JPWO2021092491A5

JPWO2021092491A5 -

Info

Publication number: JPWO2021092491A5
Application number: JP2022526215A
Authority: JP
Publication date: 2023-11-14

Claims

A gastric retention system,
(A) a plurality of radially extending arms, wherein the plurality of arms includes a first portion comprising a first polymer composition and a second portion comprising a second polymer composition; the first portion has a stiffness greater than the stiffness of the second portion as measured by a three-point bending test according to ASTM D790;
The gastroretention system is connected to the core at a proximal end via a plurality of linker parts, one linker part of the plurality of linker parts corresponding to each arm of the plurality of arms, and one linker part of the plurality of linker parts corresponding to each arm of the plurality of arms; arms of extend radially from the proximal end; and
(B) Filament connecting each arm of the plurality of arms in the circumferential direction
gastroretention system, including;

At least one linker component is
i) poly(lactic acid-co-glycolide) (PLGA) and at least one additional linker polymer;
ii) poly(lactic acid-co-glycolide) (PLGA) and polylactic acid (PLA),
iii) poly(lactic acid-co-glycolide) (PLGA) and polycaprolactone (PCL),
iv) poly(lactic acid-co-glycolide) (PLGA) and thermoplastic polyurethane (TPU),
v) thermoplastic polyurethane (TPU) and enteric polymers,
vi) polylactic acid-co-glycolide (PLGA) and enteric polymers,
vii) polylactic acid (PLA) and plasticizer;
viii) polycaprolactone (PCL) and plasticizer;
ix) thermoplastic polyurethane (TPU) and plasticizer, or
x) pH-independent degradable polymers and enteric polymers;
2. The gastroretention system of claim 1 , wherein the at least one linker component loses 80 % or more of its flexural modulus or ruptures after incubation for 14 days at 37<0>C in an aqueous solution at pH 1.6.

the supported polymer-drug-containing arm further includes a release rate controlling film coated on the arm;
The release rate controlling film is
a) poly-D,L-lactide (PDL) and poly-D,L-lactide/glycolide (PDLG),
b) high molecular weight polycaprolactone (PCL-HMW) and low molecular weight polycaprolactone (PCL-LMW),
c) Poly-D,L-lactide (PDL),
d) poly-D,L-lactide (PDL) and polyethylene glycol-polypropylene glycol-polyethylene glycol (PEG-PPG-PEG) block copolymers,
e) poly-D,L-lactide (PDL) and polyethylene glycol (PEG),
f) poly-D,L-lactide (PDL), polyethylene glycol-polypropylene glycol-polyethylene glycol (PEG-PPG-PEG) block copolymers, and polyethylene glycol (PEG), or
g) containing poly-D-lactide-polycaprolactone copolymer (PDL-PCL copolymer),
The gastric retention system according to claim 1 or 2 .

one or more radially extending arms, the one or more arms including a first portion comprising a first polymer composition and a second portion comprising a second polymer composition; the first portion has a stiffness greater than the stiffness of the second portion as measured by a three-point bending test according to ASTM D790;
the arm includes a carrier polymer-drug; a release rate controlling film is coated on the carrier polymer-drug;
The release rate controlling film is
a) poly-D,L-lactide (PDL) and poly-D,L-lactide/glycolide (PDLG),
b) high molecular weight polycaprolactone (PCL-HMW) and low molecular weight polycaprolactone (PCL-LMW),
c) Poly-D,L-lactide (PDL),
d) poly-D,L-lactide (PDL) and polyethylene glycol-polypropylene glycol-polyethylene glycol (PEG-PPG-PEG) block copolymers,
e) poly-D,L-lactide (PDL) and polyethylene glycol (PEG),
f) poly-D,L-lactide (PDL), polyethylene glycol-polypropylene glycol-polyethylene glycol (PEG-PPG-PEG) block copolymers, and polyethylene glycol (PEG), or
g) containing poly-D-lactide-polycaprolactone copolymer (PDL-PCL copolymer),
Gastric retention system.

