WO2007008666A2 - Compositions et procedes permettant d'ameliorer la vision au moyen de films minces adhesifs - Google Patents

Compositions et procedes permettant d'ameliorer la vision au moyen de films minces adhesifs Download PDF

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Publication number
WO2007008666A2
WO2007008666A2 PCT/US2006/026523 US2006026523W WO2007008666A2 WO 2007008666 A2 WO2007008666 A2 WO 2007008666A2 US 2006026523 W US2006026523 W US 2006026523W WO 2007008666 A2 WO2007008666 A2 WO 2007008666A2
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composition
contact lens
polymer
fluorinated
lens
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PCT/US2006/026523
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English (en)
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WO2007008666A3 (fr
Inventor
Gerald Horn
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Ocularis Pharma, Inc.
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Publication of WO2007008666A2 publication Critical patent/WO2007008666A2/fr
Publication of WO2007008666A3 publication Critical patent/WO2007008666A3/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0048—Eye, e.g. artificial tears
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L12/00—Methods or apparatus for disinfecting or sterilising contact lenses; Accessories therefor
    • A61L12/02—Methods or apparatus for disinfecting or sterilising contact lenses; Accessories therefor using physical phenomena, e.g. electricity, ultrasonics or ultrafiltration
    • A61L12/04—Heat
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/24—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/34—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

Definitions

  • the present invention relates to contact lens adherent thin film compositions which have improved comfort resulting from reduced dryness, reduced lens deposits, and reduced allergic reaction to lens material; improved cosmetics resulting from reduced redness; and improved vision resulting from improved depth of focus, improved distance acuity and improved near acuity.
  • contact lens wearers experience a variety of problems and complications from contact lens wear, including dry eye, allergic reactions, inflammatory responses, conjunctivitis, limbal neovascularization, pannus (more extensive neovascularization), epithelial abrasion, superficial punctate keratitis, keratitis, corneal ulceration (keratitis with loss of stromal tissue), and tight contact lens syndrome. Nearly twenty-five percent of contact lens wearers stop wearing their lenses due to these difficulties. Some studies show that about fifty percent of contact lens wearers experience bothersome dry eye at some point during the day or evening.
  • Silicone hydrogels also cause pervaporation, where the high water permeability of the silicone hydrogel lens leads to water vapor permeating through the lens and being lost to the air, with resultant drying of the corneal epithelium.
  • Soft contact lenses sticking to the epithelium is a problem related to water loss through these lenses, but is particularly troublesome with silicone hydrogel lenses.
  • Some soft contact lenses have hydrophilic or bipolar surfaces. These surfaces attract protein and mucin deposits. Hydrophobic surfaces, like those of silicone hydrogels, attract lipid deposits.
  • aqueous contact lens solutions provide poor pre-lens tear film stability.
  • Soft contact lenses such as hydrogels, retain the necessary oxygen permeability by being water filled.
  • the water in such lenses includes bonded and nonbonded water. Nonbonded water stays in an equilibrium with aqueous from the ocular epithelium, from the tear film cushion underneath the lens, from the lens itself, from water released at the anterior lens surface, and from the atmosphere.
  • the tear film fails to perform its functions of lubrication, oxygenation, and removal of debris, particularly with contact lens wear, symptoms of foreign body sensation (grittiness, scratchiness, sandiness), fatigue, and dryness result.
  • a patient may experience severe pain, especially in the presence of filamentary keratopathy.
  • Loss of the smooth refractive surface of the tear film causes blurred vision, which can vary from blink to blink, accounting for a variable manifest refraction and for complaints of variable vision throughout the day. Surface drying may produce reflex tearing and the misleading complaint of excess tears.
  • symptoms are worse late in the day, with prolonged use of the eyes (as when the patient reads or watches television), and in conditions of heat, wind, and low humidity (as on the beach or ski slopes).
  • Symptoms that are worse in the morning suggest an associated chronic blepharitis, recurrent corneal epithelial erosion, or exposure keratopathy. Further, symptoms include superficial punctate erosions, corneal filaments, coarse mucus plaques, and epithelial defects.
  • the tear film in a normal eye consists of a thin (about 6-45 um in thickness) film composed of a mucous layer lying over the corneal epithelium and an aqueous layer covering the mucous layer and epithelium, which is in turn covered by an extremely thin (0.01-0.22 um) layer of lipid molecules.
  • a continuous tear film is important for the well-being of the corneal and conjunctival epithelium and provides the cornea with an optically high quality surface.
  • the aqueous part of the tear film acts as a lubricant to the eyelids during blinking of the lids.
  • certain enzymes contained in the tear fluid for example, immunoglobulin A, lysozyme and beta lysin, are known to have bacteriostatic properties. Contact lens wear negatively affects this physiology.
  • the continuous production and drainage of aqueous tear is important to maintaining the corneal and conjunctival epithelium in a moist state, in providing nutrients for epithelian respiration, in supplying bacteriostatic agents and in cleaning the ocular surface by the flushing action of tear movement.
  • improving the protection provided by a layer that reduces aqueous evaporation leads to effectively more tear volume and a prolonged tear break up time, resulting in a more effective and physiologic lubrication of the corneal surface.
  • a lubricant must offer excellent properties of oxygen diffusion as well as reduced aqueous evaporation for greatest efficacy.
  • aqueous-deficient dry eye states such as, keratoconjunctivitis sicca (KCS)
  • KCS keratoconjunctivitis sicca
  • relief is limited by the retention time of the administered artificial tear solution in the eye.
  • the effect of an artificial tear solution administered to the eye dissipates within about five to fifteen minutes.
  • the effect of such products, while soothing initially, does not last long enough.
  • the patient is inconvenienced by the necessity of repeated administration of the artificial tear solution in the eye as needed to supplement the normal tears.
  • artificial tear preparations, lens rewetting solutions and ophthalmic lubricants and ointments utilizing active components to provide a thin protective film to reduce evaporation while allowing effective oxygen diffusion are nonexistent.
  • Such available artificial tear solutions commonly include carboxymethyl, methyl or ethyl cellulose or polyvinyl alcohol as the principal active ingredient.
  • Lubricants and ointments tend more toward replacement of oil in the lipid layer of the tear film and commonly include petrolatum, lanolin and/or mineral oil.
  • contact lens rewetting products vary in composition.
  • the solutions are typically aqueous, buffered solutions which frequently contain carboxymethyl, methyl or ethyl cellulose, polyvinyl alcohol and/or glycerin.
  • carboxymethyl, methyl or ethyl cellulose, polyvinyl alcohol and/or glycerin There is a growing understanding of the factors involved in the inflammation of the ocular environment and in particular in contact lens wear, where a vast array of contact lens materials are available and it is known that foreign materials can aggravate or modulate the normal host immune response. Spoilation by proteins has the potential to stimulate, mediate or produce excessive immunological reactions. Vitronectin, for example, is an important inflammatory marker which can be detected on the lens surface by means of an on-lens, cell-based assay.
  • the advent of disposable and frequent replacement lenses has not overcome the problems associated with lens-tear interactions. Indeed, the widespread use of high water content, ionic lenses has made the problem more acute.
  • Tight Contact Lens Syndrome occurs when a contact lens becomes poorly fitting. Because of a variety of factors, including tear film deficiencies and changes in corneal curvature with contact lens wear, a tight contact lens syndrome may occur even in patients with initially well-fitting contacts. The patient usually complains that the lens feels fine until after a few hours of wear, at which point it becomes uncomfortable. The eye may also become red. The symptoms usually resolve within a few hours after discontinuance of contact lens wear. Tight contact lens syndrome can often be diagnosed by the ophthalmologist with the pertinent history and examination, the latter of which shows a contact lens that scarcely moves on the cornea with blinking.
