EP-4734966-A2 - SYSTEM AND METHOD FOR SUSTAINED RELEASE OF AGENTS IN THE BLADDER

Abstract

Embodiments include systems and methods for treating diseases of the bladder, kidneys and urinary tract. Drug products can be administered through the urethra in a compact form. Within the bladder, the products can expand or conform to a larger size which resists passage into the urethra over a desired residence period. After a treatment period, at least a portion of the products can dissolve or degrade so that individual particles are voided in the urine. Embodiments also include drug particle delivery devices and methods of intravesical administration. A delivery device can use a straw-shaped cartridge packed with rod-shaped products that are administered into the bladder of a patient by a pressure source or actuation of a piston. The distal end of the barrel can connect to a vesical sheath or a soft tip in order to plunge directly into a patient's urethra.

Inventors

• KINSELLA, Christopher R., Jr.
• ALI, Saniya
• SANDLER, Warren
• VALENZUELA, Jackson
• NOLAN, Clay Justin
• COHEN, EARL

Assignees

• Watershed Medical, Inc.

Dates

Publication Date

20260506

Application Date

20240630

Claims (1)

1. PATENT WM1-006WO CLAIMS What is claimed is: 1. A method of treating and/or preventing an ailment in a subject, the method comprising: a) providing a plurality of linked particles, each linked particle comprised of a first particle joined to a second particle, b) delivering the plurality of linked particles into the urinary bladder of the subject, c) allowing degradation of the at least a portion of the linked particles over a retention phase to form individual particles, d) allowing excretion of the individual particles during urination, wherein each of the plurality of linked particles is comprised of an excipient portion and an active agent, and wherein the active agent is released into the urinary bladder during at least a portion of the retention phase. 2. The method of claim 1, wherein the ailment is a urinary tract infection, bladder cancer, kidney cancer, ureter cancer, urethra cancer, anticoagulant disease, overactive bladder, underactive bladder, retained urine, diabetes, heart failure, kidney failure or cystitis. 3. The method of claim 1, further comprising a step of diagnostic imaging. 4. The method of claim 1, further comprising a step of observing a color change in excreted urine over at least a portion of the period of the retention phase. 5. The method of claim 1, wherein each of the plurality of linked particles is substantially cylindrically shaped. 6. The method of claim 1, wherein each of the plurality of linked particles is buoyant in urine. PATENT WM1-006WO 7. The method of claim 1, wherein each of the plurality of linked particles has a hollow core. 8. The method of claim 1, wherein each of the plurality of linked particles has a solid core. 9. The method of claim 1, wherein the excipient portion is comprised of a degradable material. 10. The method of claim 1, wherein the active agent is a drug for the treatment of a disorder of the urinary system. 11. The method of claim 1, wherein the active agent is one or more of an anti-infective agent, an anesthetic agent, an analgesic agent, a diuretic, an anti-inflammatory agent, a coagulant or an anti-coagulant, a chemotherapeutic agent, an agent for the treatment of incontinence, a renin-angiotensin-aldosterone system (RAAS) inhibitor, an immunomodulating agent an agent for treating kidney stones, an agent for gene therapy or a contrast agent for diagnostics and monitoring. 12. The method of claim 11, wherein the anti-infective agent is an antibacterial agent. 13. The method of claim 11, wherein the anti-infective agent is an anti-fungal agent. 14. The method of claim 11, wherein the anti-infective agent is an antiviral agent. 15. The method of claim 11, wherein the anti-infective agent comprises elemental silver, silver ions, a silver salt, or a silver coordination compound. 16. The method of claim 11, wherein the anti-infective agent comprises silver bromide, silver chloride, silver iodate, silver iodide, fosfomycin, silver oxide, silver perchlorate, PATENT WM1-006WO silver tetrafluoroborate, silver acetate, silver benzoate, silver carbonate, silver lactate, silver laurate, silver palmitate, silver sulfadiazine (fosfomycin), or a degradation product of fosfomycin generated in situ. 17. The method of claim 1, wherein the step of delivering the plurality of linked particles into the urinary bladder of the subject comprises intraurethral delivery. 