Implantable repository for localized, sustained, controlled release of therapeutic agents for treatment of cancer and related symptoms and conditions

Abstract

The present application relates to implantable reservoirs for local, sustained, controlled release of therapeutic agents for the treatment of cancer and related symptoms and conditions. The present technology relates to implantable reservoirs for localized, sustained, controlled release of therapeutic agents to treat cancer. An implantable repository may include a biodegradable polymer in admixture with a topically effective therapeutic agent configured to treat cancer. The repository may be configured to be implanted within a patient proximate to cancerous tissue and, when implanted, provide for continuous exposure of the therapeutic agent at the treatment site for a period of time no less than 5 days.

Description

[0001] This application is a divisional application of Chinese patent application No. 202080040453.0, filed on April 11, 2020, entitled "Implantable Depository for Local, Sustained, and Controlled Release of Therapeutic Agents for Treating Cancer and Related Symptoms and Conditions".

[0002] Cross-reference to related applications

[0003] This application claims priority to U.S. Provisional Application No. 62 / 832,876, filed April 11, 2019, and U.S. Provisional Application No. 62 / 907,415, filed September 27, 2019, each of which is incorporated herein by reference in its entirety.

[0004] This application is incorporated herein by reference in its entirety of each of the following applications: International Application No. PCT / US2019 / 012795, filed January 8, 2019; International Application No. PCT / US2018 / 054777, filed October 6, 2018; U.S. Application No. 62 / 723,478, filed August 28, 2018; U.S. Application No. 62 / 670,721, filed May 12, 2018; U.S. Application No. 62 / 640,571, filed March 8, 2018; U.S. Application No. 62 / 614,884, filed January 8, 2018; U.S. Patent Application No. 62 / 742,357, filed October 6, 2018; and U.S. Application No. 62 / 569,349, filed October 6, 2017. Technical Field

[0005] This technology relates to implants for the localized, controlled, sustained release of therapeutic agents for treating cancer and related symptoms and conditions in vivo. Background Technology

[0006] Most chemotherapy drugs act on both normal and cancerous tissues. Therefore, one of the challenges of treating cancerous tumors with chemotherapy is maximizing the killing of cancer cells while minimizing damage to healthy tissues. Over the past few decades, polymer-based drug delivery systems have been investigated as a means of achieving high therapeutic concentrations of chemotherapy at the malignant site in cancer patients. The development of these technologies has been driven by the desire to improve overall survival and quality of life by increasing the bioavailability of drugs to the disease site, delivering them directly to cancerous tissue, and minimizing systemic side effects.

[0007] Existing chemotherapy delivery systems are either systemic or local. Systemic delivery vehicles find their targets through passive diffusion (via the leaky tumor vascular system) and / or active targeting of unique tumor cell markers. These nanomaterials are primarily intended for intravenous administration, and while they guarantee the ability to target tumor tissue with cumulative therapeutic concentrations, localization due to the removal and isolation of these nanomaterials by the reticuloendothelial system is challenging. Depending on the route of administration (e.g., intravenous) and the properties of the drug (e.g., its physical and pharmacokinetic properties), typically only a small fraction of the dose reaches the target cells; the remaining amount of drug acts on other tissues or is rapidly eliminated.

[0008] To improve drug delivery efficiency and reduce toxicity to non-target cells, various strategies have been employed to deliver drugs to specific sites in the body. For example, the use of toxin-conjugated monoclonal antibodies has been reported in cancer treatment. Antibodies provide selectivity for the target, but the problem of interaction with non-target cells during delivery to the intended site of action remains.

[0009] Alternative methods for encapsulating toxins in liposomes have also been actively investigated. Liposomes are essentially membrane bilayer structures containing lipids of biological or synthetic origin, such as phospholipids, sphingolipids, glycosphingolipids, ceramides, or cholesterol. Liposomes can encapsulate large amounts of drug molecules within their aqueous interiors or dissolve them into the hydrocarbon regions of their bilayers. Liposomes also protect their contents from rapid filtration by the kidneys and metabolic degradation, thereby increasing the drug's residence time in the body. Once taken up by target cells (e.g., via ligand-mediated endocytosis), liposomes can also facilitate cytoplasmic delivery of encapsulated drug molecules by fusing with the endosome membrane. However, the clinical utility of liposomes in targeted drug delivery is severely limited by: (1) rapid clearance by phagocytes of the reticuloendothelial system (RES), (2) lack of specific tumor targeting, and (3) premature or inappropriate drug release.

[0010] The second group of polymeric drug delivery carriers includes controlled-release drug delivery reservoir systems for implantation within the tumor or adjacent to cancerous tissue. The potential benefits of local chemotherapy at the tumor site are numerous and aim to enhance treatment efficacy and reduce patient morbidity. Direct delivery of drug-loaded implants to the disease site offers the following advantages over traditional systemic administration: 1) stable encapsulated drug molecules and preservation of anticancer activity; 2) controlled and prolonged drug release to ensure adequate diffusion and uptake into cancer cells across multiple cycles of tumor cell division; 3) loading and release of water-insoluble chemotherapeutic agents; 4) direct delivery to the disease site, resulting in less drug waste; 5) single-dose administration; and 6) reduced side effects due to avoiding systemic circulation of chemotherapeutic drugs.

[0011] Therefore, there is a need for biodegradable implantable systems that can provide local, controlled, and sustained release of therapeutic agents to treat cancer. Summary of the Invention

[0012] This technology relates to implantable polymer repositories for the localized, controlled, sustained release of therapeutic agents for treating cancer and related symptoms and conditions. For example, according to various aspects described below, including references... Figure 1-96 The subject matter technique is described. For convenience, various instances of aspects of the subject matter technique are described as numbered clauses (1, 2, 3, etc.). These are provided as examples and do not limit the subject matter technique.

[0013] 1. A repository for treating bladder cancer by sustained, controlled release of a therapeutic agent into a patient, the repository comprising:

[0014] A treatment area containing a therapeutic agent, which at least contains a chemotherapeutic agent;

[0015] A control region comprising a polymer and a release agent mixed with the polymer, wherein the release agent is configured to dissolve when the reservoir is placed in vivo to form a diffusion opening in the control region; and

[0016] The storage facility is configured to be implanted at a treatment site close to the patient's bladder, and when implanted, it releases chemotherapy agents at the treatment site for a period of not less than 7 days.

[0017] 2. A repository for treating bladder cancer by sustained, controlled release of a therapeutic agent into a patient, the repository comprising:

[0018] A treatment area containing a therapeutic agent, which at least contains a chemotherapeutic agent;

[0019] A control region comprising a polymer and a release agent mixed with the polymer, wherein the release agent is configured to dissolve when the reservoir is placed in vivo to form a diffusion opening in the control region; and

[0020] The storage facility is configured to be implanted at a treatment site close to the patient's bladder, and when implanted, it releases chemotherapy agents at the treatment site for a period of not less than 7 days.

[0021] 3. The reservoir of any of the preceding clauses, wherein the reservoir is configured to self-expand and attach to the inner surface of the bladder wall when released from the drug delivery device.

[0022] 4. The reservoir of any of the preceding clauses, wherein the reservoir is configured to self-expand and attach to the tumor on the inner surface of the bladder wall when released from the drug delivery device.

[0023] 5. A reservoir according to any of the preceding clauses, wherein the reservoir contains at least one opening extending therein, such that if positioned above the opening of the urethra within the bladder, the reservoir will not substantially obstruct the flow from the internal region of the bladder into the urethra.

[0024] 6. The reservoir of any of the preceding clauses, wherein the reservoir has a predetermined shape such that the reservoir assumes the predetermined shape when released from the drug delivery device.

[0025] 7. The storage facility of any of the preceding clauses, wherein the storage facility has a curved, predetermined shape.

[0026] 8. A storage facility of any of the preceding clauses, wherein the storage facility has a first region and a second region, each extending longitudinally and extending together with each other over all or part of their respective lengths, the first region having a first elasticity and the second region having a second elasticity less than the first elasticity.

[0027] 9. The reservoir of the foregoing clause, wherein the reservoir is stretched beyond the elastic hysteresis point of the second region, such that when released from the drug delivery device, the reservoir changes from a straight state to a bent state in which the second region stretches the reservoir into a bent shape.

[0028] 10. A storage facility of any of the preceding clauses, wherein the storage facility has a first region and a second region, each extending longitudinally and extending together with each other over all or part of their respective lengths, the first region being more hydrophilic than the second region.

[0029] 11. The reservoir of the foregoing clause, wherein when released from the drug delivery device, the reservoir changes from a straight state to a bent state in which the second region pulls the reservoir into a bent shape.

[0030] 12. A storage facility of any of the preceding clauses, wherein the storage facility includes a centerline, a first region sharing the centerline, and a second region surrounded by the first region and having a centerline offset from the centerline of the storage facility, each of the first and second regions extending longitudinally and sharing with each other over all or part of their respective lengths, and wherein the first region is more elastic or more hydrophilic than the second region, such that the storage facility is biased toward a curved shape.

[0031] 13. The reservoir of any of the preceding clauses further comprises an impermeable base region surrounding all or part of one or both of the control region and the treatment region, such that when the reservoir is located at the treatment site, chemotherapeutic agents are selectively released in a direction away from the base region.

[0032] 14. A storage container of any of the preceding clauses, wherein the storage container comprises an elongated polymer strip having a length between its longitudinal ends and a width between its transverse edges, the length being greater than the width, and wherein the storage container has a predetermined shape of an expanded configuration in which the strip is curled around an axis while the width of the strip faces the axis, thereby forming an annular shape.

[0033] 15. A repository of any of the preceding clauses, wherein the chemotherapeutic agents are at least one of the following: epirubicin, doxorubicin, mitomycin C, gemcitabine, and docetaxel.

[0034] 16. A storage facility for any of the preceding clauses, wherein the polymer includes bioabsorbable polymers.

[0035] 17. A storage facility for any of the preceding clauses, wherein the polymer includes non-bioabsorbable polymers.

[0036] 18. A storage facility of any of the preceding clauses, wherein the polymer is a first polymer and wherein the treatment area contains a second polymer.

[0037] 19. A storage facility for any of the preceding clauses, wherein the first and / or second polymer comprises a bioabsorbable polymer.

[0038] 20. A storage facility for any of the preceding clauses, wherein the first and / or second polymer comprises a non-bioabsorbable polymer.

[0039] 21. A storage facility for any of the preceding clauses, wherein the first and / or second polymer comprises thermoplastic polyurethane.

[0040] 22. A storage facility for any of the preceding clauses, wherein the first and / or second polymer comprises ethyl vinyl acetate.

[0041] 23. A storage facility of any of the preceding clauses, wherein the first polymer is non-bioabsorbable and the second polymer is bioabsorbable.

[0042] 24. A storage facility for any of the preceding clauses, wherein the first and second polymers are identical.

[0043] 25. A reservoir for any of the preceding clauses, wherein the treatment area is configured to continuously release chemotherapeutic agents at a constant rate for a period of time.

[0044] 26. A reservoir for any of the preceding clauses, wherein the treatment area is configured to continuously release chemotherapeutic agents at a rate that increases over time.

[0045] 27. The storage period for any of the preceding clauses shall be no less than 2 weeks, no less than 3 weeks, no less than 4 weeks, no less than 5 weeks, no less than 6 weeks, no less than 7 weeks, no less than 8 weeks, no less than 2 months, no less than 3 months, no less than 4 months, no less than 6 months, no less than 7 months, no less than 8 months, no less than 9 months, no less than 10 months, no less than 12 months, or no less than 1 year.

[0046] 28. A storage facility of any of the preceding clauses, wherein the chemotherapeutic agent includes mitomycin C, and the storage facility is configured to release mitomycin at a continuous rate for at least 3 weeks, at least 4 weeks, at least 5 weeks, at least 6 weeks, at least 7 weeks, or at least 8 weeks.

[0047] 29. A storage facility for any of the preceding clauses, wherein the chemotherapeutic agents include mitomycin, and the treatment area contains not less than 120 mg, 150 mg, 180 mg, 210 mg, 240 mg, 270 mg, 300 mg, 330 mg, 360 mg, 390 mg, 420 mg, 450 mg, 480 mg, or 510 mg of mitomycin.

[0048] 30. A repository of any of the preceding clauses, wherein the chemotherapeutic agent includes gemcitabine, and the repository is configured to release gemcitabine at a continuous rate for at least 3 weeks, at least 4 weeks, at least 5 weeks, at least 6 weeks, at least 7 weeks, or at least 8 weeks.

[0049] 31. A repository of any of the preceding clauses, wherein the chemotherapy agents include gemcitabine, and the treatment area contains not less than 200 mg, 300 mg, 400 mg, 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, 1000 mg, 1100 mg, 1200 mg, 1300 mg, 1400 mg, 1500 mg, 1600 mg, 1700 mg, 1800 mg, 1900 mg, 2000 mg, 2100 mg, 2200 mg, 2300 mg, 2400 mg, 2500 mg, 2600 mg, 2700 mg, 2800 mg, 2900 mg, or 3000 mg of gemcitabine.

[0050] 32. The storage facility of any of the preceding clauses, wherein the time period is a first time period, and wherein the therapeutic agent further comprises an immunotherapeutic agent and the storage facility is configured to release the immunotherapeutic agent for a second time period.

[0051] 33. The method of any of the preceding clauses, wherein the first time period is longer than the second time period.

[0052] 34. The method of any of the preceding clauses, wherein the second time period is shorter than the first time period.

[0053] 35. The method of any of the foregoing clauses, wherein the first and second time periods are different.

[0054] 36. The method of any of the preceding clauses, wherein the first and second time periods are the same.

[0055] 37. The method of any of the preceding clauses, wherein the reservoir is configured to substantially simultaneously begin releasing therapeutic doses of chemotherapeutic agents and therapeutic doses of immunotherapeutic agents.

[0056] 38. The method of any of the preceding clauses, wherein the reservoir is configured to begin releasing a therapeutic dose of chemotherapeutic agent immediately after implantation, and wherein the reservoir is configured to begin releasing a therapeutic dose of immunotherapy agent immediately after implantation, the second time being different from the first time.

[0057] 39. The method of any of the preceding clauses, wherein the second time is 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, or 8 weeks prior to the first time.

[0058] 40. The method of any of the preceding clauses, wherein the second time is 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, or 8 weeks after the first time.

[0059] 41. A repository of any of the preceding clauses, wherein immunotherapeutic agents include BCG (“BCG”).

[0060] 42. A repository of any of the preceding clauses, wherein the treatment area comprises a first part and a second part, wherein the first part contains chemotherapeutic agents and the second part contains immunotherapeutic agents.

[0061] 43. The storage facility of any of the preceding clauses, wherein the first part is closer to the outer surface of the storage facility than the second part.

[0062] 44. The storage facility of any of the preceding clauses, wherein the first portion is further away from the outer surface of the storage facility than the second portion.

[0063] 45. A storage facility of any of the preceding clauses, wherein the storage facility is configured to continuously release immunotherapeutic agents over a period of time.

[0064] 46. ​​A storage facility of any of the preceding clauses, wherein the treatment area is configured to intermittently release immunotherapy agents over a period of time.

[0065] 47. A repository of any of the preceding clauses, wherein the repository is configured to release chemotherapeutic agents at a first rate and immunotherapeutic agents at a second rate.

[0066] 48. A storage facility of any of the preceding clauses, wherein the first rate is the same as the second rate.

[0067] 49. A storage facility of any of the preceding clauses, wherein the first rate is different from the second rate.

[0068] 50. A storage facility of any of the preceding clauses, wherein the first rate is greater than the second rate.

[0069] 51. A storage facility of any of the preceding clauses, wherein the first rate is less than the second rate.

[0070] 52. The reservoir of any of the preceding clauses, wherein the reservoir is configured to be located adjacent to the bladder wall.

[0071] 53. A reservoir for any of the preceding clauses, wherein the reservoir is configured to be located adjacent to the bladder wall and to release chemotherapeutic agents to treat tumors at a thickness of the bladder wall corresponding to one or more of the following: urethral epithelium, lamina propria, muscle, fat, and peritoneum.

[0072] 54. The reservoir of any of the preceding clauses, wherein the reservoir includes a fixed portion configured to adhere to the inner surface of the bladder wall.

[0073] 55. The reservoir of any of the preceding clauses, wherein the surface of the reservoir comprises a positively charged polymer configured to fix the reservoir to the bladder wall.

[0074] 56. A storage facility of any of the preceding clauses, wherein the storage facility contains a thermosensitive gel and / or hydrogel having reverse thermogelation.

[0075] 57. The reservoir of any of the preceding clauses, wherein the reservoir includes a reinforced portion configured to penetrate at least a portion of the bladder wall thickness, thereby securing the reservoir to the bladder wall.

[0076] 58. A reservoir according to any of the preceding clauses, wherein the reservoir includes an anchoring member connected to a treatment area, a control area and / or a base area, and wherein the anchoring member is configured to self-expand and attach to at least a portion of the inner surface of the bladder wall, thereby securing the reservoir to or within the bladder.

[0077] 59. A system for treating bladder cancer by controlled sustained release of a therapeutic agent, the system comprising:

[0078] The storage facility for any of the foregoing clauses; and

[0079] A drug delivery device configured to position the reservoir in the bladder.

[0080] 60. The system of any of the preceding clauses, wherein the drug delivery device is configured to position the reservoir on the bladder wall.

[0081] 61. The system of any of the preceding clauses, wherein the drug delivery device is a catheter configured to be positioned through the urethra.

[0082] 62. A system for treating bladder cancer by controlled sustained release of a therapeutic agent, the system comprising:

[0083] The storage facility for any of the foregoing clauses; and

[0084] An anchoring component that connects to and is configured to secure the reservoir within the bladder's internal region.

[0085] 63. The system of any of the preceding clauses, wherein the anchoring member forms an expanded member in the deployed state, and wherein the reservoir is connected to the outer surface of the expanded member such that when the anchoring member is deployed in the bladder cavity, the anchoring member pushes the reservoir outward and fixes the reservoir in contact with the bladder wall and / or a tumor at the bladder wall.

[0086] 64. A system of any of the preceding clauses, wherein the expanded component comprises the shape of any of the following: a pretzel, a donut, an infinity symbol, a spring, a coil, or a paperclip.

[0087] 65. A system for treating bladder cancer, comprising:

[0088] Multiple storage facilities, each containing any of the foregoing clauses; and

[0089] A drug delivery device configured to position the reservoir in the bladder.

[0090] 66. A method for treating bladder cancer by controlled sustained release of a therapeutic agent, the method comprising:

[0091] Provide a storage facility that meets any of the foregoing terms.

[0092] 67. A method for treating bladder cancer or overactive bladder disease by controlled sustained release of a therapeutic agent, the method comprising:

[0093] The storage facility for any of the foregoing clauses shall be located at the treatment site near the patient's bladder;

[0094] The therapeutic agent should be administered to the treatment site for a period of not less than 7 days.

[0095] 68. A method for treating at least one of the following by controlled sustained release of a therapeutic agent: overactive bladder, interstitial cystitis, bladder pain syndrome, urinary tract infection, wherein the method comprises:

[0096] The storage facility for any of the foregoing clauses shall be located at the treatment site near the patient's bladder;

[0097] The therapeutic agent should be administered to the treatment site for a period of not less than 7 days.

[0098] 69. The method of any of the preceding clauses also includes fixing the reservoir in the bladder.

[0099] 70. The method of any of the preceding clauses further includes fixing the reservoir to a portion of the bladder wall.

[0100] 71. The method of any of the preceding clauses further includes fixing the reservoir to a portion of the bladder wall such that a first surface of the reservoir contacts a tumor in the bladder wall, and releasing a chemotherapeutic agent toward the first surface and the tumor.

[0101] 72. Any of the methods mentioned in the preceding clauses, wherein the time period is not less than two weeks, not less than three weeks, not less than four weeks, not less than five weeks, not less than eight weeks, not less than two months, not less than three months, not less than four months, not less than six months, not less than seven months, not less than eight months, not less than nine months, not less than ten months, not less than twelve months, not less than one year, not less than two years, or not less than three years.

[0102] 73. The method of any of the preceding clauses, wherein the chemotherapeutic agent is released once or multiple times in substantially discrete doses over a period of time after implantation.

[0103] 74. The method of any of the preceding clauses, wherein the chemotherapy agent is continuously released for a period of time after implantation.

[0104] 75. Any of the methods described in the preceding clauses may also include slowing the growth of tumors in the bladder wall.

[0105] 76. Any of the methods described in the preceding clauses also includes causing the tumor at the bladder wall to contract.

[0106] 77. Any of the methods described in the preceding clauses also includes reducing the likelihood of tumor regrowth at the bladder wall.

[0107] 78. A reservoir for treating malignant pleural effusion (“MPE”) by means of a sustained, controlled release of a therapeutic agent into a patient, the reservoir comprising:

[0108] A treatment area containing a therapeutic agent, which at least contains a chemotherapeutic agent;

[0109] A control region comprising a polymer and a release agent mixed with the polymer, wherein the release agent is configured to dissolve when the reservoir is placed in vivo to form a diffusion opening in the control region; and

[0110] The storage facility is configured to be implanted at the treatment site close to the patient's pleura, and when implanted, it releases chemotherapy agents at the treatment site for a period of not less than 7 days.

[0111] 79. The storage facility of any of the preceding clauses, wherein the storage facility is a flexible film.

[0112] 80. A reservoir according to any of the preceding clauses, wherein the reservoir has a low-profile state for administering medication to a treatment site via a drug delivery device and an expanded state for positioning near the pleura.

[0113] 81. The reservoir of the foregoing clause, wherein the reservoir curls up automatically in its small outline state and unfolds when released from the drug delivery device at the treatment site.

[0114] 82. The storage facility of any of the preceding clauses, wherein the storage facility has a curved, predetermined shape.

[0115] 83. A repository of any of the preceding clauses, wherein the chemotherapeutic agents are at least one of the following: cisplatin, pemetrexed sodium, carboplatin, irinotecan and / or irinotecan liposomes.

[0116] 84. A storage facility of any of the preceding clauses, wherein the treatment area is configured to intermittently release chemotherapeutic agents over a period of time.

[0117] 85. A storage facility of any of the preceding clauses, wherein the treatment area is configured to continuously release chemotherapeutic agents over a period of time.

[0118] 86. A storage facility for any of the preceding clauses, wherein the time period is at least 4 weeks, and wherein the treatment area is configured to release a certain dose of chemotherapy agent once a week or once every 2 weeks during that time period.

[0119] 87. A storage facility for any of the preceding clauses, wherein the time period is at least 8 weeks, and wherein the treatment area is configured to release a certain dose of chemotherapy agent once a week or once every 2 weeks during that time period.

[0120] 88. A storage facility for any of the preceding clauses, wherein the time period is at least 12 weeks, and wherein the treatment area is configured to release a certain dose of chemotherapy agent once a week, every 2 weeks, or every 3 weeks during that time period.

[0121] 89. A storage facility for any of the preceding clauses, wherein the time period is at least 16 weeks, and wherein the treatment area is configured to release a certain dose of chemotherapy agent once a week, every 2 weeks, or every 4 weeks during that time period.

[0122] 90. A repository of any of the preceding clauses, wherein the chemotherapeutic agents include cisplatin, and wherein each dose of cisplatin is less than or equal to 100 μg / ml.

[0123] 91. A repository of any of the preceding clauses, wherein the chemotherapeutic agents include pemetrexed sodium, and wherein each dose of pemetrexed sodium is less than or equal to 500 mg / m2.

[0124] 92. A repository of any of the preceding clauses, wherein the chemotherapeutic agents include irinotecan or irinotecan liposomes, and wherein each dose of irinotecan or irinotecan liposomes is less than or equal to 200 mg / m2.

[0125] 93. A repository of any of the preceding clauses, wherein the chemotherapeutic agents include irinotecan or irinotecan liposomes, and wherein each dose of irinotecan or irinotecan liposomes is less than or equal to 120 mg / m2.

[0126] 94. The storage period for any of the preceding clauses shall be no less than 2 weeks, no less than 3 weeks, no less than 4 weeks, no less than 5 weeks, no less than 6 weeks, no less than 7 weeks, no less than 8 weeks, no less than 2 months, no less than 3 months, no less than 4 months, no less than 6 months, no less than 7 months, no less than 8 months, no less than 9 months, no less than 10 months, no less than 12 months, or no less than 1 year.

[0127] 95. The reservoir of any of the preceding clauses, wherein the reservoir has a predetermined shape such that the reservoir assumes the predetermined shape when released from the drug delivery device.

[0128] 96. A storage facility for any of the foregoing clauses, wherein the therapeutic agent further comprises a tissue sclerosing agent.

[0129] 97. A storage facility for any of the preceding clauses, wherein the tissue sclerosing agent comprises at least one of the following: talc and / or doxycycline.

[0130] 98. A storage facility of any of the preceding clauses, wherein, at least prior to implantation, the portion of the treatment area containing the sclerosing agent is closer to the outer surface of the storage facility than the portion of the treatment area containing the chemotherapeutic agent.

[0131] 99. A storage facility of any of the preceding clauses, wherein the storage facility is configured to release all tissue sclerosing agents in less than one day.

[0132] 100. A storage facility of any of the preceding clauses, wherein the storage facility is configured to release all tissue sclerosing agents in less than 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 12 hours, 16 hours, or 18 hours.

[0133] 101. A storage facility of any of the preceding clauses, wherein the sclerosing agent is talc or talc slurry, and wherein the treatment area contains 3–10g, 4–8g, about 2g, 2–3g, 3–4g, 4–5g, 5–6g, 6–7g, 7–8g, 8–9g, 9–10g, about 3g, about 4g, about 5g, about 6g, about 7g, about 8g, about 9g, or about 10g of talc or talc slurry.

[0134] 102. A storage facility of any of the preceding clauses, wherein the sclerosing agent is doxycycline, and wherein the treatment area contains 200-800 mg, 300-700 mg, 400-600 mg, about 300 mg, about 400 mg, about 500 mg, about 600 mg, about 700 mg, or about 800 mg of doxycycline.

[0135] 103. A storage facility for any of the foregoing clauses, wherein the therapeutic agents further include analgesics.

[0136] 104. A storage facility of any of the preceding clauses, wherein at least prior to implantation, the portion of the treatment area containing the analgesic is closer to the outer surface of the storage facility than the portion of the treatment area containing the chemotherapeutic agent.

[0137] 105. A storage facility of any of the preceding clauses, wherein, at least prior to implantation, the portion of the treatment area containing the sclerosing agent is closer to the outer surface of the storage facility than the portion of the treatment area containing the chemotherapeutic agent and the portion containing the analgesic agent, and wherein the portion containing the analgesic agent is closer to the outer surface of the portion of the treatment area containing the chemotherapeutic agent.

[0138] 106. A repository of any of the foregoing clauses, wherein the therapeutic agents further include immunotherapeutic agents.

[0139] 107. A repository of any of the foregoing clauses, wherein the therapeutic agents further include targeted therapies.

[0140] 108. A repository of any of the preceding clauses, wherein the treatment area comprises a first part and a second part, wherein the first part contains a chemotherapeutic agent and the second part contains a sclerosing agent.

[0141] 109. The storage facility of any of the preceding clauses, wherein the first part is closer to the outer surface of the storage facility than the second part.

[0142] 110. The storage facility of any of the preceding clauses, wherein the first portion is further away from the outer surface of the storage facility than the second portion.

[0143] 111. A reservoir for any of the preceding clauses, wherein the reservoir is configured to release a chemotherapeutic agent at a first rate and a tissue sclerosing agent at a second rate.

[0144] 112. A storage facility of any of the preceding clauses, wherein the first rate is the same as the second rate.

[0145] 113. A storage facility of any of the preceding clauses, wherein the first rate is different from the second rate.

[0146] 114. A storage facility of any of the preceding clauses, wherein the first rate is greater than the second rate.

[0147] 115. A storage facility of any of the preceding clauses, wherein the first rate is less than the second rate.

[0148] 116. A storage facility of any of the preceding clauses, wherein the storage facility is configured to be located adjacent to the patient's chest wall.

[0149] 117. A storage facility of any of the preceding clauses, wherein the storage facility is configured to be located between the chest wall and the pleura.

[0150] 118. A storage facility of any of the preceding clauses, wherein the storage facility is configured to be located between the pulmonary pleura and the parietal pleura.

[0151] 119. A storage facility of any of the preceding clauses, wherein the storage facility is configured to be located at least partially within the pleural cavity.

[0152] 120. A reservoir for any of the preceding clauses, wherein the reservoir is configured to administer medication via a tube having an outer diameter of about 3 mm to about 7 mm or about 4 mm to about 6 mm.

[0153] 121. The storage facility of any of the preceding clauses, wherein the storage facility comprises a tubular component having an outer diameter of about 6 Fr to about 40 Fr.

[0154] 122. A system for treating MPE by controlled sustained release of a therapeutic agent, the system comprising:

[0155] The storage facility for any of the foregoing clauses; and

[0156] A drug delivery device configured to position the storage bank close to the patient's pleura.

[0157] 123. A system for treating MPE by controlled sustained release of a therapeutic agent, the system comprising:

[0158] The storage facility for any of the foregoing clauses; and

[0159] A drug delivery device configured to position the storage reservoir within the patient's thoracic cavity.

[0160] 124. A system for treating MPE, comprising:

[0161] Multiple storage facilities, each containing any of the foregoing clauses; and

[0162] A drug delivery device configured to position the storage bank close to the patient's pleura.

[0163] 125. A system for treating MPE, comprising:

[0164] Multiple storage facilities, each containing any of the foregoing clauses; and

[0165] A drug delivery device configured to position the storage reservoir within the patient's thoracic cavity.

[0166] 126. The system of any of the preceding clauses, wherein the drug delivery device comprises a chest tube.

[0167] 127. The system of any of the preceding clauses, wherein the drug delivery device comprises a cannula.

[0168] 128. The system of any of the preceding clauses, wherein the delivery device comprises a tubular component having an outer diameter of about 6 Fr to about 40 Fr.

[0169] 129. The system of any of the preceding clauses, wherein the delivery device comprises a tube having an outer diameter of about 3 mm to about 7 mm or about 4 mm to about 6 mm.

[0170] 130. A system of any of the preceding clauses, wherein at least two of the plurality of repositories have different sizes, different shapes and / or different therapeutic agents.

[0171] 131. A method for treating MPE by controlled sustained release of a chemotherapeutic agent, the method comprising:

[0172] Provide a storage facility that meets any of the foregoing terms.

[0173] 132. A method for treating MPE by controlled sustained release of a chemotherapeutic agent, the method comprising:

[0174] The storage facility for any of the foregoing provisions shall be located at the treatment site close to the patient's pleura; and

[0175] The chemotherapy agent is released at the treatment site for a period of not less than 7 days.

[0176] 133. A method for treating MPE by controlled sustained release of a chemotherapeutic agent, the method comprising:

[0177] Multiple repositories are located at the treatment site near the patient's pleura, each repositories being one of the foregoing provisions; and

[0178] The chemotherapy agent is released at the treatment site for a period of not less than 7 days.

[0179] 134. Any of the methods described in the preceding clauses may also include reducing the distance between the pulmonary pleura and the parietal pleura.

[0180] 135. The method of any of the preceding clauses further includes reducing the volume between the pulmonary pleura and the parietal pleura.

[0181] 136. Any of the methods mentioned in the preceding clauses also includes slowing the growth of lung cancer.

[0182] 137. Any of the methods mentioned above also includes reducing the likelihood of lung cancer recurrence.

[0183] 138. The method of any of the foregoing clauses also includes the removal of fluid from the pleural cavity.

[0184] 139. Any of the methods mentioned in the preceding clauses also includes pain reduction.

[0185] 140. Any of the methods described in the preceding clauses also includes causing inflammation of one or both pleuras.