  • the invention is a method of improving a patient's vision comprising providing a composition comprising a polymer selected from the group consisting of silicones, fluorinated silicones, perfluorocarbons, fluorinated alcohols, and fluorinated polyethers; with or without a highly volatile solvent; and applying the composition to at least one surface of a contact lens for insertion into a patient's eye.
  • a composition comprising a polymer selected from the group consisting of silicones, fluorinated silicones, perfluorocarbons, fluorinated alcohols, and fluorinated polyethers
  • the invention is a composition for application to at least one surface of a contact lens to improve a patient's vision
  • a polymer selected from the group consisting of silicones, fluorinated silicones, perfluorocarbons, fluorinated alcohols, and fluorinated polyethers; with or without a highly volatile solvent.
  • the composition comprises about 80% to about 95% polymer. According to another embodiment, the composition comprises about 85% to about 90% polymer. According to another embodiment, the composition comprises about 5% to about 25% solvent. According to another embodiment, the composition comprises about 7.5% to about 15% solvent. According to one embodiment, the composition further comprises an adherent thin film with a desired thickness for delivery of the thin film to a surface of a contact lens.
  • the polymer comprises dimethicone.
  • the dimethicone comprises a viscosity of about 10 to about 20,000 centistokes.
  • the dimethicone comprises a viscosity of about 250 to about 15,000 centistokes.
  • the dimethicone comprises a viscosity of about 12,500 centistokes.
  • the polymer comprises a fluoroguerbet.
  • the fluoroguerbet comprises a 38 carbon guerbet.
  • the polymer comprises a fluorine concentration of about 1% to about 10%. According to another embodiment, the polymer comprises a fluorine concentration of about 3% to about 5% [0026]
  • the solvent is selected from the group consisting of silicones, fluorinated silicones, perfluorocarbons, fluorinated alcohols, and fluorinated polyethers.
  • the solvent comprises cyclomethicone. According to one embodiment, the cyclomethicone comprises a viscosity of about 0.5 to about 5 centistokes. According to another embodiment, the cyclomethicone comprises a viscosity of about 1 to about 4 centistokes. According to one embodiment of the composition, the composition comprises about 75% to 93.5% dimethicone polymer and about 7.5% to 25% solvent.
  • improved vision comprises improved depth of focus.
  • improved vision comprises improved near acuity.
  • improved vision comprises improved distance acuity.
  • improved vision comprises improved quality of vision.
  • improved vision comprises reduced spherical aberration.
  • improved vision comprises an improved Strehl ratio and improved optical resolution closer to the diffraction limit.
  • improved vision comprises improved contrast sensitivity.
  • improved vision comprises improved night vision.
  • the method further comprises the step of applying the composition to at least one surfact of the contact lens during manufacturing or packaging of the contact lens.
  • the method further comprises the step of heat sterilizing the contact lens prior to application of the composition to at least one surface of the contact lens.
  • the method further comprises the step of heating the contact lens following application of the composition to at least one surface of the contact lens.
  • the method further comprises the step of packaging the contact lens with the composition.
  • the method further comprises the step of packaging the composition in a container comprising glass, polypropylene, or epoxy-lined aluminum.
  • the composition remains on the contact lens following insertion into the patient's eye for at least two hours. According to one embodiment, the composition remains on the contact lens following insertion into the patient's eye for at least four hours. According to one embodiment, the composition remains on the contact lens following insertion into the patient's eye for at least twelve hours.
  • the contact lens comprises a daily disposable lens. According to another embodiment, the contact lens comprises a continuous use contact lens. According to another embodiment, the contact lens comprises a daily wear lens. According to another embodiment, the contact lens comprises a planned replacement lens.
  • the invention comprises a method of improving a patient's vision comprising the steps of providing a composition comprising at least one polymer selected from the group consisting of silicones, fluorinated silicones, perfluorocarbons, fluorinated alcohols, and fluorinated polyethers, applying the composition to at least one surface of a contact lens for insertion into the patient's eye, and index matching the composition to the contact lens material, wherein the composition further reduces front and back light scatter.
  • the index of refraction of the composition comprises between 1.2 and 1.48.
  • the index of refraction of the composition comprises between 1.30 and 1.45.
  • the index of refraction of the composition comprises between 1.38 and 1.40.
  • FIGS. IA and IB depict results for dryness (IA) and comfort (IB) with and without the composition of the present application according to one embodiment of the invention.
  • FIG. 2 depicts results for near and distance visual acuity according to one embodiment of the invention.
  • FIG. 3 depicts the angle of incidence of a transmitted light ray at a low angle of incidence.
  • FIG. 4 depicts the angle of refraction of a transmitted light ray at a high angle of incidence.
  • FIG. 5 depicts the angles of incidence of parallel and divergent rays of light striking an optical surface and resulting spherical aberrations.
  • FIG. 6 depicts the light intensity profile, left, and airy disc and rings, right, demonstrating spherical aberration affects of the distribution of light intensity across the diffracted airy disc and rings.
  • FIGS. 7A, 7B and 7C depict the distribution of light intensity in spherical aberrations.
  • FIG. 7A depicts high spherical aberration, with light intensity distribution concentrated more peripherally.
  • FIG. 7B depicts moderate spherical aberration, with light intensity distribution increasing centrally.
  • FIG. 7C depicts low spherical aberration, with light intensity distribution concentrated more centrally.
  • FIG. 8 depicts the relationship between point spread function and spherical aberration.
  • FIGS. 9A, 9B, 9C and 9D depict the relationship between the airy disk, its rings, and the ability to resolve two object points adjacent to each other.
  • compositions for the purpose of the present invention which have the desired characteristics, have been created in several embodiments, from several classes of compounds, including silicone compositions, fluorinated silicone compositions, fluorinated alcohols, perfluorocarbons, perfluorinated polyethers, including fomblin z and fomblin z-dol lubricants.
  • silicone compositions fluorinated silicone compositions, fluorinated alcohols, perfluorocarbons, perfluorinated polyethers, including fomblin z and fomblin z-dol lubricants.
  • impurities such as silicon
  • the present invention relates to an aqueous and/or nonaqueous silicone polymer composition eye preparation for conditioning the surface of a subject's eye or contact lens.
  • the silicone composition is applied as a thin adherent film on the surface of a subject's eye or on the anterior or posterior or both contact lens surface(s) prior to insertion in a subject's eye to condition the contact lens and relieve symptoms associated with prolonged contact lens wear.
  • the silicone composition is applied directly to the eye of a subject to relieve symptoms associated with dry eye conditions.
  • the silicone composition is applied to the surface of a contact lens.
  • An adherent microfilm of the composition results on the contact lens, for example, by applying the preparation to the lens surface(s), rubbing the lens edges together for a few seconds, and then rinsing with an aqueous solution and rubbing a second time.
  • the silicone composition is a highly oxygen permeable, hydrophobic adherent film.
  • the present invention relates to a volatile and/or nonvolatile perfluorocarbon polymer composition eye preparation for conditioning the surface of a subject's eye or contact lens.
  • the perfluorocarbon composition is applied as a thin adherent film on the surface of a subject's eye or on the anterior or posterior or both contact lens surface(s) prior to insertion in a subject's eye to condition the contact lens and relieve symptoms associated with prolonged contact lens wear.
  • the perfluorocarbon composition is applied directly to the eye of a subject to relieve symptoms associated with dry eye conditions.
  • the perfluorocarbon composition is a highly oxygen permeable, hydrophobic adherent film and provides similar benefits and mechanisms of action as silicon polymers.
