DERMAL FILLERS COMPRISING SILK FIBROIN HYDROGELS AND USES THEREOF
The present specification provides compositions useful as dermal fillers and methods using such compositions to treat a condition of skin.
1 . A composition comprising a gel phase, the gel phase including
a) hydrogel particles comprising a substantially sericin-depleted silk fibroin and an amphiphilic peptide; and
b) hydrogel particles comprising a matrix polymerand,
2 . The composition of claim 1 , wherein the silk fibroin hydrogel particles comprises about 1% (w/v) to about 10% (w/v) of silk fibroin.
3 . The composition of claim 1 , wherein the final concentration of the silk fibroin is from about 3 mg/g to about 30 mg/g.
4 . The composition of claim 1 , wherein the amphiphilic peptide comprising a RGD motif or a non-RDG integrin.
5 . The composition of claim 3 , wherein the amphiphilic peptide is 23 RGD.
6 . The composition of claim 1 , wherein the amphiphilic peptide comprises of a tail region, followed by a spacer region and finally a RGD motif.
7 . The composition of claim 1 , wherein the silk fibroin hydrogel particles comprises a molar ratio of 1:10 to 10:1 moles of the amphiphilic peptide per mole of the silk fibroin.
8 . The composition of claim 6 , wherein the silk fibroin hydrogel particles comprises a molar ratio of 3:1 moles of the amphiphilic peptide per mole of the silk fibroin.
9 . The composition of claim 1 , wherein the silk fibroin hydrogel particles comprises a protein structure having a β-sheet conformation of at least 80%.
10 . The composition of claim 1 , wherein the silk fibroin hydrogel particles comprises a protein structure having a β-sheet conformation of at least 50%.
11 . The composition of claim 1 , wherein the silk fibroin hydrogel particles comprises a protein structure having a β-sheet conformation of at least 20%.
12 . The composition of claim 1 , wherein the silk fibroin hydrogel particles comprises a protein structure having an α-helical and random coil conformation of at most 20%.
13 . The composition of claim 1 , wherein the silk fibroin hydrogel particles further comprise a synthetic molecule having the formula: (molecule X) n —(spacer peptide) 0-300 −(five-amino-acid peptide tail) is conjugated to the silk fibroin.
14 . The composition of claim 1 , wherein the matrix polymer is a glycosaminoglycan, a lubricin, a polysaccharide, or any combination thereof.
15 . The composition of claim 14 , wherein the glycosaminoglycan is a chondroitin sulfate, a dermatan sulfate, a keratan sulfate, a heperan sulfate, a hyaluronan, or any combination thereof.
16 . The composition of claim 14 , wherein the polysaccharide is a dextran, a dextrin, a starch, a hetastarch, a glycogen, a polyvinyl acetate, a polyvinyl pyrrolidone, a polyethylene glycol, a polyethylene imine, a cellulose, a methyl cellulose, a carboxymethyl cellulose, a hydroxyethyl cellulose, a hydroxypropyl cellulose, a hydroxyethyl methyl cellulose, a hydroxypropyl methyl cellulose, or any combination thereof.
17 . The composition of claim 1 , wherein the matrix polymer is crosslinked.
18 . The composition of claim 17 , wherein the crosslinked matrix polymer has a degree of crosslinking of at least 1%.
19 . The composition of claim 17 , wherein the crosslinked matrix polymer has a degree of crosslinking of at most 17%.
20 . The composition of claim 17 , wherein the crosslinked matrix polymer has a degree of crosslinking of about 1% to about 17%.
21 . The composition of claim 1 , wherein the uncrosslinked matrix polymer represents about 90% or more by weight of the total matrix polymer present in the composition.
22 . The composition of claim 1 , wherein the final concentration of the matrix polymer is from about 12 mg/g to about 22.8 mg/g.
23 . The composition of claim 1 , wherein the silk fibroin hydrogel particles and matrix polymer hydrogel particles have a cross-sectional area from about 0.1 μm 2 to about 1000 μm 2 .
