Residence structures and related methods

Patent metadata

Field	Value
Publication number	US-10716752-B2
Application number	US-201916693149-A
Country	US
Kind code	B2
Filing date	Nov 22, 2019
Priority date	Jun 11, 2014
Publication date	Jul 21, 2020
Grant date	Jul 21, 2020

Abstract

Certain embodiments involve gastric residence structures which can be administered to a subject (e.g., a patient) in a configuration constrained by a retaining element, and configured to mediate a change in shape when unconstrained by the retaining element to assume a configuration in the stomach in which is retained and unable to pass through the gastric pyloric orifice of the subject under gastrointestinal physiological conditions. The residence structures can be loaded with an agent for release in the stomach.

First claim

What is claimed is:

1. An article, comprising:
a retaining element; and
a gastric residence structure constrained by the retaining element, the residence structure comprising at least three loadable polymeric arms and a second polymeric component coupled to the loadable polymeric arms by at least one degradable linker,
wherein at least one loadable polymeric arm comprises an active substance, and the second component is free of active substance,
wherein the residence structure is constructed and arranged to have a first configuration when constrained by the retaining element, and configured to mediate a change in shape as a result of release by the retaining element in the stomach to assume a second configuration, the residence structure being retained in the stomach and unable, in the second configuration, to pass through the gastric pyloric orifice of the subject under gastrointestinal physiological conditions.

2. The article of claim 1 , wherein at least one loadable polymeric arm comprises at least 10 wt % active substance of the total weight of the loadable polymeric arm.

3. The article of claim 1 , wherein at least one degradable linker comprises an enteric polymer.

4. The article of claim 1 , wherein the residence structure is retained in the stomach for at least about 1 week.

5. The article of claim 1 , wherein the residence structure can be retained in the stomach for at least about 48 hours in the second configuration,
wherein at least one loadable polymeric arm is configured to release the active substance in the stomach for at least about 48 hours, at a particular initial average rate as determined over the first 24 hours of release and at an average rate of at least about 1% of the initial average rate over a second 24 hour period after the first 24 hours of release,
wherein at least one degradable linker, 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 second configuration and passage of the residence structure out of the stomach through the gastric pyloric orifice.

6. The article of claim 1 , wherein the active substance is a biological macromolecule, a small molecule, a vitamin, or a supplement.

7. The article of 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 anticoagulant, 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, aft 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.

8. The article of 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.

9. The article of 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.

10. The article of claim 1 , wherein the active substance is prednisone, risperidone, memantine, methadone, rosuvastatin, doxycycline, buprenorphine, aripiprazole, meloxicam, or azithromycin.

11. An article, comprising:
a retaining element; and
a gastric residence structure constrained by the retaining element, the residence structure comprising multiple interconnected components including at least a plurality of loadable polymeric components, one or more second polymeric components, and at least a plurality of degradable linkers,
wherein the degradable linkers interconnect the plurality of loadable polymeric components and the one or more second polymeric components,
wherein the plurality of loadable polymeric components comprise an active substance, and the one or more second polymeric components are free of active substance,
wherein the residence structure is constructed and arranged to have a first configuration when constrained by the retaining element, and configured to mediate a change in shape as a result of release by the retaining element in the stomach to assume a second configuration, the residence structure being retained in the stomach and unable, in the second configuration, to pass through the gastric pyloric orifice of the subject under gastrointestinal physiological conditions.

12. The article of claim 11 , wherein at least one loadable polymeric component comprises at least 10 wt % active substance of the total weight of the loadable polymeric component.

13. The article of claim 11 , wherein at least one degradable linker comprises an enteric polymer.

14. The article of claim 11 , wherein the residence structure is retained in the stomach for at least about 1 week.

15. The article of claim 11 , wherein the residence structure can be retained in the stomach for at least about 48 hours in the second configuration,
wherein at least one loadable polymeric component is configured to release the active substance in the stomach for at least about 48 hours, at a particular initial average rate as determined over the first 24 hours of release and at an average rate of at least about 1% of the initial average rate over a second 24 hour period after the first 24 hours of release,
wherein at least one degradable linker, 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 second configuration and passage of the residence structure out of the stomach through the gastric pyloric orifice.

16. The article of claim 11 , wherein at least one active substance is a biological macromolecule, a small molecu

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