FLEXIBLE LINE CONFIGURATIONS FOR GASTRIC RESIDENCE SYSTEMS
A gastric residence system comprising: a plurality of arms connected at a proximal end of each arm, the plurality of arms extending radially from the proximal ends, at least one arm comprising an active pharmaceutical ingredient-containing portion and a separate tip portion at a distal end of the at least one arm; and a flexible line connecting the plurality of arms, wherein a respective portion of the flexible line is embedded within a distal end of each arm, wherein the flexible line comprises an irregular cross-section.
1 . A gastric residence system comprising:
a plurality of arms connected at a proximal end of each arm, the plurality of arms extending radially from the proximal ends, at least one arm comprising an active pharmaceutical ingredient-containing portion and a separate tip portion at a distal end of the at least one arm; and
a flexible line connecting the plurality of arms, wherein a respective portion of the flexible line is embedded within a distal end of each arm, wherein the flexible line comprises an irregular cross-section.
2 . The gastric residence system of claim 1 , wherein the irregular cross-section comprises a braided cross-section.
3 . The gastric residence system of claim 1 , wherein the irregular cross-section comprises at least one of bumps, ridges, knots, barbs, or valleys.
4 . The gastric residence system of claim 1 , wherein the active pharmaceutical ingredient-containing portion comprises 10-80% by weight of an active pharmaceutical ingredient.
5 . The gastric residence system of claim 1 , wherein each arm of the plurality of arms comprises a triangular cross-section.
6 . The gastric residence system of claim 5 , wherein the triangular cross-section has a base of 2.5-3.5 mm and a height of 2.1-3.1 mm.
7 . The gastric residence system of claim 1 , wherein the flexible line comprises one or more of poly(glycolic acid), poly(lactic-co-glycolic acid), poly(glycolide/lactide) random copolymer, poly-p-dioxanone, poly(glycolide/trimethylene carbonate) block copolymer, poly(glycolide/ε-caprolactone), poly(gycolide/p-dioxanone/trimethylene carbonate) triblock copolymer, poly(glycolide/ε-caprolactone/trimethylene carbonate) triblock copolymer, poly(glycolide/L-lactide/ε-caprolactone/trimethylene carbonate) triblock copolymer, polyglytone 6211, 100% poly-L-lactide, polyhydroxyalkanoates (PHA), poly(ethylene glycol)-co-poly(lactic acid) (PELA), polyethylene terephthalate (PET), polypropylene (PP), ultra-high molecular weight polyethylene (UHMWPE), polyamide, polyester, poly(ether ester), polytetrafluoroethylene (PTFE), or polyvinylidinefluoride (PVDF).
8 . The gastric residence system of claim 1 , wherein the flexible line comprises PLGA in a poly(glycolic acid) (PGA) to poly(lactic acid) (PLA) ratio of 95:5 to 40:60.
9 . The gastric residence system of claim 1 , wherein the flexible line comprises PLGA with an intrinsic viscosity of 0.5-3 dL/g.
10 . The gastric residence system of claim 1 , wherein the flexible line is configured to degrade in less than 14 days.
11 . The gastric residence system of claim 1 , wherein the flexible line has a diameter of 0.05-1 mm.
12 . The gastric residence system of claim 1 , wherein the flexible line has a cross-sectional area of 0.005-3.14 mm 2 .
13 . The gastric residence system of claim 1 , wherein the flexible line has a surface roughness of 5-400 μm.
14 . The gastric residence system of claim 1 , wherein the flexible line comprises a braid of at least three strands.
15 . The gastric residence system of claim 14 , wherein the braid has a braid angle of 5-40 degrees and a braid length of 0.5-3.1 mm.
16 . The gastric residence system of claim 1 , wherein the flexible line is absorbable.
17 . The gastric residence system of claim 1 , wherein the flexible line is non-absorbable.
18 . The gastric residence system of claim 1 , wherein the flexible line comprises a coating comprising polycaprolactone (PCL), polycaprolate, polyglactin 370, polyhydroxybutyrate, poly(L-lactide co-caprolactone), poly(L-lactide), poly(L-lactide-co-D,L lactide), polyglycolide, poly(L-lactide-co-glycolide), poly(DL-lactide), poly(D,L-lactide-co-glycolide), thermoplastic polyurethanes, poloxamer 188, or a combination thereof.
19 . The gastric residence system of claim 1 , wherein the separate tip portion and/or the distal end of each arm comprises polycaprolactone.
20 . The gastric residence system of claim 19 , wherein the separate tip portion and/or the distal end of each arm further comprises at least one of copovidone, Poloxamer 407, a colorant, and bismuth subcarbonate.