[0186] 141. The method of any of the preceding clauses, wherein positioning the reservoir(s) at the treatment site comprises administering the reservoir(s) through or within a tubular component having an outer diameter of about 6 Fr to about 40 Fr.

[0187] 142. The method of any of the preceding clauses, wherein positioning the reservoir(s) at the treatment site comprises administering the reservoir(s) by means of a tubular component having an outer diameter of about 3 mm to about 7 mm or about 4 mm to about 6 mm or within the tubular component.

[0188] 143. Any of the methods mentioned in the preceding clauses, wherein the time period is not less than two weeks, not less than three weeks, not less than four weeks, not less than five weeks, not less than eight weeks, not less than two months, not less than three months, not less than four months, not less than six months, not less than seven months, not less than eight months, not less than nine months, not less than ten months, not less than twelve months, or not less than one year.

[0189] 144. The method of any of the preceding clauses, wherein the release of the chemotherapeutic agent comprises releasing the chemotherapeutic agent once a week, once every two weeks, once every three weeks, or once every four weeks for a period of time.

[0190] 145. The method of any of the preceding clauses, wherein the location of the reservoir includes the location of the reservoir above, to the side, behind or below the patient's lung.

[0191] 146. The method of any of the preceding clauses, wherein the reservoir includes a first reservoir and a second reservoir, and wherein positioning the reservoir includes positioning the first reservoir at a first location above, to the side, behind or below the lung containing the patient, and positioning the second reservoir at a second location above, to the side, behind or below the lung containing the patient, and wherein the second location is different from the first location.

[0192] 147. The method of any of the preceding clauses, wherein the storage bank includes a first storage bank, a second storage bank, and a third storage bank, and wherein locating the storage bank includes locating the first storage bank at a first position above, to the side, behind, or below the lung containing the patient, locating the second storage bank at a second position above, to the side, behind, or below the lung containing the patient, and locating the third storage bank at a third position above, to the side, behind, or below the lung containing the patient, and wherein the first, second, and third positions are different.

[0193] 148. The method of any of the preceding clauses, wherein the storage bank includes a first storage bank, a second storage bank, and a third storage bank, and wherein locating the storage bank includes locating the first storage bank at a first position above, to the side, behind, or below the lung containing the patient, locating the second storage bank at a second position above, to the side, behind, or below the lung containing the patient, locating the third storage bank at a third position above, to the side, behind, or below the lung containing the patient, and locating the fourth storage bank at a fourth position above, to the side, behind, or below the lung containing the patient, and wherein the first, second, third, and fourth positions are different.

[0194] 149. The method of any of the preceding clauses, wherein at least two of the plurality of repositories have different sizes, different shapes and / or different therapeutic agents.

[0195] 150. The method of any of the preceding clauses, wherein, after implantation, the chemotherapeutic agent is released once or multiple times in substantially discrete doses.

[0196] 151. The method of any of the preceding clauses, wherein releasing the therapeutic agent includes releasing a tissue sclerosing agent.

[0197] 152. The method of any of the preceding clauses, wherein releasing the therapeutic agent comprises releasing the entire tissue sclerosing agent before releasing half of the chemotherapeutic agent.

[0198] 153. The method of any of the preceding clauses, wherein releasing the therapeutic agent comprises releasing all of the tissue sclerosing agent within the first 1 hour, 2 hours, 3 hours, 6 hours, 12 hours, or 24 hours after implantation into the storage bank.

[0199] 154. The method of any of the preceding clauses, wherein the release of the therapeutic agent comprises releasing 3–10 g, 4–8 g, 2–3 g, 3–4 g, 4–5 g, 5–6 g, 6–7 g, 7–8 g, 8–9 g, 9–10 g, about 2 g, about 3 g, about 4 g, about 5 g, about 6 g, about 7 g, about 8 g, about 9 g, or about 10 g of talc or talc slurry.

[0200] 155. The method of any of the preceding clauses, wherein releasing the therapeutic agent comprises releasing 3–10g, 4–8g, 2–3g, 3–4g, 4–5g, 5–6g, 6–7g, 7–8g, 8–9g, 9–10g, about 2g, about 3g, about 4g, about 5g, about 6g, about 7g, about 8g, about 9g, or about 10g of talc or talc slurry within the first 1 hour, 2 hours, 3 hours, 6 hours, 12 hours, or 24 hours after implantation of the storage tank.

[0201] 156. The method of any of the preceding clauses, wherein the release of the therapeutic agent comprises the release of 200-800 mg, 300-700 mg, 400-600 mg, about 300 mg, about 400 mg, about 500 mg, about 600 mg, about 700 mg, or about 800 mg of doxycycline.

[0202] 157. The method of any of the preceding clauses, wherein the release of the therapeutic agent comprises releasing 200-800 mg, 300-700 mg, 400-600 mg, about 300 mg, about 400 mg, about 500 mg, about 600 mg, about 700 mg, or about 800 mg of doxycycline within the first 1 hour, 2 hours, 3 hours, 6 hours, 12 hours, or 24 hours after implantation into the storage depot.

[0203] 158. The method of any of the preceding clauses, wherein the release of the therapeutic agent includes the release of an analgesic.

[0204] 159. A repository for treating soft tissue sarcoma (“STS”) by means of sustained controlled release of a therapeutic agent into a patient, the repository comprising:

[0205] Treatment area containing chemotherapy drugs;

[0206] A control region comprising a bioabsorbable polymer and a release agent mixed with the polymer, wherein the release agent is configured to dissolve upon placement of the reservoir in vivo to form a diffusion opening in the control region; and

[0207] The storage facility is configured to be implanted at the treatment site of the STS close to the patient, and chemotherapy agents are released at the treatment site at the first and second time points upon implantation, with the second time point being no less than 7 days after the first time point.

[0208] 160. A storage facility of any of the preceding clauses, wherein the chemotherapeutic agents comprise a first chemotherapeutic agent and a second chemotherapeutic agent, wherein the storage facility is configured to release the first chemotherapeutic agent at a first time and the second chemotherapeutic agent at a second time.

[0209] 161. A reservoir of any of the preceding clauses, wherein the reservoir is configured to release the first chemotherapeutic agent at a constant and continuous rate from the first time point to the second time point.

[0210] 162. The storage facility of any of the preceding clauses, wherein the storage facility is a flexible film.

[0211] 163. A repository of any of the preceding clauses, wherein the chemotherapeutic agents are at least one of the following: doxorubicin, imatinib, sirolimus, sunitinib, sorafenib, rapamycin, trabectedin, eribulin, gemcitabine, cidinib, rapamycin, olaratumab, ifosfamide, paclitaxel, regoraferib, and / or pazopanib.

[0212] 164. A reservoir of any of the preceding clauses, wherein the chemotherapeutic agent includes pazopanib, and wherein the reservoir is configured to continuously release pazopanib over a period of time.

[0213] 165. A storage facility of any of the preceding clauses, wherein the chemotherapeutic agent includes doxorubicin, and wherein the storage facility is configured to continuously release doxorubicin over a period of time.

[0214] 166. A reservoir of any of the preceding clauses, wherein the chemotherapeutic agent includes trabectedin, and wherein the reservoir is configured to release trabectedin intermittently over a period of time.

[0215] 167. A reservoir of any of the preceding clauses, wherein the chemotherapeutic agent includes eribulin, and wherein the reservoir is configured to release eribulin intermittently over a period of time.

[0216] 168. A repository of any of the foregoing clauses, wherein the chemotherapy agents include doxorubicin and olamulumab.

[0217] 169. A storage facility for any of the preceding clauses, wherein the time period is 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, or 8 weeks, and wherein the chemotherapy agent is administered once a week throughout the entire time period.

[0218] 170. A storage facility of any of the preceding clauses, wherein the time period is 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, or 8 weeks and the chemotherapy agent is paclitaxel and / or doxorubicin liposomes, and wherein the storage facility is configured to administer the chemotherapy agent once a week throughout the entire time period.

[0219] 171. A repository of any of the preceding clauses, wherein the treatment site is a patient’s gastrointestinal stromal sarcoma and the treatment period is 2, 3, 4, 5, 6, 7, or 8 weeks and the chemotherapy agent is imatinib and / or sunitinib, and wherein the repository is configured to administer the chemotherapy agent once a week throughout the treatment period.

[0220] 172. A storage facility for any of the preceding clauses, wherein the treatment site is a patient’s dermatofibrosarcoma and the treatment period is 2, 3, 4, 5, 6, 7, or 8 weeks and the chemotherapy agent is imatinib, and wherein the storage facility is configured to administer the chemotherapy agent to the treatment site once a week throughout the treatment period.

[0221] 173. A storage facility for any of the preceding clauses, wherein the treatment site is a patient’s perivascular epithelioid tumor and the treatment period is 2, 3, 4, 5, 6, 7, or 8 weeks and the chemotherapy agent is rapamycin, and wherein the storage facility is configured to administer the chemotherapy agent to the treatment site once a week throughout the treatment period.

[0222] 174. A repository of any of the preceding clauses, wherein the treatment site is a patient’s alveolar soft tissue sarcoma and the time period is 2, 3, 4, 5, 6, 7, or 8 weeks and the chemotherapy agent is sunitinib, and wherein the repository is configured to administer the chemotherapy agent to the treatment site once a week throughout the time period.

[0223] 175. A storage facility for any of the preceding clauses, wherein the treatment site is a patient’s leiomyosarcoma and the treatment period is 2, 3, 4, 5, 6, 7, or 8 weeks and the chemotherapy agent is rapamycin, and wherein the storage facility is configured to administer the chemotherapy agent to the treatment site once a week throughout the treatment period.

[0224] 176. A storage facility for any of the preceding clauses, wherein the treatment site is a patient’s leiomyosarcoma or liposarcoma and the treatment period is 2, 3, 4, 5, 6, 7, or 8 weeks and the chemotherapy agent is trabectedine, and wherein the storage facility is configured to administer the chemotherapy agent to the treatment site once a week throughout the treatment period.

[0225] 177. A reservoir for any of the preceding clauses, wherein the treatment area is configured to intermittently release chemotherapeutic agents over a period of time.

[0226] 178. A storage facility of any of the preceding clauses, wherein the treatment area is configured to continuously release chemotherapeutic agents over a period of time.

[0227] 179. A storage facility for any of the preceding clauses, wherein the time period is at least 4 weeks, and wherein the treatment area is configured to release a certain dose of chemotherapy agent once a week or once every 2 weeks during that time period.

[0228] 180. A storage facility for any of the preceding clauses, wherein the time period is at least 8 weeks, and wherein the treatment area is configured to release a dose of chemotherapy agent once a week or once every 2 weeks during that time period.

[0229] 181. A storage facility for any of the preceding clauses, wherein the time period is at least 12 weeks, and wherein the treatment area is configured to release a dose of chemotherapy agent once a week, every 2 weeks, or every 3 weeks during that time period.

[0230] 182. A storage facility for any of the preceding clauses, wherein the time period is at least 16 weeks, and wherein the treatment area is configured to release a certain dose of chemotherapy agent once a week, every 2 weeks, or every 4 weeks during that time period.

[0231] 183. The storage period for any of the preceding clauses shall be no less than 2 weeks, no less than 3 weeks, no less than 4 weeks, no less than 5 weeks, no less than 6 weeks, no less than 7 weeks, no less than 8 weeks, no less than 2 months, no less than 3 months, no less than 4 months, no less than 6 months, no less than 7 months, no less than 8 months, no less than 9 months, no less than 10 months, no less than 12 months, and no less than 1 year.

[0232] 184. A repository of any of the preceding clauses, wherein the chemotherapy agents comprise a first chemotherapy agent and a second chemotherapy agent different from the first chemotherapy agent.

[0233] 185. A repository of any of the preceding clauses, wherein the first chemotherapeutic agent comprises doxorubicin and the second chemotherapeutic agent comprises at least one of trabectedin, pazopanib and / or eribulin.

[0234] 186. A storage facility of any of the preceding clauses, wherein the storage facility is configured to continuously release a first chemotherapeutic agent and intermittently release a second chemotherapeutic agent over a period of time.

[0235] 187. A storage facility of any of the preceding clauses, wherein the storage facility is configured to release a first chemotherapeutic agent at a first rate and a second chemotherapeutic agent at a second rate.

[0236] 188. A storage facility of any of the preceding clauses, wherein the first rate is the same as the second rate.

[0237] 189. A storage facility of any of the preceding clauses, wherein the first rate is different from the second rate.

[0238] 190. A storage facility of any of the preceding clauses, wherein the first rate is greater than the second rate.

[0239] 191. A storage facility of any of the preceding clauses, wherein the first rate is less than the second rate.

[0240] 192. A storage facility for any of the preceding clauses, wherein the treatment site is on the patient’s head, neck and / or face.

[0241] 193. A storage facility for any of the foregoing clauses, wherein the treatment site is in the patient's gastrointestinal tract.

[0242] 194. A storage facility for any of the preceding clauses, wherein the treatment site is in the retroperitoneal space of the patient.

[0243] 195. A storage facility for any of the preceding clauses, wherein the treatment site is on the patient's limb.

[0244] 196. A storage facility for any of the foregoing clauses, wherein the treatment site is on the patient's arm.

[0245] 197. A storage facility for any of the foregoing clauses, wherein the treatment site is on the patient's leg.

[0246] 198. A storage facility for any of the preceding clauses, wherein the treatment site is on the patient's skin.

[0247] 199. A storage facility for any of the foregoing clauses, wherein the treatment site is the patient’s gynecological organs.

[0248] 200. A storage facility for any of the preceding clauses, wherein the treatment site is in the patient’s reproductive area.

[0249] 201. A repository of organs within the trunk region of a patient, as specified in any of the preceding clauses.

[0250] 202. A storage facility for any of the preceding clauses, wherein the treatment site is in the connective tissue of the patient's trunk region.

[0251] 203. A storage facility of any of the preceding clauses, wherein the storage facility is configured to be positioned in direct contact with the patient's connective tissue to administer chemotherapy agents to the connective tissue.

[0252] 204. A storage facility of any of the preceding clauses, wherein the storage facility is configured to be positioned in direct contact with the patient’s soft tissue for administration of chemotherapeutic agents to the soft tissue.

[0253] 205. A storage facility of any of the preceding clauses, wherein the storage facility is configured to be positioned in direct contact with the patient’s fat to administer chemotherapeutic agents to the fat.

[0254] 206. A storage facility of any of the preceding clauses, wherein the storage facility is configured to be positioned in direct contact with the patient’s muscles to administer chemotherapy agents to the muscles.

[0255] 207. A storage facility of any of the preceding clauses, wherein the storage facility is configured to be positioned in direct contact with the patient’s deep skin tissue to administer chemotherapy agents to the deep skin tissue.

[0256] 208. A storage facility of any of the preceding clauses, wherein the storage facility is configured to be positioned in direct contact with a patient’s blood vessels for administration of chemotherapeutic agents into the blood vessels.

[0257] 209. A storage facility of any of the preceding clauses, wherein the storage facility is configured to be positioned in direct contact with the patient's cartilage at the treatment site to administer chemotherapy agents to the cartilage.

[0258] 210. A storage facility of any of the preceding clauses, wherein the storage facility is configured to be positioned in direct contact with a patient’s tendon for administration of a chemotherapeutic agent to the tendon.

[0259] 211. A storage facility of any of the preceding clauses, wherein the storage facility is configured to be positioned in direct contact with the patient’s ligaments to administer chemotherapy agents to the ligaments.

[0260] 212. A repository of any of the preceding clauses, wherein the chemotherapeutic agents are prepared for treatment of angiosarcoma at the treatment site.

[0261] 213. A repository of any of the preceding clauses, wherein the chemotherapeutic agents are prepared for treatment of osteosarcoma at the treatment site.

[0262] 214. A repository of any of the preceding clauses, wherein the chemotherapeutic agents are prepared for treatment of Ewing sarcoma at the treatment site.

[0263] 215. A repository of any of the preceding clauses, wherein the chemotherapeutic agents are prepared for treatment of chondrosarcoma at the treatment site.

[0264] 216. A repository of any of the preceding clauses, wherein the chemotherapeutic agents are prepared for treatment of gastrointestinal stromal tumors at the treatment site.

[0265] 217. A repository of any of the preceding clauses, wherein the chemotherapeutic agents are prepared for treatment of liposarcoma at the treatment site.

[0266] 218. A repository of any of the preceding clauses, wherein the chemotherapeutic agents are prepared for treatment of fibrosarcoma at the treatment site.

[0267] 219. A repository of any of the preceding clauses, wherein the chemotherapeutic agents are prepared for treatment of hemangioendothelioma at the treatment site.

[0268] 220. A system for treating STS by controlled sustained release of a therapeutic agent, the system comprising:

[0269] The storage facility for any of the foregoing clauses, and

[0270] A drug delivery device configured to position the storage bank close to the patient's soft tissue sarcoma.

[0271] 221. A system for treating STS, comprising:

[0272] Multiple storage facilities, each containing any of the foregoing clauses, and

[0273] A drug delivery device configured to position the storage bank close to the patient's soft tissue sarcoma.

[0274] 222. A system of any of the preceding clauses, wherein at least two of the plurality of repositories have different sizes, different shapes, release profiles and / or different chemotherapeutic agents.

[0275] 223. A method for treating STS by controlled sustained release of a chemotherapeutic agent, the method comprising:

[0276] Provide a storage facility that meets any of the foregoing terms.

[0277] 224. A method for treating STS by controlled sustained release of a chemotherapeutic agent, the method comprising:

[0278] The storage facility for any of the foregoing clauses shall be located near the treatment site of the patient's soft tissue sarcoma; and

[0279] The chemotherapy agent is released at the treatment site for a period of not less than 7 days.

[0280] 225. A method for treating STS by controlled sustained release of a chemotherapeutic agent, the method comprising:

[0281] Multiple repositories are located near the patient's STS treatment site, each repository being a repository according to any of the foregoing clauses; and

[0282] The chemotherapy agent is released at the treatment site for a period of not less than 7 days.

[0283] 226. Any of the methods described in the foregoing clauses may also include slowing down the growth of STS.

[0284] 227. Any of the methods described in the preceding clauses may also include shrinking the STS.

[0285] 228. Any of the methods described in the foregoing clauses may also include reducing the likelihood of STS recurrence.

[0286] 229. Any of the methods mentioned in the preceding clauses, wherein the time period is not less than two weeks, not less than three weeks, not less than four weeks, not less than five weeks, not less than eight weeks, not less than two months, not less than three months, not less than four months, not less than six months, not less than seven months, not less than eight months, not less than nine months, not less than ten months, not less than twelve months, or not less than one year.

[0287] 230. The method of any of the preceding clauses, wherein the release of the chemotherapeutic agent comprises releasing the chemotherapeutic agent once a week, once every two weeks, once every three weeks, or once every four weeks for a period of time.

[0288] 231. The method of any of the preceding clauses, wherein at least two of the plurality of repositories have different sizes, different shapes and / or different chemotherapeutic agents.

[0289] 232. The method of any of the preceding clauses, wherein the chemotherapeutic agent is at least one of the following: doxorubicin, imatinib, sirolimus, sunitinib, sorafenib, rapamycin, trabectedin, eribulin, gemcitabine, cidinibub, rapamycin, olalimumab, ifosfamide, paclitaxel, regorafenib and / or pazopanib.

[0290] 233. The method of any of the preceding clauses, wherein the chemotherapeutic agent includes pazopanib, and wherein releasing the chemotherapeutic agent includes continuously releasing pazopanib over a period of time.

[0291] 234. The method of any of the preceding clauses, wherein the chemotherapeutic agent includes doxorubicin, and wherein releasing the chemotherapeutic agent comprises continuously releasing doxorubicin over a period of time.

[0292] 235. The method of any of the preceding clauses, wherein the chemotherapeutic agent comprises trabectedine, and wherein releasing the chemotherapeutic agent comprises intermittently releasing trabectedine over a period of time.

[0293] 236. The method of any of the preceding clauses, wherein the chemotherapeutic agent includes eribulin, and wherein releasing the chemotherapeutic agent includes intermittently releasing eribulin over a period of time.

[0294] 237. The method of any of the preceding clauses, wherein the chemotherapeutic agents include doxorubicin and olamulumab.

[0295] 238. The method of any of the preceding clauses, wherein the time period is 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, or 8 weeks, and wherein the release of chemotherapy agents includes releasing chemotherapy agents once a week throughout the entire time period.

[0296] 239. The method of any of the preceding clauses, wherein the time period is 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, or 8 weeks and the chemotherapy agent is paclitaxel and / or doxorubicin liposomes, and wherein the release of the chemotherapy agent comprises releasing the chemotherapy agent once a week throughout the entire time period.

[0297] 240. The method of any of the preceding clauses, wherein the treatment site is a patient’s gastrointestinal stromal sarcoma and the time period is 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, or 8 weeks and the chemotherapy agent is imatinib and / or sunitinib, and wherein the reservoir is configured to administer the chemotherapy agent once a week throughout the time period.

[0298] 241. The method of any of the preceding clauses, wherein the treatment site is a patient's dermatofibrosarcoma and the time period is 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, or 8 weeks and the chemotherapy agent is imatinib, and wherein the reservoir is configured to administer the chemotherapy agent to the treatment site once a week throughout the time period.

[0299] 242. The method of any of the preceding clauses, wherein the treatment site is a patient’s perivascular epithelioid tumor and the time period is 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, or 8 weeks and the chemotherapy agent is rapamycin, and wherein the reservoir is configured to administer the chemotherapy agent to the treatment site once a week throughout the time period.

[0300] 243. The method of any of the preceding clauses, wherein the treatment site is alveolar soft tissue sarcoma and the chemotherapy agent is sunitinib.

[0301] 244. The method of any of the preceding clauses, wherein the treatment site is the patient's leiomyosarcoma and the chemotherapy agent is rapamycin.

[0302] 245. The method of any of the preceding clauses, wherein the treatment site is the patient's leiomyosarcoma or liposarcoma and the chemotherapy agent is trabectedin.

[0303] 246. The method of any of the preceding clauses, wherein the chemotherapeutic agent is released intermittently over a period of time.

[0304] 247. The method of any of the preceding clauses, wherein the chemotherapeutic agent is continuously released over a period of time.

[0305] 248. The method of any of the preceding clauses, wherein the chemotherapy agent is released once a week, every two weeks, every three weeks, or every four weeks for a period of time.

[0306] 249. Any of the methods mentioned in the preceding clauses, wherein the time period is not less than 2 weeks, not less than 3 weeks, not less than 4 weeks, not less than 5 weeks, not less than 6 weeks, not less than 7 weeks, not less than 8 weeks, not less than 2 months, not less than 3 months, not less than 4 months, not less than 6 months, not less than 7 months, not less than 8 months, not less than 9 months, not less than 10 months, not less than 12 months, or not less than 1 year.

[0307] 250. The method of any of the preceding clauses, wherein the chemotherapeutic agent comprises a first chemotherapeutic agent and a second chemotherapeutic agent different from the first chemotherapeutic agent.

[0308] 251. The method of any of the preceding clauses, wherein the first chemotherapeutic agent comprises doxorubicin and the second chemotherapeutic agent comprises at least one of trabectedin, pazopanib and / or eribulin.

[0309] 252. The method of any of the preceding clauses further includes continuously releasing the first chemotherapy agent over a period of time and intermittently releasing the second chemotherapy agent.

[0310] 253. The method of any of the preceding clauses, wherein, after implantation, the chemotherapeutic agent is released once or multiple times in substantially discrete doses.

[0311] 254. The method of any of the preceding clauses further includes releasing the first chemotherapeutic agent at a first rate and releasing the second chemotherapeutic agent at a second rate.

[0312] 255. The method of any of the preceding clauses, wherein the first rate is the same as the second rate.

[0313] 256. The method of any of the preceding clauses, wherein the first rate is different from the second rate.

[0314] 257. The method of any of the preceding clauses, wherein the first rate is greater than the second rate.

[0315] 258. The method of any of the preceding clauses, wherein the first rate is less than the second rate.

[0316] 259. The method of any of the preceding clauses, wherein the treatment site is on the patient’s head, neck and / or face.

[0317] 260. The method of any of the preceding clauses, wherein the treatment site is in the patient's gastrointestinal tract.

[0318] 261. The method of any of the preceding clauses, wherein the treatment site is in the retroperitoneal space of the patient.

[0319] 262. The method of any of the preceding clauses, wherein the treatment site is on the patient's limb.

[0320] 263. The method of any of the preceding clauses, wherein the treatment site is on the patient's arm.

[0321] 264. The method of any of the preceding clauses, wherein the treatment site is on the patient's leg.

[0322] 265. The method of any of the preceding clauses, wherein the treatment site is on the patient's skin.

[0323] 266. The method of any of the preceding clauses, wherein the treatment site is in the patient's gynecological organs.

[0324] 267. The method of any of the preceding clauses, wherein the treatment site is in the patient's reproductive area.

[0325] 268. The method of any of the preceding clauses, wherein the treatment site is an organ within the patient's trunk region.

[0326] 269. The method of any of the preceding clauses, wherein the treatment site is in the connective tissue of the patient's trunk region.

[0327] 270. A repository for treating head and neck cancer by sustained, controlled release of a therapeutic agent into a patient, the repository comprising:

[0328] A treatment area containing a therapeutic agent, which at least contains a chemotherapeutic agent;

[0329] A control region comprising a bioabsorbable polymer and a release agent mixed with the polymer, wherein the release agent is configured to dissolve upon placement of the reservoir in vivo to form a diffusion opening in the control region; and

[0330] The storage facility is configured to be implanted near the patient's mouth or throat, and when implanted, it releases chemotherapy agents at the treatment site for a period of not less than 7 days.

[0331] 271. A storage facility of any of the preceding clauses, wherein the storage facility is connected to a dental implant.

[0332] 272. A storage facility of any of the preceding clauses, wherein the storage facility is connected to a dental prosthesis.

[0333] 273. A storage facility of any of the preceding clauses, wherein the storage facility is connected to dental instruments.

[0334] 274. The storage of any of the preceding clauses, wherein the dental instruments include a movable tray or container.

[0335] 275. A storage facility of any of the preceding clauses, wherein the storage facility comprises a multilayer membrane stacked above a portion of a dental implant or dental instrument.

[0336] 276. A storage facility of any of the preceding clauses, wherein the storage facility is enclosed around a portion of a dental implant or dental instrument.

[0337] 277. A storage facility of any of the preceding clauses, wherein the storage facility extends above at least a portion of the outer surface of the dental implant or dental instrument.

[0338] 278. A storage facility for any of the preceding clauses, wherein the treatment area is configured to continuously release chemotherapeutic agents over a period of time.

[0339] 279. The storage period for any of the preceding clauses shall be not less than two weeks, not less than three weeks, not less than four weeks, not less than five weeks, not less than eight weeks, not less than two months, not less than three months, not less than four months, not less than six months, not less than seven months, not less than eight months, not less than nine months, not less than ten months, not less than twelve months, and not less than one year.

[0340] 280. A repository of chemotherapy agents containing at least 20 mg, at least 50 mg, at least 100 mg, at least 200 mg, at least 300 mg, at least 400 mg, at least 500 mg, at least 600 mg, at least 700 mg, at least 800 mg, or at least 1 g of chemotherapy agents.

[0341] 281. A repository of any of the preceding clauses, wherein the chemotherapeutic agents comprise at least one of the following: paclitaxel, vincristine, ifosfamide, cytosine, doxorubicin, or cyclophosphamide, ramucirumab, docetaxel, trastuzumab, fluorouracil or 5-FU, oxaliplatin, epirubicin, capecitabine, oxaliplatin, irinotecan, fluorouracil, porphyrin sodium, aminolevulinic acid, carboplatin or cisplatin.

[0342] 282. A storage facility of any of the preceding clauses, wherein the therapeutic agents further include reagents for treating oral mucositis.

[0343] 283. A repository of any of the preceding clauses, wherein the reagent for treating oral mucositis comprises at least one of the following: benzalkonium chloride and oral mucosal adhesive.

[0344] 284. A storage facility for any of the preceding clauses, wherein the treatment area comprises a first part and a second part, wherein the first part contains a chemotherapy agent and the second part contains a reagent for treating oral mucositis.

[0345] 285. A repository of any of the foregoing clauses, wherein the therapeutic agents further include immunotherapeutic agents.

[0346] 286. A repository of immunotherapeutic agents comprising at least one of the following: nivolumab, pembrolizumab, or ramucirumab.

[0347] 287. A repository of any of the preceding clauses, wherein the treatment area comprises a first part and a second part, wherein the first part contains chemotherapeutic agents and the second part contains immunotherapeutic agents.

[0348] 288. The storage facility of any of the preceding clauses, wherein the first portion is closer to the outer surface of the storage facility than the second portion.

[0349] 289. The storage facility of any of the preceding clauses, wherein the first portion is further away from the outer surface of the storage facility than the second portion.

[0350] 290. A storage facility of any of the preceding clauses, wherein the treatment area is configured to continuously release immunotherapeutic agents over a period of time.

[0351] 291. A repository of any of the preceding clauses, wherein the repository is configured to release chemotherapeutic agents at a first rate and immunotherapeutic agents at a second rate.

[0352] 292. A storage facility of any of the preceding clauses, wherein the storage facility is configured to release a chemotherapeutic agent at a first rate and a reagent for treating oral mucositis at a second rate.

[0353] 293. A storage facility of any of the preceding clauses, wherein the first rate is the same as the second rate.

[0354] 294. A storage facility of any of the preceding clauses, wherein the first rate is different from the second rate.

[0355] 295. A storage facility of any of the preceding clauses, wherein the first rate is greater than the second rate.

[0356] 296. A storage facility of any of the preceding clauses, wherein the first rate is less than the second rate.

[0357] 297. A storage container according to any of the preceding clauses, wherein the storage container includes an anchoring member connected to a treatment area, a control area and / or a base area, and wherein the anchoring member is configured to be inserted into tissue at the treatment site, thereby securing the storage container to or inside the patient's mouth or throat.

[0358] 298. A storage facility under any of the preceding clauses, wherein the anchor comprises a bolt.

[0359] 299. A repository of any of the preceding clauses, wherein the anchor contains dental implants.

[0360] 300. A repository of any of the preceding clauses, wherein the anchor contains dental prostheses.

[0361] 301. A system for treating head and neck cancer by controlled sustained release of a therapeutic agent, the system comprising:

[0362] The storage facility for any of the foregoing clauses; and

[0363] A drug delivery device configured to position the reservoir in the patient's throat or mouth.

[0364] 302. The system of any of the preceding clauses, wherein the drug delivery device is configured to locate the reservoir in the patient’s oral mucosa and / or jawbone.

[0365] 303. The system of any of the preceding clauses, wherein the delivery device includes an actuator configured to advance a dental implant connected to a reservoir into the oral mucosa and / or jawbone of a patient.

[0366] 304. A system for treating head and neck cancer, comprising:

[0367] Multiple storage facilities, each containing any of the foregoing clauses; and

[0368] A drug delivery device configured to position the reservoir in the neck.

[0369] 305. A system for treating cancer patients suffering from malignant tumors that are typically treated with radiation, the system comprising:

[0370] The storage facility of any of the foregoing clauses is configured to provide a localized, controlled, sustained release of the therapeutic agent; and

[0371] A drug delivery device configured to position a reservoir close to the patient's tumor allows the tumor to receive a localized, continuous dose of therapeutic agent through the reservoir while protecting the patient from full-dose radiation.

[0372] Locally administered continuous doses of therapeutic agents reduce the curve of radiation-related side effects.

[0373] 306. A method for treating head and neck cancer by controlled sustained release of a therapeutic agent, the method comprising:

[0374] Provide a storage facility that meets any of the foregoing terms.

[0375] 307. A method for treating head and neck cancer by controlled sustained release of a therapeutic agent, the method comprising:

[0376] The storage facility for any of the foregoing clauses shall be located at the treatment site near the patient's throat or mouth;

[0377] The therapeutic agent should be administered to the treatment site for a period of not less than 7 days.

