Gastric residence systems having a filament for improved gastric residence
Provided are gastric residence systems comprising: a core; a plurality of arms connected to the core at a proximal end through a plurality of linker components, one linker component of the plurality of linker components corresponding to each arm of the plurality of arms, and the plurality of arms extending radially from the proximal end, and a filament circumferentially connecting each arm of the plurality of arms.
1 . A gastric residence system comprising:
a core;
a plurality of arms connected to the core at a proximal end through a plurality of linker components, one linker component of the plurality of linker components corresponding to each arm of the plurality of arms, and the plurality of arms extending radially from the proximal end; and
a filament circumferentially connecting each arm of the plurality of arms.
2 . The gastric residence system of claim 1 , wherein the filament circumferentially connects a distal end of each arm of the plurality of arms.
3 . The gastric residence system of claim 1 , wherein at least one arm of the plurality of arms comprises a segment comprising 40-60% loading of an active pharmaceutical ingredient.
4 . The gastric residence system of claim 1 , wherein the gastric residence system is configured to be folded during administration and is configured to assume an open configuration when in a patient's stomach and the linker component degrades, dissolves, disassociates, or mechanically weakens in a gastric environment.
5 . The gastric residence system of claim 4 , wherein the core undergoes elastic deformation when the gastric residence system is in the folded configuration and recoils when the gastric residence system assumes the open configuration.
6 . The gastric residence system of claim 1 , wherein the force required to compress the gastric residence system into a configuration small enough to pass through an opening having a diameter of 20 mm is at least one and a half times greater than the force required to compress a gastric residence system without a filament into a configuration small enough to pass through the opening, as measured using a radial test.
7 . The gastric residence system of claim 2 , wherein the pullout force required to separate the filament from the distal end of a first arm of the plurality of arms is greater than 1N when measured after incubating the gastric residence system in an environment of pH 1.6 for 3 days and less than 2N when measured after incubating the gastric residence system in an environment of pH 6.5 for 3 days.
8 . The gastric residence system of claim 1 , wherein the distal end of each arm of the plurality of arms comprises an enteric material comprising a polymer, an enteric polymer, a plasticizer, and an acid.
9 . The gastric residence system of claim 1 , wherein the filament comprises one or more of an elastic polymer, a biosorbable polymer, and a plasticizer.
10 . The gastric residence system of claim 8 , wherein the polymer comprises polycaprolactone or TPU, the enteric polymer comprises hydroxypropylmethylcellulose acetate succinate, the plasticizer comprises propylene glycol, the acid comprises stearic acid.
11 . The gastric residence system of claim 1 , wherein the distal end of each arm comprises a notch and the filament is positioned within the notch of each distal end.
12 . The gastric residence system of claim 1 , wherein each arm of the plurality of arms comprises a first segment comprising a first polymer composition and a second segment comprising a second polymer composition, wherein the first segment has a stiffness greater than a stiffness of the second segment, as measured using a 3-point bending test per ASTM D790.
13 . The gastric residence system of claim 12 , wherein the force required to compress the gastric residence system into a configuration small enough to pass through an opening having a diameter of 20 mm is at least 1.2 times greater than the force required to compress a gastric residence system having arms comprising only a first polymer composition into a configuration small enough to pass through the opening, as measured using an iris testing mechanism.
14 . The gastric residence system of claim 12 , wherein the first polymer composition comprises one or more of PCL, PLA, PLGA, HPMCAS, and TPU and the second polymer composition comprises one or more of a polyurethane, a polyether-polyamide copolymer, a thermoplastic elastomer, a thermoplastic polyurethane, polycaprolactone polylactic acid copolymer, a poly (trimethylene carbonate), a polyglycerol sebacate, and a silicone.
15 . The gastric residence system of claim 12 , wherein the first segment comprises 20-50% of a length of at least the first arm of the plurality of arms, the length being measured from a proximal end of the first arm, the proximal end being proximate to the core, to a distal end of the first arm and the second segment comprises 50-80% of a length of at least the first arm of the plurality of arms, the length being measured from a proximal end of the first arm, the proximal end being proximate to the core, to a distal end of the first arm.
16 . The gastric residence system of claim 12 , wherein a number of fatigue cycles required to break the gastric residence system is at least 25% greater than a number of fatigue cycles required to break a gastric residence system with arms comprising only a first polymer composition, as measured using a double funnel test.
17 . The gastric residence system of claim 1 , wherein the gastric residence system is configured to be encapsulated with a capsule when the gastric residence system is in a folded configuration to form a gastric residence dosage form suitable for administering to a patient, and the gastric residence dosage form is configured to release the gastric residence system in a stomach of the patient, allowing the gastric residence to assume an open configuration.
18 . The gastric residence system of claim 1 , wherein the gastric residence system is used to treat a human.
19 . A gastric residence system comprising:
a plurality of arms connected at a proximal end, the plurality of arms extending radially from the proximal end; and
a filament circumferentially connecting a distal end of each arm of the plurality of arms.
20 . A method of manufacturing a gastric residence system comprising:
preparing gastric residence system comprising a plurality of arms connected to a core at a proximal end through a plurality of linker components, one linker component of the plurality of linker components corresponding to each arm of the plurality of arms, and the plurality of arms extending radially;
notching each arm of the plurality of arms to form a notch in each arm;
wrapping a filament circumferentially around the gastric residence system such that the filament is positioned within each notch of each arm; and
closing each notch to secure the filament within each notch.