  • the polymer composition is comprised of a fiuorinated silicone, for example, a perfluorosilicone, a perfluorocarbon, or a perfluoroalkane.
  • a fiuorinated silicone for example, a perfluorosilicone, a perfluorocarbon, or a perfluoroalkane.
  • Fluorinating silicones and other polymers changes certain properties of the composition, for example, changing the viscosity, spreadability, and/or oleophobicity of the composition.
  • Fiuorinated polymers for example, perfluorocarbons, perfluorosilicones, such as perfluorononyl dimethicone, and perfluoroalkanes, are oleophobic or insoluble in oil. Such polymers are not diluted or degraded by natural or foreign oils present in the ocular tear film or region, and are therefore able to retain their therapeutic effect within the eye for a longer period of time.
  • the polymer composition is in the form of a fluid, a gel, or an emulsion having a viscosity of 1 to 15,000 centistokes.
  • a preferred polymer composition for application as a contact lens conditioning agent has a viscosity of about 300 to about 10,000 centistokes, preferably about 8,000 centistokes.
  • a preferred polymer composition for topical application as a dry eye treatment has a viscosity of about 1 to about 8,000 centistokes, preferably about 200 to 400 centistokes.
  • An emollient for example but not limited to, docosyl docosanoate, is added to the polymer composition to increase the viscosity of the composition forming a gel or an emulsion.
  • a silicone gum is added to the polymer composition to increase the viscosity of the composition.
  • the polymer composition comprises one of the following polymers in a substantially pure form: a silicone polymer, a nonaqueous silicone polymer, a perfluorocarbon polymer, a perfluorosilicone polymer, and a perfluoroalkane polymer.
  • the polymer composition is a blend of at least two classes of polymers.
  • the polymer composition is a blend of at least two polymers from the same class.
  • the polymer composition is a single polymer blended from at least two viscosities of the polymer.
  • the polymer composition thin film is delivered directly to the ocular surface, for example, to treat a dry eye condition.
  • One illustrative embodiment combines an aqueous solution with a hydrophobic oxygen permeable polymer composition.
  • a further embodiment results from combining a hypertonic aqueous solution, such as a 0.1% to 10% saline solution, preferably a 0.5% to 2.5% saline solution, with the hydrophobic polymer, such as in an emulsion.
  • the polymer composition thin film is delivered to an anterior contact lens surface, a posterior contact lens surface, or both the anterior and posterior surfaces of a contact lens.
  • the polymer is applied as a thin film to retard evaporation of the aqueous layer while still providing excellent oxygen diffusion to ocular tissues.
  • the polymer composition further forms an aqueous solution used in packaging, storing, shipping, or distributing a contact lens, for example, a daily wear disposable contact lens.
  • the polymer composition is used, either alone or in combination with other aqueous agents, as an overnight storage solution for daily wear contact lenses.
  • the polymer composition thin film When the polymer composition thin film is applied to the contact lens, a dramatic improvement in contact lens function, comfort, and vision results. It is contemplated that the polymer composition thin film can be applied in its pure form, as an emulsion with an isotonic aqueous solution, or with immediate sequential application of aqueous solution.
  • the adherent polymer composition reduces lens evaporation and the aqueous solution allows easier elimination of excess polymer.
  • the aqueous solution also assists in providing an increase in the underlying aqueous volume beneath the contact lens, or beneath the polymer composition fluid layer in dry eye subjects.
  • the polymer composition does not easily evaporate, which prolongs retention of this layer, along with the high oxygen diffusion properties of the preferred polymer composition.
  • the polymers have a high comfort level and low irritation potential suitable for delivery of medications to sensitive areas such as ocular tissues. Such polymers are well known for their excellent oxygen diffusion capabilities. For example, laboratory mice have been able to survive breathing an enriched silicone oil mixture. Because the surface of all soft contact lenses contain silicone either as an impurity or as part of the manufactured material, the polymer composition thin film binds well to the anterior contact lens surface, providing virtually immediate reduced evaporation with excellent oxygen diffusion. [0056]
  • the use of preinsertion polymer compositions on both sides of a hydrated lens allows for long hours of conditioning benefit that are supplemented by the less viscous topical application of similar polymer compositions to achieve hours of daily conditioning.
  • the preinsertion high viscosity gel compositions last, for example, about 10 to 12 hours.
  • the topical fluid reconditioning compositions last, for example, about 2 to 4 hours and can be repeated as needed.
  • the polymer compositions seal the ocular epithelium, preventing evaporative water loss from the ocular tissue and lubricating the mechanical motion of the eyelid.
  • Unmodified polymers stay on or near the surface of the conjunctiva and corneal epithelium and are excellent lubricants.
  • They lubricate the surface of the epithelium, relieving the mechanical distress of repeated eyelid motion over the dried epithelium.
  • the molecules also dislike both the water and proteins inside cells, solubilizing lipid deposits and reducing their accumulation on the contact lens surface over time of use.
  • the first class of compounds is nonaqueous silicone polymers, including cyclomethicone, dimethicone, and silicone gums.
  • a nonaqueous silicone polymer composition contains, for example, dimethicone dissolved in cyclomethicone. This composition is a blend of a high viscosity dimethicone gum and a low viscosity cyclomethicone liquid, resulting in a composition with a viscosity of preferably about 4,000 to 8,000 centistokes.
  • a lower viscosity blend with a higher relative concentration of cyclomethicone, is rapidly spread and even a small drop will coat the anterior contact lens surface during wear.
  • Application of the lower viscosity composition provides immediate improvement in optics, followed by a continuous, gradual improvement that results as tears continue to reach the undersurface of the contact lens with an anterior surface waterproof seal, and rehydrate the lens.
  • Cyclomethicones are unmodified silicones. They evaporate quickly after application, helping to carry oils into the top layer of epidermis. From there, they may be absorbed by the epithelium. Cyclomethicones perform a similar function in hair care products by helping nutrients enter the epithelial keratin protein.
  • Dimethicones are also unmodified silicones. They form a barrier layer on the epithelium which must be renewed as the epithelium sloughs off. Dimethicones have been found to coat the surface of the epithelium and lubricate it, providing a function similar to mucin within tear film as well as providing an overlying floating protective layer.
  • Silicones form a protective layer which helps prevent transepithelial water loss, a very useful characteristic for dry eye patients as well as for prolonged comfortable and more functional contact lens wear.
  • silicone gums add further protective coating. Silicones, including silicone gums, act to help seal moisture into the corneal epithelial keratin matrix.
  • a range of fluid properties of the polymers are possible by varying the viscosity through combination of various volatile and nonvolatile silicone, perfluorocarbon, perfluorosilicone, fluorinated alcohol or perfluorinated polyether polymers.
  • various volatile and nonvolatile silicone, perfluorocarbon, perfluorosilicone, fluorinated alcohol or perfluorinated polyether polymers are used.
  • unmodified silicones are insoluble in water and other polar compounds. However, they will emulsify well using more common emulsifying agents. It is contemplated that all silicone emulsions may be used.
  • Silicones can also be modified or changed to improve solubility.
  • silicones are fluorinated to form, for example, perfluorosilicones.
  • the silicones may be fluorinated in a range of about 0.5% to 20%. Fluorinating the silicones improves the oleophobicity of the molecules, resulting in a composition that reduces the concentration of lipid deposits on the conditioned contact lens. Additionally, the improved oleophobicity of the composition increases the duration of therapeutic effect and, accordingly, the duration of comfortable contact lens wear.
