HYDROGELS FOR VOCAL CORD AND SOFT TISSUE AUGMENTATION AND REPAIR

• US 20100055184A1
• Filed: 09/03/2009
• Published: 03/04/2010
• Est. Priority Date: 09/04/2008
• Status: Active Grant

• Current Assignee: General Hospital Corporation, Massachusetts Institute of Technology
• Original Assignee: General Hospital Corporation
• Inventors: Hillman, Robert Edward, Zeitels, Steven M., Karajanagi, Sandeep Sidram, Langer, Robert S.
• Granted Patent: US 9,216,188 B2
• Time in Patent Office: Days
• US Class Current: 424/484
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/7052 having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
• CPC Class Codes: A61L 2400/06 Flowable or injectable implant compositions
• CPC Class Codes: A61L 2430/34 for soft tissue reconstruction
• CPC Class Codes: A61L 27/26 Mixtures of macromolecular compounds
• CPC Class Codes: A61L 27/38 containing added animal cells organs or tissue containing native cells A61L27/36
• CPC Class Codes: A61L 27/3834 Cells able to produce different cell types, e.g. hematopoietic stem cells, mesenchymal stem cells, marrow stromal cells, embryonic stem cells
• 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 27/52 Hydrogels or hydrocolloids
• CPC Class Codes: A61P 19/04 for non-specific disorders of the connective tissue
• CPC Class Codes: C08J 2305/08 Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof
• CPC Class Codes: C08J 2371/02 Polyalkylene oxides
• CPC Class Codes: C08J 3/075 Macromolecular gels
• CPC Class Codes: C08J 3/246 Intercrosslinking of at least two polymers
• CPC Class Codes: C08L 71/02 Polyalkylene oxides

Abstract

The present invention provides hydrogels and compositions thereof for vocal cord repair or augmentation, as well as other soft tissue repair or augmentation (e.g., bladder neck augmentation, dermal fillers, breast implants, intervertebral disks, muscle-mass). The hydrogels or compositions thereof are injected into the superficial lamina propria or phonatory epithelium to restore the phonatory mucosa of the vocal cords, thereby restoring a patient'"'"'s voice. In particular, it has been discovered that hydrogels with an elastic shear modulus of approximately 25 Pa are useful in restoring the pliability of the phonatory mucosa. The invention also provides methods of preparing and using the inventive hydrogels.

Claims

1. A polymeric hydrogel comprising a semi-interpenetrating network of a cross-linked polymer and a water soluble polymer, wherein the hydrogel has an elastic shear modulus ranging from about 15 Pa to about 35 Pa.

4. The polymeric hydrogel of claim 1 comprising:

a cross-linked acrylated derivative of a polymer; and

a water-soluble polymer;

wherein the hydrogel is a semi-interpenetrating network of polymers, and wherein the hydrogel has an elastic shear modulus ranging from about 15 Pa to about 35 Pa.

5. The polymeric hydrogel of claim 1 comprising:

a cross-linked acrylated derivative of polyalkylene glycol; and

a water-soluble polymer selected from the group consisting of polyethers, polyols, poly(amino acids), proteins, and polysaccharides;

wherein the hydrogel is a semi-interpenetrating network of polymers; and

wherein the hydrogel has an elastic shear modulus ranging from about 15 Pa to about 35 Pa.

9. The polymeric hydrogel of claim 1 comprising:

a cross-linked acrylated derivative of polyalkylene glycol; and

a cross-linked version of a water-soluble polymer selected from the group consisting of polyethers, polyols, poly(amino acids), proteins, peptides, polysaccharides, and elastomeric polymers;

wherein the hydrogel is a semi-interpenetrating network of polymers; and

wherein the hydrogel has an elastic shear modulus ranging from about 15 Pa to about 35 Pa.

