BI-FUNCTIONAL CO-POLYMER USE FOR OPTHALMIC AND OTHER TOPICAL AND LOCAL APPLICATIONS

• US 20100226963A1
• Filed: 02/18/2010
• Published: 09/09/2010
• Est. Priority Date: 02/18/2009
• Status: Active Grant

• Current Assignee: CALM Water Therapeutics LLC
• Original Assignee: Eyeon Particle Sciences LLC
• Inventors: Loxley, Andrew, Mitchnick, Mark, Cooper, Eugene R., Kleinman, David M.
• Granted Patent: US 8,802,075 B2
• Time in Patent Office: Days
• US Class Current: 424/429
• CPC Class Codes: A61K 31/045 Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
• CPC Class Codes: A61K 31/7036 having at least one amino group directly attached to the carbocyclic ring, e.g. streptomycin, gentamycin, amikacin, validamycin, fortimicins
• CPC Class Codes: A61K 31/74 Synthetic polymeric materials
• CPC Class Codes: A61K 31/765 Polymers containing oxygen
• CPC Class Codes: A61K 31/785 Polymers containing nitrogen
• CPC Class Codes: A61K 35/02 from inanimate materials carbon A61K33/44
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/0043 Nose
• CPC Class Codes: A61K 9/0048 Eye, e.g. artificial tears
• CPC Class Codes: A61K 9/0051 Ocular inserts, ocular implants
• CPC Class Codes: A61K 9/0073 Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy; nasal sprays A61K9/0043; inhalation of vapours of volatile or heated drugs, e.g. essential oils or nicotine, A61K9/007; devices A61M
• CPC Class Codes: A61K 9/5031 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poly(lactide-co-glycolide)
• CPC Class Codes: A61K 9/5146 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyamines, polyanhydrides
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/04 Artificial tears; Irrigation solutions
• CPC Class Codes: G02C 7/04 Contact lenses for the eyes disinfection or sterilisation of contact lenses A61L12/00

Abstract

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.

Claims

1. A method for increasing the wettability of a biological surface or treating biological surface related discomfort in a subject, comprising contacting the surface with a composition comprising a copolymer having a positively charged, or hydrophobic or covalent bonding moiety and a hydrophilic moiety, wherein said contacting is effected in an amount and for a duration so as to increase the wettability or treat discomfort of said biological surface.

2. The method of claim 1 wherein the copolymer is a graft or a block copolymer.

3. The method of claim 1 wherein the copolymer is a dendrimer.

4. The method of claim 1 wherein the hydrophilic moiety is one of non-ionic or anionic.

5. The method of claim 1 wherein the copolymer creates a covalent adhesion between the copolymer and the biological surface.

6. The method of claim 2 wherein the copolymer is a graft copolymer and comprises a cationic backbone and side chains that are water soluble and non-ionic.

7. The method of claim 2 wherein the copolymer is a graft copolymer and comprises a water soluble non-ionic backbone and cationic side chains.

8. The method of claim 2 wherein the copolymer is a block copolymer and comprises at least one cationic block and at least one water soluble and non-ionic block.

9. The method of claim 2 wherein the copolymer is a block copolymer and comprises at least one block which is hydrophobic and at least one block which is water soluble and anionic.

10. The method of claim 2 wherein the copolymer is a block copolymer and comprises at least one block which is hydrophobic and at least one block which is water soluble and cationic.

11. The method of claim 1 wherein the copolymer is a block copolymer and comprises at least one block which is hydrophobic and at least one block which is water soluble and or non-ionic.

12. The method of claim 1 wherein the contacted biological surface is the surface of an eye, a mucous membrane, or skin of a subject.

