# US 12,109,305 B2 · Materials architecture for gastric residence systems

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- Number: US 12,109,305 B2
- Document ID: US12109305B2
- Status: Granted
- Kind: B2
- Application number: 16/303,118
- Filed: 2017-05-26
- Published: 2019-08-22
- Granted: 2024-10-08
- Earliest claimed: 2016-05-27
- Assignees: Lyndra Therapeutics, Inc.
- Applicants: Lyndra Therapeutics, Inc.
- Inventors: Andrew Bellinger; Rosemary Kanasty; Tyler Grant; Nupura Bhise; Robert Debenedictis; Jung Yang; Stephen Zale; John Klier
- Web page: https://patentgrep.com/patent/US12109305B2

## CPC

- A61K 9/0065: {Forms with gastric retention, e.g. floating on gastric juice, adhering to gastric mucosa, expanding to prevent passage through the pylorus}
- A61F 5/0036: {Intragastrical devices}
- A61K 47/34: Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers (A61K47/10 takes precedence)
- A61L 31/06: obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds {(A61L31/041 takes precedence)}
- A61L 31/16: Biologically active materials, e.g. therapeutic substances {(A61L31/047 takes precedence)}
- A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system
- A61P 3/02: Nutrients, e.g. vitamins, minerals
- A61P 3/04: Anorexiants; Antiobesity agents
- A61P 5/44: Glucocorticosteroids; Drugs increasing or potentiating the activity of glucocorticosteroids
- A61P 11/06: Antiasthmatics
- A61P 11/08: Bronchodilators
- A61P 25/04: Centrally acting analgesics, e.g. opioids
- A61P 25/06: Antimigraine agents
- A61P 25/08: Antiepileptics; Anticonvulsants
- A61P 25/18: Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- A61P 25/22: Anxiolytics
- A61P 25/24: Antidepressants
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 31/04: Antibacterial agents
- A61P 31/10: Antimycotics
- A61P 31/12: Antivirals
- A61P 33/00: Antiparasitic agents
- A61P 33/06: Antimalarials
- A61P 35/00: Antineoplastic agents
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A61L 31/048: {obtained by reactions only involving carbon-to-carbon unsaturated bonds (A61L31/041 takes precedence)}
- A61L 2300/602: Type of release, e.g. controlled, sustained, slow
- A61L 2300/604: Biodegradation
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61F: FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS (dental prosthetics A61C)
- A61L: METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES (preservation of bodies or disinfecting characterised by the agents employed A01N; preserving, e.g. sterilising, food or foodstuffs A23; preparations for medical, dental or toiletry purposes A61K)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The invention provides gastric residence systems with specifically tailored architectures and methods for making such systems. The components of the gastric residence systems can be manufactured by three-dimensional printing or by co-extrusion. The ability to construct precise architectures for the systems provides excellent control over drug release, in vivo stability, and residence time of the systems.

## Claims

### Claim 1

A co-extruded elongate member comprising;
at least one carrier polymer-therapeutic agent (or salt thereof);
at least one disintegrating linker, wherein the at least one disintegrating linker is a time-dependent linker and is configured to weaken to cause the elongate member to decouple or weaken; and
a reinforcing material comprising one or more of polycaprolactone (PCL), polydioxanone, polylactic acid, polycarbonate, polyether ether ketone, polyethylene, or polypropylene,
wherein the disintegrating linker comprises PCL, and
wherein the reinforcing material extends axially along the co-extruded elongate member,
wherein said elongate member is configured for use in a stellate gastric residence system having a gastric residence time between about 48 hours and one month.

### Claim 2

A co-extruded elongate member comprising:
at least two segments, each segment comprising a proximal end, a distal end, and an outer surface therebetween; and
a reinforcing material comprising one or more of polycaprolactone (PCL), polydioxanone, polylactic acid, polycarbonate, polyether ether ketone, polyethylene, or polypropylene,
wherein the at least two segments are attached together via a linker region comprising a disintegrating linker comprising PCL, wherein the at least one disintegrating linker is a time-dependent linker and is configured to weaken to cause the elongate member to decouple or weaken, and
wherein the reinforcing material extends axially along one or more of the at least two segments,
wherein said elongate member is configured for use in a stellate gastric residence system having a gastric residence time between about 48 hours and one month.

### Claim 3 (depends on 2)

The elongate member of claim 2, wherein the disintegrating linker is an enteric linker.

### Claim 4 (depends on 2)

The elongate member of claim 2, wherein the disintegrating linker comprises HPMCAS and PCL in a ratio of between about 80 HPMCAS:20 PCL to about 50 HPMCAS:50 PCL.

### Claim 5 (depends on 2)

The elongate member of claim 2, wherein the disintegrating linker further comprises a plasticizer.

### Claim 6 (depends on 5)

The elongate member of claim 5, wherein the plasticizer comprises triacetin, triethyl citrate, tributyl citrate, poloxamers, polyethylene glycol, polypropylene glycol, diethyl phthalate, dibutyl sebacate, glycerin, castor oil, acetyl triethyl citrate, acetyl tributyl citrate, polyethylene glycol monomethyl ether, sorbitol, sorbitan, a sorbitol-sorbitan mixture, or diacetylated monoglycerides, or mixtures thereof.

### Claim 7 (depends on 2)

The elongate member of claim 2, wherein the segments comprise PCL.

### Claim 8 (depends on 4)

The elongate member of claim 4, wherein the segments comprise PCL.

### Claim 9 (depends on 2)

The elongate member of claim 2, wherein the elongate member has a triangular cross-section with rounded corners and edges.

### Claim 10 (depends on 2)

The elongate member of claim 2, wherein the linker region is about 1 mm to about 2 mm in length.

