Residence structures and related methods

Patent metadata

Field	Value
Publication number	US-11077056-B2
Application number	US-202017126786-A
Country	US
Kind code	B2
Filing date	Dec 18, 2020
Priority date	Jun 11, 2014
Publication date	Aug 3, 2021
Grant date	Aug 3, 2021

Abstract

Residence structures, systems, and related methods are generally provided. Certain embodiments comprise administering (e.g., orally) a residence structure to a subject (e.g., a patient) such that the residence structure is retained at a location internal to the subject for a particular amount of time (e.g., at least about 24 hours) before being released. The residence structure may be, in some cases, a gastric residence structure. In some embodiments, the structures and systems described herein comprise one or more materials configured for high levels of active substances (e.g., a therapeutic agent) loading, high active substance and/or structure stability in acidic environments, mechanical flexibility and strength in an internal orifice (e.g., gastric cavity), easy passage through the GI tract until delivery to at a desired internal orifice (e.g., gastric cavity), and/or rapid dissolution/degradation in a physiological environment (e.g., intestinal environment) and/or in response to a chemical stimulant (e.g., ingestion of a solution that induces rapid dissolution/degradation). In certain embodiments, the structure has a modular design, combining a material configured for controlled release of therapeutic, diagnostic, and/or enhancement agents with a structural material necessary for gastric residence but configured for controlled and/or tunable degradation/dissolution to determine the time at which retention shape integrity is lost and the structure passes out of the gastric cavity. For example, in certain embodiments, the residence structure comprises a first elastic component, a second component configured to release an active substance (e.g., a therapeutic agent), and, optionally, a linker. In some such embodiments, the linker may be configured to degrade such that the residence structure breaks apart and is released from the location internally of the subject after a predetermined amount of time.

First claim

What is claimed is:

1. A gastric residence system, comprising:
one or more arms comprising a first polymeric component, wherein the first polymeric component comprises an active substance or salt thereof,
a second polymeric component; and
a linker component, said linker coupling the one or more arms with the second polymeric component;
wherein the system is configured to be folded and physically constrained during administration and is configured to assume an open retention shape upon removal of a constraint, wherein change between the folded shape and the open retention shape is mediated by the second polymeric component that undergoes elastic deformation when the residence system is in the folded shape and recoils when the gastric residence system assumes the open retention shape,
wherein the system is configured such that it is retained at the location internally of a subject for at least about 24 hours in the open retention shape, and
wherein the system releases between about 0.05 wt % and about 50 wt % of the active substance during the first day of release.

2. A gastric residence system as in claim 1 , wherein the system releases between about 0.05 wt % and about 30 wt % of the active substance during the first day of release.

3. A gastric residence system as in claim 1 , wherein the gastric residence system releases less than 20 wt % of the active substance during the first 6 hours of release.

4. A gastric residence system as in claim 1 , wherein the second polymeric component is free of active substance.

5. A gastric residence system as in claim 1 , wherein the first polymeric component comprises at least 10 wt % active substance of the total weight of the first polymeric component.

6. A gastric residence system as in claim 1 , wherein the linker component comprises an enteric polymer.

7. A gastric residence system as in claim 1 , wherein the gastric residence system is retained in the stomach for at least about 1 week.

8. A gastric residence system as in claim 1 , wherein the gastric residence system can be retained in the stomach for at least about 48 hours in the open retention shape.

9. A gastric residence system as in claim 1 wherein the linker component, after at least about 48 hours, degrades, dissolves, disassociates, and/or mechanically weakens in the gastric environment under gastrointestinal physiological conditions which results in loss of the open retention shape and passage of the gastric residence system out of the stomach through the gastric pyloric orifice.

10. A gastric residence system as in claim 1 , wherein the active substance is a biological macromolecule, a small molecule, a vitamin, or a supplement.

11. A gastric residence system as in claim 1 , wherein the active substance is a selective serotonin reuptake inhibitor, a blood thinning agent, a steroid, an antagonist, a cardiac glycoside, an alpha blocker, a cholesterol absorption inhibitor, a metabolite, an antihistamine, an opioid, a proton-pump inhibitor, an antibiotic, an anti-malarial agent, sulfonamides, a substance abuse treatment, a contraceptive, a stimulant, an analgesic, an anti-analgesic, an anti-inflammatory drug, a nonsteroidal anti-inflammatory drug, an antipyretic, an immunosuppressant, a neuroprotective agent, an antipsychotic, a statin, an antidepressant, an antiepileptic, an anti-proliferative, an anti-cancer agent, an antimigraine drug, an antimicrobial, an antifungal, an antiviral agent, an antiretroviral agent, an antiparasitic, an antimuscarinic, an anxiolytic, a bacteriostatic, a sedative, a hypnotic, a bronchodilator, an anti-asthma drug, a cardiovascular drug, an anesthetic, an anti-coagulant, a dopaminergic, an electrolyte, a gastro-intestinal drug, a muscle relaxant, a parasympathomimetic, an anorectic, an anti-narcoleptic, a protein, a peptide, a hormone, a nucleic acid, a gene construct, 3-hydroxy-3-methyl-glutaryl (HMG) co-A reductase inhibitor, a mineral, a prostaglandin, a nutritional supplement, a corticosteroid, a nutraceutical, a plant extract, or a phytohormone.