18. The method of claim 1, wherein a syringe is used in the step of delivering the plurality of linked particles into the urinary bladder of the subject. 19. The method of claim 1, wherein the retention phase is more than one month. 20. The method of claim 1, wherein each of the plurality of linked particles has a cross- sectional diameter of about 4 mm of less for insertion, and a cross-sectional diameter of about 10 mm or more during retention, and a cross-sectional diameter of about 4 mm or less for excretion. 21. The method of claim 1, wherein each of the plurality of linked particles is comprised of a matrix and the pharmacologically active agent dispersed therein. 22. The method of claim 1, wherein each of the plurality of linked particles is comprised of a coating on a core that comprises the pharmacologically active agent dispersed therein. 23. The method of claim 1, wherein the plurality of linked particles are dispersed in a liquid vehicle for delivery into the urinary bladder of the subject. 24. The method of claim 22, wherein the liquid vehicle comprises at least one of a viscosity adjusting agent, a tonicity adjusting agent, a buffer and a dispersant. PATENT WM1-006WO 25. The method of claim 1, wherein the active agent is released into the bladder at a substantially steady state. 26. The method of claim 1, where the step of delivering the plurality of linked particles into the urinary bladder of the subject further comprises disrupting biofilm with the urethra or bladder. 27. The method of claim 1, where the plurality of linked particles is administered to the bladder of the patient in a stacked arrangement. 28. A method of treating and/or preventing an ailment in a subject, the method comprising: a) providing a plurality of particles arranged in a first confirmation, each particle comprised of an excipient portion and an active agent, b) delivering the plurality of particles into the urinary bladder of the subject, c) allowing the plurality of particles to transition to a second confirmation in the bladder, d) releasing an active agent from the plurality of particles into the bladder of the subject, and e) allowing the plurality of particles to separate from one another so that they are excreted during urination. 29. The method of claim 28, wherein the shape of each particle is a cylinder, a sphere, a tear drop, a horseshoe, a pretzel, a rod, a pyramid, a cube, a prism or a straw. 30. The method of claim 28, wherein the ailment is a urinary tract infection, bladder cancer, kidney cancer, ureter cancer, urethra cancer, anticoagulant disease, overactive bladder, underactive bladder, retained urine, diabetes, heart failure, kidney failure, chronic inflammatory disease or cystitis. 31. The method of claim 28, further comprising a step of diagnostic imaging. PATENT WM1-006WO 32. The method of claim 28, further comprising a step of observing a color change in urine when the plurality of particles are excreted. 33. The method of claim 28, wherein each of the plurality of particles is substantially cylindrically shaped. 34. The method of claim 28, wherein each of the plurality of particles is buoyant in urine. 35. The method of claim 28, wherein each of the plurality of particles has a hollow core. 36. The method of claim 28, wherein each of the plurality of particles has a solid core. 37. The method of claim 28, wherein the excipient portion is comprised of a degradable material. 38. The method of claim 28, wherein the active agent is a medicament for treating a disorder of the urinary system. 39. The method of claim 28, wherein the active agent is one or more of an anti-infective agent, an anesthetic agent, an analgesic agent, a diuretic, an anti-inflammatory agent, a coagulant or an anti-coagulant, a chemotherapeutic agent, an agent for the treatment of incontinence, a renin-angiotensin-aldosterone system (RAAS) inhibitor, an immunomodulator an agent for treating kidney stones, an agent for gene therapy or a contrast agent for diagnostics and monitoring. 40. The method of claim 39, wherein the anti-infective agent is an antibacterial agent. 41. The method of claim 39, wherein the anti-infective agent is an anti-fungal agent. 