A drug-infusing device is implanted into a body cavity such as a bladder. The device is implanted in an uninflated, low profile state. After insertion into the body cavity, the device is filled with a substance, such as a drug, and assumes an increased profile. After the device is filled, it is allowed to float freely within the body cavity. Alternatively, the device can be tethered to a wall of the body cavity. The device delivers the drug at a controlled rate over an extended period of time. In order to deliver the drug at a controlled rate, the device preferably has a pressure-responsive valving member. The flow resistance of the valving member is responsive to the pressure at which the drug is stored within the infusing device. The resistance of the valving member decreases as the pressure within the infusing device decreases, thereby providing a resultant controlled flow rate.

BACKGROUND OF THE INVENTION
 I. Field of the Invention
 The present invention relates to an infuser suitable for use within the
 bladder and methods of using the infuser.
 II. Description of the Related Art
 Delivery of drugs to the bladder is typically accomplished systemically.
 Systemic drug delivery through oral, intravenous, intramuscular, or
 transdermal administration methods carries with it the obvious drawbacks
 of any systemic treatment, such as side effects. The drug may also be
 metabolized or altered by physiological processes, and the ultimate
 quantity of active drug that reaches the bladder may be reduced. In
 addition, because many drugs are not well tolerated systemically, the
 dosage must be limited, thereby reducing the total effective dose that
 reaches the bladder.
 Delivery of drugs to the bladder can also be accomplished by retrograde
 injection of the drug into the bladder via catheter. Retrograde
 introduction of drug via a urethral catheter, however, is suitable only
 for limited situations and has inherent drawbacks. See for example,
 Bladder Tissue Pharmacokinetics of Intravesical Taxol, Song, D, Wientjes,
 M G, Au, J L, Cancer Chemotherapy and Pharmacology, 1997, 40(4): 285-92;
 The Pharmacokinetics of Intravesical and Oral Oxybutynin Chloride, Massad,
 C A, Kogan, B A, Trigo-Rocha, F E, Journal of Urology, 1992, Aug., 148(2
 Pt 2): 595-7; Advances in Drug Delivery and Targeting, Goldstein, D,
 Lewis, C, Current Opinion in Oncology, 1991 Dec. 3(6): 1096-104; and
 Intravesical Hyaluronic Acid in the Treatment of Refractory Interstitial
 Cystitis, Morales, A, Emerson, L, Nickel, J C, Urology 49 (Suppl 5A):
 111-113, 1997. Retrograde introduction of drug via urethral catheter is
 primarily used only in a hospital or managed care situation. It is not
 suitable for treatment of chronic urinary-tract conditions.
 Stephen et al., U.S. Pat. No. 5,301,688, discloses a method for treating
 bladder cancers through electromotive administration of drugs into the
 bladder via a catheter. This type of treatment is suitable primarily for
 care administered on an inpatient or out-patient basis, not for chronic
 treatment.
 Tsukada, U.S. Pat. No. 5,219,334 discloses an infuser for connection to a
 catheter that is suitable for long-term delivery of drug into a patient
 through the catheter. This device requires continuous catheterization in
 order to function adequately.
 Pryor et al., U.S. Pat. No. 5,062,829, discloses a helical device for
 insertion into a body cavity, e.g., the rumen of a bovine. The helical
 device includes a drug that can be released over time and further includes
 a biodegradable portion so that, upon exhaustion of the drug, the device
 can break up and be naturally eliminated.
 Garay et al., U.S. Pat. No. 4,925,446, discloses an infusion device having
 an annular shape that is suitable for delivering materials into the
 stomach over a prolonged period of time.
 None of these prior art devices address the problem of intravesical drug
 delivery where drug delivery is intended to continue over a prolonged
 period of time while the patient maintains an active lifestyle.
 Two of the major causes of urge incontinence are detrusor instability and
 hyperreflexia Oxybutynin is a pharmacological agent that has been used to
 treat urge incontinence with some success. This drug is an anticholinergic
 agent that blocks contraction to the bladder and has direct smooth muscle
 relaxant properties. Unfortunately, this drug is associated with
 significant side effects upon oral administration, including dry skin, dry
 mouth, blurred vision, constipation, and urinary retention. In patients
 with cardiovascular disease, oxybutynin may lead to tachycardia. Because
 of the side effects, the accepted oral dose of oxybutynin is limited to
 10-15 mg per day.
 Interstitial cystitis is a debilitating condition in which the lining of
 the bladder is irritated, creating a sense of urgency and pain. The
 condition results in extreme frequency of urination, sometimes as many as
 40, 50, or more times per day and can lead to cystectomy. Sufferers of
 interstitial cystitis can be treated by administration of certain drugs,
 including pentosanpolysulfate, manufactured by Bene of Munich, Germany and
 distributed by ALZA Corporation of Palo Alto, Calif. under the trademark
 ELMIRON. However, there is currently no satisfactory method for delivery
 of pentosanpolysulfate to a patient over a prolonged period of time while
 permitting the patient to enjoy a relatively normal lifestyle.
 There is a need for a site specific delivery system of drugs for treating
 bladder and urinary tract disease that will avoid the side effects
 associated with these pharmacological agents and allow the patient to
 enjoy an active lifestyle.
 SUMMARY OF THE INVENTION
 In one aspect of the present invention, there is provided an implantable
 infusion device comprised of a reservoir containing a drug and a
 flow-restricted exit port in fluid communication with the drug in the
 reservoir. The device also is comprised of a coating adapted to inhibit
 deposition of material on the device when implanted in a body cavity of a
 mammal. For example, the coating may inhibit deposition of materials
 present in the urinary tract. The coating may be a sulfated polysaccharide
 such as pentosanpolysulfate. The coating may be a surface coating on
 surfaces of the device exposed to the body upon implantation. The coating
 may be impregnated into the device. In addition or alternatively, a
 coating may be applied to the device to increase its lubricity.
 The flow-restricted exit port may provide delivery of the drug over a
 period of at least 24 hours, 5 days, 15 days or more. The drug may be in a
 liquid form and the device may deliver the drug at a rate of less than
 about 400 .mu.l/hour.
 The device may assume a first shape during implantation and a second shape
 after implantation into the mammal. For example, the device may assume the
 first shape when empty and the second shape when filled. The first shape
 may be generally elongated and the second shape may be arcuate. The
 reservoir of the device may be elastomeric.
 The drug within the device may be effective to treat incontinence such as
 urge incontinence. For example, the drug may be oxybutynin. The drug may
 also be an anesthetic, analgesic, antibiotic, or anti-cancer agent.
 Additionally, the drug may be used to treat cystitis.
 The device may have a first end and a second end. One of the ends may be
 buoyant or both the first end and the second end may be buoyant. The
 device may be sized to fit through a urethra into a mammalian bladder.
 Another aspect of the present invention relates to an implantable infusion
 device comprised of an elongated elastomeric portion having a first end
 and a second end and adapted to contain and pressurize a liquid. The
 device may also comprise a flow controller providing an exit port in fluid
 communication with the liquid in the elastomeric portion. The flow
 controller may provide for controlled release of the liquid from the
 device. The device may also comprise a relatively inextensible member
 connecting the first and second ends of the elastomeric portion in such a
 way as to allow a relatively straight configuration of the device when
 unfilled with the liquid and to urge a curved configuration of the device
 when filled with the liquid. The relatively inextensible member may be
 inside the elastomeric portion. The elastomeric portion may include a wall
 and the relatively inextensible member may be associated with the wall.
 Alternatively, the relatively inextensible member may form a part of the
 wall. The relatively inextensible member may also be outside of the
 elastomeric portion.
 The implantable infusion device may further comprise an
 encrustation-resistant coating on the device. For example, the coating may
 be pentosanpolysulfate. The device may comprise a buoyant portion at the
 first end. In addition, the device may comprise a buoyant portion at the
 second end.
 Another aspect of the present invention relates to a system for implanting
 an infusion device. The system is comprised of an elongated infusion
 device adapted to change shape when filled. The system is also comprised
 of an introducer suitable for insertion in vivo into a patient and
 releasably enclosing the infusion device. A conduit is associated with the
 introducer and releasably attached to the infusion device. The conduit is
 used to fill the infusion device with liquid in vivo. The conduit may be
 inside the introducer. The conduit may be attached to a releasable valve
 on the infusion device. For example, the releasable valve may be a septum
 seal and the conduit may include a needle for piercing the septum seal.
 The device may further comprise an extender located within the introducer
 adapted to push the infusion device distally from the introducer.