10. The polymeric hydrogel of claim 1 comprising:

cross-linked acrylated derivative of polyethylene glycol; and

a water-soluble polymer selected from the group consisting of polyethers, polyols, poly(amino acids), proteins, and polysaccharides;

wherein the hydrogel is a semi-interpenetrating network of polymers; and

wherein the hydrogel has an elastic shear modulus ranging from about 15 Pa to about 35 Pa.

11. The polymeric hydrogel of claim 1 comprising:

cross-linked polyethylene glycol diacrylate; and

a water soluble polymer selected from the group consisting of polyethylene glycol (PEG), poly(lysine), hyaluronic acid (HA), dextrans, alginates, gelatins, elastins, collagens, celluloses, methylcelluloses, and derivatives thereof;

wherein the hydrogel is a semi-interpenetrating network of polymers; and

wherein the hydrogel has an elastic shear modulus ranging from about 15 Pa to about 35 Pa.

12. The polymeric hydrogel of claim 1 comprising:

cross-linked hyaluronic methacrylate; and

a water soluble polymer selected from the group consisting of polyethylene glycol (PEG), poly(lysine), hyaluronic acid (HA), dextrans, alginates, gelatins, elastins, collagens, celluloses, methylcelluloses, and derivatives thereof;

wherein the hydrogel is a semi-interpenetrating network of polymers; and

wherein the hydrogel has an elastic shear modulus ranging from about 15 Pa to about 35 Pa.

13. The polymeric hydrogel of claim 1, wherein the hydrogel has an elastic shear modulus ranging from about 20 Pa to about 30 Pa.

14. The polymeric hydrogel of claim 1, wherein the hydrogel has an elastic shear modulus ranging from about 20 Pa to about 25 Pa.

15. The polymeric hydrogel of claim 1, wherein the hydrogel has an elastic shear modulus of about 25 Pa.

16. The polymeric hydrogel of claim 1, wherein the water-soluble polymer is selected from the group consisting of polyethylene glycol (PEG), hyaluronic acid (HA), dextran, poly(glyceraol sebacate) (PGS), methyl cellulose, collagen, elastin, gelatin, alignate, and poly(lysine).

27. The polymeric hydrogel of claim 1, wherein the cross-linked polymer is photo-crosslinked.

28. The polymeric hydrogel of claim 1 further comprising a bioactive agent.

29. The polymeric hydrogel of claim 28, wherein the bioactive agent is a cell.

31. The polymeric hydrogel of claim 28, wherein the bioactive agent is a stem cell.

32. The polymeric hydrogel of claim 28, wherein the bioactive agent is a protein or peptide.

33. The polymeric hydrogel of claim 28, wherein the bioactive agent is a polynucleotide.

34. The polymeric hydrogel of claim 28, wherein the bioactive agent is a pharmaceutical agent.

35. The polymeric hydrogel of claim 28, wherein the bioactive agent is an anti-inflammatory agent, an anti-fibrotic agent, or an anti-proliferative agent.

38. The polymeric hydrogel of claim 28, wherein bioactive agent is encapsulated in a nanoparticle or microparticle.

68. A method of augmenting, repairing, or replacing soft tissue, the method comprising:

administering a polymeric hydrogel of claim 1 to the soft tissue of a subject.

73. A method of augmenting the phonatory mucosa of a vocal cord, the method comprising:

administering the polymeric hydrogel of claim 1 into a space created in the superficial lamina propria or phonatory epithelium of the vocal cord of a subject.

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30. (canceled)

36-37. -37. (canceled)

39. A method of preparing a polymeric hydrogel comprising steps of:

providing a first cross-linkable derivative of a polymer;

providing a second water soluble polymer;

contacting the first cross-linkable derivative of a polymer with the second water-soluble polymer; and

cross-linking the first cross-linkable derivative of polymer in the presence of the second water-soluble polymer to form a polymeric hydrogel;

wherein the hydrogel has an elastic shear modulus ranging from about 15 Pa to about 35 Pa.

40-67. -67. (canceled)

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74-90. -90. (canceled)