COMPOSITIONS AND METHODS FOR JOINING NON-CONJOINED LUMENS

• US 20080262519A1
• Filed: 12/20/2007
• Published: 10/23/2008
• Est. Priority Date: 06/21/2006
• Status: Active Grant

• Current Assignee: Board of Trustees of the Leland Stanford Junior University (Stanford Management Co.)
• Original Assignee: Board of Trustees of the Leland Stanford Junior University (Stanford Management Co.)
• Inventors: Mandrusov, Evgenia, Fuller, Gerald G., Rajadas, Jayakumar, Longaker, Michael T., Rappleye, C. Travis, Saul, Gordon M., GURTNER, Geoffrey C.
• Granted Patent: US 8,608,760 B2
• Time in Patent Office: Days
• US Class Current: 606/153
• CPC Class Codes: A61B 17/00491 Surgical glue applicators surgical adhesives A61L24/00; two-component delivery syringes A61M5/19
• CPC Class Codes: A61B 17/04 for suturing wounds; Holders or packages for needles or suture materials suture materials A61L17/00
• CPC Class Codes: A61B 17/11 for performing anastomosis; Buttons for anastomosis
• 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 17/1204 temporary occlusion
• 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 17/122 Clamps or clips , e.g. for the umbilical cord for the vas deferens A61F6/206
• CPC Class Codes: A61B 17/1227 Spring clips
• CPC Class Codes: A61B 2017/1103 Approximator
• CPC Class Codes: A61B 2017/1107 for blood vessels

Abstract

Disclosed are compositions, methods, and kits for joining together non-conjoined lumens in a patient'"'"'s body including vascular lumens. More particularly, in various aspects, this invention provides compositions, methods, and kits for joining such non-conjoined lumens, including small lumens typically requiring microsurgical technique

Claims

1. A method for joining at least two non-conjoined lumens in a patient which method comprises:

(a) providing a biocompatible phase-reversible sol-gel composition in at least the distal portion of at least one of the lumens;

(b) aligning the lumens;

(c) closing the aligned lumens to form a conduit; and

(d) removing the sol-gel composition thereby establishing flow through the conduit;

wherein the phase-transition of the sol-gel composition is triggered by an stimulus selected from a change in temperature, a change in pH, a change in ionic strength, a change in pressure, a change in electric field, a change in magnetic field, a change in electron magnetic radiation, a change in light or ultraviolet light, a change in concentration, a change in osmolarity, and combinations thereof.

2. The method of claim 1, further comprises a step before step (a), which step comprises arresting the flow of body fluid in the lumens.

3. The method of claim 1, wherein the sol-gel composition is placed in the distal portion of each lumen to be joined.

4. The method of claim 1, wherein the sol-gel composition is placed in the distal portion of a first lumen in a manner in which the sol-gel composition protrudes from the distal portion such that this protrusion can be used as a male mating functionality with the distal portion of the second lumen which acts as a female mating functionality.

5. The method of claim 1, wherein step (a) comprises:

(a1) placing the phase-reversible sol-gel in a gel phase inside at least a portion of the distal end of at least one of the lumens in a manner which imparts structural integrity to said portion of the lumen.

6. The method of claim 1, wherein step (a) comprises:

(a2) placing the phase-reversible sol-gel in a liquid phase inside at least a portion of the distal end of at least one of the lumens; and

(a3) inducing a phase transition change in the phase-reversible sol-gel in the lumen wherein the liquid phase changes to a gel phase which imparts structural integrity to said portion of the lumen.

7. The method of claim 1, wherein the sol-gel composition has an elastic modulus of at least 100 Pascals when in its gel phase.

8. The method of claim 1, wherein the sol-gel composition has an elastic modulus of at least 8,000 Pascals when in its gel phase.

9. The method of claim 1, wherein the sol-gel composition is removed by a method selected from melting, phase change, change in viscosity, dissolution in the body fluid and combinations thereof.

