Flowable hydrogels for control of cell in-migration
AssigneeIncept, LLC
InventorsPeter Jarrett, Rami El Hayek, Michael Bassett, James Biggins
Life of this patent
Estimating the term…
Abstract
Materials and methods of treating an eye with a hydrogel formed on the eye. Embodiments are provided that include post-keratectomy bandages.
Claims33
A method of treating a de-epithelialized zone on a corneal surface of an eye and having a depth of about 10 to about 200 μm comprising:
- applying a volume of a flowable aqueous solution of a hydrogel precursor substantially only in the zone on the eye and filling the zone with the precursor spontaneously crosslinking to form a covalently crosslinked hydrolytically degradable hydrogel that fills and remains substantially only within the de-epithelialized zone, and that has a height that is not more than about 200 μm above eye tissue adjacent to the de-epithelialized zone.
A system for treating a de-epithelialized zone on a corneal surface of an eye and having a depth of about 10 to about 200 μm comprising:
- a volume of a flowable aqueous solution of hydrogel precursors that has a pH of between about 6 and about 8,
- with the precursors spontaneously crosslinking to form a covalently crosslinked hydrolytically degradable hydrogel that has a solids content of between about 3% and about 15% w/w, wherein the hydrogel is fully degraded in vitro in aqueous physiological saline within no more than about 10 days after initial formation,
- wherein the precursors comprise a first precursor that comprises a succinimidyl ester functional group and a second precursor that comprises a second functional group, with the succinimidyl ester functional group and the second functional group reacting with each other to form covalent bonds to thereby form the covalently crosslinked hydrogel within about 10 to about 100 seconds of bringing the first and second precursors together in the solution,
- with one of the precursors comprising a hydrophilic polymer with a molecular weight of at least about 3,000 and the other precursor having a molecular weight of less than about 1,000,
- wherein, over a period of about 2 days beginning at formation of the hydrogel, disappearance of the hydrogel on a surface of an eye progresses from outer edges of the hydrogel to the center of the hydrogel, with remaining persistent portions of the hydrogel blocking migration of epithelial cells, and
- an applicator comprising a delivery surface sized to pick up no more than about 1 to about 100 μl of the volume and transfer the solution to a surface of an eye.
A method of reducing pain following photorefractive keratectomy that creates a de-epithelialized zone on a corneal surface comprising:
- applying a volume of a flowable aqueous solution of a hydrogel precursor substantially only in the zone on the eye and filling the zone, with the precursor spontaneously crosslinking to form a covalently crosslinked hydrolytically degradable hydrogel that fills and remains substantially only within the de-epithelialized zone, and that has a height that is not more than about 200 μm above eye tissue adjacent to the de-epithelialized zone, with the hydrogel providing for re-epithlelialization of the cornea in a period of days that is no more than a period of days for a eye that undergoes the same treatment but does not receive the hydrogel.
A kit of medical hydrogel components in a single housing that comprises:
- a tray comprising a well,
- a first hydrogel precursor in a dry form immobilized in a first deposit at a first location in the well,
- a second hydrogel precursor in a dry form immobilized in a second deposit at a second location in the well,
- water or an aqueous solution in a dropper,
- a mixing rod, and
- an applicator comprising a delivery surface sized to hold a volume of no more than about 100 μl of a liquid volume and proportioned for manual transfer of the volume to a surface of an eye;
- wherein the first precursor comprises first functional groups and the second precursor comprises second functional groups, with the first and the second functional groups chemically reacting with each other to form covalent bonds to thereby crosslink the precursors into a hydrogel.
A method of treating a patient by application of a hydrogel bandage to a cornea comprising:
- providing a first hydrogel precursor in a dry form immobilized in a first deposit at a first location in a well,
- providing a second hydrogel precursor in a dry form immobilized in a second deposit at a second location in the well,
- adding less than 1000 μl of aqueous solution to one or more of the deposits;
- mixing the deposits together with a mixing rod to form a mixture, introducing a delivery surface to the mixture and recovering a volume between about 1 and about 100 μl of the mixture transferring at between 1 and 100 μl of the volume from the delivery surface to the cornea,
- with the mixture forming a covalently crosslinked hydrogel on the cornea.
A method of treating a de-epithelialized zone on a corneal surface of an eye comprising:
- applying a first masking layer comprising a degradable material to the zone on the eye, with a plurality of tie point locations in the zone being free of contact with the first masking layer,
- applying a volume of a flowable aqueous solution of a hydrogel precursor over the first masking layer, with the precursor spontaneously crosslinking to form a covalently crosslinked hydrolytically degradable hydrogel to thereby form a second layer that contacts the first masking layer and adheres to the zone at the plurality of tie point locations.
Dependencies are inferred from the claim text.