thermal, or electrical. For example, an ultrasonic bubble detector (442) can be placed in proximity, but not in contact, with fluids flowing through a channel (404), (408), (412), transmitting ultrasonic energy through the liquid that it flows, and detect the amount of energy transmitted through it. The amount of energy transmitted through the fluid will change when gas is present in the fluid. Suitable ultrasonic bubble detectors (442) can be provided by, for example, Introtek International of Edgewood, New York; Zevek, Inc. of Salt Lake City, Utah; and Cosense, Inc.

An optical detector (442) can also be placed in proximity, but not in contact, with the fluid flowing through a channel (404), (408), (412), to shine light (for example, infrared light). ) through the fluid that is flowing, and detect the amount of light transmitted through it. Again, the amount of light transmitted through the fluid will change when gas is present in the fluid.

<td>By</td><td>its</td><td>part a detector</td><td>thermal (442)</td><td>can</td><td>to be</td>

<td>placed</td><td>in</td><td>contact with (or in</td><td>proximity to,</td><td>but</td><td>not in</td>

<td>Contact</td><td>with</td><td colspan="2">) the fluid. The thermal detector</td><td> (442)</td><td>can</td>

<td>so</td><td colspan="2">heat (for example,</td><td>through the</td><td>use</td><td>of a</td>

IMPI

<img file="MX339941B_D0041.tif" />

MEXICAN INSTITUTE OF PROPERTY _z INDUSTRIAL heater) the liquid flowing past the detector (442) and detect the temperature of the fluid at, for you J typed, 'day' downstream location. The different thermal properties of a flowing liquid, unlike a flowing liquid comprising gas, will result in different temperatures for each one that has been detected downstream. Consequently, the temperature detected downstream can indicate the presence or absence of gas in the fluid. Suitable thermal bubble detectors (442) can be provided by, for example Sensirion AG of Switzerland.

Finally, an electrical detector 442 can measure some electrical property of the fluid flowing through channel 404, 408, 412. For example, the electrical detector (442) can measure the dielectric constant, resistivity, etc. of the flowing liquid. The reading can provide an indication of the presence, or absence, of gas in the fluid.

<td>By</td><td>his part a</td><td>eliminator</td><td>of</td><td>gas</td><td>(446) can</td>

<td colspan="2">automatically remove</td><td>anyone</td><td>and</td><td>everything</td><td>gas your</td>

<td>respective</td><td>channel (404),</td><td colspan="2"> (408), (412).</td><td>By</td><td>example the</td>

<td>eliminator</td><td>gas (446)</td><td>can be</td><td colspan="3">implemented as a</td>

semi-permeable membrane (for example, permeable to gas, but not to fluid) in a wall of its respective channel (404), (408), (412). The gas present in that channel could then be expelled from the channel through the membrane. Also, a

IMPI

MEXICAN INSTITUTE OF PROPERTY • INDUSTRIAL vacuum can be applied to the membrane wall outside the channel (404), (408), (412) to speed up the process of ^v

<img file="MX339941B_D0042.tif" />

<td colspan="2">gas removal. While</td><td>the figure</td><td colspan="2">10 shows a tool (400)</td>

<td>what's wrong with it</td><td>three</td><td>channels</td><td>fluid</td><td>independently</td>

<td>controlled</td><td> (404)</td><td> , (408),</td><td>(412), is</td><td>possible in some</td>

cases, as mentioned, use less. For example, instead of using a dedicated wash solution (428) to rinse the drug reservoir (108), the drug solution (420) can itself be used for that purpose. In these modalities, two independent fluid channels (404), (412) - one (404) to infuse the drug (420) and a second (412) to aspirate the liquid (436) out of the reservoir (108) - will suffice .

Tool (400) may also include governing circuitry (444) to control and drive the first and second pumps (412), (424), vacuum suction (432), flow change, or valve system (440) , the bubble detectors (442), and / or the voids interacting with the gas eliminators (446). The control logic on which the governing circuitry (444) is based may be implemented as any computer program, physical equipment device (hardware), or a combination thereof that is capable of achieving the functionality described herein. . For example, the governing circuitry (440) may be a specific application integrated circuit (ASIC, "SftiaFazMe" c33L

<img file="MX339941B_D0043.tif" />

MEXICAN INSTITUTE • n. „,. , PROPERTY κ o-— or a gate arrangement^INIo? eⁱ'&gt; &lt;5 am* »^r'^B1 Programmable (FPGA) alternative, the governing circuitry (440) can be one or more general-purpose microprocessors (for example, any of the PENTIUM microprocessors supplied by Intel Corp.) programmed using any suitable programming language or languages ​​(for example, C ++, C #, java, Visual Basic, LISP, BASIC, PERL, etc.). Proper control programming is implemented without complications by those skilled in the art without undue experimentation.

