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

• US 8,460,708 B2
• Filed: 10/24/2011
• Issued: 06/11/2013
• Est. Priority Date: 04/28/2004
• Status: Active Grant

• Current Assignee: Angiodevice International GmbH (Angiotech Pharmaceuticals (US), Inc.)
• Original Assignee: Angiodevice International GmbH (Angiotech Pharmaceuticals (US), Inc.)
• Inventors: Daniloff, George Y., Sehl, Louis C., Trollsas, Olof Mikael, Schroeder, Jacqueline A., Gravett, David M., Toleikis, Philip M.
• Primary Examiner(s): Roberts, Lezah
• Assistant Examiner(s): Liu, Tracy
• Application Number:
  US13/279,987
• Publication Number:
  US 20120041481A1
• Time in Patent Office: 596 Days
• Field of Search: 424/484, 424/489, 424/70.11, 514/506, 514/553
• US Class Current: 424/489
• 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

Kits comprising dry power compositions are provided that readily crosslink in situ to provide crosslinked biomaterials. The dry powder 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. Exemplary uses for the crosslinked biomaterials include tissue augmentation, biologically active agent delivery, bioadhesion, and prevention of adhesions following surgery or injury.

Claims

1. A kit for use in medical applications, comprising:

(a) a dry powder composition comprising

i. a first component having a first hydrophilic polymer core substituted with m thiol groups, where m≧

2; and

ii. a second component having a second hydrophilic polymer core substituted with n electrophilic groups, where n≧

2 and m+n>

4, and wherein the electrophilic group is independently —

(CO)—

O—

(CO)—

R (where R is an alkyl group), CH═

CH—

CH═

O, —

CH═

CH—

C(CH₃)═

O, —

N═

C═

O, —

N═

C═

S, —

SO₂CH═

CH₂, —

O(CO)—

C═

CH₂, —

O(CO)—

C(CH₃)═

CH₂, —

S—

S—

(C₅H₄N), —

O(CO)—

C(CH₂CH₃)═

CH₂, —

CH═

CH—

C═

NH, —

COOH, —

(CO)O—

N(COCH₂)₂, —

O—

(CO)—

O—

N(COCH₂)₂, —

CHO, —

(CO)O—

N(COCH₂)₂—

S(O)₂OH, and —

N(COCH)₂;

(b) a first solution having a pH within the range of about 2.1-2.3, and being configured to be mixed with (a) to provide a homogeneous solution of (a) and (b); and

(c) a second solution having a pH within the range of about 6.0 to 11.0 and being configured to be mixed with the homogeneous solution of (a) and (b),

wherein the thiol group and the electrophilic groups are non-reactive in a dry environment, and wherein each of (a), (b) and (c) is packaged separately and admixed immediately prior to use.

2. The kit of claim 1, wherein prior to use, each component 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 4, 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 involves 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 11, 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 in the first solution.

15. The kit of claim 11, wherein the biologically active agent is packaged in 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 medical application involves adhering or sealing biological tissue.

19. The kit of claim 1, wherein the medical application involves bioadhesion.

20. The kit of claim 1, wherein the first hydrophilic polymer core and the second hydrophilic polymer core are independently a linear, branched, dendrimeric, hyperbranched, or star polymer.

21. The kit of claim 20, wherein the first hydrophilic polymer core and the second hydrophilic polymer core are independently selected from polyalkylene oxides;

polyols;

poly(oxyalkylene)-substituted diols and polyols;

polyoxyethylated sorbitol;

polyoxyethylated glucose;

poly(acrylic acids), analogs and copolymers thereof;

polymaleic acids;

polyacrylamides;

poly(olefinic alcohols);

poly(N-vinyl lactams);

polyoxazolines;

polyvinylamines; and

copolymers thereof

22. The kit of claim 21, wherein the first hydrophilic polymer core and the second hydrophilic polymer core are independently a polyalkylene oxide or a polyol selected from polyethylene glycol and poly(ethylene oxide)-polypropylene oxide) copolymers.

23. The kit of claim 22, wherein the hydrophilic polymer is a poly(oxyalkylene)-substituted polyol, wherein the polyol is selected from mono-, di- and tri-polyoxyethylated glycerol, mono- and di-polyoxyethylated propylene glycol, mono- and di-polyoxyethylated trimethylene glycol, and pentaerythritol.