 Another aspect of the present invention relates to a method for delivering
 a drug to a patient. The method comprises the steps of delivering an
 infusion device into the bladder of a patient, releasing the infusion
 device into the bladder to float freely in the bladder, and infusing a
 drug into the bladder from the freely floating infusion device. The
 infusing step may comprise the step of pressurizing the drug with an
 elastomeric member and releasing the drug at a controlled rate from the
 infuser. The method may also comprise the step of filling the infusion
 device with the drug while the device is in the bladder. The filling step
 may induce the infusion device to change shape. The change of shape may
 comprise a change in profile. The change of shape may be from a straight
 configuration when empty to a curved configuration when full. The
 delivering step may comprise the step of inserting the infusion device
 through the urethra into the bladder in an unfilled state inside an
 introducer, then releasing the infusion device from the introducer into
 the bladder. Alternatively, the delivering step may comprise extending at
 least a portion of the infusion device from the introducer, and then
 filling the device within the bladder. In addition, the device may be
 tethered to the bladder wall.
 The method may also comprise the step of removing the infusion device from
 the bladder after the infusing step. The infusion device used with the
 method may assume a first shape when empty and a second shape when filled.
 The removing step may comprise the step of changing the shape of the
 infusion device from the second shape to the first shape, and then
 directing the infusion device out of the urethra. The change from the
 second shape to the first shape may be accomplished by allowing drug in
 the device to be depleted by the infusing step. The change from the second
 shape to the first shape may be accomplished by opening a passageway in
 the device to allow any remaining drug in the device to exit the device.
 In this case, the method may further comprise the step of directing drug
 from the passageway through a conduit and out of the bladder. Removing the
 device may comprise passing the device out of the urethra with a flow of
 urine. Alternatively, removing the device may comprise capturing and then
 withdrawing the device.
 Infusing a drug into the bladder may comprise controlling the rate of flow
 of drug from the device into the bladder. Controlling the flow of drug may
 be accomplished by means of a pressure-responsive valve. For example, the
 drug may be under pressure and the pressure-responsive valve may control
 the flow by varying the area of a flow channel in inverse proportion to
 the pressure of the drug. In addition, the control of the flow may be
 further accomplished by a flow-resistive element positioned in a fluid
 flow path upstream of the pressure-responsive valve, thereby reducing the
 pressure of the drug entering the pressure-responsive valve.
 The infusing step of the method may comprise infusing the drug into the
 bladder for at least about 5 days. The drug used with the method may be
 used to treat incontinence such as urge incontinence. For example, the
 drug may be oxybutynin. The drug may also be used to treat pain, neuralgia
 or cystitis. The drug may be an antibiotic or an anti-cancer drug.
 Another aspect of the present invention relates to an infusion device
 comprised of a housing, a drug inside the housing, a flow controller for
 controlling the rate at which drug may be released from the housing, and a
 coating of pentosanpolysulfate on the device. The drug may be pressurized
 and the flow controller may be pressure-responsive. The flow controller
 may comprise a first pressure reducing element, a second pressure reducing
 element, and a flow channel through the first and second pressure reducing
 elements. The second pressure reducing element may alter a cross-sectional
 area of the flow path in a manner inversely related to the pressure of the
 drug.
 In yet another aspect of the present invention, an implantable infusion
 device may comprise an elongated reservoir having a first shape wherein a
 cross-sectional diameter of the elongated reservoir permits the elongated
 reservoir to be passed through a mammalian urethra. The elongated
 reservoir may be configured to expand to a second shape to hold a
 pressurized fluid substance. A check valve assembly may be disposed at a
 first end of the elongated reservoir and configured to admit the
 pressurized fluid substance into the elongated reservoir while the
 elongated reservoir is within a mammalian bladder. A flow-restricted exit
 port may be configured to dispense the pressurized fluid substance from
 the elongated reservoir while the elongated reservoir is within the
 mammalian bladder. In addition, the device may comprise a tethering means
 for tethering the device to a bladder wall. The first shape of the device
 may have a linear configuration with at least one axis of symmetry and the
 second shape may have a curved configuration that has no axial symmetry.
 The flow-restricted exit port may provide a means of rapidly purging the
 pressurized fluid substance from the elongated reservoir. The device may
 comprise a capture member which is incorporated into a release mechanism
 that is configured to allow the flow-restricted exit port to rapidly purge
 the pressurized fluid substance from the elongated reservoir. The
 flow-restricted exit port may be configured to mate with a sheath that is
 introduced into the mammalian bladder such that the pressurized fluid
 substance is rapidly dispensed through a channel of the sheath rather than
 into the mammalian bladder. The pressured fluid substance may be a
 diagnostic tool. The check valve assembly may comprise an floating disc
 which is biased to occlude an input channel. The device may comprise a
 means for tethering the device to the bladder wall. In addition, the
 device may comprise one or more of the features previously enumerated.

DETAILED DESCRIPTION OF THE INVENTION
 The present invention includes a unique intravesical infuser device
 suitable for delivery into a body cavity such as the bladder. The device
 can be filled with a substance, which results in a reversible shape change
 to prevent voiding of the filled device or obstruction of the bladder
 neck. The device provides controlled site specific delivery of the drug
 into the bladder over an extended period of time.
 With reference to FIG. 1, the infuser 10 has a proximal end 12 and a distal
 end 14. In general, for the infuser 10 to be appropriate for use in a
 human bladder, the uninflated length of the infuser 10 should be about 4
 inches and may be in a range of about 3 to 6 inches long. The uninflated
 diameter of the infuser 10 should be about 0.25 inches. Extending between
 the proximal end 12 and the distal end 14, in one preferred embodiment, is
 an elastomeric pressure member 16 suitable for containing and pressurizing
 a liquid or fluid drug. The elastomeric pressure member 16 may be made of
 any suitable elastic medical grade polymer and is preferably made of
 medical grade dimethyl siloxane (silicone). For example, the elastomeric
 pressure member 16 may be USP class VI silicone tubing, 60 +/-10 Shore A
 with a peroxide cure, having approximately a 3/16 inch inner diameter and
 approximately a 1/4 inch outer diameter. The elastomeric pressure member
 16 can also be made of other elastic materials such as coated or uncoated
 polyurethanes, polystyrenes, butyl rubbers, latex rubber or other natural
 or synthetic elastomers. The elastomeric pressure member 16 may be about
 half an inch shorter than the infuser 10. A proximal end cap 20 may be
 provided at the proximal end 12. The proximal end cap 20 may be about 0.44
 inches long and about 0.25 inches in diameter.
 A distal end cap 22 is similarly provided at the distal end 14 of the
 infuser 10. The distal end cap 22 is about 0.57 inches long and 0.25
 inches in diameter.
 A proximal collar 24 may be used to secure the pressure member 16 to the
 proximal end cap 20. Similarly, a distal collar 26 may be used to secure
 the pressure member 16 to the distal end cap 22 of the infuser 10. The
 proximal end cap 20, proximal collar 24, distal end cap 22, and distal
 collar 26 may be formed of any relatively rigid thermoplastic polymer,
 having long-term biocompatibility in vivo, such as G. E. Ultem 1000 from
 General Electric of Pittsfield, Mass. The infuser 10 may be assembled
 using a variety of adhesive compounds, such as an epoxy.
 A proximal opening 30 is provided at the proximal end 12 of the infuser 10,
 for introduction of fluid into the pressure member 16. The diameter of the
 proximal opening 30 may be about 0.1 inches. A distal opening 32 is
 provided at the distal end 14 of the infuser 10, through which drug
 pressurized by the pressure member 16 exits the infuser 10 at a controlled
 rate. The diameter of the distal opening 32 may be about 0.07 inches. Of
 course, modifications and adaptations of the device are contemplated
 herein both openings 30, 32 are at one end, or wherein one opening serves
 for the purpose of filling, delivery and purging.
 FIG. 2 illustrates the infuser 10 in its filled or inflated state. Whereas
 the empty infuser of FIG. 1 is relatively straight in profile and the
 pressure member 16 may be somewhat flaccid, the filled infuser 10
 illustrated in FIG. 2 is stretched causing the pressure member 16 to be
 relatively rigid. The embodiment illustrated in FIG. 2 includes a tensile
 member 34 connecting the proximal end 12 and the distal end 14. The
 tensile member 34 may be made from a variety of generally inextensible
 materials, including wire, fabric or polymer. For example, the tensile
 member 34 can be a polyester ribbon approximately 0.006 inches thick by
 0.085 inches wide as supplied Berwick industries, Inc. of Berwick, Pa.
 When the pressure member 16 is inflated or filled with a substance, the
 tendency is for the pressure member to extend both radially and axially.
