Bladder drug eluting device

A drug delivery system that can be deployed from a catheter and retained within the bladder for delivery of treatment drug solutions over a period of time. The delivery system includes an inflatable or expandable delivery element that can be collapsed within the catheter tip for navigation into the bladder before being inflated or expanded within the bladder. The inflated or expanded delivery element can engage the bladder walls or sized to be too large to be passed from the bladder such that the delivery element is retained within the bladder after inflation or expansion to administer a treatment drug solution over an extended period of time.

FIELD OF THE INVENTION

The present invention is generally directed to a drug elution device positionable within the bladder for prolonged delivery of treatment drugs. Specifically, the present invention is directed to a drug eluting device that can be collapsed for transport through a biological lumen to bladder before being expanded to retain the drug eluting device within the bladder.

BACKGROUND OF THE INVENTION

The bladder is a hollow organ for receiving and storing urine produced during digestion before the urine is expelled from the body. The chemical conditions within the bladder, such as the pH, are constantly changing with the influx of new urine and expelling of urine from the bladder. The chemical characteristics of the urine itself are also constantly changing depending on the individual's recent meals, overall diet, timing between meals, present hydration, acute and chronic health conditions, and a plurality of other factors. The characteristics can change dramatically on a daily or even hourly basis. The constantly changing chemical characteristics of the bladder can make effectively delivering chemical drugs to the bladder difficult. In particular, effective long term drug treatments for the bladder are particularly challenging.

Treatment drugs are typically administered to the bladder by navigating a catheter through the urethra until and end of the catheter is positioned within the bladder. The treatment drug is then supplied via the lumen defined by the catheter and expelled within the bladder. If the chemical conditions within the bladder are not optimal when the drugs are administered, the drugs may not sufficiently dissolve to cover a sufficient area or diffuse over too great an area to effectively treat the disorder. In particular, if the pH of the urine is outside a predetermined range, the treatment drug could have little to no effect. The problem is further exaggerated with treatment drugs that are administered within the bladder in a form designed to be gradually administered over time such as time release drug capsules or ampules. The changing bladder conditions and constantly refreshing urine can cause the drugs to be administered either too quickly or too slowly, thereby preventing effective delivery of the drugs.

Presently, the effectiveness of the drug administration process in the bladder is improved by doubling the concentration of the drug to overcome unfavorable conditions or by combining the treatment drugs with a buffering solution to effectively create the desired conditions for a period of time. Although these approaches can improve the efficacy of long term drug treatments to the bladder, these approaches are not without significant drawbacks. Increasing the concentration of the drugs that are initially delivered reduces the likelihood that the dosages that are administered will be insufficient. However, the increased concentration also creates a possibility of an overdose in treatment drugs, which can lead to significant complications. Similarly, the buffering solution is an added chemical solution that can create side effects leading to additional complications for the patient. Long term administration of the drugs can further exaggerate the inherent drawbacks of these treatment methods.

The inability to consistently and effectively administer treatment drugs to the bladder over a long period of time can prevent effective treatment of certain disorders, such as cancer. As such, there is a need for a means of effective long term and consistent drug delivery within a bladder.

SUMMARY OF THE INVENTION

The present invention is generally directed to a drug delivery system that can be deployed from a catheter and retained within the bladder for administering treatment drug solutions over a period of time. The delivery system generally comprises an inflatable or expandable delivery element that can be collapsed within the catheter tip and inflated or expanded after the catheter tip is navigated into the bladder. The inflated or expanded delivery element can engage the bladder walls or sized to be too large to be passed from the bladder such that the delivery element is retained within the bladder after inflation or expansion to administer a treatment drug solution over an extended period of time. Alternatively, the treatment drug can be delivered to the delivery element with a jet injection system at higher pressure to facilitate more rapid introduction of the treatment drug into bladder tissue.

In one aspect, the delivery element can define an internal space for containing a drug treatment solution with a semi-permeable exterior through which the drug treatment solution diffuse over an extended period of time. The exterior prevents complete intermixing of the drug treatment solution with the urine during the initial treatment and instead permits gradual administration of the drug treatment solution at an effective dosage over a period of time. The exterior also limits the effect of changing bladder conditions on the efficacy of the treatment drugs. In another aspect, the exterior comprises a degradable material adapted to dissolve or degrade over a predetermined period of time to gradually release the drug treatment solution. In yet another aspect, the delivery element can comprise at least one orifice through which the drug treatment solution slowly elutes through over an extended period of time.

