Non-irritating, non-blurring, photostable ophthalmic sunscreen composition

Abstract

A non-irritation, non-blurring, photostable ophthalmic sunscreen composition contains at least one of the following: bemotrizinol; bisoctrizole; tris-biphenyl triazine; and/or octyl methoxycinnamate. A liquid vehicle base is then a remainder of the solution by weight. The composition is an artificial tear formulation or an ophthalmic suspension or ointment. The composition may include at least one inorganic and/or at least one organic active ingredient. The inorganic active ingredients may include, but not be limited to zinc oxide, titanium dioxide, iron oxide, zirconium oxide, and cerium oxide. The organic active ingredients may include, but not be limited to dioxybenzone, octinoxate, octisalate, homosalate, avobenzone, octocrylene, para-aminobenzoic acid, cinoxate, methyl anthranilate, octocrylene, padimate O, ensulizole, sulisobenzone, trolamine salicylate, and ecamsule.

Claims

1. A method of protecting an eye from ultraviolet radiation damage comprising administering to the ocular surface of the eye an ophthalmic sunscreen solution, comprising: 0.25 percent to 15 percent by weight of at least one of the following active agents: bemotrizinol; bisoctrizole; and tris-biphenyl triazine; and a liquid vehicle base, wherein the liquid vehicle base is an ophthalmic artificial tear formulation.

2. The method of claim 1, wherein the ophthalmic sunscreen solution further comprises 0.25 percent to 15 percent by weight of an inorganic active ingredient.

3. The method of claim 2, wherein the inorganic active ingredient is selected from the group consisting of titanium dioxide, zinc oxide, iron oxide, zirconium oxide, cerium oxide and mixtures thereof and wherein the inorganic active ingredient is in micronized form or nanoparticle form.

4. The method of claim 3, wherein the ophthalmic sunscreen solution further comprises 0.25 percent to 15 percent by weight of an organic active ingredient and wherein the organic active ingredient is in micronized form or nanoparticle form.

5. The method of claim 4, wherein the organic active ingredient is selected from the group consisting of dioxybenzone, octinoxate, octisalate, homosalate, avobenzone, octocrylene, para-aminobenzoic acid, cinoxate, methyl anthranilate, octocrylene, 2-ethylhexyl 4-(dimethylamino)benzoate, ensulizole, sulisobenzone, trolamine salicylate and ecamsule.

6. The method of claim 5, wherein the ophthalmic sunscreen solution comprises 0.25 percent to 10 percent by weight of the at least one of the following active agents: bemotrizinol; bisoctrizole; and tris-biphenyl triazine.

7. The method of claim 5, wherein the ophthalmic sunscreen solution comprises 0.25 percent to 5 percent by weight of the at least one of the following active agents: bemotrizinol; bisoctrizole; and tris-biphenyl triazine.

8. The method of claim 5, wherein the liquid vehicle base is water-based or oil-based.

9. The method of claim 1, wherein the ophthalmic sunscreen solution further comprises an emulsifier.

10. The method of claim 9, wherein the emulsifier is selected from the group consisting of a silicone-based emulsifier, a polyethylene glycol emulsifier, a polysiloxane emulsifier, a glyscoside emulsifier, an acrylic-based emulsifier and combinations thereof.

11. The method of claim 9, wherein the emulsifier comprises polysorbate, carbomer and/or castor oil.

12. The method of claim 1, wherein the ophthalmic sunscreen solution further comprises an emollient.

13. The method of claim 12, wherein the emollient is selected from the group consisting of aloe extracts, oleaginous esters, ethers and combinations thereof.

14. The method of claim 12, wherein the emollient is an anhydrous lanolin and/or an oleaginous ingredient.

15. The method of claim 1, wherein the ophthalmic sunscreen solution further comprises a preservative.

16. The method of claim 15, wherein the preservative is an ionic-buffered preservative, a detergent or an oxidizing detergent.

