Bi-functional co-polymer use for ophthalmic and other topical and local applications
The invention contemplates a copolymer which is a graft or block copolymer useful to change wettability and surface characteristics of biological surfaces. Methods for use of these formulations and coatings to change wettability and sterically stabilize, and lubricate biological surfaces in a subject, for example, in the treatment of dry eye syndrome, and to prevent adherence of unwanted proteins, for example in the treatment of contact lens intolerance, are provided.
1. A method for prolonging the stability of an ocular surface tear film of a subject, comprising contacting said ocular surface of said subject with a composition comprising a graft copolymer having a positively charged PLL backbone and one or more hydrophilic water soluble side chains selected from the group consisting of polyethylene glycols, polysaccharides, poly(meth)acrylates, polyacrylamides, polyvinyl alcohol (PVA), polyethyloxazoline, poly-N-vinyl pyrrolidone (NVP) and poly boronic-based polymers, in an amount and for a duration so as to prolong the stability of said tear film of said subject.
2. The method of claim 1 wherein said graft copolymer creates a covalent linkage between said graft copolymer and said ocular surface.
3. The method of claim 1 , wherein said graft copolymer creates an electrolytic interaction between said graft copolymer and said ocular surface.
4. The method of claim 1 , where the PLL backbone is selected from the group consisting of: poly(L-lysine) (PLL), polylysine, and polyornithine.
5. The method of claim 1 , where said polyethylene glycols are selected from the group consisting of polyethylene glycol, polypropylene glycol, and mixtures thereof.
6. The method of claim 1 , where said polysaccharides are selected from the group consisting of dextran, carboxylated cellulosics, carboxymethyl cellulose, natural gums, carageenan, alginates and hyaluronic acid and mixtures thereof.
7. The method of claim 1 , where poly boronic based polymers are selected from polymers having boronic-based functional groups selected from the group consisting of phenylboronic acid (PBA), 2-carboxyethaneboronic acid, 1,2-dicarboxyethaneboronic acid, .beta. beta.′-d carboxyethaneboronate, beta.gamma.-dicarboxypropaneboronate, 2-nitro- and 4-nitro-3-succinamidobenzene boronic acids, 3-nitro-4-(6-aminohexylamido)phenyl boronic acid, {4-[(hexamethylenetetramine) methyl]phenyllboronic acid, 4-(N-methyl)carboxamidobenzene boronic acid, 2-{[(4-boronphenyl)methyl]-ethylammonio}ethyl and 2-{[(4-boronphenyl) methyl]diethylammoniol-ethyl groups, succinyl-3-aminophenylboronic add, 6-aminocaproyl-3-aminophenylboronic acid, 3-(N succinimidoxycarbonyl) aminophenyl borona-.e, p-(omega.-aminoethyl)phenylboronate, p-vinyl benzeneboronate, N-(3-dihydroxyborylphenyl)succinamic acid, N-(4-rtro-3-dihydroxy borylphenyl)succinamic acid, 0-dimethylaminomethylbenzene boronic acid, 4-carboxy benzene boronic acid, 4-(N-octyl)carboxamido benzene boronic acid, 3-nitro-4-carboxybenzeneboronic acid, 2-nitro-4-carboxybenzene boronic acid, 4-bromophenylboronate, p-vinylbenzene boronate, 4-(.omega.-aminoethyl)phenylboronate, catechol [2-(diethylamino)carbonyl, 4-bromomethyl]phenyl boronate, and 5-vinyl-2-dimethylaminomethyl benzeneboronic acid.
8. The method of claim 4 , wherein said polylysine is selected from the group consisting of poly-D-lysine (PDL), poly-DL-lysine, poly-e-CBZ-D-lysine, poly-e-CBZ-DL-lysine, and poly-e-CBZ-L-lysine).
9. The method of claim 4 , wherein said polyornithine is selected from the group consisting of poly-DL-ornithine, poly-L-ornithine or poly-S-CBZ-DL-ornithine.