A drug delivery system, according to a representative embodiment of the present invention, can comprise a delivery element and a catheter having a tip for receiving and deploying the delivery element, wherein the delivery element comprises an inflatable balloon. The inflatable balloon can further comprise a balloon exterior defining an interior space for receiving a treatment drug solution. In one aspect, the catheter can comprise a lumen for administering the drug solution into the interior space of the balloon to inflate the balloon. In this configuration, the balloon can comprise a sealing interface with the catheter tip such that the balloon can remain inflated in the bladder after the catheter tip separates from the balloon. The bladder exterior can comprise a semi-permeable membrane, a degradable membrane, a plurality of orifices or other means of permitting prolonged elution of the treatment drugs from the interior space of the balloon.

In operation, the catheter can be navigated through the urethra until the tip of the catheter is positioned within the bladder. The treatment drug is then supplied through the catheter lumen to inflate the balloon. The balloon can be shaped to contact the bladder wall once inflated. The treatment drug can then be eluted or forced from the balloon into the bladder wall. In one aspect, the catheter can be separated from the balloon and removed from the body while leaving the inflated balloon in place. Once the treatment drug has been administered, the balloon can be deflated by the original catheter or a second catheter navigated into the bladder in a subsequent procedure. Alternatively, the balloon wall can comprise a degradable material formulated to breakdown after a predetermined time allowing the balloon wall to be passed from the bladder wall. In some embodiments, the treatment drug can be delivered into the balloon at higher pressure for more rapid introduction into the bladder tissue using a jet injection system.

According to a representative embodiment of the present invention, the delivery element can comprise a deployable ring. The ring shape permits the ring to be retained within the bladder while allowing the urine to normally pass through the center of the ring. The edges of the ring are sized to engage the sides of the bladder wall to prevent shifting of the ring following deployment. In one aspect, the ring can comprise a ring exterior defining an interior space for receiving a treatment drug. In this configuration, the ring can be filled with the treatment drug to inflate the ring in a similar manner to the balloon. In another aspect, the ring can comprise a flexible material that unfurls and expands when deployed from the catheter tip. In this configuration, the ring can be impregnated with the treatment drug and coated to provide extended delivery of the treatment drug. Alternatively, the ring can comprise a base material coated or impregnated with the treatment drug. In some embodiments, the treatment drug can be delivered into the deployable ring at higher pressure for more rapid introduction into the bladder tissue using a jet injection system.

The above summary of the various representative embodiments of the invention is not intended to describe each illustrated embodiment or every implementation of the invention. Rather, the embodiments are chosen and described so that others skilled in the art can appreciate and understand the principles and practices of the invention. The figures in the detailed description that follow more particularly exemplify these embodiments.

DETAILED DESCRIPTION

As depicted inFIG. 1, a bladder generally comprises an expandable bladder wall defining an interior space. Two ureters are fluidly connected to the bladder to supply urine into the interior space of the bladder. Similarly, a urethra is fluidly connected to the bladder to expel urine from the bladder. A urethral sphincter controls the flow of urine from the bladder through the urethra. The description of the bladder is not intended to be limiting, but rather to aid in the description of the present invention.

As depicted inFIGS. 2-11, a drug delivery device20, according to an embodiment of the present invention, can comprise a catheter22and a deployable delivery element24capable of transitioning between a non-expanded state23and an expanded state25. The catheter22comprises an elongated body26defining a lumen28and a tip30at one end of the elongated body26. The lumen28extends the length of the catheter22providing fluid communication between one end of the catheter22and the opposite end of the catheter22. In one aspect, the tip30defines a tip space32for receiving the delivery element24in the non-expanded state23. In this configuration, the catheter22can further comprise at least one control wire extendable through the lumen28for deploying the delivery element24from the tip space32through the opposite end of the catheter22.