42. The method of claim 39, wherein the anti-infective agent is an antiviral agent. PATENT WM1-006WO 43. The method of claim 39, wherein the anti-infective agent comprises elemental silver, silver ions, a silver salt, or a silver coordination compound. 44. The method of claim 39, wherein the anti-infective agent comprises silver bromide, silver chloride, silver iodate, silver iodide, fosfomycin, silver oxide, silver perchlorate, silver tetrafluoroborate, silver acetate, silver benzoate, silver carbonate, silver lactate, silver laurate, silver palmitate, silver sulfadiazine (fosfomycin), or a degradation product of fosfomycin generated in situ. 45. The method of claim 28, wherein the step of step of delivering the plurality of linked particles into the urinary bladder of the subject comprises intraurethral delivery. 46. The method of claim 28, wherein a syringe is used in the step of delivering the plurality of linked particles into the urinary bladder of the subject. 47. The method of claim 28, wherein the plurality of particles remains in the second confirmation for more than one week or longer. 48. The method of claim 28, wherein each of the plurality of linked particles has a cross- sectional diameter of about 4 mm of less in the first confirmation, and a cross-sectional diameter of about 10 mm or more in the second confirmation, and a cross-sectional diameter of about 4 mm or less after separation. 49. The method of claim 28, wherein each particle of the plurality of particles is comprised of a matrix and the pharmacologically active agent dispersed therein. 50. The method of claim 28, wherein each of the plurality of particles is comprised of a coating on a core that comprises the pharmacologically active agent dispersed therein. PATENT WM1-006WO 51. The method of claim 28, wherein the plurality of particles is dispersed in a liquid vehicle for delivery into the urinary bladder of the subject. 52. The method of claim 51, wherein the liquid vehicle comprises at least one of a viscosity adjusting agent, a tonicity adjusting agent, a buffer and a dispersant. 53. The method of claim 28, wherein the active agent is released into the bladder over a period of about one month. 54. The method of claim 28, wherein the active agent is released into the bladder at a substantially steady state. 55. The method of claim 28, where the step of delivering the plurality of particles into the urinary bladder of the subject further comprises disrupting biofilm with the urethra or bladder. 56. The method of claim 28, where the first confirmation of the plurality of particles is a stacked arrangement. 57. The method of claim 28, where the first confirmation of the plurality of particles is a stacked arrangement with a diameter of about 4 mm or less. 58. The method of claim 28, where the second confirmation of the plurality of particles is a zigzag or circular arrangement. 59. The method of claim 28, where the second confirmation of the plurality of particles is a zigzag or circular arrangement with a diameter of about 10 mm or more. 60. An intravesical drug delivery system, the system comprised of a plurality of particles, each particle having an excipient portion and an active agent, wherein the particles are buoyant in urine. PATENT WM1-006WO 61. The intravesical drug delivery system of claim 60, wherein the particles are substantially cylindrically shaped. 62. The intravesical drug delivery system of claim 60, wherein the particles are buoyant in urine. 63. The intravesical drug delivery system of claim 60, wherein the particles have a hollow core. 64. The intravesical drug delivery system of claim 60, wherein the particles have a solid core. 65.The intravesical drug delivery system of claim 60, wherein the excipient portion is comprised of a degradable material. 66. The intravesical drug delivery system of claim 60, wherein the active agent is a drug for the treatment of a disorder of the urinary system. 67. The intravesical drug delivery system of claim 60, wherein the active agent is one or more of an anti-infective agent, an anesthetic agent, an analgesic agent, a diuretic, an anti-inflammatory agent, a coagulant or an anti-coagulant, a chemotherapeutic agent, an agent for the treatment of incontinence, a renin-angiotensin-aldosterone system (RAAS) inhibitor, an immunomodulator an agent for treating kidney stones, an agent for gene therapy or a contrast agent for diagnostics and monitoring. 68. The intravesical drug delivery system of claim 67, wherein the anti-infective agent is an antibacterial agent. 