 However, axial extension is inhibited by the tensile member 34. As a
 result, the infuser assumes a non-linear profile. In the embodiment
 illustrated in FIG. 2, the infuser 10 assumes a crescent or annular shape
 as a result of the tension induced by the tensile member 34. When the
 device is used as an intravesical infuser 10, the non-linear shape may
 advantageously inhibit undesirable spontaneous or accidental voiding of
 the filled or inflated infuser 10. In general, for the infuser 10 to be
 appropriate for use in a human bladder, the inflated volume of the infuser
 10 may be about 30 cc to about 40 cc. However, in some cases, it may be
 advantageous to increase the inflated volume above 60 cc or decrease it
 below 10 cc. Although the shape illustrated in FIG. 2 is a crescent, it
 will be understood that other shapes, including sinusoidal, helical,
 supercoiled, and random folded shapes are also within the scope of the
 present invention. From another perspective, it should be understood that
 the shape change that prevents accidental voiding of the device is a
 change in profile. Thus, if the device when implanted has a cylindrical
 shape with a diameter of 6 mm, for example, allowing it to readily
 traverse the urethra, it may well have a crescent shape with a annular
 diameter of 150 mm, 200 mm, or more when filled in the bladder. This
 change in profile itself can reduce the chance of accidental voiding.
 One feature of the shape-changing is that a first shape facilitates the
 placement of the infuser in the bladder through the urethra and a second
 shape prevents spontaneous voiding of the infuser. Preferably, the second
 shape also facilitates micturition by retaining a shape which does not
 occlude the bladder neck. For example, in the embodiment described above,
 the cylindrical first shape has a diameter that is less than the diameter
 of the urethra so that it may be placed into the bladder through the
 urethra. Once inserted, the infuser in the annular second shape does not
 pass out the urethra nor does it block the bladder neck and prevent the
 patient from micturating.
 As the contents of the device are dispensed into the bladder, the device
 may experience at least a partial shape change reversal. The shape change
 reversal may facilitate removal of the device. In one embodiment, the
 device has shape memory so that the device does not return to its original
 shape simply by dispensing its contents. In this way, even after
 dispensing some or all of the contents of the device, the device retains a
 shape which does not pass out the urethra or block the bladder neck.
 FIG. 3 illustrates the infuser 10 in longitudinal cross-section in a
 flaccid state. The infuser 10 illustrated in FIG. 3 includes an optional
 capture member 36 at both the proximal end 12 and distal end 14 of the
 infuser 10. The capture member 36 may be a loop of suture material such as
 suture 2-0, thermoplastic polymer, silicone, polytetrafluoroethylene, or
 any other suitable biocompatible material. Although a loop configuration
 is illustrated, any other suitable configuration capable of being attached
 or grasped by a retrieval device may be used. Such configurations would
 include molded handles or latching mechanisms in the infuser device 10
 itself.
 As seen in more detail in FIG. 4, the proximal end cap 20 is adapted to
 receive a hypodermic needle 38. The hypodermic needle 38 inserted into the
 proximal opening 30 can extend through a guide channel 40 to encounter a
 valving member 42. In the illustrated embodiment, the valving member 42 is
 a septum seal. The valving member 42, when configured as a septum, is
 preferably made of silicone, rubber or other biocompatible elastomeric or
 viscous material. For example, the valving member 42 may be made of a
 2-part silicon potting compound supplied by A. E. Yale Enterprises of San
 Diego, Calif. under the part numbers VSI 1065A and VSI HI PRO GREEN. The
 valving member 42 may be about 0.25 inches long and 0.161 inches in
 diameter. Septum seals, such as the valving member 42, may be pierced one
 or more times to allow access to the interior of a vessel, while resealing
 after the piercing device is removed. In the present invention, the
 combination of the guide channel 40 and the septum seal 42 tend to retain
 the infuser 10 firmly attached to the hypodermic needle 38 during
 introduction of the infuser 10 into the bladder. Still with reference to
 FIG. 4, the proximal end cap 20 may advantageously comprise an outer shell
 44 that is generally cup-shaped. A smaller needle port 46 fits
 concentrically inside the outer shell 44. The needle port is tube-shaped
 with a small proximal end extending to the proximal opening 30 and
 defining the guide channel 40 as the needle port 46 extends in a
 distal-direction. An annular flange 50 extending radially outwardly from
 the guide channel 40 attaches the needle port 46 to the interior of the
 outer shell 44. Thus, the needle port 46 surrounding the guide channel 40
 is glued, ultrasonically welded, or otherwise suitably attached to the
 outer shell 44 at the proximal opening 30 and is also attached by means of
 the flange 50 to the distal portion of the outer shell 44. The embodiment
 of the proximal end cap 20 illustrated in FIG. 4 further includes a septum
 retainer 52 sitting concentrically inside the distal end of the outer
 shell 44 and extending distally therefrom. The proximal end of the septum
 retainer 52 abuts against the annular flange 50. The distal end of the
 septum retainer 52 extends distally from the outer shell 44, coaxially
 with the outer shell 44. In one preferred embodiment, the septum retainer
 52 includes ridges or grooves 54 for retaining the pressure member 16
 securely with the proximal end cap 20. The inner diameter of the annular
 septum retainer 52 narrows at the distal end thereof. When assembled into
 the outer shell 44 to abut the flange 50, the septum retainer 52
 compresses the septum 42 against the flange 50 at the proximal end of the
 septum 42 and against the narrowed portion of the septum retainer 52 at
 the distal end thereof.
 The pressure member 16, which is preferably in the form of a tube, is slid
 over the outside of the distal portion of the septum retainer 52. It is
 then locked in place on the proximal end cap by the proximal collar 24
 that traps the pressure member 16 tightly between the septum retainer 52
 and the proximal collar 24, providing a leak-proof seal. Retention of the
 pressure member 16 under pressure is facilitated by the ridges or grooves
 54 on the septum retainer 52. The proximal collar 24 may advantageously
 further secure the capture loop 36 by capturing the ends of the capture
 loop 36 under the proximal collar 24. Similarly, the pressure exerted
 radially inwardly by the proximal collar 24 can be used to secure a
 tensile member 34. The tensile member 34 is preferably trapped between the
 pressure member 16 and the septum retainer 52 by the pressure exerted by
 the proximal collar 24 on the proximal end of the pressure member 16.
 With reference again to FIG. 3, the distal end 14 of the infuser 10
 provides controlled release of the drug from the pressure member 16 by
 means of the distal opening 32. In the illustrated embodiment, a linear
 resistor 56 is provided to control the flow of fluid from the interior of
 the pressure member 16 through the distal opening 32. In early prototype
 versions of the infuser 10, the linear resistor 56 comprises a small
 cotton string, suture or other suitable resistor element 60 surrounded by
 an impervious coating 62. We have found that cotton crochet thread
 surrounded by heat-shrink polyolefin material makes a satisfactory linear
 resistor 56. One satisfactory cotton crochet thread is 4 strand white
 wound cotton fiber approximately 0.022 inch in diameter manufactured by
 Coats and Clark, Inc. of Greensville, S.C. under the part number Article
 C-44. A cotton crochet thread manufactured by Coats and Clark, Inc. of
 Greensville, S.C. under the trademark CROSHEEN can also be used. One
 satisfactory impervious coating 62 is heat shrink polyolefin with an
 expanded inner diameter of 0.032 inches supplied by Raychem, Menlo Park,
 Calif. The resistance generated by the linear resistor 56 is a function of
 its length, diameter and the materials from which it is constructed, and,
 for any given pressure, the flow rate for a particular linear resistor 56
 can readily be determined by empirical methods. For example, the suitable
 resistor element 60 may be about 0.5 inches to 10 inches long. In the
 general case, it is typically advantageous if the infuser 10 flow rate
 remains constant within about +/-50%, preferably +/-30% or +/-20% over a
 variety of pressure conditions.
 In one preferred embodiment of the invention, the end caps 20, 22 include
 air pockets 64 to provide buoyancy. Of course, as an alternative to the
 use of air pockets, the ends caps 20, 22 could instead be made of low
 density material or could include air bladders inside or outside the end
 caps 20, 22 or other suitable means for promoting buoyancy. By making the
 end caps 20, 22 lighter than the rest of the infuser 10, the caps 20, 22
 will tend to float. Because the urethra is located in the bladder neck
 generally at the bottom of the bladder when a person is standing erect,
 the end caps 20, 22 will tend to float when the bladder fills and during
 micturition. This, in turn, presents the curved middle portion of the
 curved infuser 10 to the exit of the bladder. Because this curved portion
 extends generally transversely to the direction of flow, it is unlikely
 that the filled or inflated infuser 10 would be accidentally voided or
 would obstruct the bladder neck while the infuser 10 is in a curved or
 arcuate configuration with buoyant end caps. The buoyant end caps 20, 22,
 also help to minimize or prevent irritation of the trigone region and neck
 of the bladder, thereby minimizing patient discomfort.
