CN-122003231-A - Biocompatible systems for topical and sustained release administration, methods of making and methods of use thereof

Abstract

The present disclosure provides a biocompatible drug delivery system that is capable of delivering drugs locally and continuously, and in addition, methods of making the drug delivery system, and methods of using it in the treatment of diseases and conditions.

Inventors

• ZHONG DEGANG

Assignees

• 软壳有限责任公司

Dates

Publication Date

20260508

Application Date

20241011

Priority Date

20231013

Claims (19)

1. 1. A biocompatible delivery system for topical and sustained release administration comprising: (i) A biocompatible polymer having a plurality of electrophilic groups; (ii) A biocompatible polymer having a plurality of nucleophilic groups, and (Iii) A medicine.
2. 2. The biocompatible delivery system of claim 1, further comprising polyethylene glycol.
3. 3. The biocompatible delivery system of claim 2, further comprising a polylactic acid-glycolic acid copolymer.
4. 4. The biocompatible delivery system of claim 1, further comprising a polylactic acid-glycolic acid copolymer.
5. 5. The biocompatible delivery system of any one of claims 1-4, further comprising a filler and/or a binder.
6. 6. The biocompatible delivery system of any one of claims 1-5, wherein all components are in powder form and compressed to form a tablet.
7. 7. The biocompatible delivery system of any one of claims 1-6, wherein the biocompatible polymer having a plurality of electrophilic groups is a multi-arm polyethylene glycol-succinimidyl glutarate, and the biocompatible polymer having a plurality of nucleophilic groups is a multi-arm polyethylene glycol amine.
8. 8. The biocompatible delivery system according to any one of claims 1 to 7, in the form of a tablet, which can be applied directly to the lesion by mechanical means.
9. 9. The biocompatible delivery system according to any one of claims 1 to 8, wherein the drug is selected from cyclophosphamide, cisplatin, carboplatin, melphalan, methotrexate, 5-fluorouracil (5-FU), gemcitabine, cytarabine, vincristine, vinblastine, paclitaxel, docetaxel, etoposide, irinotecan, doxorubicin, bleomycin, mitomycin, prednisone, dexamethasone, bevacizumab, trabectedin, pemetrexed; analgesic agents such as ibuprofen, naproxen, diclofenac, celecoxib, acetaminophen, morphine, oxycodone, hydrocodone, fentanyl, lidocaine, bupivacaine, amitriptyline, duloxetine, gabapentin, pregabalin, capsaicin, prednisone, dexamethasone; antipsychotics, such as haloperidol, chlorpromazine, fluphenazine, thiodazine, oxaprozin, perphenazine, trifluoperazine, thiothioxanthene, prochlorperazine, chlorprothixene, risperidone, olanzapine, quetiapine, aripiprazole, clozapine, ziprasidone, paliperidone, lurasidone, iloperidone and asenapine, and antiinfective antibiotics, such as amoxicillin, penicillin V, flucloxiline, cephalexin, cefuroxime, ceftriaxone, doxycycline, tetracycline, minocycline, azithromycin, erythromycin, clarithromycin, gentamicin, tobramycin, amikacin, ciprofloxacin, levofloxacin, moxifloxacin, compound sulfamethoxazole (trimethoprim/sulfamethoxazole), sulfaisoxazole, clindamycin, lincomycin, vancomycin, teicoplanin, linezolide, linezolid, desimide, norgestrel, norgestone, norgestrel, amitraz, meropenem, ertapenem, and aztreonam.
10. 10. The biocompatible delivery system of claim 8, wherein the diseased region is a tumor site.
11. 11. The biocompatible delivery system of any one of claims 1-10, in the form of a tablet, convertible into a stick for injection into a body cavity.
12. 12. A patch comprising a plurality of biocompatible delivery systems according to any one of claims 1 to 11.
13. 13. The patch of claim 12, wherein the biocompatible delivery system is in the form of a tablet arranged and compressed on the patch.
14. 14. A patch according to claim 12 or 13 folded in layers for delivery into a body cavity through a trocar.
15. 15. The patch of claim 14 deployed within a body cavity and attached to a tissue surface.
16. 16. The patch of claim 15, wherein the tissue surface is at or near a tumor site.
17. 17. A method of treating a disease or disorder, optionally selected from cancer, pain, mental health, and infection, comprising administering a therapeutically effective amount of a therapeutic agent to a patient in need of treatment by a biocompatible delivery system according to any one of claims 1 to 11 or a patch according to any one of claims 12 to 16.
18. 18. The method of claim 17, wherein the disease or disorder is cancer.
19. 19. The method of claim 18, wherein the cancer is selected from lung cancer, kidney cancer, stomach cancer, esophageal cancer, intestinal cancer, bladder cancer, prostate cancer, liver cancer, pancreatic cancer, heart cancer, ovarian cancer, uterine cancer, and tumors/cancers of any organ within a body cavity.