As depicted inFIG. 3-8, according to an embodiment of the present invention, the deployable delivery element24comprises a balloon34having a deflated non-expanded state23and an inflated expanded state25. The balloon34further comprises a balloon wall36defining an interior space38for receiving a drug treatment solution. In one aspect, the balloon wall36comprises an elastic material that stretches as the treatment drug is fed into the interior space38thereby causing the balloon34to transition/inflate into the expanded state25. Similarly, in one aspect, the balloon wall36can comprise a semi-permeable material allowing the treatment drug contained within the interior space38to diffuse from the inflated balloon34over a prolonged period of time while preventing urine from entering the interior space38. In another aspect, the balloon wall36comprises a degradable material that gradually breaks down over an extended period of time, thereby gradually dispensing the treatment drug contained within the interior space38of the balloon34. In yet another aspect, the bladder wall36comprises a plurality of orifices40, as depicted inFIG. 7, through which the treatment drug solution elutes over a prolonged period of time.

As depicted inFIGS. 3-5and8, in operation, the catheter22is navigated through the urethra such that at least the tip30penetrates the urethra sphincter, wherein the balloon34is positioned within the tip space32in the deflated non-expanded space23. A quantity of the treatment drug solution is pumped through the lumen28into the interior space38of the balloon34to inflate the balloon34and transition the balloon34into the inflated expanded state25as depicted inFIG. 4. The inflation of the balloon34causes the balloon34to leave the tip space32and continue to expand within the bladder. In one aspect, the balloon34is deployed from the tip space32with the control wire before the balloon34is inflated. After the balloon34is inflated, the tip30is separated from the balloon34. In this configuration, the balloon34comprises a sealing orifice42that maintains the inflation of the balloon34as the drug treatment solution is slowly administered through the balloon wall36. Following treatment, in one aspect, the balloon34can be deflated by the tip30of a second catheter22and drained of the remaining drug treatment solution before the deflated balloon34is pulled from the bladder as depicted inFIG. 8.

In one aspect, the balloon walls36of the inflated balloon34can be sized to be proximate to the bladder walls as shown inFIGS. 5-7. The close proximity of the balloon walls36allows for dispensing of the treatment drug solution from the balloon34proximate to the bladder walls minimizing the possible dilution of the drug solution by the urine. In one aspect, the catheter22can remain attached to the balloon34throughout the treatment to provide a continuous supply of the treatment drug solution.

As depicted inFIG. 9-10, the deployable delivery element24can comprise a collapsible ring44having a collapsed non-expanded state23and an inflated expanded state25. In one aspect, the ring44can comprise a balloon having an interior space and inflatable by feeding a quantity of treatment drug solution into the ring44. In another aspect, the ring44can comprise a flexible ring44biased to expand upon deployment from tip30. As with the balloon34, the ring44is positioned within the tip space32in the non-expanded state23. After insertion of the tip30through the urethral sphincter, the ring44is inflated or expanded within the bladder.

In one aspect, the ring44comprises a semi-permeable material allowing the treatment drug contained within the ring to diffuse from the ring44over a prolonged period of time while preventing urine from entering the interior of the ring44. In another aspect, the ring44comprises a degradable material that gradually breaks down over an extended period of time, thereby gradually dispensing the treatment drug contained within the ring44. In yet another aspect, the ring44can further comprise a plurality of orifices46through which the treatment drug solution can be eluted.

As depicted inFIG. 11, in one aspect, the ring44is sized such that the outer edge of the ring44engages the bladder walls to retain the ring44within the bladder. In this configuration, the direct engagement of the ring44to the bladder walls allows for direct transfer of treatment drug solution to the bladder walls, thereby minimizing the dilution of the treatment drug solution in the urine. Alternatively, the ring44is sized to be too large to be passed through the urethral sphincter. In either configuration, urine can pass normally through the center of the ring44and out of the bladder through the urethra, thereby allowing normal bladder functions while administering the treatment drug solution.