 FIG. 5 schematically illustrates one method for introducing the infuser 10
 into the bladder. An outer sheath 66 is provided into which the infuser 10
 can fit concentrically when in the deflated or unfilled state. After
 transurethral introduction of the outer sheath 66 into the bladder, the
 deflated infuser 10 is passed through the outer sheath 66. Located
 concentrically within the outer sheath 66 is an extender 70 having a
 diameter approximately the same as that of the infuser 10. Finally, a
 hypodermic needle 38, positioned concentrically within the extender 70, is
 inserted into the septum 42 of the infuser 10 to retain the infuser 10
 against the hypodermic needle 38 and prevent loss of the infuser 10 during
 inflation or filling. The hypodermic needle 38 is connected at its
 proximal end to a fluid source (such as a source of liquid drug) (not
 shown). With the outer sheath in place in the bladder, the extender 70 and
 hypodermic needle 38 are used to push the infuser 10 through the outer
 sheath 66 into the bladder. Fluid is then introduced through the
 hypodermic needle 38 to fill the pressure member 16 with fluid and to
 induce a change of shape of the infuser 10. After the infuser 10 is
 filled, the hypodermic needle 38 is disconnected from the infuser 10 and
 withdrawn through the extender 70, The infuser 10 is allowed to float
 freely within the bladder of the patient. The extender 70 and the outer
 sheath 66 are then withdrawn from the bladder of the patient.
 FIG. 19 is a longitudinal cross-section of an alternate embodiment of the
 intravesical infuser in a flaccid state. The infuser 10 illustrated in
 FIG. 19 includes an optional capture member 236 at the distal end 14. The
 distal end 14 of the infuser 10 is also used for normal drug delivery and
 for draining of the drug, if necessary, during the removal process. The
 infuser 10 illustrated in FIG. 19 allows the introduction of fluid under
 pressure into the pressure member 16 through a check valve 242 at the
 proximal end 12. The check valve 242 prevents fluid from exiting the
 infuser through the proximal end 12 of the infuser 10 after the fluid has
 been introduced into the infuser 10. As shown in more detail below, the
 check valve 242 eliminates the need for the hypodermic needle 38 to
 puncture the valving member 42 as shown in FIGS. 4 and 5. The pressure
 valve 242 facilitates a more rapid filling of the infuser 10 by
 eliminating the flow resistance in the hypodermic needle 38.
 The check valve 242 is shown in detail in FIG. 20. A proximal endcap form
 220 is covered by an endcap bumper 224 that is more compliant and softer
 than the proximal endcap form 220. The use of the more compliant material
 on the endcap bumper 224 reduces the trauma caused by contact of the
 proximal end 12 with tissue. In one embodiment, the endcap bumper 224 is
 polymeric material. The proximal end 12 has an opening 230 which permits
 access to a check valve entrance 246. When ample fluid pressure presses
 upon a floating disc 244 at the distal end of the check valve entrance
 246, the floating disc 244 is displaced and moves away from the valve
 entrance 246 allowing fluid to enter a fluid chamber 250. The fluid in the
 fluid chamber 250 enters the lumen of the pressure member 16 through
 grooves in a check valve retainer 252. FIG. 20A is a cross-sectional view
 illustrating more clearly four grooves 254 in the check valve retainer
 252. Pressure generated by the pressure member 16 causes the floating disc
 244 to occlude the check valve entrance 246 upon completion of fluid
 introduction. A small spring 248 maintains a pressure against the floating
 disc 244 to keep the check valve 242 closed even when the pressure within
 the fluid chamber 250 is approximately the same as the pressure within the
 opening 230.
 The distal end 14 of the infuser 10 is shown in detail in FIG. 21. The
 distal end 14 incorporates the optional capture member 236. The capture
 member 236 may be made of similar material as described for the capture
 member 36 such as a 2-0 suture. It is advantageous to have the capture
 member 236 connected from the center of the distal end 14 so that the
 infuser 10 aligns itself with a pulling force applied to the capture
 member 236. The distal end 14 also incorporates a flow restrictor 256 that
 meters the flow of fluid from the pressure member 16 through a distal
 opening 232. The flow restrictor 256 can be made from a variety of
 sintered or porous metal or polymer materials. For example, the flow
 restrictor 256 can be a 0.062 inch diameter, 0.06 inch long cylinder of
 sintered titanium with a pore size of 0.1 microns as manufactured and
 supplied by Mott Corporation of Farmington, Conn. or stacked porous
 polycarbonate membrane discs 13 mm in diameter with a pore sizes of 0.01
 or 0.05 microns manufactured and supplied by Osmonics of Livermore,
 Calif., as catalog numbers 10505 and 10501, respectively.
 The flow restrictor 256 is contained within a flow restrictor housing 280.
 The flow restrictor housing 280 is contained within a distal endcap form
 222 by a valve seat 226. The valve seat 226 seals an interior lumen of the
 distal endcap form 222 constraining fluid in the pressure member 16 to
 flow through a valve seat flow channel 282. An o-ring 286 seals the valve
 seat 226 to the flow restrictor housing 280 constraining the fluid to flow
 through the flow restrictor 256 and not around the flow restrictor housing
 280. A flow restrictor housing spring 284 presses on the flow restrictor
 housing 280 forcing it against the valve seat 226 placing pressure on the
 o-ring 286 maintaining the integrity of the seal between the valve seat
 226 and the flow restrictor housing 280. The distal endcap form 222 is
 covered by a distal endcap bumper 228. The distal endcap bumper 228 is
 made of a compliant material which reduces the trauma caused by contact of
 the distal end 14 with tissue.
 On the outlet side of the flow restrictor 256, a retainer 288 holds the
 capture member 236. The capture member 236 exits the infuser 10 through
 the distal opening 232. The positioning of the capture member 236
 facilitates the removal of the infuser 10 by allowing the device to pulled
 out of the bladder through the urethra. If the capture member 236 is
 pulled while sufficient opposite pressure is maintained against the distal
 endcap bumper 228, the flow restrictor housing spring 284 compresses thus
 releasing the pressure on the o-ring 286. In this way, fluid within the
 pressure member 16 may flow around the flow resistor housing 280. This
 configuration facilitates the rapid purging of the fluid contents of the
 pressure member 16 which decreases the profile of the infuser 10 thus
 facilitating the removal of the device.
 FIG. 26 illustrates a retrieval device 270 which might be used to retrieve
 the infuser 10 from the patient. A capturing element 276 is retractably
 disposed within a retrieval channel 274. To remove the infuser 10, a
 sheath 272 is introduced into the bladder. Once introduced, the capturing
 element 276 is extended into the bladder and engages the capture member
 236. The capturing element 276 is retracted into the retrieval channel 274
 drawing the distal endcap bumper 228 into a sealed fit with a channel
 entrance 278. The compliant material used to form the distal endcap bumper
 228 facilitates sealing between the distal end 14 and the channel entrance
 278. As the pressure against the infuser 10 increases, the flow restrictor
 housing spring 284 compresses thus releasing the pressure on the o-ring
 286 and creating a fluid path from within the elastomeric pressure member
 16 to the retrieval channel 274. In this way, any remaining fluid within
 the infuser 10 may be purged from the infuser 10 to lower the profile of
 the infuser 10 for extraction through the urethra while avoiding the
 introduction of the fluid into the bladder.
 FIG. 22 is a longitudinal cross-section of the proximal end of the infuser
 10 of FIG. 19, in combination with an introducer device. An outer sheath
 266 is provided into which the infuser 10 can fit concentrically when in
 the deflated or unfilled state. After transurethral introduction of the
 outer sheath 266 into the bladder, the deflated infuser 10 is passed
 through the outer sheath 266 into the position shown in FIG. 22. Located
 concentrically within the outer sheath 66 is an extender 262 having a
 diameter approximately the same as that of the endcap bumper 224. At the
 distal end of the extender 262 is a secure coupling fitting 260 that fits
 snugly into the opening 230 of the infuser 10. For example, the secure
 coupling fitting 260 may be a luer fitting. The snug fit of the secure
 coupling fitting 260 into the opening 230 of the infuser 10 prevents loss
 of fluid during filling or inflation. An introducer channel 264 located
 within the extender 262 provides a fluid path for a fluid source (not
 shown) connected at the proximal end of the extender 262. Pressurized
 fluid from the fluid source compresses the small spring 248 and displaces
 the floating disc 244 away from the valve entrance 246. Fluid flows from
 the introducer channel 264 through the valve entrance 246, into the fluid
 chamber 250 and fills or inflates the infuser 10. When filling is
 complete, the fluid pressure in the introducer channel 264 is reduced and
 the floating disc 244 returns to its original position occluding the valve
 entrance 246. The secure coupling fitting 260 is disconnected from the
 infuser 10 and retracted into the extender 262. The retraction of the
 extender 262 releases the infuser 10 to free float in the bladder of the
 patient. The outer sheath 266 and extender 262 assembly are then withdrawn
 from the patient.