Description

Biocompatible systems for topical and sustained release administration, methods of making and methods of use thereof Cross Reference to Related Applications The present application is in accordance with section 119 (e) of U.S. code 35, 35 U.S. c. ≡119 (e)), entitled to priority of U.S. provisional patent application No. 63/590,133 filed on month 13, 2023, which provisional patent application is incorporated herein by reference in its entirety. Technical Field The present disclosure relates to a biocompatible system for topical and sustained release administration, and methods of making and using the system. Background The drug may be administered by a variety of routes including oral, inhalation, subcutaneous, intramuscular, intraperitoneal, transdermal, intrathoracic and intravenous. These methods all fall into the category of systemic administration. Once absorbed, the drug will circulate throughout the body with blood and eventually reach its target organ or tissue. In most cases, the drug must reach a certain minimum concentration to exert its therapeutic effect. To reduce the need for frequent dosing, the maximum tolerated dose of the drug may be administered clinically or the drug may be formulated as a sustained release dosage form to extend its duration of efficacy. Unfortunately, systemic administration often leads to adverse toxic reactions, as is typically exemplified by chemotherapeutic agents. Most chemotherapeutic agents are directed primarily to rapidly dividing cells, including tumor cells as well as normal cells. Therefore, these drugs, while killing tumor cells, also damage bone marrow (responsible for generating blood cells) and other rapidly proliferating cells such as hair follicles, thereby causing various degrees of adverse reactions. To alleviate or eliminate these adverse effects, topical or regional administration of the drug is often preferred clinically. Cancer is a major public health problem with rising morbidity and mortality. Cancer is a wide variety of types, each of which requires specific therapeutic strategies. Some types of cancer can achieve optimal therapeutic effects through surgical intervention, while others exhibit better responses to drug therapies such as chemotherapy. Still other treatment regimens employ a combination of surgery and chemotherapy. Lung cancer is a typical case of such combination therapies. For some patients with non-small cell lung cancer (NSCLC), the treatment regimen encompasses surgical resection, as well as combined treatment of immunotherapy with chemotherapy, and related details are described in detail by P.M. Forde et al, J.England medical (NEJM) 386:1973-85 (2022). Notably, current chemotherapy acts as a therapeutic modality in a systemic rather than local manner. Another topical treatment for lung cancer is brachytherapy (brachytherapy), as discussed in one of the papers by T.A. d' Amaton et al, chest,114:1112-5 (1998). Brachytherapy involves placing radioactive particles ("seeds") into a biocompatible Vicryl mesh, which is then secured to the lung tissue to cover the resected stoma (i.e. the staple line) of the lung tissue. In a related development, schwartz et al patented a novel implantable drug delivery composition (U.S. Pat. No. 10,888,530) in which paclitaxel was entrapped in a matrix of polylactic-co-glycolic acid (PLGA) and polyethylene glycol (PEG) 8000. The composition sheet is then firmly attached to the lung tissue by means of staple fastening. Disclosure of Invention The present disclosure provides a biocompatible system that can be used to achieve local and sustained drug delivery. Specific objects, features, and advantages of the present disclosure will be summarized in the detailed description of certain exemplary embodiments. The above objects and advantages of the present disclosure will be realized and attained by the compositions and methods particularly pointed out in the written description and claims. In one aspect, the present disclosure provides a biocompatible delivery system for localized and sustained drug release comprising (i) a biocompatible polymer having a plurality of electrophilic groups, (ii) a biocompatible polymer having a plurality of nucleophilic groups, and (iii) one or more drugs. In another aspect, the present disclosure provides a medical patch for treating a disease or disorder comprising a plurality of biocompatible delivery systems disclosed herein. In yet another aspect, the present disclosure provides a method of treating a disease or disorder comprising administering a therapeutically effective amount of a therapeutic agent to a subject in need of treatment by a biocompatible delivery system or medical patch according to any embodiment of the present disclosure. The advantages and safety benefits of the system and its application are summarized below. The system can be firmly attached to tissue by crosslinking without the use of staples for fixation. It enables local and sustained drug