The at least one linker component is
i) poly(lactic acid-co-glycolide) (PLGA) and at least one additional linker polymer;
ii) poly(lactic acid-co-glycolide) (PLGA) and polylactic acid (PLA),
iii) poly(lactic acid-co-glycolide) (PLGA) and polycaprolactone (PCL),
iv) poly(lactic acid-co-glycolide) (PLGA) and thermoplastic polyurethane (TPU),
v) thermoplastic polyurethane (TPU) and enteric polymers,
vi) polylactic acid-co-glycolide (PLGA) and enteric polymers,
vii) polylactic acid (PLA) and plasticizer;
viii) polycaprolactone (PCL) and plasticizer;
ix) thermoplastic polyurethane (TPU) and plasticizer; or
x) pH-independent degradable polymers and enteric polymers;
5. The gastroretention system of claim 4 , wherein the at least one linker loses 80% or more of its flexural modulus or ruptures after incubation for 14 days at 37<0>C in an aqueous solution at pH 1.6.

core,
a plurality of arms connected to the core at a proximal end via a plurality of linker components, and a filament circumferentially connecting each arm of the plurality of arms;
The gastric retention device of claim 4 or 5 , wherein one linker component of the plurality of linker components corresponds to each arm of the plurality of arms, the plurality of arms extending radially from a proximal end. system.

a core, a plurality of arms connected to the core at a proximal end via a plurality of linker parts, and a filament circumferentially connecting each arm of the plurality of arms, one of the plurality of linker parts; one linker component corresponding to each arm of the plurality of arms, the plurality of arms extending radially from a proximal end;
The at least one linker component is
i) poly(lactic acid-co-glycolide) (PLGA) and at least one additional linker polymer;
ii) poly(lactic acid-co-glycolide) (PLGA) and polylactic acid (PLA),
iii) poly(lactic acid-co-glycolide) (PLGA) and polycaprolactone (PCL),
iv) poly(lactic acid-co-glycolide) (PLGA) and thermoplastic polyurethane (TPU),
v) thermoplastic polyurethane (TPU) and enteric polymers,
vi) polylactic acid-co-glycolide (PLGA) and enteric polymers,
vii) polylactic acid (PLA) and plasticizer;
viii) polycaprolactone (PCL) and plasticizer;
ix) thermoplastic polyurethane (TPU) and plasticizer; or
x) pH-independent degradable polymers and enteric polymers;
The gastroretentive system, wherein the at least one linker loses 80% or more of its flexural modulus or ruptures after being incubated at 37° C. for 14 days in an aqueous solution at pH 1.6.

the arm containing the supported polymer-drug segment includes a release rate controlling film coated on said arm;
The release rate controlling film is
a) poly-D,L-lactide (PDL) and poly-D,L-lactide/glycolide (PDLG),
b) high molecular weight polycaprolactone (PCL-HMW) and low molecular weight polycaprolactone (PCL-LMW),
c) Poly-D,L-lactide (PDL),
d) poly-D,L-lactide (PDL) and polyethylene glycol-polypropylene glycol-polyethylene glycol (PEG-PPG-PEG) block copolymers,
e) poly-D,L-lactide (PDL) and polyethylene glycol (PEG),
f) poly-D,L-lactide (PDL), polyethylene glycol-polypropylene glycol-polyethylene glycol (PEG-PPG-PEG) block copolymers, and polyethylene glycol (PEG); or
g) containing poly-D-lactide-polycaprolactone copolymer (PDL-PCL copolymer),
The gastroretention system according to claim 7.

including one or more plurality of radially extending arms;
The one or more arms include a first portion comprising a first polymer composition and a second portion comprising a second polymer composition, and the first portion has a 3 point rating according to ASTM D790. 9. The gastroretention system of claim 7 or 8, having a stiffness greater than the stiffness of the second portion as measured in a bending test.

core;
a plurality of arms connected to the core at a proximal end via a plurality of linker parts, a linker portion of one of the plurality of linker parts corresponding to each arm of the plurality of arms; the plurality of arms extending radially from; and
a filament connecting each arm of the plurality of arms in the circumferential direction;
including;
the arm includes a carrier polymer-drug segment; a release rate controlling film is coated on the carrier polymer-drug segment;
The release rate controlling film is
a) poly-D,L-lactide (PDL) and poly-D,L-lactide/glycolide (PDLG),
b) high molecular weight polycaprolactone (PCL-HMW) and low molecular weight polycaprolactone (PCL-LMW),
c) Poly-D,L-lactide (PDL),
d) poly-D,L-lactide (PDL) and polyethylene glycol-polypropylene glycol-polyethylene glycol (PEG-PPG-PEG) block copolymers,
e) poly-D,L-lactide (PDL) and polyethylene glycol (PEG),
f) poly-D,L-lactide (PDL), polyethylene glycol-polypropylene glycol-polyethylene glycol (PEG-PPG-PEG) block copolymers, and polyethylene glycol (PEG); or
g) Gastroretentive system comprising poly-D-lactide-polycaprolactone copolymer (PDL-PCL copolymer).