 In preferred embodiments of the invention, it is advantageous to provide a
 pressure-responsive valve assembly to control the flow of drug out of the
 pressure member 16 of the infuser 10. Because the pressure profile of an
 elastomeric pressure member infuser decreases over time, as the volume of
 drug (and thus the pressure) inside the pressure member decreases, a
 linear resistor such as element 56 in FIG. 3 provides a time-variable
 flow. It is more advantageous to provide a relatively constant rate of
 drug delivery to the bladder. This can be accomplished, in a preferred
 embodiment, by pressure-responsive valving, as illustrated in FIG. 3A.
 In FIG. 3A, the infuser 10 is generally as described in connection with
 FIG. 3, wherein like reference numerals reflect like parts. However,
 toward the distal end 14 of the infuser 10, a pressure-responsive valve 74
 utilizing movable walls 86 to reduce the area of a flow channel 76 is used
 to control the flow of fluid out of the infuser. Appropriate valving
 mechanisms are described in more detail in connection with FIGS. 6-12, and
 any of the described valves could be adapted for use in the invention.
 The operation of one suitable type of pressure-responsive valve is
 illustrated in FIG. 6. A pressure source P1 directs fluid from a fluid
 reservoir 72 into a valve assembly 74 through a flow channel 76. When the
 fluid reaches the valve assembly 74, the valve assembly 74 is subjected to
 an exterior and interior pressure differential that creates a flow
 resistance proportional to the differential pressure in question. Thus,
 with reference to FIG. 6, the exemplary pressure P1 in the fluid reservoir
 72 is also applied to the exterior of the valve assembly 74. This pressure
 PI reduces the flow area of the portion of the flow of channel 76
 extending through the valve assembly 74 or otherwise increases resistance
 to flow through the flow channel 76, dropping the pressure in the flow
 channel 76 to a lower pressure P3 as it exits the valve assembly 74. The
 fluid continues along the flow channel 76 to the exit 80. In a preferred
 embodiment, a linear resistor 82 is provided between the fluid reservoir
 72 and the valve assembly 74 within the flow channel 76. The linear
 resistor 82 may be of the construction detailed in FIG. 3, or,
 alternatively, may be of any other desired construction, such as a
 serpentine path, capillary tubing or a series of collateral passages. As
 seen in FIG. 6, after the fluid passes through the linear resistor 82, the
 pressure P1 entering the linear resistor 82 has been reduced to a lower
 pressure P2. In that manner, when the pressure P1 is exerted on the valve
 assembly 74 (e.g., on the outside of the valve assembly 74), the ability
 of the pressure P1 to constrict the flow channel 76 within the valve
 assembly 74 will not be counteracted by the pressure P2 as effectively as
 if the pressure in the valve assembly 74 had been P1. Thus, by reducing
 the pressure inside the valve assembly 74, the linear resistor 82
 facilitates effective restriction of fluid flow by the valve assembly 74.
 Note that in this type of pressure-responsive valving, fluid flow can be
 maintained relatively constant despite variations in the pressure of the
 fluid reservoir. That is because higher pressures (which would ordinarily
 facilitate greater flow) are counteracted by greater constriction of the
 flow channel 76 through the valve assembly 74. Conversely, as the pressure
 P1 in the fluid reservoir 72 decreases, the flow channel 76 through the
 valve assembly 74 is increased in size or cross-sectional area, thus
 compensating for the reduced pressure driving fluid through the flow
 channel 76.
 In another preferred embodiment, a second resistor element, exit resistor
 84, is provided between the valve assembly 74 and the exit 80. The exit
 resistor 84 can protect against transient pressure spikes (such as those
 induced by coughing or other increases in abdominal pressure). Such
 pressure spikes, in the absence of exit resistor 84, could send pressure
 backwards through the exit 80, opening up the flow channel 76 through the
 valve assembly 74, and resulting in possible release of a bolus dosage or
 spike.
 One embodiment of a valve assembly 74 is shown in FIG. 7. In this
 embodiment, a linear resistor 82 directs fluid into a first end of the
 valve assembly 74. An exit resistor 84 directs fluid out of the exit 80
 and into the patient. The valve assembly 74 is preferably located within
 the pressure member 16 of the infuser 10. The valve assembly 74 can also
 be located outside of the pressure member 16 of the infuser 10 in fluid
 communication with the interior of the pressure member 16 of the infuser
 10.
 A longitudinal cross-section of the valve assembly 74 is schematically
 illustrated in FIGS. 8 and 9. FIG. 8 illustrates a linear resistor 82
 comprising a resistor element 60 covered by an outer sheath 66 on the
 upstream end of the valve assembly 74. A flow channel 76 extends through
 the valve assembly 74 leading to an exit resistor 84, also having a
 resistor element 60 surrounded by an outer sheath 66. The flow channel 76
 through the valve assembly 74 is defined by one or more movable walls 86.
 The movable walls 86 may be formed of any deformable material, preferably
 in the form of a sheet or a web, such as polyethylene, teflon, polyvinyl
 chloride, polytetraflouorethylene, polyvinylidine chloride, thin stainless
 steel and the like.
 As shown in FIG. 9, when an external pressure (indicated by arrows P)
 impinges on the exterior of the movable walls 86, the movable walls are
 pressed inwardly into the flow channel 76, constricting the flow channel
 76. In this manner, as the pressure P increases, the cross-sectional area
 of the flow channel 76 decreases, thereby constricting the flow of fluid
 through the valve assembly 74. It will be appreciated that a wide variety
 of configurations and materials can be used to construct movable walls
 that will compress against a flow channel upon the application of pressure
 to the movable wall. Any such pressure-responsive valve utilizing a
 movable wall, or other pressure-responsive elements, such as those in
 which the flow pressure acts against a spring or the like, are considered
 to fall within the scope of the present invention.
 A FIGS. 10-12 illustrate certain suitable embodiments of the valve assembly
 74, taken in transverse cross-section to the direction of the flow channel
 76. FIG. 10 illustrates a simple valve assembly 74, featuring at least one
 movable wall 86 against a flow channel 76. In FIG. 10, the flow channel 76
 is defined by two sheets of flexible polymer sealed at their edges 110 by
 any suitable means, such as heat sealing, solvent welding, RF welding,
 crimping, clamping, and the like.
 FIG. 11 is an embodiment similar to that illustrated in FIG. 10, except
 that the movable walls 86 or a surface against which the movable wall 86
 is placed is provided with minimum flow channels 112, such as longitudinal
 grooves, ridges, or the like, to provide at least a minimum flow channel
 through the valve 74 despite the pressure exerted against the movable wall
 86. The minimum flow channels 112 prevent the movable walls 86 from
 sticking together under high external pressure and reducing the flow
 channel 76 to an unacceptably small area. The length, height, and width of
 the flow channels 112 effects the area of the flow channel 76 and thus can
 be chosen to achieve desired flow characteristics of the valve assembly
 74.
 A similar arrangement is illustrated in FIG. 12, in which the patency of
 the flow channel 76 is maintained by a permanently formed ridge 114
 between two longitudinally extending flow channels 112. High external
 pressure would force the movable walls 86 close together, but the
 curvature of the interior of the movable wall 86 (or a ridged surface
 against which is presses) would tended to keep at least a small flow
 channel 76 open under any normal operating pressure. In addition to the
 minimum flow channels 112 or ridges 114, one may advantageously provide
 wicking elements 116, as illustrated in FIG. 12, for maintaining the flow
 channel 76 open or for providing a minimum flow channel in the event of a
 relatively high external pressure. In FIG. 12, the wicking elements 116
 are pictured as having a circular cross-sectional area. In other
 embodiments, the wicking elements may have a rectangular cross-sectional
 area or any other desired shape. Alternatively, the wicking elements may
 be comprised of webbing or a web of flat material. In a similar manner as
 described above, the length and diameter of the wicks 116 effect the area
 of the flow channel 76 and thus can be chosen to achieve desired flow
 characteristics of the valve assembly 74.
 An alternate embodiment of a pressure-responsive valve 74 is shown in FIGS.
 23A-B. A tortuous flow channel 76 is created by bonding the movable walls
 86 to form flow barriers 118. The fluid is constrained to flow around the
 flow barriers 118 to reach the exit resistor 84 and exit the valve
 assembly 74. The movable walls may be bonded using any method for bonding
 thermoplastics such as heat sealing, ultrasound welding, and solvent
 bonding. The number and width of the flow barriers 118 determines the
 degree of constriction of the flow channel 76 by the external pressure
 acting on the valve assembly 74. Increasing the width or number of flow
 barriers 118 acts to reduce the flow through the flow channel 76 at the
 same pressure.