In one embodiment, tool (400) is configured to carefully control the refilling process so that the pressure within the drug reservoir (108) (i.e., the pressure of the fluid at an outlet of the needle (200)) does not exceeds a certain critical value. This prevents damage to the pump (100) and also prevents the unwanted expulsion of the drug through the cannula (120) and into the patient. The pressure within the drug reservoir (108) must be maintained below the critical value in several ways. For example, if liquid is infused into the drug reservoir (108) pneumatically, then the governing circuitry (444) can keep the injection pressure below the critical value. A relay pressure release valve can also be used in pneumatic drive as a failsafe mechanism.

<img file="MX339941B_D0044.tif" />

MEXICAN INSTITUTE OF INDUSTRIAL PROPERTY

As another example, if the liquid is infused using mechanical pumps (eg, gear, diaphragm, peristaltic, syringe, etc.), the pressure within the drug reservoir (108) can be controlled by integrating a pressure sensor at the point of higher hydraulic pressure. The governing circuitry (444) can monitor the pressure sensor and employ a conventional feedback system to prevent the pressure at this point from exceeding the critical value. As yet another example, the governing circuitry (444) can measure the volume of fluid delivered to the drug reservoir (108) to avoid overloading. In general, it is only when the tank 108 reaches full capacity that the internal pressure begins to rise.

For its part, the needle 200 can be a single lumen needle, or the needle 200 can include first and second lumens therethrough. In the case of the single lumen needle 200, the needle lumen will be in fluid communication with each of the three fluid channels 404, 408, 412, as illustrated in FIG. 11, or, where a separate wash solution (428) and pump (424) thereof are not used, just with each of the first and third channels (404), (412). In the case of the double lumen needle (200), the first and second lumens can be fluidly isolated from each other. As illustrated in Figure 12, the first lumen may be in fluid communication with the first and second channels 404, 408 (or just

<img file="MX339941B_D0045.tif" />

. MEXICAN INSTITUTE OF THE PKOWDAD with the first channel (404) where the cfe ^ Tava 'solution separated (428) and the pump (424) of the same itu sun used ·) —and the second lumen can be in fluid communication with the third channel (412).

Example methods of charging and / or recharging the drug reservoir (108) of the pump (100) can be understood with reference to Figures 11 and 12. Referring first to Figure 11, in this example, the entire process of Refilling is conducted through a single needle (200) (having a single lumen) and a single charging port (152) of the implantable drug delivery pump (100). The three valves (A), (B), and (C) in the valve system (440) are initially closed as the needle (200) is inserted into the loading port (152). As previously described with reference to Figures 6A-6D, the needle (200) can be advanced into the loading port (152) until its tip contacts the stop (220) and its outlet port is in fluid communication with the drug chamber or reservoir (108). At that point, the governing circuitry (444) can cause valve (C) to open and any fluid in reservoir (108) can be removed using suction. In particular, the governing circuitry (444) can cause the vacuum suction pump (432) to apply negative pressure to the third fluid channel (412) so that it sucks up any fluid in the drug reservoir (108) within the reservoir of waste (436). The pump

<img file="MX339941B_D0046.tif" />

<img file="MX339941B_D0047.tif" />

Vacuum suction (432) can then be turned off and valve (C) will be closed by the governing circuitry (47Γ4Τ. Circuitry (444) can then cause valve (A) to open and the second pump (424) to apply a positive pressure to the second fluid channel (408) so that a wash solution is drawn from the wash tank (428) through the second channel (408) and the lumen of the needle (200) into the drug chamber ( 108). Once enough wash solution (428) has been pumped into the drug reservoir (108), the governing circuitry (444) can cause the second pump (424) to be shut off and the valve (A) to be closed. These two steps can be repeated as many times as necessary for effectiveness. Alternatively, during these two steps, valves (A) and (C) in valve system (440) can constantly be kept open, the second pump (424) can continuously pump flush solution into the drug reservoir (108 ), and the vacuum suction pump (432) can continuously remove fluid from the drug reservoir (108). In this way, the washing and emptying of the drug tank (108) occurs in cascade. In yet another embodiment, where a separate wash solution (428) and pump (424) thereof are not used (as described above), the drug reservoir (108) of pump (100) may instead be rinsed, during this purging step, with the drug solution (420). To do this,

<img file="MX339941B_D0048.tif" />

X -λ.,. , -. · ;,

MEXIC INSTITUTE.-! Ο -'¡Υ - '., · Λ

FROM THE PrhJrIt Γ? Λ 3

|, | _'Σ— '^ ¡^ &gt;&gt; a C¿fJ first pump (416) are operated by the gufaernarTúg ^' t ^ '^ j circuitry in a manner similar to that described just for valve (A) and the second pump (424), respectively.