At least one linker component is
i) poly(lactic acid-co-glycolide) (PLGA) and at least one additional linker polymer;
ii) poly(lactic acid-co-glycolide) (PLGA) and polylactic acid (PLA),
iii) poly(lactic acid-co-glycolide) (PLGA) and polycaprolactone (PCL),
iv) poly(lactic acid-co-glycolide) (PLGA) and thermoplastic polyurethane (TPU),
v) thermoplastic polyurethane (TPU) and enteric polymers,
vi) polylactic acid-co-glycolide (PLGA) and enteric polymers,
vii) polylactic acid (PLA) and plasticizer;
viii) polycaprolactone (PCL) and plasticizer;
ix) thermoplastic polyurethane (TPU) and plasticizer; or
x) pH-independent degradable polymers and enteric polymers;
11. The gastroretention system of claim 10, wherein the at least one linker component loses 80% or more of its flexural modulus or ruptures after incubation for 14 days at 37<0>C in an aqueous solution at pH 1.6.

one or more radially extending arms, the one or more arms including a first portion comprising a first polymer composition and a second portion comprising a second polymer composition; 12. The gastroretention system of claim 10 or 11, wherein the first portion has a stiffness greater than the stiffness of the second portion as measured in a three-point bending test according to ASTM D790.

one or more radially extending arms, the one or more arms including a first portion comprising a first polymer composition and a second portion comprising a second polymer composition; the first portion has a stiffness greater than the stiffness of the second portion as measured by a three-point bending test according to ASTM D790; the arm further includes at least one linker; and the arm further includes at least one linker; teeth,
i) poly(lactic acid-co-glycolide) (PLGA) and at least one additional linker polymer;
ii) poly(lactic acid-co-glycolide) (PLGA) and polylactic acid (PLA),
iii) poly(lactic acid-co-glycolide) (PLGA) and polycaprolactone (PCL),
iv) poly(lactic acid-co-glycolide) (PLGA) and thermoplastic polyurethane (TPU),
v) thermoplastic polyurethane (TPU) and enteric polymers,
vi) polylactic acid-co-glycolide (PLGA) and enteric polymers,
vii) polylactic acid (PLA) and plasticizer;
viii) polycaprolactone (PCL) and plasticizer;
ix) thermoplastic polyurethane (TPU) and plasticizer, or
x) pH-independent degradable polymers and enteric-coated polymers
including;
The gastroretentive system, wherein the at least one linker loses 80% or more of its flexural modulus or ruptures after incubation for 14 days at 37° C. in an aqueous solution at pH 1.6.

the arm containing the supported polymer-drug further comprises a release rate controlling film coated on the arm;
The release rate controlling film is
a) poly-D,L-lactide (PDL) and poly-D,L-lactide/glycolide (PDLG),
b) high molecular weight polycaprolactone (PCL-HMW) and low molecular weight polycaprolactone (PCL-LMW),
c) Poly-D,L-lactide (PDL),
d) poly-D,L-lactide (PDL) and polyethylene glycol-polypropylene glycol-polyethylene glycol (PEG-PPG-PEG) block copolymers,
e) poly-D,L-lactide (PDL) and polyethylene glycol (PEG),
f) poly-D,L-lactide (PDL), polyethylene glycol-polypropylene glycol-polyethylene glycol (PEG-PPG-PEG) block copolymers, and polyethylene glycol (PEG), or
g ) Poly-D-lactide-polycaprolactone copolymer (PDL-PCL copolymer)
14. The gastroretention system of claim 13, comprising:

core;
a plurality of arms connected to the core at a proximal end via a plurality of linker parts, one linker part of the plurality of linker parts corresponding to each arm of the plurality of arms;
the plurality of arms extending radially from the proximal end; and
The gastroretention system of claim 13 or 14 , comprising a filament circumferentially connecting each arm of the plurality of arms.

