Compositions and methods for joining non-conjoined lumens

• US 8,608,760 B2
• Filed: 12/20/2007
• Issued: 12/17/2013
• 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: Gurtner, Geoffrey C., Fuller, Gerald G., Longaker, Michael T., Rajadas, Jayakumar, Saul, Gordon, Rappleye, C. Travis, Mandrusov, Evgenia
• Primary Examiner(s): ANDERSON, GREGORY A
• Application Number:
  US11/962,077
• Publication Number:
  US 20080262519A1
• Time in Patent Office: 2,189 Days
• Field of Search: 606/153, 606/151
• 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) placing a biocompatible phase-reversible sol-gel composition in a liquid phase or a gel phase in at least the distal portion of at least one of the lumens, which phase-reversible sol-gel composition is capable of phase transition from a liquid phase to a gel phase and from the gel phase to the liquid phase, wherein when the sol-gel composition is placed in the lumen in the liquid phase, a phase transition is induced wherein the liquid phase changes to the gel phase, and wherein the gel phase of the sol-gel composition provides structural support to said portion of the lumen;

(b) aligning the lumens;

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

(d) removing the sol-gel composition by inducing a phase transition of the sol-gel composition from the gel phase to the liquid phase 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 comprising 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 composition in a gel phase inside at least a portion of the distal end of at least one of the lumens in a manner which provides structural support to said portion of the lumen.

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

(a2) placing the phase-reversible sol-gel composition 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 composition in the lumen wherein the liquid phase changes to a gel phase which provides structural support 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 a thermoreversible sol-gel having a transition temperature of from about 0°

C. to about 45°

C.

10. The method of claim 9, wherein the transition temperature is from about 15°

C. to about 35°

C.

11. The method of claim 10, 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.

12. The method of claim 11, wherein the cooling is conducted by applying water or an aqueous solution or ice.

13. The method of claim 9, wherein the thermoreversible sol-gel comprises an aqueous solvent and 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.

14. The method of claim 13, wherein the polymer is present in an amount of about 5% to about 35% by weight.

15. The method of claim 14, wherein the polymer is present in an amount of about 15% to about 20% by weight.

16. 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.

17. The method of claim 16, 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.

18. The method of claim 17, 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.

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

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

21. 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).

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

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