High molecular weight esthetic compositions
Described are high molecular weight glycosaminoglycan (GAG) hydrogel compositions comprising GAGs covalently crosslinked with a carbohydrate crosslinker, and methods of making the high molecular weight GAG hydrogel compositions. Further described are methods of using the high molecular weight glycosaminoglycan (GAG) hydrogel compositions for reparative or plastic surgery, esthetic dermatology, facial contouring, body contouring, and gingival augmentation.
1 . A hydrogel product comprising a hyaluronic acid hydrogel crosslinked by amide bonds, obtained by a method comprising:
crosslinking a hyaluronic acid (HA) having a molecular weight of 2.1 to 10 MDa with a crosslinker, to obtain the hyaluronic acid hydrogel crosslinked by amide bonds, wherein:
the crosslinker is a di- or multinucleophile functional crosslinker comprising a spacer group selected from the group consisting of di-, tri-, tetra-, and oligosaccharides;
a concentration of the HA is between 2% to 10% (w/w); and
a molar ratio of the crosslinker to the HA is less than or equal to 2 mol % per HA disaccharide.
2 . The hydrogel product according to claim 1 , wherein the spacer group is trehalose.
3 . The hydrogel product according to claim 1 , wherein the di- or multinucleophile functional crosslinker is diaminotrehalose (DATH).
4 . The hydrogel product according to claim 1 , wherein the HA has a molecular weight of 2.1-3.5 MDa.
5 . The hydrogel product according to claim 1 , wherein:
the HA has a molecular weight of 2.1-3.5 MDa;
the crosslinker is diaminotrehalose (DATH); and
during the crosslinking, the concentration of HA is between 3-5% (w/w) and the molar ratio of DATH to HA is between 0.9-1.1 mol % per HA disaccharide.
6 . The hydrogel product according to claim 1 , wherein the hydrogel product is essentially free of synthetic non-carbohydrate structures or linkers.
7 . The hydrogel product according to claim 1 , wherein the crosslinked HA molecules have an apparent molecular weight (Mwapp) above 1.0 MDa.
8 . The hydrogel product according to claim 1 , wherein the crosslinked HA molecules have an apparent molecular weight (Mwapp) of 2.1 MDa or above.
9 . The hydrogel product according to claim 1 , wherein the hydrogel product has a HA concentration of 10-45 mg/mL.
10 . The hydrogel product according to claim 1 , wherein the crosslinking comprises:
(1) providing a solution of the HA molecules;
(2) activating carboxyl groups on the HA molecules with a coupling agent to form activated HA molecules;
(3) crosslinking the activated HA molecules via their activated carboxyl groups using a di- or multinucleophile functional crosslinker to obtain a HA hydrogel crosslinked by amide bonds.
11 . The hydrogel product according to claim 1 , wherein the concentration of the HA is between 3-5% (w/w) during the crosslinking.
12 . The hydrogel product according to claim 1 , wherein the molar ratio of crosslinker to HA is between 0.9-1.1 mol % per HA disaccharide during the crosslinking.
13 . The hydrogel product according to claim 1 , further comprising a local anesthetic.
14 . The hydrogel product according to claim 13 , wherein the local anesthetic comprises lidocaine.
15 . A syringe comprising the hydrogel product according to claim 1 .
16 . A method of performing a reparative or esthetic dermatologic treatment, the method comprising:
injecting a subject with the hydrogel product of claim 1 .
17 . The method of claim 16 , wherein the injecting is performed as a subdermal, intradermal, subcutaneous, intramuscular, submuscular, or intragingival injection.
18 . The method of claim 16 , wherein the reparative or esthetic dermatologic treatment comprises dermal filling.
19 . The method of claim 18 , wherein the injection is administered to fill lines, fine lines, wrinkles, or skin cracks.
20 . The method of claim 19 , wherein the lines, fine lines, wrinkles, or skin cracks are located on the face, neck, hands, feet, knees, or elbows.