12. A gastric residence system as in claim 1 , wherein the active substance is a selective serotonin reuptake inhibitor, an antidepressant, an anxiolytic, a sedative, a hypnotic, an opioid, an antimigraine drug, a cholesterol absorption inhibitor, a substance abuse treatment, an immunosuppressant, an HMG co-A reductase inhibitor, a blood thinning agent, a cardiac glycoside, an antibiotic, a contraceptive, an analgesic, an anesthetic, a nonsteroidal anti-inflammatory drug, an antiepileptic, or an alpha blocker.

13. A gastric residence system as in claim 1 , wherein the active substance is meloxicam, escitalopram, clopidogrel, prasugrel, prednisone, naloxone, montelukast, digoxin, tamsulosin, ezetimibe, colchicine, loratadine, cetirizine, loperamide, omeprazole, entecavir, ciprofloxacin, azithromycin, quinine, lumefantrine, chloroquine, amodiaquine, pyrimethamine, proguanil, chlorproguanil-dapsone, sulfadoxine, sulfamethoxypyridazine, mefloquine, atovaquone, primaquine, halofantrine, clindamycin, artemisinin, artemisinin derivatives, artemether, dihydroartemisinin, arteether, artesunate, synthroid/levothyroxine, varenicline, risperidone, memantine, methadone, rosuvastatin, doxycycline, buprenorphine, aripiprazole, caffeine, folic acid, calcium, iodine, iron, zinc, thiamine, niacin, vitamin C, or vitamin D.

14. A gastric residence system as in claim 1 , wherein the active substance is prednisone, risperidone, memantine, methadone, rosuvastatin, doxycycline, buprenorphine, aripiprazole, meloxicam, or azithromycin.

15. A gastric residence system as in claim 1 , wherein the active substance is chemically bonded to a polymer of the first polymeric component.

16. A gastric residence system as in claim 1 , wherein the first polymeric component comprises polycaprolactone (PCL).

17. A gastric residence system as in claim 1 , wherein the first polymeric component comprises, poly(ethylene-co-vinyl acetate), or polyethylene glycol (PEG).

18. A gastric residence system as in claim 1 , wherein the active substance is loaded into the first polymeric component by a process comprising powder mixing, solvent loading, melt loading, or physical blending.

19. A gastric residence system as in claim 1 , wherein the open retention shape is selected from the groups consisting of square, circle, oval, polygon, tubes, rings, and star or star-like/stellate.

20. A gastric residence system as in claim 1 , comprising three or more arms comprising the first polymeric component.

21. A gastric residence system as in claim 1 , comprising a plurality of active substances.

22. A gastric residence system as in claim 1 , wherein the first polymeric component comprises the active substance or salt thereof entrapped within a polymer matrix.

23. A gastric residence system as in claim 1 , wherein the subject is a human.

24. A gastric residence system, comprising:
a first polymeric component; and
an active substance or a salt thereof present within the first polymeric component; wherein:
as measured using simulated gastric fluid, the active substance or salt thereof is released from the first polymeric component on a fifth day of release at a rate of at least about 1% of an initial average rate; and
at least about 0.05 wt % of the active substance or salt thereof is released during the second day of release;
at least about 0.05 wt % of the active substance or salt thereof is released during the fifth day of r

Assignees

• Massachusetts Inst Technology
• Brigham & Womens Hospital Inc

Inventors

• Bellinger Andrew
• Zhang Shiyi
• Traverso Carlo Giovanni
• Langer Robert S
• Mo Stacy
• Grant Tyler
• Jafari Mousa
• Glettig Dean Liang
• Diciccio Angela
• Wood Jr Lowell L
• Eckhoff Philip A

Classifications

• C08G63/08

  Lactones or lactides · CPC title

• C08G18/73

  acyclic · CPC title

• C08G18/4277

  Caprolactone and/or substituted caprolactone · CPC title

• A61K47/6901

  Conjugates being cells, cell fragments, viruses, ghosts, red blood cells or viral vectors · CPC title

• A61K47/58

  obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. poly[meth]acrylate, polyacrylamide, polystyrene, polyvinylpyrrolidone, polyvinylalcohol or polystyrene sulfonic acid resin · CPC title