one or more first arms comprising a carrier polymer and a drug, the one or more first arms attached to a second arm via a polymeric linker, the polymeric linker comprising:
i) poly(lactic acid-co-glycolide) (PLGA) and at least one additional linker polymer;
ii) poly(lactic acid-co-glycolide) (PLGA) and polylactic acid (PLA),
iii) poly(lactic acid-co-glycolide) (PLGA) and polycaprolactone (PCL),
iv) poly(lactic acid-co-glycolide) (PLGA) and thermoplastic polyurethane (TPU),
v) thermoplastic polyurethane (TPU) and enteric polymers,
vi) polylactic acid-co-glycolide (PLGA) and enteric polymers,
vii) polylactic acid (PLA) and plasticizer;
viii) polycaprolactone (PCL) and plasticizer;
ix) thermoplastic polyurethane (TPU) and plasticizer, or
x) pH-independent degradable polymers and enteric-coated polymers
including;
the polymeric linker loses 20% or more of its flexural modulus or breaks after being incubated at 37° C. for 21 days in an aqueous solution at pH 1.6;
the gastroretentive system is retained within the stomach for a period of at least 24 hours;
the plurality of supported polymer-drug-containing arms further comprising a release rate controlling film coated on the arms;
The release rate controlling film is
a) poly-D,L-lactide (PDL) and poly-D,L-lactide/glycolide (PDLG),
b) high molecular weight polycaprolactone (PCL-HMW) and low molecular weight polycaprolactone (PCL-LMW),
c) Poly-D,L-lactide (PDL),
d) poly-D,L-lactide (PDL) and polyethylene glycol-polypropylene glycol-polyethylene glycol (PEG-PPG-PEG) block copolymers,
e) poly-D,L-lactide (PDL) and polyethylene glycol (PEG),
f) poly-D,L-lactide (PDL), polyethylene glycol-polypropylene glycol-polyethylene glycol (PEG-PPG-PEG) block copolymers, and polyethylene glycol (PEG), or
g) Poly D-lactide-polycaprolactone copolymer (PDL-PCL copolymer)
gastroretention system, including;

core;
a plurality of arms connected to the core at a proximal end via a plurality of linker parts, one linker part of the plurality of linker parts corresponding to each arm of the plurality of arms, and radially from the proximal end; the plurality of arms extending to; and
a filament connecting each arm of the plurality of arms in the circumferential direction;
17. The gastroretention system of claim 16, comprising:

including one or more radially extending arms;
The one or more arms include a first portion comprising a first polymer composition and a second portion comprising a second polymer composition, wherein the first portion has a 18. The gastroretention system of claim 16 or 17, having a stiffness greater than the stiffness of the second portion as measured by a point bending test.

A gastric retention system,
(A) a plurality of first arms comprising a carrier polymer and a drug, wherein the plurality of first arms are attached to a second arm via a polymeric linker, the polymeric linker comprising:
i) poly(lactic acid-co-glycolide) (PLGA) and at least one additional linker polymer;
ii) poly(lactic acid-co-glycolide) (PLGA) and polylactic acid (PLA),
iii) poly(lactic acid-co-glycolide) (PLGA) and polycaprolactone (PCL),
iv) poly(lactic acid-co-glycolide) (PLGA) and thermoplastic polyurethane (TPU),
v) thermoplastic polyurethane (TPU) and enteric polymers,
vi) polylactic acid-co-glycolide (PLGA) and enteric polymers,
vii) polylactic acid (PLA) and plasticizer;
viii) polycaprolactone (PCL) and plasticizer;
ix) thermoplastic polyurethane (TPU) and plasticizer, or
x) pH-independent degradable polymers and enteric polymers;
the polymeric linker loses 80% or more of its flexural modulus or breaks after being incubated at 37° C. for 14 days in an aqueous solution at pH 1.6;
the gastroretentive system is retained within the stomach for a period of at least 24 hours;
the plurality of supported polymer-drug-containing arms further comprising a release rate controlling film coated on the arms;
The release rate controlling film is
a) poly-D,L-lactide (PDL) and poly-D,L-lactide/glycolide (PDLG),
b) high molecular weight polycaprolactone (PCL-HMW) and low molecular weight polycaprolactone (PCL-LMW),
c) Poly-D,L-lactide (PDL),
d) poly-D,L-lactide (PDL) and polyethylene glycol-polypropylene glycol-polyethylene glycol (PEG-PPG-PEG) block copolymers,
e) poly-D,L-lactide (PDL) and polyethylene glycol (PEG),
f) poly-D,L-lactide (PDL), polyethylene glycol-polypropylene glycol-polyethylene glycol (PEG-PPG-PEG) block copolymers, and polyethylene glycol (PEG), or
g) Contains poly D-lactide-polycaprolactone copolymer (PDL-PCL copolymer),
The plurality of arms further includes a first portion comprising a first polymer composition and a second portion comprising a second polymer composition, and the first portion has a 3 point rating according to ASTM D790. having a stiffness greater than the stiffness of the second portion as measured by a bending test;
The plurality of arms are connected to the core at their proximal ends via a plurality of linker parts, one linker part of the plurality of linker parts corresponding to each arm of the plurality of arms, and one linker part of the plurality of linker parts corresponding to each arm of the plurality of arms; the arms extend radially from the proximal end; and
(B) Filament connecting each arm of the plurality of arms in the circumferential direction
gastroretention system, including;

