Hyaluronic acid-based gels including lidocaine
AssigneeAllergan, Inc.
InventorPierre F. Lebreton
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Abstract
Disclosed herein are cohesive soft tissue fillers, for example, dermal and subdermal fillers, based on hyaluronic acids and pharmaceutically acceptable salts thereof. In one aspect, hyaluronic acid-based compositions described herein include a therapeutically effective amount of at least one anesthetic agent, for example, lidocaine. The present hyaluronic acid-based compositions including lidocaine have an enhanced stability and cohesivity, relative to conventional compositions including lidocaine, for example when subjected to sterilization techniques or when stored for long periods of time. Methods and processes of preparing such hyaluronic acid-based compositions are also provided.
Claims41
A soft tissue filler composition comprising:
- a hyaluronic acid (HA) component crosslinked with a crosslinking agent selected from the group consisting of 1,4-butanediol diglycidyl ether (BDDE), 1,4-bis(2,3-epoxypropoxy)butane, 1,4-bisglycidyloxybutane, 1,2-bis(2,3-epoxypropoxy)ethylene and 1-(2,3-epoxypropyl)-2,3-epoxycyclohexane, and 1,4-butanediol diglycidyl ether;
- wherein the HA is not crosslinked to a non-HA biopolymer;
- and
- lidocaine combined with said crosslinked HA component;
- wherein the lidocaine is freely released in vivo;
- and
- wherein the composition is sterile.
A method of preparing a soft tissue filler composition, the method comprising the steps of:
- providing a HA component crosslinked with at least one crosslinking agent selected from the group consisting of 1,4-butanediol diglycidyl ether (BDDE), 1,4-bis(2,3-epoxypropoxy)butane, 1,4-bisglycidyloxybutane, 1,2-bis(2,3-epoxypropoxy)ethylene and 1-(2,3-epoxypropyl)-2,3-epoxycyclohexane, and 1,4-butanediol diglycidyl ether or combinations thereof;
- dialyzing the HA component against a phosphate buffer so that the pH is about 7.2;
- adjusting the pH of said HA component from about 7.2 to an adjusted pH of about 7.5 to about 8;
- and
- adding lidocaine HCl to said HA component at said adjusted pH of about 7.5 to about 8 to obtain said soft tissue filler composition.
A cohesive soft tissue filler composition, the composition comprising:
- a hyaluronic acid (HA) component crosslinked with 1,4-butanediol diglycidyl ether (BDDE);
- and
- unbound lidocaine HCI combined with the crosslinked HA component,
- wherein said cohesive soft tissue filler composition has an extrusion force of between about 10 N and about 13 N and has a viscosity of between about 5 Pa*s and about 450 Pa*s after sterilization.
A method of preparing a cohesive HA-based filler composition, the method comprising the steps of:
- providing dry uncrosslinked NaHA material and hydrating said dry uncrosslinked NaHA material in an alkaline solution to obtain an alkaline, uncrosslinked NaHA gel;
- crosslinking said uncrosslinked NaHA gel with 1,4-butanediol diglycidyl ether (BDDE) to form a crosslinked alkaline HA composition with a pH above about 7.5;
- adding a solution containing about lidocaine HCI to said HA component having said adjusted pH above about 7.5 to obtain said HA-based filler composition;
- homogenizing said HA-based filler composition thereby forming a homogenized HA-based filler composition;
- and sterilizing said homogenized HA-based filler composition thereby forming said cohesive HA-based filler composition,
- wherein said cohesive HA-based filler composition has an extrusion force of between about 10 N and about 13 N at an extrusion rate of about 12.5 mm/minute and has a viscosity of between about 5 Pa*s and about 450 Pa*s when measured at about 5 Hz.
A method of adding lidocaine to a crosslinked hyaluronic acid (HA) composition comprising:
- providing a 1,4-butanediol diglycidyl ether (BDDE) crosslinked HA composition having a pH of about 7.2 or lower;
- increasing the pH of the composition to at least about 7.5;
- adding lidocaine to the composition;
- and
- sterilizing the composition by autoclaving the composition.
A composition comprising a crosslinked hyaluronic acid (HA) at a concentration of about 20 mg/mL to about 30 mg/mL and lidocaine at a concentration of about 0.1% to about 5% by weight, wherein the composition has a pH above about 7.5.
A sterile composition comprising a crosslinked hyaluronic acid (HA) at a concentration of about 22 mg/mL and lidocaine at a concentration of about 0.2% to about 1% by weight, wherein the composition is stable during storage under ambient conditions for at least 3 months.
Dependencies are inferred from the claim text.