Extended or continuous wear silicone hydrogel contact lenses for the extended release of comfort molecules

Patent metadata

Field	Value
Publication number	US-9238003-B2
Application number	US-201313765495-A
Country	US
Kind code	B2
Filing date	Feb 12, 2013
Priority date	Feb 4, 2005
Publication date	Jan 19, 2016
Grant date	Jan 19, 2016

Abstract

A drug delivery system is disclosed. The drug delivery system includes a recognitive polymeric hydrogel through which a drug is delivered by contacting biological tissue. The recognitive polymeric hydrogel is formed by using a bio-template, which is a drug or is structurally similar to the drug, functionalized monomers, preferably having complexing sites, and cross-linking monomers, which are copolymerized using a suitable initiator. The complexing sites of the recognitive polymeric hydrogel that is formed preferably mimics receptor sites of a target biological tissue, biological recognition, or biological mechanism of action. The system in accordance with an embodiment of the invention is a contact lens for delivering a drug through contact with an eye.

First claim

What is claimed is:

1. A comfort agent delivery system comprising:
a contact lens, the contact lens comprising a recognitive weakly cross-linked polymeric hydrogel matrix with complexing memory sites that complex a comfort agent and release the comfort agent from the hydrogel matrix over time while in contact with a surface of an eye,
wherein the weakly cross-linked polymeric hydrogel is formed by the steps of generating a solution comprising amounts of a bio-template, a functionalized monomer or macromer, and a cross-linking monomer, complexing the functionalized monomer or macromer and the bio-template through non-covalent interactions, initiating copolymerization of the functionalized monomer or macromer and the cross-linking monomer, and loading the comfort agent into the memory site,
wherein the release rate of the contact lenses is adjusted by either altering the ratio of the functionalized monomer(s) or macromere(s) to the biotemplate, or altering the molecular weight of the comfort agent and/or a drug,
wherein the weakly cross-linked polymeric hydrogel provides controlled release of the comfort agent and optionally the drug for at least 50 days.

2. The composition of claim 1 , wherein the contact lenses having the complexing memory sites are produced by the process comprising:
a) identifying receptor sites at a target biological tissue that are associated with a biological mechanism of a comfort agent and/or drug at the target biological tissue;
b) synthesizing or selecting the functionalized monomer with functional groups that mimic the receptor sites of the target biological tissue to form the matrix for binding the comfort agent and/or drug on the functionalized monomer within a weakly cross-linked polymeric hydrogel;
c) forming the polymeric hydrogel comprising: forming a solution comprising amounts of bio-template, the functionalized monomer and a cross-linking monomer; complexing the functionalized monomer and the bio-template in the solution through non-covalent interactions, and initiating copolymerization of the functionalized monomer and the cross-linking monomer;
d) forming the weakly cross-linked polymeric hydrogel into contact lens;
e) loading the contact lens with the comfort agent and/or drug, wherein the drug complexes with the functionalized monomer as a result of the monomer having the functional groups mimicking the receptor sites at the biological tissue wherein the drug is identified as having a biological mechanism of action.

3. The composition of claim 1 , wherein the ratio of the functionalized monomer to the biotemplate is increased to provide an increased controlled release rate.

4. The composition of claim 1 , wherein the ratio of the functionalized monomer(s) to the biotemplate is at least 2.

5. The composition of claim 1 , wherein at least about 500 μg of the comfort agent and/or drug is delivered over a period of up to 60 days in a constant manner.

6. The composition of claim 5 , wherein at least about 1000 μg of the comfort agent and/or drug is delivered over a period of up to 60 days in a constant manner.

7. The composition of claim 1 , wherein the comfort agent is a lubricating agent useful for treating keratoconjunctivitis sicca (dry eye) and making contact lenses more comfortable.

8. The composition of claim 1 , wherein the hydrogel matrix comprises silicone-based or silicone-containing macromer or polymer chains.

9. The composition of claim 1 , wherein the complexing sites comprise amino acid functional groups.

10. The composition of claim 1 , wherein the contact lens further includes a drug.

11. The composition of claim 10 , wherein the drug is selected from the group consisting of an antibiotic, an anti-inflammatory, an antihistamine, an antiviral agent, a cancer drug, an anesthetic, a cycloplegic, a mydriatics, a lubricant agent, a hydrophilic agent, a decongestant, a vasoconstrictor, vasodilater, an immuno-suppressant, an immuno-modulating agent, an anti-glaucoma agent, an anti-infective, hyperosmolar agent, vitamins, growth factors, growth factor antagonists, sympathomimetics, an adrenergic agonist, an anti-cataract agent, an anti-hypertensive agent, an anti-macular degeneration agent, an ocular permeation enhancing agent, an anti-retinal disease agent, an anti-retinitis pigmentosa agent, an anti-diabetic retinopathy agent, an ocular diagnostic agent, and combinations thereof.

12. The composition of claim 1 , wherein the weakly cross-linked hydrogel matrix comprises: carbon-based polymers or organic-based macromers selected from the group consisting of Polyethylene glycol (200) dimethacrylate (PEG200DMA), ethylene glycol dimethacrylate (EGDMA), tetraethyleneglycol dimethacrylate (TEGDMA), N,N′-Methylene-bis-acrylamide, polyethylene glycol (600) dimethacrylate (PEG600DMA) and combinations thereof; or silicone-based monomers or macromers selected from the group consisting of polydimethyl siloxane-based monomer, tris(trimethylsiloxy)silyl propyl methacrylate (TRIS) and combinations thereof; or hydrophilic TRIS derivatives selected from the group consisting of tris(trimethylsiloxy)silyl propyl vinyl carbamate (TPVC), tris(trimethylsiloxy)silyl propyl glycerol methacrylate (SIGMA), tris(trimethylsiloxy)silyl propyl methacryloxyethylcarbamate (TSMC), polydimethylsiloxane (PDMS) and combinations thereof; or monomers or macromers with pendent silicone groups selected from the group consisting of methacrylate end-capped fluoro-grafted PDMS cross linker, a methacrylate end-capped urethane-siloxane copolymer cross linker, a styrene-capped siloxane polymer containing polyethylene oxide and polypropylene oxide blocks, siloxane containing hydrophilic grafts or amino acid residue grafts, siloxanes containing hydrophilic blocks or containing amino acid residue grafts, and combinations thereof.

Assignees

• Byrne Mark E
• Venkatesh Siddarth
• White Charles
• Ali Maryam
• Univ Auburn

Inventors

• Byrne Mark E
• Venkatesh Siddarth
• White Charles
• Ali Maryam

Classifications

• A61L2300/406

  Antibiotics · CPC title

• A61L27/54

  Biologically active materials, e.g. therapeutic substances {(A61L27/227 takes precedence)} · CPC title

• A61L2300/426

  Immunomodulating agents, i.e. cytokines, interleukins, interferons · CPC title

• G02B1/043

  Contact lenses · CPC title

• A61L2300/452

  Lubricants · CPC title