A topical formulation and a method of preparing the same
A topical formulation with a thymine-thymine compound and alkanediol solvent system addresses sun-induced skin damage by absorbing UV light and stimulating cellular repair, providing enhanced photo-protection and repair mechanisms.
Patent Information
- Application Number
- PCT/US2025/027099
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2025-02-28
- Filing Date
- 2025-04-30
- Publication Date
- 2025-11-06
AI Technical Summary
Existing topical formulations fail to effectively protect and treat skin damage caused by sun exposure, such as wrinkles, fine lines, and age spots, and there is a need for improved formulations that can reverse these effects.
A topical formulation containing a thymine-thymine compound in combination with a solvent system, including alkanediols like butylene glycol, which absorbs UV light, stimulates cellular DNA repair mechanisms, and provides broad-spectrum photo-protection.
The formulation effectively protects against UVA and UVB rays, boosts SPF to SPF 60, and stimulates the body's natural defense mechanisms to repair skin damage, offering a stable and effective solution for sun-induced skin issues.
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Abstract
Description
A TOPICAL FORMULATION AND A METHOD OF PREPARING THE SAME CROSS REFERENCE TO RELATED APPLICATION(S)
[0001] The present application claims priority to U.S. Provisional Patent Application No. 63 / 764,726 filed on February 28, 2025 and U.S. Provisional Patent Application No. 63 / 641,075 filed on May 1, 2024, the entire contents of which are incorporated in their entirety. FIELD OF THE INVENTION
[0002] The present invention relates to a topical formulation and a method of preparing the same. The topical formulation includes a thymine-thymine compound in combination with a solvent system comprising an alkanediol. BACKGROUND OF THE INVENTION
[0003] Overexposure to the sun and other toxic free radical sources and irritants induces skin damage, resulting in a variety of disfiguring skin conditions. Among these skin conditions, wrinkles, fine lines, loss of elasticity, sagging, dryness, age spots are caused by sun damage and aging. Wrinkles of the skin are either deep furrows and creases or fine lines. Wrinkles can occur on any part of the body, but especially where sun exposure is greatest, such as on the face, neck, forearms and hands.
[0004] It has been estimated that the majority of sun related damage to the skin is the result of outdoor exposure to the sun’s ultraviolet rays. Commercially available sunscreen compositions offer a solution to the harmful effects of over-exposure to these ultraviolet rays. However, due to changing atmospheric conditions, increasing number of skin cancer incidents, and increasing awareness of the problem, there is a continuous need of new topical formulations that can protect and / or treat the skin.
[0005] In particular, there is a need for a topical formulation that can reverse the damage that is caused by sun exposure. SUMMARY
[0006] It is an object of certain embodiments of the disclosure to provide a topical formulation, a method of preparing, and a method of using the topical formulation for protecting against atmospheric or extrinsic aging and treating skin damage caused by the sun.
[0007] In an embodiment, a topical formulation is provided. The topical formulation includes a thymine-thymine compound including a compound of Formula (I) or a salt thereof:wherein: each R1is independently H, (C1-C6)alkyl, (C3-C7)carbocycle or RaC(=O; or the two R1groups together form a —(C3-C8)alkyl-group, a —(C2-C6)alkyl-Y—(C2-C6)alkyl-group or a — (C1-C6)alkyl-Y′—(C1-C6)alkyl-group; or the dashed bonds labeled “a” are absent and the dashed bonds labeled “b” are double bonds; or all the dashed bonds are single bonds; R2is H, (C1-C6)alkyl or aryl, wherein aryl is optionally substituted with one or more (e.g. 1, 2, 3, 4 or 5) Z1groups; R3is H, (C1-C6)alkyl or aryl, wherein aryl is optionally substituted with one or more (e.g. 1, 2, 3, 4 or 5) Z1groups; R4is hydroxy, carboxy, (C1-C6)alkoxycarbonyl, —OPO3H2, —ORc, or —NRdRe; and R5is H; or R4and R5taken together are oxo; Y is O, S, NH, P, P(═O) or POH; Y′ is Si(Rb)2 or —Si(Rb)2—O—Si(Rb)2—; each Rais independently (C1-C6)alkyl, (C3-C7)carbocycle or aryl, wherein aryl is optionally substituted with one or more (e.g.1, 2, 3, 4 or 5) Z1groups; each Rbis independently (C1-C6)alkyl, (C3-C7)carbocycle or aryl, wherein aryl is optionally substituted with one or more (e.g.1, 2, 3, 4 or 5) Z1groups; Rcis Rfor a C1-C20saturated or C2-C20unsaturated carbon chain that is optionally substituted with one or more groups independently selected from oxo (═O), hydroxy, mercapto, (C1-C6)alkoxy, (C1-C6)alkoxycarbonyl, (C1-C6)alkanoyloxy, NRdRe, carboxy, and aryl, wherein aryl is optionally substituted with one or more (e.g.1, 2, 3, 4 or 5) Z1groups; Rd is H, (C1-C6)alkyl, or (C1-C6)alkanoyl; Reis H or a C1-C20saturated or C2-C20unsaturated carbon chain that is optionally substituted with one or more groups independently selected from oxo (═O), hydroxy, mercapto, (C1-C6)alkoxy, (C1-C6)alkoxycarbonyl, (C1-C6)alkanoyloxy, NRdRe, carboxy, and aryl, wherein aryl is optionally substituted with one or more (e.g.1, 2, 3, 4 or 5) Z1groups; each Rf, is:each Z1is independently selected from (C1-C6)alkyl, halogen, —CN, —ORn1, —NRq1Rr1, —NRn1CORp1, —NRn1CO2Rp1, NO2, —C(O)Rn1, —C(O)ORn1and —C(O)NRq1Rr1, wherein any (C1-C6)alkyl of Z1is optionally substituted with one or more (e.g.1, 2, 3, 4, 5 or 6) halogen; each Rn1is independently selected from H and (C1-C6)alkyl, wherein any (C1-C6)alkyl of Rn1 is optionally substituted with one or more (e.g.1, 2, 3, 4, 5 or 6) halogen; each Rp1is independently (C1-C6)alkyl; and Rq1 and Rr1 are each independently selected from H and (C1-C6)alkyl or Rq1 and Rr1together with the nitrogen to which they are attached form a piperidine, pyrrolidine, morpholine, azetidine, thiomorpholine, piperazine or 4-methylpiperazine. The topical formulation further includes a solvent system. The topical formulation as described herein includes the thymine-thymine compound in an amount of about 0.01 wt% to about 10 wt%, based on total weight of the topical formulation.
[0008] In some embodiments, the solvent system may include propanediol, an alkanediol including a 4 carbon to 20 carbon backbone, or a combination thereof. In some embodiments, the alkanediol may include butylene glycol, pentylene glycol or hexylene glycol.
[0009] In some embodiments, the topical formulation may further include a surfactant. In some embodiments, the surfactant may include an oleyl alcohol or its ethoxylates, polyglycerol esters or a combination thereof.
[0010] In some embodiments, the topical formulation may further include a phospholipid. The phospholipid may include a liposome.
[0011] In some embodiments, the topical formulation may further include a preservative. In some embodiments, the preservative may include phenoxyethanol.
[0012] In some embodiments, the topical formulation may include water.
[0013] In some embodiments, the topical formulation may include an antioxidant.
[0014] In some embodiments, the antioxidant may include resveratrol, ubiquinone, vitamin C, ascorbic acid, emblica, a green tea polyphenol, or a combination thereof.
[0015] In some embodiments, the topical formulation may protect against UVA and UVB waves.
[0016] In some embodiments, the thymine-thymine compound of Formula (I) may be a compound of Formula Ia: or a salt thereof
[0017] In some embodiments, the thymine-thymine compound of Formula (I) may be a compound of Formula Ib: or a salt thereof.
[0018] In some embodiments, the thymine-thymine compound of Formula (I), wherein each R1of the thymine-thymine compound of Formula (I) is independently H or (C1-C6)alkyl.
[0019] In some embodiments, the thymine-thymine compound of Formula (I), wherein each R1of the thymine-thymine compound of Formula (I) is H.
[0020] In some embodiments, the thymine-thymine compound of Formula (I) may be selected from the group consisting of: , and salts thereof.
[0021] In another embodiment, a method of preparing a topical formulation is provided. The method includes mixing a thymine-thymine compound including a compound of Formula (I) and a solvent system to form a topical formulation. The mixing occurs at a temperature of about 45°C to about 60°C for at least about 1 hour, wherein the compound of Formula (I) is:wherein: each R1is independently H, (C1-C6)alkyl, (C3-C7)carbocycle or RaC(=O; or the two R1groups together form a —(C3-C8)alkyl-group, a —(C2-C6)alkyl-Y—(C2-C6)alkyl-group or a — (C1-C6)alkyl-Y′—(C1-C6)alkyl-group; or the dashed bonds labeled “a” are absent and the dashed bonds labeled “b” are double bonds; or all the dashed bonds are single bonds; R2is H, (C1-C6)alkyl or aryl, wherein aryl is optionally substituted with one or more (e.g. 1, 2, 3, 4 or 5) Z1groups; R3is H, (C1-C6)alkyl or aryl, wherein aryl is optionally substituted with one or more (e.g. 1, 2, 3, 4 or 5) Z1groups; R4is hydroxy, carboxy, (C1-C6)alkoxycarbonyl, —OPO3H2, —ORc, or —NRdRe; and R5is H; or R4and R5taken together are oxo; Y is O, S, NH, P, P(═O) or POH; Y′ is Si(Rb)2or —Si(Rb)2—O—Si(Rb)2—; each Ra is independently (C1-C6)alkyl, (C3-C7)carbocycle or aryl, wherein aryl is optionally substituted with one or more (e.g.1, 2, 3, 4 or 5) Z1groups; each Rb is independently (C1-C6)alkyl, (C3-C7)carbocycle or aryl, wherein aryl is optionally substituted with one or more (e.g.1, 2, 3, 4 or 5) Z1groups; Rc is Rf or a C1-C20 saturated or C2-C20 unsaturated carbon chain that is optionally substituted with one or more groups independently selected from oxo (═O), hydroxy, mercapto, (C1-C6)alkoxy, (C1-C6)alkoxycarbonyl, (C1-C6)alkanoyloxy, NRdRe, carboxy, and aryl, wherein aryl is optionally substituted with one or more (e.g.1, 2, 3, 4 or 5) Z1groups; Rdis H, (C1-C6)alkyl, or (C1-C6)alkanoyl; Re is H or a C1-C20 saturated or C2-C20 unsaturated carbon chain that is optionally substituted with one or more groups independently selected from oxo (═O), hydroxy, mercapto, (C1-C6)alkoxy, (C1-C6)alkoxycarbonyl, (C1-C6)alkanoyloxy, NRdRe, carboxy, and aryl, wherein aryl is optionally substituted with one or more (e.g.1, 2, 3, 4 or 5) Z1groups; each Rf, is:each Z1is independently selected from (C1-C6)alkyl, halogen, —CN, —ORn1, —NRq1Rr1, —NRn1CORp1, —NRn1CO2Rp1, NO2, —C(O)Rn1, —C(O)ORn1 and —C(O)NRq1Rr1, wherein any (C1-C6)alkyl of Z1is optionally substituted with one or more (e.g.1, 2, 3, 4, 5 or 6) halogen; each Rn1 is independently selected from H and (C1-C6)alkyl, wherein any (C1-C6)alkyl of Rn1is optionally substituted with one or more (e.g.1, 2, 3, 4, 5 or 6) halogen; each Rp1 is independently (C1-C6)alkyl; and Rq1 and Rr1 are each independently selected from H and (C1-C6)alkyl or Rq1 and Rr1together with the nitrogen to which they are attached form a piperidine, pyrrolidine, morpholine, azetidine, thiomorpholine, piperazine or 4-methylpiperazine.
[0022] In some embodiments, the method may further include treating the topical formulation. In some embodiments, the treating may include milling, roller milling, or colloid milling.
[0023] In some embodiments, the topical formulation may include the thymine-thymine compound in an amount of about 0.01 wt% to about 10 wt% based on total weight of the topical formulation.
[0024] In an embodiment, a method of treating is also provided. The method of treating includes treating a skin of a subject for effects of radical-induced damage including applying a topical formulation as described herein.
[0025] In some embodiments, the method of treating includes applying an effective amount of the topical formulation.
[0026] In some embodiments, the skin may be brightened after applying the topical formulation.
[0027] In some embodiments, the topical formulation may prevent cyclopyrimidine dimer (CPD) formation when compared to skin that is not treated with the topical formulation. In some embodiments, the applying of the topical formulation may periodically be repeated.
[0028] The term “administering the topical formulation” as used herein refers to applying topically onto a skin of a subject, e.g., on the face, neck, hands, feet, elbows, knees, and the like. As used herein, the terms “application,” “apply,” and “applying” with respect to a disclosed topical formulation or method of using a disclosed topical formulation, refer to any manner of administering a topical formulation to the skin, for example, the skin of a person, such as the skin of a patient, which, in medical or cosmetology practice, delivers the formulation to the subject's skin surface. Smearing, rubbing, spreading, spraying a disclosed topical formulation, with or without the aid of suitable devices, on a subject's skin are all included within the scope of the term “application,” as used herein. The term “topical” or “topically” with respect to administration or application of a disclosed skincare formulation refers to epicutaneous administration or application, onto skin. The application can be manually (e.g., directly with the hands) or manipulated with an applicator, cloth, device, roll-on, wipes, unit dose sponge applicators, liquid applied with swabs or cotton balls, impregnated gauze or other substrates, coated silicone sheets or other sheet goods, coated bandages or externally fixed devices, towelettes, individually packages pledgettes or pads, transdermal delivery system, etc. Administration can be self- administration or administration by a medical professional or caregiver. DETAILED DESCRIPTION
[0029] According to various embodiments, the topical formulation of the present disclosure has a unique mechanism of action compared to existing agents and compositions in the market. The topical formulation of the present disclosure absorbs UV light and provides photo-protection to the skin. The resulting photo-products may initiate the body’s natural defense mechanisms by increasing cellular production of DNA repairing enzymes. Thus, the topical formulation of the present disclosure provides a stable formulation for protecting the skin and stimulating a repair process of the skin.
[0030] It has been surprisingly found that preparing a topical formulation including a thymine- thymine compound of Formula (I) or a salt thereof and a solvent system including, at least, butylene glycol or propanediol was able to form a stable formulation and effectively treat and / or protect the skin. Unlike solvents already known in the cosmetic industry, such as dimethyl sulfoxide (DMSO), the present solvent system was not known to be used in a topical formulation. In fact, the present solvent system in combination with the thymine-thymine compound of Formula (I) has been found to produce a hazy solution, though there was no grit or graininess in the final topical formulation. It was also found that by utilizing the solvent system as described herein, a low amount of thymine-thymine compound of Formula (I) can be incorporated in the topical formulation to be effective. That is, the amount of thymine-thymine compound of Formula (I) can be about 10 wt% or less, about 5 wt% or less, 1 wt% or less, or even as low as 0.5% or less to be effective in the formulation.
[0031] In another embodiment, an additional topical formulation may further include a thymine- thymine compound of Formula (I) in combination with a mineral active agent. A thymine-thymine compound as described herein was not known to be a sun screening agent, nor have a strong absorption across a broad UV range. Thus, when the present inventors incorporated a thymine- thymine compound according to Formula (I), it was surprising to find that it boosted the SPF value of the sunscreen to SPF 60. Without being bound by theory, the inventors believe that the thymine- thymine compound of Formula (I) acts on the secondary case of the erythema, edema and other damage caused by UV by interacting with ROS (reactive oxygen species) and upregulating innate defenses.
