Residence structures and related methods

Patent metadata

Field	Value
Publication number	US-10182985-B2
Application number	US-201515317566-A
Country	US
Kind code	B2
Filing date	Jun 11, 2015
Priority date	Jun 11, 2014
Publication date	Jan 22, 2019
Grant date	Jan 22, 2019

Abstract

Certain embodiments comprise administering a residence structure to a subject (e.g., a patient) such that the residence structure is retained at a location internal to the subject for a particular amount of time (e.g., at least about 24 hours) before being released. In certain embodiments, the structure has a modular design, combining a material configured for controlled release of therapeutic, diagnostic, and/or enhancement agents with a structural material necessary for gastric residence but configured for controlled and/or tunable degradation/dissolution to determine the time at which retention shape integrity is lost and the structure passes out of the gastric cavity. For example, in certain embodiments, the residence structure comprises a first elastic component, a second component configured to release an active substance, and, optionally, a linker. In some such embodiments, the linker may be configured to degrade.

First claim

What is claimed is:

1. A gastric residence structure comprising:
a loadable polymeric component;
an elastic polymeric component; and
a separate linker component, said linker connecting the loadable polymeric component with the elastic polymeric component;
wherein the gastric residence structure is configured to be folded and physically constrained during administration and is configured to assume an open retention shape upon removal of a constraint,
wherein change between the folded shape and the open retention shape is mediated by the elastic polymeric component that undergoes elastic deformation when the residence structure is in the folded shape and recoils when the gastric residence structure assumes the open retention shape, and
wherein said linker degrades, dissolves, disassociates, or mechanically weakens in a gastric environment which results in loss of retention shape integrity and passage out of a gastric cavity.

2. The gastric residence structure of claim 1 , wherein the loadable polymeric component comprises at least about 60 wt % of the total structure weight.

3. The gastric residence structure of claim 1 , wherein the gastric residence structure has a folding force of at least about 0.2 N.

4. The gastric residence structure of claim 1 , wherein the residence structure has an open cross-sectional dimension of at least about 2 cm.

5. The gastric residence structure of claim 1 , wherein the residence structure is configured such that it is retained in the gastric cavity for at least about 24 hours.

6. The gastric residence structure of claim 1 , wherein the loadable polymeric component comprises an active substance.

7. The gastric residence structure of claim 6 , wherein the gastric residence structure is configured such that the active substance is released from the loadable polymeric component at a particular initial average rate as determined over the first 24 hours of release, and wherein the active substance is released at an average rate of at least about 1% of the initial average rate over a 24 hour period after the first 24 hours of release.

8. The gastric residence structure of claim 1 , wherein the open retention shape is a multi-armed star shape.

9. The gastric residence structure of claim 1 , wherein the elastic polymeric component comprises a polymer selected from the group consisting of polyesters, polyethers, polysiloxanes, polyamides, polyacrylates, polymethacrylates, polyanhydrides, and polyurethanes.

10. The gastric residence structure of claim 1 , wherein the loadable polymeric component comprises polycaprolactone (PCL), poly(ethylene-co-vinyl acetate), or polyethylene glycol (PEG).

11. The gastric residence structure of claim 1 , wherein the folded shape has a convex hull at least about 10% less than a convex hull of the open retention shape.

12. The gastric residence structure of claim 1 , wherein the folded shape has a largest cross-sectional dimension at least about 10% less than a largest cross-sectional dimension of the open retention shape.

13. A method for delivering a residence structure, comprising: administering to a subject a containing structure containing a gastric residence structure as in claim 6 .

14. The method of 13 , wherein the subject is a human.

15. A gastric residence structure comprising:
a plurality of loadable polymeric components; and
a central elastic polymeric component;
wherein the plurality of polymeric components are each connected to the central elastic polymeric component via a separate linker component,
wherein the gastric residence structure is configured to be folded and physically constrained during administration and is configured to assume an open retention shape upon removal of a constraint,
wherein change between the folded shape and the open retention shape is mediated by the elastic polymeric component that undergoes elastic deformation when the residence structure is in the folded shape and recoils when the gastric residence structure assumes the open retention shape, and
wherein said linker degrades, dissolves, disassociates, or mechanically weakens in a gastric environment which results in loss of retention shape integrity and passage out of a gastric cavity.

16. The gastric residence structure of claim 15 , wherein the plurality of loadable polymeric components comprise at least about 60 wt % of the total structure weight.

17. The gastric residence structure of claim 15 , wherein the gastric residence structure has a folding force of at least about 0.2 N.

18. The gastric residence structure of claim 15 , wherein the residence structure has an open cross-sectional dimension of at least about 2 cm.

19. The gastric residence structure of claim 15 , wherein the residence structure is configured such that it is retained in the gastric cavity for at least about 24 hours.

20. The gastric residence structure of claim 15 , wherein one or more of the plurality of loadable polymeric components comprise an active substance.

21. The gastric residence structure of claim 20 , wherein the gastric residence structure is configured such that the active substance is released from the plurality of loadable polymeric components at a particular initial average rate as determined over the first 24 hours of release; and
wherein the active substance is released at an average rate of at least about 1% of the initial average rate over a 24 hour period after the first 24 hours of release.

22. The gastric residence structure of claim 15 , wherein the open retention shape is a multi-armed star shape.

23. The gastric residence structure of claim 15 , wherein the central elastic polymeric component comprises a polymer selected from the group consisting of polyesters, polyethers, polysiloxanes, polyamides, polyacrylates, polymethacrylates, polyanhydrides, and polyurethanes.

24. The gastric residence structure of claim 15 , wherein the plurality of loadable polymeric components comprise polycaprolactone (PCL), poly(ethylene-co-vinyl acetate), or polyethylene glycol (PEG).

25. The gastric residence structure of claim 15 , wherein the folded shape has a convex hull at least about 10% less than a convex hull of the open retention shape.

26. The gastric residence structure of claim 15 , wherein the folded shape has a largest cross-sectional dimension at least about 10% less than a largest cross-sectional dimension of the open retention shape.

27. A method for delivering a residence structure, comprising: administering, to a subject, a containing structure containing a gastric residence structure as in claim 20 .

28. The method of 27 , wherein the subject is a human.

29. A gastric residence structure comprising:
at least three loadable polymeric components; and
a central elastic polymeric component;
wherein the at least three loadable polymeric components are connected to the central elastic polymeric component via separate linker components,
wherein the gastric residence structure is configured to be folded and physically constrained during administration and is configured to assume an open retention shape upon removal of a constraint,
wherein change between the folded shape and the open retention shape is mediated by the elastic polymeric component that undergoes elastic deformation when the residence structure is in the folded shape and recoils when the gastric residence structure

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

• C08G18/73

  acyclic · CPC title

• A61K31/357

  having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel · CPC title

• A61K31/7048

  having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin {, digitoxin or digoxin} · CPC title

• C08G83/006

  After treatment of hyperbranched macromolecules · CPC title

• C08L2203/02

  for biomedical use · CPC title