A gastroretention system comprising a plurality of arms including drug-eluting segments, the plurality of arms affixed to a central elastic body, the drug-eluting segments comprising:
supporting polymer,
memantine or its salts, and
Contains donepezil or its salts,
The drug eluting segment further comprises a coating comprising a release rate modifying polymer film, and
The gastroretentive system has a steady state concentration of memantine C of between about 60 ng/ml and about 160 ng/ml after administration of the gastroretentive system to a human. _ssss and a steady state concentration of donepezil, C, between about 30 ng/ml and about 60 ng/ml. _ssss configured to give, and
The gastroretentive system is configured to reside in the stomach for a period of between 4 and 14 days.

A gastroretention system comprising an arm comprising a drug-eluting segment, the arm affixed to a central elastic body, the drug-eluting segment comprising:
supporting polymer,
memantine or its salts, and
Contains donepezil or its salts,
the drug eluting segment further comprises a coating comprising a release rate modifying polymer film;
The gastroretentive system has a memantine C of between about 80 ng/ml and about 200 ng/ml after administration of the gastroretentive system to a human. _maxmax and C of donepezil between about 40 ng/ml and about 80 ng/ml. _maxmax configured to give, and
The gastroretentive system is configured to reside in the stomach for a period of between 4 and 14 days.

A gastroretention system according to any one of claims 1 to 19, wherein the polymeric linker comprises poly(lactic acid-co-glycolide) (PLGA) and at least one additional linker polymer.

Claims 2, 5, 7, 11, 13, wherein the at least one additional linker polymer comprises polylactic acid (PLA), a carrier polymer, polycaprolactone (PCL), or thermoplastic polyurethane (TPU), 23. The gastroretention system according to any one of 16, 19 and 22.

Any one of claims 3, 4, 8, 10, 14, 16, 19, 20, 21 and 23, wherein the support polymer comprises PCL and the at least one additional linker polymer comprises PCL. Gastric retention system as described in.

The polymer linker is
(a) poly(lactic acid-co-glycolide) (PLGA), and
The gastroretention system according to any one of claims 1 to 24, comprising (b) polylactic acid (PLA), polycaprolactone (PCL), or thermoplastic polyurethane (TPU).

The gastroretention system according to any one of claims 1 to 25, wherein the polymeric linker comprises PLGA.

The gastroretention system according to any one of claims 1 to 26, wherein the support polymer is TPU or PCL.

A gastroretention system according to any one of claims 1 to 27, wherein the linker polymer comprises polylactic acid (PLA), polycaprolactone (PCL), or thermoplastic polyurethane (TPU).

A gastroretentive system according to any preceding claim, wherein the linker polymer comprises a time-dependently degradable polymer.

30. The gastroretentive system of claim 29, wherein the time-dependent degradable polymer comprises poly(lactic acid-co-glycolide) (PLGA).

The polymer linker is
(a) pH-independent degradable polymer, and
A gastroretentive system according to any one of claims 1 to 30, comprising (b) an enteric polymer.