[0032] In an embodiment a topical formulation is provided. The topical formulation includes a thymine-thymine compound of Formula (I) or a salt thereof and a solvent system, wherein the thymine-thymine compound of Formula (I) is included in an amount of about 0.01 wt% to about 10 wt%, based on total weight of the topical formulation. The thymine-thymine compound of Formula (I) or a salt thereof is as follows:wherein: each R1is independently H, (C1-C6)alkyl, (C3-C7)carbocycle or RaC(=O; or the two R1groups together form a —(C3-C8)alkyl-group, a —(C2-C6)alkyl-Y—(C2-C6)alkyl-group or a — (C1-C6)alkyl-Y′—(C1-C6)alkyl-group; or the dashed bonds labeled “a” are absent and the dashed bonds labeled “b” are double bonds; or all the dashed bonds are single bonds; R2is H, (C1-C6)alkyl or aryl, wherein aryl is optionally substituted with one or more (e.g. 1, 2, 3, 4 or 5) Z1groups; R3is H, (C1-C6)alkyl or aryl, wherein aryl is optionally substituted with one or more (e.g. 1, 2, 3, 4 or 5) Z1groups; R4is hydroxy, carboxy, (C1-C6)alkoxycarbonyl, —OPO3H2, —ORc, or —NRdRe; and R5is H; or R4and R5taken together are oxo; Y is O, S, NH, P, P(═O) or POH; Y′ is Si(Rb)2or —Si(Rb)2—O—Si(Rb)2—; each Ra is independently (C1-C6)alkyl, (C3-C7)carbocycle or aryl, wherein aryl is optionally substituted with one or more (e.g.1, 2, 3, 4 or 5) Z1groups; each Rb is independently (C1-C6)alkyl, (C3-C7)carbocycle or aryl, wherein aryl is optionally substituted with one or more (e.g.1, 2, 3, 4 or 5) Z1groups; Rc is Rf or a C1-C20 saturated or C2-C20 unsaturated carbon chain that is optionally substituted with one or more groups independently selected from oxo (═O), hydroxy, mercapto, (C1-C6)alkoxy, (C1-C6)alkoxycarbonyl, (C1-C6)alkanoyloxy, NRdRe, carboxy, and aryl, wherein aryl is optionally substituted with one or more (e.g.1, 2, 3, 4 or 5) Z1groups; Rd is H, (C1-C6)alkyl, or (C1-C6)alkanoyl; Reis H or a C1-C20saturated or C2-C20unsaturated carbon chain that is optionally substituted with one or more groups independently selected from oxo (═O), hydroxy, mercapto, (C1-C6)alkoxy, (C1-C6)alkoxycarbonyl, (C1-C6)alkanoyloxy, NRdRe, carboxy, and aryl, wherein aryl is optionally substituted with one or more (e.g.1, 2, 3, 4 or 5) Z1groups; each Rf, is:each Z1is independently selected from (C1-C6)alkyl, halogen, —CN, —ORn1, —NRq1Rr1, —NRn1CORp1, —NRn1CO2Rp1, NO2, —C(O)Rn1, —C(O)ORn1and —C(O)NRq1Rr1, wherein any (C1-C6)alkyl of Z1is optionally substituted with one or more (e.g.1, 2, 3, 4, 5 or 6) halogen; each Rn1is independently selected from H and (C1-C6)alkyl, wherein any (C1-C6)alkyl of Rn1 is optionally substituted with one or more (e.g.1, 2, 3, 4, 5 or 6) halogen; each Rp1 is independently (C1-C6)alkyl; and Rq1 and Rr1 are each independently selected from H and (C1-C6)alkyl or Rq1 and Rr1 together with the nitrogen to which they are attached form a piperidine, pyrrolidine, morpholine, azetidine, thiomorpholine, piperazine or 4-methylpiperazine.
[0033] In some embodiments, each R1of the thymine-thymine compound of Formula (I) is independently H or (C1-C6)alkyl. In some embodiments, each R1of the thymine-thymine compound of Formula (I) is H.
[0034] In some embodiments, the solvent system may include propanediol, an alkanediol including a four carbon to 20 carbon backbone, or a combination thereof. In some embodiments, the alkanediol may include butylene glycol, pentylene glycol, or hexylene glycol.
[0035] In some embodiments, the topical formulation may further include a surfactant. In some embodiments, the surfactant may include an olelyl alcohol or its ethoxylates, polyglycerol esters, or a combination thereof.
[0036] In some embodiments, the sunscreen formulation may further include a phospholipid. In some embodiments, the phospholipid may include a liposome.
[0037] In some embodiments, the sunscreen formulation may further include a preservative. Suitable preservatives include, for example, phenoxyethanol, a solution of paraben, pentanediol and sorbic acid, as well as silver complexes which are known under the commercial reference Surfacine® and other classes of substances set out in annex 6, parts A and B of the cosmetic regulations, i.e. a suitable preservative.
[0038] In some embodiments, the topical formulation may further include water.
[0039] In some embodiments, the topical formulation may include an antioxidant. The antioxidant included may provide a broad action spectrum of protection covering many oxidation pathways and quenching many types of reactive oxygen species (ROS). In some embodiments, the antioxidant may include resveratrol, ubiquinone, ascorbic acid, vitamin C, emblica, a green tea polyphenol, or a combination thereof. In some embodiments, the antioxidant may be included in an amount of about 2% or less. In other embodiments, the antioxidant may be included in an amount of about 1.8% or less, about 1.5% or less, about 1.3% or less, about 1% or less, about 0.8% or less, about 0.5% or less, about 0.2% or less, about 0.1% or less, or about 0.001% or less. In some embodiments, the topical formulation may include two or more antioxidants, three or more antioxidants, four or more antioxidants, five or more antioxidants, or six or more antioxidants, wherein the antioxidants are any of the antioxidants as described herein.
[0040] In some embodiments, the topical formulation of the present disclosure may have a sun protection factor (SPF) of about 15 to about 90, about 30 to about 70, about 40 to about 50, or about 50. In some embodiments, the topcial formulation of the present disclosure covers a broad spectrum. As understood herein, the term “broad spectrum” refers to the Food and Drug Administration (“FDA”) broad spectrum requirement for attenuation of UVA and UVB. That is, the topical formulation can protect against a wavelength of about 250 nm to about 500 nm, about 270 nm to about 470 nm, about 300 nm to about 450 nm, or about 320 nm to about 400 nm.
[0041] In some embodiments, the thymine-thymine compound of Formula (I) may be a compound of Formula Ia or a salt thereof: .
[0042] In some embodiments, the thymine-thymine compound of Formula (I) may be a compound of Formula Ib or a salt thereof:.
[0043] In some embodiments, the thymine-thymine compound of Formula (I) may be selected from the group of: , , , , , and salts thereof.
[0044] In some embodiments, the thymine-thymine compound of Formula (I) may be selected form the group:.
[0045] In some embodiments, the topical formulation may further include an emulsifier. Suitable emulsifiers include, without limitations, PEG- 30 Dipolyhydroxystearate, PEG-4 Dilaurate, PEG- 8 Dioleate, PEG-40 Sorbitan Peroleate, PEG-7 Glyceryl Cocoate, PEG-20 Almond Glycerides, PEG-25 Hydrogenated Castor Oil, Glyceryl Stearate (and) PEG-100 Stearate, PEG-7 Olivate, PEG-8 Oleate, PEG-8 Laurate, PEG-60 Almond Glycerides, PEG-20 Methyl Glucose Sesquistearate, PEG-40 Stearate, PEG-100 Stearate, PEG-80 Sorbitan Laurate, Steareth-2, Steareth-12, Oleth-2, Ceteth-2, Laureth-4, Oleth-10, Oleth-10 / Polyoxyl 10 Oleyl Ether, Ceteth- 10, lsosteareth-20, Ceteareth-20, Oleth-20, Steareth-20, Steareth-21 , Ceteth-20, lsoceteth-20, Laureth-23, Steareth-100, Glyceryl Stearate Citrate, Glyceryl Stearate SE (self-emulsifying), stearic acid, or a combination thereof.
[0046] In some embodiments, the topical formulation may include a preservative. The preservative may be phenoxyethanol. The preservative may be included in an amount of about 0.1 wt% to about 20 wt%, about 0.3 wt% to about 18 wt%, about 0.5 wt% to about 15 wt%, about 0.7 wt% to about 13 wt%, about 1 wt% to about 10 wt%, about 2 wt% to about 8 wt%, or about 3 wt% to about 6 wt%, based on total weight of the topical formulation.
[0047] In some embodiments, the topical formulation may include an additional solvent. Suitable additional solvents that may be used in the topical compositions described herein include, without limitations, polysorbate 20, water, ethoxylated or propoxylated diglycol, ethanol, propanol, isopropanol, glycerin, methoxyisopropanol, PPG-2 methyl ether, PPG-3 methyl ether, propylene glycol butyl ether, PPG-2 butyl ether, phenoxyisopropanol, butoxyethanol, butoxydiglycol, methoxydiglycol, phenoxyethanol, PPG-3 butyl ether, PPG-2 propyl ether, propylene glycol propyl ether, or dipropylene glycol dimethyl ether, or mixtures and combinations or individual ethoxylates, propoxylates and glyceryl esters thereof. In certain embodiments, the additional solvent may include water.
[0048] In some embodiments, the solvent system may be included in an amount of about 5 wt% to about 8090 wt%, about 10 wt% to about 85 wt%, about 15 wt% to about 80 wt%, about 20 wt% to about 75 wt%, about 25 wt% to about 70 wt%, about 30 wt% to about 65 wt%, about 35 wt% to about 60 wt%, about 40 wt% to about 55 wt%, or about 45 wt% to about 50 wt%, based on total weight of the topical formulation.
[0049] In some embodiments, the antioxidant may include resveratrol, ubiquinone, such as coenzyme Q10, vitamin C, an ascorbate, ascorbic acid, emblica, a green tea polyphenol, or a combination thereof.
[0050] Certain plants, such as green tea, that are composed of a high content of polyphenols which are bioflavonoids and have antioxidant properties and may be included in any of the topical formulations described herein.
[0051] In certain embodiments, the topical formulation includes an effective amount of polyphenol isolates, derived from green tea with potent antioxidant properties, to assist in minimizing free-radical induced skin damage. Suitable green tea polyphenols include, but are not limited to, catechins, such as epigallocatechin gallate (EGCG), epigallocatechin (EGC), epicatechin gallate (ECG), and epicatechin (EC), cis and trans isomers thereof, salts thereof, equivalent derivatives thereof, and combinations thereof.
[0052] In certain embodiments, the sunscreen formulation may include any of the green tea polyphenols described herein in combination with at least one additional antioxidant.
[0053] In one embodiment, the one or more antioxidants may be selected from the group of cinnamic acid, ferulic acid, caffeic acid, p-coumaric acid, sinapinic acid, cis and trans isomers thereof, salts thereof, equivalent derivatives thereof, and combinations thereof.
[0054] In certain embodiments, the one or more antioxidants may be selected from the group of gallic acid, delphinidin, luteolin, quercetin, cyanidin, taxifolin, kaempferol, malvidin, hesperidin, pelargonidin, apigenin, naringenin, chrysin, ergothioneine, glutathione, emblica, cis and trans isomers thereof, salts thereof, equivalent derivatives thereof, and combinations thereof.
[0055] In certain embodiments, the one or more antioxidants may be selected from the group of apigenin, ergothioneine, glutathione, emblica, cis and trans isomers thereof, salts thereof, equivalent derivatives thereof, and combinations thereof.
[0056] In certain embodiments, the antioxidant may include resveratrol. The resveratrol may be included in an amount of about 0.001 wt% to about 2 wt%, about 0.005 wt% to about 1.8 wt%, about 0.01 wt% to about 1.5 wt%, about 0.05 wt% to about 1.2 wt%, about 0.1 wt% to about 1 wt%, or about 0.5 wt% to about 0.8 wt%, based on total weight of the topical formulation.
[0057] In certain embodiments, the antioxidant may include emblica, such as Phyllanthus emblica fruit extract. The emblica may be included in an amount of about 0.001 wt% to about 2 wt%, about 0.005 wt% to about 1.8 wt%, about 0.01 wt% to about 1.5 wt%, about 0.05 wt% to about 1.2 wt%, about 0.1 wt% to about 1 wt%, or about 0.5 wt% to about 0.8 wt%, based on total weight of the topical formulation.
[0058] In certain embodiments, the antioxidant may include ubiquinone. The ubiquinone may be included in an amount of about 0.001 wt% to about 2 wt%, about 0.005 wt% to about 1.8 wt%, about 0.01 wt% to about 1.5 wt%, about 0.05 wt% to about 1.2 wt%, about 0.1 wt% to about 1 wt%, or about 0.5 wt% to about 0.8 wt%, based on total weight of the topical formulation.
[0059] In certain embodiments, the antioxidant may include ascorbic acid, ascorbate or vitamin C. The ascorbic acid, ascorbate or vitamin C may be included in an amount of about 0.001 wt% to about 2 wt%, about 0.005 wt% to about 1.8 wt%, about 0.01 wt% to about 1.5 wt%, about 0.05 wt% to about 1.2 wt%, about 0.1 wt% to about 1 wt%, or about 0.5 wt% to about 0.8 wt%, based on total weight of the topical formulation.
[0060] In some embodiments, the ascorbate may include ascorbic acid, or its derivatives, such as ascorbyl palmitate, sodium ascorbate, potassium ascorbate, ammonium ascorbate, triethanolamine ascorbate, ascorbyl phosphate or magnesium ascorbyl phosphate, ascorbic acid polypeptides, ascorbyl glucosamine, ascorbic acid polymers, esters of ascorbic acid, amides of ascorbic acid, L- ascorbic acid, tetrahexyldecyl ascorbate, known as vitamin C, or other derivatives, or related compounds, including botanical or herbal extracts, such as extracts of acerola, citrus extracts, strawberry, which may supply L-ascorbic acid or its derivatives.
[0061] In certain embodiments, the antioxidant may include biotin or vitamin B. The biotin or vitamin B may be included in an amount of about 0.001 wt% to about 2 wt%, about 0.005 wt% to about 1.8 wt%, about 0.01 wt% to about 1.5 wt%, about 0.05 wt% to about 1.2 wt%, about 0.1 wt% to about 1 wt%, or about 0.5 wt% to about 0.8 wt%, based on total weight of the topical formulation.
[0062] In certain embodiments, the antioxidant may include a green tea polyphenol, such as a Camellia Sinensis leaf polyphenol. The green tea polyphenol, such as a Camellia Sinensis leaf polyphenol may be included in an amount of about 0.001 wt% to about 2 wt%, about 0.005 wt% to about 1.8 wt%, about 0.01 wt% to about 1.5 wt%, about 0.05 wt% to about 1.2 wt%, about 0.1 wt% to about 1 wt%, or about 0.5 wt% to about 0.8 wt%, based on total weight of the topical formulation.
[0063] In certain embodiments, the antioxidant may include emblica, ubiquinone, ascorbic acid, biotin, resveratrol, and Camellia Sinensis leaf polyphenol.
[0064] In some embodiments, the topical formulation may be substantially free of cyclomethicone, low molecular weight dimethicone, dry esters, for example branched seters, such as isopropyl esters, squalane, squalene, hemisqualane or a combination thereof.
[0065] In some embodiments, the topical formulation does not include cyclomethicone, low molecular weight dimethicone, dry esters, for example branched seters, such as isopropyl esters, squalane, squalene, hemisqualane or a combination thereof.
[0066] In certain embodiments, the topical formulation may further include a cosmetically acceptable excipient. Exemplary cosmetically acceptable excipients, include, without limitations, epidermal penetration enhancer, solvent, mild surfactants, oil bodies, emulsifiers, pearlescent waxes, consistency regulators, thickeners, rheology modifiers, suspending agents, chelating agents, preservatives, super fatting agents, stabilizers, polymers, silicone or siloxane compounds, fats, waxes, lecithins, phospholipids, UV photoprotective factors, biogenic active ingredients, additional antioxidants, deodorants, antiperspirants, antidandruff agents, film formers, swelling agents, insect repellents, self-tanning agents, tyrosinase inhibitors, hydrotropes, solubilizers, perfume oils, dyes, zinc oxide, fatty alcohols, esters of fatty acids, adjuvants, Natural or Synthetic Triglycerides Including Glyceryl Esters and Derivatives, hydrocarbon oils, super-fatting agents, polymers, biogenic active ingredients, hydrotropic agents, bacteria-inhibiting agents, colorants, UV screening agents, agents that absorb UV light and provide photo protection to the skin, or combinations thereof. In certain embodiments, the topical composition includes a cosmetically acceptable excipient selected from the group of solvents, emulsifiers, consistency regulators, thickeners, suspending agents, additional antioxidants, preservatives, perfume oils, or a combination thereof. In certain embodiments, the topical composition is free or substantially free of silicone compounds.
[0067] In certain embodiments, the solvent system includes an alkanediol (e.g., propylene glycol which may also be referred to as propanediol) that is present in the topical formulation in an amount of from about 2 wt.% to about 25 wt.%, from about 5 wt.% to about 15 wt.%, or from about 8 wt.% to about 12 wt.%, based on total weight of the sunscreen formulation.
[0068] In certain embodiments, the cosmetically acceptable excipient includes glycerin in the topical formulation in an amount of from about 2 wt.% to about 25 wt.%, from about 5 wt.% to about 15 wt.%, or from about 8 wt.% to about 12 wt.%, based on total weight of the topical formulation.
