Methods of using in situ hydration of hydrogel articles for sealing or augmentation of tissue or vessels

• US 8,105,622 B2
• Filed: 08/08/2007
• Issued: 01/31/2012
• Est. Priority Date: 08/14/1998
• Status: Expired due to Term

• Current Assignee: Incept LLC
• Original Assignee: Incept LLC
• Inventors: Sawhney, Amarpreet S.
• Primary Examiner(s): PAK, JOHN D
• Application Number:
  US11/890,929
• Publication Number:
  US 20080017201A1
• Time in Patent Office: 1,637 Days
• Field of Search: 424/426, 424/486, 424/444
• US Class Current: 424/426
• CPC Class Codes: A61B 17/12022 Occluding by internal devices, e.g. balloons or releasable wires plugging an opening in the wall of an organ A61B17/0057; occluders for the cervical canal A61F6/146; vas deferens occluders A61F6/20
• CPC Class Codes: A61B 17/12099 characterised by the location of the occluder
• CPC Class Codes: A61B 17/12104 in an air passage
• CPC Class Codes: A61B 17/12109 in a blood vessel
• CPC Class Codes: A61B 17/12186 liquid materials adapted to be injected
• CPC Class Codes: A61B 17/1219 expandable in contact with liquids
• CPC Class Codes: A61B 2017/00898 expandable upon contact with fluid
• CPC Class Codes: A61K 6/19 Self-expanding, e.g. for filling teeth
• CPC Class Codes: A61K 6/52 Cleaning; Disinfecting
• CPC Class Codes: A61K 6/54 Filling; Sealing
• CPC Class Codes: A61K 6/69 Medicaments
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61K 9/0036 Devices retained in the vagina or cervix for a prolonged period, e.g. intravaginal rings, medicated tampons, medicated diaphragms
• CPC Class Codes: A61K 9/0085 Brain, e.g. brain implants; Spinal cord
• CPC Class Codes: A61K 9/2027 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61L 2300/418 Agents promoting blood coagulation, blood-clotting agents, embolising agents
• CPC Class Codes: A61L 24/0015 Medicaments; Biocides
• CPC Class Codes: A61L 24/0031 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 31/145 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: A61L 33/0064 : Hydrogels or hydrocolloids
• CPC Class Codes: C08L 33/14 : of esters containing halogen, nitrogen, sulfur, or oxygen atoms in addition to the carboxy oxygen
• CPC Class Codes: C08L 39/06 : Homopolymers or copolymers of N-vinyl-pyrrolidones
• CPC Class Codes: C08L 71/02 : Polyalkylene oxides

Abstract

Pharmaceutically acceptable hydrogel polymers of natural, recombinant or synthetic origin, or hybrids thereof, are introduced in a dry, less hydrated, or substantially deswollen state and rehydrate in a physiological environment to undergo a volumetric expansion and to affect sealing, plugging, or augmentation of tissue, defects in tissue, or of organs. The hydrogel polymers may deliver therapeutic entities by controlled release at the site. Methods to form useful devices from such polymers, and to implant the devices are provided.

Claims

1. A method to seal a lumen or void in a body of a patient comprising:

placing a sterilized pharmaceutically acceptable covalently crosslinked hydrogel polymerized from at least one synthetic hydrophilic polyethylene glycol macromer into the lumen or void,

wherein the hydrogel has a substantially less than equilibrium level of hydration for undergoing a volumetric expansion of at least about 50% after swelling with physiological fluid and, after implantation, swells from exposure to a fluid from the body to press against tissue surrounding the lumen or void to seal and thereby occlude the lumen or void,

wherein the hydrogel, at the substantially less than equilibrium level of hydration, has a shape selected from the group consisting of a rod and a sheet rolled from one edge to another to form a roll, with the rod or roll outer diameter being no more than 1.5 mm.

2. The method of claim 1 wherein the volumetric expansion is between about 50% and about 700%.

3. The method of claim 1 wherein the volumetric expansion is between about 100% and about 500%.

4. The method of claim 1 wherein the volumetric expansion is between about 150% and about 400%.

5. The method of claim 1 wherein the hydrogel is biodegradable.

6. The method of claim 1 wherein the fluid from the body is blood.

8. The method of claim 1 wherein the lumen or void is created by a needle.

9. The method of claim 1 wherein the lumen or void is selected from the group consisting of a naturally occurring body passageway, a fallopian tube, an arteriovenous malformation, and a bone canal.

10. The method of claim 1 wherein the macromer, before polymerization, comprises a functional group polymerizable by a polymerization reaction that is selected from the group consisting of free radical, condensation, anionic, and cationic.

11. The method of claim 1 wherein the macromer is polymerized by an electrophile-nucleophile reaction.

12. The method of claim 1 wherein the hydrogel further comprises a therapeutic bioactive molecule.

13. The method of claim 12 wherein the therapeutic bioactive molecule is selected from the group consisting of peptides, antibiotics, antitumor agents, hemostatics, and analgesics.

14. The method of claim 1 wherein the hydrogel further comprises a contrast agent.

15. The method of claim 14 wherein the contrast agent is a radio-opaque contrast agent.

16. The method of claim 14 wherein the shape is the sheet rolled from one edge to another to form a roll.

17. The method of claim 14 wherein the shape is the rod.

7. The method of claim wherein the lumen or void is created by a biopsy procedure.

18. A method to seal a lumen or void in a body of a patient comprising:

placing a sterilized pharmaceutically acceptable covalently crosslinked hydrogel polymerized from at least one synthetic hydrophilic polyethylene glycol macromer into the lumen or void,

wherein the hydrogel has a substantially less than equilibrium level of hydration for undergoing a volumetric expansion of at least about 50% after swelling with physiological fluid and, after implantation, swells from exposure to a fluid from the body to press against tissue surrounding the lumen or void to seal and thereby occlude the lumen or void,

wherein the hydrogel, at the substantially less than equilibrium level of hydration, has a shape selected from the group consisting of a rod and a sheet rolled from one edge to another to form a roll, with the rod or roll outer diameter being about 1.5 mm.

19. The method of claim 18 wherein the volumetric expansion is between about 50% and about 700%.

20. The method of claim 18 wherein the volumetric expansion is between about 100% and about 500%.

21. The method of claim 18 wherein the volumetric expansion is between about 150% and about 400%.

22. The method of claim 18 wherein the hydrogel is biodegradable.

23. The method of claim 18 wherein the fluid from the body is blood.

24. The method of claim 18 wherein the lumen or void is created by a biopsy procedure.

25. The method of claim 18 wherein the lumen or void is created by a needle.

26. The method of claim 18 wherein the lumen or void is selected from the group consisting of a naturally occurring body passageway, a fallopian tube, an arteriovenous malformation, and a bone canal.

27. The method of claim 18 wherein the macromer, before polymerization, comprises a functional group polymerizable by a polymerization reaction that is selected from the group consisting of free radical, condensation, anionic, and cationic.

28. The method of claim 18 wherein the macromer is polymerized by an electrophile-nucleophile reaction.

29. The method of claim 18 wherein the hydrogel further comprises a therapeutic bioactive molecule.

30. The method of claim 29 wherein the therapeutic bioactive molecule is selected from the group consisting of peptides, antibiotics, antitumor agents, hemostatics, and analgesics.

31. The method of claim 18 wherein the hydrogel further comprises a contrast agent.

32. The method of claim 31 wherein the contrast agent is a radio-opaque contrast agent.

33. The method of claim 31 wherein the shape is the sheet rolled from one edge to another to form a roll.

34. The method of claim 18 wherein the shape is the rod.