### Claim 11 (depends on 2)

The elongate member of claim 2, wherein the segments are about 2 mm to about 20 mm in length.

### Claim 12 (depends on 1)

The co-extruded elongate member of claim 1, wherein the reinforcing material extends axially along a single side of the outer surface of the co-extruded elongate member.

### Claim 13 (depends on 1)

The co-extruded elongate member of claim 1, wherein the reinforcing material comprises polycaprolactone without therapeutic agent or salt thereof.

### Claim 14 (depends on 2)

The elongate member of claim 2, wherein the reinforcing material extends axially along a single side of the outer surface of one or more of the at least two segments.

### Claim 15 (depends on 2)

The elongate member of claim 2, wherein the reinforcing material comprises polycaprolactone without therapeutic agent or salt thereof.

### Claim 16 (depends on 2)

A gastric residence system comprising an elongate member of claim 2.

### Claim 17 (depends on 2)

A method of manufacturing the elongate member of claim 2 for use in a gastric residence system, comprising:
co-extruding the elongate member.

### Claim 18 (depends on 17)

The method of claim 17, wherein co-extruding the elongate member comprises:
co-extruding a ribbon comprising at least two ribbon strip regions comprising a carrier polymer-therapeutic agent (or salt thereof) blend and at least one ribbon strip region comprising a linker region blend, wherein each ribbon strip region of carrier polymer-agent blend is separated from an adjacent ribbon strip region of carrier polymer-agent blend by a ribbon strip region comprising a linker blend.

### Claim 19 (depends on 17)

The method of claim 17, where co-extruding the elongate member comprises:
co-extruding a ribbon comprising two ribbon strip regions comprising a carrier polymer-therapeutic agent (or salt thereof) blend and a ribbon strip region comprising a linker blend, wherein the two regions of carrier polymer-agent blend are separated by the linker region.

### Claim 20 (depends on 19)

The method of claim 19, further comprising cutting the ribbon in a direction perpendicular to the direction of extrusion to form the elongate member.

### Claim 21 (depends on 17)

The method of claim 17, where co-extruding the elongate member comprises:
co-extruding a ribbon comprising a region comprising a carrier polymer-therapeutic agent (or salt thereof) blend and a region comprising a linker.

### Claim 22 (depends on 21)

The method of claim 21, further comprising cutting the ribbon in a direction perpendicular to the direction of extrusion to form the elongate member.

### Claim 23 (depends on 18)

The method of claim 18, wherein the carrier polymer of the carrier polymer-therapeutic agent (or salt thereof) blend is selected from the group consisting of polycaprolactone and polydioxanone.

### Claim 24 (depends on 18)

The method of claim 18, wherein the therapeutic agent (or salt thereof) of the carrier polymer-therapeutic agent (or salt thereof) blend is selected from the group consisting of analgesics; anti-analgesics; anti-inflammatory drugs; antipyretics; antidepressants; antiepileptics; antipsychotic agents; neuroprotective agents; anti-proliferatives; anti-cancer agents; antihistamines; antimigraine drugs; hormones; prostaglandins; antimicrobials; antibiotics; antifungals; antivirals; antiparasitics; anti-muscarinics; anxiolytics; bacteriostatics; immunosuppressant agents; sedatives; hypnotics; antipsychotics; bronchodilators; anti-asthma drugs; cardiovascular drugs; anesthetics; anti-coagulants; enzyme inhibitors; steroidal agents; steroidal or non-steroidal anti-inflammatory agents; corticosteroids; dopaminergics; electrolytes; gastro-intestinal drugs; muscle relaxants; nutritional agents; vitamins; parasympathomimetics; stimulants; anorectics; anti-narcoleptics; antimalarial drug; quinine; lumefantrine; chloroquine; amodiaquine; pyrimethamine; proguanil; chlorproguanil-dapsone; sulfonamides; sulfadoxine; sulfamethoxypyridazine; mefloquine; atovaquone; primaquine; halofantrine; doxycycline; clindamycin; artemisinin; artemisinin derivatives; artemether; dihydroartemisinin; arteether; and artesunate.

### Claim 25 (depends on 18)

The method of claim 18, wherein the linker region comprises a material selected from the group consisting of an enteric linker and a time-dependent linker.

### Claim 26 (depends on 18)

The method of claim 18, wherein the linker region comprises hydroxypropyl methyl cellulose acetate succinate (HPMC-AS) and polycaprolactone.

### Claim 27 (depends on 17)

The method of claim 17, wherein the co-extruding is at a rate sufficient to prepare between about 30 and about 500 elongate members per minute.

### Claim 28 (depends on 17)

The method of claim 17, wherein the co-extruding is performed at a rate sufficient to produce elongate members between about 5 to about 50 times faster than single-component extrusion at the same linear extrusion rate.

### Claim 29 (depends on 18)

The method of claim 18, wherein at least one junction between a carrier polymer-agent region and a linker region is co-extruded in an interlocking configuration.

### Claim 30 (depends on 18)

The method of claim 18, wherein at least one carrier polymer-agent region is co-extruded in an islands-in-the-sea configuration.

### Claim 31 (depends on 18)

The method of claim 18, wherein at least one linker region is co-extruded in an islands-in-the-sea configuration.

### Claim 32 (depends on 30)

The method of claim 30, wherein the island components of the islands-in-the-sea configuration comprise at least one material selected from the group consisting of an enteric polymer and a time-dependent polymer.

### Claim 33 (depends on 18)

The method of claim 18, wherein the linker regions uncouple after about seven days in fasted-state simulated gastric fluid.

### Claim 34 (depends on 17)

The method of claim 17, wherein co-extruding the elongate member comprises:
co-extruding a carrier polymer-therapeutic agent (or salt thereof) blend and a reinforcing material.