 The design in FIG. 24 displays yet another method for creating a
 pressure-responsive valve. The valve assembly 74 of FIG. 24 has no linear
 resistor 82 as shown in FIG. 7. Instead, an opening 88 is located
 proximally in one movable wall 86 and provides the entrance for fluid into
 the valve assembly 74. The exit resistor 84 is located distal of the
 opening 88. The diameter of the opening 88 and the spacing between the
 opening 88 and the exit resistor 84 effects the amount of fluid leaving
 the valve 74. As the external pressure acting on the valve 74 decreases,
 the diameter of the opening 88 increases, the flow through the valve 74
 increases. The distance between the opening 88 and the exit resistor 84
 effects the area of the flow channel 76 and thus can be chosen to achieve
 desired flow characteristics the valve assembly 74.
 In all the above described embodiments of the valve assembly 74, mechanical
 means were described to effect the flow characteristics of the flow
 channel 76. In addition, material properties of the movable walls 86 can
 be varied to effect the degree of compression caused by the external
 pressure. For example, high durometer polymers compress less and are,
 therefore, less effected by changes in pressure than low durometer
 polymers. Thus, a low durometer polymer provides a greater reduction of
 flow at high pressure by greater compression of the flow channel 76 and,
 therefore, provides a greater range of resistance for a given range of
 pressures than a high durometer material.
 FIGS. 17A and 17B illustrate an alternative pressure-responsive valve
 assembly 142 which operates according to the principles just described.
 FIG. 17A is a cross-section of the valve 142 when the pressure in the
 pressure member 16 is relatively high. The high pressure causes a
 compressible disc 144 to deform and press against a flow plate 146. The
 compressible disc 144 may be made of any suitable pliable material such as
 polystyrene. Varying the physical properties or shape of the discs
 provides a method for effecting the compressibility of the compressible
 disc 114 and thus can be used to achieve desired flow characteristics of
 the valve assembly 74. When pressure is applied, the compressible disc 144
 provides a partial occlusion of the flow channels 148. The partial
 occlusion acts as a resistance to flow. In this way, the pressure in each
 successive valve chamber 150 is less than the preceding chamber. The
 number of chambers which are used depends upon the desired flow rate, the
 pressure range within the pressure member 16 and the patient's bladder,
 the dimensions of the valve 142 and the dimensions and material properties
 of the compressible disc 144. FIG. 17B is a cross-section of the valve 142
 when the pressure within the pressure member 16 has decreased below that
 shown in FIG. 17A. Note that the compressible disc 144 is no longer
 pressing against the flow plate 146 and flow resistance through the flow
 channels 148 has decreased.
 FIGS. 18A and 18B illustrate yet another pressure-responsive valve assembly
 152. FIG. 18A is a cross-section of the valve 152 when the pressure in the
 pressure member 16 is relatively high. The high pressure causes a needle
 154 to press towards a mated seat 156 thereby deforming a spring 158. In
 this position, the needle 154 provides a partial occlusion of a flow
 channel 160 between the needle 154 and the seat 156. The pressure member
 16 and the needle 154 are isolated by a flexible membrane 162, although
 other embodiments may incorporate an o-ring between the needle 154 and the
 seat 156 to prevent fluid in the pressure member 16 to enter the flow
 channel 160. A fluid channel 164 provides a path for fluid to flow from
 within the pressure member 16 to the flow channel 160. The difference in
 pressure at the entrance and the exit of fluid channel 164 determines the
 degree of occlusion of the flow channel 160. Decreasing pressure within
 the pressure member 16 decreases the driving force through the fluid
 channel 164. FIG. 18B is a cross-section of the valve 152 when pressure
 within the pressure member 16 has decreased below that shown in FIG. 18A.
 Note that the spring 158 presses the needle 154 toward the flexible
 membrane 162 and away from the seat 156, decreasing the resistance to flow
 through the channel 160.
 The embodiments of the infuser illustrated in FIGS. 2 and 3 include a
 fabric tensile member 34 in the interior the pressure member 16. However,
 it should be appreciated that the term tensile member is interpreted
 broadly in the present invention. Multiple embodiments of the tensile
 member are illustrated in FIGS. 13A-13E. FIG. 13A is a cross-section of
 the pressure member 16 in the infuser 10 having a thin side 120 and a
 thick side 122. Because the thick wall 122 is less extensible than the
 thin wall 120, the infuser 10 will form into an arcuate, curved, or
 circular shape upon inflation. Note that the thick wall 122 can be a
 gradual thickening of the device, or alternatively, can be a ridge or
 stripe of thickened material. If the thick wall 122 runs along the same
 side of the pressure member 16 for its entire length, the two ends 12, 14
 of the infuser 10 will curve toward each other. Alternatively, if the
 thick wall 122 spirals around the pressure member 16 along its length, the
 infuser will tend to assume a helical or spiral structure. Alternating the
 location of the thick wall 122 from side to side can form any of a number
 of potential geometric shapes.
 FIG. 13B illustrates an embodiment in which the tensile member 34 is inside
 the pressure member 16. The tensile member 34 can be formed of any
 inextensible material, including wire, fabric, or polymer. We have found
 that a polyester ribbon has advantageous properties.
 FIG. 13C illustrates an embodiment in which the tensile member 34 is
 located on or in the wall of the pressure member 16. The tensile member 34
 can be fully embedded, partially embedded, or adhered to the inside wall
 or the outside wall of the pressure member 16. This can be done by
 coextrusion of the tensile member 34 with the pressure member 16, or by
 subsequent welding or adhesive bonding to the pressure member 16.
 In yet another embodiment, as illustrated in FIG. 13D, the tensile member
 34 is located external to the pressure member 16 as illustrated in FIG.
 13D. In this embodiment, the pressure member 16 assumes a curved or
 arcuate shape, while the tensile member forms a straight line between the
 two ends 12, 14 of the infuser 10. This embodiment has the advantage of
 reducing the risk of premature voiding of the infuser 10 even if one of
 the ends 12, 14 approaches the urethra, and also of providing a grasping
 point for subsequent removal of the infuser 10, taking the place of the
 capture loop 36.
 FIG. 13E illustrates an embodiment in which the tensile member 34 comprises
 a different material from the rest of the pressure member 16. The tensile
 member 34 may, for example, be a relatively inextensible material by
 comparison to the remainder of the pressure member 16. It may be welded or
 bonded to the pressure member 16, or, preferably, it is coextruded with
 the material forming the pressure member 16. If silicone is used for the
 pressure member 16, for example, a more highly cross-linked, less
 extensible silicone may be coextruded with the remainder of the pressure
 member 16, forming a part of the wall of the pressure member 16.
 Alternatively, it is possible to use a material that is more extensible
 than the remainder of the pressure member 16, in which case the coextruded
 material will stretch more than the remaining pressure member and the
 curvature will be away from the coextruded material.
 It should be recognized that there are various equivalent methods for
 deforming an infuser subsequent to implantation. The present invention
 should not be interpreted so narrowly as to avoid other shape-changing
 techniques.
 FIG. 14 is a schematic representation of an alternative shape-changing
 technique. In this embodiment, a tensile member 34 connects the proximal
 and distal ends of the infuser 10. The tensile member may be axially
 shortened, with respect to the infuser 10, as illustrated in FIG. 15. In
 the illustrated embodiment, a ratchet mechanism 124 allows the tensile
 member 34 to be pulled out of an opening in the infuser 10 and to lock in
 that short position. An ultimate coil shape is illustrated in FIG. 15.
 However, depending upon the geometry of the infuser 10 and the location of
 the tensile member inside or outside of the infuser 10, the ultimate shape
 can be circular, supercoiled, arcuate, or any of various other desirable
 configurations.
 The method of the present invention is further illustrated in FIGS.
 16A-16E. In FIG. 16A, the infuser 10 is inserted into the bladder 130 of
 the patient through the urethra 132 utilizing an outer sheath 66, and an
 extender 70. A hypodermic needle 38 is inserted through the outer sheath
 66 and the extender 70 into the septum 42 of the infuser 10. FIG. 16B
 illustrates filling of the infuser 10 through a cannula or other fluid
 carrying device within the extender 70. Note that the infuser 10 assumes
 an arcuate or circular shape upon filling. After filling is completed, the
 needle 38 is withdrawn, letting the infuser 10 float freely within the
 bladder 130, as illustrated in FIG. 16C.
