SUPERABSORBENT, FREEZE DRIED HYDROGELS FOR MEDICAL APPLICATIONS

• US 20070231366A1
• Filed: 08/18/2006
• Published: 10/04/2007
• Est. Priority Date: 03/29/2006
• Status: Active Grant

• Current Assignee: Incept LLC
• Original Assignee: Incept LLC
• Inventors: Pai, Suresh S., Bennett, Steven L., Co, Fred H., Sershen, Scott R., SAWHNEY, Amarpreet S.
• Granted Patent: US 8,795,709 B2
• Time in Patent Office: Days
• US Class Current: 424/426
• CPC Class Codes: A61B 2017/0065 the implement being an adhesive
• CPC Class Codes: A61L 24/0031 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 24/046 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds A61L24/043 takes precedence
• CPC Class Codes: A61L 24/10 Polypeptides; Proteins A61L24/043 takes precedence
• CPC Class Codes: C08L 71/02 Polyalkylene oxides

Abstract

Methods are provided for making freeze dried hydrogel and structures therefrom that may be introduced into a patient'"'"'s body for medical applications. Precursor components are combined to initiate crosslinking. The combined precursor components are placed in a chilled tray, and allowed to crosslink to a desired level of complete crosslinking before and/or after being placed onto the tray. The partially crosslinked hydrogel is frozen and freeze dried. After freeze drying, the hydrogel is conditioned to substantially complete crosslinking, and formed into one or more structures, e.g., plugs, hemostatic, or other medical devices. For example, the hydrogel may be cut, machined, rolled, folded, compressed, and/or cored into that may be loaded into delivery devices that may be introduced into a body to implant or otherwise deliver the structures into the body, e.g., to seal a puncture or other passage through tissue.

Claims

1. A method for making superabsorbent hydrogel, comprising:

forming a mixture by combining precursor components to initiate crosslinking of the precursor components;

freezing the mixture before crosslinking is complete; and

freeze drying the mixture to form the hydrogel.

2. The method of claim 1, further comprising conditioning the hydrogel after freeze drying.

3. The method of claim 1, wherein the precursor components comprise a first electrophilic precursor and a second nucleophilic precursor.

4. The method of claim 2, wherein the hydrogel substantially completes crosslinking when the hydrogel is conditioned.

5. The method of claim 4, wherein the hydrogel has substantially no unreacted reactive ester end groups after the hydrogel is conditioned.

6. The method of claim 1, further comprising placing the combined precursor components onto a chilled tray or container before freezing the mixture.

7. The method of claim 6, wherein the mixture is frozen on the tray or container.

8. The method of claim 6, further comprising forming the freeze dried hydrogel into one or more structures.

9. The method of claim 8, wherein the one or more structures are formed by at least one of cutting, machining, rolling, coring, and compressing the hydrogel.

10. The method of claim 8, wherein the one or more structures comprise a structure that is sized for introduction into a body lumen.

11. The method of claim 1, wherein crosslinking of the precursor components is initiated in an aqueous phase.

12. The method of claim 1, wherein crosslinking of the precursor components comprises covalent crosslinking.

13. The method of claim 1, wherein the hydrogel substantially completes crosslinking when the mixture is freeze dried.

14. The method of claim 1, wherein the precursor components comprise a highly branched active PEG.

15. The method of claim 14, wherein the precursor components further comprise an oligopeptide with two or more lysine groups.

28. A method for depositing a material within a patient'"'"'s body, comprising:

making a freeze dried hydrogel according to the method of claim 1; and

introducing the freeze dried hydrogel into the patient'"'"'s body.

29. The method of claim 28, wherein introducing the freeze dried hydrogel comprises introducing the freeze dried hydrogel into a passage within the patient'"'"'s body.

30. The method of claim 28, wherein the passage comprises a puncture through tissue.

31. The method of claim 28, wherein the passage comprises a body lumen.

32. An implant sized for introduction into a patient'"'"'s body, comprising a hydrogel formed by the method of claim 1.

33. The implant of claim 32, wherein the hydrogel comprises an open-cell hydrogel.

34. The implant of claim 32, wherein the hydrogel comprises at least one macromolecular species.

35. The implant of claim 32, wherein the precursor components comprise PEG.

36. The implant of claim 32, wherein the precursor components comprise a highly branched active PEG.

37. The implant of claim 36, wherein the precursor components further comprise an oligopeptide with two or more lysine groups.

38. The implant of claim 32, wherein the precursor components comprise a first electrophilic precursor and a second nucleophilic precursor.

39. The implant of claim 32, wherein the hydrogel comprises at least one polymeric species.

40. The implant of claim 32, wherein the hydrogel is degradable when implanted within a patient'"'"'s body.

41. The implant of claim 32, wherein the hydrogel is substantially non-degradable when implanted within a patient'"'"'s body.

42. The implant of claim 32, wherein the hydrogel is degradable by hydrolysis.

43. The implant of claim 32, wherein the hydrogel has a density between 0.05 and 0.30 grams per cubic centimeter (g/cc).

44. The implant of claim 32, wherein the hydrogel has a rate of magnitude of expansion between about five and fifty (5-50) times the initial volume when exposed to an aqueous environment.

45. The implant of claim 32, wherein the hydrogel has a rate of swelling such that, when exposed to an aqueous environment, the hydrogel expands between about five hundred and three thousand percent (500-3000%) of the initial mass within about five to sixty (5-60) seconds.

16. A method for making hydrogel, comprising:

combining precursor components to initiate crosslinking of the precursor components to form a hydrogel;

placing the hydrogel onto a tray or container chilled below the freezing point of the combined precursor components;

freezing the hydrogel before crosslinking is complete;

freeze drying the frozen hydrogel; and

conditioning the freeze dried hydrogel to substantially complete crosslinking of the precursor components.

17. The method of claim 16, further comprising forming the hydrogel into one or more structures.

18. The method of claim 16, wherein the hydrogel is placed onto the tray or container before crosslinking is complete.

19. The method of claim 16, wherein the hydrogel is placed onto the tray or container after a predetermined amount of crosslinking has occurred.

20. The method of claim 16, wherein the hydrogel is placed onto the tray or container immediately upon combining the precursor components, and wherein the hydrogel is maintained on the tray or container at a predetermined temperature until a predetermined percentage of complete crosslinking is achieved, whereupon the hydrogel is freeze dried.

21. The method of claim 16, wherein conditioning the hydrogel comprises one or more conditioning steps selected from the group comprising:

exposing the hydrogel to a controlled-humidity environment;

further drying the hydrogel using heat;

exposing the hydrogel to a controlled gas environment;

exposing the hydrogel to an aerosolized buffer solution; and

desiccating the hydrogel.

22. The method of claim 21, wherein the hydrogel is conditioned using multiple successive stages, each stage comprising one or more of the conditioning steps.

23. The method of claim 16, wherein the step of freeze drying the hydrogel comprises:

a first stage comprising exposing the hydrogel to a freeze drying temperature and a vacuum; and

a second stage comprising at least one of increasing the freeze drying temperature, and reducing the vacuum.

24. The method of claim 23, wherein the second stage comprises reducing the vacuum for a second stage duration, and wherein the freeze drying temperature is increased at least intermittently during the second stage duration.

25. The method of claim 24, wherein the freeze drying temperature is increased at a steady rate during the second stage duration.

26. The method of claim 16, wherein the hydrogel substantially completes crosslinking when the hydrogel is conditioned.

27. The method of claim 26, wherein the hydrogel has substantially no unreacted reactive ester end groups after the hydrogel is conditioned.