17. The method of claim 1, wherein the ophthalmic sunscreen solution further comprises a chelating agent.

18. The method of claim 1, wherein the ophthalmic sunscreen solution further comprises an antioxidant.

19. The method of claim 1, wherein the ophthalmic sunscreen solution further comprises an ophthalmic demulcent.

20. The method of claim 19, wherein the ophthalmic demulcent is a cellulose derivative demulcent or a liquid polyol.

21. The method of claim 1, further comprising a hypertonicity agent.

22. The method of claim 21, wherein the hypertonicity agent is sodium chloride.

23. The method of claim 1, further comprising an ophthalmic lubricant.

24. The method of claim 1, further comprising an ophthalmic astringent.

25. The method of claim 1, wherein the at least one of the following active agents: bemotrizinol; bisoctrizole; and tris-biphenyl triazine is in micronized or nanoparticle form.

26. The method of claim 1, wherein the method does not cause blurred vision.

Description

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

(1) Examples of ophthalmic sunscreen compositions of the present invention provide an SPF of up to 50 or higher. As the eyes are usually not in direct exposure to UV radiation as opposed to the skin, such high SPF ratings may not be necessary for the present invention, and as such, the concentration of the active (and inactive) ingredients may be much lower than those proposed for dermal use.

(2) The application of much lower concentrations of these ingredients will lead to much lower incidences of ophthalmic irritation/stinging when applied, and will lessen the known side-effects of such ingredients. Further, by reducing the concentrations of these ingredients, possible absorption of these ingredients into the eye (i.e., through the Cornea) will be reduced as to prevent possible intra-ocular effects (e.g., cataract formation).

(3) Compositions of the present invention are now described, but are not limited to these embodiments.

(4) Ophthalmic sunscreen compositions according to the present invention may contain a liquid vehicle base, such as an artificial tear formulation, which may be water and/or oil-based, or an ophthalmic suspension or ointment and include at least one inorganic and at least one organic active ingredient.

(5) Inorganic active ingredients may include, but not be limited to zinc oxide, titanium dioxide, iron oxide, zirconium oxide, and cerium oxide, optionally in micronized form as to prevent blurred vision when applied.

(6) Organic active ingredients may include, but not be limited to dioxybenzone, octinoxate, octisalate, homosalate, avobenzone, octocrylene, para-aminobenzoic acid, cinoxate, methyl anthranilate, octocrylene, padimate O, ensulizole, sulisobenzone, trolamine salicylate, and ecamsule.

(7) The inactive ingredients of the present invention shall also include emulsifier(s) and/or emollient(s). Silicone-based emulsifiers like polyethylene glycols, polysiloxanes, glycosides are excellent choices. Acrylic-based emulsifiers, and mixtures thereof may also be used safely for the present preparation. Emollients may include, but not be limited to aloe extracts, oleaginous esters, and ethers, or a combination thereof.

(8) The composition of the present invention shall also include, but not be limited to preservatives, chelating agents, and/or antioxidants.

(9) The following examples describe a composition of the present invention, but it is obviously not intended to limit the scope of the invention.

Example 1

(10) An ophthalmic sunscreen solution can be synthesized by mixing 5% micronized zinc oxide and 3% octinoxate in an ophthalmic artificial tear formulation. This solution may contain carboxymethylcellulose sodium 0.1%; glycerin 0.25%; boric acid; calcium chloride dihydrate; erythritol; levocarnitine; magnesium chloride hexahydrate; potassium chloride; purified water; sodium borate decahydrate; and sodium citrate dihydrate.

Example 2

(11) An ophthalmic sunscreen solution can be synthesized by mixing a range of 5% micronized titanium dioxide and 3% octisalate in an ophthalmic artificial tear solution.

Example 3

(12) An ophthalmic sunscreen ointment can be synthesized by mixing a range of 5% micronized zinc oxide and 3% octinoxate in an ophthalmic ointment consisting of hypromellose, boric acid, sodium perborate, phosphonic acid, potassium chloride, purified water, and sodium chloride.

(13) The present disclosure describes the composition of an ophthalmic sunscreen utilizing Tinosorb (preferably Tinosorb M, IUPAC name 2,2-methanediylbis[6-(2H-benzotriazol-2-yl)-4-(2,4,4-trimethylpentan-2-yl)phenol]) as its active ingredient. Tinosorb is the trade name of a number of UV absorbers including the following: bemotrizinol (Tinosorb S); bisoctrizole (Tinosorb M); tris-biphenyl triazine (Tinosorb A2B); and octyl methoxycinnamate (Tinosorb OMC). Tinosorb M is a photostable sunscreen composition that possesses multiple chemical characteristics over all other sunscreen agents currently available, that render it as an ideal candidate for use in a sunscreen formulation that is designed specifically to be directly applied to the ocular surface.