[0069] In certain embodiments, the cosmetically acceptable excipient includes water in the topical formulation in an amount of from about 5 wt.% to about 95 wt.%, about 10 wt.% to about 95 wt.%, about 20 wt.% to about 80 wt.%, from about 35 wt.% to about 70 wt.%, or from about 50 wt.% to about 60 wt.%, based on total weight of the topical formulation.
[0070] In certain embodiments, the cosmetically acceptable excipient includes natural gums (e.g., a natural plant gum). Suitable natural gums include, without limitations, guar gum, carob gum, konjac gum, xanthan gum, sclerotium gum, acacia gum, cellulose gum (modified or not), or a combination thereof.
[0071] In certain embodiments, the cosmetically acceptable excipient includes the natural gum in the topical formulation in an amount of from above 0 wt.% to about 5 wt.%, from about 0.1 wt.% to about 2 wt.%, or from about 0.2 wt.% to about 0.8 wt.%, based on total weight of the topical formulation.
[0072] In certain embodiments, the cosmetically acceptable excipient includes an emulsifier. In some embodiments, the emulsifier may include salts of stearic acid, polyglyceryl-3- methylglycosedistearate, or a combination thereof.
[0073] Further suitable emulsifiers are phosphate esters and the salts thereof such as cetyl phosphate (Amphisol®A), diethanolamine cetyl phosphate (Amphisol®DEA), potassium cetyl phosphate (Amphisol®K), sodium cetearyl sulfate, sodium glyceryl oleate phosphate, hydrogenated vegetable glycerides phosphate and mixtures thereof. Further suitable emulsifiers are sorbitan oleate, sorbitan sesquioleate, sorbitan isostearate, sorbitan trioleate, Cetearyl Glucoside, Lauryl Glucoside, Decyl Glucoside, Sodium Stearoyl Glutamate, Sucrose Polystearate and Hydrated Polyisobutene. Furthermore, one or more synthetic polymers may be used as an emulsifier. For example, PVP eicosene copolymer, acrylates / C10-3o alkyl acrylate crosspolymer, acrylates / steareth-20 methacrylate copolymer, PEG-22 / dodecyl glycol copolymer, PEG- 45 / dodecyl glycol copolymer, and mixtures thereof.
[0074] In certain embodiments, the cosmetically acceptable excipient includes a chelating agent. Suitable chelating agents include, without limitations, disodium ethylenediaminetetraacetic acid (EDTA), diethylenetriaminepentaacetic acid (DTPA), N-(hydroxyethyl)-ethylenediaminetriacetic acid (HEDTA), and nitrilotriacetic acid (NTA).
[0075] In certain embodiments, the cosmetically acceptable excipient includes the chelating agent in the topical formulation in an amount of from above 0 wt.% to about 5 wt.%, from about 0.01 wt.% to about 0.5 wt.%, or from about 0.05 wt.% to about 0.3 wt.%, based on total weight of the topical formulation. In one embodiment, the cosmetically acceptable excipient includes a chelating agent that is EDTA in the topical formulation in an amount of from above 0 wt.% to about 5 wt.%, from about 0.01 wt.% to about 0.5 wt.%, or from about 0.05 wt.% to about 0.3 wt.%, based on total weight of the topical formulation.
[0076] In certain embodiments, the cosmetically acceptable excipient includes additional antioxidants such as a form of Vitamin E. Suitable forms of Vitamin E that may be included in the topical composition can be selected from alpha, beta, delta, and gamma tocopherols, and alpha, beta, delta and gamma tocotrienols, and combinations thereof.
[0077] In certain embodiments, any combination of any of the forms of Vitamin E may be present (individually or cumulatively) in the topical formulation in an amount of from about 0.001 wt.% to about 2 wt.%, from about 0.005 wt.% to about 1.8 wt.%, from about 0.01 wt.% to about 1.5 wt.%, from about 0.05 wt.% to about 1.2 wt%, about 0.1 wt.% to about 1 wt.%, or about 0.5 wt.% to about 0.8 wt.% based on total weight of the topical formulation.
[0078] In certain embodiments, the cosmetically acceptable excipient in the topical formulation includes a preservative. Suitable preservative agents include, for example, a solution of paraben, pentanediol and sorbic acid, as well as silver complexes which are known under the commercial reference Surfacine® and other classes of substances set out in annex 6, parts A and B of the cosmetic regulations, i.e. a suitable preservative.
[0079] In certain embodiments, the cosmetically acceptable excipient includes a preservative in an amount of above 0 to about 5 wt.%, from about 0.3 wt.% to about 3 wt.%, or from about 0.5 wt.% to about 2 wt.%, based on total weight of the topical formulation.
[0080] In certain embodiments, the cosmetically acceptable excipient includes a perfume oil. Suitable perfume oils include mixtures of natural and synthetic fragrances. Natural fragrances are extracts from flowers (lily, lavender, rose, jasmine, neroli, ylang-ylang), stems and leaves (geranium, patchouli, petitgrain), fruits (aniseed, coriander, cumin, juniper), fruit peels (bergamot, lemon, orange), roots (mace, angelica, celery, cardamom, costus, iris, calmus), woods (pinewood, sandalwood, guaiac wood, cedarwood, rosewood), herbs and grasses (tarragon, lemongrass, sage, thyme), needles and branches (spruce, fir, pine, dwarf-pine), resins and balsams (galbanum, elemi, benzoin, myrrh, olibanum, opoponax). Typical synthetic fragrance compounds are products of the ester, ether, aldehyde, ketone, alcohol and hydrocarbon type. Fragrance compounds of the ester type are, for example, benzyl acetate, phenoxyethyl isobutyrate, p-tert-butylcyclohexyl acetate, linalyl acetate, dimethylbenzylcarbinyl acetate, phenylethyl acetate, linalyl benzoate, benzyl formate, ethyl-methylphenyl glycinate, allyl cyclohexylpropionate, styrallyl propionate and benzyl salicylate. The ethers include, for example, benzyl ethyl ether, the aldehydes include, for example, the linear alkanals having 8 to 18 carbon atoms, citral, citronellal, citronellyloxyacetaldehyde, cyclamen aldehyde, hydroxycitronellal, lilial and bourgeonal, and the ketones include, for example, the ionones, α-isomethylionone and methyl cedryl ketone, the alcohols include anethole, citronellol, eugenol, isoeugenol, geraniol, linalool, phenylethyl alcohol and terpineol, and the hydrocarbons include mainly the terpenes and balsams.
[0081] Essential oils of relatively low volatility, which are mostly used as aroma components, are also suitable as perfume oils, e.g. sage oil, chamomile oil, oil of cloves, melissa oil, mint oil, cinnamon leaf oil, linden blossom oil, juniper berry oil, vetiver oil, olibanum oil, galbanum oil, labolanum oil and lavandin oil. Other suitable oils include bergamot oil, dihydromyrcenol, lilial, lyral, citronellol, phenylethyl alcohol, α-hexylcinnamaldehyde, geraniol, benzylacetone, cyclamen aldehyde, linalool, boisambrene forte, ambroxan, indole, hedione, sandelice, lemon oil, mandarin oil, orange oil, allyl amyl glycolate, cyclovertal, lavandin oil, clary sage oil, β- damascone, geranium oil bourbon, cyclohexyl salicylate, Vertofix coeur, iso-E-super, Fixolide NP, evernyl, iraldein gamma, phenylacetic acid, geranyl acetate, benzyl acetate, rose oxide, romilat, irotyl and floramat alone or in mixtures.
[0082] In certain embodiments, the cosmetically acceptable excipient includes a perfume oil that is an essential oil selected from the group of a lavender oil, a bergamot oil, a eucalyptus oil, a chamomile oil, a melaleuca oil, or a combination thereof. In one embodiment, the cosmetically acceptable excipient includes a lavender oil, a chamomile oil, or a combination thereof.
[0083] In certain embodiments, the perfume oil (each perfume oil individually or all perfume oils in the topical composition cumulatively) is present in the topical formulation an amount of above 0 wt.% to about 5 wt.%, from above 0 wt.% to about 1 wt.%, or from about 0.01 wt.% to about 0.3 wt.%, based on total weight of the topical formulation.
[0084] In certain embodiments, the topical formulation provides one or more of moisturization of the skin, environmental protection, brightening of complexion, and anti-aging benefits. In certain embodiments, the texture of the sunscreen formulation is one or more of smooth, silky, soft, and non-oily. In some embodiments, the topical formulation repairs photo-damage in skin. In some embodiments, the topical formulation stimulates repairing photo-damage in skin.
[0085] In some embodiments, the topical formulation may prevent skin cancer or reduce the likelihood of contracting skin cancer by applying the topical formulation to the skin.
[0086] The topical formulation described herein may be formulated in any dermatological acceptable vehicle such as a serum, emulsion, cream, foam, spray, ointment, gel, lotion, or as a pad or roll-on applied formulation, which may contain ingredients to improve, modify, or stabilize the composition physically or cosmetically.
[0087] In another embodiment, an additional topical formulation is provided. The additional formulation may include a mineral active agent. The additional topical formulation may further include a thymine-thymine compound comprising a compound of Formula (I) or a salt thereof as described herein. The topical formulation of the present disclosure may be applied to the skin of a person to protect from sun exposure. In some embodiments, the topical formulation may have a SPF value greater than 50.
[0088] In some embodiments, the thymine-thymine compound of Formula (I) or salts thereof is included in an amount of about 0.1 wt% to about 10 wt%, about 1 wt% to about 9 wt%, about 2 wt% to about 8 wt%, about 3 wt% to about 7 wt%, or about 4 wt% to about 6 wt%, based on total weight of the topical formulation.
[0089] In some embodiments, the topical formulation may include an alkanediol. In some embodiments, the alkanediol may include a four carbon to 20 carbon backbone, or a combination thereof. In some embodiments, the alkanediol may include propanediol, butylene glycol, pentylene glycol, hexylene glycol, or a combination thereof. In some embodiments, the alkanediol may be included in an amount of about 1 wt% to about 25 wt%, about 5 wt% to about 20 wt%, or about 10 wt% to about 15%, based on total weight of the topical formulation.. In some embodiments, propanediol may be included in an amount of about 1 wt% to about 25 wt%, about 5 wt% to about 20 wt%, or about 10 wt% to about 15 wt%, based on total weight of the topical formulation. In some embodiments, buylene glycol may be included in an amount of about 0.1 wt% to about 10 wt%, about 0.5 wt% to about 8 wt%, or about 1 wt% to about 5 wt%, based on total weight of the topical formulation.
[0090] In some embodiments, the mineral active agent may include zinc oxide, titanium oxide, or a combination thereof. In some embodiments, the mineral active agent may be in combination with a silane or an alternative type of silicone and prepared as a solution. For example, the mineral active agent may be zinc oxide and triethoxycaprylyl silane. In some embodiments, the zinc oxide may be coated with triethoxycaprylyl silane or alternative type of silicone.
[0091] In some embodiments, the mineral active agent may be included in an amount of about 1% to about 45%, about 5% to about 40%, about 10% to about 35%, about 15% to about 30%, or about 20% to about 25%, based on total weight of the topical formulation. In some embodiments, the mineral active agent may be zinc oxide and triethoxycaprylyl silane and may be included in an amount of about 1% to about 45%, about 5% to about 40%, or about 10% to about 35%, based on total weight of the topical formulation.
[0092] In some embodiments, the topical formulation may further include a chelating agent. Suitable chelating agents may include, without limitations, disodium ethylenediaminetetraacetic acid (EDTA), diethylenetriaminepentaacetic acid (DTPA), N-(hydroxyethyl)- ethylenediaminetriacetic acid (HEDTA), and nitrilotriacetic acid (NTA).
[0093] In some embodiments, the chelating agent may be included in an amount of from above 0 wt.% to about 5 wt.%, from about 0.01 wt.% to about 0.5 wt.%, or from about 0.05 wt.% to about 0.3 wt.%, based on total weight of the topical formulation. In one embodiment, the cosmetically acceptable excipient includes a chelating agent that is EDTA in the topical formulation in an amount of from above 0 wt.% to about 5 wt.%, from about 0.01 wt.% to about 0.5 wt.%, or from about 0.05 wt.% to about 0.3 wt.%, based on total weight of the topical formulation.
[0094] In some embodiments, the topical formulation may include an antioxidant. In some embodiments, the antioxidant may include caffeine, Vitamin B, a hydroxy acid, or a combination thereof. In some embodiments, the antioxidant may be caffeine. In some embodiments, the caffeine may be included in an amount of about 0.01 wt% to about 5 wt%, about 0.1 wt% to about 4 wt%, about 0.2 wt% to about 3 wt%, about 0.4 wt% to about 2 wt%, or about 0.5 wt% to about 1wt%, based on total weight of the topical formulation. In some embodiments, antioxidant may be a hydroxy acid. In some embodiments, the hydroxy acid may be lactic acid. In some embodiments, the hydroxy acid, i.e. lactic acid, may be included in an amount of about 0.01 wt% to about 5 wt%, about 0.1 wt% to about 4 wt%, about 0.2 wt% to about 3 wt%, about 0.4 wt% to about 2 wt%, or about 0.5 wt% to about 1wt%, based on total weight of the topical formulation.
[0095] In some embodiments, the antioxidant may further include a form of Vitamin E. Suitable forms of Vitamin E that may be included in the topical composition can be selected from alpha, beta, delta, and gamma tocopherols, and alpha, beta, delta and gamma tocotrienols, and combinations thereof. In some embodiments, the form of Vitamin E may be vitamin E acetate. In some embodiments, the Vitamin E, for example, vitamin E acetate, may be included in an amount of about 0.1 wt% to about 5 wt%, about 0.2 wt% to about 4 wt%, about 0.5 wt% to about 3 wt%, or about 1 wt% to about 2 wt%, based on total weight of the topical formulation.
[0096] In some embodiments, the topical formulation may further include an emulsifier. In some embodiments, the emulsifier may include sucrose cocoate, a polyethylene glycol ether of oleyl alcohol, or a combination thereof. In some embodiments, the emulsifier may be any of the suitable emulsifiers described herein. In some embodiments, the emulsifier may be included in an amount of about 0.1 wt% to about 5 wt%, 0.2 wt% to about 4 wt%, about 0.5 wt% to about 3 wt%, or about 1 wt% to about 2 wt%, based on total weight of the topical formulation. In some embodiments, sucrose cocoate may be included in an amount of about 0.01 wt% to about 5 wt%, 0.1 wt% to about 3 wt%, or about 0.5 wt% to about 2 wt%, based on total weight of the topical formulation. In some embodiments, a polyethylene glycol ether of oleyl alcohol may be included in an amount of about 0.5 wt% to about 15 wt%, 1 wt% to about 10 wt%, or about 3 wt% to about 8 wt%, based on total weight of the topical formulation.
[0097] In some embodiments, the topical formulation may include a biogenic agent. In some embodiments, the biogenic agent may include panthenol. In some embodiments, the biogenic agent may be included in an amount of about 0.01 wt% to about 5 wt%, about 0.1 wt% to about 4 wt%, about 0.5 wt% to about 3 wt%, or about 1 wt% to about 2 wt%, based on total weight of the topical formulation. In some embodiments, panthenol may be included in an amount of about 0.01 wt% to about 5 wt%, about 0.1 wt% to about 3 wt%, or about 1 wt% to about 2 wt%, based on total weight of the topical formulation.
[0098] In some embodiments, the topical formulation may further include biotin or Vitamin B. In some embodiments, the vitamin B may be niacinamide. In some embodiments, the Vitamin B may be included in an amount of about 1 wt% to about 10 wt%, about 2 wt% to about 9 wt%, about 3 wt% to about 8 wt%, about 4 wt% to about 7 wt%, or about 5 wt%, based on total weight of the topical formulation. In some embodiments, niacinamide may be included in an amount of about 0.5 wt% to about 15 wt%, about 1 wt% to about 12 wt%, or about 4 wt% to about 8 wt%, based on total weight of the topical formulation.
[0099] In some embodiments, the topical formulation may further include a UV filter. In some embodiments, the UV filter may include octinoxate. In some embodiments, the UV filter may be included in an amount of about 1 wt% to about 15 wt%, about 2 wt% to about 12 wt%, about 3 wt% to about 10 wt%, or about 5 wt% to about 7.5 wt%, based on total weight of the topical formulation. In some embodiments, octinoxate may be included in an amount of about 1 wt% to about 20 wt%, about 5 wt% to about 15 wt%, or about 8 wt% to about 12 wt%, based on total weight of the topical formulation.
