Hydrogel compositions useful for the sustained release of macromolecules and methods of making same
First Claim
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1. A method for preparing a homogenous porous hydrogel for sustained delivery of drugs, said method comprising the steps of:
- (a) forming a polymerizable liquid mixture containing about 60 weight percent to about 95 weight percent polymerizable comonomers, wherein at least one of the comonomers is hydrophilic, and sufficient amounts of a crosslinker and a liquid diffusion enhancer which is miscible with the comonomers, to yield a homogenous porous copolymer having the equilibrium water content (EWC) value in the range from about 20% to about 85%;
wherein the polymerizable liquid mixture contains about 1 weight percent to about 50 weight percent diffusion enhancer selected from the group consisting of tetrahydrofurfuryl alcohol, cyclohexyl alcohol, acetone, ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol monobutyl ether, glyceryl isopropylidene ether dioxane, tetrahydrofuran, ethyl acetate, and dimethyl sulfoxide; and
(b) forming a hydrogel useful for sustained release of macromolecules consisting of the homogenous porous copolymer.
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Abstract
A method of producing a homogenous porous hydrogel useful for drug delivery is described. The pores of the hydrogel are created by diffusion enhancers to facilitate sustained delivery of macromolecules. Also described are various articles produced from these hydrogels.
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Citations
26 Claims
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1. A method for preparing a homogenous porous hydrogel for sustained delivery of drugs, said method comprising the steps of:
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(a) forming a polymerizable liquid mixture containing about 60 weight percent to about 95 weight percent polymerizable comonomers, wherein at least one of the comonomers is hydrophilic, and sufficient amounts of a crosslinker and a liquid diffusion enhancer which is miscible with the comonomers, to yield a homogenous porous copolymer having the equilibrium water content (EWC) value in the range from about 20% to about 85%;
wherein the polymerizable liquid mixture contains about 1 weight percent to about 50 weight percent diffusion enhancer selected from the group consisting of tetrahydrofurfuryl alcohol, cyclohexyl alcohol, acetone, ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol monobutyl ether, glyceryl isopropylidene ether dioxane, tetrahydrofuran, ethyl acetate, and dimethyl sulfoxide; and
(b) forming a hydrogel useful for sustained release of macromolecules consisting of the homogenous porous copolymer. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13)
(a) introducing active agent, and optionally, a pharmaceutically acceptable carrier, into the reservoir of the hydrogel prepared according to claim 1, in an amount sufficient to provide extended sustained release of the active agent;
(b) introducing at least one polymerizable liquid monomer into the upper portion of the reservoir in an amount to fill the reservoir, said liquid monomer having an equilibrium water content value in its polymerized state which exceeds the equilibrium water content value of the cartridge; and
(c) polymerizing said monomer to seal the opening of the reservoir with a plug of water-swellable, water-insoluble polymer to form a delivery device which provides a predetermined release of the active agent.
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13. A delivery device produced according to the method of claim 12.
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14. A method for preparing a homogenous porous hydrogel article for sustained delivery of drugs, said method comprising the steps of:
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(a) forming a polymerizable liquid mixture containing about 60 weight percent to about 95 weight percent comonomers comprising 2-hydroxyethyl methacrylate (HEMA), about 10 to about 50 weight percent of a liquid diffusion enhancer which is miscible with the comonomers, and a crosslinker;
(b) polymerizing the polymerizable liquid mixture into a xerogel which upon exposure to water forms a hydrogel consisting of a homogenous copolymer having pores spaced regularly throughout, wherein said pores are each about 10 Angstroms to about 1.0 microns in diameter and contain the liquid diffusion enhancer, said hydrogel having the equilibrium water content (EWC) value in the range from about 35% to about 85%, wherein said hydrogel is in the form of a cartridge having walls of uniform thickness which define a reservoir, wherein said article is useful for sustained release of macromolecules having a molecular weight of up to 100,000. - View Dependent Claims (15, 16, 17, 18, 19, 20, 21, 22, 23)
(a) introducing active agent, and optionally, a pharmaceutically acceptable carrier, into the reservoir of the hydrogel prepared according to claim 14, in an amount sufficient to provide extended sustained release of the active agent;
(b) introducing at least one polymerizable liquid monomer into the upper portion of the reservoir in an amount to fill the reservoir, said liquid monomer having an equilibrium water content value in its polymerized state which exceeds the equilibrium water content value of the cartridge; and
(c) polymerizing said monomer to seal the opening of the reservoir with a plug of water-swellable, water-insoluble polymer to form a delivery device which provides a predetermined release of the active agent.
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20. A delivery device produced according to the method of claim 19.
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21. The method according to claim 14, wherein said polymerizable liquid mixture contains about 60 weight percent HEMA, about 20 weight percent dimethylacrylamide, and a diffusion enhancer comprising about 20 weight percent isopropyl alcohol.
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22. The method according to claim 14, wherein said polymerizable liquid mixture contains about 77 weight percent HEMA, about 2 weight percent methylacrylamide, and about 20% polyethylene glycol.
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23. The method according to claim 14, wherein said polymerizable liquid mixture contains about 80 weight percent HEMA and a diffusion enhancer comprising about 20 weight percent polyethylene glycol.
- 24. A hydrogel comprising a homogeneous copolymer matrix having pores spaced regularly throughout the matrix, wherein said pores are each about 10 Angstroms to about 1.0 microns in diameter and contain a liquid diffusion enhancer, said liquid diffusion enhancer consisting of about 10 to about 50% by weight of the total weight of the hydrogel prior to exposure to water, wherein said hydrogel has an equilibrium water content (EWC) in the range of about 35% to about 85%.
Specification