[0378] 308. The method of any of the preceding clauses further includes fixing the storage bank above one or more of the patient's teeth.

[0379] 309. The method of any of the preceding clauses further includes fixing the storage bank to the patient's oral mucosa and / or jawbone.

[0380] 310. Any of the methods mentioned in the preceding clauses, wherein the time period is not less than two weeks, not less than three weeks, not less than four weeks, not less than five weeks, not less than eight weeks, not less than two months, not less than three months, not less than four months, not less than six months, not less than seven months, not less than eight months, not less than nine months, not less than ten months, not less than twelve months, and not less than one year.

[0381] 311. A repository for treating breast cancer by sustained, controlled release of a therapeutic agent into a patient, the repository comprising:

[0382] A treatment area containing a therapeutic agent, which at least contains a chemotherapeutic agent;

[0383] A control region comprising a bioabsorbable polymer and a release agent mixed with the polymer, wherein the release agent is configured to dissolve upon placement of the reservoir in vivo to form a diffusion opening in the control region; and

[0384] The storage facility is configured to be implanted near the patient's breast at the treatment site, and the therapeutic agent is released at the treatment site for a period of not less than 7 days upon implantation.

[0385] 312. The reservoir of any of the preceding clauses, wherein the reservoir has a predetermined shape such that the reservoir assumes the predetermined shape when released from the drug delivery device.

[0386] 313. The storage facility of any of the preceding clauses, wherein the storage facility has a curved, predetermined shape.

[0387] 314. The storage facility of any of the preceding clauses, wherein the storage facility has a predetermined spiral shape.

[0388] 315. A storage facility of any of the preceding clauses, wherein the treatment area is configured to continuously release chemotherapeutic agents over a period of time.

[0389] 316. The storage period for any of the preceding clauses shall be not less than two weeks, not less than three weeks, not less than four weeks, not less than five weeks, not less than eight weeks, not less than two months, not less than three months, not less than four months, not less than six months, not less than seven months, not less than eight months, not less than nine months, not less than ten months, not less than twelve months, and not less than one year.

[0390] 317. A repository of chemotherapy agents containing at least 20 mg, at least 50 mg, at least 100 mg, at least 200 mg, at least 300 mg, at least 400 mg, at least 500 mg, at least 600 mg, at least 700 mg, at least 800 mg, or at least 1 g of chemotherapy agents.

[0391] 318. A repository of any of the preceding clauses, wherein the chemotherapeutic agents contain at least one of the following: doxorubicin or paclitaxel.

[0392] 319. A repository of any of the foregoing clauses, wherein the therapeutic agents further include immunotherapeutic agents.

[0393] 320. A repository of immunotherapeutic agents comprising at least one of the following: nivolumab, pembrolizumab, or ramucirumab.

[0394] 321. A repository of any of the preceding clauses, wherein the treatment area comprises a first part and a second part, wherein the first part contains chemotherapeutic agents and the second part contains immunotherapeutic agents.

[0395] 322. The storage facility of any of the preceding clauses, wherein the first portion is closer to the outer surface of the storage facility than the second portion.

[0396] 323. The storage facility of any of the preceding clauses, wherein the first portion is further away from the outer surface of the storage facility than the second portion.

[0397] 324. A storage facility of any of the preceding clauses, wherein the treatment area is configured to continuously release immunotherapy agents for a period of time.

[0398] 325. A repository of any of the preceding clauses, wherein the repository is configured to release chemotherapeutic agents at a first rate and immunotherapeutic agents at a second rate.

[0399] 326. A storage facility of any of the preceding clauses, wherein the first rate is the same as the second rate.

[0400] 327. A storage facility of any of the preceding clauses, wherein the first rate is different from the second rate.

[0401] 328. A storage facility of any of the preceding clauses, wherein the first rate is greater than the second rate.

[0402] 329. A storage facility of any of the preceding clauses, wherein the first rate is less than the second rate.

[0403] 330. A repository of any of the preceding clauses, wherein the repository is configured to be located within a tumor in the breast.

[0404] 331. A storage facility of any of the preceding clauses, wherein the storage facility is configured to be located within the tumor bed after removal of a tumor from the breast.

[0405] 332. A system for treating breast cancer by controlled sustained release of a therapeutic agent, the system comprising:

[0406] The storage facility for any of the foregoing clauses, and

[0407] A drug delivery device configured to position the storage bank in the breast.

[0408] 333. The system of any of the preceding clauses, wherein the drug delivery device is configured to locate the reservoir within a tumor in the breast.

[0409] 334. The system of any of the preceding clauses, wherein the drug delivery device is configured to locate the reservoir within the tumor bed after the tumor in the breast has been removed.

[0410] 335. The system of any of the preceding clauses, wherein the drug delivery device comprises a needle.

[0411] 336. A system for treating breast cancer, comprising:

[0412] Multiple storage facilities, each containing any of the foregoing clauses, and

[0413] A drug delivery device configured to position the storage bank in the breast.

[0414] 337. A method for treating breast cancer by controlled sustained release of a therapeutic agent, the method comprising:

[0415] Provide a storage facility that meets any of the foregoing terms.

[0416] 338. A method for treating breast cancer by controlled sustained release of a therapeutic agent, the method comprising:

[0417] The storage facility for any of the foregoing clauses shall be located at the treatment site close to the patient's breast;

[0418] The therapeutic agent should be administered to the treatment site for a period of not less than 7 days.

[0419] 339. The method of any of the preceding clauses also includes fixing the storage bank inside the breast.

[0420] 340. Any of the methods mentioned in the preceding clauses, wherein the time period is not less than two weeks, not less than three weeks, not less than four weeks, not less than five weeks, not less than eight weeks, not less than two months, not less than three months, not less than four months, not less than six months, not less than seven months, not less than eight months, not less than nine months, not less than ten months, not less than twelve months, or not less than one year.

[0421] 341. A repository for treating pancreatic and / or liver cancer by sustained, controlled release of a therapeutic agent into a patient, the repository comprising:

[0422] The treatment area containing the therapeutic agent;

[0423] A control region comprising a bioabsorbable polymer and a release agent mixed with the polymer, wherein the release agent is configured to dissolve upon placement of the reservoir in vivo to form a diffusion opening in the control region; and

[0424] The storage facility is configured to be implanted at a treatment site close to the patient's pancreas, and chemotherapy agents are released at the treatment site for a period of not less than 7 days upon implantation.

[0425] 342. The storage facility of any of the preceding clauses, wherein the storage facility is configured to be located above, to the side, behind or below the pancreas.

[0426] 343. A storage facility of any of the preceding clauses, wherein the storage facility is configured to be located adjacent to the outer surface of the pancreas.

[0427] 344. The storage vessel of any of the preceding clauses, wherein the storage vessel includes a fixed portion configured to adhere to the surface of the pancreas.

[0428] 345. The reservoir of any of the preceding clauses, wherein the reservoir includes a reinforced portion configured to penetrate at least a portion of the thickness of the pancreas, thereby securing the reservoir to the surface of the pancreas.

[0429] 346. The storage facility of any of the preceding clauses, wherein the storage facility comprises a sheet or membrane disposed above the surface of the pancreas.

[0430] 347. A storage facility of any of the preceding clauses, wherein the storage facility contains microbeads or pellets configured to be positioned at a treatment site.

[0431] 348. A repository of any of the preceding clauses, wherein pancreatic cancer comprises a tumor, and wherein the repository is configured to be located above, to the side, behind or below the tumor.

[0432] 349. A reservoir for any of the preceding clauses, wherein pancreatic cancer comprises a tumor, and wherein the reservoir is configured to be located near an artery supplying the tumor.

[0433] 350. A repository of any of the preceding clauses, wherein the repository contains intravascular stents.

[0434] 351. A reservoir of any of the preceding clauses, wherein the reservoir is administered to the pancreas via intravascular administration.

[0435] 352. The reservoir of any of the preceding clauses, wherein the reservoir has a predetermined shape such that the reservoir assumes the predetermined shape when released from the drug delivery device.

[0436] 353. A storage facility of any of the preceding clauses, wherein the storage facility has a curved, predetermined shape.

[0437] 354. A reservoir of any of the preceding clauses, wherein the treatment area is configured to continuously release therapeutic agents at a substantially constant rate over a period of time.

[0438] 355. A reservoir of any of the preceding clauses, wherein the treatment area is configured to continuously release therapeutic agents at an increased rate over a period of time.

[0439] 356. A storage facility of any of the preceding clauses, wherein the time period includes a first time period and a second time period following the first time period, and wherein the treatment area is configured to release a therapeutic agent at a first rate during the first time period and at a second rate during the second time period, the second rate being less than the first rate.

[0440] 357. The storage period of any of the preceding clauses shall be not less than two weeks, not less than three weeks, not less than four weeks, not less than five weeks, not less than eight weeks, not less than two months, not less than three months, not less than four months, not less than six months, not less than seven months, not less than eight months, not less than nine months, not less than ten months, not less than twelve months, and not less than one year.

[0441] 358. A repository of any of the preceding clauses, wherein the therapeutic agents include chemotherapeutic agents.

[0442] 359. A repository of any of the foregoing clauses, wherein the chemotherapy agents include paclitaxel.

[0443] 360. A repository of any of the foregoing clauses, wherein chemotherapy agents include irinotecan.

[0444] 361. The storage of any of the preceding clauses, wherein the chemotherapeutic agents include at least one of the following: cisplatin, oxaliplatin, capecitabine, albumin-bound, irinotecan, 5-fluorouracil, gemcitabine, vinorelbine, pemetrexed, or combinations thereof.

[0445] 362. A repository of any of the foregoing clauses, wherein the therapeutic agents include targeted agents.

[0446] 363. A repository of drugs for any of the preceding clauses, wherein the targeted agents include at least one of the following: palbociclib, abecilib, tepifenab, tanomastat, marimastat, erlotinib, or algenpanticel-L, ibilimumab.

[0447] 364. A repository of any of the preceding clauses, wherein the therapeutic agents include immunotherapeutic agents.

[0448] 365. A repository of immunotherapeutic agents comprising at least one of the following: nivolumab, pembrolizumab, or ramucirumab.

[0449] 366. A repository of any of the preceding clauses, wherein the immunotherapeutic agents are configured to reduce the growth and / or spread of cancer tissue by targeting programmed death ligand 1 and / or programmed cell death protein 1.

[0450] 367. A storage facility of any of the preceding clauses, wherein the treatment area contains at least 20 mg, 50 mg, at least 100 mg, at least 200 mg, at least 300 mg, at least 400 mg, at least 500 mg, at least 600 mg, at least 700 mg, at least 800 mg, or at least 1 g of therapeutic agent.

[0451] 368. A storage facility for any of the preceding clauses, wherein the treatment area is configured to administer doses over a period of time at approximately 0.1 mg / day to approximately 200 mg / day, approximately 0.1 mg / day to approximately 150 mg / day, approximately 0.1 mg / day to approximately 100 mg / day, approximately 0.1 mg / day to approximately 90 mg / day, approximately 0.1 mg / day to approximately 80 mg / day, approximately 0.1 mg / day to approximately 70 mg / day, or approximately 0.1 mg / day. - Rate-release therapeutic agents of approximately 60 mg / day, approximately 0.1 mg / day to approximately 50 mg / day, approximately 0.1 mg / day to approximately 40 mg / day, approximately 0.1 mg / day to approximately 30 mg / day, approximately 1 mg / day to approximately 30 mg / day, approximately 1 mg / day to approximately 20 mg / day, approximately 5 mg / day to approximately 20 mg / day, approximately 10 mg / day to approximately 20 mg / day, or approximately 15 mg / day to approximately 20 mg / day.

[0452] 369. A storage facility for any of the foregoing clauses, wherein the treatment area also contains anesthetics.

[0453] 370. A storage facility for any of the preceding clauses, wherein the anesthetic agents include at least one of the following: bupivacaine, ropivacaine, mepivacaine, eticaine, levobupivacaine, trimethaine, carticaine, articaine, lidocaine, prilocaine, benzocaine, procaine, tetracaine, or chloroprocaine.

[0454] 371. A storage facility for any of the preceding clauses, wherein the treatment area also contains anti-inflammatory drugs.

[0455] 372. A repository of anti-inflammatory drugs comprising at least one of the following: prednisolone, betamethasone, cortisone, dexamethasone, hydrocortisone, methylprednisolone, aspirin, ibuprofen, naproxen sodium, diclofenac, diclofenac-misoprostol, celecoxib, piroxicam, indomethacin, meloxicam, ketoprofen, sulindac, diflunisal, nabumetone, oxapazine, tometidine, disalicylate, etodoxacin, fenprofen, flurbiprofen, ketoprofen, meclofenamic acid, mefenamic acid, or a COX-2 inhibitor.

[0456] 373. A storage facility for any of the preceding clauses, wherein the treatment area also contains antibiotics and / or antimicrobial agents.

[0457] 374. The stored contents of any of the preceding clauses, wherein the antibiotics and / or antimicrobial agents include at least one of the following: amoxicillin, amoxicillin / clavulanate, cephalexin, ciprofloxacin, clindamycin, metronidazole, azithromycin, levofloxacin, sulfamethoxazole. Trimethoprim / trimethoprim, tetracycline (one or more), minocycline, tigecycline, doxycycline, rifampin, triclosan, chlorhexidine, penicillin (one or more), aminoglycide, quinolone, fluoroquinolone, vancomycin, gentamicin, cephalosporin (one or more), carbapenem, imipenem, ertapenem, antimicrobial peptides, bactericidal peptides - bee venom peptides, Xenopus antimicrobial peptides, skin antimicrobial peptides, antimicrobial peptides, α-defensin or α-endogenous antimicrobial peptides (α-protegrin).

[0458] 375. A storage facility for any of the preceding clauses, wherein the treatment area also contains an antifungal agent.

[0459] 376. A repository of any of the preceding clauses, wherein the antifungal region comprises a first part and a second part, wherein the first part contains a therapeutic agent and the second part contains an immunotherapeutic agent.

[0460] 377. The storage facility of any of the preceding clauses, wherein the first portion is closer to the outer surface of the storage facility than the second portion.

[0461] 378. The storage facility of any of the preceding clauses, wherein the first portion is further away from the outer surface of the storage facility than the second portion.

[0462] 379. A storage facility for any of the preceding clauses, wherein the treatment area is configured to continuously release treatment for a period of time.

[0463] 380. A storage facility of any of the preceding clauses, wherein the storage facility is configured to release a therapeutic agent at a first rate and an immunotherapeutic agent at a second rate.

[0464] 381. A storage facility of any of the preceding clauses, wherein the first rate is the same as the second rate.

[0465] 382. A storage facility of any of the preceding clauses, wherein the first rate is different from the second rate.

[0466] 383. A storage facility of any of the preceding clauses, wherein the first rate is greater than the second rate.

[0467] 384. A storage facility of any of the preceding clauses, wherein the first rate is less than the second rate.

[0468] 385. A system for treating pancreatic cancer by controlled sustained release of a therapeutic agent, the system comprising:

[0469] The storage facility for any of the foregoing clauses, and

[0470] The drug delivery device is configured to be positioned near the pancreas.

[0471] 386. The system of any of the preceding clauses, wherein the drug delivery device is configured to position the reservoir on the surface of the pancreas.

[0472] 387. The system of any of the preceding clauses, wherein the delivery device is a needle.

[0473] 388. The system of any of the preceding clauses, wherein the drug delivery device comprises a catheter.

[0474] 389. The system of any of the preceding clauses, wherein the drug delivery system is configured to facilitate access to the pancreas via an artery.

[0475] 390. The system of any of the preceding clauses, wherein the drug delivery system is configured to facilitate entry into the pancreas via the GI tract.

[0476] 391. A system for treating pancreatic cancer, comprising:

[0477] Multiple storage facilities, each containing any of the foregoing clauses, and

[0478] A drug delivery device configured to position a storage bank within the pancreas.

[0479] 392. A method for treating pancreatic cancer by controlled sustained release of a therapeutic agent, the method comprising:

[0480] Provide a storage facility that meets any of the foregoing terms.

[0481] 393. A method for treating pancreatic cancer by controlled sustained release of a therapeutic agent, the method comprising:

[0482] The storage facility for any of the foregoing clauses shall be located at the treatment site close to the patient's pancreas;

[0483] The therapeutic agent should be administered to the treatment site for a period of not less than 7 days.

[0484] 394. The method of any of the preceding clauses further includes fixing the storage bank to the pancreas.

[0485] 395. The method of any of the preceding clauses, wherein locating the reservoir at the treatment site includes access to the pancreas via an artery.

[0486] 396. The method of any of the preceding clauses, wherein locating the reservoir at the treatment site includes access to the pancreas through an incision in the patient's skin.

[0487] 397. The method of any of the preceding clauses, wherein locating the reservoir at the treatment site includes access to the pancreas via the patient's GI tract.

[0488] 398. The method of any of the preceding clauses, wherein positioning the reservoir at the treatment site includes positioning the reservoir through the patient's bile duct.

[0489] 399. The method of any of the preceding clauses, wherein positioning the reservoir at the treatment site includes positioning the reservoir in the patient's bile duct.

[0490] 400. The method of any of the preceding clauses, wherein positioning the storage bank at the treatment site includes positioning a stent in the patient's bile duct.

[0491] 401. The method of any of the preceding clauses, wherein pancreatic cancer comprises a tumor, and wherein the location of the reservoir at the treatment site includes the location of the reservoir within an artery supplying the tumor.

[0492] 402. Any of the methods mentioned in the preceding clauses, wherein the time period is not less than two weeks, not less than three weeks, not less than four weeks, not less than five weeks, not less than eight weeks, not less than two months, not less than three months, not less than four months, not less than six months, not less than seven months, not less than eight months, not less than nine months, not less than ten months, not less than twelve months, and not less than one year.

[0493] 403. A repository for treating lung cancer by sustained, controlled release of a therapeutic agent into a patient, the repository comprising:

[0494] The treatment area containing the therapeutic agent;

[0495] A control region comprising a bioabsorbable polymer and a release agent mixed with the polymer, wherein the release agent is configured to dissolve upon placement of the reservoir in vivo to form a diffusion opening in the control region; and

[0496] The storage facility is configured to be implanted near the patient's lungs at the treatment site, and when implanted, it releases chemotherapy agents at the treatment site for a period of not less than 7 days.

[0497] 404. The storage facility of any of the preceding clauses, wherein the storage facility is configured to be located above, to the side, behind or below the lung.

[0498] 405. The storage facility of any of the preceding clauses, wherein the storage facility is disposed on a buttress configured to be located at the edge of the lung.

[0499] 406. The storage facility of any of the preceding clauses, wherein the storage facility includes a fixation portion configured to adhere to the surface of lung tissue.

[0500] 407. The reservoir of any of the preceding clauses, wherein the reservoir includes a reinforced portion configured to penetrate at least a portion of the thickness of the lung tissue, thereby securing the reservoir to the lung tissue.

[0501] 408. A storage container of any of the preceding clauses, wherein the storage container includes an anchoring member connected to a treatment area, a control area and / or a base area, and wherein the anchoring member is configured to expand to a position on at least a portion of the lung tissue surface, thereby securing the storage container to the lung or inside the lung.

[0502] 409. A reservoir of any of the preceding clauses, wherein the treatment area is configured to continuously release therapeutic agents at a substantially constant rate over a period of time.

[0503] 410. A reservoir of any of the preceding clauses, wherein the treatment area is configured to continuously release therapeutic agents at an increased rate over a period of time.

[0504] 411. A storage facility of any of the preceding clauses, wherein the time period includes a first time period and a second time period following the first time period, and wherein the treatment area is configured to release a therapeutic agent at a first rate during the first time period and at a second rate during the second time period, the second rate being less than the first rate.

[0505] 412. A repository of any of the preceding clauses, wherein the therapeutic agents include chemotherapeutic agents.

[0506] 413. A repository of any of the preceding clauses, wherein the chemotherapy agents comprise at least one of the following: paclitaxel, cisplatin, carboplatin, albumin-bound paclitaxel, docetaxel, gemcitabine, vinorelbine, or pemetrexed.

[0507] 414. A repository of any of the preceding clauses, wherein the therapeutic agents include targeted agents.

[0508] 415. A repository of drugs for any of the preceding clauses, wherein the targeted agents include at least one of the following: bevacizumab, erlotinib, afatinib, gefitinib, crizotinib, or ceritinib.

[0509] 416. A repository of any of the preceding clauses, wherein the therapeutic agent is configured to target vascular endothelial growth factor.

[0510] 417. A repository of any of the preceding clauses, wherein the therapeutic agent is configured to target the epidermal growth factor receptor.

[0511] 418. A repository of any of the foregoing clauses, wherein the therapeutic agents include immunotherapy.

[0512] 419. A repository of immunotherapies comprising at least one of the following: nivolumab, pembrolizumab, or ramucirumab (cyramza).

[0513] 420. A repository of any of the preceding clauses, wherein the therapeutic agent is configured to target programmed death ligand 1 or programmed cell death protein 1.

[0514] 421. The storage period of any of the preceding clauses shall be not less than two weeks, not less than three weeks, not less than four weeks, not less than five weeks, not less than eight weeks, not less than two months, not less than three months, not less than four months, not less than six months, not less than seven months, not less than eight months, not less than nine months, not less than ten months, not less than twelve months, and not less than one year.

[0515] 422. A storage facility for any of the preceding clauses, wherein the therapeutic agent contains at least 1 mg, 10 mg or 100 mg of the therapeutic agent.

[0516] 423. A storage facility of any of the preceding clauses, wherein the treatment area contains at least 20 mg, 50 mg, at least 100 mg, at least 200 mg, at least 300 mg, at least 400 mg, at least 500 mg, at least 600 mg, at least 700 mg, at least 800 mg, or at least 1 g of therapeutic agent.

[0517] 424. A storage facility for any of the preceding clauses, wherein the treatment area is configured to administer doses over a period of time at approximately 0.1 mg / day to approximately 200 mg / day, approximately 0.1 mg / day to approximately 150 mg / day, approximately 0.1 mg / day to approximately 100 mg / day, approximately 0.1 mg / day to approximately 90 mg / day, approximately 0.1 mg / day to approximately 80 mg / day, approximately 0.1 mg / day to approximately 70 mg / day, or approximately 0.1 mg / day. - Rate-release therapeutic agents of approximately 60 mg / day, approximately 0.1 mg / day to approximately 50 mg / day, approximately 0.1 mg / day to approximately 40 mg / day, approximately 0.1 mg / day to approximately 30 mg / day, approximately 1 mg / day to approximately 30 mg / day, approximately 1 mg / day to approximately 20 mg / day, approximately 5 mg / day to approximately 20 mg / day, approximately 10 mg / day to approximately 20 mg / day, or approximately 15 mg / day to approximately 20 mg / day.

[0518] 425. A storage facility for any of the preceding clauses, wherein the treatment area contains 100 mg to 600 mg of paclitaxel.

[0519] 426. A storage facility of any of the preceding clauses, wherein the treatment area contains 100 mg to 600 mg of cisplatin.

[0520] 427. A storage facility for any of the preceding clauses, wherein the treatment area further contains immunotherapy agents.

[0521] 428. A repository of immunotherapeutic agents comprising at least one of the following: nivolumab, pembrolizumab, or ramucirumab.

[0522] 429. A storage facility for any of the preceding clauses, wherein the treatment area also contains anesthetics.

[0523] 430. A storage facility for any of the preceding clauses, wherein the anesthetic agents include at least one of the following: bupivacaine, ropivacaine, mepivacaine, eticaine, levobupivacaine, trimethaine, carticaine, articaine, lidocaine, prilocaine, benzocaine, procaine, tetracaine, or chloroprocaine.

[0524] 431. A storage facility for any of the preceding clauses, wherein the treatment area also contains anti-inflammatory drugs.

[0525] 432. A repository of anti-inflammatory drugs comprising at least one of the following: prednisolone, betamethasone, cortisone, dexamethasone, hydrocortisone, methylprednisolone, aspirin, ibuprofen, naproxen sodium, diclofenac, diclofenac-misoprostol, celecoxib, piroxicam, indomethacin, meloxicam, ketoprofen, sulindac, diflunisal, nabumetone, oxapazine, tometidine, disalicylate, etodoxacin, fenprofen, flurbiprofen, ketoprofen, meclofenamic acid, mefenamic acid, or a COX-2 inhibitor.

[0526] 433. A storage facility for any of the preceding clauses, wherein the treatment area also contains antibiotics and / or antimicrobial agents.

[0527] 434. A storage facility for any of the preceding clauses, wherein the antibiotics and / or antimicrobial agents include at least one of the following: amoxicillin, amoxicillin / clavulanate, cephalexin, ciprofloxacin, clindamycin, metronidazole, azithromycin, levofloxacin, sulfamethoxazole. Trimethoprim / trimethoprim, tetracycline (one or more), minocycline, tigecycline, doxycycline, rifampin, triclosan, chlorhexidine, penicillin (one or more), aminoglycoside, quinolone, fluoroquinolone, vancomycin, gentamicin, cephalosporin (one or more), carbapenem, imipenem, ertapenem, antimicrobial peptides, bactericidal peptides - bee venom peptides, Xenopus antimicrobial peptides, skin antimicrobial peptides, antimicrobial peptides, α-defensins or α-endogenous antimicrobial peptides.

[0528] 435. A storage facility for any of the preceding clauses, wherein the treatment area also contains an antifungal agent.

[0529] 436. The stored product of any of the preceding clauses, wherein the antifungal agent comprises at least one of the following: ketoconazole, clotrimazole, miconazole, econazole, etaconazole, fluconazole, bifenazate, terconazole, butonazole, tiaconazole, oxiconazole, thioconazole, saconazole, voriconazole, terbinafine, amorolfine, naftifine, griseofulvin, haloperidol, butenafine, tolnaftate, nystatin, cyclohexylamide, ciclopirox ketone, flucytosine, terbinafine, or amphotericin B.

[0530] 437. A storage facility for any of the preceding clauses, wherein the treatment area comprises a first part and a second part, wherein the first part contains a therapeutic agent and the second part contains at least one immunotherapeutic agent, anesthetic, anti-inflammatory drug, antibiotic or antifungal agent.

[0531] 438. The storage facility of any of the preceding clauses, wherein the first portion is closer to the outer surface of the storage facility than the second portion.

[0532] 439. The storage facility of any of the preceding clauses, wherein the first portion is further away from the outer surface of the storage facility than the second portion.

[0533] 440. A storage facility for any of the preceding clauses, wherein the treatment area is configured to continuously release immunotherapeutic agents, anesthetics, anti-inflammatory drugs, antibiotics and / or antifungal agents for a period of time.

[0534] 441. A storage facility of any of the preceding clauses, wherein the storage facility is configured to release a therapeutic agent at a first rate and an immunotherapeutic agent, anesthetic, anti-inflammatory drug, antibiotic, or antifungal agent at a second rate.

[0535] 442. A storage facility of any of the preceding clauses, wherein the first rate is the same as the second rate.

[0536] 443. A storage facility of any of the preceding clauses, wherein the first rate is different from the second rate.

[0537] 444. A storage facility of any of the preceding clauses, wherein the first rate is greater than the second rate.

[0538] 445. A storage facility of any of the preceding clauses, wherein the first rate is less than the second rate.

[0539] 446. A medical device for sealing a resected portion of the lung edge, comprising:

[0540] Staple buttress; and

[0541] The storage facility for any of the foregoing clauses.

[0542] 447. The medical device of any of the preceding clauses, wherein the reservoir is connected to the inner surface of the rib.

[0543] 448. The system of any of the preceding clauses, wherein the rib includes a reinforcement region configured to receive staples via an anastomosis device and a drug release region containing a reservoir.

[0544] 449. A system for treating lung cancer by controlled sustained release of a therapeutic agent, the system comprising:

[0545] The storage facility for any of the foregoing clauses; and

[0546] A drug delivery device configured to position the reservoir above, to the side, behind, or below the lungs.

[0547] 450. The system of any of the preceding clauses, wherein the drug delivery device is a syringe.

[0548] 451. The system of any of the preceding clauses, wherein the drug delivery device is an anastomosis device.

[0549] 452. The system of any of the preceding clauses further includes a rib configured to be fixed to the edge portion of the lung by a nail, wherein the rib includes a storage reservoir.

[0550] 453. The system of any of the preceding clauses further includes a rib configured to be fixed to the edge portion of the lung by a nail, wherein the reservoir is connected to the rib.

[0551] 454. The system of any of the preceding clauses further includes a rib configured to be fixed to a peripheral portion of the lung by a staple, wherein the rib includes a reinforcement region configured to receive the staple via an anastomosis device and a drug release region separate from the reinforcement region containing a reservoir.

[0552] 455. A system for treating lung cancer, comprising:

[0553] Multiple repositories, each containing any one of the terms __ to __; and

[0554] The drug delivery device is configured to be positioned near the lung tissue for storage.

[0555] 456. The system of any of the preceding clauses, wherein the drug delivery device includes a navigation mode for intrabronchial drug delivery for multiple reservoirs.

[0556] 457. The system of any of the preceding clauses, wherein the navigation mode includes endobronchial ultrasound or electromagnetic navigation bronchoscopy.

[0557] 458. A method for treating lung cancer by controlled sustained release of a therapeutic agent, the method comprising:

[0558] Provide a storage facility that meets any of the foregoing terms.

[0559] 459. A method for treating lung cancer by controlled sustained release of a therapeutic agent, the method comprising:

[0560] The storage facility for any of the foregoing clauses shall be located at the treatment site close to the patient's lungs;

[0561] The chemotherapy agent is released to the treatment site for a period of not less than 7 days.

[0562] 460. The method of any of the preceding clauses further includes fixing the reservoir above, to the side, behind or below the lung.

[0563] 461. The method of any of the preceding clauses further includes a fixed storage facility and a portion of the lung.

[0564] 462. Any of the methods mentioned in the preceding clauses, wherein the time period is not less than two weeks, not less than three weeks, not less than four weeks, not less than five weeks, not less than eight weeks, not less than two months, not less than three months, not less than four months, not less than six months, not less than seven months, not less than eight months, not less than nine months, not less than ten months, not less than twelve months, or not less than one year.

[0565] 463. A storage facility of any of the preceding clauses, wherein a control area surrounds only a portion of the treatment area such that, upon implantation, the remaining exposed portion of the treatment area comes into direct contact with bodily fluids at the treatment site.

[0566] 464. A storage facility for any of the preceding clauses, wherein the therapeutic agent is not included at least in the pre-implantation control area.

[0567] 465. A storage facility for any of the preceding clauses, wherein the polymer includes bioabsorbable polymers.

[0568] 466. A storage facility for any of the preceding clauses, wherein the polymer includes non-bioabsorbable polymers.

[0569] 467. A storage facility of any of the preceding clauses, wherein the polymer is a first polymer and wherein the treatment area contains a second polymer.

[0570] 468. A storage facility for any of the preceding clauses, wherein the first and / or second polymer comprises a bioabsorbable polymer.

[0571] 469. A storage facility for any of the preceding clauses, wherein the first and / or second polymer comprises a non-bioabsorbable polymer.

[0572] 470. A storage facility of any of the preceding clauses, wherein the first polymer is non-bioabsorbable and the second polymer is bioabsorbable.

[0573] 471. A storage facility for any of the preceding clauses, wherein the first and second polymers are identical.

[0574] 472. A storage facility for any of the preceding clauses, wherein the first and second polymers are different.

[0575] 473. A storage facility of any of the preceding clauses, wherein the release agent is a first release agent and the treatment area contains a second release agent.

[0576] 474. A storage facility for any of the preceding clauses, wherein the first and second releasing agents are the same.

[0577] 475. A storage facility for any of the preceding clauses, wherein the first and second releasing agents are different.

[0578] 476. A storage facility of any of the preceding clauses, wherein the weight percentage of the first release agent in the control area differs from the weight percentage of the second release agent in the treatment area.