32. The gastroretentive system of claim 31, wherein the pH independent degradable polymer comprises PLGA.

including a plurality of first arms;
each first arm is attached to said second arm via a separate polymeric linker;
the second arm is an elastic central member;
The gastroretention system is configured to be collapsed and physically restrained during administration and configured to assume an open retention configuration upon removal of the restraint, and
The change between the folded configuration and the open retention configuration is such that the retention structure undergoes elastic deformation when in the folded configuration and when the gastric retention structure assumes the open retention configuration. A gastroretention system according to any one of claims 1 to 32, mediated by the resilient central member that recoils.

A gastroretention system according to any one of the preceding claims, wherein the gastroretention system is confined within a capsule configured to disintegrate in the stomach.

supporting polymer,
at least one drug or a pharmaceutically acceptable salt thereof; and
a release rate controlling film coated on at least a portion of the surface of the arm;
Arm for use in a gastroretention system according to any of claims 1 to 34, wherein the release rate controlling film comprises high molecular weight polycaprolactone (PCL-HMW) and low molecular weight polycaprolactone (PCL-LMW). .

An arm for use in a gastroretention system according to any one of claims 1 to 34, comprising:
supporting polymer,
at least one drug or a pharmaceutically acceptable salt thereof; and
a release rate controlling film coated on at least a portion of the surface of the arm;
The release rate controlling film comprises poly-D,L-lactide (PDL).

37. The arm of claim 36, wherein the release rate controlling film further comprises a polyethylene glycol-polypropylene glycol-polyethylene glycol (PEG-PPG-PEG) block copolymer.

37. The arm of claim 36, wherein the release rate controlling film further comprises polyethylene glycol (PEG).

An arm for use in a gastroretention system according to any one of claims 1 to 34, comprising:
supporting polymer,
at least one drug or a pharmaceutically acceptable salt thereof; and
a release rate controlling film coated on at least a portion of the surface of the arm;
The release rate controlling film includes a poly-D-lactide-polycaprolactone copolymer (PDL-PCL copolymer).

An arm or gastroretention system according to any one of claims 1 to 39 , wherein the release rate controlling film is applied with a pan coating.

An arm or gastroretention system according to any one of claims 1 to 39 , wherein the release rate controlling film is applied by dip coating.

The at least one drug or pharmaceutically acceptable salt thereof may be a drug, prodrug, biological formulation, statin, rosuvastatin, non-steroidal anti-inflammatory drug (NSAID), meloxicam, selective serotonin reuptake inhibitor (SSR). ), escitalopram, citalopram, blood thinners, clopidogrel, steroids, prednisone, antipsychotics, aripiprazole, risperidone, painkillers, buprenorphine, opioid antagonists, naloxone, anti-asthmatics, montelukast, nootropics, memantine, cardiac Glycosides, digoxin, alpha blockers, tamsulosin, cholesterol absorption inhibitors, ezetimibe, gout medications, colchicine, antihistamines, loratadine, cetirizine, opioids, loperamide, proton pump inhibitors. Omeprazole, antivirals, entecavir, antibiotics, doxycycline, ciprofloxacin, azithromycin, antimalarials, levothyroxine, substance abuse drugs, methadone, varenicline, contraceptives, stimulants, caffeine, nutrients, folic acid, calcium, Iodine, iron, zinc, thiamin, niacin, vitamin C, vitamin D, biotin, plant extracts, plant hormones, vitamins, minerals, proteins, polypeptides, polynucleotides, hormones, anti-inflammatory agents, antipyretics, antidepressants, anti-inflammatory agents. Epilepsy agent, antipsychotic agent, neuroprotective agent, antiproliferative agent, anticancer agent, antimigraine agent, prostaglandin, antibacterial agent, antifungal agent, antiparasitic agent, antimuscarinic agent, anxiolytic agent, bacteriostatic agent, Immunosuppressants, sedatives, hypnotics, bronchodilators, cardiovascular drugs, anesthetics, bronchodilators Cardiovascular drugs, anesthetics, anticoagulants, enzyme inhibitors, corticosteroids, dopamine agonists, Electrolytes, gastrointestinal drugs, muscle relaxants, parasympathetic stimulants, anal diseases, anti-insomnia agents, quinine, lumefantrine, chloroquine, amodiaquine, pyrimethamine, proguanamine, amodiaquine, pyrimethamine, prog heat treatment, chlorprog heat treatment dapsone, sulfonamide, Contains one or more of the following: sulfadoxine, sulfamethoxypyridazine, mefloquine, atovaquone, primaquine, halofantrine, doxycycline, clindamycin, artemisin, artemisin derivatives, artemtel, dihydroartemisin, artetel, aldesunate , an arm or gastroretention system according to any one of claims 1 to 41 .