69. The intravesical drug delivery system of claim 67, wherein the anti-infective agent is an anti-fungal agent. PATENT WM1-006WO 70. The intravesical drug delivery system of claim 67, wherein the anti-infective agent is an antiviral agent. 71. The intravesical drug delivery system of claim 67, wherein the anti-infective agent comprises elemental silver, silver ions, a silver salt, or a silver coordination compound. 72. The intravesical drug delivery system of claim 67, wherein the anti-infective agent comprises silver bromide, silver chloride, silver iodate, silver iodide, fosfomycin, silver oxide, silver perchlorate, silver tetrafluoroborate, silver acetate, silver benzoate, silver carbonate, silver lactate, silver laurate, silver palmitate, silver sulfadiazine (fosfomycin), or a degradation product of fosfomycin generated in situ. 73. An intravesical delivery system, the system comprised of: a) an insertion tip, b) a body, c) a pressure source, and d) a loading funnel, wherein an intravesical formulation passes from the loading funnel through the body and out of the insertion tip into a bladder of a subject. 74. The intravesical delivery system of claim 73, wherein the intravesical formulation is comprised of particles. 75. The intravesical delivery system of claim 74, wherein the particles are contained within two structures connected by a tether. 76. The intravesical delivery system of claim 74, wherein the particles are contained within two cylinder-shaped structures connected by a tether. PATENT WM1-006WO 77. The intravesical delivery system of claim 74, wherein the particles are contained within two rod-shaped structures connected by a tether. 78. The intravesical delivery system of claim 74, wherein each particle of the formulation has an excipient portion and an active agent. 79. The intravesical delivery system of claim 78, wherein the active agent is a drug for the treatment of a disorder of the urinary system. 80. The intravesical delivery system of claim 78, wherein the active agent is one or more of an anti-infective agent, an anesthetic agent, an analgesic agent, a diuretic, an anti-inflammatory agent, a coagulant or an anti-coagulant, a chemotherapeutic agent, an agent for the treatment of incontinence, a renin-angiotensin-aldosterone system (RAAS) inhibitor, an immunomodulator an agent for treating kidney stones, an agent for gene therapy or a contrast agent for diagnostics and monitoring. 81. The intravesical delivery system of claim 73, wherein the insertion tip is comprised of an inflatable balloon. 82. The intravesical delivery system of claim 73, wherein the insertion tip is variable in length. 83. The intravesical delivery system of claim 73, wherein the insertion tip is comprised of a threaded lock ring set. 84. The intravesical delivery system of claim 83, wherein the threaded lock ring set is adjusted to a size of the subject’s urethra. 85. The intravesical delivery system of claim 73, wherein the insertion tip is comprised of an internal sheath. PATENT WM1-006WO 86. The intravesical delivery system of claim 73, wherein the insertion tip is comprised of a plurality of soft grapple members. 87. The intravesical delivery system of claim 83, wherein the threaded lock ring set is adjusted to a size of the subject’s urethra. 88. A method of delivering a substance or formulation into the bladder of a subject using the intravesical delivery system of claim 73. 89. A method of delivering a substance or formulation into the bladder of a subject, the method comprised of: a) inserting a tip region of a catheter through the urethra and into the bladder, b) securing the tip region, and c) using a pressure source to force the substance or formulation into the bladder from a loading funnel. 88. The method of claim 89, wherein the substance or formulation is comprised of particles. 89. The method of claim 88, wherein the particles are contained within two structures connected by a tether. 90. The intravesical delivery system of claim 88, wherein the particles are contained within two cylinder-shaped structures connected by a tether. 91. The intravesical delivery system of claim 88, wherein the particles are contained within two rod-shaped structures connected by a tether. 92. The method of claim 88, wherein each particle of the formulation has an excipient portion and an active agent. PATENT WM1-006WO 93. The method of claim 92, wherein the active agent is a drug for the treatment of a disorder of the urinary system. 