[0579] 477. A storage facility of any of the preceding clauses, wherein the weight percentage of the first release agent in the control area is the same as the weight percentage of the second release agent in the treatment area.

[0580] 478. A storage facility of any of the preceding clauses, wherein the weight percentage of the first release agent in the control area is greater than the weight percentage of the second release agent in the treatment area.

[0581] 479. A storage facility of any of the preceding clauses, wherein the thickness of the controlled area is equal to or less than 1 / 10, 1 / 15, 1 / 20, 1 / 25, 1 / 30, 1 / 40, 1 / 50 or 1 / 100 of the thickness of the treatment area.

[0582] 480. The storage facility of any of the preceding clauses further includes a base region surrounding all or part of one or both of the control region and the treatment region, wherein the base region contains a polymer and does not include a release agent or a therapeutic agent.

[0583] 481. A repository of any of the preceding clauses, wherein the base region comprises multiple discrete subregions.

[0584] 482. A repository of any of the preceding clauses, wherein at least the preimplantation basal subregions are directly adjacent to each other within the repository.

[0585] 483. A storage facility of any of the preceding clauses, wherein, at least prior to implantation, the basic subregions are separated from each other within the storage facility by all or part of the treatment area and / or all or part of the control area.

[0586] 484. A storage facility of any of the preceding clauses, wherein the basic subregions have the same thickness.

[0587] 485. A storage facility of any of the preceding clauses, wherein the underlying subregions have different thicknesses.

[0588] 486. A repository of any of the preceding clauses, wherein the base region comprises multiple discrete subregions.

[0589] 487. A storage facility of any of the preceding clauses, wherein at least the pre-implantation therapeutic subregions are directly adjacent to each other within the storage facility.

[0590] 488. A storage facility of any of the preceding clauses, wherein, at least prior to implantation, the therapeutic subregions are separated from each other within the storage facility by all or part of a control area and / or all or part of a base area.

[0591] 489. A storage facility of any of the preceding clauses, wherein the therapeutic subregions have the same thickness.

[0592] 490. A storage facility of any of the preceding clauses, wherein the therapeutic subregions have different thicknesses.

[0593] 491. A repository of any of the preceding clauses, wherein the control area comprises multiple discrete sub-regions.

[0594] 492. A storage facility of any of the preceding clauses, wherein at least the pre-implantation control subregions are directly adjacent to each other within the storage facility.

[0595] 493. A storage facility of any of the preceding clauses, wherein, at least prior to implantation, the control subregions are separated from each other within the storage facility by all or part of the treatment area and / or all or part of the basal area.

[0596] 494. A storage facility of any of the preceding clauses, wherein the control sub-regions have the same thickness.

[0597] 495. A storage facility of any of the preceding clauses, wherein the control sub-regions have different thicknesses.

[0598] 496. A storage facility of any of the preceding clauses, wherein the controlled subregion contains the same concentration of the releasing agent.

[0599] 497. A storage facility of any of the preceding clauses, wherein a controlled subregion contains different concentrations of the releasing agent.

[0600] 498. A storage facility for any of the preceding clauses, wherein the storage facility is configured to release chemotherapy agents at the treatment site in vivo for a duration of not less than 1 day, not less than 2 days, not less than 3 days, not less than 4 days, not less than 5 days, not less than 6 days, not less than 7 days, not less than 8 days, not less than 9 days, not less than 10 days, not less than 11 days, not less than 12 days, not less than 13 days, not less than 14 days, not less than 15 days, not less than 16 days, not less than 17 days, not less than 18 days. Not less than 19 days, not less than 20 days, not less than 21 days, not less than 22 days, not less than 23 days, not less than 24 days, not less than 25 days, not less than 26 days, not less than 27 days, not less than 28 days, not less than 29 days, not less than 30 days, not less than 40 days, not less than 50 days, not less than 60 days, not less than 70 days, not less than 90 days, not less than 100 days, not less than 200 days, not less than 300 days, or not less than 365 days.

[0601] 499. A storage container of any of the preceding clauses, wherein the treatment area comprises a covered portion and an exposed portion, wherein the covered portion is covered by a control area such that when the storage container is initially positioned at the treatment site in the body, the control area is located between the covered portion of the treatment area and the physiological fluid at the treatment site, and the exposed portion of the treatment area is exposed to the physiological fluid.

[0602] 500. A warehouse for any of the preceding clauses, wherein:

[0603] The storage facility has a total surface area including the exposed surface area of ​​the covered area plus the exposed surface area of ​​the treatment area, and

[0604] When the reservoir is initially located at the treatment site in the body, the ratio of the exposed surface area of ​​the treatment area to the exposed surface area of ​​the covered area is approximately 5% to approximately 20%, or approximately 5% to approximately 15%, or approximately 5% to approximately 10%.

[0605] 501. A storage facility for any of the preceding clauses, wherein the exposed surface area of ​​the control area is less than the exposed surface area of ​​the treatment area.

[0606] 502. The storage facility of any of the preceding clauses, wherein the exposed surface area of ​​the control area is greater than the exposed surface area of ​​the treatment area.

[0607] 503. A storage facility of any of the preceding clauses, wherein the control area is a first control area and wherein the storage facility includes a second control area.

[0608] 504. The storage facility of any of the preceding clauses, wherein the first control area is located on the first side of the treatment area and the second control area is located on the second side of the treatment area opposite to the first side.

[0609] 505. A storage facility of any of the preceding clauses, wherein the storage facility comprises a plurality of control areas and a plurality of treatment areas, and wherein each treatment area is separated from an adjacent treatment area by one or more control areas.

[0610] 506. A storage facility for any of the preceding clauses, wherein each in the treatment area and each in the control area is a micro-thin layer.

[0611] 507. A storage facility of any of the preceding clauses, wherein the storage facility contains approximately 2 to approximately 100 treatment areas.

[0612] 508. A storage facility of any of the preceding clauses, wherein the storage facility contains approximately 2 to approximately 50 treatment areas.

[0613] 509. A storage facility of any of the preceding clauses, wherein the storage facility contains approximately 2 to approximately 10 treatment areas.

[0614] 510. A reservoir for any of the preceding clauses, wherein the treatment area is surrounded by a control area such that when the reservoir is located at a treatment site in the body, the control area is between the treatment area and the physiological fluid at the treatment site.

[0615] 511. A storage facility of any of the preceding clauses, wherein the control area comprises a first control layer and a second control layer.

[0616] 512. The storage facility of any of the preceding clauses, wherein the second control layer is adjacent to the treatment area and the first control layer encloses / surrounds the treatment area and the second control layer.

[0617] 513. The storage facility of any of the preceding clauses, wherein the first control layer and the second control layer together surround the treatment area.

[0618] 514. The storage facility of any of the preceding clauses, wherein the first control layer is disposed on a first side of the treatment area and the second control layer is disposed on a second side of the treatment area opposite to the first side.

[0619] 515. A repository of any of the preceding clauses, wherein the first control layer comprises a first plurality of sublayers and the second control layer comprises a second plurality of sublayers.

[0620] 516. A storage facility of any of the preceding clauses, wherein a first control layer includes a first amount of release agent and a second control layer includes a second amount of release agent different from the first amount.

[0621] 517. The reservoir of any of the preceding clauses, wherein the second control layer is positioned between the first control layer and the treatment area, and wherein the first control layer includes a first concentration of the release agent and the second control layer includes a second concentration of the release agent greater than the first concentration.

[0622] 518. The reservoir of any of the preceding clauses, wherein the second control layer is positioned between the first control layer and the treatment area, and wherein the first control layer includes a first concentration of the release agent and the second control layer includes a second concentration of the release agent less than the first concentration.

[0623] 519. The storage facility of any of the preceding clauses, wherein the second control layer is located between the first control layer and the treatment area, and wherein:

[0624] The first control layer includes up to 5% by weight of the release agent, up to 10% by weight of the release agent, up to 15% by weight of the release agent, up to 20% by weight of the release agent, up to 25% by weight of the release agent, up to 30% by weight of the release agent, up to 35% by weight of the release agent, up to 40% by weight of the release agent, up to 45% by weight of the release agent, or 50% by weight of the release agent.

[0625] The second control layer includes up to 5% by weight of the release agent, up to 10% by weight of the release agent, up to 15% by weight of the release agent, up to 20% by weight of the release agent, up to 25% by weight of the release agent, up to 30% by weight of the release agent, up to 35% by weight of the release agent, up to 40% by weight of the release agent, up to 45% by weight of the release agent, or up to 50% by weight of the release agent.

[0626] 520. A storage facility of any of the preceding clauses, wherein a second control layer is positioned between a first control layer and a treatment area, and wherein the first control layer includes a first amount of a release agent and the second control layer includes a second amount of a release agent, the second amount being at least 2X, at least 3X, at least 4X, or at least 5X of the first amount.

[0627] 521. A storage facility for any of the preceding clauses, wherein the thickness of the control area is less than or equal to 1 / 10 of the thickness of the treatment area.

[0628] 522. A storage facility for any of the preceding clauses, wherein the thickness of the control area is less than or equal to 1 / 15 of the thickness of the treatment area.

[0629] 523. A storage facility for any of the preceding clauses, wherein the thickness of the control area is less than or equal to 1 / 20 of the thickness of the treatment area.

[0630] 524. A storage facility for any of the preceding clauses, wherein the thickness of the control area is less than or equal to 1 / 25 of the thickness of the treatment area.

[0631] 525. A storage facility for any of the preceding clauses, wherein the thickness of the control area is less than or equal to 1 / 30 of the thickness of the treatment area.

[0632] 526. A storage facility for any of the preceding clauses, wherein the thickness of the control area is less than or equal to 1 / 35 of the thickness of the treatment area.

[0633] 527. A storage facility for any of the preceding clauses, wherein the thickness of the control area is less than or equal to 1 / 40 of the thickness of the treatment area.

[0634] 528. A storage facility for any of the preceding clauses, wherein the thickness of the control area is less than or equal to 1 / 45 of the thickness of the treatment area.

[0635] 529. A storage facility for any of the preceding clauses, wherein the thickness of the control area is less than or equal to 1 / 50 of the thickness of the treatment area.

[0636] 530. A storage facility for any of the preceding clauses, wherein the thickness of the control area is less than or equal to 1 / 75 of the thickness of the treatment area.

[0637] 531. A storage facility for any of the preceding clauses, wherein the thickness of the control area is less than or equal to 1 / 100 of the thickness of the treatment area.

[0638] 532. The storage container of any of the preceding clauses, wherein the storage container is a flexible solid that is structurally capable of being handled by the clinician during the normal course of surgery without breaking into multiple pieces and / or losing its overall shape.

[0639] 533. A storage facility of any of the preceding clauses, wherein the storage facility is configured to be placed at the surgical site and to release chemotherapy agents in the body for up to 7 days without breaking into multiple pieces.

[0640] 534. A storage facility of any of the preceding clauses, wherein the storage facility has a width and a thickness, and wherein the ratio of the width to the thickness is 21 or greater.

[0641] 535. A storage facility of any of the preceding clauses, wherein the ratio is 30 or greater.

[0642] 536. A storage facility of any of the preceding clauses, wherein the ratio is 40 or greater.

[0643] 537. A storage facility of any of the preceding clauses, wherein the storage facility has a surface area and a volume, and wherein the ratio of surface area to volume is at least 1.

[0644] 538. A storage container of any of the preceding clauses, wherein the diffusion opening comprises at least one or more holes and / or one or more channels.

[0645] 539. A reservoir of any of the preceding clauses, wherein two or more thin layers of a bioabsorbable polymer are bonded together by thermocompression to form a therapeutic area.

[0646] 540. A storage facility for any of the preceding clauses, wherein the control area and the treatment area are combined by thermocompression.

[0647] 541. A storage facility for any of the preceding clauses, wherein the control area and the treatment area are thermally combined.

[0648] 542. A reservoir of any of the preceding clauses, wherein dissolution of the release agent after placement in vivo at the treatment site causes the control area and the treatment area to change from a state of lower porosity to a state of higher porosity, thereby facilitating the release of the chemotherapeutic agent from the reservoir.

[0649] 543. A storage facility of any of the preceding clauses, wherein at least the controlled area does not contain chemotherapy agents prior to implantation of the storage facility at the treatment site.

[0650] 544. A storage facility of any of the preceding clauses, wherein the treatment area does not contain any release agent prior to implantation of the storage facility at the treatment site.

[0651] 545. A storage facility of any of the preceding clauses, wherein the release agent is a first release agent and the treatment area includes a second release agent mixed with a chemotherapeutic agent.

[0652] 546. A storage facility of any of the preceding clauses, wherein the release agent is a first release agent and the polymer is a first polymer, and the treatment area includes a second polymer and a second release agent mixed with a chemotherapeutic agent.

[0653] 547. A storage facility for any of the preceding clauses, wherein the first releasing agent is the same as the second releasing agent.

[0654] 548. A storage facility for any of the preceding clauses, wherein the first releasing agent is different from the second releasing agent.

[0655] 549. A storage facility of any of the preceding clauses, wherein the concentration of a first releasing agent in the control area is greater than the concentration of a second releasing agent in the treatment area.

[0656] 550. A storage facility of any of the preceding clauses, wherein the concentration of the first release agent in the control area is less than the concentration of the second release agent in the treatment area.

[0657] 551. A storage facility of any of the preceding clauses, wherein the concentration of the first release agent in the control area is the same as the concentration of the second release agent in the treatment area.

[0658] 552. A storage facility of any of the preceding clauses, wherein the concentration of a first releasing agent in the control area differs from the concentration of a second releasing agent in the treatment area.

[0659] 553. A storage facility for any of the preceding clauses, wherein the treatment area comprises multiple microlayers.

[0660] 554. A storage facility of any of the preceding clauses, wherein the mass of the chemotherapy agents constitutes at least 50% of the total mass of the storage facility.

[0661] 555. The storage facility of any of the preceding clauses, wherein the ratio of the mass of the chemotherapeutic agent in the storage facility to the mass of the polymer in the storage facility is at least 3:1.

[0662] 556. The storage facility of any of the preceding clauses, wherein the ratio of the mass of the chemotherapeutic agent in the storage facility to the mass of the polymer in the storage facility is at least 4:1.

[0663] 557. The storage facility of any of the preceding clauses, wherein the ratio of the mass of the chemotherapeutic agent in the storage facility to the mass of the polymer in the storage facility is at least 5:1.

[0664] 558. The storage facility of any of the preceding clauses, wherein the ratio of the mass of the chemotherapeutic agent in the storage facility to the mass of the polymer in the storage facility is at least 6:1.

[0665] 559. The storage facility of any of the preceding clauses, wherein the ratio of the mass of the chemotherapeutic agent in the storage facility to the mass of the polymer in the storage facility is at least 7:1.

[0666] 560. The storage facility of any of the preceding clauses, wherein the ratio of the mass of the chemotherapeutic agent in the storage facility to the mass of the polymer in the storage facility is at least 8:1.

[0667] 561. The storage facility of any of the preceding clauses, wherein the ratio of the mass of the chemotherapeutic agent in the storage facility to the mass of the polymer in the storage facility is at least 10:1.

[0668] 562. The storage facility of any of the preceding clauses, wherein the ratio of the mass of the chemotherapeutic agent in the storage facility to the mass of the polymer in the storage facility is at least 16:1.

[0669] 563. A storage facility of any of the preceding clauses, wherein the treatment area comprises at least 60% by weight of chemotherapy agents, 60% by weight of chemotherapy agents, at least 70% by weight of chemotherapy agents, at least 80% by weight of chemotherapy agents, at least 90% by weight of chemotherapy agents, or 100% by weight of chemotherapy agents.

[0670] 564. A repository of any of the preceding clauses, wherein the repository comprises at least 15% by weight of chemotherapy agents, at least 20% by weight of chemotherapy agents, at least 30% by weight of chemotherapy agents, at least 40% by weight of chemotherapy agents, at least 50% by weight of chemotherapy agents, at least 60% by weight of chemotherapy agents, at least 70% by weight of chemotherapy agents, at least 80% by weight of chemotherapy agents, at least 90% by weight of chemotherapy agents, or 100% by weight of chemotherapy agents.

[0671] 565. The repository of any of the preceding clauses further includes analgesics, wherein the analgesics include at least one of the following: simple analgesics, local anesthetics, NSAIDs, and opioids.

[0672] 566. The storage facility of any of the preceding clauses further comprises analgesics, wherein the analgesics comprise a local anesthetic selected from at least one of the following: bupivacaine, ropivacaine, mepivacaine, and lidocaine.

[0673] 567. The storage facility of any of the preceding clauses further comprises antibiotics, antifungal agents, and / or antimicrobial agents, wherein the antibiotics, antifungal agents, and / or antimicrobial agents are selected from at least one of the following: amoxicillin, amoxicillin / clavulanate, cephalexin, ciprofloxacin, clindamycin, metronidazole, azithromycin, levofloxacin, sulfamethoxazole, and sulfamethoxazole. Trimethoprim / trimethoprim, tetracycline (one or more), minocycline, tigecycline, doxycycline, rifampin, triclosan, chlorhexidine, penicillin (one or more), aminoglycosides, quinolones, fluoroquinolones, vancomycin, gentamicin, cephalosporins (one or more), carbapenem, imipenem, ertapenem, antimicrobial peptides, bactericidal peptides - bee venom peptides, Xenopus antimicrobial peptides, skin antimicrobial peptides, antimicrobial peptides, α- -Defensins and α-endogenous antimicrobial peptides, ketoconazole, clotrimazole, miconazole, econazole, etaconazole, fluconazole, bifenazate, terbinafine, butanazole, tiaconazole, oxiconazole, thioconazole, saconazole, voriconazole, terbinafine, amorolfine, naftifine, griseofulvin, haloperidol, butenafine, tolnaftate, nystatin, cyclohexylamide, ciclopirox ketone, flucytosine, terbinafine, and amphotericin B.

[0674] 568. The repository of any of the preceding clauses shall further contain anti-inflammatory drugs selected from at least one of the following: steroids, prednisolone, betamethasone, cortisone, dexamethasone, hydrocortisone and methylprednisolone, nonsteroidal anti-inflammatory drugs (NSAIDs), aspirin, ibuprofen, naproxen sodium, diclofenac, diclofenac-misoprostol, celecoxib, piroxicam, indomethacin, meloxicam, ketoprofen, sulindac, diflunisal, nabumetone, oxaprazin, tometidine, disalicylate, etodoxacin, fenofosine, flurbiprofen, ketoprofen, meclofenamic acid, mefenamic acid and COX-2 inhibitors.

[0675] 569. The storage facility of any of the preceding clauses further comprises at least one of the following: adrenaline, chlorpheniramine, or transexamic acid.

[0676] 570. A storage facility for any of the preceding clauses, wherein the releasing agent is a nonionic surfactant.

[0677] 571. A storage facility for any of the preceding clauses, wherein the releasing agent is hydrophilic.

[0678] 572. A storage facility for any of the preceding clauses, wherein the releasing agent is polysorbate.

[0679] 573. A storage facility for any of the preceding clauses, wherein the releasing agent is Tween 20.

[0680] 574. A storage facility for any of the preceding clauses, wherein the releasing agent is Tween 80.

[0681] 575. A storage facility for any of the preceding clauses, wherein the release agent is non-polymeric.

[0682] 576. A storage facility for any of the preceding clauses, wherein the releasing agent is not a plasticizer.

[0683] 577. A reservoir of any of the preceding clauses, wherein the polymer is configured to degrade only after substantially all of the chemotherapeutic agent has been released from the reservoir.

[0684] 578. A storage facility for any of the preceding clauses, wherein the polymer is a copolymer.

[0685] 579. A storage facility for any of the preceding clauses, wherein the polymer is a terpolymer.

[0686] 580. A storage facility for any of the preceding clauses, wherein the polymer comprises at least one of the following: polyglycolic acid (PGA), polycaprolactone (PCL), poly(DL-lactic acid) (PLA), poly(α-hydroxy acid), poly(lactide-co-glycolic acid) (PLGA or DLG), poly(DL-lactide-co-caprolactone) (DL-PLCL), poly(trimethylene carbonate) (PTMC), polydioxanone (PDO), poly(4-hydroxybutyrate) (PHB), polyhydroxyalkanoate (PHA), poly(phosphazene), polyphosphate), poly(amino acid), polyphenolic peptide, poly(butylene succinate) (PBS), polyethylene oxide, polypropylene fumarate, poly(phosphazene), ... Imino carbonates, poly(lactide-co-caprolactone) (PLCL), poly(glycolic acid-co-caprolactone) (PGCL) copolymers, poly(D,L-lactic acid), polyglycolic acid, poly(L-lactide-co-D,L-lactide), poly(L-lactide-co-glycolic acid), poly(D,L-lactide-co-glycolic acid), poly(glycolic acid-trimethylene carbonate), poly(ethyl glutamate-co-glutamic acid), poly(tert-butoxy-glutamic acid carbonyl methyl ester), poly(glycerol sebacate), tyrosine-derived polycarbonates, poly1,3-bis-(p-carboxyphenoxy)hexane-co-sebacate, polyphosphazenes, glycine ethyl ester polyphosphazenes, polycaprolactone co-butyl acrylate, polyhydroxybutyrate Copolymers, copolymers of maleic anhydride, copolymers of poly(trimethylene carbonate), polyethylene glycol (PEG), hydroxypropyl methylcellulose and cellulose derivatives, polysaccharides (e.g., hyaluronic acid, chitosan, and starch), proteins (e.g., gelatin and collagen) or PEG derivatives, polyaspirin, polyphosphagene, collagen, starch, pregelatinized starch, hyaluronic acid, chitosan, gelatin, alginate, albumin, fibrin, vitamin E analogs such as α-tocopherol acetate, d-α-tocopherol succinate, D-lactide, D,L-lactide, L-lactide, D,L-lactide-caprolactone (DL-CL) D,L-lactide-glycolic acid-caprolactone (DL-G-CL), dextran, vinylpyrrolidone, polyvinyl alcohol (PVA), PVA-g-PLGA, PEGT-PBT copolymer (multi-reactive), methacrylate, poly(N-isopropylacrylamide), PEO-PPO-PEO (Planick), PEO-PPO-PAA copolymer, PLGA-PEO-PLGA, PEG-PLG, PLA-PLGA, poloxamer 407, PEG-PLGA-PEG triblock copolymer, SAIB (sucrose isobutyrate acetate), hydroxypropyl cellulose, hydroxypropyl methylcellulose, hydroxyethyl methylcellulose, carboxymethyl cellulose or its salts. Poly(hydroxyethyl methacrylate), poly(methoxyethyl methacrylate), poly(methoxyethoxyethyl methacrylate), polymethyl methacrylate (PMMA), methyl methacrylate (MMA), gelatin, polyvinyl alcohol, propylene glycol and poly(DL-lactide-co-glycolic acid-co-caprolactone).

[0687] 581. A storage facility for any of the preceding clauses, wherein the polymer is one of poly(DL-lactide-co-glycolic acid-co-caprolactone) and poly(DL-lactide-co-glycolic acid) (PLGA).

[0688] 582. A storage facility for any of the preceding clauses, wherein the polymer is poly(DL-lactide-co-glycolic acid-co-caprolactone) in a molar ratio of 60:30:10.

[0689] 583. A storage facility of any of the preceding clauses, wherein the polymer is poly(DL-lactide-co-glycolic acid) (PLGA) in a molar ratio of 50:50.

[0690] 584. A storage facility for any of the preceding clauses, wherein the polymer is ester-terminated.

[0691] 585. A storage facility of any of the preceding clauses, wherein the polymer is a terpolymer, said terpolymer comprising three polymers selected from the group consisting of: polyglycolic acid (PGA), polycaprolactone (PCL), poly(L-lactic acid) (PLA), poly(DL-lactic acid) (PLA), poly(trimethylene carbonate) (PTMC), polydioxanone (PDO), poly(4-hydroxybutyrate) (PHB), polyhydroxyalkanoate (PHA), poly(phosphazene), and polyethylene glycol.

[0692] 586. A storage facility of any of the preceding clauses, wherein the polymer is a first polymer and the treatment area includes a second polymer mixed with a chemotherapeutic agent.

[0693] 587. A storage facility for any of the preceding clauses, wherein the first polymer and the second polymer are identical.

[0694] 588. A storage facility for any of the preceding clauses, wherein the first polymer and the second polymer are different.

[0695] 589. A storage facility for any of the preceding clauses, wherein the first polymer and / or the second polymer comprises at least one of the following: polyglycolic acid (PGA), polycaprolactone (PCL), poly(DL-lactic acid) (PLA), poly(α-hydroxy acid), poly(lactide-co-glycolic acid) (PLGA or DLG), poly(DL-lactide-co-caprolactone) (DL-PLCL), poly(trimethylene carbonate) (PTMC), polydioxanone (PDO), poly(4-hydroxybutyrate) (PHB), polyhydroxyalkanoate (PHA), poly(phosphazene), polyphosphate), poly(amino acid), polyphenolic peptide, poly(butylene succinate) (PBS), poly(phosphazene ... Ethylene oxide, polypropylene fumarate, polyimide carbonate, poly(lactide-co-caprolactone) (PLCL), poly(glycolic acid-co-caprolactone) (PGCL) copolymer, poly(D,L-lactic acid), polyglycolic acid, poly(L-lactide-co-D,L-lactide), poly(L-lactide-co-glycolic acid), poly(D,L-lactide-co-glycolic acid), poly(glycolic acid-trimethylene carbonate), poly(ethyl glutamate-co-glutamic acid), poly(tert-butoxy-methyl glutamate), poly(glycerol sebacate), tyrosine-derived polycarbonate, poly1,3-bis-(p-carboxyphenoxy)hexane-co-sebacate, polyphosphazene, glycine ethyl ester polyphosphazene , Polycaprolactone co-butyl acrylate, copolymers of polyhydroxybutyrate, copolymers of maleic anhydride, copolymers of poly(trimethylene carbonate), polyethylene glycol (PEG), hydroxypropyl methylcellulose and cellulose derivatives, polysaccharides (e.g., hyaluronic acid, chitosan, and starch), proteins (e.g., gelatin and collagen) or PEG derivatives, polyaspirin, polyphosphogenin, collagen, starch, pregelatinized starch, hyaluronic acid, chitosan, gelatin, alginate, albumin, fibrin, vitamin E analogs such as α-tocopherol acetate, d-α-tocopherol succinate, D-lactide, D,L-lactide, L-lactide, D,L-lactide-caprolactone (DL-CL), D,L- Lactose-glycolic acid-caprolactone (DL-G-CL), dextran, vinylpyrrolidone, polyvinyl alcohol (PVA), PVA-g-PLGA, PEGT-PBT copolymer (multi-reactive), methacrylate, poly(N-isopropylacrylamide), PEO-PPO-PEO (Planic), PEO-PPO-PAA copolymer, PLGA-PEO-PLGA, PEG-PLG, PLA-PLGA, poloxamer 407, PEG-PLGA-PEG triblock copolymer, SAIB (sucrose isobutyrate acetate), hydroxypropyl cellulose, hydroxypropyl methylcellulose, hydroxyethyl methylcellulose, carboxymethyl cellulose or its salts. Poly(hydroxyethyl methacrylate), poly(methoxyethyl methacrylate), poly(methoxyethoxyethyl methacrylate), polymethyl methacrylate (PMMA), methyl methacrylate (MMA), gelatin, polyvinyl alcohol, propylene glycol, poly(DL-lactide-co-glycolic acid-co-caprolactone).

[0696] 590. A storage facility for any of the preceding clauses, wherein the first polymer and the second polymer are selected from the following: poly(DL-lactide-co-glycolic acid-co-caprolactone) and poly(DL-lactide-co-glycolic acid) (PLGA).

[0697] 591. A storage facility for any of the preceding clauses, wherein the first polymer and / or the second polymer is poly(DL-lactide-co-glycolic acid-co-caprolactone) and has a molar ratio of 60:30:10.

[0698] 592. A storage facility for any of the preceding clauses, wherein the first polymer and / or the second polymer is poly(DL-lactide-co-glycolic acid) and has a molar ratio of 50:50.

[0699] 593. A storage facility for any of the preceding clauses, wherein the first polymer and / or the second polymer are ester-terminated.

[0700] 594. A storage facility for any of the preceding clauses, wherein the first polymer and / or the second polymer is a terpolymer, said terpolymer comprising three polymers selected from the group consisting of: polyglycolic acid (PGA), polycaprolactone (PCL), poly(L-lactic acid) (PLA), poly(trimethylene carbonate) (PTMC), polydioxanone (PDO), poly(4-hydroxybutyrate) (PHB), polyhydroxyalkanoate (PHA), poly(phosphazene), and polyethylene glycol.

[0701] 595. A storage facility for any of the preceding clauses, wherein the ratio of the release agent to the polymer in the controlled area is less than or equal to 1:1.

[0702] 596. A storage facility for any of the preceding clauses, wherein the ratio of the release agent to the polymer in the controlled area is less than or equal to 1:2.

[0703] 597. A storage facility of any of the preceding clauses, wherein the ratio of the release agent to the polymer in the controlled area is less than or equal to 1:3.

[0704] 598. A storage facility of any of the preceding clauses, wherein the ratio of the release agent to the polymer in the controlled area is less than or equal to 1:4.

[0705] 599. A storage facility for any of the preceding clauses, wherein the ratio of the release agent to the polymer in the controlled area is less than or equal to 1:5.

[0706] 600. A storage facility of any of the preceding clauses, wherein the ratio of the release agent to the polymer in the controlled area is less than or equal to 1:6.

[0707] 601. A storage facility of any of the preceding clauses, wherein the ratio of the release agent to the polymer in the controlled area is less than or equal to 1:7.

[0708] 602. A storage facility of any of the preceding clauses, wherein the ratio of the release agent to the polymer in the controlled area is less than or equal to 1:8.

[0709] 603. A storage facility for any of the preceding clauses, wherein the ratio of the release agent to the polymer in the controlled area is less than or equal to 1:9.

[0710] 604. A storage facility of any of the preceding clauses, wherein the ratio of the release agent to the polymer in the controlled area is less than or equal to 1:10.

[0711] 605. A storage facility for any of the preceding clauses, wherein the ratio of the release agent to the polymer in the controlled area is less than or equal to 1:15.

[0712] 606. A warehouse for any of the preceding clauses, wherein:

[0713] The polymer is the first polymer, and the treatment area also includes a second polymer.

[0714] The storage tank has a polymer mass equal to the sum of the mass of the first polymer and the mass of the second polymer, and

[0715] The ratio of the mass of the chemotherapy agent in the storage facility to the mass of the polymer in the storage facility is approximately 1:1.

[0716] 607. A storage facility for any of the preceding clauses, wherein the first polymer is the same as the second polymer.

[0717] 608. A storage facility for any of the preceding clauses, wherein the first polymer is different from the second polymer.

[0718] 609. A storage facility of any of the preceding clauses, wherein the ratio of the mass of the chemotherapeutic agent in the storage facility to the mass of the polymer in the storage facility is at least 2:1.

[0719] 610. The storage facility of any of the preceding clauses, wherein the ratio of the mass of the chemotherapeutic agent in the storage facility to the mass of the polymer in the storage facility is at least 3:1.

[0720] 611. The storage facility of any of the preceding clauses, wherein the ratio of the mass of the chemotherapeutic agent in the storage facility to the mass of the polymer in the storage facility is at least 4:1.

[0721] 612. The storage facility of any of the preceding clauses, wherein the ratio of the mass of the chemotherapeutic agent in the storage facility to the mass of the polymer in the storage facility is approximately 5:1.

[0722] 613. The storage facility of any of the preceding clauses, wherein the ratio of the mass of the chemotherapeutic agent in the storage facility to the mass of the polymer in the storage facility is at least 6:1.

[0723] 614. The storage facility of any of the preceding clauses, wherein the ratio of the mass of the chemotherapeutic agent in the storage facility to the mass of the polymer in the storage facility is at least 7:1.

