Methods and compositions for skin ultraviolet protection
By combining high molecular weight acrylate copolymers and ammonium acryloyl dimethyl taurate/vinylpyrrolidone copolymers with UV filters, the problems of SPF value decrease and greasiness in existing sunscreen compositions after reducing homosalate are solved, achieving a highly efficient, water-resistant and aesthetically pleasing sun protection effect.
Patent Information
- Application Number
- CN202480045832.7
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Priority Date
- 2023-07-07
- Filing Date
- 2024-07-03
- Publication Date
- 2026-02-13
AI Technical Summary
Existing sunscreen compositions, after reducing or eliminating homosalate, are difficult to maintain a high SPF value and tend to be greasy. Traditional alternatives are also ineffective or have side effects. There is a need for a sunscreen composition that contains little or no homosalate, is highly water-resistant, non-greasy, and easy to apply.
A combination of high molecular weight acrylate copolymer and ammonium acryloyl dimethyl taurate/vinylpyrrolidone copolymer with ultraviolet filter is used to form a uniform hydrophobic layer, which improves the sun protection factor and enhances the product's water resistance and aesthetics.
It achieves high SPF stability and water resistance while avoiding a greasy feel, providing a comfortable user experience, and does not rely on traditional chemical filters.
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Abstract
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority to U.S. Provisional Patent Application Serial No. 63 / 525,403, filed July 7, 2023, which is incorporated herein by reference in its entirety. BACKGROUND
[0002] A. FIELD
[0003] The present invention relates generally to compositions and methods for blocking and protecting skin from ultraviolet (UV) radiation. More particularly, to topical compositions comprising a copolymer and a UV filter.
[0004] B. DESCRIPTION OF RELATED ART
[0005] Certain sunscreen compositions are known in the art. Many conventional sunscreen compositions rely on chemical ultraviolet (UV) radiation filtering ingredients to achieve a suitable SPF, thereby protecting the skin from UV radiation exposure. These conventional sunscreen compositions can result in an oily, uncomfortable skin feel when applied to the skin due to the need for high concentrations of chemical UV filters to achieve the desired SPF value.
[0006] One of the ingredients used as a solubilizer for other chemical UV filters, as well as a UV filter, in sunscreen compositions is homosalate. Due to safety concerns regarding the potential endocrine disrupting properties of homosalate, it is not recommended to use homosalate in sunscreen compositions at concentrations greater than 10%. To reduce homosalate in sunscreen compositions, but still maintain the desired SPF after reducing or removing homosalate, oils can be added to the composition. These added oils to replace homosalate can increase the oiliness of the composition when applied to the skin.
[0007] To have the UV filtering ingredients uniformly protect the skin (e.g., avoid UV damage or differences in UV exposure levels), these ingredients must form a uniform composition film layer that covers the skin. Oily or greasy compositions do not spread evenly on the skin and have a tendency to migrate and pool from the point of application, or have a tendency to be easily removed from the skin. In addition to lacking a pharmaceutically or cosmetically suitable skin feel, sunscreen compositions containing little or no homosalate can also exhibit a reduction in the effective SPF provided by the active UV filtering ingredients.
[0008] Others have attempted to create compositions and methods for protecting skin from solar ultraviolet radiation exposure using reduced amounts or no homosalate. Certain attempts have used various compositions containing cyano-containing acrylates, nanotitanium dioxide, or polyethylene glycol-5. However, many attempts have been unsuccessful, have addressed only a few of the undesirable outcomes, or have unacceptable side effects. Thus, there is a need for new pharmaceutically acceptable or cosmetically acceptable sunscreen compositions that contain little or no homosalate, but are still effective at protecting skin from ultraviolet radiation.
[0009] Further, there is a need in the art for compositions having improved SPF ratings, particularly for sunscreen compositions having improved SPF ratings that are highly water resistant, non-greasy, and easy to apply. SUMMARY
[0010] The present invention satisfies this need by providing stable compositions that are also effective at blocking ultraviolet radiation. In particular, it has been discovered that alkyl polymers can provide stability to the compositions and increase the sun protection factor without the need for additional ultraviolet filters.
[0011] In one example, a sunscreen composition is disclosed. In one example, the sunscreen composition includes a ultraviolet filter, a high molecular weight acrylate copolymer, and any one of, any combination of, or all of an ammonium acryloyldimethyltaurate / vinylpyrrolidone copolymer. The amounts of each ingredient within the composition can vary (e.g., the amounts can range from as low as 0.000001 wt / wt%, as high as 80 wt / wt%, or any range therebetween). In one example, the composition includes at least one high molecular weight acrylate copolymer, an ammonium acryloyldimethyltaurate / vinylpyrrolidone copolymer, and at least one ultraviolet filter. The composition can also include one or more ingredients described herein. For example, the composition can include one or more additional ingredients selected from one or more conditioning agents, humectants, pH adjusting agents, structuring agents, inorganic salts, and preservatives.
