Fragmented Hydrogels

• US 20120238644A1
• Filed: 11/05/2010
• Published: 09/20/2012
• Est. Priority Date: 11/09/2009
• Status: Active Grant

• Current Assignee: Spotlight Technology Partners LLC
• Original Assignee: Spotlight Technology Partners LLC
• Inventors: Gong, Glen, Pai, Suresh Subraya, Sershen, Scott Robert
• Granted Patent: US 8,795,727 B2
• Time in Patent Office: Days
• US Class Current: 514/781
• CPC Class Codes: A61K 31/225 Polycarboxylic acids
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 31/58 containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin digitoxin A61K31/7048
• CPC Class Codes: A61K 31/7036 having at least one amino group directly attached to the carbocyclic ring, e.g. streptomycin, gentamycin, amikacin, validamycin, fortimicins
• CPC Class Codes: A61K 31/722 Chitin, chitosan
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• 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 47/36 Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
• CPC Class Codes: A61K 9/06 Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels composition of ointments, creams or gels A61K47/00
• CPC Class Codes: A61K 9/146 with organic macromolecular compounds
• CPC Class Codes: A61L 24/0031 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 24/08 Polysaccharides A61L24/043 takes precedence
• CPC Class Codes: A61L 26/0023 Polysaccharides
• CPC Class Codes: A61L 26/008 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 27/20 Polysaccharides
• CPC Class Codes: A61L 27/52 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 31/042 Polysaccharides
• CPC Class Codes: A61L 31/145 Hydrogels or hydrocolloids
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• 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: C08J 2371/02 : Polyalkylene oxides
• CPC Class Codes: C08J 2405/08 : Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof
• CPC Class Codes: C08J 3/075 : Macromolecular gels
• CPC Class Codes: C08J 3/12 : Powdering or granulating
• CPC Class Codes: C08K 5/06 : Ethers; Acetals; Ketals; Ortho-esters
• CPC Class Codes: C09D 105/08 : Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof

Abstract

Fragmented polysaccharide based hydrogel compositions and methods of making and using the same are provided. The subject polysaccharide based hydrogel compositions are prepared by combining a polysaccharide component with a hydrophilic polymer and a cross-linking agent. Also provided are kits and systems for use in preparing the subject compositions.

Claims

1. A hydrogel composition, comprising

a polysaccharide substrate or derivative thereof having a molecular weight of 160 Dalton to 80,300 Dalton and comprising at least two reactive nucleophilic groups;

a synthetic, hydrophilic polymer of a molecular weight of 200 Dalton to 100000 Dalton and comprising at least two nucleophilic reactive groups; and

a crosslinking agent.

2. The composition of claim 1, wherein the polysaccharide substrate is chitosan, carboxymethylcellulose, carboxymethylchitosan or a derivative thereof.

3. The composition of claim 1, wherein the synthetic hydrophilic polymer substrate is a polyethylene glycol having at least two nucleophilic active groups.

4. The composition of claim 1, wherein the crosslinking agent is a polyethylene glycol having at least two electrophilic active groups.

5. The composition of claim 1, wherein the crosslinking agent is an aldehyde.

6. The composition of claim 1, wherein the crosslinking agent is a glutaraldehyde.

7. The composition of claim 1, wherein the crosslinking agent is heat treated glutaraldehyde.

8. The composition of claim 1, wherein the composition comprises a thickening agent.

9. The composition of claim 1, wherein the composition comprises a foaming agent.

10. The composition of claim 1, wherein the composition comprises a biologically active agent and or a pharmaceutically active agent.

11. The composition of claim 1, wherein the composition comprises a visualization agent and/or a radiopaque agent.

12. The composition of claim 1, wherein the polysaccharide substrate is soluble in an alkaline aqueous solution.

13. The composition of claim 1, wherein the polysaccharide substrate is soluble in an aqueous solution with a concentration of at least 30 mM.

14. A method of making a fragmented hydrogel composition, comprising:

combining components of the hydrogel composition of claim 1 in a solution;

allowing the solution to cure for a sufficient period of time to form a cured hydrogel composition; and

fragmenting the cured hydrogel composition to form a fragmented hydrogel composition.

15. The method of claim 14, wherein fragmenting comprises cryogenic milling and/or cryogenic grinding.

16. The method of claim 14, wherein the hydrogel composition is dried after complete or partial curing.

17. The method of claim 16, wherein the hydrogel composition is fragmented after drying.

18. The method of claim 14, wherein the fragmented hydrogel composition is fractionated by size.

19. The method of claim 18, wherein a specific range of particle sizes is selected from the fragmented hydrogel particulate.

