Hydrogels for vocal cord and soft tissue augmentation and repair

• US 9,216,188 B2
• Filed: 09/03/2009
• Issued: 12/22/2015
• Est. Priority Date: 09/04/2008
• Status: Active Grant

• Current Assignee: General Hospital Corporation, Massachusetts Institute of Technology
• Original Assignee: Massachusetts Institute of Technology, The General Hospital Corporation (Mass General Brigham, Inc.)
• Inventors: Zeitels, Steven M., Hillman, Robert Edward, Karajanagi, Sandeep Sidram, Langer, Robert S.
• Primary Examiner(s): SINGH, ANOOP KUMAR
• Application Number:
  US12/553,800
• Publication Number:
  US 20100055184A1
• Time in Patent Office: 2,301 Days
• US Class Current: 1/1
• 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 method of treating a subject having phonatory mucosa with decreased pliability causing diminished functional vibratory capacity and diminished phonation, the method comprising

locating a phonatory mucosa with diminished functional vibratory capacity in the subject;

and

injecting into the phonatory mucosa a hydrogel material that comprises an elastic shear modulus ranging from about 15 to about 121 Pa measured at a frequency of 10 Hz in an amount effective to increase pliability of the phonatory mucosa sufficiently to allow the phonatory mucosa to vibrate and improve phonation;

wherein the hydrogel material comprises a first cross-linked synthetic polymer and a second polymer,

wherein the first cross-linked synthetic polymer comprises a cross-linked form of polyethylene glycol, polylysine, polyvinyl alcohol, or hyaluronic acid, and

wherein the second polymer is selected from the group consisting of polyethers, polyacrylates, polyesters, polyanhydrides, polyols, polypeptides, polyvinyl alcohols, proteins, polysaccharides, gelatins, elastins, collagens, celluloses, methylcelluloses, hyaluronic acid, dextrans, alginates, and derivatives thereof, and

wherein the hydrogel material comprises an interpenetrating or semi-interpenetrating network of the first and second polymers.

2. The method of claim 1, wherein the phonatory mucosa is a part of a vocal cord of the subject.

3. The method of claim 2, wherein the hydrogel material is injected into a superficial lamina propria of the phonatory mucosa.

4. The method of claim 1, wherein the phonatory mucosa is part of the larynx.

5. The method of claim 1, wherein a superficial lamina propria is missing from the phonatory mucosa.

6. The method of claim 1, wherein the hydrogel material comprises crosslinked polyethylene glycol diacrylate (PEG-DA) and polyethylene glycol (PEG) in a ratio of about 30:

70.

7. The method of claim 1, wherein the hydrogel material has an elastic shear modulus ranging from about 15 to about 35 Pa measured at a frequency of 10 Hz.

8. The method of claim 1, wherein the hydrogel material has an elastic shear modulus ranging from about 20 to about 30 Pa measured at a frequency of 10 Hz.

9. The method of claim 1, wherein the hydrogel material has an elastic shear modulus ranging from about 21 to about 25 Pa measured at a frequency of 10 Hz.

10. The method of claim 1, wherein the first cross-linked synthetic polymer comprises an acrylated polymer or a methacrylated polymer of polyethylene glycol, polylysine, polyvinyl alcohol, or hyaluronic acid.

11. The method of claim 1, wherein

The first cross-linked synthetic polymer comprises polyethylene glycol diacrylate (PEG-DA);

and

the second polymer is selected from the group consisting of polyethylene glycol (PEG), polyols, polyacrylates, polypeptides, poly(lysine), gelatins, elastins, collagens, celluloses, methylcelluloses, polysaccharides, and derivatives thereof.

12. The method of claim 11, wherein the second polymer comprises polyethylene glycol (PEG).

13. The method of claim 12, wherein the molecular weight of the PEG-DA is about 10 to about 20 kDa and the molecular weight of the PEG is about 10 to about 20 kDa.

14. The method of claim 11, wherein the second polymer comprises a polysaccharide.

15. The method of claim 14, wherein the polysaccharide is selected from the group consisting of hyaluronic acids, dextrans, and alginates.

16. The method of claim 11, wherein the second polymer comprises a collagen.

17. The method of claim 1, wherein the

first cross-linked synthetic polymer comprises hyaluronic acid methacrylate;

the second polymer is selected from the group consisting of polyethylene glycol (PEG), polypeptides, hyaluronic acid (HA), dextrans, alginates, gelatins, elastins, collagens, celluloses, methylcelluloses, and derivatives thereof; and

wherein the hydrogel material comprises an interpenetrating network of the polymers.

18. The method of claim 7, wherein the phonatory mucosa is a part of a vocal cord of the subject.

19. The method of claim 18, wherein the hydrogel material is injected into a superficial lamina propria of the phonatory mucosa.

20. The method of claim 7, wherein the phonatory mucosa is part of the larynx.

21. The method of claim 7, wherein the hydrogel material comprises crosslinked polyethylene glycol diacrylate (PEG-DA) and polyethylene glycol (PEG) in a ratio of about 30:

70.

22. The method of claim 7, wherein

the first cross-linked synthetic polymer comprises polyethylene glycol diacrylate (PEG-DA);

and

the second polymer is selected from the group consisting of polyethylene glycol (PEG), polyols, polyacrylates, polypeptides, gelatins, elastins, collagens, celluloses, methylcelluloses, polysaccharides, and derivatives thereof.

23. The method of claim 7, wherein the

the first cross-linked synthetic polymer comprises hyaluronic acid methacrylate;

and

the second polymer is selected from the group consisting of polyethylene glycol (PEG), polypeptides, hyaluronic acid (HA), dextrans, alginates, gelatins, elastins, collagens, celluloses, methylcelluloses, and derivatives thereof.