[0100] In some embodiments, the topical formulation may further include a silicone polymer. In some embodiments, the silicone polymer may include lauryl PEG-9 polydimethylsiloxyethly dimethicone, dimethicone or a combination thereof. In some embodiments, the lauryl PEG-9 polydimethylsiloxyethly dimethicone may be included in an amount of 0.001 wt% to about 1 wt%, about 0.005 wt% to about 0.9 wt%, about 0.01 wt% to about 0.8 wt%, about 0.1 wt% to about 0.7 wt%, about 0.15 wt% to about 0.6 wt%, or about 0.25 wt% to about 0.5 wt%, based on total weight of the topical formulation. In some embodiments, the dimethicone may be included in an amount of about 0.1 wt% to about 5 wt%, about 0.5 wt% to about 4 wt%, about 1 wt% to about 3 wt%, or about 1.5 wt% to about 2.5 wt%, based on total weight of the topical formulation.
[0101] In some embodiments, the topical formulation may further include an emollient. In some embodiments, the emollient may be octyldodecyl neopentanoate, neopentyl glycoldiheptanoate, ethylhexyl stearate, or a combination thereof. In some embodiments, the emollient may be octyldodecyl neopentanoate. In some embodiments, the octyldodecyl neopentanoate may be included in an amount of about 1 wt% to about 5 wt%, about 1.5 wt% to about 4.5 wt%, about 2 wt% to about 4 wt%, or about 2.5 wt% to about 3.5 wt%, based on total weight of the topical formulation. In some embodiments, the emollient may be neopentyl glycoldiheptanoate. In some embodiments, the neopentyl glycoldiheptanoate may be included in an amount of about 1 wt% to about 15 wt%, about 2 wt% to about 12 wt%, about 5 wt% to about 10 wt%, or about 6 wt% to about 8 wt%, based on total weight of the topical formulation. In some embodiments, the emollient may be ethylhexyl stearate. In some embodiments, ethylhexyl stearate may be included in ana amount of about 1 wt% to about 15 wt%, about 2 wt% to about 12 wt%, about 5 wt% to about 10 wt%, or about 6 wt% to about 8 wt%, based on total weight of the topical formulation.
[0102] In some embodiments, the topical formulation may further include sodium hyaluronate. In some embodiments, sodium hyaluronate may be included in an amount of about 0.01 wt% to about 1 wt%, about 0.05 wt% to about 0.9 wt%, about 0.1 wt% to about 0.8 wt%, about 0.2 wt% to about 0.7 wt%, about 0.3 wt% to about 0.6 wt%, or about 0.4 wt% to about 0.5 wt%, based on total weight of the topical formulation.
[0103] In some embodiments, the topical formulation may further include an additional polymer. For example, the polymer may be Sepiplus S. In some embodiments, the additional polymer may be included in an amount of about 1 wt% to about 15%, about 2 wt% to about 12 wt%, about 5 wt% to about 10 wt%, or about 6 wt% to about 8 wt%, based on total weight of the topical formulation. In some embodiments, Sepiplus S may be included in an amount of about 0.1 wt% to about 20 wt%, about 1 wt% to about 15 wt%, or about 5 wt% to about 10 wt%, based on total weight of the topical formulation.
[0104] In some embodiments, the topical formulation may further include a natural gum, for example. xanthan gum. Suitable natural gums may also include, without limitations, guar gum, carob gum, konjac gum, sclerotium gum, acacia gum, cellulose gum (modified or not), or a combination thereof. In some embodiments, a natural gum may be included in an amount of about 0.01 wt% to about 1 wt%, about 0.05 wt% to about 0.9 wt%, about 0.1 wt% to about 0.8 wt%, about 0.15 wt% to about 0.75 wt%, about 0.2 wt% to about 0.7 wt%, about 0.25 wt% to about 0.6 wt%, or about 0.3 wt% to about 0.5 wt%, based on total weight of the topical formulation. In some embodiments, xanthan gum may be included in an amount of about 0.01 wt% to about 1 wt%, about 0.05 wt% to about 8 wt%, or about 0.1 wt% to about 5 wt%, based on total weight of the topical formulation.
[0105] In some embodiments, the topical formulation may further include potassium hydroxide. In some embodiments, the potassium hydroxide may be included in an amount of about 0.1 wt% to about 5 wt%, about 0.25 wt% to about 4.5 wt%, about 0.5 wt% to about 4 wt%, about 0.75wt% to about 3.5 wt%, about 1 wt% to about 3 wt%, or about 1.5 wt% to about 2.5 wt%, based on total weight of the topical formulation.
[0106] The topical formulation according to the disclosure may also contain one or one more additional cosmetically acceptable excipients as described below. Fatty Alcohols
[0107] Guerbet alcohols based on fatty alcohols having from 6 to 18, preferably from 8 to 10 carbon atoms including cetyl alcohol, stearyl alcohol, cetearyl alcohol, oleyl alcohol, octyldodecanol, benzoate of C12-C15 alcohols, acetylated lanolin alcohol, etc. Esters of Fatty Acids
[0108] Esters of linear C6-C24fatty acids with linear C3-C24alcohols, esters of branched C6- C13carboxyl acids with linear C6-C24 fatty alcohols, esters of linear C6-C24 fatty acids with branched alcohols, especially 2-ethylhexanol, esters of hydroxycarboxylic acids with linear or branched C6-C22 fatty alcohols, especially dioctyl malates, esters of linear and / or branched fatty acids with polyhydric alcohols (for example propylene glycol, dimer diol or trimer triol) and / or Guerbet alcohols, for example caproic acid, caprylic acid, 2-ethylhexanoic acid, capric acid, lauric acid, isotridecanoic acid, myristic acid, palmitic acid, palmitoleic acid, stearic acid, isostearic acid, oleic acid, elaidic acid, petroselinic acid, linoleic acid, linolenic acid, elaeostearic acid, arachidic acid, gadoleic acid, behenic acid and erucic acid and mixtures thereof (obtained, for example, in the pressure removal of natural fats and oils, in the reduction of aldehydes from Roelen's oxosynthesis or in the dimerization of unsaturated fatty acids) with alcohols, for example, isopropyl alcohol, caproic alcohol, capryl alcohol, 2-ethylhexyl alcohol, capric alcohol, lauryl alcohol, isotridecyl alcohol, myristyl alcohol, cetyl alcohol, palmoleyl alcohol, stearyl alcohol, isostearyl alcohol, oleyl alcohol, elaidyl alcohol, petroselinyl alcohol, linoyl alcohol, linolenyl alcohol, elaeostearyl alcohol, arachidyl alcohol, gadoleyl alcohol, behenyl alcohol, erucyl alcohol and brassidyl alcohol and mixtures thereof (obtained, for example, in the high-pressure hydrogenation of methyl esters based on fats and oils or aldehydes from Roelen's oxosynthesis and as monomer fractions in the dimerization of unsaturated fatty alcohols).
[0109] Examples of such ester oils are isopropyl myristate, isopropyl palmitate, isopropyl stearate, isopropyl isostearate, isopropyl oleate, n-butyl stearate, n-hexyl laurate, n-decyl oleate, isooctyl stearate, iso-nonylstearate, isononyl isononanoate, 2-ethylhexylpalmitate, 2-hexyllaurate, 2- hexyldecylstearate, 2-octyldodecylpalmitate, oleyloleate, oleylerucate, erucyloleate, erucylerucate, cetearyl octanoate, cetyl palmitate, cetyl stearate, cetyl oleate, cetyl behenate, cetyl acetate, myristyl myristate, myristyl behenate, myristyl oleate, myristyl stearate, myristyl palmitate, myristyl lactate, propylene glycol dicaprylate / caprate, stearyl heptanoate, diisostearyl malate, octyl hydroxystearate, etc. Other Adjuvants
[0110] Diethylhexyl 2,6-naphthalate, di-n-butyl adipate, di(2-ethylhexyl)-adipate, di(2-ethyl hexyl)-succinate and diisotridecyl acelaat, and also diol esters, such as ethylene glycol dioleate, ethylene glycol diisotridecanoate, propylene glycol di(2-ethylhexanoate), propylene glycol diisostearate, propylene glycol dipelargonate, butanediol diisostearate and neopentyl glycol dicaprylate. Esters of C6-C24fatty alcohols and / or Guerbet alcohols with aromatic carboxylic acids, saturated and / or unsaturated, especially benzoic acid, esters of C2-C12 dicarboxylic acids with linear or branched alcohols having from 1 to 22 carbon atoms or polyols having from 2 to 10 carbon atoms and from 2 to 6 hydroxy groups. Natural or Synthetic Triglycerides Including Glyceryl Esters and Derivatives
[0111] Di- or triglycerides, based on C6-C18fatty acids, modified by reaction with other alcohols (caprylic / capric triglyceride, wheat germ glycerides, etc.). Fatty acid esters of polyglycerin (polyglyceryl-n such as polyglyceryl-4 caprate, polyglyceryl-2 isostearate, etc. or castor oil, hydrogenated vegetable oil, sweet almond oil, wheat germ oil, sesame oil, hydrogenated cottonseed oil, coconut oil, avocado oil, corn oil, hydrogenated castor oil, shea butter, cocoa butter, soybean oil, mink oil, sunflower oil, safflower oil, macadamia nut oil, olive oil, hydrogenated tallow, apricot kernel oil, hazelnut oil, borage oil, etc.
[0112] Waxes including esters of long-chain acids and alcohols as well as compounds having wax-like properties, e.g., carnauba wax, beeswax (white or yellow), lanolin wax, candelilla wax, ozokerite, japan wax, paraffin wax, microcrystalline wax, ceresin, cetearyl esters wax, synthetic beeswax, etc. Also, hydrophilic waxes as Cetearyl Alcohol or partial glycerides. Pearlescent Waxes:
[0113] Alkylene glycol esters, especially ethylene glycol distearate; fatty acid alkanolamides, especially coco fatty acid diethanolamide; partial glycerides, especially stearic acid monoglyceride; esters of polyvalent, unsubstituted or hydroxy-substituted carboxylic acids with fatty alcohols having from 6 to 22 carbon atoms, especially long-chained esters of tartaric acid; fatty substances, for example fatty alcohols, fatty ketones, fatty aldehydes, fatty ethers and fatty carbonates, which in total have at least 24 carbon atoms, especially lauryl and distearyl ether; fatty acids, such as stearic acid, hydroxystearic acid or behenic acid, ring-opening products of olefin epoxides having from 12 to 22 carbon atoms with fatty alcohols having from 12 to 22 carbon atoms and / or polyols having from 2 to 15 carbon atoms and from 2 to 10 hydroxy groups, and mixtures thereof. Hydrocarbon Oils:
[0114] Mineral oil (light or heavy), petrolatum (yellow or white), microcrystalline wax, paraffinic and isoparaffinic compounds, hydrogenated isoparaffinic molecules as polydecenes and polybutene, hydrogenated polyisobutene, squalane, isohexadecane, isododecane and others from plant and animal kingdom. Silicones or Siloxanes (Organosubstituted Polysiloxanes)
[0115] Dimethylpolysiloxanes, methylphenylpolysiloxanes, cyclic silicones, and also amino-, fatty acid-, alcohol-, polyether-, epoxy-, fluorine-, glycoside- and / or alkyl-modified silicone compounds, which at room temperature may be in either liquid or resinous form. Linear polysiloxanes, dimethicone (Dow Corning 200 fluid, Rhodia Mirasil DM), dimethiconol, cyclic silicone fluids, cyclopentasiloxanes volatiles (Dow Corning 345 fluid), phenyltrimethicone (Dow Corning 556 fluid). Also suitable are simethicones, which are mixtures of dimethicones having an average chain length of from 200 to 300 dimethylsiloxane units with hydrogenated silicates. A detailed survey by Todd et al. of suitable volatile silicones may in addition be found in Cosm. Toil.91, 27 (1976). Emulsifiers
[0116] Any conventionally usable emulsifier can be used for the compositions. Emulsifier systems may comprise for example: carboxylic acids and their salts: alkaline soap of sodium, potassium and ammonium, metallic soap of calcium or magnesium, organic basis soap such as Lauric, palmitic, stearic and oleic acid etc. Alkyl phosphates or phosphoric acid esters, acid phosphate, diethanolamine phosphate, potassium cetyl phosphate. Ethoxylated carboxylic acids or polyethylene glycol esters, PEG-n acylates. Linear fatty alcohols having from 8 to 22 carbon atoms, branched from 2 to 30 mol of ethylene oxide and / or from 0 to 5 mol propylene oxide with fatty acids having from 12 to 22 carbon atoms and with alkylphenols having from 8 to 15 carbon atoms in the alkyl group. Fatty alcohol polyglycol ether such as laureth-n, ceteareth-n, steareth-n, oleth-n. Fatty acid polyglycolether such as PEG-n stearate, PEG-n oleate, PEG-n cocoate. Monoglycerides and polyol esters. C12-C22 fatty acid mono- and di-esters of addition products of from 1 to 30 mol of ethylene oxide with polyols. Fatty acid and polyglycerol ester such as monostearate glycerol, diisostearoyl polyglyceryl-3-diisostearates, polyglyceryl-3-diisostearates, triglyceryl diisostearates, polyglyceryl-2-sesquiisostearates or polyglyceryl dimerates. Mixtures of compounds from a plurality of those substance classes are also suitable. Fatty acid polyglycolesters such as monostearate diethylene glycol, fatty acid and polyethylene glycol esters, fatty acid and saccharose esters such as sucro esters, glycerol and saccharose esters such as sucro glycerides. Sorbitol and sorbitan, sorbitan mono- and di-esters of saturated and unsaturated fatty acids having from 6 to 22 carbon atoms and ethylene oxide addition products. Polysorbate-n series, sorbitan esters such as sesquiisostearate, sorbitan, PEG-(6)-isostearate sorbitan, PEG-(10)- sorbitan laurate, PEG-17-dioleate sorbitan. Glucose derivatives, C8-C22 alkyl-mono and oligo- glycosides and ethoxylated analogues with glucose being preferred as the sugar component. O / W emulsifiers such as methyl gluceth-20 sesquistearate, sorbitan stearate / sucrose cocoate, methyl glucose sesquistearate, cetearyl alcohol / cetearyl glucoside. W / O emulsifiers such as methyl glucose dioleate / methyl glucose isostearate. Sulfates and sulfonated derivatives, dialkylsulfosuccinates, dioctyl succinate, alkyl lauryl sulfonate, linear sulfonated paraffins, sulfonated tetrapropyene sulfonate, sodium lauryl sulfates, ammonium and ethanolamine lauryl sulfates, lauryl ether sulfates, sodium laureth sulfates, sulfosuccinates, acetyl isothionates, alkanolamide sulfates, taurines, methyl taurines, imidazole sulfates. Polysiloxane / polyalkyl / polyether copolymers and derivatives, dimethicone, copolyols, silicone polyethylene oxide copolymer, silicone glycol copolymer. Propoxylated or POE-n ethers (Meroxapols), Polaxamers or poly(oxyethylene)m-block-poly(oxypropylene)n- block(oxyethylene). Zwitterionic surfactants that carry at least one quaternary ammonium group and at least one carboxylate and / or sulfonate group in the molecule. Zwitterionic surfactants that are especially suitable are betaines, such as N-alkyl-N,N-dimethylammonium glycinates, cocoalkyldimethylammonium glycinate, N-acylaminopropyl-N,N-dimethylammonium glycinates, cocoacylaminopropyldimethylammonium glycinate and 2-alkyl-3-carboxymethyl-3- hydroxyethylimidazolines each having from 8 to 18 carbon atoms in the alkyl or acyl group and also cocoacylaminoethylhydroxyethylcarboxymethylglycinate, N-alkyl betaine, N- alkylaminobetaines. Alkylimidazolines, alkylopeptides, lipoaminoacides, self-emulsifying bases and the compounds as described in K. F. DePolo, A short textbook of cosmetology, Chapter 8, Table 8-7, p 250-251.