21 . The gastric residence system of claim 1 , wherein the separate tip portion and/or the distal end of each arm has a flexural modulus of at least 50 MPa.
22 . The gastric residence system of claim 1 , wherein the separate tip portion and/or the distal end of each arm has a flexural strength of at least 5 N.
23 . The gastric residence system of claim 1 , wherein the separate tip portion and/or the distal end of each arm has a maximum force of at least 3 N.
24 . The gastric residence system of claim 1 , wherein a force required to release the flexible line from a first arm of the plurality of arms is at least 4N.
25 . A gastric residence system comprising:
a plurality of arms connected at a proximal end of each arm, the plurality of arms extending radially from the proximal ends, at least one arm comprising an active pharmaceutical ingredient-containing portion and a separate tip portion at a distal end of the at least one arm; and
a flexible line connecting the plurality of arms, wherein a respective portion of the flexible line is embedded within a distal end of each arm, wherein the flexible line comprises one or more of poly(glycolic acid), poly(lactic-co-glycolic acid), poly(glycolide/lactide) random copolymer, poly-p-dioxanone, poly(glycolide/trimethylene carbonate) block copolymer, poly(glycolide/ε-caprolactone), poly(gycolide/p-dioxanone/trimethylene carbonate) triblock copolymer, poly(glycolide/ε-caprolactone/trimethylene carbonate) triblock copolymer, poly(glycolide/L-lactide/ε-caprolactone/trimethylene carbonate) triblock copolymer, polyglytone 6211, 100% poly-L-lactide, polyhydroxyalkanoates (PHA), poly(ethylene glycol)-co-poly(lactic acid) (PELA), polyethylene terephthalate (PET), polypropylene (PP), ultra-high molecular weight polyethylene (UHMWPE), polyamide, polyester, poly(ether ester), polytetrafluoroethylene (PTFE), or polyvinylidinefluoride (PVDF).
26 . A gastric residence system comprising:
a plurality of arms connected at a proximal end of each arm, the plurality of arms extending radially from the proximal ends, at least one arm comprising an active pharmaceutical ingredient-containing portion; and
a flexible line connecting the plurality of arms, wherein a respective portion of the flexible line is embedded within a distal end of each arm, wherein the flexible line comprises an irregular cross-section.
27 . A method for manufacturing a gastric residence system comprising:
using a mold, preparing a gastric residence system comprising a plurality of arms connected at a proximal end of each arm, the plurality of arms extending radially from the proximal ends;
heating a distal end of each arm to at least partially melt the respective distal end;
embedding a respective portion of at least one flexible line into each melted distal end; and
cooling the melted distal ends such that melted distal ends solidify with the at least one flexible line embedded.
28 . The method of claim 27 , wherein heating the distal end of each arm comprises directing a laser at the distal end of each arm or convection heating the distal end of each arm.
29 . A method for measuring strength of a flexible line of a gastric residence system comprising:
receiving a gastric residence system, the gastric residence system comprising:
a plurality of arms connected at a proximal end of each arm, the plurality of arms extending radially from the proximal ends; and
a flexible line connecting the plurality of arms, wherein a respective portion of the flexible line is embedded within a distal end of each arm;
detaching a first arm and a second arm from the gastric residence system, wherein the first arm and the second arm are adjacent arms of the gastric residence system connected by a piece of the flexible line;
placing the first arm in a first clamp and the second arm in a second clamp, wherein the first clamp is positioned adjacent to the second clamp;
moving the first clamp away from the second clamp until the piece of the flexible line releases from the first arm or the second arm; and
measuring the force required to release the piece of the flexible line.
30 . A gastric residence system comprising:
six arms affixed to a central elastomer;
each arm comprising a proximal end, a distal end, and an outer surface therebetween, wherein the proximal end of each arm is attached to the central elastomer and projects radially from the central elastomer, each arm having its distal end not attached to the central elastomer component and located at a larger radial distance from the central elastomer component than the proximal end;
at least one arm comprising an active pharmaceutical ingredient-containing portion, wherein the at least one arm comprises:
a first inert segment;
a first disintegrating matrix segment attached to the first inert segment;
a second inert segment attached to the first disintegrating matrix segment;
a second disintegrating matrix segment attached to the second inert segment;
a third inert segment attached to the second disintegrating matrix segment;
the active pharmaceutical ingredient-containing portion attached to the third inert segment; and
a fourth inert segment attached to the active pharmaceutical ingredient-containing portion;
and
a flexible line connecting each arm, wherein a respective portion of the flexible line is embedded within a distal end of each arm.