13. The method of claim 1 wherein the copolymer comprises 0.001 to 40% of said composition.

14. The method of claim 1 wherein the copolymer comprises 0.001 to 25% of said composition.

15. The method of claim 1 wherein said composition further comprises a second polymer.

16. The method of claim 1 wherein said composition further comprises a PLURONIC block copolymer.

17. The method of claim 1 wherein said composition further comprises one or more of a surfactant, a preservative, and a pharmaceutical ingredient selected from the group consisting of:

demulcents [Cellulose derivatives (Carboxymethylcellulose sodium, Hydroxyethyl cellulose, Hydroxypropyl methylcellulose, Methylcellulose), Dextran 70, Gelatin, Polyols (Glycerin, Polyethylene glycol 300, Polyethylene glycol 400, Polysorbate 80, Propylene glycol), Polyvinyl alcohol, Povidone] emollients (Lanolin, mineral oil, paraffin, petrolatum, white ointment, white petrolatum, white wax, yellow wax), sodium chloride, and vasoconstrictors (Ephedrine hydrochloride, Naphazoline hydrochloride, Phenylephrine hydrochloride, Tetrahydrozoline hydrochloride).

18. The method of claim 1 wherein the composition is contacted to said biological surface in an amount sufficient to change tribological properties of the biological surface of the subject.

19. The method of claim 1 wherein the composition is contacted topically to an eye of a subject.

20. The method of claim 1 wherein the composition is topically administered to an eye of a subject to treat dry eye, ophthalmic irritation, or corneal epithelial disease.

21. The method of claim 19 where the composition is contacted to the eye by an eye drop or an eye care solution.

22. The method of claim 19 further comprising administering to the eye of the subject a second, different eye drop.

33. The method of claim 2, wherein the graft copolymer is PLL-g-PEG.

23. A composition comprising a copolymer having a positively charged, or hydrophobic, or covalent bonding moiety and a hydrophilic moiety and a pharmaceutically acceptable carrier.

26. A kit comprising an extraocular device coated with the composition of claim 23, and packaging materials therefore.

27. The kit of claim 26, wherein the packaging materials permit contacting of the extraocular device through the nozzle of an eye care solution container.

28. A method for manufacture of a contact lens, comprising providing a contact lens and contacting said lens with the composition of claim 23.

32. The kit of claim 26, wherein said extraocular device is an intracorneal inlay.

34. The composition of claim 23, comprising a low viscosity artificial tear less than 20 cP, having prolonged tear film break up time.

35. The composition of claim 23, wherein the positively charged moiety is sufficient as a preservative in a topical ophthalmic formulation.

36. The composition of claim 23, in a volume sufficient for instillation in the eye, wherein the copolymer is PLL-g-PEG at a concentration of 0.1 to 3 wt %.

37. The method of claim 28, wherein the copolymer is immobilized on an extraocular device at the time of manufacture.

38. The method of claim 37 where the copolymer is immobilized on the extraocular device covalently.

39. The method of claim 38, said immobilization being effected via an aldehyde plasma polymer interlayer and reductive amination.

40. The method of claim 37, wherein the extraocular device is a contact lens.

24. A pharmaceutical formulation comprising an effective amount of a composition comprising a copolymer having a positively charged, or hydrophobic, or covalent bonding moiety and a hydrophilic moiety and a pharmaceutically acceptable carrier.

25. A kit comprising a sterile pharmaceutical formulation of claim 24 and packaging materials therefore which permit use as an artificial tear product introducible into the eye.

29. A method of storing a contact lens for at least 1 hour, comprising providing the contact lens and said pharmaceutical formulation of claim 24.

30. A kit comprising a contact lens and the pharmaceutical formulation of claim 24, in a container that is unopened subsequent to manufacture.

31. A kit comprising a contact lens and the pharmaceutical formulation of claim 24, in a container that is reusable.

41. A copolymer coated nanoparticle, the surface of said nanoparticle comprising a copolymer having a positively charged, or hydrophobic, or covalent bonding moiety and a hydrophilic moiety.

42. The nanoparticle of claim 41, further comprising an active agent.