  • Exemplary perfluorosilicones include perfiuorononyl dimethicone and dimethicone propylethylenediamine behenate. Preferred perfluorosilicones are hydrophobic, oxygen permeable, oleophobic, and have a range of possible viscosities for various topical applications.
  • Polymer compositions dissolve well in and will dissolve non-polar materials. Non-polar materials include essential oils, mineral oil, fixed oils, light esters, and sunscreen agents. In addition, polymer compositions greatly minimize, if not eliminate, irritation from sunscreen agents, making possible added ultraviolet light (uv) protection over the corneal surface. Solubility decreases, however, as the size and viscosity of the polymer composition increases.
  • a second class of compounds is perfluorocarbon polymers, which offer similar properties of hydrophobicity, oxygen permeability, and variation in viscosity as the silicone polymers.
  • some perfluorocarbons are more hydrophobic and can be used to retard protein and mucin deposits and to absorb the lipid deposits, like the silicone polymers.
  • Perfluorocarbons offer many of the same characteristics as the silicones - hydrophobic, highly oxygen permeable, with a greater range of lipophilicity, and may be used as dry eye and contact lens conditioning agents. According to one embodiment, lipophilic perfluorocarbons are preferred. Viscosity can be increased for preinsertion contact lens conditioning gels and less viscous compositions used for topical application to the eye or lens during wear.
  • perfluorocarbons used in preferred embodiments to provide dry eye and/or contact lens conditioning include perfluoromethylcyclohexylpiperidine (PFMCP), perfluorooctyl ethane (PFOE), perflubron (PFOB), perfluorohexyl bromide (PFHB), perfluorooctyl iodide (PFOI), and dibromoperfluorohexane (diBrPFH).
  • PFMCP perfluoromethylcyclohexylpiperidine
  • PFOE perfluorooctyl ethane
  • PFOB perflubron
  • PFHB perfluorohexyl bromide
  • PFOI perfluorooctyl iodide
  • diBrPFH dibromoperfluorohexane
  • derivatives of perfluorocarbons such as perfluoroalkanes, that are oxygen permeable and hydrophobic are also used to form the composition.
  • exemplary perfluoroalkanes include perfluorohexylhexane (F6H6) and perfluorohexyloctane (F6H8).
  • Perfluoroalkanes may also be combined with silicone oils, for example, in a ratio of 70% perfluoroalkane to 30% silicone.
  • One exemplary combination is perfluorononyl dimethicone.
  • the exemplary perfluorocarbons offer a range of lipid solubilities from nearly insoluble to fairly highly lipid soluble.
  • Perfluoroalkanes may also be combined with emollients, such as docosyl docosanoate, to increase the viscosity of the composition and increase the adherence of the composition to the eye or contact lens.
  • Perfluorocarbons are biochemically inert and have been used as blood substitutes.
  • the perfluorocarbons have additional properties which allow their use as an emulsion or allow lipophilic drugs to be carried in the more lipid soluble perfluorocarbons. These agents condition contact lenses and seal the surfaces from water loss to optimize shape retention and reduce deposits.
  • a third class of compounds is fluorinated alcohols.
  • Fluorinated alcohols offer similar properties of hydrophobicity, oxygen permeability, and variation in viscosity as the silicone and perfluorocarbon polymers.
  • some fluorinated alcohols are hydrophobic and can be used to retard protein and mucin deposits and to absorb the lipid deposits, like the silicone and perfluorocarbon polymers.
  • Exemplary fluorinated alcohols include the perfluoroalkylethanols and omega-perfluoroisopropoxy-perfluoroalkyl ethanols having two to twelve carbon atoms in the perfluoroalkyl groups, as well as the propanol homologues thereof.
  • the perfluoroalkyl ethanols having six to twelve carbon atoms in the perfluoroalkyl groups, and mixture thereof.
  • the composition comprises dioctyldodecylfluoroheptyl citrate.
  • a fourth class of compounds are perfluorinated polyethers, including Fomblin Z and Fomblin Z-dol lubricants.
  • Polyethylene glycol zdols, polypropylene glycol zdols, or dihydroxy derivatives of perfluoropolyoxyalkane are preferred embodiments.
  • Perfluorinated polyethers offer similar properties of hydrophobicity, oxygen permeability, and variation in viscosity as the silicone, perfluorocarbon and fluorinated alcohol polymers.
  • Silicones, perfluorosilicones, perfluorocarbons, fluorinated alcohols and perfluorinated polyethers all have properties of hydrophobicity and oxygen permeability that may make them suitable as dry eye and/or contact lens conditioning agents.
  • Fluorinated polymers for example, perfluorocarbons, perfluorosilicones and perfluoroalkanes, are also oleophobic (they do not dissolve oil). This has advantages for prevention of oil deposits on contact lens surfaces.
  • Perfluorocarbons and other fluorinated polymers also reduce adherence of oils, proteins and other lipids to the surface of the contact lens.
  • the composition comprises a combination of two or more polymers selected from the group consisting of silicones, perfluorosilicones, perfluorocarbons, fluorinated alcohols and perfluorinated polyethers. Combining these polymers confers further advantages for a dry eye and/or contact lens conditioning agent, adding properties such as oleophobicity (oil insolubility) while retaining some silicone properties and promoting better adherence. Examples of such a compound include perfluorononyl dimethicone, with a range of viscosities. Other similar combinations of perfiuorocarbon and silicone are possible.
  • the polymer composition further comprises a therapeutic agent.
  • the therapeutic agent is lipophilic.
  • exemplary therapeutic agents include an anti- rejection agent such as cyclosporine, an antibiotic, an antimicrobial, a vasoconstrictor, a pupil size management agent, a glaucoma agent, a macular degeneration agent, or an agent to arrest the development of cataracts.
  • the therapeutic agent may be a slow-release composition.
  • the therapeutic agent is cyclosporin, a known anti rejection drug with properties for relieving dry eye. Cyclosporin will not solubilize in an aqueous environment and cannot be carried in an aqueous vehicle.
  • silicone polymers and the more lipophilic perfluorocarbons, can solubilize cyclosporin.
  • Application of an adherent thin film layer of the composition to the surface of the eye or contact lens allows for slow release of cyclosporin to the ocular tissue.
  • Therapeutic release of cyclosporin to ocular tissue over time further minimizes the inflammatory reaction and treats dry eye more potently.
  • the therapeutic agent is an anti-infective.
  • Anti-infectives include, but are not limited to, antibacterial agents, , antifungal agents, antimycobacterial agents, antiparasitic agents, antiviral agents, and vaccines.
  • anti-infectives include, but are not limited to, polymoxin B, bacitracin, sulfacetamide, erythromycin, fluoroquinolones, levofloxacin, neomycin, tobramycin, vancomycin, aminoglycosides, ciprofloxacin, norfloxacin, oflaxacin, amphoB, fluconazole, chlorhexidine, natamycin, acyclovir, and trifluridine.
  • the therapeutic agent is a vasoconstrictor. It is desireable when wearing contact lenses to minimize vasodilation and redness.
  • alpha agonist vasoconstrictors normally used topically to reduce redness, are not medically safe when soft contact lenses are worn.
  • the free water within a soft contact lens acts as a reservoir and can significantly increase the concentration of alpha agonist delivered to the eye. Rebound redness is a known problem of topical alpha agonists when concentrations that are too high are delivered, or when repeat exposure more than once or twice a day results.
  • Topical vasoconstrictors for example, oxymetazoline
  • Additional exemplary vasoconstrictors include, but are not limited to, epinephrine, norepinephrine, levonordefrin, amphetamine, methamphetamine, hydroxyamphetamine, ephedrine, phenylephrine, isoproterenol, dopamine, methoxamine, tyramine, and metaraminol.