94. The method of claim 92, wherein the active agent is one or more of an anti-infective agent, an anesthetic agent, an analgesic agent, a diuretic, an anti-inflammatory agent, a coagulant or an anti-coagulant, a chemotherapeutic agent, an agent for the treatment of incontinence, a renin-angiotensin-aldosterone system (RAAS) inhibitor, an agent for treating kidney stones, an immunomodulating agent, an agent for gene therapy or a contrast agent for diagnostics and monitoring. 95. The method of claim 89, wherein an inflatable balloon is used in the step of securing the tip region. 96. The method of claim 89, further comprising a step of adjusting the length of the tip region of the catheter using a threaded lock ring set. 97. The method of claim 89, wherein an internal sheath is used in the step of securing the tip region. 98. The method of claim 89, wherein a plurality of soft grapple members is used in the step of securing the tip region. 99. A method for delivering an active agent into the bladder of a subject, the method comprising: a) inserting a distal end of a lumen device through a patient’s urethra and into the patient’s bladder, wherein an opposing proximal end of the lumen device remains outside of the patient; b) securing the distal end of the lumen device; b) driving a plurality of particles out of a lumen in the distal end of the lumen device and into the bladder and out of the lumen, c) removing the lumen device from the patient’s urethra; and PATENT WM1-006WO d) allowing the plurality of particles to degrade or dissolve thereby releasing an active agent into the patient’s bladder. 100. The method of claim 99, wherein the particles are contained within two structures connected by a tether. 101. The method of claim 99, wherein the particles are contained within two cylinder- shaped structures connected by a tether. 102. The method of claim 99, wherein the particles are contained within two rod-shaped structures connected by a tether. 103. The method of claim 99, wherein each particle of the plurality of particles has an excipient portion and an active agent. 104. The method of claim 103, wherein the active agent is a drug for the treatment of a disorder of the urinary system. 105. The method of claim 103, wherein the active agent is one or more of an anti- infective agent, an anesthetic agent, an analgesic agent, a diuretic, an anti-inflammatory agent, a coagulant or an anti-coagulant, a chemotherapeutic agent, an agent for the treatment of incontinence, a renin-angiotensin-aldosterone system (RAAS) inhibitor, an immunomodulator an agent for treating kidney stones, an agent for gene therapy or a contrast agent for diagnostics and monitoring. 106. The method of claim 99, wherein an inflatable balloon is used in the step of securing the tip region. 107. The method of claim 99, further comprising a step of adjusting the length of the tip region of the catheter using a threaded lock ring set. PATENT WM1-006WO 108. The method of claim 99, wherein an internal sheath is used in the step of securing the tip region. 109. The method of claim 99, wherein a plurality of soft grapple members is used in the step of securing the tip region. 110. The method of claim 99, wherein the subject suffers from a disorder of the urinary system. 111. The method of claim 99, wherein the disorder of the urinary system is one or more of a urinary tract infection, bladder cancer, kidney cancer, ureter cancer, urethra cancer, anticoagulant disease, overactive bladder, underactive bladder, retained urine, diabetes, heart failure, kidney failure or cystitis 112. The method of claim 99, further comprising a step of treating the subject for a disorder of the urinary system. 113. The method of claim 103, where the active agent is one or more of a urease inhibitor, a chelating agent, an antibacterial agent and an enzyme. 114. The method of claim 99, wherein the particles are substantially cylindrically shaped. 115. The method of claim 99, wherein the particles are buoyant in urine. 116. The method of claim 99, wherein the particles are comprised of an excipient portion that degrades in the bladder. 117. The method of claim 116, wherein the excipient portion degrades over a period of time that is more than one month. PATENT WM1-006WO 118. The method of claim of claim 103, wherein the active agent is a drug for the treatment of a disorder of the urinary system. 