[0724] 615. The storage facility of any of the preceding clauses, wherein the ratio of the mass of the chemotherapeutic agent in the storage facility to the mass of the polymer in the storage facility is at least 8:1.

[0725] 616. The storage facility of any of the preceding clauses, wherein the ratio of the mass of the chemotherapeutic agent in the storage facility to the mass of the polymer in the storage facility is at least 10:1.

[0726] 617. The storage facility of any of the preceding clauses, wherein the ratio of the mass of the chemotherapeutic agent in the storage facility to the mass of the polymer in the storage facility is at least 16:1.

[0727] 618. A storage facility of any of the preceding clauses, wherein the storage facility is configured to inhibit the growth of bacteria and fungi such that the number of bacteria in the storage facility is 10X, 20X, 30X, 40X or 50X the number of bacteria present in a control storage facility that does not contain the chemotherapeutic agent.

[0728] 619. A reservoir for the sustained controlled release of a therapeutic agent, comprising:

[0729] The treatment area containing the therapeutic agent;

[0730] A control region comprising a bioabsorbable polymer and a release agent mixed with the polymer, wherein the release agent is configured to dissolve upon contact with a liquid to form a diffusion opening in the control region; and

[0731] Specifically, when the storage tank is in contact with liquid, it is configured to release the therapeutic agent into the surrounding fluid for at least 14 days.

[0732] Approximately 20% to 50% of the treatment is released during the first 3 to 5 days of the 14-day period, and at least 80% of the remaining treatment is released during the last 11 days of the 14-day period.

[0733] 620. A storage facility of any of the foregoing provisions, wherein at least 85% of the remaining therapeutic agent is released in the 11th day following the 14th day.

[0734] 621. A storage tank of any of the preceding clauses, wherein the releasing agent is configured to dissolve to form a diffusion opening when the storage tank is placed in contact with a phosphate-buffered saline solution.

[0735] 622. The reservoir of any of the preceding clauses further includes a contact-dissolving and releasing agent in response to physiological fluids in the controlled area and the treatment site.

[0736] 623. The reservoir of any of the preceding clauses further includes a diffusion opening in the controlled area created by the dissolution of the release agent in response to physiological fluid at the treatment site.

[0737] 624. A storage depot for releasing therapeutic agents to treat or control a specific condition or disease, comprising:

[0738] A therapeutic area comprising a therapeutic agent and a bioabsorbable polymer carrier;

[0739] The device comprises a bioabsorbable polymer layer and a control region of a release agent mixed with the polymer, wherein the release agent is configured to dissolve within a first time period after in vivo placement to form a diffusion opening in the control region; and

[0740] The storage facility is configured as a treatment site implanted in the body, and a therapeutic agent is released at the treatment site for a second time period upon implantation.

[0741] The second time period is longer than the first time period;

[0742] The polymer carrier in the treatment area and the polymer layer in the control area after the second time period contain a highly porous polymer structure configured to degrade in vivo without core acidification.

[0743] 625. The storage facility of any of the preceding clauses, wherein at the end of the second time period, the mass of the highly porous polymer structure is not greater than 50% of the mass of the storage facility prior to in vivo placement.

[0744] 626. A storage facility of any of the preceding clauses, wherein the highly porous polymer structure is configured to degrade in vivo via surface etching.

[0745] 627. A reservoir for the controlled sustained release of a therapeutic agent, comprising:

[0746] A treatment area containing the therapeutic agent, the treatment area extending along a first axis; and

[0747] A control region that at least partially surrounds the treatment area and extends along a first axis, the control region comprising a bioabsorbable polymer and a release agent mixed with the polymer, wherein the release agent is configured to dissolve when the reservoir is placed in the body to form a diffusion opening in the control region;

[0748] The storage facility is configured as a treatment site implanted in the body, and a therapeutic agent is released at the treatment site for a period of not less than 3 days upon implantation.

[0749] 628. A storage facility of any of the preceding clauses, wherein the maximum lateral dimension of the storage facility along the first axis is at least 5 times the maximum lateral dimension along the second axis orthogonal to the first axis.

[0750] 629. A storage facility of any of the preceding clauses, wherein the maximum lateral dimension of the storage facility along the first axis is at least 10 times the maximum lateral dimension along the second axis orthogonal to the first axis.

[0751] 630. A storage facility of any of the preceding clauses, wherein the storage facility is substantially cylindrical.

[0752] 631. A storage facility of any of the preceding clauses, wherein the storage facility is substantially cylindrical.

[0753] 632. A storage facility for any of the preceding clauses, wherein the treatment area is substantially cylindrical.

[0754] 633. The storage facility of any of the preceding clauses further includes at least one opening extending through the treatment area.

[0755] 634. The storage container of any of the preceding clauses, wherein the opening forms a cylindrical inner cavity extending parallel to the first axis.

[0756] 635. A storage container of any of the preceding clauses, wherein the opening comprises an inner cavity extending along a second axis substantially perpendicular to the first axis.

[0757] 636. The storage facility of any of the preceding clauses further includes a plurality of elongated openings extending parallel to the second axis.

[0758] 637. A storage facility of any of the preceding clauses, wherein the treatment area comprises a plurality of separate, elongated subregions extending substantially parallel to the first axis.

[0759] 638. A storage facility of any of the preceding clauses, wherein each of the elongated subregions is substantially cylindrical.

[0760] 639. A storage facility of any of the preceding clauses, wherein each of the elongated subregions is radially separated from each other by a control area.

[0761] 640. A storage facility of any of the preceding clauses, wherein the outermost radial dimension of the storage facility varies along a first axis.

[0762] 641. A storage facility of any of the preceding clauses, wherein the outermost radial dimension of the treatment area varies along a first axis.

[0763] 642. A storage facility of any of the preceding clauses, wherein the treatment area is a series of separate areas covered and connected by a continuous control area.

[0764] 643. The storage facility mentioned above, wherein the control area is narrower in areas without internal treatment areas.

[0765] 644. The storage facility of the foregoing clause, wherein the control area is designed to be bent or disconnected during or after administration.

[0766] 645. A storage facility of any of the preceding clauses, wherein the control area has a thickness that varies along the length of the storage facility along a first axis.

[0767] 646. A storage facility of any of the preceding clauses, wherein the control area has a thickness that varies radially about a first axis.

[0768] 647. A storage facility of any of the preceding clauses, wherein the variable thickness of the control area causes the storage facility to bend or flex when arranged within the body.

[0769] 648. A storage tank according to any of the preceding clauses, wherein the storage tank is configured to bend or flex when placed in contact with physiological fluids in the body.

[0770] 649. A storage container of any of the preceding clauses, wherein the storage container comprises an elongated polymer strip having a length between its longitudinal ends and a width between its transverse edges, the length being greater than the width, and wherein the storage container has a predetermined shape of an expanded configuration in which the strip is curled around an axis while the width of the strip faces the axis, thereby forming an annular shape.

[0771] 650. A storage facility of any of the preceding clauses, wherein the storage facility is formed in a ring or semi-ring shape.

[0772] 651. A storage facility of any of the preceding clauses, wherein the storage facility has a first region and a second region, each extending longitudinally and extending together with each other over all or part of their respective lengths, the first region having a first elasticity and the second region having a second elasticity less than the first elasticity.

[0773] 652. The reservoir of the foregoing clause, wherein the reservoir is stretched beyond the elastic hysteresis point of the second region, such that when released from the drug delivery device, the reservoir changes from a straight state to a bent state in which the second region stretches the reservoir into a bent shape.

[0774] 653. A storage facility of any of the preceding clauses, wherein the storage facility has a first region and a second region, each extending longitudinally and extending together with each other over all or part of their respective lengths, the first region being more hydrophilic than the second region.

[0775] 654. The reservoir of the foregoing clause, wherein when released from the drug delivery device, the reservoir changes from a straight state to a bent state in which the second region pulls the reservoir into a bent shape.

[0776] 655. A storage facility of any of the preceding clauses, wherein the control area has first and second portions, the first and second portions having a first thickness, and the first and second portions being separated along a first axis by a third portion having a second thickness different from the first thickness.

[0777] 656. A storage tank according to any of the preceding clauses, wherein the storage tank extends along a first axis from a first end to a second end, and wherein the control area has a thickness that increases from the first end to the second end.

[0778] 657. A storage facility of any of the preceding clauses, wherein the storage facility extends along a first axis from a first end to a second end, and wherein the control area does not cover the treatment area at the first end of the storage facility.

[0779] 658. A storage facility of any of the preceding clauses, wherein the storage facility extends along a first axis from a first end to a second end, and wherein the control area does not cover the treatment area at the first or second end.

[0780] 659. A storage facility of any of the preceding clauses, wherein the control area has a plurality of discrete openings formed therein.

[0781] 660. A storage facility of any of the preceding clauses, wherein the control area has an opening extending along a first axis.

[0782] 661. A storage facility of any of the preceding clauses, wherein an extended opening in the controlled area extends along the entire length of the storage facility.

[0783] 662. A storage facility of any of the preceding clauses, wherein the control area is contained within a plurality of annular holes formed therein.

[0784] 663. A reservoir of any of the preceding clauses, wherein the treatment area is a first treatment area, and the reservoir further includes a second treatment area, each of the first and second treatment areas extending along a first axis, wherein the first and second treatment areas are configured to release a therapeutic agent at different rates.

[0785] 664. A storage facility of any of the preceding clauses, wherein the treatment area is a first treatment area, and the storage facility further includes a second treatment area, each of the first and second treatment areas extending along a first axis, wherein the first and second treatment areas contain different therapeutic agents.

[0786] 665. A storage facility for any of the preceding clauses, wherein the first and second treatment areas are coaxially aligned.

[0787] 666. The storage facility of any of the preceding clauses, wherein the first and second treatment areas extend parallel to each other along the length of the storage facility.

[0788] 667. The storage facility of any of the preceding clauses further includes a delayed region configured to dissolve more slowly in vivo than the control region or treatment region.

[0789] 668. The reservoir of any of the preceding clauses further includes a region configured to reduce the delay in the arrival of physiological fluids in the body through the control or treatment area.

[0790] 669. A storage facility of any of the preceding clauses, wherein the delay region and the treatment region are arranged coaxially such that the control region at least partially surrounds the treatment region and the delay region.

[0791] 670. A storage facility of any of the preceding clauses, wherein the delay region is a first delay region, and the storage facility further includes a second delay region, the first and second delay regions being axially separated from each other by a treatment region.

[0792] 671. A storage facility of any of the preceding clauses, wherein the first and second delay regions have different dimensions.

[0793] 672. The storage facility of any of the preceding clauses, wherein the delay region and the control region are arranged coaxially such that the control region and the delay region together at least partially surround the treatment region.

[0794] 673. The storage facility of any of the preceding clauses, wherein the first and second delay regions are axially separated from each other by a control region.

[0795] 674. The storage facility of any of the preceding clauses, wherein the storage facility extends along a first axis from a first end to a second end, and wherein a delay region is disposed above the first end of the storage facility.

[0796] 675. A storage tank according to any of the preceding clauses, wherein the storage tank extends along a first axis from a first end to a second end, and wherein the delay region includes a first end cap disposed above the first end of the storage tank and a second end cap disposed above the second end of the storage tank.

[0797] 676. A reservoir for any of the preceding clauses, wherein the treatment area comprises a covered portion and an exposed portion, wherein the covered portion is covered by a control area such that when the reservoir is initially positioned at a treatment site in the body, the control area is located between the covered portion of the treatment area and the physiological fluid at the treatment site, and the exposed portion of the treatment area is exposed to the physiological fluid.

[0798] 677. A storage facility under any of the preceding clauses, wherein the therapeutic agent in the treatment area accounts for at least 50% of the total weight of the storage facility.

[0799] 678. The storage facility of any of the preceding clauses, wherein the time period is not less than 7 days, not less than 15 days, not less than 30 days, not less than 45 days, not less than 60 days, or not less than 90 days.

[0800] 679. A storage facility of any of the preceding clauses, wherein approximately 40% to approximately 60% of the therapeutic agent is released in the treatment area during the first half of the time period.

[0801] 680. A storage facility of any of the preceding clauses, wherein at least 90% of the therapeutic agent is released in the treatment area during the time period.

[0802] 681. A storage facility of any of the preceding clauses, wherein the storage facility is configured to release approximately 2 μg to approximately 5 mg of therapeutic agent to the treatment site daily.

[0803] 682. A storage facility for any of the preceding clauses, wherein the storage facility is configured to release the therapeutic agent at the treatment site in the body for a duration of not less than 8 days, not less than 9 days, not less than 10 days, not less than 11 days, not less than 12 days, not less than 13 days, not less than 14 days, not less than 15 days, not less than 16 days, not less than 17 days, not less than 18 days, not less than 19 days, not less than 20 days, not less than 21 days, not less than 22 days, not less than 23 days, not less than 24 days, not less than 25 days, not less than 26 days, not less than 27 days, not less than 28 days, not less than 29 days, not less than 30 days, not less than 40 days, not less than 50 days, not less than 60 days, not less than 70 days, not less than 90 days, not less than 100 days, not less than 200 days, not less than 300 days, or not less than 365 days.

[0804] 683. A reservoir of any of the preceding clauses, wherein the therapeutic agent is released at a substantially steady-state rate throughout the time period.

[0805] 684. A storage facility for any of the foregoing clauses, wherein,

[0806] The storage facility has a total surface area including the exposed surface area of ​​the control area plus the exposed surface area of ​​the treatment area, and

[0807] When the reservoir is initially located at the treatment site in the body, the ratio of the exposed surface area of ​​the treatment area to the exposed surface area of ​​the control area is approximately 5% to approximately 20%, or approximately 5% to approximately 15%, or approximately 5% to approximately 10%.

[0808] 685. A storage facility under any of the preceding clauses, wherein the exposed surface area of ​​the control area is less than the exposed surface area of ​​the treatment area.

[0809] 686. A storage facility under any of the preceding clauses, wherein the exposed surface area of ​​the control area is greater than the exposed surface area of ​​the treatment area.

[0810] 687. A storage facility of any of the preceding clauses, wherein the control area is a first control area and wherein the storage facility includes a second control area.

[0811] 688. The storage facility of any of the preceding clauses, wherein the first control area is located on the first side of the treatment area and the second control area is located on the second side of the treatment area opposite to the first side.

[0812] 689. A storage facility of any of the preceding clauses, wherein the storage facility comprises a plurality of control areas and a plurality of treatment areas, and wherein each treatment area is separated from an adjacent treatment area by one or more control areas.

[0813] 690. A storage facility of any of the preceding clauses, wherein the storage facility contains approximately 2 to approximately 10 treatment areas.

[0814] 691. A storage facility of any of the preceding clauses, wherein the control area comprises a first control layer and a second control layer.

[0815] 692. The storage facility of any of the preceding clauses, wherein the second control layer is adjacent to the treatment area and the first control layer encloses / surrounds the treatment area and the second control layer.

[0816] 693. A storage facility for any of the preceding clauses, wherein the first control layer and the second control layer together surround the treatment area.

[0817] 694. A repository of any of the preceding clauses, wherein the first control layer comprises a first plurality of sublayers and the second control layer comprises a second plurality of sublayers.

[0818] 695. A storage facility of any of the preceding clauses, wherein a first control layer includes a first amount of release agent and a second control layer includes a second amount of release agent different from the first amount.

[0819] 696. The reservoir of any of the preceding clauses, wherein the second control layer is positioned between the first control layer and the treatment area, and wherein the first control layer includes a first concentration of the release agent and the second control layer includes a second concentration of the release agent greater than the first concentration.

[0820] 697. A reservoir of any of the preceding clauses, wherein a second control layer is positioned between a first control layer and a treatment area, and wherein the first control layer comprises a first concentration of a release agent and the second control layer comprises a second concentration of a release agent less than the first concentration.

[0821] 698. The storage facility of any of the preceding clauses, wherein the second control layer is located between the first control layer and the treatment area, and wherein...

[0822] The first control layer comprises up to 5% by weight of a releasing agent, up to 10% by weight of a releasing agent, up to 15% by weight of a releasing agent, up to 20% by weight of a releasing agent, up to 25% by weight of a releasing agent, up to 30% by weight of a releasing agent, up to 35% by weight of a releasing agent, up to 40% by weight of a releasing agent, up to 45% by weight of a releasing agent, or 50% by weight of a releasing agent; and

[0823] The second control layer includes up to 5% by weight of the release agent, up to 10% by weight of the release agent, up to 15% by weight of the release agent, up to 20% by weight of the release agent, up to 25% by weight of the release agent, up to 30% by weight of the release agent, up to 35% by weight of the release agent, up to 40% by weight of the release agent, up to 45% by weight of the release agent, or up to 50% by weight of the release agent.

[0824] 699. A storage facility of any of the preceding clauses, wherein a second control layer is positioned between a first control layer and a treatment area, and wherein the first control layer includes a first amount of a release agent and the second control layer includes a second amount of a release agent, the second amount being at least 2X, at least 3X, at least 4X, or at least 5X of the first amount.

[0825] 700. A storage facility of any of the preceding clauses, wherein the thickness of the controlled area is less than or equal to 1 / 10, 1 / 15, 1 / 20, 1 / 25, 1 / 30, 1 / 35, 1 / 40, 1 / 45, 1 / 50, 1 / 75 or 1 / 100 of the thickness of the treatment area.

[0826] 701. A storage facility of any of the preceding clauses, wherein the storage facility comprises an elongated cylindrical structure configured for implantation in a patient.

[0827] 702. A storage facility of any of the preceding clauses, wherein the storage facility comprises one of a plurality of beads or microspheres.

[0828] 703. A storage facility of any of the foregoing clauses, wherein the beads or microspheres have different release profiles.

[0829] 704. A storage container of any of the preceding clauses, wherein the beads or microspheres contain varying amounts of a releasing agent.

[0830] 705. A storage facility of any of the preceding clauses, wherein the beads or microspheres comprise their respective control areas of varying thicknesses.

[0831] 706. A storage facility of any of the preceding clauses, wherein the beads or microspheres have different sizes.

[0832] 707. A storage facility of any of the preceding clauses, wherein the storage facility contains one of a variety of pellets.

[0833] 708. A storage facility for any of the preceding clauses, wherein the pellets have different release profiles.

[0834] 709. A storage facility for any of the preceding clauses, wherein the pellets contain varying amounts of a releasing agent.

[0835] 710. A storage facility for any of the preceding clauses, wherein the pellets comprise their respective control areas of varying thicknesses.

[0836] 711. A storage facility for any of the preceding clauses, wherein the pellets have different sizes.

[0837] 712. A storage facility for any of the preceding clauses, wherein the pellets are substantially cylindrical.

[0838] 713. A reservoir of any of the preceding clauses, wherein the reservoir comprises a plurality of substantially cylindrical beads, each comprising a treatment area and a control area, and wherein the plurality of beads are substantially aligned along a common longitudinal axis.

[0839] 714. A storage facility of any of the preceding clauses, wherein the storage facility is biodegradable and / or biodegradable.

[0840] 715. A storage container of any of the preceding clauses, wherein the storage container is a flexible solid that is structurally capable of being handled by the clinician during the normal course of surgery without breaking into multiple pieces and / or losing its overall shape.

[0841] 716. A storage facility of any of the preceding clauses, wherein the storage facility is configured to be placed subcutaneously within the patient and to release the therapeutic agent in the body for up to 7 days without breaking into multiple pieces.

[0842] 717. A storage facility of any of the preceding clauses, wherein the storage facility has a surface area and a volume, and wherein the ratio of surface area to volume is at least 1.

[0843] 718. A storage container of any of the preceding clauses, wherein the diffusion opening comprises at least one or more holes and / or one or more channels.

[0844] 719. A reservoir of any of the preceding clauses, wherein, after placement in vivo at the treatment site, the dissolution of the release agent causes the control area and the treatment area to change from a state of lower porosity to a state of higher porosity, thereby facilitating the release of the therapeutic agent from the reservoir.

[0845] 720. A storage facility of any of the preceding clauses, wherein the release agent is a first release agent and the treatment area includes a second release agent mixed with the treatment agent.

[0846] 721. A storage container of any of the preceding clauses, wherein the release agent is a first release agent and the polymer is a first polymer, and the treatment area includes a second polymer and a second release agent mixed with the therapeutic agent.

[0847] 722. A storage facility for any of the preceding clauses, wherein the first releasing agent is the same as the second releasing agent.

[0848] 723. A storage facility for any of the preceding clauses, wherein the first releasing agent is different from the second releasing agent.

[0849] 724. A storage facility of any of the preceding clauses, wherein the concentration of a first releasing agent in the control area is greater than the concentration of a second releasing agent in the treatment area.

[0850] 725. A storage facility of any of the preceding clauses, wherein the concentration of the first releasing agent in the control area is less than the concentration of the second releasing agent in the treatment area.

[0851] 726. A storage facility of any of the preceding clauses, wherein the concentration of the first release agent in the control area is the same as the concentration of the second release agent in the treatment area.

[0852] 727. A storage facility of any of the preceding clauses, wherein the concentration of a first releasing agent in the control area differs from the concentration of a second releasing agent in the treatment area.

[0853] 728. A storage facility for any of the preceding clauses, wherein the treatment area comprises multiple microlayers.

[0854] 729. A storage facility of any of the preceding clauses, wherein the mass of the therapeutic agent accounts for at least 50% of the mass of the storage facility.

[0855] 730. A storage facility of any of the preceding clauses, wherein the ratio of the mass of the therapeutic agent in the storage facility to the mass of the polymer in the storage facility is at least 1:1, at least 2:1, 3:1, at least 4:1, at least 5:1, at least 6:1, at least 7:1, at least 8:1, at least 9:1, at least 10:1, or at least 16:1.

[0856] 731. A storage facility of any of the preceding clauses, wherein the treatment area contains a bioabsorbable polymer and a therapeutic agent.

[0857] 732. A storage facility of any of the preceding clauses, wherein the treatment area comprises at least 40% by weight of the therapeutic agent, at least 50% by weight of the therapeutic agent, at least 60% by weight of the therapeutic agent, 60% by weight of the therapeutic agent, at least 70% by weight of the therapeutic agent, at least 80% by weight of the therapeutic agent, at least 90% by weight of the therapeutic agent, or 100% by weight of the therapeutic agent.

[0858] 733. A storage facility of any of the preceding clauses, wherein the storage facility comprises at least 15% by weight of the therapeutic agent, at least 20% by weight of the therapeutic agent, at least 30% by weight of the therapeutic agent, at least 40% by weight of the therapeutic agent, at least 50% by weight of the therapeutic agent, at least 60% by weight of the therapeutic agent, at least 70% by weight of the therapeutic agent, at least 80% by weight of the therapeutic agent, at least 90% by weight of the therapeutic agent, 99% by weight of the therapeutic agent, or 99.99% by weight of the therapeutic agent.

[0859] 734. A storage facility for any of the preceding clauses, wherein the releasing agent is a nonionic surfactant.

[0860] 735. A storage facility for any of the preceding clauses, wherein the releasing agent is hydrophilic.

[0861] 736. A storage facility for any of the preceding clauses, wherein the releasing agent is polysorbate.

[0862] 737. A storage facility for any of the preceding clauses, wherein the releasing agent is Tween 20.

[0863] 738. A storage facility for any of the preceding clauses, wherein the releasing agent is Tween 80.

[0864] 739. A storage facility for any of the preceding clauses, wherein the release agent is non-polymeric.

[0865] 740. A storage facility for any of the preceding clauses, wherein the releasing agent is not a plasticizer.

[0866] 741. A reservoir of any of the preceding clauses, wherein the polymer is configured to degrade only after substantially all of the therapeutic agent has been released from the reservoir.

[0867] 742. A storage facility for any of the preceding clauses, wherein the polymer is a copolymer.

[0868] 743. A storage facility for any of the preceding clauses, wherein the polymer is a terpolymer.

[0869] 744. A storage facility for any of the preceding clauses, wherein the polymer comprises at least one of the following: polyglycolic acid (PGA), polycaprolactone (PCL), poly(DL-lactic acid) (PLA), poly(α-hydroxy acid), poly(lactide-co-glycolic acid) (PLGA or DLG), poly(DL-lactide-co-caprolactone) (DL-PLCL), poly(trimethylene carbonate) (PTMC), polydioxanone (PDO), poly(4-hydroxybutyrate) (PHB), polyhydroxyalkanoate (PHA), poly(phosphazene), polyphosphate), poly(amino acid), polyphenolic peptide, poly(butylene succinate) (PBS), polyethylene oxide, poly(phosphazene), ... Propylene glycol fumarate, polyimide carbonate, poly(lactide-co-caprolactone) (PLCL), poly(glycolic acid-co-caprolactone) (PGCL) copolymer, poly(D,L-lactic acid), polyglycolic acid, poly(L-lactide-co-D,L-lactide), poly(L-lactide-co-glycolic acid), poly(D,L-lactide-co-glycolic acid), poly(glycolic acid-trimethylene carbonate), poly(ethyl glutamate-co-glutamic acid), poly(tert-butoxy-methyl glutamate), poly(glycerol sebacate), tyrosine-derived polycarbonate, poly1,3-bis-(p-carboxyphenoxy)hexane-co-sebacate, polyphosphazene, glycine ethyl ester polyphosphazene, poly Copolymers of caprolactone co-butyl acrylate, polyhydroxybutyrate, maleic anhydride, poly(trimethylene carbonate), polyethylene glycol (PEG), hydroxypropyl methylcellulose and cellulose derivatives, polysaccharides (e.g., hyaluronic acid, chitosan, and starch), proteins (e.g., gelatin and collagen) or PEG derivatives, polyaspirin, polyphosphogenin, pregelatinized starch, hyaluronic acid, chitosan, gelatin, alginate, albumin, fibroin, vitamin E analogs such as α-tocopherol acetate, d-α-tocopherol succinate, D-lactide, D,L-lactide, L-lactide, D,L-lactide-caprolactone (DL-CL), D,L-lactide- Glycol-caprolactone (DL-G-CL), dextran, vinylpyrrolidone, polyvinyl alcohol (PVA), PVA-g-PLGA, PEGT-PBT copolymer (multi-reactive), methacrylate, poly(N-isopropylacrylamide), PEO-PPO-PEO (Planic), PEO-PPO-PAA copolymer, PLGA-PEO-PLGA, PEG-PLG, PLA-PLGA, poloxamer 407, PEG-PLGA-PEG triblock copolymer, SAIB (sucrose isobutyrate acetate), hydroxypropyl cellulose, hydroxypropyl methylcellulose, hydroxyethyl methylcellulose, carboxymethyl cellulose or its salts. Poly(hydroxyethyl methacrylate), poly(methoxyethyl methacrylate), poly(methoxyethoxyethyl methacrylate), polymethyl methacrylate (PMMA), polyvinyl alcohol, propylene glycol, and poly(DL-lactide-co-glycolic acid-co-caprolactone).

[0870] 745. A storage facility for any of the preceding clauses, wherein the polymer is one of poly(DL-lactide-co-glycolic acid-co-caprolactone) and poly(DL-lactide-co-glycolic acid) (PLGA).

[0871] 746. A storage facility of any of the preceding clauses, wherein the polymer is poly(DL-lactide-co-glycolic acid-co-caprolactone) in a molar ratio of about 60:30:10.

[0872] 747. A storage facility of any of the preceding clauses, wherein the polymer is poly(DL-lactide-co-glycolic acid) (PLGA) in a molar ratio between about 10:90 and about 90:10.

[0873] 748. A storage facility of any of the preceding clauses, wherein the polymer is poly(DL-lactide-co-glycolic acid) (PLGA) in a molar ratio of about 50:50.

[0874] 749. A storage facility of any of the preceding clauses, wherein the polymer is ester-terminated.

[0875] 750. A storage facility of any of the preceding clauses, wherein the polymer is a terpolymer, said terpolymer comprising three polymers selected from the group consisting of: polyglycolic acid (PGA), polycaprolactone (PCL), poly(L-lactic acid) (PLA), poly(DL-lactic acid) (PLA), poly(trimethylene carbonate) (PTMC), polydioxanone (PDO), poly(4-hydroxybutyrate) (PHB), polyhydroxyalkanoate (PHA), poly(phosphazene), and polyethylene glycol.

[0876] 751. A storage container of any of the preceding clauses, wherein the polymer is a first polymer and the treatment area includes a second polymer mixed with the therapeutic agent.

[0877] 752. A storage facility for any of the preceding clauses, wherein the first polymer and / or the second polymer comprises at least one of the following: polyglycolic acid (PGA), polycaprolactone (PCL), poly(DL-lactic acid) (PLA), poly(α-hydroxy acid), poly(lactide-co-glycolic acid) (PLGA or DLG), poly(DL-lactide-co-caprolactone) (DL-PLCL), poly(trimethylene carbonate) (PTMC), polydioxanone (PDO), poly(4-hydroxybutyrate) (PHB), polyhydroxyalkanoate (PHA), poly(phosphazene), polyphosphate), poly(amino acid), polyphenolic peptide, poly(butylene succinate) (PBS). Polyethylene oxide, polypropylene fumarate, polyimide carbonate, poly(lactide-co-caprolactone) (PLCL), poly(glycolic acid-co-caprolactone) (PGCL) copolymer, poly(D,L-lactic acid), polyglycolic acid, poly(L-lactide-co-D,L-lactide), poly(L-lactide-co-glycolic acid), poly(D,L-lactide-co-glycolic acid), poly(glycolic acid-trimethylene carbonate), poly(ethyl glutamate-co-glutamic acid), poly(tert-butoxy-methyl glutamate), poly(glycerol sebacate), tyrosine-derived polycarbonate, poly1,3-bis-(p-carboxyphenoxy)hexane-co-sebacate, polyphosphazene, glycine ethyl ester Polyphosphazene, copolymers of polycaprolactone co-butyl acrylate, copolymers of polyhydroxybutyrate, copolymers of maleic anhydride, copolymers of poly(trimethylene carbonate), polyethylene glycol (PEG), hydroxypropyl methylcellulose and cellulose derivatives, polysaccharides (e.g., hyaluronic acid, chitosan, and starch), proteins (e.g., gelatin and collagen) or PEG derivatives, polyaspirin, polyphosphogenin, pregelatinized starch, hyaluronic acid, chitosan, gelatin, alginate, albumin, fibroin, vitamin E analogs such as α-tocopherol acetate, d-α-tocopherol succinate, D-lactide, D,L-lactide, L-lactide, D,L-lactide-caprolactone (DL-CL), D,L-lactide Ester-glycolic acid-caprolactone (DL-G-CL), dextran, vinylpyrrolidone, polyvinyl alcohol (PVA), PVA-g-PLGA, PEGT-PBT copolymer (multi-reactive), methacrylate, poly(N-isopropylacrylamide), PEO-PPO-PEO (Planic), PEO-PPO-PAA copolymer, PLGA-PEO-PLGA, PEG-PLG, PLA-PLGA, poloxamer 407, PEG-PLGA-PEG triblock copolymer, SAIB (sucrose isobutyrate acetate), hydroxypropyl cellulose, hydroxypropyl methylcellulose, hydroxyethyl methylcellulose, carboxymethyl cellulose or its salts. Poly(hydroxyethyl methacrylate), poly(methoxyethyl methacrylate), poly(methoxyethoxyethyl methacrylate), polymethyl methacrylate (PMMA), polyvinyl alcohol, propylene glycol, poly(DL-lactide-co-glycolic acid-co-caprolactone).

[0878] 753. A storage facility for any of the preceding clauses, wherein the first polymer and / or the second polymer is selected from the following: poly(DL-lactide-co-glycolic acid-co-caprolactone) and poly(DL-lactide-co-glycolic acid) (PLGA).

[0879] 754. A storage facility for any of the preceding clauses, wherein the first polymer and / or the second polymer is poly(DL-lactide-co-glycolic acid-co-caprolactone) and has a molar ratio of about 60:30:10.