[0012] Methods of using the disclosed compositions are also disclosed herein. In one aspect, the disclosed compositions are sunscreens. In certain examples, the method includes topically applying any one of the compositions disclosed herein to the skin and / or facial and / or ocular area in need thereof. In one aspect, any one of the compositions disclosed herein is topically applied and the composition is left on the area of application, removed from the area of application after a period of time, and / or removed directly after application.
[0013] In certain aspects, the compositions of the present application are formulated as topical skin compositions. The compositions can have a dermatologically acceptable vehicle or carrier for the compounds, compositions, and extracts. The compositions can also include moisturizers or humectants, surfactants, silicone-containing compounds, UV agents, oils, and / or other ingredients as indicated in this specification or known in the art. The compositions can be emulsions, creams, body butters, masks, scrubs, lotions, gels, serums, emulsions (e.g., oil-in-water, water-in-oil, silicone-in-water, water-in-silicone, water-in-oil-in-water, oil-in-water-in-oil, silicone-in-water-in-oil, etc.), solutions (e.g., aqueous or aqueous-alcoholic), anhydrous bases (e.g., lipsticks or powders), ointments, milks, pastes, aerosols, solid forms, eye gels, etc. The compositions can be in powder form (e.g., dry, lyophilized, granulated, etc.). The compositions can be formulated for topical skin application at least 1, 2, 3, 4, 5, 6, 7, or more times per day during use. In certain aspects of the present application, the compositions can be storage stable or color stable, or both. It is also contemplated that the viscosity of the compositions can be selected to achieve a desired result, e.g., depending on the type of composition desired, such compositions can have a viscosity from about 1 cps to well over 1 million cps, or any range or integer therebetween (e.g., 2 cps, 3 cps, 4 cps, 5 cps, 6 cps, 7 cps, 8 cps, 9 cps, 10 cps, 20 cps, 30 cps, 40 cps, 50 cps, 60 cps, 70 cps, 80 cps, 90 cps, 100 cps, 200 cps, 300 cps, 400 cps, 500 cps, 600 cps, 700 cps, 800 cps, 900 cps, 1000 cps, 2000 cps, 3000 cps, 4000 cps, 5000 cps, 6000 cps, 7000 cps, 8000 cps, 9000 cps, 10000 cps, 20000 cps, 30000 cps, 40000 cps, 50000 cps, 60000 cps, 70000 cps, 80000 cps, 90000 cps, 100000 cps, 200000 cps, 300000 cps, 400000 cps, 500000 cps, 600000 cps, 700000 cps, 800000 cps, 900000 cps, 1000000 cps, 2000000 cps, 3000000 cps, 4000000 cps, 5000000 cps, 10000000 cps, etc., measured using a Brookfield viscometer with a TC spindle at 25°C, 2.5 rpm).
[0014] The compositions of the present invention can also be modified to have a desired oxygen radical scavenging capacity (ORAC) value. In some non-limiting aspects, the compositions of the present invention or any components or extracts thereof specified throughout this specification can be modified to have a value of at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 35, 40, 45, 50, 55, 60, 7 per milligram. ORAC values of 0, 80, 90, 95, 100, 200, 300, 400, 500, 600, 700, 800, 900, 1000, 2000, 3000, 4000, 5000, 6000, 7000, 8000, 9000, 10000, 15000, 20000, 30000, 50000, 100000 or more, or any derivable range thereof.
[0015] In a non-limiting aspect, the pH of the composition may be from about 6 to about 9. In some aspects, the pH may be 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, or 14. The composition may contain triglycerides. Non-limiting examples include short-chain, medium-chain, and long-chain triglycerides. In some aspects, the triglyceride is a medium-chain triglyceride (e.g., caprylic / capric triglyceride). The composition may also contain preservatives. Non-limiting examples of preservatives include phenoxyethanol, methylparaben, propylparaben, or any mixture thereof. In some embodiments, the composition is free of parabens.
[0016] The compositions of the present invention may have UVA and UVB absorption properties. The compositions may have a sun protection factor (SPF) of 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60 or higher, or any integer or derived thereof. The compositions may be sunscreen lotions, sprays, or creams.
[0017] The compositions of the present invention may also comprise any one, any combination, or all of the following additional ingredients: water, conditioning agents, chelating agents, humectants, pH adjusters, inorganic salts, preservatives, thickeners, silicone compounds, essential oils, structuring agents, vitamins, pharmaceutical ingredients, or antioxidants, or any combination or mixture of these ingredients. In some aspects, the composition may comprise at least two, three, four, five, six, seven, eight, nine, ten, or more, or all, of these additional ingredients specified in the foregoing sentences. Non-limiting examples of these additional ingredients are indicated throughout this specification and are incorporated herein by reference. The content of such ingredients may be from 0.0001% to 99.9% by weight or volume of the composition, or any integer or range thereof disclosed elsewhere herein, which is incorporated herein by reference.