[0117] Nonionic bases such as PEG-6 beeswax (and) PEG-6 stearate (and) polyglyceryl-2- isostearate, glyceryl stearate (and) PEG-100 stearate, PEG-5 glyceryl stearate, sorbitan oleate (and) polyglyceryl-3 ricinoleate, sorbitan stearate and sucrose cocoate, glyceryl stearate and laureth-23, cetearyl alcohol and ceteth-20, cetearyl alcohol and polysorbate 60 and PEG-150 and stearate-20, cetearyl alcohol and cetearyl polyglucoside, cetearyl alcohol and ceteareth-20, cetearyl alcohol and PEG-40 castor oil, cetearyl alcohol and PEG-40 castor oil and sodium cetearyl sulfate, stearyl alcohol and steareth-7 and steareth-10, cetearyl alcohol and szeareth-7 and steareth- 10, glyceryl stearate and PEG-75 stearate, propylene glycol ceteth-3 acetate, propylene glycol isoceth-3 acetate, cetearyl alcohol and ceteth-12 and oleth-12, PEG-6 stearate and PEG-32 stearate, PEG-6 stearate and ceteth-20 and steareth-20, PEG-6 stearate and ceteth-20 and glyceryl stearate and steareth-20, glyceryl stearate and ceteareth-20.
[0118] Anionic alkaline bases such as PEG-2 stearate SE, glyceryl stearate SE, propylene glycol stearate. Anionic acid bases such as cetearyl Alcohol and Sodium cetearyl sulfate, cetearyl alcohol and sodium lauryl sulfate, trilaneth-4 phosphate and glycol stearate and PEG-2 stearate, glyceryl stearate and sodium lauryl Sulfate. Cationic acid bases such as cetearyl alcohol and cetrimonium bromide. Adjuvants and Additives
[0119] The cosmetic topical compositions, for example creams, gels, lotions, alcoholic and aqueous / alcoholic solutions, emulsions, wax / fat compositions, stick preparations, powders or ointments, may in addition contain, as further adjuvants and additives such as, mild surfactants, super-fatting agents, consistency regulators, thickeners, polymers, stabilizers, biogenic active ingredients, swelling agents, further UV light-protective factors, antioxidants, hydrotropic agents, preservatives, self-tanning agents, solubilizers, perfume oils, colorants, bacteria-inhibiting agents and the like. Super-Fatting Agents
[0120] Substances suitable for use as super-fatting agents are, for example, lanolin and lecithin and also polyethoxylated or acetylated lanolin and lecithin derivatives, polyol fatty acid esters, monoglycerides and fatty acid alkanolamides, the latter simultaneously acting as foam stabilizers. Surfactants
[0121] Examples of suitable mild surfactants, that is to say surfactants especially well tolerated by the skin, include fatty alcohol polyglycol ether sulfates, monoglyceride sulfates, mono- and / or di-alkyl sulfosuccinates, fatty acid isethionates, fatty acid sarcosinates, fatty acid taurides, fatty acid glutamates, alpha-olefin sulfonates, ethercarboxylic acids, alkyl oligoglucosides, fatty acid glucamides, alkylamidobetaines and / or protein fatty acid condensation products, the latter preferably being based on wheat proteins. Consistency Regulators / Thickeners and Rheology Modifiers
[0122] Silicium dioxide, magnesium silicates, aluminium silicates, polysaccharides or derivatives thereof for example hyaluronic acid, xanthan gum, guar-guar, agar-agar, alginates, carrageenan, gellan, pectines, or modified cellulose such as hydroxycellulose, hydroxypropylmethylcellulose. In addition polyacrylates or homopolymer of reticulated acrylic acids and polyacrylamides, carbomer (CARBOPOL types 980, 981, 1382, ETD 2001, ETD2020, ULTREZ 10) or SALCARE range such as SALCARE SC80 (steareth-10 allyl ether / acrylates copolymer), Salcare SC81 (acrylates copolymer), Salcare SC91 and Salcare AST (sodium acrylates copolymer / PPG-1 trideceth-6), SEPIGEL 305 (polyacrylamide / laureth-7), SIMULGEL NS and SIMULGEL EG (hydroxyethyl acrylate / sodium acryloyldimethyl taurate copolymer), STABILEN 30 (acrylates / vinyl isodecanoate crosspolymer), PEMULEN TR-1 (acrylates / C10-30 alkyl acrylate crosspolymer), LUVIGEL EM (sodium acrylates copolymer), ACULYN 28 (acrylates / beheneth- 25 methacrylate copolymer), etc. Polymers
[0123] As anionic, zwitterionic, amphoteric and non-ionic polymers come into consideration, for example, vinyl acetate / crotonic acid copolymers, vinylpyrrolidone / vinyl acrylate copolymers, vinyl acetate / butyl maleate / isobornyl acrylate copolymers, methyl vinyl ether / maleic anhydride copolymers and esters thereof, uncrosslinked polyacrylic acids and polyacrylic acids crosslinked with polyols, acrylamidopropyl-trimethylammonium chloride / acrylate copolymers, octyl acrylamide / methyl methacrylate-tert-butylaminoethyl methacrylate / 2-hydroxypropyl methacrylate copolymers, polyvinylpyrrolidone, vinylpyrrolidone / vinyl acetate copolymers, vinylpyrrolidone / dimethylaminoethyl methacrylate / vinyl caprolactam terpolymers and also optionally derivatized cellulose ethers and silicones. Furthermore, the polymers as described in EP 1093796 (pages 3-8, paragraphs 17-68) may be used. Biogenic Active Ingredients
[0124] Biogenic active ingredients are to be understood as meaning, for example, tocopherol, tocopherol acetate, tocopherol palmitate, deoxyribonucleic acid, retinol, bisabolol, allantoin, phytantriol, panthenol, AHA acids, amino acids, ceramides, pseudoceramides, essential oils, plant extracts, peptides, growth factors, exosomes and vitamin complexes. Antioxidants
[0125] In addition to the primary light-protective substances it is also possible to use secondary light-protective substances of the antioxidant kind that interrupt the photochemical reaction chain triggered when UV radiation penetrates the skin or hair. Typical examples of such antioxidants are amino acids (e.g. glycine, histidine, tyrosine, tryptophan) and derivatives thereof, imidazoles (e.g. urocanic acid) and derivatives thereof, peptides, such as D,L-carnosine, D-carnosine, L- carnosine and derivatives thereof (e.g. anserine), carotinoids, carotenes, lycopene and derivatives thereof, chlorogenic acid and derivatives thereof, lipoic acid and derivatives thereof (e.g. dihydrolipoic acid), aurothioglycose, propylthiouracil and other thiols (e.g. thioredoxin, glutathione, cysteine, cystine, cystamine and the glycosyl, N-acetyl, methyl, ethyl, propyl, amyl, butyl, lauryl, palmitoyl, oleyl, linoleyl, cholesteryl and glyceryl esters thereof) and also salts thereof, dilauryl thiodipropionate, distearyl thiodipropionate, thiodipropionic acid and derivatives thereof (esters, ethers, peptides, lipids, nucleotides, nucleosides and salts) and also sulfoximine compounds (e.g. buthionine sulfoximines, homocysteine sulfoximine, buthionine sulfones, penta- , hexa-, hepta-thionine sulfoximine), also (metal) chelating agents (e.g. hydroxy fatty acids, palmitic acid phytic acid, lactoferrin), hydroxy acids (e.g. citric acid, lactic acid, malic acid), humic acid, bile acid, bile extracts, bilirubin, biliverdin, EDTA, EDDS, EGTA and derivatives thereof, unsaturated fatty acids and derivatives thereof (e.g. linolenic acid, linoleic acid, oleic acid), folic acid and derivatives thereof, ubiquinone and ubiquinol and derivatives thereof, vitamin C and derivatives (e.g. ascorbyl palmitate, magnesium ascorbyl phosphate, ascorbyl acetate), tocopherols and derivatives (e.g. vitamin E acetate), vitamin A and derivatives (e.g. vitamin A palmitate) and also coniferyl benzoate of benzoin resin, rutinic acid and derivatives thereof, glycosylrutin, ferulic acid, furfurylidene glucitol, carnosine, butyl hydroxytoluene, butyl hydroxyanisole, nordihydroguaiaretic acid, trihydroxybutyrophenone, uric acid and derivatives thereof, mannose and derivatives thereof, superoxide dismutase, N-[3-(3,5-di-tert-butyl-4- hydroxyphenyl)propionyl]sulfanilic acid (and salts thereof, for example the disodium salts), selenium and derivatives thereof (e.g. selenium methionine), stilbene and derivatives thereof (e.g. stilbene oxide, trans-stilbene oxide) and the derivatives suitable according to the invention (salts, esters, ethers, sugars, nucleotides, nucleosides, peptides and lipids) of those mentioned active ingredients. HALS (=“Hindered Amine Light Stabilizers”) compounds may also be mentioned. Hydrotropic Agents
[0126] To improve the flow behaviour, it is also possible to employ hydrotropic agents, for example ethoxylated or non-ethoxylated mono-alcohols, diols or polyols with a low number of carbon atoms or their ethers (e.g. ethanol, isopropanol, 1,2-dipropanediol, propylene glycol, glycerin, ethylene glycol, ethylene glycol monoethylether, ethylene glycol monobutylether, propylene glycol monomethylether, propylene glycol monoethylether, propylene glycol monobutylether, diethylene glycol monomethylether; diethylene glycol monoethylether, diethylene glycol monobutylether and similar products). The polyols that come into consideration for that purpose have preferably from 2 to 15 carbon atoms and at least two hydroxy groups. The polyols may also contain further functional groups, especially amino groups, and / or may be modified with nitrogen. Typical examples are as follows: glycerol, alkylene glycols, for example ethylene glycol, diethylene glycol, propylene glycol, butylene glycol, hexylene glycol and also polyethylene glycols having an average molecular weight of from 100 to 1000 Dalton; technical oligoglycerol mixtures having an intrinsic degree of condensation of from 1.5 to 10, for example technical diglycerol mixtures having a diglycerol content of from 40 to 50% by weight; methylol compounds, such as, especially, trimethylolethane, trimethylolpropane, trimethylolbutane, pentaerythritol and dipentaerythritol; lower alkyl-glucosides, especially those having from 1 to 8 carbon atoms in the alkyl radical, for example methyl and butyl glucoside; sugar alcohols having from 5 to 12 carbon atoms, for example sorbitol or mannitol; sugars having from 5 to 12 carbon atoms, for example glucose or saccharose; amino sugars, for example glucamine; dialcohol amines, such as diethanolamine or 2-amino-1,3-propanediol. Preservatives and Bacteria-Inhibiting Agents
[0127] Suitable preservatives include, for example, Methyl-, Ethyl-, Propyl-, Butyl-parabens, Benzalkonium chloride, 2-Bromo-2-nitro-propane-1,3-diol, Dehydroacetic acid, Diazolidinyl Urea, 2-Dichloro-benzyl alcohol, DMDM hydantoin, Formaldehyde solution, Methyldibromoglutanitrile, Phenoxyethanol, Sodium Hydroxymethylglycinate, Imidazolidinyl Urea, Triclosan and further substance classes listed in the following reference: K. F. DePolo-A short textbook of cosmetology, Chapter 7, Table 7-2, 7-3, 7-4 and 7-5, p 210-219, as well as “green” (sustainable,or formadehyde-free) preservatives, such as, but not limited to Biomix Free II, Ethylhexylglycerin, Spectrastat, Spectrastat G2 Natural, and others. Bacteria-Inhibiting Agents
[0128] Typical examples of bacteria-inhibiting agents are preservatives that have a specific action against gram-positive bacteria, such as 2,4,4′-trichloro-2′-hydroxydiphenyl ether, chlorhexidine (1,6-di(4-chlorophenyl-biguanido)hexane) or TCC (3,4,4′-trichlorocarbanilide). A large number of aromatic substances and ethereal oils also have antimicrobial properties. Typical examples are the active ingredients eugenol, menthol and thymol in clove oil, mint oil and thyme oil. A natural deodorizing agent of interest is the terpene alcohol farnesol (3,7,11-trimethyl-2,6,10-dodecatrien- 1-ol), which is present in lime blossom oil. Glycerol monolaurate has also proved to be a bacteriostatic agent. Colorants
[0129] There may be used as colorants the substances that are suitable and permitted for cosmetic purposes, as compiled, for example, in the publication “Kosmetische Farbemittel” of the Farbstoffkommission der Deutschen Forschungsgemeinschaft, Verlag Chemie, Weinheim, 1984, pages 81 to 106. UV Screening Agents Additional sun screening agents may be included from a range of organic UV screening agents selected from the group consisting of 1(+ / −)-1,7,7-trimethyl-3-[(4- methylphenyl)methylene]bicyclo-[2.2.1]heptan-2-one; p-methyl benzylidene camphor,1,7,7- trimethyl-3-(phenylmethylene)bicyclo[2.2.1]heptan-2-one; benzylidene camphor, (2-Hydroxy-4- methoxyphenyl)(4-methylphenyl)methanone, 2,4-dihydroxybenzophenone, 2,2′,4,4′- tetrahydroxybenzophenone, 2-Hydroxy-4-methoxy benzophenone, 2-Hydroxy-4-methoxy benzophenone-5-sulfonic acid, 2,2′-dihydroxy-4,4′-dimethoxybenzophenone, 2,2′-Dihydroxy-4- methoxybenzophenone, Alpha-(2-oxoborn-3-ylidene)toluene-4-sulphonic acid and its salts, 1-[4- (1,1-dimethylethyl)phenyl]-3-(4-methoxyphenyl)propane-1,3-dione, Methyl N,N,N-trimethyl-4- [(4,7,7-trimethyl-3-oxobicyclo[2,2,1]-hept-2-ylidene)methyl]anilinium sulphate, 3,3,5-Trimethyl cyclohexyl-2-hydroxy benzoate, Isopentyl p-methoxycinnamate, Menthyl-o-aminobenzoate,2- Ethylhexyl 2-cyano,3,3-diphenylacrylate, 2-ethylhexyl 4-(dimethylamino)benzoate, 2-ethylhexyl 4-methoxycinnamate, 2-ethylhexyl salicylate, Benzoic acid,4,4′,4″-(1,3,5-triazine-2,4,6- triyltriimino)tris-,tris(2-ethylhexyl)ester, 4-aminobenzoic acid, Benzoic acid, 4-amino-, ethyl ester, polymer with oxirane, 2-phenyl-1H-benzimidazole-5-sulphonic acid,2-Propenamide, N-[[4- [(4,7,7-trimethyl-3-oxobicyclo[2.2.1]hept-2-ylidene)methyl]phenyl]methyl]-, homopolymer. Triethanolamine salicylate, 3,3′-(1,4-phenylenedimethylene)bis[7,7-dimethyl-2-oxo- bicyclo[2.2.1]heptane-1 methanesulfonic acid], Titanium dioxide, 2,2′-Methylene-bis-[6-(2H- benzotriazol-2-yl)-4-(1,1,3,3-tetramethylbutyl)-phenol], Bis-Ethylhexyloxyphenol Methoxyphenyl Triazine,1H-Benzimidazole-4,6-disulfonic acid, 2,2′-(1,4-phenylene)bis-, disodium salt, Benzoic acid, 4,4′-[[6-[[4-[[(1,1-dimethylethyl)amino]carbonyl]- phenyl]amino]1,3,5-triazine-2,4-diyl]diimino]bis-, Phenol, 2-(2H-benzotriazol-2-yl)-4-methyl-6- [2-methyl-3-[1,3,3,3-tetramethyl-1-[(trimethylsily)oxy]disiloxanyl]propyl]- ,Dimethicodiethylbenzalmalonate, Benzenesulfonic acid, 3-(2H-benzotriazol-2-yl)-4-hydroxy-5-(1-methyl propyl)-, monosodium salt, Benzoic acid, 2-[4-(diethylamino)-2-hydroxybenzoyl]-,hexyl ester, 1-Dodecanaminium, N-[3-[[4-(dimethylamino)benzoyl]amino]-propyl] N,N-dimethyl-, salt with 4-methylbenzenesulfonic acid (1:1), 1-Propanaminium, N,N,N-trimethyl-3-[(1-oxo-3-phenyl-2-propenyl) amino]-, chloride, 1H-Benzimidazole-4,6-disulfonic acid, 2,2′-(1,4-phenylene)bis-, 1,3,5-Triazine, 2,4,6-tris(4-methoxyphenyl)-,1,3,5-Triazine, 2,4,6-tris[4-[(2- ethylhexyl)oxy]phenyl]-, 1-Propanaminium, 3-[[3-[3-(2H-benzotriazol-2-yl)-5-(1,1- dimethylethyl)-4-hydroxyphenyl]-1-oxopropyl]amino]-N,N-diethyl-N-methyl-, methyl sulfate (salt), 2-Propenoic acid, 3-(1H-imidazol-4-yl)-, Benzoic acid, 2-hydroxy-, [4-(1- methylethyl)phenyl]methyl ester, 1,2,3-Propanetriol, 1-(4-aminobenzoate), Benzeneacetic acid, 3,4-dimethoxy-a-oxo-, 2-Propenoic acid, 2-cyano-3,3-diphenyl-, ethyl ester, Anthralinic acid, p- menth-3-yl ester, 2,2′-bis(1,4-phenylene)-1H-benzimidazole-4,6-disulphonic acid mono sodium salt or Disodium phenyl dibenzimidazole tetrasulfonate, 1,3,5-Triazine-2,4,6-triamine and N,N′- bis[4-[5-(1,1-dimethylpropyl)-2-benzoxazolyl]phenyl]-N″-(2-ethylhexyl). Agents that absorb UV light and provide photo protection to the skin
[0130] Suitable agents that absorb UV light, provide photo protection to the skin, and optionally provide sunless tanning may include a compound of formula II: or a salt thereof, wherein: R1is H, (C1-C6)alkyl, (C3-C7)carbocycle or RaC(═O)—; R2is H, (C1-C6)alkyl or aryl, wherein aryl is optionally substituted with one or more (e.g.1, 2, 3, 4 or 5) Z1groups; R4is H, (C1-C10)alkyl, (C3-C7)carbocycle or RaC(═O)—; Rais or (C1-C6)alkyl, (C3-C7)carbocycle or aryl, wherein aryl is optionally substituted with one or more (e.g.1, 2, 3, 4 or 5) Z1groups; each Z1is independently selected from (C1-C6)alkyl, halogen, —CN, —ORn1, —NRq1Rr1, — NRn1CORp1, —NRn1CO2Rp1, NO2, —C(O)Rn1, —C(O)ORn1 and —C(O)NRq1Rr1, wherein any (C1-C6)alkyl of Z1is optionally substituted with one or more (e.g. 1, 2, 3, 4, 5 or 6) halogen; each Rn1 is independently selected from H and (C1-C6)alkyl, wherein any (C1-C6)alkyl of Rn1 is optionally substituted with one or more (e.g. 1, 2, 3, 4, 5 or 6) halogen; each Rp1 is independently (C1-C6)alkyl; and Rq1 and Rr1 are each independently selected from H and (C1-C6)alkyl or Rq1 and Rr1 together with the nitrogen to which they are attached form a piperidine, pyrrolidine, morpholine, azetidine, thiomorpholine, piperazine or 4-methylpiperazine.