As depicted inFIGS. 2-11, a method of a administering a treatment drug solution over an extended period of time from within a bladder comprises navigating a catheter22having a tip30with a deployable delivery element24contained therein, wherein the delivery element24is in a non-expanded state23when positioned within the catheter tip30. The method further comprises deploying the delivery element24from the tip30and expanding the delivery element24within the bladder. In one aspect, the method can also comprise transferring a quantity of drug treatment solution through the catheter22to expand the delivery element24into an expanded state25. In another aspect, the method can also comprise pushing the delivery element24from the catheter tip30with a control wire, wherein the delivery element24is folded such that the delivery element24is biased to transition into the expand state25upon exiting the catheter tip30. The method further comprises diffusing the quantity of treatment drug solution from the delivery element24over a period of time. Finally, the method also comprises deflating the delivery element24and removing the delivery element24from the bladder through the urethra with the catheter22.

In an alternative embodiment illustrated withinFIGS. 12-14, deployable delivery element24, for example, balloon34or collapsible ring44can delivered and placed within the bladder as previously described. Once the deployable delivery element24is properly positioned and in expanded state25, a medical professional can utilize a jet injection system50such as, for example, the jet injection systems described in U.S. Patent Publication Nos. 2008/0119784, 2008/0119823, 2009/0312696, 2011/0046600, 2011/0172631, 2011/0015614, 2011/0238006, 2011/0245762, 2011/0264036, 2011/0282318, 2012/0053515, 2012/0109049, 2012/0109050, 2012/0302826 and U.S. Pat. Nos. 7,850,649 and 7,993,264, all publication and patents being incorporated herein by reference, to rapidly deliver the treatment drug solution into the deployable delivery element24. Correspondingly, the rate at which the drug treatment solution is then administered into the bladder tissue is greatly increased so as to further reduce the potential for dilution and to facilitate treatments where a medical professional desires rapid introduction of the drug treatment solution as opposed to a slower, time delayed delivery of the drug treatment solution.

As illustrated inFIG. 12, jet injection system50can comprise an injector52and an applicator lumen54. Injector52can comprise an automated injector55including a user interface56and a connector member58. Connector member58can include a surface opening (not shown) for communication with a drug treatment solution supply60. User interface56can comprise an input means allowing a medical profession to control and selectively deliver pressurized drug treatment solution through the connector member58and into the applicator lumen54. Representative input means can include for example, a foot pedal107, switches, buttons or a touch-screen capable of receiving touch commands as well as displaying system information including a mode of operation as well as operating parameters.

As seen inFIGS. 13 and 14, applicator lumen54preferably comprises a polymeric tubular device62having a proximal attachment end64and a distal delivery end66. Polymeric tubular device62is generally formed so as to have a burst strength of at least about 2,000 psi. In a preferred embodiment, the non-metal, polymeric tubular device is formed to have a burst strength ranging from about 2,000 psi to about 5,000 psi. In one representative embodiment, non-metal, polymeric tubular device200is formed of a single high strength polymer such as, for example, a polyimide, polyetherimide available from General Electric under the trade name Ultem® and linear aromatic polymers such as PEEK™ available from Victrex plc. Alternatively, the non-metal, polymeric tubular device62can be formed from a reinforced polymer that is reinforced with reinforcing materials such as, for example, nano-particles, clays or glass. Alternatively, the polymeric tubular device62can be reinforced with a reinforcing fiber such as, for example, tubes braided with carbon fiber, synthetic para-aramid fiber such as Kevlar available from E.I. du Pont de Nemours and Company or other high-strength polymers braided within polymeric tubular device62. Generally, polymeric tubular device62is extruded though other appropriate fabrication methods including molding can be utilized as well.

As illustrated inFIG. 12, polymeric tubular device62can be configured to be advanced through the catheter22following deployment and placement of the deployable delivery element24. Alternatively, deployable delivery element24can be retained within the polymeric tubular device62such that the deployable delivery element24is positioned and deployed directly out of the applicator lumen54. With the deployable delivery element24positioned and deployed within the bladder, the medical professional can actuate the injector52to deliver high pressure drug treatment solution into the deployable delivery element24through a delivery orifice68at the distal delivery end66. In this manner, the medical professional can quickly deliver the drug treatment solution into the deployable delivery element24at a higher rate and higher pressure for quicker delivery through the deployable delivery element24and into the bladder tissue.