  • the therapeutic agent is a pupil size management agent.
  • Pupil size management agents include, but are not limited to, alpha- 1 antagonists, which include imidazoline, phentolamine, and phenoxybenzamine; cholinergic agents; and alpha-2 agonists.
  • alpha 1 antagonist refers to any agent that binds to the alpha 1 adrenergic receptor, which includes alpha 1 adrenergic receptor antagonists.
  • the alpha 1 adrenergic antagonist is iris smooth muscle dilator selective.
  • the alpha 1 antagonist is in the phentolamine family, known as imidazolines, an alkylating agent such as phenoxybenzamine, or a piperazinyl quinazoline with more potent alpha- 1 adrenergic antagonist activity than dapiperazole.
  • the alpha 1 antagonist is phentolamine or phenoxybenzamine, but any alpha 1 antagonist can be used in the present invention.
  • Cholinergic agents include, but are not limited to, pilocarpine and aceclidine.
  • Alpha-2 agonists include, but are not limited to, brimonidine.
  • Pupil size management agents are described in more detail in U.S. Patent Numbers 6,291,498, 6,420,407, 6,515,006, and 6,730,065 to common inventor, Gerald Horn, whose teachings are incorporated by reference in their entirety.
  • the therapeutic agent is an agent to treat glaucoma.
  • Glaucoma therapeutic agents include, but are not limited to, beta-blockers, prostaglandin analogs, alpha-agonists, carbonic anhydrase inhibitors, and cholinergic agents.
  • the therapeutic agent is an agent to treat macular degeneration.
  • Macular degeneration therapeutic agents include, but are not limited to, antioxidants such as vitamin C, vitamin E and beta-carotene, zinc, and copper, and pharmaceuticals such as verteporfin (Visudyne; Novartis Pharmaceuticals Corp.) and pegaptanib sodium (Macugen; Eyetech Pharmaceuticals, Inc. and Pfizer Ophthalmics).
  • the therapeutic agents is an agent to treat allergic conjunctivitis.
  • Allergic conjunctivitis therapeutic agents include, but are not limited to, cromolyn, lodoxamide, olopatadine, antihistamines such as emedastine and levocabastine, corticosteroids, and inflammatory mediators such as azelastine, nedocromil and pemirolast.
  • the polymer composition fUrther contains solubilized fatty acids.
  • the essential fatty acids include, for example, castor oil, corn oil, sunflower oil or light mineral oil, tocopheryl, and soluble forms of vitamin C. These additives offer improved tear film function.
  • the polymer composition further comprises a sunscreen.
  • UVA and UVB sunscreen agents for example but not limited to, oxybenzone, ethylhexyl methoxycinnamate, p-t-butyl p- methoxydibenzoylmethane, avobenzone, oxybenzone, octyl salicylate, octocrylene and octyl p-methoxycinnamate are solubilized in the polymer composition.
  • Sunscreen dissolved in polymer composition is nonirritating and affords improved uv protection to the eye.
  • the therapeutic agents When such therapeutic agents are added to the polymer composition gels or topicals, the therapeutic agents slow release from the adherent films and increase the availability of such therapeutic agents.
  • aqueous compounds can be soaked into a contact lens for slow release
  • the present invention allows for embodiments with slow release of nonaqueous compounds on the adherent surface film while optimizing contact lens performance and minimizing the amount of a therapeutic agent necessary to treat a dry eye. Further, the volume of a therapeutic agent dissolved within the polymer composition is better controlled than with the high available water volume used by depot absorption of a therapeutic agent into a soft contact lens.
  • the polymer composition is adapted to treat a defect of an ocular epithelium, for example, the corneal epithelium or the stroma.
  • an ocular epithelium for example, the corneal epithelium or the stroma.
  • Many types of eye surgery require delivery of therapeutic agents and protection of disrupted corneal epithelium and/or stroma.
  • the polymer composition is applied to the surface of the eye, either with or without a protective contact lens, to seal the ocular or corneal epithelium from disruption.
  • the polymer composition further includes a therapeutic agent, for example, an antibiotic, to protect and to treat the defective or damaged ocular epithelium.
  • a therapeutic agent for example, an antibiotic
  • Delivery of therapeutic agents within a silicone polymer, perfluorocarbon polymer, fluorinated alcohol, fluorinated silicon polymer, and/or perfluorinated polyether both protects the disrupted ocular tissue and provides therapeutic agents to treat the defective or damaged epithelium.
  • Laser eye surgery procedures are particularly well suited for treatment according to the invention. Current laser eye surgery art requires placement of a protective contact lens over the procedure created defect. Such lenses reduce oxygen permeability.
  • a silicone polymer, perfluorocarbon polymer, fluorinated alcohol, fluorinated silicon polymer, and/or perfluorinated polyether retains oxygen permeability while acting as a protective bandage to cover the defect.
  • the polymer composition can obtain a long half-life, and maintain sealant protection of the treated epithelium.
  • the polymer composition further includes a therapeutic agent, such as an antibiotic, to treat the damaged epithelium during healing.
  • a first clinical evaluation was conducted to evaluate the therapeutic effects of applying a hydrophobic composition to the surface of a contact lens inserted into a subject's eye.
  • a silicone polymer gel composition consisting of a blend of dimethicone and cyclomethicone, was provided to twenty subjects. The composition is a blend of one low viscosity silicone polymer and one high viscosity silicone polymer, resulting in a blended composition for application to the contact lens surface with a viscosity of about 8,000 centistokes.
  • Twenty subjects administered the blended silicone polymer gel composition to both the anterior and posterior surfaces of one contact lens and inserted the conditioned contact lens into the subject's right eye. An unconditioned contact lens was inserted into the subject's left eye.
  • tear break up time testing demonstrated an increase in TBU of 20-35% following administration of the blended silicone polymer composition.
  • a clinical evaluation was conducted to determine the effect on near and distance high and low contrast visual acuity of applying a silicone polymer gel composition to the surface of contact lenses inserted into subjects' eyes.
  • This silicone polymer gel composition consisting of a specific blend of dimethicone and cyclomethicone, was provided to twenty subjects.
  • the composition is a blend of one low viscosity silicone polymer and one high viscosity silicone polymer, resulting in a blended composition for application to the contact lens surface.
  • compositions comprised of the previously described silicones, fluorinated silicones, perfluorcarbons, fluorinated alcohols, fluorinated polyethers and combinations thereof, when, formulated and combined to produce certain highly desirable viscosities and adherent film thicknesses, are able to alter the effects of light diffraction sufficiently to improve depth of focus, quality of vision, and to improve distance and near vision when the adherent thin films are applied to the surface of a contact lens prior to insertion of the lens in the eye.
  • This effect is surprising, in part, because the effect is long lasting following an initial application of the thin film, and because no improvement in diffraction or refraction of light with thin films applied to contact lenses has been known to occur heretofor.
  • the results of clinical experimentation indicate that the improvement in the depth of focus and near vision may be dependent upon the specific composition used.
  • the equilibrated thickness of the adherent thin film on the contact lens may be a function of the polymer itself, the percentage of solvent in the composition, or the viscosity of the composition.
  • This thin film thickness is similar to the variability of paint thickness as applied, which may vary depending on the pigments used, the amount of solvent within which the pigments are mixed, and the viscosity of the paint.
  • All contact lenses exhibit light scatter, which can be particularly annoying and even visually disabling at night.
  • Light scatter including backscatter, is commonly caused by optical aberrations within the surface of the contact lens, deposits of mucin and other proteins on the lens surface, inhomogeneities, and the fundamental properties of light reflectance at boundaries of different indices.
