Compositions and systems for forming crosslinked biomaterials and associated methods of preparation and use

• US 8,067,031 B2
• Filed: 04/28/2005
• Issued: 11/29/2011
• Est. Priority Date: 04/28/2004
• Status: Active Grant

• Current Assignee: Angiodevice International GmbH
• Original Assignee: Angiodevice International GmbH
• Inventors: Schroeder, Jacqueline, Gravett, David M., Trollsas, Olof Mikael, Sehl, Louis C., Toleikis, Philip M., Daniloff, George Y.
• Primary Examiner(s): Krass; Frederick
• Assistant Examiner(s): Sutton; Darryl C
• Application Number:
  US11/118,088
• Publication Number:
  US 20050281883A1
• Time in Patent Office: 2,406 Days
• Field of Search: 424/423
• US Class Current: 424/484
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• CPC Class Codes: A61K 9/1075 Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers A61K9/0026 takes precedence
• CPC Class Codes: A61K 9/1647 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61K 9/5153 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61L 24/043 Mixtures of macromolecular materials
• CPC Class Codes: A61L 27/16 obtained by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/26 Mixtures of macromolecular compounds
• CPC Class Codes: A61L 27/50 Materials characterised by their function or physical properties , e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
• CPC Class Codes: A61L 31/041 Mixtures of macromolecular compounds
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 41/00 Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

Crosslinkable compositions are provided that readily crosslink in situ to provide crosslinked biomaterials. The composition contains at least two biocompatible, non-immunogenic components having reactive groups thereon, with the functional groups selected so as to enable inter-reaction between the components, i.e., crosslinking. In one embodiment, a first component has nucleophilic groups and a second component has electrophilic groups. Additional components may have nucleophilic or electrophilic groups. Methods for preparing and using the compositions are also provided as are kits for delivery of the compositions. Exemplary uses for the crosslinked compositions include tissue augmentation, biologically active agent delivery, bioadhesion, and prevention of adhesions following surgery or injury.

Claims

1. A kit for forming cross-linked biomaterials for medical applications, comprising:

(a) a dry powder composition comprising pentaerythritol tetrakis [1-(1′

-oxo-5-succimidylpentanoate)-2-poly(oxyethylene) ether and pentaerythritol tetrakis [mercaptoethyl poly(oxyethylene) ether;

(b) a first solution having a pH of 2.1-2.3; and

(c) a second solution having a pH of 9.6, 9.65-9.75, 9.7, or 10, wherein each of (a), (b) and (c) is packaged separately prior to use.

2. The kit of claim 1, wherein prior to use, each of (a), (b) and (c) is in a separate sterile package.

3. The kit of claim 1, further comprising a delivery device.

4. The kit of claim 3, wherein the delivery device is a multi-component spray device.

5. The kit of claim 4, wherein the multi-component spray device is a multiple-compartment syringe system having multiple barrels, a mixing head, and an exit orifice.

6. The kit of claim 5, wherein the dry powder composition, the first solution, and the second solution are housed separately in the multiple-compartment syringe system.

7. The kit of claim 3, wherein the delivery device is a pressurized delivery device.

8. The kit of claim 7, wherein the pressurized delivery system comprises:

a plurality of fluid component inlets each adapted to communicate with a source of different fluid components;

at least one carrier fluid inlet adapted to communicate with a source of a pressurized carrier fluid;

a diffuser surface located downstream from the plurality of fluid component inlets and the at least one carrier fluid inlet; and

an outlet extending through the diffuser surface,

wherein the diffuser surface is adapted to receive fluid components thereon and has a shape effective to direct and maintain each received fluid component in a different flow path toward the outlet for mixing and dispensing therethrough by the pressurized carrier fluid from the at least one carrier fluid inlet.

9. The kit of claim 8, wherein the pressurized carrier fluid is pressurized air.

10. The kit of claim 8, wherein the fluid components are the first solution and the second solution.

11. The kit of claim 1, wherein the kit further comprises a biologically active agent and the medical application comprises delivering the biologically active agent.

12. The kit of claim 11, wherein the biologically active agent is packaged with the dry powder composition.

13. The kit of claim 12, further comprising a pharmaceutically acceptable carrier packaged with the biologically active agent and the dry powder composition.

14. The kit of claim 11, wherein the biologically active agent is packaged as a solution with the first solution.

15. The kit of claim 11, wherein the biologically active agent is packaged as a solution with the second solution.

16. The kit of claim 11, further comprising a pharmaceutically acceptable carrier as a fourth component.

17. The kit of claim 16, wherein the biologically active agent is packaged with the pharmaceutically acceptable carrier.

18. The kit of claim 1, wherein the kit further comprises living cells or genes, and the medical application comprises delivering the living cells or genes.

19. The kit of claim 1, wherein the medical application comprises adhering or sealing biological tissue.

20. The kit of claim 1, wherein the medical application comprises bioadhesion.

21. The kit of claim 1, wherein the medical application comprises an ophthalmic application.

22. The kit of claim 1, wherein the medical application comprises tissue augmentation.

23. The kit of claim 1, wherein the medical application comprises adhesion prevention.

24. The kit of claim 1, wherein the medical application comprises forming a synthetic implant or coating a synthetic implant.

25. The kit of claim 1, wherein the medical application comprises the treatment of aneurysms.

26. The kit of claim 1, wherein the medical application is a laparoscopic procedure.

27. The kit of claim 11 wherein the biologically active agent is an anti-fibrotic agent.

28. The kit of claim 27 wherein the biologically active agent is paclitaxel.

29. The kit of claim 1 wherein the first solution includes hydrogen chloride.

30. The kit of claim 1 wherein the second solution includes sodium phosphate and sodium carbonate.