119. The method of claim 103, wherein the active agent is one or more of an anti- infective agent, an anesthetic agent, an analgesic agent, a diuretic, an anti-inflammatory agent, a coagulant or an anti-coagulant, a chemotherapeutic agent, an agent for the treatment of incontinence, a renin-angiotensin-aldosterone system (RAAS) inhibitor, an immunomodulator an agent for treating kidney stones, an agent for gene therapy or a contrast agent for diagnostics and monitoring. 120. The method of claim 103, wherein the active agent is an antibacterial agent, anti- fungal agent or an antiviral agent. 121. The method of claim 103, wherein the active agent is comprised of elemental silver, silver ions, a silver salt, or a silver coordination compound. 122. The method of claim 99, wherein the subject is male. 123. The method of claim 99, wherein the subject is female. 124. The method of claim 103, wherein the particles are comprised of a coating on a core that comprises the active agent dispersed therein. 125. The method of claim 99, wherein the particles are dispersed in a liquid vehicle for delivery into the urinary bladder of the subject. 126. The method of claim 125, wherein the liquid vehicle comprises at least one of a viscosity adjusting agent, a tonicity adjusting agent, a buffer and a dispersant. 127. The method of claim 99, further comprising a step of determining a specific volume or number of particles to be administered based on a desired dose of the active agent. PATENT WM1-006WO 128. A system for intravesical administration of an active agent, the system comprised of: a) a plurality of particles arranged in a first confirmation, each particle comprised of an excipient portion and the active agent, b) wherein the plurality of particles is configured to expand to a second confirmation upon exposure to fluid, c) wherein the plurality of particles is configured to release an active agent from the plurality of particles upon exposure to fluid, and d) wherein the plurality of particles is configured to separate into individual particles after a retention period in fluid. 129. The system of claim 128, wherein each of the plurality of particles is substantially cylindrically shaped. 130. The system of claim 128, wherein each of the plurality of particles is buoyant in urine. 131. The system of claim 128, wherein each of the plurality of particles has a hollow core. 132. The system of claim 128, wherein each of the plurality of particles has a solid core. 133. The system of claim 128, wherein the active agent is a drug for the treatment of a disorder of the urinary system. 134. The system of claim 128, wherein the active agent is one or more of an anti- infective agent, an anesthetic agent, an analgesic agent, a diuretic, an anti-inflammatory agent, a coagulant or an anti-coagulant, a chemotherapeutic agent, an agent for the treatment of incontinence, a renin-angiotensin-aldosterone system (RAAS) inhibitor, an PATENT WM1-006WO immunomodulator an agent for treating kidney stones, an agent for gene therapy or a contrast agent for diagnostics and monitoring. 135. The system of claim 134, wherein the anti-infective agent is an antibacterial agent. 136. The system of claim 134, wherein the anti-infective agent is an anti-fungal agent. 137. The system of claim 134, wherein the anti-infective agent is an antiviral agent. 138. The system of claim 134, wherein the anti-infective agent comprises elemental silver, silver ions, a silver salt, or a silver coordination compound. 139. The system of claim 134, wherein the anti-infective agent comprises silver bromide, silver chloride, silver iodate, silver iodide, fosfomycin, silver oxide, silver perchlorate, silver tetrafluoroborate, silver acetate, silver benzoate, silver carbonate, silver lactate, silver laurate, silver palmitate, silver sulfadiazine (fosfomycin), or a degradation product of fosfomycin generated in situ. 140. The system of claim 128, wherein the shape of each particle is a cylinder, a sphere, a tear drop, a horseshoe, a pretzel, a rod, a pyramid, a cube, a prism or a straw. 141. A method of treating an ailment, the method comprised of intravesical administration of the system of claim 128. 