 Alternatively, the infuser 10 can be tethered to the bladder wall using any
 of a variety of conventional tethering means, including sutures, staples,
 and adhesives. Installation and removal of the tethering means can be
 accomplished in a number of ways, including cystoscopically. To help
 facilitate removal of the device, dissolvable sutures can also be used. In
 addition, a layer of pentosanpolysulfate, can be applied to the tethering
 means, especially when non-dissolvable tethering means are used, such as a
 non-dissolvable suture. Additional information regarding the
 pentosanpolysulfate coating may be found in U.S. patent application Ser.
 No. 08/942,972, filed Oct. 3, 1997, entitled "PENTOSANPOLYSULFATE COATING
 FOR MEDICAL DEVICES" which is a file wrapper continuation of a parent U.S.
 patent application Ser. No. 08/642,391, the disclosure of which is
 incorporated herein by reference.
 After the substance or drug has been infused, the infuser 10 can either be
 refilled for additional intravesical delivery of drug or the infuser can
 be removed from the patient and replaced with another infuser 10 as
 needed. Refilling can be accomplished in a fashion similar to that of
 filling. The capture loop 36 or other capture arrangements can be used to
 manipulate the infuser 10 within the bladder 130 during refilling.
 FIG. 16D illustrates one technique for removal of the infuser after the
 drug has been depleted or the treatment has run its course. A cystoscope
 134 is introduced into the bladder 130 of the patient and a scalpel, a
 needle or other rupturing or cutting tool 136 is utilized to puncture or
 rupture the infuser 10, thereby releasing the internal pressure to allow
 the infuser to deflate to an unfilled state. If desired, the remaining
 drug within the bladder can be flushed or otherwise withdrawn if release
 of a substantial quantity of drug would not be well tolerated.
 Alternatively, the infuser can be emptied by activation of a releasing
 mechanism which allows low resistance flow through the valve assembly in
 order to deflate to an unfilled state prior to removal of the infuser 10
 from the patient. In one preferred embodiment, the drug is withdrawn from
 the infuser through a conduit (such as the needle 38 and any attached
 tube) directly out of the bladder, so that release of a bolus dose of drug
 into the bladder 130 is avoided.
 FIG. 16E illustrates the removal of the infuser 10 from the bladder 130 of
 the patient. The cystoscope 134 is used to introduce a retrieval tool 140
 of any suitable design. The retrieval tool 140 grasps the capture loop 36,
 allowing the deflated infuser 10 to be withdrawn from the bladder 130 via
 the urethra 132. In other embodiments, the retrieval tool may include
 graspers, hooks, clamps, magnets, adhesives or any other design that
 allows for the attachment and retrieval of the infuser.
 The method of the present invention is further illustrated in FIGS. 25A-25D
 in conjunction with the infuser 10 illustrated in FIG. 19. In FIG. 25A,
 the infuser 10 is inserted into the bladder 130 of the patient through the
 urethra 132 using an introducer. After transurethral introduction of the
 outer sheath 266 of the introducer into the bladder, the deflated infuser
 10 is passed through the outer sheath 266 into a position as illustrated
 in FIG. 25A. The secure coupling fitting 260 fits snugly into the opening
 230 of the infuser 10. In this position, fluid drug flows through the
 introducer channel 264 located within the extender 262 of the introducer.
 Fluid flows from the introducer channel 264 through the valve entrance
 246, into the fluid chamber 250 and fills or inflates the infuser 10.
 When filling is complete, the secure coupling fitting 260 is disconnected
 from the infuser 10 as shown in FIG. 25B to free float in the bladder of
 the patient. The extender 262 is retracted into the outer sheath 266 and
 both are then withdrawn from the patient.
 FIG. 25C illustrates one technique for removal of the infuser after the
 drug has been depleted or the treatment has run its course. A retrieval
 device 270 is introduced into the bladder 130 of the patient. The
 capturing element 276 is extended from the retrieval channel 274. The
 capturing element 276 engages the capture member 236. The capturing
 element 276 is retracted into the sheathe 272. In FIG. 25D, the distal
 endcap bumper 228 is snuggly seated against the channel entrance 278. The
 remaining fluid within the infuser 10 is flowing from within the infusor
 10 through the retrieval channel 274 and out of the bladder so that
 release of a bolus dose of drug into the bladder 130 is avoided.
 Of course, it will be appreciated that the illustrated embodiments
 represent only one preferred method for practicing the invention. Numerous
 minor variations are possible without departing from the spirit of the
 invention. For example, instead of a needle and septum valving
 arrangement, any number of various valving mechanisms and latching
 mechanisms could be used to connect the infuser 10 to the extender 70 or
 the hypodermic needle 38 (or a cannula or locking member taking the place
 of hypodermic needle 38). Thus, the external source of fluid may be
 attached to the interior of the pressure member 16 via a valving
 mechanism, and the infuser 10 may be physically attached to and releasable
 from the extender 70. In addition, numerous other capture arrangements are
 possible besides the use of a capture loop 36. For example, a magnetic
 mechanism may be utilized to draw one end of the infuser 10 into
 sufficiently close proximity to the cystoscope 134 that capture can be
 effected. A basket or expanding and contracting mesh ("Chinese finger
 trap") apparatus may similarly be used.
 In other embodiments of the invention, the collars 24, 26 or other portions
 of the infuser may be made radiopaque in order to facilitate visualization
 of the infuser by ultrasound, X-ray or other visualization means.
 In one embodiment of the invention, mechanically driven, electrically
 driven, or osmotically driven infusion means is substituted for the
 pressure member 16. Alternatively, the substance or drug utilized in the
 invention can be impregnated into a controlled release or bioerodable
 material that effects a shape change upon introduction into the bladder.
 In one important aspect of the invention, the entire infuser 10 or
 appropriate portions thereof may be coated with a biocompatible coating. A
 major problem that has been experienced with most devices that are left in
 the bladder for more than a few days is encrustation and infection.
 Various salts, proteins, and other materials in the urine can rapidly
 build up on foreign objects left within the bladder. This, in turn, leads
 to irritation and difficulty in removing the device without injuring the
 patient. In some cases, the entire infuser 10 may be coated. In other
 cases, only appropriate portions of the infuser 10 are coated such as the
 proximal end cap 20 and distal end cap 22.
 We have discovered that certain polysaccharide coatings can reduce or even
 prevent encrustation. These coatings include pentosanpolysulfate, heparin
 and other sulfonated polysaccharides or drugs. Silicone and many
 biocompatible plastics will not readily accept a coating of these
 biocompatible materials. We have found that this obstacle can be overcome
 by surface pretreatment of the device by any of a number of surface
 modification techniques. These include corona discharge, ionic discharge,
 chemical etching such as by treatment with a strong base, and plasma
 treatment. One technique is disclosed in previously incorporated U.S.
 patent application Ser. No. 08/942,972, filed Oct. 3, 1997, entitled
 "PENTOSANPOLYSULFATE COATING FOR MEDICAL DEVICES."
 An infuser according to the invention may be used as a self contained means
 of delivering therapeutic agents to a variety of functioning organs within
 a living organism. The infuser may be introduced into the functioning
 organ through a natural orifice or created orifice.
 In one embodiment, the device is inserted into the patient containing a
 therapeutic or diagnostic agent in condensed form. When the device is
 within the bladder, it is filled with a reconstitution agent which causes
 a shape change in the device and activates the agent within the device.
 For example, the device may be filled with a saline solution which
 activates a drug in power form within the device.
 In the methods of using the device falling within the scope of the present
 invention, a wide variety of drugs or other substances, including contrast
 agents can be administered to the bladder. These drugs or other substances
 can be provided in a variety of forms, including liquids and hydratable
 powders. These drugs and other materials can be used for a variety of
 purposes, including the treatment of urinary incontinence, urinary tract
 cancer, urinary tract infections, inflammatory conditions of the urinary
 tract, and to provide pain relief.
 Urinary incontinence, including urge incontinence and neurogenic
 incontinence, can be treated using the device of the present invention.
 Preferably, anticholinergic and/or antispasmodic agents are used. In
 addition, antimuscarinic agents, .beta.-2 agonists, norepinephrine uptake
 inhibitors, serotonin uptake inhibitors, calcium channel blockers,
 potassium channel openers, and muscle relaxants can also be used. Suitable
 drugs for the treatment of incontinence include oxybutynin, S-oxybutytin,
 emepronium, verapamil, imipramine, flavoxate, atropine, propantheline,
 tolterodine, rociverine, clenbuterol, darifenacin (Pfizer, Europe, USA,
 Japan), terodiline, trospium, hyoscyamin, propiverine, desmopressin,
 vamicamide (Fujiwara Co., Japan), YM-46303 (Yamanouchi Co., Japan),
 lanperisone (Nippon Kayaku Co., Japan), inaperisone, NS-21 (Nippon
 Shinyaku Orion, Formenti, Japan/Italy), NC-1800 (Nippon Chemiphar Co.,
 Japan), ZD-6169 (Zeneca Co., United Kingdom), and stilonium iodide. In
 addition, the substance released from the device may used for diagnostic
 purposes.