  • light reflecting off the anterior lens surface, light reflecting off the posterior lens surface, and light reflecting off the anterior corneal surface scatter light and cause unwanted glare, halo, starburst, reduced contrast and other disturbing visual phenomena that degrade the visual image.
  • Spectacle lenses which are in contact with air on either side, air having an index of refraction of 1.0, have similar reflectance problems.
  • antireflective coatings applied to the anterior and posterior lens surfaces can reduce unwanted light scatter and reflection.
  • a material of index equal to the square root of the index of the optical material is ideal, at a thickness typically equal to one-quarter the wavelength of light.
  • a material with these properties produces near ideal destructive interference of light at the anterior surface of the coating and reflected light from its posterior surface.
  • glass has an index of about 1.5, and the ideal coating would have an index of about 1.2.
  • transparent low index materials are difficult to develop.
  • Magnesium fluoride, with an index of 1.38 is typically used.
  • the composition of this invention is a biocompatible material that can be applied to the exterior surface of a contact lens to index match to create an antireflective thin film on the surface of the contact lens.
  • the range of contact lens refractive indices must be considered. For most lenses, the index is generally in a range of about 1.43-1.48, slightly less for very high water content lenses. Index matching requires the introduction of a material with an index less than that of the optical material, preferably closer to its square root. While tears have a refractive index of about 1.38, the normal tear film thickness of 2 microns or greater is too thick to allow for antireflective properties, and too inhomogeneous.
  • silicone gels can be applied to the surface of a contact lens to index match. With an index of 1.40, silicone gels provided a homogenous thin film of less than 1 micron and can be maintained on the lens surface for a clinically significant period of time.
  • fluorinated molecules including fluorinated silicones, can be applied to the surface of a contact lens to index match. Fluorinated molecules exhibit a reduction in refractive index as the fluorine concentration is increased. Fluorinated alcohols have refractive indices of about 1.35 to 1.38, depending on the percent fluorination. For example, 3.5% fluorine exhibits a refractive index of about 1.38.
  • a fluorinated alcohol gel, such as those previously described, produces a very thin film, is long lasting, and very stable. A very thin tear film layer also results from the dramatic decrease in wetting angle on the contact lens surface.
  • sol-gels can be applied to the surface of a contact lens to index match.
  • Sol-gels are thin films containing homogenous pores, wherein each pore is on a scale approaching the wavelength of light, typically in the range of about 50 to 100 nm. These porous materials serve to effectively reduce the index and obtain a more ideal index match.
  • the sol- gel is a dioctyldodecyl fluoroheptyl citrate, an emollient ester with fluorine molecules retained within the material. This composition provides a microporous homogeneous structure with excellent spreadability characteristics. The microporous nature of the material effectively reduces the index of refraction when applied to a contact lens surface as well.
  • the practical difference between distance and near vision is about 50 cm. That is, an object one meter away from the eye is said to provide incident rays of parallel light and is treated via distance nonaccommodated optics for emmetropic focus. Normal reading vision is about 50 cm away, or slightly less, and requires accommodation. Any slight improvement in depth of field that reduces the nonaccommodated image degradation to less than one meter effectively extends the range of emmetropic focus into what is traditionally considered optics that require accommodation, or near focus. This is particularly relevant to presbyopia, where individuals can no longer maintain such focus, or are unable to do so for very long periods of time. An object near, or less than one meter away, has divergent rays of light rather than parallel ones incident to the cornea.
  • the rays travel from the air to the antireflective coating to glass or plastic lens to antireflective coating to air. This light travels a path through the following indices: from 1.0 to 1.38 to 1.5 to 1.38 to 1.0.
  • the light rays travel from air to a combination tear film / antireflective coating to the cornea to the intraocular fluids.
  • This light travels a path through the following indices: from 1.0 to 1.38 to 1.46 to 1.38.
  • This index change effectively allows light rays of higher angles of incidence to undergo more refraction than those of lower angles of incidence.
  • distance parallel light rays undergo no such additional refraction.
  • Near objects defined as less than one meter from eye objects
  • the result is maintained emmetropic focus for objects less than one meter away, traditionally requiring accommodation.
  • Index matching via the gel means the refracted ray moves closer to the normal drawn through the optic surface. For parallel rays of light striking tangentially, there is no significant change. For divergent rays of light, an improved accommodative focus may occur, as described above. Such light rays, when striking an optical surface at an angle of incidence other than perpendicular, result in spherical aberration. This effect is more pronounced as the distance from the lens center increases, with peripheral light rays striking the lens tangentially refracted in front of, or anterior to, the light rays central to it. This principle is depicted in FIG. 5.
  • Spherical aberration is a very large source of image degradation.
  • Spherical aberration relates to changes in intensity of light distribution in the diffraction limited focal point, defined by the point spread function. Alternatively this can be seen to relate to light distribution in the central as compared to the peripheral rings of diffracted light that represents the diffraction limited result of focus through any circular aperture, as in focusing into the eye. .
  • FIGS. 6, 7A, 7B and 7C depict the light intensity profile, left, and airy disc and rings, right, demonstrating spherical aberration affects of the distribution of light intensity across the diffracted airy disc and rings.
  • FIG. 7A depicts high spherical aberration, with light intensity distribution concentrated more peripherally.
  • FIG. 7B depicts moderate spherical aberration, with light intensity distribution increasing centrally.
  • FIG. 7C depicts low spherical aberration, with light intensity distribution concentrated more centrally.
  • FIG. 8 depicts the relationship between PSF and spherical aberration, with high spherical aberration on the left, low spherical aberration on the right, and an increase in peak intensity of PSF with low spherical aberration.
  • the increase in intensity is measured as an improved value in the Strehl ratio, which is a measure of how close to the diffraction limit two adjacent objects can be resolved.
  • 1.0 represents a theoretical ideal diffraction limited focus.
  • Decreasing the spherical aberrations via the polymer composition improves the intensity of the PSF via more light distributed to the central disk and allows resolution of detail previously not resolvable - that is, improves the Strehl ratio closer to the ideal diffraction limit. In this manner, depth of focus can be increased, and near objects that are imperfectly focused in a presbyope will have improved resolving power after application of the composition of the present invention to the contact lens.
  • FIG. 9A illustrates the effect of adjacent viewed objects and the resulting inability to resolve the individual images.
  • correction of spherical aberration includes a redistribution of light such that less light intensity is focused within the airy rings, and more within the central disk.
  • the composition is not present, resulting in increased spherical aberration.
  • the composition is present, resulting in a redistribution of light and decreased spherical aberration.
  • FIG. 9D illustrates the correction of spherical aberration of adjacent viewed objects.
  • the composition is not present, resulting in increased spherical aberration.
  • the composition is present, resulting in an improved ability to resolve the individual images.
  • Spherical aberrations increase with scotopic and mesopic lighting conditions.
  • the application of the composition improves night vision and dim light vision, including contrast sensitivity
  • compositions of the present invention have large molecular spacing, allowing oxygen to permeate. At a critical thickness, the overlap of these large spaces can induce a novel effect reducing the normal effects of diffraction on light, with reduced airy ring size. Just as is known to occur in applications in astronomy, reducing such diffraction effects improves resolution. Similarly, components of letters at near distance normally not resolvable in a presbyope may become resolvable with reduced diffraction effects.
  • two 52 year old contact lens wearers were measured for their near acuity with and without application of a composition comprised primarily of dioctyldodecyl fluoroheptyl citrate. Subject 2 had a mild monovision contact lens correction, but still underwent a similar improvement in near vision. In both cases the test object was held at arms length, about 18 inches from the eye.
  • the light that is transmitted is diffracted in all directions.