42. An arm or gastroretentive system according to any one of claims 1 to 41 , wherein the at least one drug or pharmaceutically acceptable salt thereof comprises risperidone.

The intragastric device according to any one of claims 1 to 3, 6 to 12, 15, 17, and 19, wherein the filament circumferentially connects the distal end of each arm of the plurality of arms. Retention system.

The gastroretention system according to any one of claims 1, 6 to 12, 15, 17, and 19, wherein the plurality of arms are configured to carry an active pharmaceutical ingredient.

A gastroretention system according to any one of claims 1-3, 5-12, 15, 17 and 19, wherein the linker component degrades, dissolves, dissociates or mechanically weakens in the gastric environment.

Claims 1, 4 , 7, 10, 13, 16, wherein the gastroretention system is configured to be collapsed during administration and configured to assume an open configuration when in a patient's stomach. 22. The gastroretention system according to any one of , 19, 20 and 21 .

Claims 1, 7, 10 and 19 , wherein the core undergoes elastic deformation when the gastroretention system is in the collapsed configuration and recoils when the gastroretention system assumes the open configuration. The gastroretention system according to any one of .

The force required for the gastric retention system to be compressed into a configuration small enough to pass through an opening having a diameter of 20 mm, as measured in a radial test, is 22. A force according to any one of claims 1, 4, 7, 10, 13, 16, 19, 20 and 21 that is at least 1.5 times greater than the force required to be compressed into a configuration small enough to pass through the aperture. gastric retention system.

When measured after incubating the gastroretention system in an environment of pH 1.6 for 3 days, the pullout force required to separate the filament from the distal end of the first arm of the plurality of arms is: The gastroretention system according to any one of claims 1-3, 6-12, 15, 17 and 19, wherein the gas retention system is greater than 1 N.

Gastric retention according to any one of claims 1 to 3, 6 to 12, 15, 17, and 19, wherein the filament comprises one or more of an elastic polymer, a bioabsorbable polymer, and a plasticizer. system.

22. A gastroretention system according to any one of claims 4, 13, 16, 20 and 21, comprising a core.

Claims 1, 4, 7, 10, 13 , wherein each arm of the plurality of arms includes a first segment comprising a first polymer composition and a second segment comprising a second polymer composition. , 16, 19, 20 and 21 .

The force required for the gastroretentive system to be compressed into a configuration small enough to pass through a 20 mm diameter opening, as measured using a squeeze test mechanism, has only the first polymer composition. The method of claims 1, 4, 7, 10, 13, 16, 19, 20 and 21 , wherein the force is at least 1.2 times greater than the force required for the gastroretention system to be compressed into a configuration small enough to pass through the opening. Gastric retention system according to any one of the items .

Any one of claims 1, 4, 9, 12, 13, 18, 19 and 53 , wherein the first polymer composition comprises one or more of PCL, PLA, PLGA, HPMCAS, and TPU. Gastric retention system as described in Section .

An arm or gastroretentive agent according to any one of claims 35, 36, 39, 42 and 43 , wherein the at least one drug or pharmaceutically acceptable salt thereof comprises rosuvastatin or a calcium salt of rosuvastatin. system.

one or more first structural members attached to a second structural member via a polymeric linker, wherein the glass transition temperature of the polymeric linker decreases to below body temperature after 7 to 14 days in an aqueous environment. gastric retention system.

A gastroretention system comprising an arm comprising a drug-eluting segment, the arm affixed to a central elastic body, the drug-eluting segment comprising:
a supporting polymer, and rosuvastatin or a salt thereof;
the drug eluting segment further comprises a coating comprising a release rate modifying polymer film;
The gastroretentive system is configured to provide a mean steady state concentration ( _Css ) of rosuvastatin between about 0.5 ng/ml and about 10 ng/ml after administration of the gastroretentive system to a human. and wherein the gastroretention system is configured to reside in the stomach for a period of between 4 and 14 days.