24 . The composition of claim 1 , wherein the silk fibroin hydrogel particles and matrix polymer hydrogel particles have a cross-sectional area from about 0.1 μm 2 to about 10 μm 2 .
25 . The composition of claim 1 , wherein the silk fibroin hydrogel particles and matrix polymer hydrogel particles have a cross-sectional area from about 20 μm 2 to about 50 μm 2 .
26 . The composition of claim 1 , wherein the composition further comprises a carrier phase.
27 . The composition of claim 26 , wherein the carrier phase comprises saline.
28 . The composition of claim 26 , wherein the carrier phase comprises a surfactant solution.
29 . The composition of claim 26 , wherein the gel phase is 50% to 99% of the total formulation volume, the remainder being a carrier solution.
30 . The composition of claim 29 , wherein the gel phase is 75% of the total formulation volume, the remainder being a carrier solution.
31 . The composition of claim 1 , wherein the composition further comprising lidocaine.
32 . The composition of claim 1 , wherein, upon injection, the hydrogel particles remains substantially at the injection site for one month to eighteen months.
33 . A composition comprising a gel phase, the gel phase including hydrogel particles comprising a substantially sericin-depleted silk fibroin and a matrix polymer.
34 . The composition of claim 33 , wherein the matrix polymer is a glycosaminoglycan, a lubricin, a polysaccharide, or any combination thereof.
35 . The composition of claim 34 , wherein the glycosaminoglycan is a chondroitin sulfate, a dermatan sulfate, a keratan sulfate, a heperan sulfate, a hyaluronan, or any combination thereof.
36 . The composition of claim 34 , wherein the polysaccharide is a dextran, a dextrin, a starch, a hetastarch, a glycogen, a polyvinyl acetate, a polyvinyl pyrrolidone, a polyethylene glycol, a polyethylene imine, a cellulose, a methyl cellulose, a carboxymethyl cellulose, a hydroxyethyl cellulose, a hydroxypropyl cellulose, a hydroxyethyl methyl cellulose, a hydroxypropyl methyl cellulose, or any combination thereof.
37 . The composition of claim 33 , wherein the matrix polymer is crosslinked.
38 . The composition of claim 33 , wherein the crosslinked matrix polymer has a degree of crosslinking of at least 1%.
39 . The composition of claim 33 , wherein the crosslinked matrix polymer has a degree of crosslinking of at most 17%.
40 . The composition of claim 33 , wherein the crosslinked matrix polymer has a degree of crosslinking of about 1% to about 17%.
41 . The composition of claim 33 , wherein the uncrosslinked matrix polymer represents about 90% or more by weight of the total matrix polymer present in the composition.
42 . The composition of claim 33 , wherein the final concentration of the matrix polymer is from about 12 mg/g to about 22.8 mg/g.
43 . The composition of claim 33 , wherein the hydrogel particles comprises about 1% (w/v) to about 10% (w/v) of silk fibroin.
44 . The composition of claim 33 , wherein the final concentration of the silk fibroin is from about 3 mg/g to about 30 mg/g.
45 . The composition of claim 33 , wherein the hydrogel particles further comprise an amphiphilic peptide.
46 . The composition of claim 33 , wherein the silk fibroin hydrogel particles and matrix polymer hydrogel particles have a cross-sectional area from about 0.1 μm 2 to about 1000 μm 2 .
47 . The composition of claim 33 , wherein the silk fibroin hydrogel particles and matrix polymer hydrogel particles have a cross-sectional area from about 0.1 μm 2 to about 10 μm 2 .
48 . The composition of claim 33 , wherein the silk fibroin hydrogel particles and matrix polymer hydrogel particles have a cross-sectional area from about 20 μm 2 to about 50 μm 2 .
49 . The composition of claim 33 , wherein the composition further comprises a carrier phase.
50 . The composition of claim 49 , wherein the carrier phase comprises saline.
51 . The composition of claim 49 , wherein the carrier phase comprises a surfactant solution.