[0131] Specific groups of compounds and specific compounds of Formula II that may be incorporated in the topical composition described herein and methods of preparing such compounds are described in U.S. Patent No.9,987,211, which is incorporated herein by reference in its entirety.
[0132] Suitable agents that absorb UV light and provide photo protection to the skin may include a compound of formula III:wherein: each R1is independently H, (C1-C6)alkyl, (C3-C7)carbocycle or RaC(═O; or the two R1groups together form a —(C3-C8)alkyl-group, a —(C2-C6)alkyl-Y—(C2-C6)alkyl-group or a —(C1- C6)alkyl-Y′—(C1-C6)alkyl-group; or the dashed bonds labeled “a” are absent and the dashed bonds labeled “b” are double bonds; or all the dashed bonds are single bonds; R2is H, (C1-C6)alkyl or aryl, wherein aryl is optionally substituted with one or more (e.g.1, 2, 3, 4 or 5) Z1groups; R3is H, (C1-C6)alkyl or aryl, wherein aryl is optionally substituted with one or more (e.g.1, 2, 3, 4 or 5) Z1groups; R4is hydroxy, carboxy, (C1-C6)alkoxycarbonyl, —OPO3H2, —ORc, or —NRdRe; and R5is H; or R4and R5taken together are oxo; Y is O, S, NH, P, P(═O) or POH; Y′ is Si(Rb)2 or —Si(Rb)2—O—Si(Rb)2—; each Ra is independently (C1-C6)alkyl, (C3-C7)carbocycle or aryl, wherein aryl is optionally substituted with one or more (e.g.1, 2, 3, 4 or 5) Z1groups; each Rb is independently (C1-C6)alkyl, (C3-C7)carbocycle or aryl, wherein aryl is optionally substituted with one or more (e.g.1, 2, 3, 4 or 5) Z1groups; Rc is Rf or a C1-C20 saturated or C2-C20 unsaturated carbon chain that is optionally substituted with one or more groups independently selected from oxo (═O), hydroxy, mercapto, (C1-C6)alkoxy, (C1-C6)alkoxycarbonyl, (C1-C6)alkanoyloxy, NRdRe, carboxy, and aryl, wherein aryl is optionally substituted with one or more (e.g.1, 2, 3, 4 or 5) Z1groups; Rd is H, (C1-C6)alkyl, or (C1-C6)alkanoyl; Reis H or a C1-C20saturated or C2-C20unsaturated carbon chain that is optionally substituted with one or more groups independently selected from oxo (═O), hydroxy, mercapto, (C1-C6)alkoxy, (C1-C6)alkoxycarbonyl, (C1-C6)alkanoyloxy, NRdRe, carboxy, and aryl, wherein aryl is optionally substituted with one or more (e.g.1, 2, 3, 4 or 5) Z1groups; each Rf, is:each Z1is independently selected from (C1-C6)alkyl, halogen, —CN, —ORn1, —NRq1Rr1, — NRn1CORp1, —NRn1CO2Rp1, NO2, —C(O)Rn1, —C(O)ORn1 and —C(O)NRq1Rr1, wherein any (C1-C6)alkyl of Z1is optionally substituted with one or more (e.g.1, 2, 3, 4, 5 or 6) halogen; each Rn1 is independently selected from H and (C1-C6)alkyl, wherein any (C1-C6)alkyl of Rn1 is optionally substituted with one or more (e.g.1, 2, 3, 4, 5 or 6) halogen; each Rp1 is independently (C1-C6)alkyl; and Rq1and Rr1are each independently selected from H and (C1-C6)alkyl or Rq1and Rr1together with the nitrogen to which they are attached form a piperidine, pyrrolidine, morpholine, azetidine, thiomorpholine, piperazine or 4-methylpiperazine; or a salt thereof.
[0133] Specific groups of compounds and specific compounds of Formula III that may be incorporated in the topical composition described herein and methods of preparing such compounds are described in U.S. Patent No.9,364,406 and in U.S. Patent No.9,987,211, which are incorporated herein by reference in its entirety. Sunscreening Agents
[0134] Sunscreen formulations disclosed herein may include sun screening agents such as avobenzone, ecamsule, methyl anthranilate, oxybenzone, dioxybenzone, sulisobenzone, octinoxate, homosalate, octocrylene and octisalate. Such compositions may comprise organic UV filters, so-called hydrophilic or lipophilic sun-protection filters, which are effective in the UVA region and / or UVB region and ( / or IR and / or VIS region (absorbers). These substances can be selected, in particular, from cinnamic acid derivatives, salicylic acid derivatives, camphor derivatives, triazine derivatives, β,β-diphenylacrylate derivatives, p-aminobenzoic acid derivatives and polymeric filters and silicone filters, which are described in the WO93 / 04665. Further examples of organic filters are indicated in patent application EP-A 0487404. Particularly suitable for a combination are: para-aminobenzoic acid and derivatives thereof: PABA, Ethyl PABA, Ethyl dihydroxypropyl PABA, Ethylhexyl dimethyl PABA, for example marketed by ISP under the name “Escalol 507”, Glyceryl PABA, PEG-25 PABA, for example marketed under the name “Uvinul P25” by BASF.
[0135] Other UV filter ingredients which may be incorporated in the sunscreen formulation of the disclosure include:
[0136] Salicylates: Homosalate marketed by Merck under the name “Eusolex HMS”; Ethylhexyl salicylate, for example marketed by Symrise under the name “Neo Heliopan OS”, Dipropylene glycol salicylate, for example marketed by Scher under the name “Dipsal”, TEA salicylate, for example marketed by Symrise under the name “Neo Heliopan TS”.
[0137] β,β-Diphenylacrylate derivatives: Octocrylene, for example marketed by Merck under the name “Eusolex® OCR”, “Uvinul N539” from BASF, Octocrylene, for example marketed by BASF under the name “Uvinul N35”.
[0138] Benzophenone derivatives: Benzophenone-1, for example marketed under the name “Uvinul 400”; Benzophenone-2, for example marketed under the name “Uvinul D50”; Benzophenone-3 or Oxybenzone, for example marketed under the name “Uvinul M40”; Benzophenone-4, for example marketed under the name “Uvinul MS40”; Benzophenone-9, for example marketed by BASF under the name “Uvinul DS-49”, Benzophenone-5, Benzophenone- 6, for example marketed by Norquay under the name “Helisorb 11”, Benzophenone-8, for example marketed by American Cyanamid under the name “Spectra-Sorb UV-24”, Benzophenone-12 n- hexyl 2-(4-diethylamino-2-hydroxybenzoyl)benzoate or 2-hydroxy-4-methoxybenzophenone, marketed by Merck, Darmstadt, under the name Eusolex® 4360.
[0139] Benzylidenecamphor derivatives: 3-Benzylidenecamphor, for example marketed by Chimex under the name “Mexoryl SD”, 4-Methylbenzylidenecamphor, for example marketed by Merck under the name “Eusolex 6300”, benzylidenecamphorsulfonic acid, for example marketed by Chimex under the name “Mexoryl SL”, Camphor benzalkonium methosulfate, for example marketed by Chimex under the name “Mexoryl SO”, terephthalylidenedicamphorsulfonic acid, for example marketed by Chimex under the name “Mexoryl SX”, Polyacrylamidomethylbenzylidenecamphor marketed by Chimex under the name “Mexoryl SW”.
[0140] Phenylbenzimidazole derivatives: phenylbenzimidazolesulfonic acid, for example marketed by Merck under the name “Eusolex 232”, disodium phenyl dibenzimidazole tetrasulfonate, for example marketed by Symrise under the name “Neo Heliopan AP”.
[0141] Phenylbenzotriazole derivatives: Drometrizole trisiloxane, for example marketed by Rhodia Chimie under the name “Silatrizole”,
[0142] Methylenebis(benzotriazolyl)tetramethylbutylphenol in solid form, for example marketed by Fairmount Chemical under the name “MIXXIM BB / 100”, or in micronized form as an aqueous dispersion, for example marketed by BASF under the name “Tinosorb M”.
[0143] Triazine derivatives: ethylhexyltriazone, for example marketed under the name “Uvinul T150” by BASF, diethylhexylbutamidotriazone, for example marketed under the name “Uvasorb HEB” by Sigma 3V, 2,4,6-tris(diisobutyl 4′-aminobenzalmalonate)-s-triazine or 2,4,6- tris(biphenyl)-1,3,5-triazine. marketed as Tinosorb A2B by BASF, 2,2′-[6-(4-methoxyphenyl)- 1,3,5-triazine-2,4-diyl]bis[5-(2-ethylhexyl)oxy]phenol, marketed as Tinosorb S by BASF, N2,N4- bis[4-[5-(1,1-dimethylpropyl)-2-benzoxazolyl]phenyl]-N-6-(2-ethylhexyl)-1,3,5-triazine-2,4,6- triamine marketed as Uvasorb K 2A by Sigma 3V.
[0144] Anthraniline derivatives: Menthyl anthranilate, for example marketed by Symrise under the name “Neo Heliopan MA”.
[0145] Imidazole derivatives: Ethylhexyldimethoxybenzylidenedioxoimidazoline propionate.
[0146] Benzalmalonate derivatives: polyorganosiloxanes containing functional benzalmalonate groups, such as, for example, polysilicone-15, for example marketed by Hoffmann LaRoche under the name “Parsol SLX”.
[0147] 4,4-Diarylbutadiene derivatives: 1,1-Dicarboxy(2,2′-dimethylpropyl)-4,4- diphenylbutadiene.
[0148] Benzoxazole derivatives: 2,4-bis[5-(1-dimethylpropyl)benzoxazol-2-yl(4-phenyl) imino]- 6-(2-ethylhexyl)imino-1,3,5-triazine, for example marketed by Sigma 3V under the name Uvasorb K2A, and mixtures comprising this.
[0149] Suitable organic UV-protecting substances can preferably be selected from: Ethylhexyl salicylate, Phenylbenzimidazolesulfonic acid, Benzophenone-3, Benzophenone-4, Benzophenone-5, n-Hexyl 2-(4-diethylamino-2-hydroxybenzoyl)benzoate, 4- Methylbenzylidenecamphor, Terephthalylidenedicamphorsulfonic acid, Disodium phenyldibenzimidazoletetrasulfonate, Methylenebis(benzotriazolyl)tetramethylbutylphenol, Ethylhexyl Triazone, Diethylhexyl Butamido Triazone, Drometrizole trisiloxane, Polysilicone- 15,1,1-Dicarboxy(2,2′-dimethylpropyl)-4,4-diphenylbutadiene, 2,4-bis[5-1 (dimethylpropyl)benzoxazol-2-yl(4-phenyl) imino]-6-(2-ethylhexyl)imino-1,3,5-triazine and mixtures thereof.
[0150] The compositions of the invention may comprise further inorganic UV filters, so-called particulate UV filters. These combinations with particulate UV filters are possible both as powder and also as dispersion or paste. In an embodiment the inorganic UV filter is a titanium dioxide, such as, for example, coated titanium dioxide (for example Eusolex® T-2000, Eusolex® T- AQUA, Eusolex® T-AVO, Eusolex® T-OLEO), a zinc oxide (for example Sachtotec), an iron oxide or a cerium oxide and / or zirconium oxide. Furthermore, combinations with pigmentary titanium dioxide or zinc oxide are also possible, where the particle size of these pigments are greater than or equal to 200 nm, for example Hombitan® FG or Hombitan® FFPharma.
[0151] Compositions of the invention may comprise inorganic UV filters which have been after treated by conventional methods, as described, for example, in Cosmetics & Toiletries, 1990, 105, 53-64. One or more of the following aftertreatment components can be: amino acids, beeswax, fatty acids, fatty acid alcohols, anionic surfactants, lecithin, phospholipids, sodium, potassium, zinc, iron or aluminium salts of fatty acids, polyethylenes, silicones, proteins (particularly collagen or elastin), alkanolamines, silicon dioxide, aluminium oxide, further metal oxides, phosphates, such as sodium hexametaphosphate, or glycerin.
[0152] In an embodiment, particulate UV filters used in compositions of the invention are: ^ untreated titanium dioxides, such as, the products Microtitanium Dioxide MT 500 B from Tayca; titanium dioxide P25 from Degussa, ^ after treated micronized titanium dioxides with aluminium oxide and silicon dioxide aftertreatment, such as, the product “Microtitanium Dioxide MT 100 SA from Tayca; or the product “Tioveil Fin” from Uniqema, ^ after treated micronized titanium dioxides with aluminium oxide and / or aluminium stearate / laurate aftertreatment, such as, Microtitanium Dioxide MT 100 T from Tayca, Eusolex T-2000 from Merck, ^ after treated micronized titanium dioxides with iron oxide and / or iron stearate aftertreatment, such as, the product “Microtitanium Dioxide MT 100 F” from Tayca, ^ after treated micronized titanium dioxides with silicon dioxide, aluminium oxide and silicone aftertreatment, such as, the product “Microtitanium Dioxide MT 100 SAS”, from Tayca, ^ after treated micronized titanium dioxides with sodium hexametaphosphates, such as, the product “Microtitanium Dioxide MT 150 W” from Tayca.
[0153] The treated micronized titanium dioxides employed for the combination may also be after treated with: ^ octyltrimethoxysilanes; such as, the product Tego Sun T 805 from Evonik Goldschmidt GmbH, ^ silicon dioxide; such as, for example, the product Parsol T-X from DSM, ^ aluminium oxide and stearic acid; such as, the product UV-Titan M160 from Sachtleben, ^ aluminium and glycerin; such as, the product UV-Titan from Sachtleben, ^ aluminium and silicone oils, such as, the product UV-Titan M262 from Sachtleben, ^ sodium hexametaphosphate and polyvinylpyrrolidone, ^ polydimethylsiloxanes, such as, the product 70250 Cardre UF TiO2SI3” from Cardre, ^ polydimethylhydrogenosiloxanes, such as, for example, the product Microtitanium Dioxide USP Grade Hydrophobic” from Color Techniques.