[0880] 755. A storage facility of any of the preceding clauses, wherein the first polymer and / or the second polymer is poly(DL-lactide-co-glycolic acid) and has a molar ratio of about 50:50.

[0881] 756. A storage facility of any of the preceding clauses, wherein the first polymer and / or the second polymer is ester-terminated.

[0882] 757. A storage facility for any of the preceding clauses, wherein the first polymer and / or the second polymer is a terpolymer, said terpolymer comprising three polymers selected from the group consisting of: polyglycolic acid (PGA), polycaprolactone (PCL), poly(L-lactic acid) (PLA), poly(trimethylene carbonate) (PTMC), polydioxanone (PDO), poly(4-hydroxybutyrate) (PHB), polyhydroxyalkanoate (PHA), poly(phosphazene), and polyethylene glycol.

[0883] 758. A storage facility of any of the preceding clauses, wherein the ratio of polymer to release agent in the controlled area is at least 1:1, at least 2:1, at least 3:1, at least 4:1, at least 5:1, at least 6:1, at least 7:1, at least 8:1, at least 9:1, at least 10:1, or at least 15:1.

[0884] 759. A storage tank of any of the preceding clauses, wherein the releasing agent is configured to dissolve to form a diffusion opening when the storage tank is placed in contact with a phosphate-buffered saline solution.

[0885] 760. A system for administering a therapeutic agent to a treatment site, the system comprising:

[0886] A shaft with an internal cavity;

[0887] A actuator connected to the inner cavity for operation; and

[0888] A storage tank disposed within an inner cavity and configured to be moved away from the shaft by the actuation of a thruster, the storage tank comprising:

[0889] A treatment area containing the therapeutic agent, the treatment area extending along a first axis;

[0890] A control region at least partially surrounds the treatment area and extends along a first axis, the control region comprising a bioabsorbable polymer and a release agent mixed with the polymer, wherein the release agent is configured to dissolve upon placement of a reservoir in vivo to form a diffusion opening in the control region; and

[0891] The storage facility is configured as a treatment site implanted in the body, and a therapeutic agent is released at the treatment site for a period of not less than 3 days upon implantation.

[0892] 761. A system of Article 760, wherein the repository comprises a repository of any of the preceding articles.

[0893] 762. The system of Article 760, wherein the shaft comprises a needle, and wherein the actuator comprises a plunger.

[0894] 763. A system for administering a therapeutic agent to a treatment site, the system comprising:

[0895] An expandable component, configured to expand from a volume-reduced configuration for drug delivery to a volume-expanded configuration for placement at a treatment site; and

[0896] A storage container carried by an expandable component, the storage container comprising:

[0897] A treatment area containing the therapeutic agent, the treatment area extending along a first axis;

[0898] A control region at least partially surrounds the treatment area and extends along a first axis, the control region comprising a bioabsorbable polymer and a release agent mixed with the polymer, wherein the release agent is configured to dissolve upon placement of a reservoir in vivo to form a diffusion opening in the control region; and

[0899] The storage facility is configured as a treatment site implanted in the body, and a therapeutic agent is released at the treatment site for a period of not less than 3 days upon implantation.

[0900] 764. A system of Clause 763, wherein the repository comprises a repository of any of the preceding clauses.

[0901] 765. A system according to any of the preceding clauses, wherein the expandable component includes a support.

[0902] 766. The system of any of the preceding clauses, wherein the expandable component comprises a spherical, hemispherical, ellipsoidal or semi-ellipsoidal structure.

[0903] 767. The system of any of the preceding clauses, wherein the expandable component includes a curved outer surface, and wherein the reservoir is disposed above the curved outer surface.

[0904] 768. A system of any of the preceding clauses, wherein the storage tank substantially covers at least one surface of the expandable component.

[0905] 769. The system of any of the preceding clauses, wherein the expandable component comprises a shape memory material.

[0906] 770. The system of any of the preceding clauses, wherein the reservoir is disposed in a smooth coating and wherein the smooth coating comprises a hydrogel.

[0907] 771. A method for administering a therapeutic agent to a treatment site within the body, the method comprising:

[0908] The reservoir is located at the body's therapeutic site containing physiological fluid, and the reservoir comprises:

[0909] A treatment area containing the therapeutic agent, the treatment area extending along a first axis;

[0910] A control region that at least partially surrounds the treatment area and extends along a first axis, the control region comprising a bioabsorbable polymer and a release agent mixed with the polymer; and

[0911] The release agent is dissolved in the treatment site to form a diffusion opening in the control area, thereby releasing the therapeutic agent from the storage tank to the treatment site for a period of not less than 3 days.

[0912] 772. The method of Clause 771, wherein the repository comprises a repository of any of the preceding clauses.

[0913] 773. The method of any of the preceding clauses, wherein positioning the reservoir includes subcutaneously inserting the reservoir into the treatment site using a needle.

[0914] 774. The method of any of the preceding clauses, wherein locating the reservoir includes locating the reservoir near the nerve bundle at the treatment site.

[0915] 775. The method of any of the preceding clauses further includes dissolving the release agent at a first rate and degrading the polymer at a second rate, wherein the first rate is greater than the second rate.

[0916] 776. The method of any of the preceding clauses further includes a contact-dissolving and releasing agent in response to physiological fluid between the control area and the treatment site.

[0917] 777. The method of any of the preceding clauses further includes generating a diffusion opening in the control area by dissolving the release agent in response to physiological fluid at the treatment site.

[0918] 778. The method of any of the preceding clauses, wherein the release agent is a first release agent and the treatment area includes a second release agent, and wherein the method further comprises generating microchannels in the treatment area and the control area by dissolving the first and / or second release agents.

[0919] 779. The method of any of the preceding clauses, wherein at least some microchannels penetrate both the treatment area and the control area.

[0920] 780. The method of any of the preceding clauses further includes increasing the porosity of the storage tank by dissolving the releasing agent.

[0921] 781. The method of any of the preceding clauses, wherein, after implantation, the therapeutic agent is released once or multiple times in substantially discrete doses.

[0922] 782. The method of any of the preceding clauses, wherein the therapeutic agent is released at a substantially steady-state rate for a period of time.

[0923] 783. Any of the methods described in the preceding clauses, wherein the time period is not less than 8 days, not less than 9 days, not less than 10 days, not less than 11 days, not less than 12 days, not less than 13 days, not less than 14 days, not less than 15 days, not less than 16 days, not less than 17 days, not less than 18 days, not less than 19 days, not less than 20 days, not less than 21 days, not less than 22 days, not less than 23 days, not less than 24 days, not less than 25 days, not less than 26 days, not less than 27 days, not less than 28 days, not less than 29 days, not less than 30 days, not less than 40 days, not less than 50 days, not less than 60 days, not less than 70 days, not less than 90 days, not less than 100 days, not less than 200 days, not less than 300 days, or not less than 365 days.

[0924] 784. The method of any of the preceding clauses, wherein the reservoir is a first reservoir and the method further includes positioning a second reservoir at the treatment site.

[0925] 785. A system for treating patients with cancer, the system comprising:

[0926] A reservoir for the local sustained release of a therapeutic agent, the reservoir comprising:

[0927] The treatment area containing the therapeutic agent; and

[0928] A control region comprising a polymer and a release agent mixed with the polymer, wherein the release agent is configured to dissolve when the reservoir is placed in vivo to form a diffusion opening in the control region;

[0929] A radiation source configured to deliver a therapeutically effective dose of radiation to a tumor, thereby exposing the patient to that dose of radiation and subjecting the patient to radiation-related complications; and

[0930] The storage facility is configured to be implanted near the treatment site of the tumor, and when implanted, it releases a therapeutic agent at the treatment site for a period of time, which is sufficient to reduce the radiation dose effective for the patient's treatment, thereby reducing radiation-related complications.

[0931] 786. A method for treating patients with cancer, the method comprising:

[0932] Administering a local, continuous dose of a therapeutic agent to the patient's tumor, wherein the administered dose of the therapeutic agent comprises:

[0933] The location of the storage facility is near the patient's tumor, and the storage facility contains:

[0934] The treatment area containing the therapeutic agent; and

[0935] A control region comprising a polymer and a release agent mixed with the polymer, wherein the release agent is configured to dissolve when the reservoir is placed in vivo to form a diffusion opening in the control region;

[0936] The patient is given a therapeutically effective radiation dose, in which both the tumor and non-target tissues are exposed to the radiation dose, and the non-target tissues experience radiation-related side effects.

[0937] The radiation dose effective for the patient when combined with a local, continuous dose of the therapeutic agent is less than the radiation dose effective for the patient in the absence of a local, continuous dose of the therapeutic agent, and the non-target tissues experience a reduced side effect curve associated with the smaller therapeutically effective radiation dose.

[0938] 787. A repository for treating prostate cancer by sustained, controlled release of a therapeutic agent into a patient, the repository comprising:

[0939] The treatment area comprises a biodegradable polymer mixed with a therapeutic agent configured to treat prostate cancer, wherein a reservoir is configured to be implanted at the treatment site of the patient's prostate, and the therapeutic agent is released at the treatment site for a period of not less than 7 days upon implantation.

[0940] The reservoir of Clause 788.7 further comprises a release agent mixed with the polymer, wherein the release agent is configured to dissolve when the reservoir is placed in the body to form a diffusion opening in the treatment area.

[0941] 789. A repository for treating prostate cancer by sustained, controlled release of a therapeutic agent into a patient, the repository comprising:

[0942] A treatment area containing a therapeutic agent configured to treat prostate cancer;

[0943] A control region comprising a biodegradable polymer and a release agent mixed with the polymer, wherein the release agent is configured to dissolve upon placement of the reservoir in vivo to form a diffusion opening in the control region; and

[0944] The storage facility is configured to be implanted at the treatment site of the patient's prostate, and a therapeutic agent is released at the treatment site for a period of not less than 7 days upon implantation.

[0945] 790. A storage facility of Article 789, wherein the treatment area further contains a polymer mixed with the therapeutic agent.

[0946] 791. A storage facility of any of the preceding clauses, wherein the treatment area further comprises a release agent mixed with the therapeutic agent.

[0947] 792. A storage facility of Clause 789, wherein the treatment area further contains a release agent and polymer mixed with the therapeutic agent.

[0948] 793. A storage facility of any one of clauses 789 to 792, wherein the controlled area prior to implantation of the storage facility does not contain any therapeutic agent.

[0949] 794. A storage facility of any one of clauses 787 to 793, wherein the storage facility comprises a substantially impermeable base region, and wherein the treatment region is configured to release a therapeutic agent in a direction away from the substantially impermeable base region.

[0950] 795. A reservoir of any one of clauses 787 to 794, wherein the reservoir includes one or more radiopaque elements configured to improve the visibility of the reservoir within the body.

[0951] 796. A storage facility of Article 795, wherein the non-radiotransmissive element contains a contrast agent selected from barium sulfate, iodine, air and carbon dioxide.

[0952] 797. A storage facility of any of the preceding clauses, wherein the storage facility is typically cylindrical.

[0953] 798. A storage facility of any of the preceding clauses, wherein the storage facility comprises one or more microbeads configured to be positioned at a treatment site.

[0954] 799. A storage facility of any of the preceding clauses, wherein the storage facility contains one or more pellets configured to be positioned at a treatment site.

[0955] 800. A storage facility of any of the preceding clauses, wherein the storage facility comprises one or more disks configured to be positioned at a treatment site.

[0956] 801. A storage facility of any of the preceding clauses, wherein the storage facility has an average diameter along its length of about 0.5 mm to about 3 mm, about 0.5 mm to about 2 mm, about 0.5 mm to about 1.5 mm, not greater than 1.5 mm, or not greater than 1.0 mm.

[0957] 802. A storage vault according to any of the preceding clauses, wherein the storage vault has a first end and a second end opposite to the first end and a longitudinal axis extending therebetween, and wherein the storage vault has a length measured along its longitudinal axis of about 5 mm to about 4 cm, about 5 mm to about 3 cm, about 5 mm to about 2.5 cm, about 1 cm to about 3 cm, about 1 cm to 2 cm, about 1 cm or less, about 1.1 cm or less, about 1.2 cm or less, about 1.3 cm or less, about 1.4 cm or less, about 1.5 cm or less, about 1.6 cm or less, about 1.7 cm or less, about 1.8 cm or less, about 1.9 cm or less, or about 2 cm or less.

[0958] 803. A storage facility for any of the preceding clauses, wherein:

[0959] The storage container has an average diameter along its length of about 0.5 mm to about 3 mm, about 0.5 mm to about 2 mm, about 0.5 mm to about 1.5 mm, not greater than 1.5 mm, or not greater than 1.0 mm, and the storage container has a first end and a second end opposite to the first end, and a longitudinal axis extending therebetween.

[0960] The storage facility has a length measured along its longitudinal axis of approximately 5 mm to approximately 4 cm, approximately 5 mm to approximately 3 cm, approximately 5 mm to approximately 2.5 cm, approximately 1 cm to approximately 3 cm, approximately 1 cm to 2 cm, approximately 1 cm or less, approximately 1.1 cm or less, approximately 1.2 cm or less, approximately 1.3 cm or less, approximately 1.4 cm or less, approximately 1.5 cm or less, approximately 1.6 cm or less, approximately 1.7 cm or less, approximately 1.8 cm or less, approximately 1.9 cm or less, or approximately 2 cm or less.

[0961] 804. A storage facility of any of the preceding clauses, wherein the storage facility has a length and wherein the ratio of the length of the storage facility to the average cross-sectional dimension of the storage facility along its length is at least 10 / 1, at least 12.5 / 1, at least 15 / 1, at least 17.5 / 1, at least 20 / 1, at least 22.5 / 1, at least 25 / 1, at least 27.5 / 1, at least 30 / 1, at least 32.5 / 1, at least 35 / 1, at least 37.5 / 1, or at least 40 / 1.

[0962] 805. The storage facility of any of the preceding clauses, wherein the storage facility has a volume not exceeding 10 mm. 3 11mm3 12mm 3 13mm 3 14mm 3 15mm 3 16mm 3 17mm 3 18mm 3 19mm 3 20mm 3 21mm 3 or 22mm 3 .

[0963] 806. A repository of any of the foregoing clauses, wherein therapeutic agents include chemotherapeutic agents.

[0964] 807. A storage facility of any of the preceding clauses, wherein the storage facility is configured to release the therapeutic agent at the treatment site for a period of not less than 30 days.

[0965] 808. A storage facility of any of the preceding clauses, wherein the storage facility is configured to release the therapeutic agent at the treatment site for a period of not less than 35 days.

[0966] 809. A storage facility of any of the preceding clauses, wherein the storage facility is configured to release the therapeutic agent at the treatment site for a period of not less than 40 days.

[0967] 810. A storage facility of any of the preceding clauses, wherein the storage facility is configured to release the therapeutic agent at the treatment site for a period of not less than 45 days.

[0968] 811. A storage facility of any of the preceding clauses, wherein the storage facility is configured to release the therapeutic agent at the treatment site for a period of approximately 30 days and approximately 45 days.

[0969] 812. A repository of any of the preceding clauses, wherein the therapeutic agents include chemotherapeutic agents, which are antimicrotubule agents.

[0970] 813. A storage facility for any of the foregoing clauses, wherein the therapeutic agents include docetaxel.

[0971] 814. A storage facility of Article 812, wherein the treatment area contains not less than 1 mg, not less than 2 mg, not less than 3 mg, not less than 4 mg, not less than 5 mg, not less than 6 mg, not less than 7 mg, not less than 8 mg, not less than 9 mg, not less than 10 mg, not less than 11 mg, not less than 12 mg, not less than 13 mg, not less than 14 mg, not less than 15 mg, not less than 16 mg, not less than 17 mg, not less than 18 mg, less than 19 mg, not less than 20 mg, not less than 22 mg, not less than 24 mg, not less than 26 mg, not less than 28 mg, not less than 30 mg, not less than 32 mg, not less than 34 mg, not less than 36 mg, not less than 38 mg, or not less than 40 mg of docetaxel.

[0972] 815. A storage facility for any of the preceding clauses, wherein the treatment area contains not less than 1 mg of docetaxel.

[0973] 816. A storage facility of any of the preceding clauses, wherein the treatment area contains between about 1 mg and about 2 mg of docetaxel.

[0974] 817. A storage facility for any of the preceding clauses, wherein the treatment area contains not less than 2 mg of docetaxel.

[0975] 818. A storage facility for any of the preceding clauses, wherein the treatment area contains not less than 3 mg of docetaxel.

[0976] 819. A storage facility for any of the preceding clauses, wherein therapeutic agents include paclitaxel.

[0977] 820. A repository of any of the foregoing clauses, wherein the therapeutic agents include cabazitaxel.

[0978] 821. A storage facility of Article 819, wherein the treatment area contains not less than 3 mg, not less than 4 mg, not less than 5 mg, not less than 6 mg, not less than 7 mg, not less than 8 mg, not less than 9 mg, not less than 10 mg, not less than 11 mg, not less than 12 mg, not less than 13 mg, not less than 14 mg, not less than 15 mg, not less than 16 mg, not less than 17 mg, not less than 18 mg, less than 19 mg, not less than 20 mg, not less than 22 mg, not less than 24 mg, not less than 26 mg, not less than 28 mg, not less than 30 mg, not less than 32 mg, not less than 34 mg, not less than 36 mg, not less than 38 mg, not less than 40 mg, not less than 42 mg, not less than 44 mg, not less than 46 mg, not less than 48 mg, not less than 50 mg, not less than 52 mg, not less than 54 mg, not less than 56 mg, not less than 58 mg, or not less than 60 mg of paclitaxel.

[0979] 822. The storage period of any of the preceding clauses shall be not less than 2 weeks, not less than 3 weeks, not less than 4 weeks, not less than 5 weeks, not less than 6 weeks, not less than 7 weeks, not less than 8 weeks, not less than 2 months, not less than 3 months, not less than 4 months, not less than 6 months, not less than 7 months, not less than 8 months, not less than 9 months, not less than 10 months, not less than 11 months, not less than 12 months, not less than 13 months, not less than 14 months, not less than 15 months, not less than 16 months, not less than 17 months, or not less than 18 months.

[0980] 823. A reservoir of any of the preceding clauses, wherein the treatment area is configured to continuously release a therapeutic agent at a substantially constant rate for a period of time.

[0981] 824. A reservoir for any of the preceding clauses, wherein the therapeutic agent includes a chemotherapeutic agent, and the reservoir is configured to continuously release the chemotherapeutic agent over a period of time.

[0982] 825. A reservoir for any of the preceding clauses, wherein the therapeutic agent includes a chemotherapeutic agent, and the reservoir is configured to intermittently release the chemotherapeutic agent over a period of time.

[0983] 826. A repository of any of the preceding clauses, wherein therapeutic agents include antiandrogens.

[0984] 827. A repository of any of the preceding clauses, wherein the therapeutic agents include antiandrogens, said antiandrogens comprising abiraterone acetate, apalutimide, darolutimide, enzalutimide, and bicalutimide.

[0985] 828. A reservoir for any of the preceding clauses, wherein the reservoir is configured to continuously release anti-androgens over a period of time.

[0986] 829. A reservoir for any of the preceding clauses, wherein the treatment area is configured to intermittently release anti-androgens over a period of time.

[0987] 830. A storage facility of any of the preceding clauses, wherein the therapeutic agent comprises abiraterone acetate, and wherein the treatment area contains at least 4 mg, at least 6 mg, at least 8 mg, at least 10 mg, at least 20 mg, at least 30 mg, at least 40 mg, at least 50 mg, at least 60 mg, at least 70 mg, or at least 80 mg of abiraterone acetate.

[0988] 831. A storage facility of any of the preceding clauses, wherein the therapeutic agent includes enzalutamide, and wherein the treatment area contains at least 0.5 mg, at least 1 mg, at least 2 mg, at least 3 mg, at least 4 mg, at least 5 mg, at least 6 mg, at least 7 mg, at least 8 mg, at least 9 mg, at least 10 mg, at least 11 mg, at least 12 mg, at least 13 mg, at least 14 mg, or at least 15 mg of enzalutamide.

[0989] 832. A storage facility of any of the preceding clauses, wherein the therapeutic agent includes enzalutamide, and wherein the treatment area contains not less than 3 mg of enzalutamide.

[0990] 833. A storage facility of any of the preceding clauses, wherein the therapeutic agent includes enzalutamide, and wherein the treatment area contains not less than 4 mg of enzalutamide.

[0991] 834. A storage facility for any of the preceding clauses, wherein the therapeutic agent includes enzalutamide, and wherein the treatment area contains not less than 5 mg of enzalutamide.

[0992] 835. A storage facility of any of the preceding clauses, wherein the therapeutic agent includes enzalutamide, and wherein the treatment area contains between about 3 mg and about 4 mg of enzalutamide.

[0993] 836. A storage facility of any of the preceding clauses, wherein the therapeutic agent includes bicalutamide, and wherein the treatment area contains at least 0.5 mg, at least 1 mg, at least 2 mg, at least 3 mg, at least 4 mg, at least 5 mg, at least 6 mg, at least 7 mg, at least 8 mg, at least 9 mg, at least 10 mg, at least 11 mg, at least 12 mg, at least 13 mg, at least 14 mg, or at least 15 mg of bicalutamide.

[0994] 837. A storage facility of any of the preceding clauses, wherein the therapeutic agent includes bicalutamide, and wherein the treatment area contains not less than 3 mg of bicalutamide.

[0995] 838. A storage facility of any of the preceding clauses, wherein the therapeutic agent includes bicalutamide, and wherein the treatment area contains not less than 4 mg of bicalutamide.

[0996] 839. A storage facility for any of the preceding clauses, wherein the therapeutic agent includes bicalutamide, and wherein the treatment area contains not less than 5 mg of bicalutamide.

[0997] 840. A storage facility of any of the preceding clauses, wherein the therapeutic agent includes bicalutamide, and wherein the therapeutic area contains between about 3 mg and about 4 mg of bicalutamide.

[0998] 841. A storage facility for any of the preceding clauses, wherein the therapeutic agents include bicalutamide and enzalutamide, and wherein the treatment area contains not less than 3 mg of bicalutamide and not less than 3 mg of enzalutamide.

[0999] 842. A storage facility of any of the preceding clauses, wherein the therapeutic agents include bicalutamide and enzalutamide, and wherein the therapeutic area contains between about 3 mg and about 4 mg of bicalutamide and between about 3 mg and about 4 mg of enzalutamide.

[1000] 843. A repository of any of the preceding clauses, wherein therapeutic agents include chemotherapeutic agents and antiandrogens.

[1001] 844. A repository of any of the preceding clauses, wherein the chemotherapeutic agents include at least one of docetaxel and paclitaxel and the antiandrogens include at least one of abiraterone acetate, apalutamide, dalotamidine enzalutamide and bicalutamide.

[1002] 845. A repository of any of the preceding clauses, wherein the chemotherapeutic agents include at least one of docetaxel, paclitaxel and cabazitaxel and the antiandrogens include at least one of enzalutamide and bicalutamide.

[1003] 846. A repository of any of the preceding clauses, wherein the chemotherapeutic agents include docetaxel and the antiandrogens include at least one of enzalutamide and bicalutamide.

[1004] 847. A storage facility for any of the preceding clauses, wherein the polymer comprises at least one of the following: polyglycolic acid (PGA), polycaprolactone (PCL), poly(DL-lactic acid) (PLA), poly(α-hydroxy acid), poly(lactide-co-glycolic acid) (PLGA or DLG), poly(DL-lactide-co-caprolactone) (DL-PLCL), poly(trimethylene carbonate) (PTMC), polydioxanone (PDO), poly(4-hydroxybutyrate) (PHB), polyhydroxyalkanoate (PHA), poly(phosphazene), polyphosphate, poly(amino acid), polyphenolic peptide, poly(butylene succinate) (PBS), polyethylene oxide, polypropylene fumarate, polyimide carbonate, poly(lactide-co-caprolactone) (PGA) PLCL), poly(glycolic acid-co-caprolactone) (PGCL) copolymer, poly(D,L-lactic acid), polyglycolic acid, poly(L-lactide-co-D,L-lactide), poly(L-lactide-co-glycolic acid), poly(D,L-lactide-co-glycolic acid), poly(glycolic acid-trimethylene carbonate), poly(ethyl glutamate-co-glutamic acid), poly(tert-butoxy-glutamic acid carbonyl methyl ester), poly(glycerol sebacate), tyrosine-derived polycarbonate, poly1,3-bis-(p-carboxyphenoxy)hexane-co-sebacate, polyphosphazene, glycine ethyl ester polyphosphazene, polycaprolactone co-butyl acrylate, copolymers of polyhydroxybutyrate, copolymers of maleic anhydride, copolymers of poly(trimethylene carbonate), polyethylene glycol (PEG), PEG 400, PEG 500, PEG 600, PEG 700, PEG 800, PEG 900, PEG 10K, hydroxypropyl methylcellulose and cellulose derivatives, polysaccharides (e.g., hyaluronic acid, chitosan, and starch), proteins (e.g., gelatin and collagen) or PEG derivatives, polyaspirin, polyphosphoric acid, collagen, starch, pregelatinized starch, hyaluronic acid, chitosan, gelatin, alginate, albumin, fibrin, vitamin E analogs such as α-tocopherol acetate, d-α-tocopherol succinate, D-lactide, D,L-lactide, L-lactide, D,L-lactide-caprolactone (DL-CL), D,L-lactide-glycolide-caprolactone (DL-G-CL), dextran, poly... Vinylpyrrolidone, polyvinyl alcohol (PVA), PVA-g-PLGA, PEGT-PBT copolymer (multi-reactive), methacrylate, poly(N-isopropylacrylamide), PEO-PPO-PEO (Planic), PEO-PPO-PAA copolymer, PLGA-PEO-PLGA, PEG-PLG, PLA-PLGA, poloxamer 407, PEG-PLGA-PEG triblock copolymer, SAIB (sucrose isobutyrate acetate), hydroxypropyl cellulose, hydroxypropyl methylcellulose, hydroxyethyl methylcellulose, carboxymethyl cellulose or its salts. Poly(hydroxyethyl methacrylate), poly(methoxyethyl methacrylate), poly(methoxyethoxyethyl methacrylate), polymethyl methacrylate (PMMA), methyl methacrylate (MMA), gelatin, propylene glycol and poly(DL-lactide-co-glycolic acid-co-caprolactone).

[1005] 848. A storage facility for any of the preceding clauses, wherein the polymer comprises polyester.

[1006] 849. A storage facility for any of the preceding clauses, wherein the polymer comprises synthetic polyether.

[1007] 850. A storage facility for any of the preceding clauses, wherein the polymer comprises polyester and synthetic polyether.

[1008] 851. A storage facility of any of the preceding clauses, wherein the polymer comprises PEG.

[1009] 852. A storage facility for any of the preceding clauses, wherein the polymer comprises PEG10K.

[1010] 853. A storage facility for any of the preceding clauses, wherein the polymer comprises PLGA.

[1011] 854. A storage facility of any of the preceding clauses, wherein the polymer comprises PLGA having a lactide to glycolide ratio of 50:50.

[1012] 855. A storage facility of any of the preceding clauses, wherein the polymer comprises PLGA having a lactide to glycolide ratio of 75:25.

[1013] 856. A storage facility for any of the preceding clauses, wherein the polymer comprises PLGA and PEG.

[1014] 857. Storage facilities of the polymers contained in Article 856, wherein the polymers contain no more than 5% PEG.

[1015] 858. Storage facilities of the polymers contained in Article 856, wherein the polymers contain no more than 10% PEG.

[1016] 859. A storage facility for any of the preceding clauses, wherein the polymer comprises PLGA and PEG10K.

[1017] 860. Storage facilities of the polymer contained in Article 858, wherein the polymer contains no more than 5% PEG10K.

[1018] 861. Storage facilities of the polymer contained in Article 858, wherein the polymer contains not more than 10% PEG10K.

[1019] 862. The storage facility of any of the preceding clauses, wherein the polymer comprises a first polymer and a second polymer, and the treatment area comprises the first polymer and the second polymer in a ratio of 5:5:40 to the therapeutic agent.

[1020] 863. A storage container of Article 862, wherein the first polymer is PEG and the second polymer is PLGA.

[1021] 864. A storage container of Article 862, wherein the first polymer is PEG10K and the second polymer is PLGA.

[1022] 865. A storage facility of any of the preceding clauses, wherein the polymer comprises a first polymer and a second polymer, and the treatment area comprises the first polymer and the second polymer in a ratio of 3:7:40 to the therapeutic agent.

[1023] 866. A storage container of Article 865, wherein the first polymer is PEG and the second polymer is PLGA.

[1024] Article 867. A storage container in which the first polymer is PEG10K and the second polymer is PLGA.

[1025] 868. A storage facility of any of the preceding clauses, wherein the polymer comprises a first polymer and a second polymer, and the treatment area comprises the first polymer and the second polymer in a ratio of 1:9:40 to the therapeutic agent.

[1026] 869. A storage container of Article 868, wherein the first polymer is PEG and the second polymer is PLGA.

[1027] 870. A storage container of Article 868, wherein the first polymer is PEG10K and the second polymer is PLGA.

[1028] 871. A storage facility of any of the preceding clauses, wherein the time period is a first time period and the therapeutic agent comprises a chemotherapeutic agent and an antiandrogen, wherein the storage facility is configured to release the chemotherapeutic agent for a continuous first time period and release the antiandrogen for a continuous second time period.

[1029] 872. The storage facility of Clause 871, wherein the first time period is longer than the second time period.

[1030] 873. The storage facility of Clause 871, wherein the first time period is shorter than the second time period.

[1031] 874. A storage facility of any one of clauses 871 to 873, wherein the first and second time periods are different.

[1032] 875. The storage facility of Clause 871, wherein the first and second time periods are the same.

[1033] 876. A reservoir of any one of clauses 871 to 875, wherein the reservoir is configured to substantially simultaneously begin releasing therapeutic doses of chemotherapeutic agents and therapeutic doses of antiandrogens.

[1034] 877. A reservoir of any one of clauses 871 to 875, wherein the reservoir is configured to begin releasing a therapeutic dose of a chemotherapeutic agent immediately after implantation, and wherein the reservoir is configured to begin releasing a therapeutic dose of an antiandrogen immediately after implantation, the second time being different from the first time.

[1035] 878. A storage facility of any one of clauses 871 to 877, wherein the second time is one day, two days, three days, four days, five days, six days, one week, two weeks, three weeks, four weeks, five weeks, six weeks, seven weeks, or eight weeks prior to the first time.

[1036] 879. A storage facility of any one of clauses 871 to 877, wherein the second time is one day, two days, three days, four days, five days, six days, one week, two weeks, three weeks, four weeks, five weeks, six weeks, seven weeks, or eight weeks after the first time.

[1037] 880. A repository of any one of clauses 871 to 879, wherein the repository is configured to release a chemotherapeutic agent at a first rate and an antiandrogen at a second rate.

[1038] 881. The storage facility of Articles 871 to 880, wherein the first rate is the same as the second rate.

[1039] 882. A storage facility of any one of clauses 871 to 880, wherein the first rate is different from the second rate.

[1040] 883. Storage facilities of clauses 871 to 880 and 882, wherein the first rate is greater than the second rate.

[1041] 884. A storage facility of any one of clauses 871 to 880 and 882, wherein the first rate is less than the second rate.

[1042] 885. A repository of any of the preceding clauses, wherein the treatment area comprises a first part and a second part, wherein the first part comprises a chemotherapeutic agent and the second part comprises an anti-androgen.

[1043] 886. A reservoir of Article 885, wherein a first portion completely surrounds a second portion such that when the reservoir is implanted at a treatment site, the first portion is between the second portion and adjacent tissue.

[1044] 887. A reservoir of Article 885, wherein the second portion completely surrounds the first portion such that when the reservoir is implanted at the treatment site, the second portion is between the first portion and adjacent tissue.

[1045] 888. A storage facility of Article 885, wherein the first part is closer to the outer surface of the storage facility than the second part.