20. The method of claim 17, further comprising rehydrating the fragmented hydrogel composition prior to use.

21. A method of reducing bleeding of a wound on a subject, comprising:

positioning the fragmented hydrogel composition of claim 1 over at least a portion of the wound, wherein the positioning of the fragmented hydrogel composition reduces bleeding of the wound as compared to the absence of the fragmented hydrogel composition.

22. A method of filling a void in a tissue, comprising:

positioning the fragmented hydrogel composition of claim 1 in the void, wherein the positioning of the fragmented hydrogel composition partially or completely fills the void.

23. A method of reducing adhesion or friction between two or more adjacent tissues, comprising:

positioning the fragmented hydrogel composition of claim 1 between the two or more adjacent tissues, wherein the positioning of the fragmented hydrogel composition reduces adhesion or friction between the two or more adjacent tissues as compared to the absence of the fragmented hydrogel composition.

24. A method of delivering a therapeutic or palliative agent to a subject, comprising:

administering the fragmented hydrogel composition of claim 1 to a subject, wherein the administering provides delivery of the therapeutic or palliative agent to the subject.

25. A method of augmenting an existing target tissue, comprising:

administering the fragmented hydrogel composition of claim 1 to an existing target tissue, wherein the administering provides for augmenting the existing target tissue as compared to the absence of the fragmented hydrogel composition.

26. A method of reducing leakage across suture lines, anastomoses, or incisions, comprising:

positioning the fragmented hydrogel composition of claim 1 over at least a portion of the suture line, anastomoses, or incision wherein the positioning of the fragmented hydrogel composition reduces leakage of fluid across the suture line, anastomoses, or incision as compared to the absence of the fragmented hydrogel composition.

27. A method of filling or closing a targeted vasculature or aneurysm;

comprising;

depositing the fragmented hydrogel composition of claim 1 within the targeted vasculature or aneurysm, wherein the deposition of the fragmented hydrogel composition fills or closes the targeted vasculature or aneurysm.

28. A method of providing a moist environment that covers and protects an exposed surface tissue of a subject, comprising:

positioning the fragmented hydrogel composition of claim 1 over at least a portion of the exposed surface tissue, wherein the positioning of the fragmented hydrogel composition provides a moist environment that covers and protects the exposed surface tissue as compared to the absence of the fragmented hydrogel composition.

29. A method of applying a fragmented hydrogel composition to a medical implant, comprising:

depositing the fragmented hydrogel composition of claim 1 on a medical implant.

30. The method of claim 29, wherein the surface of the medical implant is coated with the fragmented hydrogel composition.

31. The method of claim 29, wherein a recess, void, or lumen in the medial implant is coated or filled with the fragmented hydrogel composition.

32. A method of forming a tissue scaffold, comprising:

forming the fragmented hydrogel composition of claim 1 into a scaffold for tissue engineering or regeneration, wherein the tissue scaffold optionally further comprises mammalian cells.

33. A method of forming an energy barrier between a target tissue and an adjacent tissue, comprising:

positioning the fragmented hydrogel composition of claim 1 between a target tissue and an adjacent tissue, wherein the positioning of the fragmented hydrogel composition reduces transmission of energy from the target tissue to the adjacent tissue as compared to the absence of the fragmented hydrogel composition.

34. A method of adhering two or more tissues to each other, comprising:

positioning the fragmented hydrogel composition of claim 1 between at least two tissues, wherein the positioning of the fragmented hydrogel composition provides for adhering of the two tissues to each other as compared to the absence of the fragmented hydrogel composition.

35. A kit, comprising:

the fragmented hydrogel composition of claim 1, and

a delivery device to provide for delivery of the fragmented hydrogel to a target area or tissue.

36. The kit of claim 35, wherein the fragmented hydrogel composition is provided in a first container and a buffer solution is provided in a second container.

37. The kit of claim 36, wherein the container for the fragmented hydrogel composition comprises a first syringe and the container for the buffer solution comprises a second syringe.

38. The kit of claim 36, wherein the container for the fragmented hydrogel composition comprises a pouch and the container for the buffer solution comprises a syringe.

39. The kit of claim 35, wherein the fragmented hydrogel composition and a buffer solution are provided within a single syringe.

40. The kit of claim 39, wherein the syringe is a dual chamber syringe, and wherein the fragmented hydrogel composition is provided in a first chamber of the syringe and the buffer solution is provided in a second chamber of the syringe.

41. The kit of claim 35, wherein the fragmented hydrogel composition is provided as a dry particulate in a container.

42. The kit of claim 35, wherein the fragmented hydrogel composition is provided as a semi- or fully hydrated particulate in a container.