(14) Bisoctrizole (marketed by BASF as Tinosorb M and by MPI as Milestab 360, INCI methylene bis-benzotriazolyl tetramethylbutylphenol) is a benzotriazole-based organic compound that is added to sunscreens to absorb UV rays. Bisoctrizole is a broad-spectrum ultraviolet radiation absorber, absorbing UVB as well as UVA rays, which makes it an ideal active ingredient for an ophthalmic sunscreen composition. It also reflects and scatters UV adding to its SPF capability for this specific application. Bisoctrizole is a hybrid UV absorber, the only organic UV filter produced and microfine organic particles (<200 nm), like microfine zinc oxide and titanium dioxide. Where other organic UV absorbers need to be dissolved in either the oil or water phase, bisoctrizole dissolves poorly in both. Bisoctrizole is added to the water phase of a sunscreen as a 50% suspension, whereas mineral micropigments are usually added to the oil phase. The bisoctrizole particles are stabilized by the surfactant decyl glucoside. This allows for an ideal ophthalmic preparation that could be used in suspension form.

(15) Bisoctrizole shows very little photodegradation and has a stabilizing effect on other UV absorbers, octyl methoxycinnamate (octinoxate) in particular. This is an extremely important factor when considering the very low concentration of the active ingredient that can be used in a formulation that is to be applied directly on the ocular surface. When formulated into a dermatologic sunscreen, bisoctrizole has minimal skin penetration. Work is still in progress by our laboratory to study its penetration into the Conjunctival or Corneal Tissues, but as an Ophthalmic Sunscreens, it should impregnate the surface layers of the Conjunctiva & Cornea so that its not washed out by blinking or the natural tears constantly irrigating the ocular surface. Bisoctrizole may penetrate the Conjunctiva and build a concentration in the episcleral connective tissue, and permeate through the Cornea and build an effective concentration in the eye's anterior chamber (aqueous humour) and serve as an effective barrier for UVA & UVB light that enters the eye, potentially preventing cataract formation and/or macular degeneration.

(16) Unlike some other organic sunscreen actives, Tinosorb has shown no estrogenic effects in vitro. Although there is very little systemic absorption of such agents when used on the ocular surface, it is a positive finding that this agent is safe in this regard. Tinosorb one of the first UV filters that have been made available in micronized nano form, and used in this format, it will minimize significant irritation to the eye or affecting the users' vision. Further, Tinosorb used in Particulate form (smaller than 100 nanometers) causes significantly less/no blurring for the user. From a preparation standpoint, Nanoparticle easily dispersible in oil or glycol systems, making it an ideal preparation for an ophthalmic emulsion.

(17) Advances in our understanding of the sun protective effects of organic and inorganic ingredients has lead to the development of sunscreen preparations with very effective protection against the ultraviolet rays of the sun. Until now, the effects of these ingredients has only been described for the skin, and the prior art has warned against the use of such ingredients directly on the ocular surface. In fact, people are asked to rinse their eyes thoroughly in case such ingredients get into their eyes. The present invention describes the specific use of such ingredients, particularly Tinosorb, onto the ocular surface itself. The present invention proposes formulations that provide UV protection for the eyes, while causing minimal irritation without making vision blurry.

(18) Examples of embodiments of the present invention include compositions that are manufactured as ophthalmic solutions, emollients, creams, or ointments that can be instilled directly on the eyes. It is understood that the use of the term ophthalmic solution shall include emollients, creams and ointments that can be instilled directly on the eyes.

(19) An embodiment of the present invention includes an ophthalmic solution comprised of diluted forms of Tinosorb an inorganic active ingredient by itself, or mixed with a weak concentration of another organic active ingredient.

(20) An example embodiment of the present invention includes an ophthalmic sunscreen composition, which is comprised of Tinosorb in an artificial tear vehicle.

(21) Another example embodiment of the present invention includes an ophthalmic sunscreen composition, which is comprised of Tinosorb with an organic sunscreen (e.g., Avobenzone) in an artificial tear vehicle.

(22) Another example embodiment of the present invention includes an ophthalmic sunscreen composition, which is comprised of Tinosorb with an inorganic sunscreen (e.g., Zinc Oxide) in an artificial tear vehicle.