[0018] Kits comprising the compositions of the present invention are also envisioned. In some embodiments, the composition is contained in a container. The container may be a bottle, dispenser, or pouch. The container may dispense a predetermined amount of the composition. In some aspects, the composition may be dispensed as a spray, mist, flocculent, or liquid. The surface of the container may include markings. The markings may be text, abbreviations, pictures, or symbols.
[0019] It is also envisioned that the compositions disclosed throughout this specification can be used as leave-on or rinse-off compositions. For example, a leave-on composition may be one that is applied topically to the skin and remains on the skin for a period of time (e.g., at least 5, 6, 7, 8, 9, 10, 20, or 30 minutes, or at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 hours, or overnight or throughout the day). Alternatively, a rinse-off composition may be a product designed to be applied to the skin and then removed or rinsed off from the skin (e.g., with water) within a period of time (e.g., less than 5, 4, 3, 2, or 1 minute). Examples of rinse-off compositions may be facial cleansers, shampoos, conditioners, or soaps. Examples of leave-on compositions include skin moisturizers, sunscreens, face masks, night creams, or day creams.
[0020] It is contemplated that any embodiment discussed in this specification can be implemented with respect to any method or composition of the invention, and vice versa. Furthermore, the compositions of the invention can be used to implement the methods of the invention.
[0021] In some embodiments, the compositions of the present invention may be pharmaceutically or cosmetically applicable, or may have a comfortable tactile feel. "Pharmaceutically applicable," "cosmetically applicable," and / or "comfortable tactile feel" describes compositions having specific tactile properties that feel comfortable on the skin (e.g., compositions that are not too thin or oily, compositions with a silky texture, compositions that are non-sticky or viscous, etc.). Pharmaceutically or cosmetically applicable may also relate to creamy or lubricating properties of the composition, or moisturizing properties of the composition.
[0022] Products comprising the compositions of the present invention are also envisioned. In a non-limiting aspect, such products may be cosmetic products. These cosmetic products may be those described in other parts of this specification or known to those skilled in the art. Non-limiting examples of products include moisturizers, creams, lotions, skin softeners, serums, gels, washes, body lotions, scrubs, foundations, night creams, lipsticks, facial cleansers, toners, sunscreens, face masks, anti-aging products, deodorants, antiperspirants, perfumes, colognes, etc.
[0023] Aspects 1 to 20 are also disclosed in the context of this invention. Aspect 1 is a sunscreen composition comprising at least one high molecular weight acrylate copolymer, ammonium acryloyldimethyl taurate / vinylpyrrolidone copolymer, and at least one ultraviolet filter. Aspect 2 is a sunscreen composition of aspect 1, wherein the high molecular weight acrylate copolymer comprises acrylates / C10-30 alkyl acrylate crosspolymer. Aspect 3 is a sunscreen composition of aspect 1 or 2, wherein the ultraviolet filter comprises avobenzone, octocrylene, and / or octisalate. Aspect 4 is a sunscreen composition of any one of aspects 1 to 3, wherein the sunscreen composition does not contain homosalate. Aspect 5 is a sunscreen composition of any one of aspects 1 to 4, wherein the sunscreen composition does not contain vinylpyrrolidone / eicosane copolymer. Aspect 6 is a sunscreen composition of any one of Aspects 1 to 5, wherein the sunscreen composition does not contain an additional emulsifier. Aspect 7 is a sunscreen composition of any one of Aspects 1 to 6, wherein the sunscreen composition further contains cetearyl alcohol. Aspect 8 is a sunscreen composition of any one of Aspects 1 to 7, wherein the sunscreen composition contains 0.01 to 1 wt% of one or more high molecular weight acrylate copolymers. Aspect 9 is a sunscreen composition of any one of Aspects 1 to 8, wherein the sunscreen composition contains 0.01 to 1 wt% of ammonium acryloyldimethyl taurate / vinylpyrrolidone copolymer. Aspect 10 is a sunscreen composition of any one of Aspects 1 to 9, wherein the sunscreen composition contains 3 to 20 wt% of one or more ultraviolet filters. Aspect 11 is a sunscreen composition of any one of Aspects 1 to 10, wherein the sunscreen composition has a sun protection factor (SPF) greater than 30. Aspect 12 is a sunscreen composition of any one of Aspects 1 to 10, wherein the sunscreen composition has a sun protection factor (SPF) greater than 50. Aspect 13 is a sunscreen composition of any one of Aspects 1 to 10, wherein the sunscreen composition has an SPF greater than 30 after 80 minutes of exposure to water. Aspect 14 is a sunscreen composition of any one of Aspects 1 to 10, wherein the sunscreen composition has an SPF greater than 50 after 80 minutes of exposure to water. Aspect 15 is a sunscreen composition of any one of Aspects 1 to 14, wherein the sunscreen composition is a polymeric suspension. Aspect 16 is a method for protecting an individual's skin from ultraviolet radiation, the method comprising applying an effective amount of a sunscreen composition of any one of Aspects 1 to 15 to the skin. Aspect 17 is the method of Aspect 16, wherein the sunscreen composition is applied to the skin before exposure to water.Aspect 18 is the method of aspect 16 or 17, wherein the application of the sunscreen agent forms a uniform hydrophobic layer. Aspect 19 is the method of any one of aspects 16 to 18, wherein the individual's skin includes facial skin. Aspect 20 is the method of aspect 19, wherein the sunscreen composition does not contain a vinylpyrrolidone / eicosane copolymer.