52 . The composition of claim 49 , wherein the gel phase is 50% to 99% of the total formulation volume, the remainder being a carrier solution.
53 . The composition of claim 52 , wherein the gel phase is 75% of the total formulation volume, the remainder being a carrier solution.
54 . The composition of claim 33 , wherein the composition further comprising lidocaine.
55 . The composition of claim 33 , wherein, upon injection, the hydrogel particles remains substantially at the injection site for one month to eighteen months.
56 . A method of treating a soft tissue condition in an individual in need thereof, the method comprising the step of administering a composition of claim 1 into a skin region of the individual, wherein the administration improves the condition.
57 . The method of claim 56 , wherein the soft tissue condition is a breast tissue condition, a facial tissue condition, a neck condition, a skin condition, an upper arm condition, a lower arm condition, a hand condition, a shoulder condition, a back condition, a torso including abdominal condition, a buttock condition, an upper leg condition, a lower leg condition including calf condition, a foot condition including plantar fat pad condition, an eye condition, a genital condition, or a condition effecting another body part, region or area.
58 . The method of claim 57 , wherein the breast tissue condition is a breast imperfection, a breast defect, a breast augmentation, or a breast reconstruction.
59 . The method of claim 57 , wherein the facial tissue condition is a facial imperfection, a facial defect, a facial augmentation, or a facial reconstruction.
60 . The method of claim 57 , wherein the facial tissue condition is a dermal divot, a sunken check, a thin lip, a nasal imperfection or defect, a retro-orbital imperfection or defect, a facial fold, a facial line, a facial wrinkle, or other size, shape or contour imperfection or defect of the face.
61 . The method of claim 60 , wherein the wrinkle is a glabellar line, a nasolabial line, a perioral line, or a marionette line.
62 . The method of claim 57 , wherein the facial tissue condition is skin dehydration, a lack of skin elasticity, skin roughness, a lack of skin tautness, a skin stretch line or mark, or skin paleness.
63 . The method of claim 56 , wherein the soft tissue condition is Parry-Romberg syndrome or lupus erythematosus profundus.
64 . The method of claim 56 , wherein the soft tissue condition is urinary incontinence, fecal incontinence, or gastroesophageal reflux disease (GERD).
65 . A method of treating a soft tissue condition in an individual in need thereof, the method comprising the step of administering a composition of claim 33 into a skin region of the individual, wherein the administration improves the condition.
66 . The method of claim 65 , wherein the soft tissue condition is a breast tissue condition, a facial tissue condition, a neck condition, a skin condition, an upper arm condition, a lower arm condition, a hand condition, a shoulder condition, a back condition, a torso including abdominal condition, a buttock condition, an upper leg condition, a lower leg condition including calf condition, a foot condition including plantar fat pad condition, an eye condition, a genital condition, or a condition effecting another body part, region or area.
67 . The method of claim 66 , wherein the breast tissue condition is a breast imperfection, a breast defect, a breast augmentation, or a breast reconstruction.
68 . The method of claim 66 , wherein the facial tissue condition is a facial imperfection, a facial defect, a facial augmentation, or a facial reconstruction.
69 . The method of claim 66 , wherein the facial tissue condition is a dermal divot, a sunken check, a thin lip, a nasal imperfection or defect, a retro-orbital imperfection or defect, a facial fold, a facial line, a facial wrinkle, or other size, shape or contour imperfection or defect of the face.
70 . The method of claim 69 , wherein the wrinkle is a glabellar line, a nasolabial line, a perioral line, or a marionette line.
71 . The method of claim 66 , wherein the facial tissue condition is skin dehydration, a lack of skin elasticity, skin roughness, a lack of skin tautness, a skin stretch line or mark, or skin paleness.
72 . The method of claim 65 , wherein the soft tissue condition is Parry-Romberg syndrome or lupus erythematosus profundus.
73 . The method of claim 65 , wherein the soft tissue condition is urinary incontinence, fecal incontinence, or gastroesophageal reflux disease (GERD).