A gastroretention system comprising an arm comprising a drug-eluting segment, the arm affixed to a central elastic body, the drug-eluting segment comprising:
a support polymer, and a composition comprising rosuvastatin or a salt thereof;
the drug eluting segment further comprises a coating comprising a release rate modifying polymer film;
The gastroretentive system is configured to provide a C _max of rosuvastatin between about 1 ng/ml and about 50 ng/ml after administration of the gastroretentive system to a human, and the gastroretentive system comprises: , a gastroretention system configured to remain in the stomach for a period between 4 and 14 days.

Any of claims 2, 5, 7, 11, 13, 16, 19, 22, 25, 26, 30, 32 and 55, wherein the PLGA comprises poly(D,L-lactic acid-co-glycolide) (PDLG). The gastric retention system according to item 1.

56. The gastroretention system of any one of claims 2, 5, 7, 11, 13, 16, 19, 22, 25, 26, 30, 32 and 55, wherein the PLGA comprises acid terminated PLGA.

58. The gastroretention system of any one of claims 16, 19, 22, 25, 26, 31, 22 and 57, wherein the polymeric linker further comprises an enteric polymer.

63. The gastroretentive system of claim 62, wherein the enteric polymer comprises (acetic acid/succinic acid) hydroxypropyl methylcellulose (HPMCAS).

42. The arm of any one of claims 3, 4, 8, 10, 14, 16, 19 and 35-41, wherein the release rate controlling film is substantially free of porogen.

44. The arm of any one of claims 35-43, wherein the increase in weight of the arm due to the addition of the release rate controlling film is about 2% to about 6% of the weight of the uncoated arm.

44. An arm according to any one of claims 35 to 43, wherein the rate of release of drug from the arm in an aqueous medium is substantially linear over at least 96 hours.

44. An arm according to any one of claims 35 to 43, wherein the rate of release of drug from the arm is substantially the same before and after thermal cycling.

A gastroretention system comprising an arm according to any one of claims 35-43 and 64-67.

one or more arms according to any one of claims 35-43 and 64-67, and
central elastic polymer component
A gastroretention system comprising:
the one or more arms are each connected to the central elastic polymeric part via a separate linker part;
the gastroretention system is configured to be collapsed and physically restrained during administration and configured to assume an open retention configuration upon removal of the restraint;
The change between the folded configuration and the open retention configuration is such that the retention system undergoes elastic deformation when in the collapsed configuration and recoils when the gastric retention system assumes the open retention configuration. mediated by said elastomeric polymer component, and
A gastroretentive system in which the linker degrades, dissolves, dissociates, or mechanically weakens in the gastric environment, resulting in loss of retained shape integrity and expulsion out of the gastric cavity.

Claims 16, 19, 22, 25, 26, 31, wherein the polymeric linker further loses 80% or more of its flexural modulus or ruptures after being incubated at 37°C for 3 days in an aqueous solution at pH 6.5. , 33, 57 and 62.

16, 19, 22, 25, 26, 31, wherein the polymeric linker further loses 40% or more of its flexural modulus or ruptures after incubation for 21 days at 37°C in an aqueous solution at pH 1.6. , 33, 57 and 62.

Claims 16, 19, 22, 25, 26, 31, wherein the polymeric linker further loses 20% or more of its flexural modulus or ruptures after incubation for 21 days at 37°C in an aqueous solution at pH 1.6. , 33, 57 and 62.

Claims 16, 19, 22, 25, 26, 31, wherein the polymeric linker further loses 20% or more of its flexural modulus or ruptures after incubation for 14 days at 37°C in an aqueous solution at pH 1.6. , 33, 57 and 62.

Claims 16, 19, 22, 25, 26, 31, wherein the polymeric linker further loses 20% or more of its flexural modulus or ruptures after being incubated at 37°C for 7 days in an aqueous solution at pH 1.6. , 33, 57 and 62.

Claims 16, 19, 22, 25, 26, 31, wherein the polymeric linker further loses 20% or more of its flexural modulus or ruptures after incubation for 3 days at 37°C in an aqueous solution at pH 1.6. , 33, 57 and 62.