  • Any reduction in interference pattern formation on the retina can potentially improve the resolution of the eye.
  • the micropores within the composition of the invention offer new potential in this regard, possibly providing a micro pinhole effect. Additionally, the composition can also assist plasmon formation at the surface of the thin film, hi this case, micropores structures
  • compositions produce a minimum amount of redness, a maximum quantitative and duration comfort score, a maximum qualitative and duration presbyopic vision correction effect, and a maximum qualitative and duration distance vision correction effect.
  • Table 5 indicates the results of various compositions containing varying percentages of cyclomethicone or dimethicone. The results, as reported in Table 5, indicate that compositions containing between 5% to 20% cyclomethicone in combination with dimethicone produced moderate improvement in visual performance as well as improved comfort and wearability. The mixtures containing the most ideal set of clinical properties are highlighted in bold.
  • Silicones, fluorinated silicones, perfluorocarbons, fluorinated alcohols, perfluorinated polyethers and combinations thereof, which have a relatively high viscosity, can be combined with a solvent having a low viscosity and high volatility to arrive at a desired viscosity.
  • the composition is a blend of two silicones, one highly viscous with high molecular weight, and the other very low viscosity, blended to produce a composition with a desired viscosity.
  • the low viscosity silicone acts as a solvent for the high viscosity silicone.
  • the composition comprises a high viscosity dimethicone and a low viscosity cyclomethicone.
  • the two silicones are combined and vigorously agitated to produce a blend. When effectively agitated, the composition produces an adherent thin film that can be applied to the surface of a contact lens.
  • the polymer solvent combination can be applied to the surface of a soft contact lens to enhance the performance characteristics of the lens.
  • a preferred combination comprises a range of about 5% to about 25% solvent, a range of percentage of solvent producing a thin film with a viscosity shown to improve visual performance in terms of both distance and near vision acuity, contrast sensitivity, depth perception, depth of focus, and enhancement of the overall quality of vision.
  • the low viscosity silicone is cyclomethicone.
  • Cyclomethicone is a highly volatile solvent, which, when used as a carrier, means that the material has a measurable vapor pressure.
  • cyclomethicone will form a combination with dimethicone having a viscosity in a range from about 10 centistokes to about 20,000 centistokes, preferably about 12,500 centistokes.
  • the percentage of cyclomethicone within the combination decreases, the viscosity of the overall mixture increases.
  • a combination with a cyclomethicone percentage ranging from about 75% down to about 20% produces a thin film with high comfort, but with little effect on vision.
  • a combination with a cyclomethicone percentage at about 25% to about 5% has been shown to improve visual performance, measured in terms of quality of vision, improved depth of focus, and quantifiable acuity measured at both distance and near.
  • Combinations containing only about 5% cyclomethicone show diminished comfort and vision benefits, with a total loss of visual performance and comfort benefit when the thin film contains 0% cyclomethicone and 100% dimethicone.
  • compositions produced the desired results in terms of both comfort and vision.
  • a cyclomethicone percentage in the range of about 5% to about 80% is preferred; to reduce redness, a range of about 7.5% to about 80% cyclomethicone is preferred; to improve presbyopic effect, a range of about 5% to about 25% cyclomethicone is preferred; to improve presbyopic duration, a range of about 7.5% to about 25% cyclomethicone is preferred; to improve distance acuity, a range of about 5% to about 80% cyclomethicone is preferred; and to improve the duration of distance improvement, a range of about 5% to about 80% cyclomethicone is preferred.
  • the preferred composition for minimizing redness and for maximizing comfort, distance and near acuity is a composition with a cyclomethicone concentration in the range of about 7.5% to about 25%, with a range of about 7.5% to about 12% cyclomethicone being the most preferred embodiment.
  • the composition comprises a blend of about 5% to 25% by weight cyclomethicone with a viscosity of about 4 centistokes and about 75% to 95% by weight dimethicone with a viscosity of about 12,500 centistokes.
  • the composition comprises a blend of about 7.5% to 25% by weight cyclomethicone with a viscosity of about 4 centistokes and about 75% to 93.5% by weight dimethicone with a viscosity of about 12,500 centistokes.
  • the preferred carrier is a volatile silicone having a boiling point in the range of about 99 degree Celsius to about 260 degree Celsius, a CFS of about 1 to 20, and a solubility in water of less than about 0.1%.
  • the carrier is cyclomethicone.
  • the degree of substitution on the siloxane carrier (higher substitution produces a composition with lower solubility) affects the polymer's solubility.
  • the silicones may be either cyclic or linear polydimethyl siloxanes.
  • the number of silicon atoms in the cyclic silicones is about 3 to about 7, most preferably 4 or 5.
  • the general formula for the cyclic silicones is:
  • Viscosities are generally less than 10 centipoise (cP) at 25 degree Celsius.
  • linear polydimethyl siloxanes generally have a viscosity of less than about 5 cP at 25 degree Celsius.
  • Silicones of the above described types are widely available e.g., from Dow Corning as 344,345 and 200 fluids; Union Carbide as Silicone 7202 and 7158, and Stauffer Chemical as S WS-03314.
  • volatile hydrocarbons are used as carriers in the thin film combinations. These hydrocarbons may include straight chain and branched hydrocarbons and may contain from about 10 to about 16 carbon atoms, preferably from about 12 to about 16 carbon atoms.
  • short chain alcohols such as ethanol are used as solvents to produce the present compositions.
  • Water is not useful in compositions of the present invention either alone or in mixtures with other volatile carriers.
  • both surfaces of a contact lens are coated with the thin film of the composition prior to insertion of the lens into the eye.
  • Each surface treated with a thin film coating confers additional advantages.
  • Treatment of the inner surface provides added comfort with decreased morbidity from epithelial touch, and longer retention of tear film thickness between the inner contact lens surface and the corneal epithelium.
  • Treatment of the outer surface results in longer tear break up time, improved vision at both distance and near, as well as improved depth of focus.
  • Treatment of either surface provides a decrease in the quantity of evaporation, pervaporation and lens deposits of aqueous and mucin, both of which create a hydrophobic film on the lens surface, and deposits of lipid, which slowly dissolve the viscous thin film.
  • the thin film composition is applied to the contact lens surface during or directly following the contact lens manufacturing process, prior to the packaging and distribution of the contact lens.
  • the contact lens has an adherent thin film polymer layer on at least one surface of the contact lens at the time of purchase or use of the contact lens. This embodiment has the benefit of having the thin film polymer adherent layer already applied to the contact lens surface so that the contact lens wearer does not have to condition the lens with the composition prior to insertion of the lens into the eye.
  • the process of applying the adherent thin film to the surface of the contact lens using heat may be a separate step conducting during or following the process of manufacturing and packaging a contact lens.
  • the adherent thin film may be applied during the manufacture of the lens, during heat sterilization of the lens, during packaging of the lens, or during another appropriate step of the manufacturing process.
  • the contact lens is heated to a temperature of about 120°C to about 150 0 C, more preferably about 120 0 C to about 130°C, most preferably about 12O 0 C to about 125 0 C.
  • the temperature of the heating process should not exceed 150 degrees Celsius.
  • Heat sterilization of contact lenses is typically carried out at a temperature range of 121 to 124 degrees Celsius, with standard pressures and times.
  • the thin film composition is applied to the contact lens surface, for example, by the eye doctor, eye technician or the contact lens wearer.
  • a drop of the thin film composition is placed on one or both surfaces of the contact lens. Then the lens is rubbed between the fingers for a few seconds up to 10 seconds. Then the lens is irrigated with a saline solution or a contact lens wetting solution, rubbed briefly again between the fingers, irrigated again and then inserted in the eye.