After the final waste removal step is completed and the drug chamber (108) has been flushed, the governing circuitry (444) can close valves (A) and (C) and open valve (B) to load depositing drug (108) with drug solution (420). In particular, once valve (B) opens, governing circuitry (444) can cause the first pump (416) to apply positive pressure to the first fluid channel (404) so ​​that it conducts drug from reservoir (420). , through the first channel (404) and the lumen of the needle (200), to the drug reservoir (108) of the implanted drug delivery pump (100). Once a sufficient amount of the drug solution (420) has been pumped into the drug reservoir (108), the governing circuitry (444) can cause the first pump (416) to shut down and the valve (B) to be closed.

During the entire process described with reference to Figure 11, the flow rates of the various fluids and the various injection and suction pressures can all be controlled by the governing circuitry (444). For example, the governing circuitry (444) can monitor or track the pressure in the pressure chamber.

IJ

ΊΠΎ ivir j ιτυτο μ · χ; γ, ·,.; · .'Ζ OF THE PROFi í Z ',} \.'_K.

.Vi J

INSTITUTE K · drug (108), as described above, pfáráp) A¡ev that exceeds a critical value.

Referring now to Figure 12, in a second example, the entire refilling process is conducted through a single needle (200) (having a double lumen structure) and a single pump charge port (152) implantable for drug delivery (100). The two lumens of the needle (200) provide two isolated, parallel paths for fluid to travel in and out of the drug reservoir (108). As indicated in figure 12, one of these lumens can be in fluid communication with the third channel (412) and be dedicated to the aspiration of fluid from the drug tank (108), while another lumen can be in fluid communication with the first and second channels (404), (408) (or only the first channel (404) where a separate wash solution (428) and the pump (424) thereof are not used) and be used to infuse liquid (that is to say, drug and / or wash solutions (420), (428)) within the drug reservoir (108).

The three valves (A), (B) and (C) in the valve system (440) are initially closed as the needle (200) is inserted into the loading port (152). Then, once the needle (200) has been properly inserted, the governing circuitry (444) opens the valve (C) and any fluid in the drug reservoir (108) is removed by suction. The ruling circuitry (444)

<img file="MX339941B_D0049.tif" />

It then pumps the drug reservoir (108) filled with the wash solution (428) by opening the valve (A). Again, during this last step, the suction can either be turned off and perform multiple suction / flushing steps (by opening and closing valves (A) and (C) alternately), or the suction may stay on to perform a continuous rinse. of the drug reservoir (108). In both cases, once the final waste removal step is complete and the drug chamber (108) has been purged, the valves (A) and (C) can be closed by the governing circuitry (444) and the valve (B) open to fill the drug reservoir (108) with the drug solution (420).

Again, the flow rates of the various fluids and the various injection and suction pressures can all be controlled by the governing circuitry (444), for example to prevent the internal pressure for the drug reservoir (108) from exceeding a critical value. Furthermore, as described above, the separate wash solution 428 and pump 424 therefor may be omitted and instead use the drug solution 420 as the wash / rinse solution.

Figure 13 shows the tool (400) coupled to an input and deployment device (448) in accordance with an embodiment of the invention. More specifically, a cartridge 452, in which can house the pumps 416, 424, 432,

<img file="MX339941B_D0050.tif" />

tanks 420, 428, 436, channels 404, 408, 412, and valve system 440 shown in FIG. 10, is coupled at one end to the entry and deployment (448) and at the other end to the needle (200). The governing circuitry (444) is commonly part of the input and display device (448), but may in other embodiments be part of the cartridge (452) and interact with the input and display device (448). As shown, the input and display device (448) has one or more input buttons (456) and a display screen (460). The display screen (460) can display, for example, the drug and / or the dose of it that is administered, the cycle in which the tool (400) is (for example, emptying, rinsing, loading, waiting , or ready), the status of the implantable pump (100) (eg, full, empty), the pressure within the drug reservoir (108), or any other information of interest to a tool operator (400). For their part, the input buttons (456) allow an operator to control the tool (400) (for example, select the dose of the drug that is administered, the mode of operation, the parameters related to pumping and bleeding, and the drug which will be loaded into the drug reservoir (108)), to navigate through various options presented by the display screen (460), etc.

<img file="MX339941B_D0051.tif" />

As understood by someone of ordinary skill in the art, the tool (400) described with reference to Figures 10-13 can also be used to empty, rinse, and / or charge / recharge the electrolyte chamber (112). One way to do this is simply to replace the drug solution (420) with an appropriate electrolyte solution, and then operate the tool (400) as described above.

Accordingly, as described herein, an operator can quickly or accurately charge the drug reservoir (108) and / or the electrolyte chamber (112) of the implantable drug delivery pump (100) in situ by one or more self-sealing charging ports (152), accessible by means of a needle. Furthermore, as described, this can be done in a way that minimizes the risk of damage to the pump 100, and thereby maximizes its effective lifetime.

Having described certain embodiments of the invention, it will be apparent to those of ordinary skill in the art that other embodiments incorporating the concepts disclosed herein can be used without departing from the spirit and scope of the invention. Therefore, the described modalities should be considered in all aspects as illustrative only and not restrictive.

<img file="MX339941B_D0052.tif" />