(23) Another example embodiment of the present invention includes an ophthalmic sunscreen composition, which is comprised of Tinosorb with an organic, as well as an inorganic sunscreen an artificial tear

(24) vehicle.

(25) Another example of this invention includes said solution containing embodiments comprised of an emulsifier, silicone- or acrylic-based, glycosides, polyethylene glycols, or a mixture thereof.

(26) Another example of this invention includes embodiments comprised of sunscreen composition comprising an emulsifier selected from the group consisting of Arlacel P 135, DC 9011 silicone elastomer, Abil WE 09, Abil EM-90, Emulgade 68/50, Simulgel A, Simulgel EG, and mixtures thereof.

(27) Another example of this invention includes embodiments comprised of an emollient. Said emollient may be selected from the group consisting of Aloe extracts, ethers, oleaginous esters, and mixtures thereof.

(28) Another example of this invention includes embodiments comprised of an emollient selected from the group consisting of actiphyte of aloe vera, Cetiol OE, Lexol IPL, octyl palmitate, neopentyl glycol heptanoate, neopentyl glycol diheptanoate, Trivent NP-13, CJ2is alkyl benzoate, and mixtures thereof.

(29) Compositions of the present invention are now described, but are not limited to these embodiments.

(30) Ophthalmic sunscreen compositions according to the present invention may contain a liquid vehicle base, such as an artificial tear formulation, which may be water and/or oil-based, or an ophthalmic suspension or ointment and include at least one form of Tinosorb (e.g., Tinosorb M) by itself, or mixed with an organic- and/or an inorganic molecule with UV protecting features. Tinosorb can be used in nano form, and refers to a number of UV absorbers: Bemotrizinol (Tinosorb S), Bisoctrizole (Tinosorb M), Tris-Biphenyl Triazine (Tinosorb A2B), Octyl methoxycinnamate (Tinosorb OMC).

(31) Inorganic active ingredients may include, but not be limited to zinc oxide, titanium dioxide, iron oxide, zirconium oxide, and cerium oxide, optionally in micronized form as to prevent blurred vision when applied.

(32) Organic active ingredients may include, but not be limited to dioxybenzone, octinoxate, octisalate, homosalate, avobenzone, octocrylene, para-aminobenzoic acid, cinoxate, methyl anthranilate, octocrylene, padimate O, ensulizole, sulisobenzone, trolamine salicylate, and ecamsule.

(33) The inactive ingredients of the present invention shall also include emulsifier(s) and/or emollient(s). Silicone-based emulsifiers like polyethylene glycols, polysiloxanes, glycosides are excellent choices.

(34) Acrylic-based emulsifiers, and mixtures thereof may also be used safely for the present preparation. Emollients may include, but not be limited to aloe extracts, oleaginous esters, and ethers, or a combination thereof.

(35) The composition of the present invention shall also include, but not be limited to preservatives, chelating agents, and/or antioxidants.

(36) The following examples describe a composition of the present invention, but it is obviously not intended to limit the scope of the invention.

(37) Example 1: An ophthalmic sunscreen solution can be synthesized by mixing 5% micronized Tinosorb M in an ophthalmic artificial tear formulation. This solution may contain carboxymethylcellulose sodium 0.1%; glycerin 0.25%; boric acid; calcium chloride dihydrate; erythritol; levocarnitine; magnesium chloride hexahydrate; potassium chloride; purified water; sodium borate decahydrate; and sodium citrate dihydrate.

(38) Example 2: An ophthalmic sunscreen solution can be synthesized by mixing a range of 5% Tinosorb with micronized titanium dioxide and 3% octisalate in an ophthalmic artificial tear solution. This solution may contain carboxymethylcellulose sodium 0.1%; glycerin 0.25%; boric acid; calcium chloride dihydrate; erythritol; levocarnitine; magnesium chloride hexahydrate; potassium chloride; purified water; sodium borate decahydrate; and sodium citrate dihydrate.

(39) Example 3: An ophthalmic sunscreen ointment can be synthesized by mixing 5% micronized Tinosorb M in an ophthalmic ointment consisting of hypromellose, boric acid, sodium perborate, phosphonic acid, potassium chloride, purified water, and sodium chloride.

(40) Although several embodiments have been described in detail for purposes of illustration, various modifications may be made to each without departing from the scope and spirit of the invention. Accordingly, the invention is not to be limited, except as by the appended claims.