[1046] 889. A storage facility of Clause 885, wherein the first part is further away from the outer surface of the storage facility than the second part.

[1047] 890. A storage container of any of the preceding clauses, wherein the storage container is generally cylindrical and comprises a first and a second semi-cylinder configured to be positioned within the cavity of a drug delivery device, such that a generally flat side of the first semi-cylinder forms a complete cylinder toward a generally flat side of the second semi-cylinder.

[1048] 891. A repository of any of the preceding clauses, wherein the repository is configured to be at least partially located within a tumor of the prostate.

[1049] 892. A repository of any of the preceding clauses, wherein the prostate cancer comprises a tumor, and wherein the repository is configured to be located entirely within the tumor of the prostate.

[1050] 893. A repository of any of the preceding clauses, wherein prostate cancer comprises a tumor, and wherein the repository is configured to be located above, to the side, behind or below the tumor.

[1051] 894. A reservoir for any of the preceding clauses, wherein the prostate cancer comprises a tumor, and wherein the reservoir is configured to be located near an artery supplying the tumor.

[1052] 895. A system for treating prostate cancer by controlled sustained release of a therapeutic agent, the system comprising:

[1053] Multiple storage facilities, each being one of the storage facilities specified in Clauses 787 to 894.

[1054] 896. A system of Article 895 in which multiple reservoirs together have a diffusion radius that surrounds the entire prostate.

[1055] 897. A system of Article 895, wherein multiple repositories together comprise at least 6 mg of chemotherapeutic agent.

[1056] 898. A system comprising multiple repositories together containing at least 3 mg of antiandrogens.

[1057] Article 899. A system comprising multiple repositories together including at least 6 mg of chemotherapeutic agent and at least 3 mg of antiandrogen.

[1058] Article 895 of Clause 900 stipulates a system in which multiple repositories comprise a first repository and a second repository, each having a different therapeutic agent.

[1059] 901. Clause 895 of the system, wherein multiple repositories include a first repository containing chemotherapeutic agents and a second repository containing antiandrogens.

[1060] 902. A system of any one of Article 899 or Article 900, wherein first and second reservoirs are loaded within a drug delivery device such that the first reservoir discharges the drug delivery device at a first location within the prostate at a first time, and the second reservoir discharges the drug delivery device at a second location within the prostate at a second time.

[1061] 903. A system for treating prostate cancer by controlled sustained release of a therapeutic agent, the system comprising:

[1062] Storage facilities under any one of clauses 787 to 894; and

[1063] A drug delivery device configured to locate the storage bank in or within the prostate.

[1064] 904. A system for treating prostate cancer by controlled sustained release of a therapeutic agent, the system comprising:

[1065] Multiple storage facilities, each being one of the storage facilities specified in Articles 787 to 894; and

[1066] A drug delivery device configured to locate the storage bank in or within the prostate.

[1067] 905. The system of any of the preceding clauses, wherein the drug delivery device comprises a catheter.

[1068] 906. The system of any of the preceding clauses, wherein the drug delivery device comprises a hollow needle.

[1069] 907. The system of any of the preceding clauses, wherein the drug delivery device comprises a needle and an elongated member configured to be slidably received through the lumen of the needle.

[1070] 908. The system of any of the preceding clauses, wherein the drug delivery device comprises a needle, a tubular braid configured to be positioned within the lumen of the needle, and an elongated member configured to be positioned within the lumen of the braid.

[1071] 909. The system of any of the preceding clauses, wherein the drug delivery device includes a drug delivery axis and a needle with a curved, predetermined shape on the distal portion, wherein the needle is configured to deliver drug to the prostate via the drug delivery axis.

[1072] 910. The system of any of the preceding clauses, wherein the delivery device is configured to locate the reservoir in or within the prostate via a rectal route.

[1073] 911. The system of any of the foregoing clauses further includes an ultrasonic probe.

[1074] 912. The system of any of the preceding clauses, wherein the drug delivery device is configured to locate the reservoir in or within the prostate via a perineal route.

[1075] 913. The system of any of the preceding clauses further includes a biopsy grid.

[1076] 914. The system of any of the preceding clauses, wherein the drug delivery device is configured to locate the reservoir in or within the prostate via the urethral route.

[1077] 915. The system of any of the preceding clauses, wherein the drug delivery device is a catheter configured for positioning through the urethra.

[1078] 916. The system of any of the preceding clauses, wherein the drug delivery device includes a prostate endoscope.

[1079] 917. The system of any of the preceding clauses, wherein the delivery device is configured to locate the reservoir in or within the prostate via an arterial route.

[1080] 918. The system of any of the preceding clauses, wherein the drug delivery device is disposable.

[1081] 919. The system of any of the preceding clauses, wherein the drug delivery device includes a needle and a disposable sleeve configured to be positioned within the lumen of the needle, wherein the disposable sleeve includes one or more pre-loaded reservoirs of any of the preceding clauses.

[1082] 920. A system according to any of the preceding clauses, wherein the drug delivery device includes one or more features configured to reduce cytotoxic exposure to the caregiver.

[1083] 921. The system of any of the preceding clauses, wherein the plurality of repositories includes at least one repositories configured for placement in at least one prostatic lobe / lobule.

[1084] 922. A method for treating prostate cancer by controlled sustained release of a therapeutic agent, the method comprising:

[1085] Provide a storage facility for any of the terms 787 to 894.

[1086] 923. A sustained-release formulation of a therapeutic agent for use in the treatment of prostate cancer, wherein the formulation is configured to release the therapeutic agent for a duration of not less than 7 days, and wherein the therapeutic agent is selected from the following: paclitaxel, docetaxel, abiraterone acetate, apalutamide, darotamide, enzalutamide, and bicalutamide.

[1087] 924. A method for treating prostate cancer by controlled sustained release of a therapeutic agent, the method comprising:

[1088] The storage facility of any one of clauses 787 to 894 shall be located at the treatment site in or within the patient's prostate; and

[1089] The therapeutic agent should be administered to the treatment site for a period of not less than 7 days.

[1090] 925. The method of Clause 924, in which multiple reservoirs administer toxic doses to the entire prostate gland for prostate cancer.

[1091] 926. A method for treating prostate cancer by controlled sustained release of a therapeutic agent, the method comprising:

[1092] Locating multiple repositories at or within the prostate as a treatment site in the patient, each repository being a repository specified in any of clauses 787 to 894; and

[1093] The therapeutic agent should be administered to the treatment site for a period of not less than 7 days.

[1094] 927. The method of any of the preceding clauses, wherein locating a plurality of repositories includes locating a first repository at a first location within the prostate and locating a second repositories at a second location within the prostate.

[1095] 928. The method of Article 924, wherein the first repository includes chemotherapeutic agents and the second repository includes antiandrogens.

[1096] 929. The method of any of the preceding clauses, wherein the prostate cancer is contained in a tumor in the first lobe of the prostate, and wherein locating a plurality of reservoirs includes locating a first reservoir adjacent to the first lobe of the tumor and locating a second reservoir in the second lobe of the prostate, which is different from the first lobe.

[1097] 930. The method of any of the preceding clauses, wherein prostate cancer comprises cancerous tissue and / or precancerous tissue within the prostate.

[1098] 931. The method of Clause 927, wherein locating multiple repositories includes locating first and second repositories in the prostate near cancerous tissue and / or precancerous tissue.

[1099] 932. The method of Clause 928, wherein a first reservoir has a first diffusion radius and a second reservoir has a second diffusion radius, and wherein the method further comprises positioning the first and second reservoirs such that (a) the first and second diffusion radii overlap, and (b) one or both of the first and second diffusion radii overlap cancerous tissue and / or precancerous tissue.

[1100] 933. The method of Clause 928, wherein a first reservoir has a first diffusion radius and a second reservoir has a second diffusion radius, and wherein the method further comprises positioning the first and second reservoirs such that (a) the first and second diffusion radii do not overlap, and (b) one or both of the first and second diffusion radii overlap cancerous tissue and / or precancerous tissue.

[1101] 934. The method of Clause 928, wherein a first reservoir has a first diffusion radius and a second reservoir has a second diffusion radius, and wherein the method further comprises positioning the first and second reservoirs such that (a) the first and second diffusion radii are spaced apart, and (b) one or both of the first and second diffusion radii overlap cancerous tissue and / or precancerous tissue.

[1102] 935. The method of Clause 928, wherein a first reservoir has a first treatment area and a second reservoir has a second treatment area, and wherein the method further comprises positioning the first and second reservoirs such that (a) the first and second treatment areas overlap, and (b) one or both of the first and second treatment areas overlap cancerous tissue and / or precancerous tissue.

[1103] 936. The method of Clause 928, wherein a first reservoir has a first treatment area and a second reservoir has a second treatment area, and wherein the method further comprises positioning the first and second reservoirs such that (a) the first and second treatment areas do not overlap, and (b) one or both of the first and second treatment areas overlap cancerous tissue and / or precancerous tissue.

[1104] 937. The method of Clause 928, wherein a first reservoir has a first treatment area and a second reservoir has a second treatment area, and wherein the method further comprises positioning the first and second reservoirs such that (a) the first and second treatment areas are spaced apart, and (b) one or both of the first and second treatment areas overlap cancerous tissue and / or precancerous tissue.

[1105] 938. The method of any of the preceding clauses, wherein the location of the storage bank at the treatment site includes access to the prostate via the rectal route.

[1106] 939. The method of any of the preceding clauses, wherein the location of the storage bank at the treatment site includes access to the prostate via a perineal route.

[1107] 940. The method of any of the preceding clauses, wherein the location of the reservoir at the treatment site includes access to the prostate via the urethra.

[1108] 941. The method of any of the preceding clauses, wherein the location of the reservoir at the treatment site includes access to the prostate via an arterial route.

[1109] 942. The method of any of the preceding clauses, wherein the prostate cancer comprises a tumor, and wherein the location of the reservoir at the treatment site includes the location of the reservoir within an artery supplying the tumor.

[1110] 943. Any of the methods described in the preceding clauses, wherein the time period is not less than two weeks, not less than three weeks, not less than four weeks, not less than five weeks, not less than eight weeks, not less than two months, not less than three months, not less than four months, not less than six months, not less than seven months, not less than eight months, not less than nine months, not less than ten months, not less than twelve months, not less than thirteen months, not less than fourteen months, not less than fifteen months, not less than sixteen months, not less than seventeen months, or not less than eighteen months.

[1111] 944. Any of the methods mentioned above also includes reducing the likelihood of prostate cancer recurrence.

[1112] 945. Any of the methods described in the preceding clauses also includes reducing the size of the prostate cancer.

[1113] 946. Any of the methods described in the preceding clauses also includes reducing pain associated with prostate cancer.

[1114] 947. Any of the methods described in the preceding clauses also includes reducing the radiation dose required to treat prostate cancer.

[1115] 948. Any of the methods described in the preceding clauses may also include reducing the radiation side effect curve.

[1116] 949. Any of the methods described in the preceding clauses also includes improving the sensitivity of prostate cancer to radiotherapy.

[1117] 950. The method of any of the preceding clauses further includes shielding non-target tissues from radiation with at least a portion of the storage tank.

[1118] 951. The method of any of the preceding clauses, which releases a toxic concentration of the therapeutic agent into the prostate tissue without administering a toxic concentration of the therapeutic agent into tissue immediately adjacent to the prostate tissue.

[1119] 952. The method of any of the preceding clauses, wherein the reservoir is located adjacent to the sac, the method comprising releasing a toxic concentration of the therapeutic agent to the prostate tissue without administering a toxic concentration of the therapeutic agent to tissue immediately adjacent to the prostate tissue.

[1120] 953. The method of any of the preceding clauses, wherein the reservoir is located within the prostate adjacent to the sac, the method comprising releasing a toxic concentration of the therapeutic agent into the prostate tissue without administering a toxic concentration of the therapeutic agent into tissue immediately adjacent to the prostate tissue.

[1121] 954. The method of any of the preceding clauses, wherein the reservoir is located less than one centimeter from the sac, the method comprising releasing a toxic concentration of the therapeutic agent into the prostate tissue without administering a toxic concentration of the therapeutic agent into tissue immediately adjacent to the prostate tissue.

[1122] 955. The method of any of the preceding clauses, wherein the reservoir is located within the prostate at a distance of less than one centimeter from the sac, the method comprising releasing a toxic concentration of the therapeutic agent into the prostate tissue without administering a toxic concentration of the therapeutic agent into tissue immediately adjacent to the prostate tissue.

[1123] 956. The method of any of the preceding clauses further includes releasing a toxic concentration of the therapeutic agent into the intracapsular space without administering a toxic concentration of the therapeutic agent into the extracapsular space.

[1124] 957. Method of treating prostate cancer using any of the systems described in clauses 895 to 919.

[1125] 958. A repository for treating prostate cancer by sustained, controlled release of a therapeutic agent into a patient, the repository comprising:

[1126] The treatment area comprises a biodegradable polymer mixed with a therapeutic agent configured to treat prostate cancer, the therapeutic agent comprising a chemotherapeutic agent; wherein a reservoir is configured to be implanted at the treatment site of the patient's prostate, and the therapeutic agent is released at the treatment site for a period of not less than 15 days upon implantation.

[1127] Article 959.953 of the Civil Code, which provides a storage facility for releasing chemotherapy agents at the treatment site for a period of not less than 30 days.

[1128] 960. A repository of therapeutic agents containing anti-androgens, as specified in Clause 953 or Clause 954.

[1129] 961. A repository of antiandrogens, wherein the antiandrogen is at least one of bicalutamide and enzalutamide.

[1130] 962. A reservoir of any one of clauses 953 to 956, wherein the reservoir is configured to administer medication to the prostate via a needle.

[1131] 963. A storage vault of any one of clauses 953 to 957, wherein the storage vault has a first end, a second end and a length measured along the longitudinal axis of the storage vault between the first and second ends, and wherein the storage vault has a cross-sectional dimension that is substantially constant along its length.

[1132] 964. A storage vault of any one of clauses 953 to 958, wherein the storage vault has a cross-sectional dimension between about 0.7 mm and about 1.2 mm.

[1133] 965. A repository of any one of clauses 953 to 959, wherein the polymer comprises poly(lactide-co-glycolic acid) (PLGA) and polyethylene glycol (PEG).

[1134] 966. A repository for treating prostate cancer by sustained, controlled release of a therapeutic agent into a patient, the repository comprising:

[1135] A substantially cylindrical component formed from a biodegradable polymer and a therapeutic agent configured to treat prostate cancer, the therapeutic agent comprising a chemotherapeutic agent, wherein a reservoir is configured for implantation at the treatment site of a patient’s prostate, and the therapeutic agent is released at the treatment site for a period of approximately 30 to approximately 45 days upon implantation.

[1136] 967. The storage container of claim 961, wherein the therapeutic agent further comprises an anti-androgen.

[1137] 968. The storage container of claim 962, wherein the antiandrogen is at least one of bicalutamide and enzalutamide.

[1138] 969. The storage container of claim 963, wherein the chemotherapeutic agent is docetaxel.

[1139] 970. The storage container of claim 963 or claim 964, wherein the substantially cylindrical component has a cross-sectional dimension between about 0.7 mm and about 1.2 mm.

[1140] 971. A reservoir according to any one of claims 961 to 965, wherein the substantially cylindrical component is configured to administer medication to the prostate via a needle.

[1141] 972. A system for treating prostate cancer by means of sustained, controlled release of a therapeutic agent into a patient, the system comprising:

[1142] Multiple reservoirs, each containing a biodegradable polymer mixed with a therapeutic agent configured to treat prostate cancer, wherein at least some reservoirs include the therapeutic agent comprising a chemotherapeutic agent, and wherein each reservoir is configured to be implanted at a treatment site in a patient's prostate, and releases the chemotherapeutic agent at the treatment site for a period of not less than 15 days upon implantation.

[1143] 973. Clause 967 of the system, wherein each reservoir is configured to release chemotherapy agents at the treatment site for a duration of not less than 30 days.

[1144] 974. The system of Clause 967 or Clause 968 further includes a tubular drug delivery device, wherein each reservoir is loaded within the drug delivery device such that the reservoirs are configured to be sequentially discharged from the drug delivery device into the prostate.

[1145] 975. A system of any one of clauses 967 to 969, wherein at least two of the plurality of repositories have different lengths.

[1146] 976. A system of any one of clauses 967 to 970, wherein a plurality of reservoirs together contain about 1 mg to about 4 mg of therapeutic agent.

[1147] 977. The system of any one of claims 967 to 971, wherein at least some of the storage containers include therapeutic agents comprising anti-androgens. Attached Figure Description

[1148] Many aspects of this disclosure can be better understood with reference to the following figures. The components in the figures are not necessarily to scale. Rather, the purpose is to clearly illustrate the principles of this disclosure.

[1149] Figure 1 This is an isometric view of the storage facility configured according to this technology.

[1150] Figure 2 Describe the release curves of one or more storage tanks of this technology over time.

[1151] Figure 3 This is an isometric view of a storage facility according to some embodiments of this technology.

[1152] Figure 4 This is an isometric view of a storage facility according to some embodiments of this technology.

[1153] Figure 5 This is a cross-sectional view of a storage tank according to some embodiments of this technology.

[1154] Figure 6 This is a cross-sectional view of a storage tank according to some embodiments of this technology.

[1155] Figure 7 This is a cross-sectional view of a storage tank according to some embodiments of this technology.

[1156] Figure 8 This is an isometric view of a storage facility according to some embodiments of this technology.

[1157] Figure 9 Is Figure 8 The image shows a cross-sectional view of the storage tank.

[1158] Figure 10 This is a cross-sectional view of a storage tank according to some embodiments of this technology.

[1159] Figure 11 This is a cross-sectional view of a storage tank according to some embodiments of this technology.

[1160] Figure 12 This is a cross-sectional view of a storage tank according to some embodiments of this technology.

[1161] Figure 13 This is an isometric view of a storage facility according to some embodiments of this technology.

[1162] Figure 14A –H is a storage container with different cross-sectional areas and shapes according to this technology.

[1163] Figure 15 Describes the maximum flexural load of the implant over time, starting from the start of testing an implanted sample immersed in a buffer solution.

[1164] Figure 16A –16E describes various storage facility implementation schemes including barrier areas according to this technology.

[1165] Figure 17 is a schematic representation of the core acidification technology in the prior art.

[1166] Figure 18 is a scanning electron microscope image of a prior art polymer tablet after 20 days of degradation.

[1167] Figure 19A This is a schematic representation of the degradation of the storage tank in this technology.

[1168] Figure 19B and 19C These are scanning electron microscope (“SEM”) images of the cross-section of the storage tank of this technology at different time points during the degradation process.

[1169] Figure 20 This is a perspective view of a storage facility according to some implementation schemes of this technology.

[1170] Figure 21 This is a cross-sectional view of a storage tank according to some embodiments of this technology.

[1171] Figure 22 This is a cross-sectional view of a storage tank according to some embodiments of this technology.

[1172] Figure 23 This is a cross-sectional view of a storage tank according to some embodiments of this technology.

[1173] Figure 24A This is a perspective view of a storage facility according to some implementation schemes of this technology.

[1174] Figure 24B Is Figure 24A The image shows a cross-sectional view of the storage tank along line BB.

[1175] Figure 24C Is Figure 24AThe image shows a cross-sectional view of the storage tank obtained along line CC.

[1176] Figure 24D This is a perspective view of a storage facility according to some implementation schemes of this technology.

[1177] Figure 25 This is a perspective view of a storage facility according to some implementation schemes of this technology.

[1178] Figure 26 This is a perspective view of a storage facility according to some implementation schemes of this technology.

[1179] Figure 27 This is a perspective view of a storage facility according to some implementation schemes of this technology.

[1180] Figure 28 This is a perspective view of a storage facility according to some implementation schemes of this technology.

[1181] Figure 29A This is a side cross-sectional view of a storage tank according to some embodiments of this technology.

[1182] Figure 29B Is Figure 29A The image shows a cross-sectional view of the storage tank along line BB.

[1183] Figure 30 This is a side cross-sectional view of a storage tank according to some embodiments of this technology.

[1184] Figure 31 This is a side cross-sectional view of a storage tank according to some embodiments of this technology.

[1185] Figure 32 This is a perspective view of a storage facility according to some implementation schemes of this technology.

[1186] Figure 33 This is a side cross-sectional view of a storage tank according to some embodiments of this technology.

[1187] Figure 34 This is a side cross-sectional view of a storage tank according to some embodiments of this technology.

[1188] Figure 35 This is a side cross-sectional view of a storage tank according to some embodiments of this technology.

[1189] Figure 36A This is a side cross-sectional view of a storage tank according to some embodiments of this technology.

[1190] Figure 36B Is Figure 36A The image shows a cross-sectional view of the storage tank along line BB.

[1191] Figure 36C This is a side cross-sectional view of a storage tank according to some embodiments of this technology.

[1192] Figure 36D This is a side cross-sectional view of a storage tank according to some embodiments of this technology.

[1193] Figure 37A This is a side cross-sectional view of a storage tank according to some embodiments of this technology.

[1194] Figure 37B describe Figure 37A The image shows the instance release curve of the storage facility over time.

[1195] Figure 38A This is a side cross-sectional view of a storage tank according to some embodiments of this technology.

[1196] Figure 38B describe Figure 38A The image shows the instance release curve of the storage facility over time.

[1197] Figure 39A This is a side cross-sectional view of a storage tank according to some embodiments of this technology.

[1198] Figure 39B describe Figure 39A The image shows the instance release curve of the storage facility over time.

[1199] Figure 40A This is a perspective view of a storage facility according to some implementation schemes of this technology.

[1200] Figure 40B This is a perspective view of a storage facility according to some implementation schemes of this technology.

[1201] Figure 41A This is a side view of a storage tank in its straightened state according to some embodiments of this technology.

[1202] Figure 41B Is Figure 41A The image shows a side view of the storage tank in a bent state.

[1203] Figure 42A This is a side view of a storage tank in its straightened state according to some embodiments of this technology.

[1204] Figure 42B Is Figure 42A The image shows a side view of the storage tank in a bent state.

[1205] Figure 43A This is a perspective view of a storage container in a straightened state according to some embodiments of this technology.

[1206] Figure 43B Is Figure 43A The image shows a cross-sectional view of the storage tank along line BB.

[1207] Figure 43C Is Figure 43A The image shows a side view of the storage tank in a bent state.

[1208] Figure 44 This is a side view of a storage tank arranged at a target site in the body according to some embodiments of this technology.

[1209] Figure 45 This is a side view of a storage tank arranged at a target site in the body according to some embodiments of this technology.

[1210] Figure 46 This is a side view of a storage tank according to some embodiments of this technology.

[1211] Figure 47 This is a side view of a storage tank according to some embodiments of this technology.

[1212] Figure 48A and 48B This is a perspective view of a storage facility according to some implementation schemes of this technology.

[1213] Figure 49A –C are perspective, top, and side views of a storage container according to some embodiments of the present technology, respectively.

[1214] Figure 50A This is an end view of a storage container in a bent state according to some embodiments of this technology.

[1215] Figure 50B Is Figure 50A The image shows a side view of the storage tank in its extended position.

[1216] Figure 51 This describes several storage facilities implemented according to some embodiments of this technology.

[1217] Figure 52A This is an end view of multiple storage tanks according to some implementation schemes of this technology.

[1218] Figure 52B Is Figure 52A The image shows a side view of the storage facility.

[1219] Figure 52C Explanation in Figure 52A and 52B The method for manufacturing the storage tank is shown in the image.

[1220] Figure 53 This is a schematic partial cross-sectional view of the human bladder.

[1221] Figure 54 Is Figure 53 The image shows an enlarged cross-sectional side view of the bladder wall.

[1222] Figure 55 This is a direct-on view of the reservoir of tumors located near the bladder wall according to this technique.

[1223] Figure 56 It is an enlarged cross-sectional side view of the bladder wall, showing the reservoir of this technology positioned against the bladder wall.

[1224] Figure 57 This is a schematic diagram of the top cross-section of a reservoir located inside the bladder.

[1225] Figure 58 and 59 It is a schematic side cross-sectional view showing one or more of the storage cavities of this technology located in or near the pleural cavity of a mammalian patient.

[1226] Figure 60 This is a schematic illustration of human patients showing common anatomical locations of soft tissue sarcomas.

[1227] Figure 61 This is a schematic diagram of the head and neck region in a human patient.

[1228] Figure 62 and 63 Describes an oral device configured for use with a storage bank of this technology.

[1229] Figure 64 This is a schematic diagram of the breast area in a human patient.

[1230] Figure 65 This is a schematic diagram of the pancreas in a human patient.

[1231] Figure 66 This is a schematic diagram of the lungs of a human patient.

[1232] Figure 67 These are nail support ribs configured for use with storage tanks of this technology.

[1233] Figures 68-70 It is implanted after the excision surgery according to this technique. Figure 67 A schematic diagram of the central nail support rib.

[1234] Figure 71 It is a table displaying the different side effects associated with cancer and / or cancer treatment and the corresponding reservoirs of this technology configured to treat these side effects.

[1235] Figure 72ADescribe the normal human prostate and the cancerous human prostate.

[1236] Figure 72B –72D is a different view of the selected parts of the human prostate and its regional anatomy.

[1237] Figure 73A and 73B This describes an example of a technology repository configured for the treatment of prostate cancer.

[1238] Figure 74 This displays multiple storage repositories of this technology implanted within a cancerous prostate.

[1239] Figure 75 Examples describing the therapeutic agent coverage of multiple reservoirs of this technology implanted in the prostate of a human patient.

[1240] Figure 76 This is a graph showing several release curves of the storage tank of this technology.

[1241] Figure 77A –77D shows an example method of implanting the reservoir of this technology into the prostate of a human patient via the transrectal route.

[1242] Figure 78 This demonstrates an example method of implanting the storage bank of this technology into the prostate of a human patient via a perineal approach.

[1243] Figure 79A –79C shows an example method of implanting the reservoir of this technology into the prostate of a human patient via a transurethral route.

[1244] Figure 80 This demonstrates an example method of implanting the reservoir of this technology into the prostate of a human patient via a transvascular route.

[1245] Figure 81A –81I shows an example method of implanting a reservoir of the present technology into the prostate of a human patient via a drug delivery component having a side opening.

[1246] Figure 82A –82C describes an example method of implanting a reservoir of the present technology into the prostate of a human patient via a mesh-like drug delivery component.

[1247] Figure 83A –83E describes an example method of implanting a reservoir of the present technology into the prostate of a human patient via a curved drug delivery component.

[1248] Figure 84 Describes a storage container configured according to this technology for administering two or more therapeutic agents.

[1249] Figure 85ADescribes a storage container configured according to this technology for administering two or more therapeutic agents.

[1250] Figure 85B Display used in Figure 85A The example drug delivery system shown is a storage facility.

[1251] Figure 86A Describes a storage container configured according to this technology for administering two or more therapeutic agents.

[1252] Figure 86B Display used in Figure 86A The example drug delivery system shown is a storage facility.

[1253] Figure 87A –87C describes an example of a treatment system configured according to the present technology to administer two or more reservoirs at controlled intervals.

[1254] Figure 88 This describes a treatment system configured according to the present technology to administer medication to two or more reservoirs at controlled intervals.

[1255] Figure 89A –89C shows an example system and method for implanting a reservoir of the present technology into the prostate of a human patient at controlled intervals.

[1256] Figure 90 Describes a storage container configured according to this technology for administering two or more therapeutic agents.

[1257] Figure 91 Describes a storage container configured according to this technology for administering two or more therapeutic agents.

[1258] Figure 92 This is a schematic illustration of two reservoirs configured according to this technology for the direct release of therapeutic agents, shown as implanted in a cancerous prostate.

[1259] Figure 93 This describes a therapeutic system configured according to the present technology to administer one or more storage tanks for drug delivery.

[1260] Figure 94A –94C describes a system and method for implanting one or more repositories into the prostate of a human patient according to the present technology.

[1261] Figure 95A –95C describes systems and methods for implanting one or more repositories into the prostate of a human patient according to this technology.

[1262] Figure 96 This is a graph showing the percentage change in tumor volume over time in several instance libraries of this technique. Detailed Implementation

[1263] This technology relates to implantable repositories for the sustained and controlled release of therapeutic agents, and related devices, systems, and methods of use. The following references... Figure 1 –52C and part I describe an example of this technology's storage library. The following refers to… Figures 53-57 Section II describes the selected apparatus, system, and method for using this technology repository to treat bladder cancer. The following refers to... Figure 58 and 59 Section III describes the selected apparatus, system, and method for using this technology to store pleural effusions for the treatment of malignant pleural effusions. The following refers to... Figure 60 The selected apparatus, system, and method described in Section IV are used in the treatment of soft tissue sarcoma using this technology repository. See below for further details. Figures 61-63 Section V describes the selected apparatus, system, and method for using this technology repository to treat head and neck tumors. The following refers to... Figure 64 The selected apparatus, system, and method described in section VI are used in the treatment of breast cancer using this technology repository. See below for reference. Figure 65 The selected apparatus, system, and method described in section VII are used in the treatment of pancreatic cancer using this technology. See below for further details. Figures 67-70 Section VIII describes the selected apparatus, system, and method for using this technology repository to treat lung cancer. The following references... Figure 71-96 The apparatus, system and method selected as described in Part IX are used in the technical repository for prostate cancer.

[1264] I. Examples of Storage Facilities for This Technology

[1265] This document discloses implantable repositories and related devices, systems, and methods for treating cancer through the sustained, controlled release of a locally effective therapeutic agent when the repositories are implanted at a treatment site within the body. As understood in the art, “release” of a therapeutic agent includes movement of the therapeutic agent away from the repositories and the continued presence of the therapeutic agent at the treatment site after the repositories are implanted, regardless of the relative movement of the therapeutic agent with respect to the extent of the repositories. Thus, any therapeutic agent that remains substantially fixed in its position relative to its initial implantation is still considered “released” as long as it provides therapeutic efficacy at the treatment site.

[1266] The numerous repositories of this technology are configured to be implanted close to cancerous tissue and to deliver a persistent, locally effective therapeutic agent to the targeted tumor. Because the repositories disclosed herein deliver the therapeutic agent locally, this technology can deliver certain therapeutic agents (e.g., chemotherapy agents) locally to the tumor in much larger quantities than could be delivered systemically, without exposing the patient to levels of agent toxicity. For example, administering a local dose of acute chemotherapy to the prostate at a typical concentration of systemic chemotherapy would still expose the body to only 1% of the drugs used in systemic chemotherapy.

[1267] The reservoir of this technology is configured to deliver high, sustained local doses to cancerous tissue over periods of days, weeks, or months. The reservoir can provide high local concentrations of the therapeutic agent for a duration sufficient to cause toxicity to cancerous or neoplastic tissue while avoiding toxic exposure outside the target tissue, and particularly avoiding toxic exposure to the aforementioned key non-target structures. This pharmacokinetic profile can optimize cancer treatment while minimizing complications.

[1268] As used herein, when referring to cancer, “treat” or “treatment” or “treating” includes eradicating cancerous tissue, slowing the development of cancerous tissue, reducing the mass and / or volume of cancerous tissue, eliminating or reducing the frequency or intensity of side effects of cancerous tissue, increasing the sensitivity of cancerous tissue to more conventional treatments (such as systemic drug therapy, radiation, etc.), preventing recurrence of cancerous tissue, and / or reducing the side effects of chemotherapy and / or radiation therapy targeting cancerous tissue. As used herein, “cancer” or “cancerous tissue” includes cancerous tissue as well as non-cancerous or precancerous tissue (i.e., tissue at high risk of developing into cancer).

[1269] As used herein, “cancer” or “cancer tissue” includes cancerous tissue as well as non-cancer or precancerous tissue (i.e., tissue at high risk of developing into cancer). For example, “cancer” and “cancer tissue” as used herein include prostatic intraepithelial neoplasia (“PIN”). Additionally, devices, systems, and methods may be used to administer therapeutic agents formulated to treat conditions other than cancer, such as benign prostatic hyperplasia (“BPH”).