142. The method of claim 141, wherein the ailment is a urinary tract infection, bladder cancer, kidney cancer, ureter cancer, urethra cancer, anticoagulant disease, overactive bladder, underactive bladder, retained urine, diabetes, heart failure, kidney failure or cystitis. PATENT WM1-006WO 143. A method of treating and/or preventing an ailment in a subject, the method comprising: a) providing a plurality of particles, each particle comprised of a first particle joined to a second particle by a linkage, b) delivering the plurality of particles into the urinary bladder of the subject, c) allowing degradation of the linkage and/or particles over a retention phase, d) allowing excretion of the linkage and particles during urination, wherein each of the plurality of particles is comprised of an excipient portion and an active agent, and wherein the active agent is released into the urinary bladder during at least a portion of the retention phase. 144. The method of claim 143, wherein the ailment is a urinary tract infection, bladder cancer, kidney cancer, ureter cancer, urethra cancer, anticoagulant disease, overactive bladder, underactive bladder, retained urine, diabetes, heart failure, kidney failure or cystitis. 145. The method of claim 143, further comprising a step of diagnostic imaging. 146. The method of claim 143, further comprising a step of observing a color change in excreted urine over at least a portion of the period of the retention phase. 146. The method of claim 143, wherein each of the plurality of particles is substantially cylindrically shaped. 147. The method of claim 143, wherein each of the plurality of particles is buoyant in urine. 148. The method of claim 143, wherein each of the plurality of particles has a hollow core. 149. The method of claim 143, wherein each of the plurality of particles has a solid core. PATENT WM1-006WO 150. The method of claim 143, wherein the excipient portion is comprised of a degradable material. 151. The method of claim 143, wherein the active agent is a drug for the treatment of a disorder of the urinary system. 152. The method of claim 143, wherein the active agent is one or more of an anti- infective agent, an anesthetic agent, an analgesic agent, a diuretic, an anti-inflammatory agent, a coagulant or an anti-coagulant, a chemotherapeutic agent, an agent for the treatment of incontinence, a renin-angiotensin-aldosterone system (RAAS) inhibitor, an immunomodulating agent an agent for treating kidney stones, an agent for gene therapy or a contrast agent for diagnostics and monitoring. 153. The method of claim 143, wherein the step of delivering the plurality of particles into the urinary bladder of the subject comprises intraurethral delivery. 154. The method of claim 143, wherein a syringe is used in the step of delivering the plurality of particles into the urinary bladder of the subject. 155. The method of claim 143, wherein the retention phase is more than one month. 156. The method of claim 143, wherein each of the plurality of particles is comprised of a matrix and the pharmacologically active agent dispersed therein. 157. The method of claim 143, wherein each of the plurality of particles is comprised of a coating on a core that comprises the pharmacologically active agent dispersed therein. 158. The method of claim 143, wherein the plurality of particles is dispersed in a liquid vehicle for delivery into the urinary bladder of the subject. PATENT WM1-006WO 159. The method of claim 158, wherein the liquid vehicle comprises at least one of a viscosity adjusting agent, a tonicity adjusting agent, a buffer and a dispersant. 160. The method of claim 143, wherein the active agent is released into the bladder over a period of about one month. 161. The method of claim 143, wherein the active agent is released into the bladder at a substantially steady state. 162. The method of claim 143, where the step of delivering the plurality of particles into the urinary bladder of the subject further comprises disrupting biofilm with the urethra or bladder. 163. The method of claim 143, where the plurality of particles is administered to the bladder of the patient in a stacked arrangement. 164. The method of claim 143, where the first of the plurality of particles provide for buoyancy and the second of the plurality of particles is provided for administering an active agent. 165. The method of claim 1, wherein one or more of the plurality of particles has a hollow core. 166. The method of claim 1, wherein one or more of the plurality of particles has a solid core.

