# US 2014/0193466 A1 · Silk compositions and methods of using same

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- Number: US 2014/0193466 A1
- Document ID: US20140193466A1
- Status: Published application
- Kind: A1
- Application number: 14/124,836
- Filed: 2012-06-07
- Published: 2014-07-10
- Earliest claimed: 2011-06-07
- Assignees: Cornell University
- Applicants: Cornell University
- Inventors: Brian D Lawrence; Alejandro Navas; Mark I. Rosenblatt
- Web page: https://patentgrep.com/patent/US20140193466A1

## CPC

- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61K 9/0051: {Ocular inserts or implants}
- A61K 9/70: Web, sheet or filament bases {; Films; Fibres of the matrix type containing drug (hollow drug-filled fibres A61K9/0092)}
- A61K 9/7007: {Drug-containing films, membranes or sheets (A61K9/0041, A61K9/0043, A61K9/006, A61K9/0063 take precedence)}
- A61K 38/1767: {from invertebrates}
- Y10T 428/24628: Nonplanar uniform thickness material
- Y10T 428/24802: Discontinuous or differential coating, impregnation or bond [e.g., artwork, printing, retouched photograph, etc.]
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- Y10T: TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION

## Abstract

The present invention provides for silk-derived compositions for treating a wide variety of ocular conditions. The composition is produced by processing the silk cocoon into a water-based solution (i.e., a dissolved silk), which is then cast into a film. The film may be transparent to visible light, and curved in shape for easy application to the ocular surface. The silk film may either self-adhere or be sutured to cover the wound. The degradation time of the film may range from 1 minute to 24 hours, or from 2 hours to 20 hours. The present compositions can help regenerate damaged corneal tissue, thus promoting healing.

## Claims

### Claim 1

A degradable composition comprising fibroin, wherein fibroin comprises β-sheet conformation ranging from about 0% to about 30%, and wherein, upon contacting with a body fluid, less than about 20% (w/w) of the composition degrades after about 1 minute, and greater than about 80% (w/w) of the composition degrades after about 24 hours.

### Claim 2

A degradable composition comprising fibroin, wherein the composition comprises about 1% (w/w) to about 12% (w/w) water, and wherein, upon contacting with a body fluid, less than about 20% (w/w) of the composition degrades after about 1 minute, and greater than about 80% (w/w) of the composition degrades after about 24 hours.

### Claim 3

A degradable composition comprising fibroin, wherein the composition comprises about 1% (w/w) to about 12% (w/w) water, wherein fibroin comprises β-sheet conformation ranging from about 0% to about 30%, and wherein, upon contacting with a body fluid, less than about 20% (w/w) of the composition degrades after about 1 minute, and greater than about 80% (w/w) of the composition degrades after about 24 hours.

### Claim 4 (depends on 1)

The composition of claim 1, wherein fibroin comprises β-sheet conformation ranging from about 5% to about 15%.

### Claim 5 (depends on 1)

The composition of claim 1, wherein fibroin comprises α-helical conformation ranging from about 1% to about 80%.

### Claim 6 (depends on 1)

The composition of claim 1, wherein the composition comprises about 5% (w/w) to about 10% (w/w) water.

### Claim 7 (depends on 1)

The composition of claim 1, wherein upon contacting with a body fluid, less than about 20% (w/w) of the composition degrades after about 2 hours, and greater than about 80% (w/w) of the composition degrades after about 20 hours.

### Claim 8 (depends on 1)

The composition of claim 1, wherein upon contacting with a body fluid, less than about 10% (w/w) of the composition degrades after about 1 minute, and greater than about 90% (w/w) of the composition degrades after about 24 hours.

### Claim 9 (depends on 1)

The composition of claim 1, wherein upon contacting with a body fluid, greater than about 80% (w/w) of the composition degrades after about 10 hours.

### Claim 10 (depends on 1)

The composition of claim 1, wherein upon contacting with a body fluid, greater than about 90% (w/w) of the composition degrades after about 10 hours.

### Claim 11 (depends on 1)

The composition of claim 1, wherein fibroin is obtained from silkworm silk, spider silk or genetically engineered silk.

### Claim 12 (depends on 11)

The composition of claim 11, wherein the silkworm silk is obtained from Bombyx mori.

### Claim 13 (depends on 11)

The composition of claim 11, wherein the spider silk is obtained from Nephila clavipes.

### Claim 14 (depends on 1)

The composition of claim 1, wherein fibroin is in an amount ranging from about 80% to 100%.

### Claim 15 (depends on 1)

The composition of claim 1, wherein the composition is transparent.

### Claim 16 (depends on 1)

The composition of claim 1, wherein the composition is opaque.

### Claim 17 (depends on 1)

The composition of claim 1, wherein the composition is a film, a fiber, a foam, a hydrogel, a matrix, a mesh, a three-dimensional scaffold, a microparticle, a nanoparticle or a mat.

### Claim 18 (depends on 17)

The composition of claim 17, wherein the composition is a film.

### Claim 19 (depends on 18)

The composition of claim 18, wherein the film has a curved surface.

### Claim 20 (depends on 18)

The composition of claim 18, wherein the film has a flat surface.

### Claim 21 (depends on 18)

The composition of claim 18, wherein the film has a thickness ranging from about 1 μm to about 500 μm.

### Claim 22 (depends on 21)

The composition of claim 21, wherein the film has a thickness ranging from about 10 μm to about 200 μm.

### Claim 23 (depends on 22)

The composition of claim 22, wherein the film has a thickness ranging from about 50 μm to about 100 μm.