[0154] In a particular embodiment, compositions of the invention may include untreated zinc oxides, such as, the product Z-Cote from BASF (Sunsmart), Nanox from Elementis. In another particular embodiment, compositions of the invention may include after treated zinc oxides, such as, the following products: ^ “Zinc Oxide CS-5” from Toshibi (ZnO after treated with polymethylhydrogeno-siloxanes); ^ Nanogard Zinc Oxide FN from Nanophase Technologies; ^ “SPD-Z1” from Shin-Etsu (ZnO after treated with a silicone-grafted acrylic polymer, dispersed in cyclodimethylsiloxanes; ^ “Escalol Z100” from ISP (aluminium oxide-after treated ZnO dispersed in an ethylhexyl methoxycinnamate / PVP-hexadecene / methicone copolymer mixture); and ^ “Fuji ZNO-SMS-10” from Fuji Pigment (ZnO after treated with silicon dioxide and polymethylsilesquioxane). ^ Zano M Plus (Evercare) ^ Zano 10 Plus (Evercare) ^ Zinclear dispersions (Antaria)
[0155] In another particular embodiment, compositions of the invention may include untreated cerium oxide micropigment, for example with the name “Colloidal Cerium Oxide” from Rhone Poulenc. In another particular embodiment, compositions of the invention may include untreated and / or after treated iron oxides with the name Nanogar from Arnaud.
[0156] By way of example, it is also possible to employ mixtures of various metal oxides, such as, for example, zinc oxide and cerium oxide, with and without aftertreatment, such as, for example, the product Sunveil A from Ikeda. In addition, mixtures of aluminium oxide, silicon dioxide and silicone-after treated titanium dioxide, zinc oxide mixtures, such as, the product UV- Titan M261 from Sachtleben, can also be used in combination with the UV protection agents according to the invention. Methods of Use
[0157] In some embodiments, the present disclosure is directed to a method of treating a skin of a subject for effects of radical-induced damage. Radical-induced damage may encompass damage from free radicals from sunlight (UVB, UVA, Visible Light), HEV (blue) light, Infrared (IR), pollution, irritants, allergens, and various environmental toxins that are destructive to the skin, for example, by hydrolyzing elastin fibers in the skin and desynthesizing collagen in the lower dermal layers of the skin. Exemplary radical-induced damage that may be treated, prevented, minimized, reduced, or attenuated after administering to a skin of a subject an effective amount of any of the sunscreen formulations described herein includes, without limitations, skin wrinkles, appearance of fine lines, skin roughness, skin sagging, skin firmness, reduction in skin elasticity, age spots, hyperpigmentation, scars, skin surface irregularities, rosacea, acne, psoriasis, reduction in the skin’s regenerative and renewal process, weather-beaten appearance, yellowing, redness, dryness, ichthyosis, and other damaging skin conditions.
[0158] In certain embodiments, the present disclosure is directed to a method of brightening a skin of a subject by administering to the skin of a subject an effective amount of any of the topical formulation described herein, wherein the skin is brightened after administration of the sunscreen formulation.
[0159] In certain embodiments, the present disclosure is directed to a method treating a skin of a subject for effects of atmospheric or extrinsic aging by administering to the skin of a subject an effective amount of any of the sunscreen formulations described herein, wherein the skin exhibits reduction or attenuation of effects of atmospheric or extrinsic aging after administration.
[0160] In certain embodiment, the present disclosure is directed to a treatment regimen method that includes administering to a skin of a subject that has been subjected to a dermatological procedure an effective amount of any of the sunscreen formulation described herein. Dermatological procedure that may benefit for subsequent (i.e., post procedure) administration of the sunscreen formulation described herein include, without limitations, non-ablative dermatological procedures, chemical peel, micro-abrasion, laser, and the like. In certain embodiments, the methods described herein further include performing the dermatological procedure after administration of the sunscreen formulation and / or before administration of the sunscreen formulation, depending on the treatment regimen. In certain embodiments, the sunscreen formulation described herein is helpful in improving the outcomes of dermatological procedures, e.g., by speeding healing, quelling discomfort, quenching reactive oxygen species (ROS), inducing collagen formation, or any combination thereof.
[0161] As used herein, the terms “treatment” or “treating” with respect to a skin condition generally mean “having positive effect on a skin condition” and encompass reduction, amelioration, and / or alleviation of at least one symptom of a skin condition, a reduction, amelioration, and / or alleviation in the severity of the skin conditions, or delay, prevention, or inhibition of the progression of the skin condition, or the perception thereof. Treatment, as used herein, therefore does not require total curing of the condition. A formulation of the present disclosure that is useful for treatment of a skin condition, or a method of treating a skin condition, need only reduce the severity of a skin condition, reduce the severity of symptoms associated therewith, provide improvement to a patient's quality of life, or delay, prevent, or inhibit the onset of one or more symptoms of a skin condition. As used herein, these terms also encompass aesthetic improvements to the skin upon application of the disclosed formulations having a combination of, for example, an ascorbate component and green tea polyphenols.
[0162] As used herein, the phrase “effective amount” refers to an amount of a topical formulation of the present disclosure, or component thereof, effective to treat a skin condition as noted above, including a range of effects, from a detectable local improvement in an area of topical application to substantial relief of symptoms to an improvement in one or more aesthetic criteria, including, but not limited to, a perceived improvement in damage from free radicals from sunlight (UVB, UVA, Visible Light), HEV (blue) light, Infrared (IR), pollution, irritants, allergens, and various environmental toxins, skin wrinkles, appearance of fine lines, skin roughness, skin sagging, skin firmness, skin elasticity, age spots, hyperpigmentation, scars, skin surface irregularities, rosacea, acne, psoriasis, skin’s regenerative and renewal process, weather-beaten appearance, yellowing, redness, dryness, ichthyosis, and other damaging skin conditions.
[0163] The effective amount will vary with the particular condition or conditions being treated, the severity of the condition, the duration of the treatment, the specific components of the formulation being used, and other factors. In certain embodiments, the sunscreen formulation described herein are suitable for administration by frequent periodic application, such as by a once, twice, thrice or four times daily application or more, e.g., for a duration of at least 1 day, at least 3 days, at least 5 days, at least 7 days, at least 10 days, at least 14 days, at least 21 days, at least 30 days, and so on. Accordingly, in certain embodiments, the methods described herein further include periodically repeating the administration of the sunscreen formulation.
[0164] In certain embodiments, the sunscreen formulations described herein are suitable for a pre or post procedure administration, such as before or after a dermatological procedure.
[0165] In certain embodiments, since the sunscreen formulation may be homogenous. Method of Preparation
[0166] The instant disclosure is also directed to a method of preparing any of the topical formulations described herein. The method includes preparing a topical formulation including mixing a thymine-thymine compound of Formula (I) and a solvent system comprising an alkanediol to form a topical formulation; wherein the mixing occurs at a temperature of about 45°C to about 60°C for at least about 1 hour. The compound of Formula (I) being: wherein: each R1is independently H, (C1-C6)alkyl, (C3-C7)carbocycle or RaC(=O; or the two R1groups together form a —(C3-C8)alkyl-group, a —(C2-C6)alkyl-Y—(C2-C6)alkyl-group or a — (C1-C6)alkyl-Y′—(C1-C6)alkyl-group; or the dashed bonds labeled “a” are absent and the dashed bonds labeled “b” are double bonds; or all the dashed bonds are single bonds; R2is H, (C1-C6)alkyl or aryl, wherein aryl is optionally substituted with one or more (e.g. 1, 2, 3, 4 or 5) Z1groups; R3is H, (C1-C6)alkyl or aryl, wherein aryl is optionally substituted with one or more (e.g. 1, 2, 3, 4 or 5) Z1groups; R4is hydroxy, carboxy, (C1-C6)alkoxycarbonyl, —OPO3H2, —ORc, or —NRdRe; and R5is H; or R4and R5taken together are oxo; Y is O, S, NH, P, P(═O) or POH; Y′ is Si(Rb)2 or —Si(Rb)2—O—Si(Rb)2—; each Rais independently (C1-C6)alkyl, (C3-C7)carbocycle or aryl, wherein aryl is optionally substituted with one or more (e.g.1, 2, 3, 4 or 5) Z1groups; each Rbis independently (C1-C6)alkyl, (C3-C7)carbocycle or aryl, wherein aryl is optionally substituted with one or more (e.g.1, 2, 3, 4 or 5) Z1groups; Rcis Rfor a C1-C20saturated or C2-C20unsaturated carbon chain that is optionally substituted with one or more groups independently selected from oxo (═O), hydroxy, mercapto, (C1-C6)alkoxy, (C1-C6)alkoxycarbonyl, (C1-C6)alkanoyloxy, NRdRe, carboxy, and aryl, wherein aryl is optionally substituted with one or more (e.g.1, 2, 3, 4 or 5) Z1groups; Rdis H, (C1-C6)alkyl, or (C1-C6)alkanoyl; Re is H or a C1-C20 saturated or C2-C20 unsaturated carbon chain that is optionally substituted with one or more groups independently selected from oxo (═O), hydroxy, mercapto, (C1-C6)alkoxy, (C1-C6)alkoxycarbonyl, (C1-C6)alkanoyloxy, NRdRe, carboxy, and aryl, wherein aryl is optionally substituted with one or more (e.g.1, 2, 3, 4 or 5) Z1groups;each Z1is independently selected from (C1-C6)alkyl, halogen, —CN, —ORn1, —NRq1Rr1, —NRn1CORp1, —NRn1CO2Rp1, NO2, —C(O)Rn1, —C(O)ORn1 and —C(O)NRq1Rr1, wherein any (C1-C6)alkyl of Z1is optionally substituted with one or more (e.g.1, 2, 3, 4, 5 or 6) halogen; each Rn1 is independently selected from H and (C1-C6)alkyl, wherein any (C1-C6)alkyl of Rn1is optionally substituted with one or more (e.g.1, 2, 3, 4, 5 or 6) halogen; each Rp1 is independently (C1-C6)alkyl; and Rq1and Rr1are each independently selected from H and (C1-C6)alkyl or Rq1and Rr1 together with the nitrogen to which they are attached form a piperidine, pyrrolidine, morpholine, azetidine, thiomorpholine, piperazine or 4-methylpiperazine.
[0167] In some embodiments, the mixing may occur at a temperature of about 45°C, about 50°C, about 55°C, or about 60°C. In some embodiments, the mixing may occur for about 1 hour to about 48 hours, about 2 hour to about 42 hours, about 3 hours to about 36 hours, about 4 hours to about 30 hours, about 5 hours to about 24 hours, about 6 hours to about 18 hours, about 8 hours to about 16 hours, or about 10 hours to about 12 hours.
[0168] In some embodiments, the method may further include including mixing at least one cosmetic acceptable excipient.
[0169] In some embodiments, the method may further include treating the topical formulation. The treating may include milling, roller milling, or colloidal milling.
[0170] In some embodiments, the topical formulation may include 0.01 wt% to about 10 wt% of the thymine-thymine compound of Formula (I) based on total weight of the topical formulation. In some embodiments, the thymine-thymine compound may be included in an amount of about 0.01wt%, about 0.1 wt%, about 0.5 wt%, about 1 wt%, about 2 wt%, about 4 wt%, about 5 wt%, about 8 wt%, or about 10 wt% in the topical formulation. ILLUSTRATIVE EXAMPLES
[0171] The following examples are set forth to assist in understanding the invention and should not, of course, be construed as specifically limiting the invention described and claimed herein. Such variations of the invention, including the substitution of all equivalents now known or later developed, which would be within the purview of those skilled in the art, and changes in formulation or minor changes in experimental design, are to be considered to fall within the scope of the invention incorporated herein. Example 1
[0172] A topical formulation in accordance with embodiments described herein was formulated into a cream having the composition described in Table 1 below. Table 1:
[0153] The formulation of Table 1 was prepared according to the following manufacturing method. A stainless-steel container was used to prepare the formulation to protect the components from light. Water was mixed with bubbling of nitrogen, and was heated to 90-95 °C. The heating is stopped after a time, where disodium EDTA is added. The container is then cooled to 75-80°C while mixing. The product is then maintained under a nitrogen blanket in a batch container, while premixing glycerin and xanthan gum was done in a stainless steel container. The premix was then added to the batch while mixing.
[0154] The “Oil Phase” was prepared by mixing Caprylic / Capric Triglyceride, Tribehinin PEG 20 Esters, Stearyl / PPG-3 Myristyl Ether Dimer Dilinoleate, Tocopheryl Acetate, Glyceryl Stearate, PEG-100 Stearate, Cetyl Alcohol, Dimethicone, and Isosorbide Dicaprylate in the stainless-steel container. The mixture would was heated at 75-80°C.
[0155] The “oil-phase” was added to the batch container and was mixed for 10-15 minutes at 75- 80°C. The sodium acrylates copolymer and lecithin was added after the first time, where mixing continued for 30 minutes. The contents of the stainless-steel container was transferred to the batch vessel through a colloid mill. The uniformity was then verified before continuing to mix.
[0156] Once the batch was mixed well, triethanolamine 99% was added and mixed for an additional 10 minutes. The temperature was maintained at 75-80°C.
[0157] In a separate stainless-steel container, a premix of propanediol and the thymine- thymine compound of Formula (I) was mixed for 1 hour with a homomixer and was then heated to 65°C and mixed for an additional hour at 65°C. The premixed phase was then cooled and held overnight.
[0158] After holding, the premix phase was added to the batch container described above while mixing. Butylene Glycol, Hexylresorcinol and propyl gallate was then added to the stainless-steel container which was mixed until dissolved.
[0159] Ammonium acryloldimethyltaurate / VP copolymer was added to the batch mix until homogenous, which was then cooled to 70°C. The batch was then slowly cooled to 45-50°C while being mixed. Once cooled, phenoxyethanol was added and mixed for 10 minutes.
[0160] The mixture was then mixed with homogenization for 20 minutes, where the remaining ingredients were added individually mixing for two minutes after each addition: Arbutin, Bearberry Extract, Mulberry Extract, Hexanoyl Dipeptide-3 Norleucine Acetate, Willow Bark Extract, Emblica, and Ergothioneine.
[0161] The batch was then cooled to 20-25°C and then homomixed for 7-10 minutes. The mixture was then discharged into drums that were charged with nitrogen. Example 2
[0173] A sunscreen formulation in accordance with embodiments described herein was formulated into a cream having the composition described in Table 2 below. Table 2 – Sunscreen Formulation
[0174] For simplicity of explanation, the embodiments of the methods of this disclosure are depicted and described as a series of acts. However, acts in accordance with this disclosure can occur in various orders and / or concurrently, and with other acts not presented and described herein. Furthermore, not all illustrated acts may be required to implement the methods in accordance with the disclosed subject matter. In addition, those skilled in the art will understand and appreciate that the methods could alternatively be represented as a series of interrelated states via a state diagram or events.
[0175] In the foregoing description, numerous specific details are set forth, such as specific materials, dimensions, processes parameters, etc., to provide a thorough understanding of the present invention. The particular features, structures, materials, or characteristics may be combined in any suitable manner in one or more embodiments. The words “example” or “exemplary” are used herein to mean serving as an example, instance, or illustration. Any aspect or design described herein as “example” or “exemplary” is not necessarily to be construed as preferred or advantageous over other aspects or designs. Rather, use of the words “example” or “exemplary” is intended to present concepts in a concrete fashion. As used in this application, the term “or” is intended to mean an inclusive “or” rather than an exclusive “or”. That is, unless specified otherwise, or clear from context, “X includes A or B” is intended to mean any of the natural inclusive permutations. That is, if X includes A; X includes B; or X includes both A and B, then “X includes A or B” is satisfied under any of the foregoing instances. In addition, the articles “a” and “an” as used in this application and the appended claims should generally be construed to mean “one or more” unless specified otherwise or clear from context to be directed to a singular form. Reference throughout this specification to “an embodiment”, “certain embodiments”, or “one embodiment” means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment. Thus, the appearances of the phrase “an embodiment”, “certain embodiments”, or “one embodiment” in various places throughout this specification are not necessarily all referring to the same embodiment.
[0176] Reference throughout this specification to numerical ranges should not be construed as limiting and should be understood as encompassing the outer limits of the range as well as each number and / or narrower range within the enumerated numerical range.
[0177] The term “about”, when referring to a physical quantity, is to be understood to include measurement errors within, and inclusive of 10%. For example, “about 100°C” should be understood to mean “100±10°C”.
[0178] The present invention has been described with reference to specific exemplary embodiments thereof. The specification and drawings are, accordingly, to be regarded in an illustrative rather than a restrictive sense. Various modifications of the invention in addition to those shown and described herein will become apparent to those skilled in the art and are intended to fall within the scope of the appended claims.