Description

SYSTEM AND METHOD FOR SUSTAINED RELEASE OF AGENTS IN THE BLADDER RELATED APPLICATIONS [0001] The present application claims priority to U.S. provisional patent application No.63/524,229 filed June 30, 2023 and U.S. provisional patent application No. 63/541,493 filed September 29, 2023. The contents of these applications are incorporated herein by reference. FIELD OF THE INVENTION [0002] The invention relates generally to the medical devices, and, more particularly, to devices and methods for intravesical administration of a pharmacologically active agent to treat or prevent a disorder of the urinary system. BACKGROUND [0003] A urinary tract infection (“UTI”) is an infection that affects part of the urinary tract. When it affects the lower urinary tract it is known as a bladder infection (i.e., cystitis) and when it affects the upper urinary tract it is known as a kidney infection (i.e., pyelonephritis). Symptoms from a lower urinary tract infection include pain with urination, frequent urination, and feeling the need to urinate despite having an empty bladder. The most common cause of UTI is Escherichia coli, though other bacteria or fungi can also be the cause. Risk factors include female anatomy, sexual intercourse, diabetes, obesity, and family history. In uncomplicated cases, UTIs are treated with a short course of antibiotics (e.g., nitrofurantoin). Nearly one in five adults develops a UTI, and many of these individuals are at risk for a recurring infection. [0004] The prevalence of UTI risk increases with age. They are particularly common in older adults who use catheters or live in a nursing home or other full-time care facilities. Other conditions common in older adults (e.g., Alzheimer’s disease, Parkinson’s disease and diabetes) can lead to urinary retention or neurogenic bladder which increases the risk of UTIs. More than 10 percent of women over age 65 report PATENT WM1-006WO having a UTI within the past year. That number increases to almost 30 percent in women over 85. Men also tend to experience more UTIs as they age. According to a recent study, more than one-third of all infections in people in nursing homes are UTIs. In many cases, chronic urinary tract infections can require continuous medication, which leads to progressive levels of resistance to antibiotics and ultimately to kidney problems. [0005] If not treated timely or properly, an infection from a UTI can spread. A UTI can ultimately lead to a bladder infection. This presents the risk of the infection spreading to the kidney via the ureter which can lead to more serious consequences including kidney failure and sepsis (i.e., urosepsis). This occurs frequently in elderly patients. In many cases, elderly patients do not present typical signs of infection until they’ve become septic at which point hospitalization is needed. [0006] UTIs and complications caused by UTIs are also expensive to treat as they often require hospitalization. In many cases, a UTI is only treated after the infection has developed and becomes symptomatic. Current treatments aimed at preventing the formation of UTIs require continuous prophylactic oral medication that have side-effects common with long–term medication. Further, long term consumption of antibiotics can lead to drug resistant bacteria. In many cases, UTIs reduce the quality of life, in particular when kidney damage leads to kidney failure requiring dialysis or implantation of a donor kidney. [0007] Conventionally, UTIs are treated with oral antibiotics. A high dose of antibiotics is needed so that an effective amount reaches the urinary tract. With systemic delivery of drugs to treat UTIs, the volume of distribution of the therapy is equal to the total amount of urine that enters the bladder. Therefore, the therapy is voided with each emptying of the bladder and requires constant replenishment. In other cases, the drug target can be limited (i.e., the bladder wall) but cannot practically be reached without raising the concentration of the drug in the urine to the desired therapeutic concentration. PATENT WM1-006WO [0008] Intravesical therapy refers to a treatment wherein a therapeutic is put directly into the bladder (e.g., through a catheter or similar device) rather than being given orally or injected into a vein. Intravesical therapy is an attractive option for treating UTIs because it allows local delivery of a medicament while minimizing side effects. Intravesical administration of pharmaceutically active agents can also be beneficial for treating other diseases of the bladder/urinary tract such as interstitial cystitis, overactive bladder and cancers. [0009] Efforts at treating UTIs via intravesical therapy have had limited success. Antibiotics injected into the bladder are generally voided before they can induce a significant therapeutic effect. Implantable devices require surgical procedures for their implantation and removal. Recent improvements include implantable devices that graduall