[1270] As used herein, a "reservoir" comprises a composition configured to deliver at least one therapeutic agent in a controlled and sustained manner to a treatment site in a patient's body. The reservoir also comprises the therapeutic agent itself. The reservoir may comprise a physical structure or carrier configured to perform or enhance one or more treatment-related functions, such as facilitating implantation and / or retention at or near a treatment site (e.g., at or near a tumor), modulating the release profile of the therapeutic agent, increasing release toward the treatment site, decreasing release away from the treatment site, or combinations thereof. In some embodiments, a "reservoir" includes, but is not limited to, rods, discs, films, sheets, strips, bands, capsules, coatings, matrices, flakes, pills, pellets, or other drug delivery devices or combinations thereof. Furthermore, as used herein, a "reservoir" may refer to a single reservoir or multiple reservoirs. As an example, the statement “a reservoir can be configured to release 2g of therapeutic agent to a treatment site” describes (a) a single reservoir configured to release 2g of therapeutic agent to a treatment site, and (b) multiple reservoirs configured to release 2g of therapeutic agent to a treatment site.

[1271] Figure 1This is an isometric view of an implantable reservoir 100 according to several embodiments of the present technology. The reservoir 100 may comprise a polymer matrix configured for implantation at a treatment site. The polymer matrix may comprise a treatment region 200 containing a locally effective therapeutic agent. The treatment region 200 may comprise all or a portion of the polymer matrix. The reservoir 100 may include a therapeutic agent with a high therapeutic payload, particularly exhibiting mechanical properties (e.g., flexural strength) sufficient to withstand storage, handling, implantation, and / or retention at the treatment site compared to other known membranes having an equivalent thickness or polymer weight percentage. For example, in some embodiments, the reservoir 100 contains at least 50% by weight of the therapeutic agent.

[1272] According to some implementation schemes, such as Figure 1 As shown, reservoir 100 optionally includes a control region 300 configured to regulate the release of a therapeutic agent from reservoir 100 in a controlled and continuous manner. Control region 300 may contain at least one bioabsorbable polymer and at least one release agent mixed with the polymer, and treatment region 200 may contain at least one bioabsorbable polymer and at least one release agent mixed with the polymer and the therapeutic agent. Control region 300 may optionally include the therapeutic agent, or control region 300 may not include the therapeutic agent at all. Treatment region 200 may optionally not include the release agent at all. The release agent in control region 300 may be the same as or different from the release agent in treatment region 200. The bioabsorbable polymer in control region 300 may be the same as or different from the bioabsorbable polymer in treatment region 200. As detailed below, in some embodiments, treatment region 200 and / or control region 300 may have different components and / or formulations.

[1273] When exposed to fluids (e.g., physiological fluids), the release agent can have a faster dissolution rate than the degradation rate of bioabsorbable polymers. Therefore, when fluid comes into contact with the reservoir 100 (e.g., after the reservoir 100 is implanted at the treatment site), the release agent dissolves faster than polymer degradation within the surrounding polymer of the control region 300 and / or treatment region 200. As the release agent dissolves, the space vacated by the dissolved release agent forms diffusion openings (e.g., channels, cavities, pores, etc.) in the surrounding polymer region. The formation of these diffusion openings can enhance the release of the therapeutic agent from the polymer region and into the surrounding physiological fluid. In some embodiments, the release rate of the therapeutic agent is higher when diffusion openings are present in the polymer region compared to when diffusion openings are not present in the polymer region.

[1274] In addition to other parameters, the concentration and type of the release agent can be selected to regulate the release of the therapeutic agent at a controlled dose rate from the treatment area 200 and / or through the control area 300 into the surrounding fluid over a desired time period. For example, a higher concentration of the release agent can increase the release rate of the therapeutic agent, while a lower concentration of the release agent can decrease the release rate of the therapeutic agent. The treatment area 200 may contain a different concentration and / or type of release agent than the control area 300, or it may contain the same concentration and / or type of release agent.

[1275] The position and / or geometry of the control area 300 can be configured to adjust the release curve of the therapeutic agent from the treatment area 200. For example... Figure 1 As shown, at least a portion of the control region 300 may be disposed on or adjacent to the treatment region 200, such that when the reservoir 100 is initially positioned in the body, the control region 300 lies between at least a portion of the treatment region 200 and the physiological fluid at the treatment site. For example, the control region 300 may cover all or a portion of one or more surfaces of the treatment region 200. When the reservoir 100 is exposed to the physiological fluid, the therapeutic agent is eluted from the exposed surface of the treatment region 200 through a diffusion opening created by the dissolution of the release agent and through the control region 300. Generally, the therapeutic agent is eluted from the exposed surface of the treatment region 200 at a faster (e.g., larger) rate than through the control region 300. As a result, the control region 300 prolongs the release of the therapeutic agent from the treatment region 200 to provide a longer release time and regulate the dose rate, for example, to provide the desired level of therapeutic effect and avoid complications associated with overdose.

[1276] The reservoir 100 of this technology is configured to release a therapeutic agent in a highly controlled, predetermined manner, specifically tailored to the medical condition being treated and the therapeutic agent used. As described in more detail below in Part II, the release kinetics of the reservoir can be customized for a particular application by varying one or more of the following aspects: the reservoir composition and / or structure, such as the shape and / or size of the reservoir, treatment region 200, and / or control region 300; the exposed surface area of ​​treatment region 200; the type of polymer (in treatment region 200 and / or control region 300); the weight percentage of the therapeutic agent, polymer, and / or release agent (in a specific area or generally throughout reservoir 100); and the composition of treatment region 200 and control region 300.

[1277] like Figure 2As shown, in many embodiments, the reservoir 100 (or the system of reservoir 100) is configured to release a disproportionately larger volume of therapeutic agent during a first time period each day than during a longer second time period. In some embodiments, the reservoir 100 (or the system of reservoir 100) is configured to release the therapeutic agent for at least 14 days after implantation (or immersion in fluid), wherein approximately 20% to approximately 50% of the therapeutic agent payload is released in a controlled, abrupt manner during the first 3-5 days, and at least 80% of the remaining therapeutic agent payload is released at a slower rate over the following 10-11 days. In some embodiments, at least 90% of the therapeutic agent payload is released by the end of the 14 days. As discussed herein, many other release profiles are possible.

[1278] Depending on the type of cancer targeted and / or the physiological conditions of the treatment site, the release profile of the reservoir 100 can be tuned by adjusting its structure, composition, and manufacturing methods to achieve the desired duration and rate of release of the therapeutic agent. For example, in some embodiments, the reservoir 100 can be configured to release the therapeutic agent at a constant rate throughout the entire duration of release. In a particular embodiment, the reservoir 100 can be configured to release the therapeutic agent at a constant rate for a first time period and at a non-constant rate for a second time period (which may occur before or after the first time period).

[1279] In some embodiments, the reservoir 100 is configured to release no more than 20%, no more than 25%, no more than 30%, no more than 35%, no more than 40%, no more than 45%, no more than 50%, no more than 55%, no more than 60%, no more than 65%, or no more than 70% of the therapeutic agent during the first, second, third, fourth, fifth, sixth, eighth, ninth, tenth, eleventh, twelfth, or thirteenth days of the release duration, and wherein at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% of the remaining therapeutic agent is released during the remaining days of the release duration. The planned duration of release can be at least 1 day, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days, at least 7 days, at least 8 days, at least 9 days, at least 10 days, at least 11 days, at least 12 days, at least 13 days, at least 14 days, at least 15 days, at least 16 days, at least 17 days, at least 18 days, at least 19 days, at least 20 days, at least 21 days, at least 22 days, at least 23 days, at least 24 days, at least 25 days, at least 26 days, at least 27 days, at least 28 days, at least 29 days, or at least 30 days.

[1280] In some embodiments, the reservoir 100 is configured to release at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% of the therapeutic agent in the reservoir 100 during a predetermined duration of treatment. The planned duration of treatment can be at least 1 day, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days, at least 7 days, at least 8 days, at least 9 days, at least 10 days, at least 11 days, at least 12 days, at least 13 days, at least 14 days, at least 15 days, at least 16 days, at least 17 days, at least 18 days, at least 19 days, at least 20 days, at least 21 days, at least 22 days, at least 23 days, at least 24 days, at least 25 days, at least 26 days, at least 27 days, at least 28 days, at least 29 days, at least 30 days, at least 40 days, at least 50 days, at least 60 days, at least 70 days, at least 90 days, at least 100 days, at least 200 days, at least 300 days, or at least 365 days.

[1281] In some embodiments, the reservoir 100 is configured to release a therapeutic agent to the treatment site at a rate of approximately 50 mg / day to approximately 600 mg / day, 100 mg / day to approximately 500 mg / day, approximately 100 mg / day to approximately 400 mg / day, or approximately 100 mg / day to approximately 300 mg / day. Generally, the release rate can be selected to administer the desired dose to provide a therapeutic effect while still controlling toxicity.

[1282] In some embodiments, the reservoir 100 is configured to release a therapeutic agent to the treatment site at a rate of approximately 50 mg / day to approximately 600 mg / day, approximately 100 mg / day to approximately 500 mg / day, approximately 100 mg / day to approximately 400 mg / day, or approximately 100 mg / day to approximately 300 mg / day during a first release phase. The reservoir 100 may also be configured to release a therapeutic agent to the treatment site at a rate of approximately 500 mg / day to approximately 600 mg / day, approximately 100 mg / day to approximately 500 mg / day, approximately 100 mg / day to approximately 400 mg / day, or approximately 100 mg / day to approximately 300 mg / day during a second release phase. The release rate during the first phase may be the same as, different from, less than, or greater than the release rate during the second phase. Furthermore, the first phase may be longer or shorter than the second phase. The first phase may occur before or after the second phase.

[1283] In some implementations, the storage tank 100 is configured to release no more than 50 mg, no more than 100 mg, no more than 150 mg, no more than 200 mg, no more than 250 mg, no more than 300 mg, no more than 350 mg, no more than 400 mg, no more than 450 mg, no more than 500 mg, no more than 600 mg, no more than 700 mg, no more than 800 mg, no more than 900 mg, no more than 1000 mg, at least 10 mg, at least 20 mg, at least 30 mg, at least 40 mg, or at least 50 mg on any day during the first release phase. A therapeutic agent of at least 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, 110 mg, 120 mg, 130 mg, 140 mg, 150 mg, 160 mg, 170 mg, 180 mg, 190 mg, 200 mg, 210 mg, 220 mg, 230 mg, 240 mg, 250 mg, 260 mg, 270 mg, 280 mg, 290 mg, or 300 mg. This can be used to provide different levels of pain relief at different times after surgery, and it can also be used to control toxicity. In such an implementation scheme, the storage facility 100 can be configured to release, on any day during the second release phase, no more than 50 mg, no more than 100 mg, no more than 150 mg, no more than 200 mg, no more than 250 mg, no more than 300 mg, no more than 350 mg, no more than 400 mg, no more than 450 mg, no more than 500 mg, no more than 600 mg, no more than 700 mg, no more than 800 mg, no more than 900 mg, no more than 1000 mg, at least 10 mg, at least 20 mg, at least 30 mg, at least 40 mg, or at least 50 mg. Therapeutic agents of at least 60 mg, at least 70 mg, at least 80 mg, at least 90 mg, at least 100 mg, at least 110 mg, at least 120 mg, at least 130 mg, at least 140 mg, at least 150 mg, at least 160 mg, at least 170 mg, at least 180 mg, at least 190 mg, at least 200 mg, at least 210 mg, at least 220 mg, at least 230 mg, at least 240 mg, at least 250 mg, at least 260 mg, at least 270 mg, at least 280 mg, at least 290 mg, or at least 300 mg. The first and / or second release phases can be 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 8 days, 9 days, 10 days, 11 days, 12 days, 13 days, 14 days, 15 days, 16 days, 17 days, 18 days, 19 days, 20 days, 21 days, 22 days, 23 days, 24 days, 25 days, 26 days, 27 days, 28 days, 29 days, or 30 days.The reservoir 100 can be configured to release the therapeutic agent at a first rate during a first phase and at a second rate during a second phase. The first rate can be the same as, different from, less than, or greater than the second rate. In some embodiments, the first rate is at least 2, 3, 4, 5, 6, 7, 8, 9, or 10 times greater than the second rate, or vice versa. Furthermore, the first phase can be longer or shorter than the second phase. The first phase can occur before or after the second phase.

[1284] In some embodiments, the reservoir 100 is configured to release a therapeutic agent of no more than 50 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, 400 mg, 450 mg, 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, or 1000 mg on any day during the release duration.

[1285] In some embodiments, the reservoir 100 is configured to release a therapeutic agent at a treatment site in vivo and / or in the presence of one or more fluids for a duration of not less than 1 day, not less than 2 days, not less than 3 days, not less than 4 days, not less than 5 days, not less than 6 days, not less than 7 days, not less than 8 days, not less than 9 days, not less than 10 days, not less than 11 days, not less than 12 days, not less than 13 days, not less than 14 days, not less than 15 days, not less than 16 days, or not less than 17 days. Not less than 18 days, not less than 19 days, not less than 20 days, not less than 21 days, not less than 22 days, not less than 23 days, not less than 24 days, not less than 25 days, not less than 26 days, not less than 27 days, not less than 28 days, not less than 29 days, not less than 30 days, not less than 40 days, not less than 50 days, not less than 60 days, not less than 70 days, not less than 90 days, not less than 100 days, not less than 200 days, not less than 300 days, or not less than 365 days.

[1286] The release kinetics of the reservoir of this technology can be tailored for a specific application by varying one or more of the following aspects: the structure and / or composition of the reservoir, such as the exposed surface area of ​​the treatment region 200, the porosity of the control region 300 during and after the dissolution of the release agent, the concentration of the therapeutic agent in the treatment region, the post-manufacturing properties of the polymer, the structural integrity of the reservoir to avoid sudden release of the therapeutic agent, the relative thickness of the treatment region 200 compared to the control region 300, and other properties of the reservoir. Several embodiments of the reservoir of this technology combine one or more of these properties in a manner that produces extraordinary two-stage release profiles in animal studies that are significantly superior to those of existing injectable or implantable systems, while also overcoming the drawbacks of the disclosed intended devices. For example, several embodiments exhibit two-stage release profiles that administer an adequate mass of the therapeutic agent over a 14-day phase to treat pain associated with joint replacement surgery or other applications, while maintaining sufficient structural integrity to withstand joint forces to avoid sudden release of excessive therapeutic agent. This surprising result enables the reservoir of this technology to at least reduce (if there is no alternative) the use of opioids and / or enhance other existing pain relief systems for orthopedic surgical applications, non-orthopedic surgical applications, and other applications (e.g., oncology).

[1287] For example, the release curve can be adjusted by (at least partially) controlling the amount of exposed surface area of ​​treatment area 200, because of a reservoir having treatment area 200 that is only partially covered by control area 300 (see, for example) Figure 2 , 4 -8 and 13) and the implementation scheme in which the treatment area 200 is completely enclosed by the control area 300 (see example) Figure 9 Compared to A–12), a higher proportion of the total payload will typically be released over a shorter time period. More specifically, a reservoir design with a treatment area 200 containing an exposed surface will typically release the therapeutic agent at a high, substantially linear rate for a first time period and then at a lower, substantially linear rate for a second time period. Alternatively, a reservoir design with a treatment area 200 containing a surface substantially covered by one or more control areas 300 can achieve zero-order release, such that the release of the therapeutic agent payload is substantially at the same rate.

[1288] like Figure 3As shown, in some embodiments, the storage reservoir 100 may comprise a multilayer polymer film having a treatment region 200 and first and second control regions 300a, 300b positioned on opposing surfaces 100a, 100b of the treatment region 200. The storage reservoir 100 may be in the form of a flexible rectangular strip having a length L, a width W, and a height H (or thickness). In some embodiments, the storage vault 100 has (a) a length L of about 5–40 mm, about 10–30 mm, about 15–20 mm, about 20–35 mm, about 20–30 mm, about 20–25 mm, about 26–30 mm, about 5 mm, about 10 mm, about 11 mm, about 12 mm, about 13 mm, about 14 mm, about 15 mm, about 16 mm, about 17 mm, about 18 mm, about 19 mm, about 20 mm, about 21 mm, about 22 mm, about 23 mm, about 24 mm, about 25 mm, about 26 mm, about 27 mm, about 28 mm, etc. (a) Approximately 29mm, approximately 30mm, approximately 10–15mm, approximately 12–16mm, approximately 15–20mm, approximately 21–23mm, approximately 22–24mm, approximately 23–25mm, approximately 24–26mm, approximately 25–27mm, approximately 26–28mm, approximately 27–29mm, or approximately 28–30mm; (b) Width W is approximately 5–40mm, approximately 10–30mm, approximately 15–20mm, approximately 20–35mm, approximately 20–30mm, approximately 20–25mm, approximately 26–30mm, approximately 5mm, approximately 10mm, approximately 11mm, approximately 12mm. Approximately 13mm, 14mm, 15mm, 16mm, 17mm, 18mm, 19mm, 20mm, 21mm, 22mm, 23mm, 24mm, 25mm, 26mm, 27mm, 28mm, 29mm, 30mm, approximately 10–15mm, 12–16mm, 15–20mm, 21–23mm, 22–24mm, 23–25mm, 24–26mm, 25–27mm, 26–28mm, 27–29mm, or 28–30mm. mm, (c) height H is from about 0.4 mm to about 4 mm, about 1 mm to about 3 mm, about 1 mm to about 2 mm, at least 0.4 mm, at least 0.5 mm, at least 0.6 mm, at least 0.7 mm, at least 0.8 mm, at least 0.9 mm, at least 1 mm, at least 1.2 mm, at least 1.4 mm, at least 1.5 mm, at least 1.6 mm, at least 1.7 mm, at least 1.8 mm, at least 2 mm, at least about 3 mm, not greater than 0.5 mm, not greater than 0.6 mm, not greater than 0.7 mm, not greater than 0.8 mm, not greater than 0.9 mm, etc.).In some embodiments, the storage tank 100 may have an LxWxH ratio of approximately 26 mm x approximately 16 mm x approximately 1 mm, and in some embodiments approximately 27 mm x approximately 17 mm x approximately 1 mm. In some embodiments, the storage tank 100 may have other shapes and / or sizes, such as those described below.

[1289] Additionally, configuration Figure 3Some implementations of the storage tank shown in the diagram enable the thickness of control regions 300a and 300b, individually or collectively, to be less than or equal to 1 / 10 of the thickness of treatment region 200. The thickness of control regions 300a and 300b may also, individually or collectively, not exceed 1 / 12.5, 1 / 15, 1 / 17.5, 1 / 20, 1 / 22.5, 1 / 25, 1 / 30, 1 / 40, 1 / 50, 1 / 75, or 1 / 100 of the thickness of treatment region 200. In those embodiments having multiple sub-control regions, one or more of the sub-control regions may individually be less than or equal to the thickness of a treatment area of ​​1 / 10, 1 / 12.5, 1 / 15, 1 / 17.5, 1 / 20, 1 / 22.5, 1 / 25, 1 / 27.5, 1 / 30, 1 / 32.5, 1 / 35, 1 / 37.5, 1 / 40, 1 / 42.5, 1 / 45, 1 / 47.5, 1 / 50, 1 / 55, 1 / 60, 1 / 65, 1 / 70, 1 / 75, 1 / 80, 1 / 85, 1 / 90, 1 / 95, or 1 / 100. In those embodiments where the control region comprises a single control region, the control region may have a thickness less than or equal to 1 / 10, 1 / 12.5, 1 / 15, 1 / 17.5, 1 / 20, 1 / 22.5, 1 / 25, 1 / 27.5, 1 / 30, 1 / 32.5, 1 / 35, 1 / 37.5, 1 / 40, 1 / 42.5, 1 / 45, 1 / 47.5, 1 / 50, 1 / 55, 1 / 60, 1 / 65, 1 / 70, 1 / 75, 1 / 80, 1 / 85, 1 / 90, 1 / 95, or 1 / 100 of the thickness of the treatment area. In those embodiments with multiple sub-control zones, one or more sub-control zones may individually be less than or equal to 1 / 10, 1 / 12.5, 1 / 15, 1 / 17.5, 1 / 20, 1 / 22.5, 1 / 25, 1 / 27.5, 1 / 30, 1 / 32.5, 1 / 35, 1 / 37.5, 1 / 40, 1 / 42.5, 1 / 45, 1 / 47.5, 1 / 50, 1 / 55, 1 / 60, 1 / 65, 1 / 70, 1 / 75, 1 / 80, 1 / 85, 1 / 90, 1 / 95, or 1 / 100 of the thickness of the storage tank. In those embodiments where the control area comprises a single control area, the control area may have a thickness less than or equal to 1 / 10, 1 / 12.5, 1 / 15, 1 / 17.5, 1 / 20, 1 / 22.5, 1 / 25, 1 / 27.5, 1 / 30, 1 / 32.5, 1 / 35, 1 / 37.5, 1 / 40, 1 / 42.5, 1 / 45, 1 / 47.5, 1 / 50, 1 / 55, 1 / 60, 1 / 65, 1 / 70, 1 / 75, 1 / 80, 1 / 85, 1 / 90, 1 / 95, or 1 / 100 of the thickness of the storage tank.

[1290] Control regions 300a and 300b may cover only a portion of the treatment region 200, such that a portion of each of the lateral surfaces (e.g., sidewalls) of the treatment region 200 is immediately exposed to physiological fluid upon implantation of the reservoir 100 in vivo. For example, at least prior to implantation, the exposed surface of the treatment region 200 may account for approximately 2% to approximately 15%, approximately 3% to approximately 12%, approximately 5% to approximately 10%, approximately 6% to approximately 8%, approximately 2%, approximately 3%, approximately 4%, approximately 5%, approximately 6%, approximately 7%, approximately 8%, approximately 9%, and approximately 10% of the surface area of ​​the reservoir 100. In some embodiments, at least prior to implantation, the ratio of the exposed surface of the treatment area 200 to the exposed surface of the control area 300 may be approximately 2% to approximately 15%, approximately 3% to approximately 12%, approximately 5% to approximately 10%, approximately 6% to approximately 8%, approximately 2%, approximately 3%, approximately 4%, approximately 5%, approximately 6%, approximately 7%, approximately 8%, approximately 9%, or approximately 10% of the surface area of ​​the storage repository 100.

[1291] When the reservoir 100 is exposed to physiological fluid (or any similar fluid in an in vitro environment), the therapeutic agent will elute from the exposed surface 202 (other than through control regions 300a, 300b), allowing for a faster release of the therapeutic agent than if the treatment region 200 had no exposed area. Thus, the surface area of ​​the exposed surface 202 can be adjusted to provide an initial controlled, sudden release, followed by a gradually decreasing release (e.g., with...). Figure 3 (Similar to the illustration). The initial, more aggressive release of the therapeutic agent is partially slowed by control regions 300a, 300b that initially reduce the surface area of ​​the treatment region 200 exposed to the fluid. Unlike the reservoir 100 of this technique, many conventional drug elution techniques provide an initial, uncontrolled, and sudden release of the drug upon exposure to physiological fluids. Several embodiments of the reservoir of this technique not only enable sufficient therapeutic agent to be infused to maintain a dose for several days or weeks for sustained and durable in vivo pharmacological therapy, but they also release the therapeutic agent as prescribed and thus prevent the majority of the entire payload from being released uncontrolled, which could potentially lead to patient complications and / or reduce the remaining payload, leaving insufficient therapeutic agent in the reservoir to administer a therapeutic dose for the remaining release duration.

[1292] In some implementation schemes, configuration Figure 3 The reservoir 100 shown allows approximately 20% to 50% of the analgesic to be released during the first 3 to 5 days of the 14-day period, and at least 80% of the remaining analgesic to be released during the last 9 to 11 days of the 14-day period. This release profile provides a higher dose of therapeutic agent during the acute phase following surgery compared to the subacute phase. In some embodiments, [the following is omitted as it is not explicitly stated in the original text]. Figure 3The reservoir 100 shown is configured to release approximately 100 mg to approximately 500 mg of analgesic to the treatment site daily, and in some cases, to release no more than 400 mg or no more than 300 mg of analgesic daily for the first 3 days after implantation and no more than 200 mg daily for the remaining days.

[1293] will also Figure 3 Several embodiments of the reservoir 100 shown are configured to maintain their structural integrity even after most of the releasing agent has been eluted from the reservoir 100. As the releasing agent (one or more) dissolves and the therapeutic agent (one or more) is eluted, the functional mechanical aspects of the reservoir 100 can change over time. Such mechanical aspects include structural integrity, flexural strength, tensile strength, or other mechanical properties of the reservoir. If the reservoir 100 undergoes too rapid degradation, it may mechanically fail and release an undesirable therapeutic agent into the body. Figure 3 Several embodiments of the reservoir 100 shown are configured to contain sufficient therapeutic agent to administer 100 mg to 500 mg of therapeutic agent daily while maintaining its structural integrity, such that the reservoir remains substantially intact for at least 14 days post-implantation. For example, the reservoir may be considered sufficiently intact if it does not break into multiple component blocks, where two or more resulting blocks are at least 5% of the reservoir's original size. Alternatively or additionally, the reservoir may be considered sufficiently intact if the release rate of the therapeutic agent is not increased by more than three times compared to the release rate of the therapeutic agent in a control reservoir immersed in a buffer solution.

[1294] The therapeutic agent may be at least 50%-95% of the total weight of the storage bank 100 before implantation, or 55%-85% of the total weight of the storage bank 100 before implantation, or 60%-75% of the total weight of the storage bank 100 before implantation. Similarly, the polymer may be no more than 5%-50% of the total weight of the storage bank 100 before implantation, or 10%-50% of the total weight of the storage bank 100 before implantation, or 15%-45% of the total weight of the storage bank 100 before implantation, or 20%-40% of the total weight of the storage bank 100 before implantation, or no more than 25%, no more than 30%, no more than 35%, or no more than 40%. The ratio of the mass of the therapeutic agent in storage 100 to the mass of the polymer in storage 100 may be at least 16:1, 15:1, 14:1, 13:1, 12:1, 11:1, 10:1, 9:1, 8:1, 7:1, 6:1, 5:1, 4:1, 3:1 or 2:1.

[1295] Figure 3Several embodiments of the reservoir 100, shown in the foregoing paragraphs, having one or more combinations of the parameters described herein, have provided extraordinary results in animal studies as described herein. For example, the reservoir 100 is configured such that (a) the thickness of each or collectively the control regions 300a-b is less than or equal to 1 / 50th the thickness of the treatment region 200, (b) the mass of the therapeutic payload is sufficient to release approximately 100 mg to approximately 500 mg of analgesic to the treatment site daily, and (c) the structural integrity allows the reservoir to remain substantially intact for at least 14 days post-implantation. These embodiments are capable of releasing approximately 20% to approximately 50% of the analgesic payload in the first approximately 3 to approximately 5 days of the 14-day period, and then releasing at least 80% of the remaining analgesic payload in the latter approximately 9 to approximately 11 days of the 14-day period. This was unexpected, at least in part because (a) providing such a large payload of therapeutic agent in the treatment area was expected to cause the reservoir 100 to fail mechanically 14 days or earlier after implantation, and (b) no disclosed device achieves a release curve in which approximately 20% to approximately 50% of the analgesic is released in approximately 3 to approximately 5 days before the 14-day period and then at least 80% of the remaining analgesic is released in approximately 9 to approximately 11 days after the 14-day period.

[1296] In some implementations, one or more control areas 300 of the storage vault 100 may include two or more sub-control areas. For example, such as Figure 4 As shown, the storage container 100 may have a first control region 300a and a second control region 300b, each of which respectively includes first and second sub-control regions 302a, 302b and 302c, 302d. One, some, or all of the first and second control regions 300a, 300b and / or sub-control regions 302a-302d may have the same or different amounts of releasing agent, the same or different concentrations of releasing agent, the same or different releasing agent, the same or different amo...

Claims

1. A depot for treating prostate cancer, the depot comprising: A biodegradable polymer mixed with a locally acting therapeutic agent configured to treat prostate cancer, wherein the depot is configured to be implanted at a treatment site of the prostate of a patient and, when implanted, releases the therapeutic agent at the treatment site for a period of not less than 15 days.

2. The depot of claim 1, wherein the therapeutic agent comprises a chemotherapeutic agent.

3. A depot according to claim 1 or claim 2, wherein the depot is configured to release the therapeutic agent at the treatment site for no less than 30 days.

4. The depot of any one of claims 1 to 3, wherein the therapeutic agent comprises an anti-androgen.

5. The depot of claim 4, wherein the antiandrogen is at least one of bicalutamide and enzalutamide.

6. The depot of any one of claims 1 to 5, wherein the depot is configured for administration to the prostate via a needle.

7. A reservoir according to any one of claims 1 to 6, wherein the reservoir has a first end, a second end and a length measured along a longitudinal axis of the reservoir between the first and second ends, and wherein the reservoir has a cross-sectional dimension that is substantially constant along its length.

8. The depot of any one of claims 1 to 7, wherein the depot has a cross-sectional dimension of between about 0.7 mm and about 1.2 mm.

9. The depot of any one of claims 1 to 8, wherein the polymer comprises poly(lactide-co-glycolide) (PLGA) and polyethylene glycol (PEG).

10. A depot for treating prostate cancer by localized, sustained, controlled release of a therapeutic agent to a patient, the depot comprising: A substantially cylindrical member formed from a biodegradable polymer and a therapeutic agent configured to treat prostate cancer, the therapeutic agent comprising a chemotherapeutic agent, wherein the reservoir is configured to be implanted at a treatment site of the patient's prostate and, when implanted, release the therapeutic agent at the treatment site for a period of about 30 days to about 45 days.

11. The depot of claim 10, wherein the therapeutic agent further comprises an anti-androgen.

12. The depot of claim 11, wherein the antiandrogen is at least one of bicalutamide and enzalutamide.

13. The depot according to any one of claims 9 to 12, wherein the chemotherapeutic agent is docetaxel.

14. A depot according to any one of claims 10 to 13, wherein the substantially cylindrical member has a cross-sectional dimension of between about 0.7 mm and about 1.2 mm.

15. The depot of any one of claims 10 to 14, wherein the substantially cylindrical member is configured for administration to the prostate via a needle.

16. A system for treating prostate cancer by sustained, controlled release of a therapeutic agent to a patient, the system comprising: A plurality of reservoirs, each comprising a biodegradable polymer mixed with a therapeutic agent configured to treat prostate cancer, wherein at least some of the reservoirs include a therapeutic agent comprising a chemotherapeutic agent, and wherein each reservoir is configured to be implanted at a treatment site of a patient's prostate and, when implanted, release the chemotherapeutic agent at the treatment site for a period of not less than 15 days.

17. The system of claim 16, wherein each reservoir is configured to release the chemotherapeutic agent at the treatment site for no less than 30 days.

18. The system of claim 16 or claim 17, further comprising a tubular delivery device, wherein each depot is loaded within the delivery device such that the depots are configured to be sequentially discharged from the delivery device into the prostate.

19. The system of any one of claims 16 to 18, wherein at least two of the plurality of reservoirs have different lengths.

20. The system of any one of claims 16 to 19, wherein the plurality of reservoirs together contain about 1 mg to about 4 mg of therapeutic agent.

21. The system of any one of claims 16 to 20, wherein at least some of the depots comprise a therapeutic agent comprising an anti-androgen.

22. An implantable depot for treating prostate cancer, the depot comprising: A biodegradable polymer mixed with a locally acting therapeutic agent configured to treat prostate cancer, wherein the depot is configured to be implanted at a treatment site of the prostate of a patient and when implanted provides sustained exposure of the therapeutic agent to cancerous tissue at the treatment site for a period of not less than 15 days.

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