  • a drop of the thin film composition is placed on one or both surfaces of the contact lens.
  • the lens is rubbed briefly to spread the composition on the lens. Then the lens is placed in a saline solution or contact lens wetting solution for about 3 to 5 minutes in a contact lens container. Then the container is shaken vigorously for 5 seconds up to 15 seconds. Then the lens is removed from the container and inserted in the eye.
  • a drop of the thin film composition is placed on one or both surfaces of the contact lens. Then the lens is rubbed briefly to spread the composition on the lens. Then the lens is placed in a saline solution or contact lens wetting solution for at least 10 minutes up to overnight in a contact lens container. Then the lens is removed from the container, irrigated with saline solution or contact lens wetting solution and inserted in the eye.
  • the composition is provided to the user in a package from which the user can dispense the composition.
  • the composition is packaged in a bottle, optionally containing a dropper or application tip, a unit-dose sterile sealed dropper, or another container used or contemplated by those in the field.
  • the improvement in near vision is dependent on the percentage of the composition consisting of the volatile cyclomethicone. Therefore, it is very important to maintain stability of this composition during manufacture, sterilization, packaging, dispensing and use so that the cyclomethicone does not volatilize away before the contact lens is treated for use.
  • Containers made of glass, polypropylene, epoxy coated aluminum tubes and other suitable materials which can serve as an effective barrier against the volatilizing of the cyclomethicone are important for product stability. Also, manufacturing, sterilization and packaging processes which maintain the desired percentage of cyclomethicone in the composition will also be important for product effectiveness.
  • the combination is particularly sensitive to cyclomethicone' s volatility as a solvent.
  • Exemplary containers include a glass container, a polypropylene container, or an aluminium container with an epoxy lining. These exemplary containers may prevent cyclomethicone vaporization and minimize the loss of a desired percentage of cyclomethicone in the mixture over a necessary period of time.
  • the thin film mixtures of this invention have been used to coat contact lenses and store them for several weeks with retention of the improved visual performance.
  • Daily wear soft lenses which now constitute about 10% of the soft contact lens market, may be coated with adherent thin films of the present invention, either at the time of manufacture or prior to use, to improve their comfort and visual performance.
  • Lenses tested include Focus dailies, Accuvue dailies, Accuvue II, and Frequency 55 torics.
  • the present invention may also be used to coat lenses on a daily basis to extend the life of extended wear (with removal daily just for insertion of the present invention) or daily wear contact lenses, which are reworn for a period of time, and thereby lengthen the time duration before the quality of the contact lens surface becomes degraded.
  • the composition is applied to a surface of the contact lens on a periodic basis, for example, hourly, daily, or as needed, according to one of the methods of application contemplated above.
  • the contact lens treated according to this method can be manufactured to include an initial adherent thin film layer of the composition, supplemented with subsequent administrations of the composition according to the needs of the user.
  • the present invention may also be used to coat these lenses daily for the purpose of improving comfort.
  • the present invention may also be used to coat these lenses daily for the purpose of improving visual performance, including distance and near acuity, depth of focus, and quality of vision.

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Abstract

L'invention porte sur une composition et un procédé permettant d'améliorer la vision d'un patient. La composition comprend un polymère choisi dans le groupe composé des silicones, des silicones fluorés, des perfluorocarbones, des alcools fluorés et des polyéthers fluorés avec ou sans solvant. Le procédé de l'invention consiste à appliquer la composition sur au moins une surface d'une lentille de contact apte à être insérée dans l'oeil d'un patient. Le polymère, ou une combinaison du polymère et d'un solvant, produit un film mince adhésif d'une épaisseur désirée permettant de distribuer le film mince adhésif à la surface d'une lentille de contact.
PCT/US2006/026523 2005-07-08 2006-07-10 Compositions et procedes permettant d'ameliorer la vision au moyen de films minces adhesifs WO2007008666A2 (fr)

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WO2012119059A1 (fr) * 2011-03-03 2012-09-07 Allergan, Inc. Formulations ophtalmiques non aqueuses à base de silicone
WO2014121028A1 (fr) * 2013-02-01 2014-08-07 Ocularis Pharma, Llc Procédés et compositions pour l'administration ophtalmique quotidienne de phentolamine pour améliorer les performances visuelles
US9395557B2 (en) 2014-11-12 2016-07-19 Vance M. Thompson Partial corneal conjunctival contact lens
US9668916B2 (en) 2013-11-04 2017-06-06 Vance M. Thompson Conjunctival cover and methods therefor
US9795560B2 (en) 2013-02-01 2017-10-24 Ocularis Pharma, Llc Aqueous ophthalmic solutions of phentolamine and medical uses thereof
US9869883B2 (en) 2015-03-11 2018-01-16 Vance M. Thompson Tear shaping for refractive correction
WO2018206656A1 (fr) 2017-05-12 2018-11-15 Novaliq Gmbh Compositions pharmaceutiques comprenant des alcanes semifluorés pour le traitement d'états liés aux lentilles de contact
US10678067B2 (en) 2018-04-06 2020-06-09 Vance M. Thompson Tear shaping for refractive correction
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US11357738B2 (en) 2015-09-30 2022-06-14 Novaliq Gmbh Semifluorinated compounds and their compositions
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CN110650734A (zh) * 2017-05-12 2020-01-03 诺瓦利克有限责任公司 治疗与隐形眼镜有关病症的包含半氟化烷烃的药物组合物
US11723861B2 (en) 2017-09-27 2023-08-15 Novaliq Gmbh Ophthalmic compositions comprising latanoprost for use in the treatment of ocular diseases
US11896559B2 (en) 2017-10-04 2024-02-13 Novaliq Gmbh Opthalmic compositions comprising F6H8
US11703695B2 (en) 2018-04-06 2023-07-18 Tearoptix, Inc. Tear shaping for refractive correction
US10678067B2 (en) 2018-04-06 2020-06-09 Vance M. Thompson Tear shaping for refractive correction
US11400077B2 (en) 2018-10-26 2022-08-02 Ocuphire Pharma, Inc. Methods and compositions for treatment of presbyopia, mydriasis, and other ocular disorders
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US10993932B2 (en) 2018-10-26 2021-05-04 Ocuphire Pharma, Inc. Methods and compositions for treatment of presbyopia, mydriasis, and other ocular disorders
US11564839B2 (en) 2019-04-05 2023-01-31 Amo Groningen B.V. Systems and methods for vergence matching of an intraocular lens with refractive index writing
US11583389B2 (en) 2019-04-05 2023-02-21 Amo Groningen B.V. Systems and methods for correcting photic phenomenon from an intraocular lens and using refractive index writing
US11583388B2 (en) 2019-04-05 2023-02-21 Amo Groningen B.V. Systems and methods for spectacle independence using refractive index writing with an intraocular lens
US11931296B2 (en) 2019-04-05 2024-03-19 Amo Groningen B.V. Systems and methods for vergence matching of an intraocular lens with refractive index writing
US11944574B2 (en) 2019-04-05 2024-04-02 Amo Groningen B.V. Systems and methods for multiple layer intraocular lens and using refractive index writing
US11529230B2 (en) 2019-04-05 2022-12-20 Amo Groningen B.V. Systems and methods for correcting power of an intraocular lens using refractive index writing
US11678975B2 (en) 2019-04-05 2023-06-20 Amo Groningen B.V. Systems and methods for treating ocular disease with an intraocular lens and refractive index writing
US11566005B2 (en) 2021-05-18 2023-01-31 Ocuphire Pharma, Inc. Highly pure phentolamine mesylate and methods for making same
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