### Claim 24 (depends on 18)

The composition of claim 18, wherein the film has a tensile strength ranging from about 1 to about 200 MPa.

### Claim 25 (depends on 18)

The composition of claim 18, wherein the film has a tensile modulus ranging from about 0.1 to about 5 GPa.

### Claim 26 (depends on 18)

The composition of claim 18, wherein the film is surface-patterned.

### Claim 27 (depends on 18)

The composition of claim 18, wherein the film is smooth.

### Claim 28 (depends on 1)

The composition of claim 1, further comprising a pharmacologically and/or biologically active agent.

### Claim 29 (depends on 28)

The composition of claim 28, wherein the pharmacologically or biologically active agent is chosen from proteins, peptides, nucleic acids, carbohydrates, glycoproteins, lipoproteins, RNA/protein composites, cells, nucleic acid analogues, nucleotides, oligonucleotides, peptide nucleic acids, aptamers, viruses, small molecules, or combinations thereof.

### Claim 30 (depends on 28)

The composition of claim 28, wherein the pharmacologically or biologically active agent is a cell.

### Claim 31 (depends on 30)

The composition of claim 30, wherein the cell is chosen from epithelial cells, stem cells, smooth muscle cells, skeletal muscle cells, cardiac muscle cells, endothelial cells, urothelial cells, fibroblasts, myoblasts, chondrocytes, chondroblasts, osteoblasts, osteoclasts, keratinocytes, hepatocytes, bile duct cells, pancreatic islet cells, thyroid cells, parathyroid cells, adrenal cells, hypothalamic cells, pituitary cells, ovarian cells, testicular cells, salivary gland cells, adipocytes, precursor cells and mixture thereof.

### Claim 32 (depends on 28)

The composition of claim 28, wherein the pharmacologically or biologically active agent is mixed with the composition.

### Claim 33 (depends on 28)

The composition of claim 28, wherein the pharmacologically or biologically active agent is coated on the composition.

### Claim 34

A method for treating an ocular condition in a subject comprising applying a degradable composition to an eye of the subject, wherein the composition comprises fibroin, wherein fibroin comprises β-sheet conformation ranging from about 0% to about 30%, and wherein, upon contacting with the eye, less than about 20% (w/w) of the composition degrades after about 1 minute, and greater than about 80% (w/w) of the composition degrades after about 24 hours.

### Claim 35 (depends on 34)

The method of claim 34, wherein upon contacting with the eye, greater than about 80% (w/w) of the composition degrades after about 10 hours.

### Claim 36 (depends on 34)

The method of claim 34, wherein the ocular condition is an ocular surface disorder.

### Claim 37 (depends on 34)

The method of claim 34, wherein the ocular condition is chosen from corneal ulcer, corneal erosion, corneal abrasion, corneal degeneration, corneal perforation, corneal scarring, an epithelial defect, keratoconjunctivitis, idiopathic uveitis, corneal transplantation, dry eye syndrome, age-related macular degeneration (AMD, wet or dry), diabetic eye conditions, blepharitis, glaucoma, ocular hypertension, post-operative eye pain and inflammation, posterior segment neovascularization (PSNV), proliferative vitreoretinopathy (PVR), cytomegalovirus retinitis (CMV), endophthalmitis, choroidal neovascular membranes (CNVM), vascular occlusive diseases, allergic eye disease, tumors, retinitis pigmen-tosa, eye infections, scleritis, ptosis, miosis, eye pain, mydriasis, neuralgia, cicatrizing ocular surface diseases, ocular infections, inflammatory ocular diseases, ocular surface diseases, corneal diseases, retinal diseases, ocular manifestations of systemic diseases, hereditary eye conditions, ocular tumors, increased intraocular pressure, herpetic infections, ptyrigium (scleral tumor), wounds sustained to ocular surface, post-photorefractive keratotomy eye pain and inflammation, thermal or chemical burns to the cornea, scleral wounds, or conjunctival wounds.

### Claim 38 (depends on 34)

The method of claim 34, wherein the ocular condition is caused by aging, an autoimmune condition, trauma, infection, a degenerative disorder (such as keratoconus), endothelial dystrophies, and/or a surgery.

### Claim 39 (depends on 34)

The method of claim 34, wherein the composition is self-adhered or sutured to the eye.

### Claim 40 (depends on 34)

The method of claim 34, wherein the silk fibroin is obtained from silkworm silk, spider silk or genetically engineered silk.

### Claim 41 (depends on 40)

The method of claim 40, wherein the silkworm silk is obtained from Bombyx mori.

### Claim 42 (depends on 40)

The method of claim 40, wherein the spider silk is obtained from Nephila clavipes.

### Claim 43 (depends on 34)

The method of claim 34, wherein the composition is a film, a gel, a hydrogel, an ocular implant, a punctal plug, a contact lens, particles, microparticles, nanoparticles, a mucoadhesive formulation, an in-situ forming gel or film, an iontophoresis formulation, a tablet, a rod, a fiber mat, a fiber, or a patch.

### Claim 44 (depends on 43)

The method of claim 43, wherein the composition is a film.

### Claim 45 (depends on 44)

The method of claim 44, wherein the film has a curved surface.

### Claim 46 (depends on 44)

The method of claim 44, wherein the film has a flat surface.

### Claim 47 (depends on 44)

The method of claim 44, wherein the film has a thickness ranging from about 1 μm to about 500 μm.

### Claim 48 (depends on 34)

The method of claim 34, wherein the composition is transparent.

### Claim 49 (depends on 34)

The method of claim 34, wherein the composition is opaque.