10. The method of claim 1, wherein the sol-gel composition is a thermoreversible sol-gel having a transition temperature of from about 0°

C. to about 45°

C.

11. The method of claim 10, wherein the transition temperature is from about 15°

C. to about 35°

C.

12. The method of claim 11, wherein the sol-gel composition is removed from the joined lumens by cooling the joined lumens to a temperature that is below the transition temperature of the sol-gel composition.

13. The method of claim 12, wherein the cooling is conducted by applying water or an aqueous solution or ice.

14. The method of claim 10, wherein the thermoreversible sol-gel comprises a polymer selected from the group consisting of poloxamer 118, poloxamer 188, poloxamer 338, poloxamer 407, Tetronic®

1107 and Tetronic®

1307 or a mixture thereof, and an aqueous solvent.

15. The method of claim 14, wherein the polymer is present in an amount of about 5% to about 35% by weight.

16. The method of claim 15, wherein the polymer is present in an amount of about 15% to about 20% by weight.

17. The method of claim 1, wherein the phase-transition of the sol-gel composition is triggered by a stimulus which comprises a change in ionic strength.

18. The method of claim 17, wherein the sol-gel composition is a gel in an environment having an ionic strength higher than the ionic strength of the body fluid in the lumen and becomes a liquid in an environment having an ionic strength equal to or lower than the ionic strength of the body fluid in the lumen.

19. The method of claim 18, wherein the sol-gel composition is placed in at least one of the lumens as a gel, and wherein the sol-gel composition is removed by reducing the ionic strength to an ionic strength that is equal to the ionic strength of the body fluid in the lumen with the body fluid thereby inducing the sol-gel composition to undergo a phase transition from the gel phase to a liquid phase.

20. The method of claim 1, wherein the sol-gel composition is removed by dissolving the sol-gel composition with body fluid.

21. The method of claim 1, wherein joining of the lumens is conducted by suturing.

22. The method of claim 1, further comprising a step of partially suturing the lumens, where said step is performed before and/or after step (a).

23. The method of claim 1, wherein joining of the lumens is conducted using a biocompatible adhesive.

24. The method of claim 1, wherein joining of the lumens is conducted using laser.

25. A vessel of a cardiovascular system of a mammal, wherein the vessel has a phase-reversible sol-gel composition positioned in the vessel in a manner and in an amount sufficient to hold walls of the vessel open in a fashion similar to when blood flows through the vessel, wherein the phase-transition of the sol-gel composition is triggered by an environment condition selected from a change in temperature, a change in pH, a change in ionic strength, a change in pressure, a change in electric field and combinations thereof.

26. The vessel of claim 25, wherein the phase-reversible sol-gel is a thermoreversible sol-gel having a transition temperature of about 0°

C. to about 45°

C.

27. The vessel of claim 25, wherein the phase-reversible sol-gel is a sol-gel whose phase transition is induced by a stimulus comprising a change in ionic strength.

28. The vessel of claim 25, wherein the phase-reversible sol-gel is a sol-gel whose phase transition is induced by a stimulus comprising a change in pH.

29. A kit for connecting at least two non-conjoined lumens within a living mammal, comprising:

a delivering device; and

a phase-reversible sol-gel composition whose phase-transition is triggered by an environment condition selected from a change in temperature, a change in pH, a change in ionic strength, a change in pressure, a change in electric field or a combination thereof.

30. The kit of claim 29, wherein the delivering device is a syringe.

31. The kit of claim 30, wherein the composition is loaded in the syringe.

32. The kit of claim 29, where delivery device is a catheter or a laparoscopic tool.

33. The kit of claim 29, further comprising a triggering component.

34. The kit of claim 29, wherein the delivery device is coupled with a triggering component.

35. The kit of claim 29, further comprising at least one clamp for closing at least one of the non-conjoined lumen.

36. The kit of claim 29, further comprising a biocompatible adhesive for sealing the lumens.