Claims
CLAIMS What is claimed is:
1. A topical formulation comprising: a thymine-thymine compound comprising a compound of Formula (I) or a salt thereof:wherein: each R1is independently H, (C1-C6)alkyl, (C3-C7)carbocycle or RaC(=O; or the two R1groups together form a —(C3-C8)alkyl-group, a —(C2-C6)alkyl-Y—(C2-C6)alkyl-group or a —(C1-C6)alkyl-Y′—(C1-C6)alkyl-group; or the dashed bonds labeled “a” are absent and the dashed bonds labeled “b” are double bonds; or all the dashed bonds are single bonds; R2is H, (C1-C6)alkyl or aryl, wherein aryl is optionally substituted with one or more (e.g.1, 2, 3, 4 or 5) Z1groups; R3is H, (C1-C6)alkyl or aryl, wherein aryl is optionally substituted with one or more (e.g.1, 2, 3, 4 or 5) Z1groups; R4is hydroxy, carboxy, (C1-C6)alkoxycarbonyl, —OPO3H2, —ORc, or —NRdRe; and R5is H; or R4and R5taken together are oxo; Y is O, S, NH, P, P(═O) or POH; Y′ is Si(Rb)2 or —Si(Rb)2—O—Si(Rb)2—; each Rais independently (C1-C6)alkyl, (C3-C7)carbocycle or aryl, wherein aryl is optionally substituted with one or more (e.g.1, 2, 3, 4 or 5) Z1groups; each Rbis independently (C1-C6)alkyl, (C3-C7)carbocycle or aryl, wherein aryl is optionally substituted with one or more (e.g.1, 2, 3, 4 or 5) Z1groups; Rc is Rf or a C1-C20 saturated or C2-C20 unsaturated carbon chain that is optionally substituted with one or more groups independently selected from oxo (═O), hydroxy, mercapto, (C1-C6)alkoxy, (C1-C6)alkoxycarbonyl, (C1-C6)alkanoyloxy, NRdRe, carboxy, and aryl, wherein aryl is optionally substituted with one or more (e.g. 1, 2, 3, 4 or 5) Z1groups; Rdis H, (C1-C6)alkyl, or (C1-C6)alkanoyl; Re is H or a C1-C20 saturated or C2-C20 unsaturated carbon chain that is optionally substituted with one or more groups independently selected from oxo (═O), hydroxy, mercapto, (C1-C6)alkoxy, (C1-C6)alkoxycarbonyl, (C1-C6)alkanoyloxy, NRdRe, carboxy, and aryl, wherein aryl is optionally substituted with one or more (e.g. 1, 2, 3, 4 or 5) Z1groups; each Rf, is:each Z1is independently selected from (C1-C6)alkyl, halogen, —CN, —ORn1, — NRq1Rr1, —NRn1CORp1, —NRn1CO2Rp1, NO2, —C(O)Rn1, —C(O)ORn1and — C(O)NRq1Rr1, wherein any (C1-C6)alkyl of Z1is optionally substituted with one or more (e.g.1, 2, 3, 4, 5 or 6) halogen; each Rn1 is independently selected from H and (C1-C6)alkyl, wherein any (C1- C6)alkyl of Rn1 is optionally substituted with one or more (e.g.1, 2, 3, 4, 5 or 6) halogen; each Rp1 is independently (C1-C6)alkyl; and Rq1 and Rr1 are each independently selected from H and (C1-C6)alkyl or Rq1 and Rr1together with the nitrogen to which they are attached form a piperidine, pyrrolidine, morpholine, azetidine, thiomorpholine, piperazine or 4-methylpiperazine; a solvent system comprising an alkanediol, wherein the thymine-thymine compound is included in an amount of about 0.01 wt% to about 10 wt%, based on total weight of the topical formulation.
2. The topical formulation of claim 1, wherein the alkanediol comprises propanediol, a glycol comprising a four carbon to 20 carbon backbone, or a combination thereof.
3. The topical formulation of claim 2, wherein the glycol comprises butylene glycol, pentylene glycol, or hexylene glycol.
4. The topical formulation of claim 1, further comprising a surfactant.
5. The topical formulation of claim 4, wherein the surfactant comprises an oleyl alcohol or its ethoxylates, polyglycerol esters or a combination thereof.
6. The topical formulation of claim 1, further comprising a phospholipid.
7. The topical formulation of claim 6, wherein the phospholipid comprises a liposome.
8. The topical formulation of claim 1, further comprising a preservative.
9. The topical formulation of claim 8, wherein the preservative comprises phenoxyethanol.
10. The topical formulation of claim 1, further comprising water.
11. The topical formulation of claim 1, further comprising an antioxidant.
12. The topical formulation of claim 11, wherein the antioxidant comprises resveratrol, ubiquinone, vitamin C, ascorbic acid, emblica, a green tea polyphenol, or a combination thereof.
13. The topical formulation of claim 1, wherein the topical formulation protects against UVA and UVB waves.
14. The topical formulation of claim 1, wherein the thymine-thymine compound of Formula (I) is a compound of Formula Ia: or a salt thereof.
15. The topical formulation of claim 1, wherein the thymine-thymine compound of Formula (I) is a compound of Formula Ib:or a salt thereof.
16. The topical formulation of claim 1, wherein each R1of the thymine-thymine compound of Formula (I) is independently H or (C1-C6)alkyl.
17. The topical formulation of claim 1, wherein each R1of the thymine-thymine compound of Formula (I) is H.
18. The topical formulation of claim 1, wherein the thymine-thymine compound of Formula (I) is selected from the group consisting of: , , , , , , , , ,, ,19. The topical formulation of claim 1, wherein the thymine-thymine compound of Formula (I) is selected from the group consisting of: .
20. A method of preparing a topical formulation comprising: mixing a thymine-thymine compound comprising a compound of Formula (I) and a solvent system to form a topical formulation, wherein the mixing occurs at a temperature for about 45°C to about 60°C for at least about 1 hour, wherein the compound of Formula (I) iswherein: each R1is independently H, (C1-C6)alkyl, (C3-C7)carbocycle or RaC(=O; or the two R1groups together form a —(C3-C8)alkyl-group, a —(C2-C6)alkyl-Y—(C2-C6)alkyl-group or a —(C1-C6)alkyl-Y′—(C1-C6)alkyl-group; or the dashed bonds labeled “a” are absent and the dashed bonds labeled “b” are double bonds; or all the dashed bonds are single bonds; R2is H, (C1-C6)alkyl or aryl, wherein aryl is optionally substituted with one or more (e.g.1, 2, 3, 4 or 5) Z1groups; R3is H, (C1-C6)alkyl or aryl, wherein aryl is optionally substituted with one or more (e.g.1, 2, 3, 4 or 5) Z1groups; R4is hydroxy, carboxy, (C1-C6)alkoxycarbonyl, —OPO3H2, —ORc, or —NRdRe; and R5is H; or R4and R5taken together are oxo; Y is O, S, NH, P, P(═O) or POH; Y′ is Si(Rb)2or —Si(Rb)2—O—Si(Rb)2—; each Ra is independently (C1-C6)alkyl, (C3-C7)carbocycle or aryl, wherein aryl is optionally substituted with one or more (e.g.1, 2, 3, 4 or 5) Z1groups; each Rb is independently (C1-C6)alkyl, (C3-C7)carbocycle or aryl, wherein aryl is optionally substituted with one or more (e.g.1, 2, 3, 4 or 5) Z1groups; Rc is Rf or a C1-C20 saturated or C2-C20 unsaturated carbon chain that is optionally substituted with one or more groups independently selected from oxo (═O), hydroxy, mercapto, (C1-C6)alkoxy, (C1-C6)alkoxycarbonyl, (C1-C6)alkanoyloxy, NRdRe, carboxy, and aryl, wherein aryl is optionally substituted with one or more (e.g. 1, 2, 3, 4 or 5) Z1groups; Rd is H, (C1-C6)alkyl, or (C1-C6)alkanoyl; Reis H or a C1-C20saturated or C2-C20unsaturated carbon chain that is optionally substituted with one or more groups independently selected from oxo (═O), hydroxy, mercapto, (C1-C6)alkoxy, (C1-C6)alkoxycarbonyl, (C1-C6)alkanoyloxy, NRdRe, carboxy, and aryl, wherein aryl is optionally substituted with one or more (e.g. 1, 2, 3, 4 or 5) Z1groups;each Z1is independently selected from (C1-C6)alkyl, halogen, —CN, —ORn1, — NRq1Rr1, —NRn1CORp1, —NRn1CO2Rp1, NO2, —C(O)Rn1, —C(O)ORn1 and — C(O)NRq1Rr1, wherein any (C1-C6)alkyl of Z1is optionally substituted with one or more (e.g.1, 2, 3, 4, 5 or 6) halogen; each Rn1is independently selected from H and (C1-C6)alkyl, wherein any (C1- C6)alkyl of Rn1 is optionally substituted with one or more (e.g.1, 2, 3, 4, 5 or 6) halogen; each Rp1is independently (C1-C6)alkyl; and Rq1 and Rr1 are each independently selected from H and (C1-C6)alkyl or Rq1 and Rr1together with the nitrogen to which they are attached form a piperidine, pyrrolidine, morpholine, azetidine, thiomorpholine, piperazine or 4- methylpiperazine.
21. The method of claim 21, further comprising treating the topical formulation.
22. The method of claim 21, wherein the treating comprises, milling, roller milling or colloid milling.
23. The method of claim 21, wherein the topical formulation comprises the thymine-thymine compound in an amount of about 0.01 wt% to about 10 wt%, based on total weight of the topical formulation.
24. A method of treating a skin of a subject for effects of radical-induced damage comprising applying a topical formulation of any one of claims 1-23.
25. The method of treating of claim 24, wherein the sunscreen formulation is applied in an effective amount.
26. The method of claim 24, wherein the skin is brightened after applying the sunscreen formulation.
27. The method of claim 24, wherein the topical formulation prevents cyclopyrimidine dimer (CPD) formation when compared to skin that is not treated with the topical formulation.
28. The method of claim 24, wherein the applying of the sunscreen formulation is periodically repeated.
29. A topical formulation comprising: a mineral active agent; a thymine-thymine compound comprising a compound of Formula (I) or a salt thereof: wherein: each R1is independently H, (C1-C6)alkyl, (C3-C7)carbocycle or RaC(=O; or the two R1groups together form a —(C3-C8)alkyl-group, a —(C2-C6)alkyl-Y—(C2-C6)alkyl-group or a — (C1-C6)alkyl-Y′—(C1-C6)alkyl-group; or the dashed bonds labeled “a” are absent and the dashed bonds labeled “b” are double bonds; or all the dashed bonds are single bonds; R2is H, (C1-C6)alkyl or aryl, wherein aryl is optionally substituted with one or more (e.g. 1, 2, 3, 4 or 5) Z1groups; R3is H, (C1-C6)alkyl or aryl, wherein aryl is optionally substituted with one or more (e.g. 1, 2, 3, 4 or 5) Z1groups; R4is hydroxy, carboxy, (C1-C6)alkoxycarbonyl, —OPO3H2, —ORc, or —NRdRe; and R5is H; or R4and R5taken together are oxo; Y is O, S, NH, P, P(═O) or POH; Y′ is Si(Rb)2or —Si(Rb)2—O—Si(Rb)2—; each Ra is independently (C1-C6)alkyl, (C3-C7)carbocycle or aryl, wherein aryl is optionally substituted with one or more (e.g.1, 2, 3, 4 or 5) Z1groups; each Rb is independently (C1-C6)alkyl, (C3-C7)carbocycle or aryl, wherein aryl is optionally substituted with one or more (e.g.1, 2, 3, 4 or 5) Z1groups; Rc is Rf or a C1-C20 saturated or C2-C20 unsaturated carbon chain that is optionally substituted with one or more groups independently selected from oxo (═O), hydroxy, mercapto, (C1-C6)alkoxy, (C1-C6)alkoxycarbonyl, (C1-C6)alkanoyloxy, NRdRe, carboxy, and aryl, wherein aryl is optionally substituted with one or more (e.g.1, 2, 3, 4 or 5) Z1groups; Rdis H, (C1-C6)alkyl, or (C1-C6)alkanoyl; Re is H or a C1-C20 saturated or C2-C20 unsaturated carbon chain that is optionally substituted with one or more groups independently selected from oxo (═O), hydroxy, mercapto, (C1-C6)alkoxy, (C1-C6)alkoxycarbonyl, (C1-C6)alkanoyloxy, NRdRe, carboxy, and aryl, wherein aryl is optionally substituted with one or more (e.g.1, 2, 3, 4 or 5) Z1groups; each Rf, is:each Z1is independently selected from (C1-C6)alkyl, halogen, —CN, —ORn1, —NRq1Rr1, —NRn1CORp1, —NRn1CO2Rp1, NO2, —C(O)Rn1, —C(O)ORn1 and —C(O)NRq1Rr1, wherein any (C1-C6)alkyl of Z1is optionally substituted with one or more (e.g.1, 2, 3, 4, 5 or 6) halogen; each Rn1 is independently selected from H and (C1-C6)alkyl, wherein any (C1-C6)alkyl of Rn1is optionally substituted with one or more (e.g.1, 2, 3, 4, 5 or 6) halogen; each Rp1 is independently (C1-C6)alkyl; and Rq1and Rr1are each independently selected from H and (C1-C6)alkyl or Rq1and Rr1 together with the nitrogen to which they are attached form a piperidine, pyrrolidine, morpholine, azetidine, thiomorpholine, piperazine or 4-methylpiperazine; wherein the sunscreen formulation has a SPF greater than about 50.
30. The topical formulation of claim 29, wherein the mineral active agent comprises zinc oxide, titanium oxide, or a combination thereof.
31. The topical formulation of claim 29, further comprising an antioxidant.
32. The topical formulation of claim 31, wherein the antioxidant comprises caffeine or hydroxy acid.
33. The topical formulation of claim 29, wherein the mineral active agent is zinc oxide.
34. The topical formulation of claim 29, further comprising an emollient.
35. The topical formulation of claim 34, wherein the emollient comprises octyldodecyl neopentanoate, neopentyl glycoldiheptanoate, ethylhexyl stearate, or a combination thereof.
36. The topical formulation of claim 29, further comprising a preservative.
37. The topical formulation of claim 36, wherein the preservative comprises phenoxyethanol.
38. The topical formulation of claim 29, further comprising an emulsifier.
39. The topical formulation of claim 29, further comprising a UV filter agent.
40. The topical formulation of claim 39, wherein the UV filter agent comprises octinoxate.
41. The topical formulation of claim 29, further comprising a solvent.
42. The topical formulation of claim 41, wherein the solvent comprises water, glycerin, or a combination thereof.
43. The topical formulation of claim 29, wherein the mineral active agent further comprises isostearic acid, polyhydroxysteric acid, C12-C15 alkyl benzoate, or a combination thereof.
44. The topical formulation of claim 29, wherein the formulation protects against UVA and UVB waves.
45. The topical formulation of claim 29, wherein the formulation is homogenous.
46. The topical formulation of claim 29, wherein the mineral active agent is included in an amount of about 20% to about 50%, based on total weight of the sunscreen formulation.
47. The topical formulation of claim 29, wherein the thymine-thymine compound of Formula (I) is a compound of Formula Ia: or a salt thereof.
48. The topical formulation of claim 29, wherein the thymine-thymine compound of Formula (I) is a compound of Formula Ib:or a salt thereof.
49. The topical formulation of claim 29, wherein each R1of the thymine-thymine compound of Formula (I) is independently H or (C1-C6)alkyl.
50. The topical formulation of claim 29, wherein each R1of the thymine-thymine compound of Formula (I) is H.
51. The topical formulation of claim 29, wherein the thymine-thymine compound of Formula (I) is selected from the group consisting of : , , , , , , , , ,, 52. The topical formulation of claim 29, wherein the thymine-thymine compound of Formula (I) is selected from the group consisting of: .
53. The topical formulation of claim 29, wherein the thymine-thymine compound of Formula (I) is included in an amount of about 0.1 wt% to about 10 wt%.
54. A method of treating a skin of a subject for effects of radical-induced damage comprising applying a topical formulation of any one of claims 29-53.
55. The method of treating of claim 54, wherein the sunscreen formulation is applied in an effective amount.
56. The method of claim 54, wherein the skin is brightened after applying the sunscreen formulation.
57. The method of claim 54, wherein the topical formulation prevents cyclopyrimidine dimer (CPD) formation when compared to skin that is not treated with the topical formulation.
58. The method of claim 54, wherein the applying of the sunscreen formulation is periodically repeated.
Citation Information
Patent Citations
Sunless tanning compounds and compositions
US20170000712A1
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Alcohol-free perfume and preparation method thereof
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