 Urinary tract cancer, such as bladder cancer and prostate cancer, may be
 treated using the device of the present invention by infusing
 antiproliferative agents, cytotoxic agents and/or chemotherapeutics.
 Suitable drugs for the treatment of urinary tract cancer include Bacillus
 Calmette Guerin (BCG) vaccine, cisplatin, doxorubicin, methotrexate,
 vinblastine, thiotepa, mitomycin, fluorouracil, leuprolide, flutamide,
 diethylstilbestrol, estramustine, megestrol acetate, cyproterone,
 flutamide, and cyclophosphamide. Treatment of urinary tract cancer can be
 effected in conjunction with other conventional cancer treatment
 techniques, including surgical excision, and radiation therapy.
 In a similar manner, infections involving the bladder, the prostate, and
 the urethra, can be treated using the device of the present invention.
 Antibiotics, antibacterial, antifungal, antiprotozoal, antiviral and other
 antiinfective agents can be administered for treatment of such infections.
 Suitable drugs for the treatment of such infections include mitomycin,
 ciprofloxacin, norfloxacin, ofloxacin, methanamine, nitrofurantoin,
 ampicillin, amoxicillin, nafcillin, trimethoprim, sulfa,
 trimethoprimsulfamethoxazole, erythromycin, doxycycline, metronidazole,
 tetracycline, kanamycin, penicillins, cephalosporins, and aminoglycosides.
 Inflammatory conditions such as interstitial cystitis, prostatitis, and
 urethritis can also be treated using the device of the present invention.
 Drugs having an antiinflammatory and/or coating effect are useful in this
 regard. Suitable drugs include dimethyl sulfoxide (DMSO), heparin,
 pentosanpolysulfate sodium, and flavoxate.
 The device of the present invention can also be used to provide pain relief
 to the patient. In this regard, a variety of anesthetic and/or analgesic
 agents can be infused through the device of the present invention,
 including lidocaine hydrochloride, procaine hydrochloride, salicyl
 alcohol, tetracaine hydrochloride, phenazopyridine hydrochloride,
 acetaminophen, acetylsalicylic acid, flufenisal, ibuprofen, indoprofen,
 indomethacin, naproxen, codeine, oxycodone, and fentanyl citrate.
 The device of the present invention can also be used to administer drugs
 and other materials for a variety of other purposes. For example, the
 device can be used to administer glycine for purposes such as bladder
 irrigation.
 The treatment method of the present invention provides for slow,
 continuous, intermittent or periodic release of a desired quantity of drug
 over a desired period of time. In one preferred embodiment, the volume of
 the infuser is such that it can deliver the desired dose of drug over an
 extended period of time, e.g., 24 hours, 5 days, 10 days, 15 days or even
 20, 25, 30, 60, 90 days or more. The rate of delivery in order to
 accomplish this result is relatively slow. Thus, the present invention
 contemplates the drug delivery rates within the range of 0.1, 1, 5, 10,
 25, 50, 75, 100, 150, or 200 .mu.l/hr. Of course, slower or faster
 delivery rates can be selected depending upon the drug being delivered and
 the disease being treated. In any particular situation, and for any
 particular disease state, the concentration of the drug and the rate of
 delivery can be selected by the physician based on conventional
 methodologies.
 The infuser device of the present invention has been successfully tested in
 adult pigs. The practice of the present invention is illustrated in the
 following non-limiting examples.
 EXAMPLE 1
 Female swine in the weight range 40-45 kg were sedated using 10 ml of
 ketamine chloride and 3 ml of atropine. Upon achieving proper sedation, an
 endotrachial tube was placed in the animal's airway and the animal
 maintained on isoflurane gas between 0.5% and 4% as an intraoperative
 anesthesia. Following standard sterile procedures, a 21 Fr Storz
 cystoscope was used to visualize and position a 0.038 inch guidewire in
 the bladder of the pig. Removing the cystoscope, a 23 Fr introducer sheath
 and obturator were passed over the guidewire into the bladder of the
 animal. The obturator and guidewire were removed. An infuser mounted on a
 23 gauge needle at the distal end of a launcher tube was placed through
 the introducer sheath into the bladder. A 60 cc syringe mounted in an
 infusion assist device was attached to the proximal end of the launcher
 tube through a section of tubing. The tubing was primed before attachment
 to purge all air from the system. The 60 cc syringe was filled with 35 cc
 of tritium labeled sodium pentosanpolysulfate drug. Total counts of the
 radioactivity of the tritium labeled drug for the 35 cc were measured from
 a 100 .mu.l sample of drug using a Beckman scintillation counter prior to
 beginning the study. The infuser was positioned in the bladder such that
 the majority of the infuser extended beyond the introducer sheath. Thirty
 cc of drug was injected into the infuser and the infuser expanded into the
 filled state. The 23 gauge needle was withdrawn from the infuser, and the
 introducer sheath and launcher assemblies were removed from the patient,
 allowing the infuser to float freely within the bladder. The pigs were
 allowed to recover from the anesthesia and were returned to their cages.
 The total urine output from the pigs was collected and measured daily for
 thirty days. Total urine output varied between 1.75-3.5 liters/day. A 100
 .mu.l sample of urine was taken from each daily collection and placed in a
 Beckman scintillation counter to determine the number of radioactive
 counts within the sample. The measurement gave the total counts in the
 daily collection which was compared to the original measurement of total
 counts made at the beginning of the study to determine the amount of drug
 in the daily collection. Average counts of a 100 .mu.l sample from a daily
 collection typically measured 750-1000 counts. In this manner, it was
 determined the output of the device varied between 2 cc per day at the
 beginning of the study to 0.75 cc per day on the thirtieth day of the
 study. At the end of the thirty days, the animal was sacrificed by
 injection of 12 ml of Beuthanasia-D and its bladder removed. Histological
 specimens were taken from the neck, trigone, base, and dome areas of the
 bladder, fixed in formaldehyde, imbedded in parafin, sectioned, and
 stained with H&E. Examination of the sections showed normal tissue with no
 apparent injury caused by the infuser.
 EXAMPLE 2
 The infuser may be used in human patients to treat neurogenic bladder
 disease or urge incontinence using anticholinergic or antimuscarinic drugs
 such as oxybutynin or flavoxate. A patient is prepared in the dorsal
 lithotomy position. Standard cystoscopic procedures are performed on the
 patient using local anesthesia and accepted sterile techniques. An
 introducer sheath and an obturator are transureturally positioned to allow
 access to the bladder. To minimize patient discomfort, water soluble
 lidocaine jelly is used to facilitate the passage of the introducer
 sheath/obturator within the urethra. The obturator is removed and the
 infuser is passed through the introducer into the bladder. The infuser is
 connected to a source of therapeutic agent through the introducer sheath.
 The infuser is filled with about 30 cc of the therapeutic agent from the
 source. The source of therapeutic agent may comprise a hypodermic needle
 which penetrates a septum in the infusor or a pressure source which opens
 a check valve in the infuser. After filling is complete, the source is
 uncoupled from the infuser so that the infuser floats freely within the
 bladder. The introducer is removed from the urethra.
 The infuser remains in the patient's bladder for 30 days infusing the
 therapeutic agent to relieve the symptoms of urge incontinence or
 neurogenic bladder disease without the side effects associated with
 alternate drug administration routes such as oral or intravenous methods.
 After 30 days, the patient is prepared in a similar fashion as described
 above. A cystoscope is inserted through the urethra into the bladder and
 the infuser is located by visualization. Any residual therapeutic agent
 remaining in the infuser is removed to reduce the profile of the infuser
 to facilitate its removal. The removal of the therapeutic agent may be
 accomplished by passing a needle or cutting tool though a working channel
 of the cystoscope to rupture the infuser. Alternatively, a tool to access
 a release mechanism in the infuser may purge the contents of the infuser.
 The bladder may be flushed in order to remove the released drug if
 necessary. A retrieval tool is passed through a working channel of the
 cystoscope. The retrieval tool grasps the infuser and removes the infuser
 from the bladder. The infuser and cystoscope are removed from the urethra.
 A subsequent infuser may be introduced into the bladder following the
 procedure described above if additional therapy is necessary.
 Although this invention has been described in terms of certain preferred
 embodiments, other embodiments which will be apparent to those of ordinary
 skill in the art in view of the disclosure herein are also within the
 scope of this invention. Accordingly, the scope of the invention is
 intended to be defined only by reference to the appended claims.