[0024] "Topical application" refers to applying or coating a composition to the surface of the lips or stratum corneum. "Topical skin compositions" include compositions suitable for topical application to the skin, lips, and / or stratum corneum. Such compositions are generally dermatologically acceptable because they do not exhibit excessive toxicity, incompatibility, instability, allergic reactions, etc., when applied to the lips, skin, and / or stratum corneum. The topical skin care compositions of the present invention may have a selected viscosity to avoid significant dripping or pooling after application to the lips, skin, and / or stratum corneum.
[0025] "Keratinous tissue" includes the keratin-containing layer that forms the outermost protective covering of mammals, including but not limited to the lips, skin, hair, and nails.
[0026] The terms “about” or “approximately” are defined as close to the degree understood by one of ordinary skill in the art. In a non-limiting example, these terms are defined as deviations within ±10%, preferably within ±5%, more preferably within ±1%, and most preferably within ±0.5%.
[0027] The term “substantially” and its variations are defined as, to a large extent but not necessarily entirely, as understood by one of ordinary skill in the art, in a non-limiting instance, substantially meaning a deviation within the range of ±10%, ±5%, ±1%, or ±0.5%.
[0028] The terms “inhibition” or “reduction” or any variations thereof include any measurable reduction or complete inhibition made to achieve a desired result. The terms “promotion” or “increase” or any variations thereof include any measurable increase made to achieve a desired result, such as a measurable increase in a protein or molecule (e.g., matrix proteins such as fibronectin, laminin, collagen, or elastin, or molecules such as hyaluronic acid).
[0029] The term “effective”, as it is used in this specification and / or claims, means sufficient to achieve the desired, anticipated, or anticipated result.
[0030] When an element is used without a quantifier in conjunction with the terms “comprising,” “including,” “having,” or “containing,” or any variations thereof, in the claims and / or specification, it may mean “one,” but it is also consistent with the meaning of “one or more,” “at least one,” and “more than one.”
[0031] As used in this specification and claims, the words “comprising” (and any form of inclusion, such as “comprising” and “including”), “having” (and any form of having, such as “having” and “having”), “including” (and any form of inclusion, such as “including” and “comprising”), or “containing” (and any form of containing, such as “containing” and “including”) are inclusive or open-ended and do not exclude additional, unlisted elements or method steps.
[0032] The compositions comprising and methods of use may “comprising,” “substantially constitute,” or “comprise” any of the ingredients or steps disclosed throughout this specification. Regarding the phrase “substantially constitute,” a fundamental and novel characteristic of the compositions and methods of the present invention is the ability to filter ultraviolet radiation.
[0033] Other objects, features, and advantages of the present invention will become apparent from the following detailed description. However, it should be understood that while the detailed description and embodiments point to specific embodiments of the invention, they are given by way of illustration only. Furthermore, variations and modifications from this detailed description that are within the spirit and scope of the invention will be apparent to those skilled in the art. Detailed Implementation
[0034] As described above, several unique aspects of this invention involve the use of chemical sunscreen filters and alkyl polymers such as acrylate / C10-30 alkanol acrylate crosspolymers, combined with thickening systems such as ammonium acryloyldimethyl taurate / vinylpyrrolidone (VP) copolymers. This enables the achievement of sun protection factor (SPF) of 50 or higher and the benefits of high water resistance without the addition of conventional chemical sunscreen filters such as homosalate. Compared to conventional emulsion-based systems, this composition comprises a unique oil-based polymer suspension containing UV filters.
[0035] The inventors unexpectedly discovered that adding small amounts of acrylate / C10-30 alkanol acrylate crosspolymers and ammonium acryloyldimethyl taurate / VP copolymers helps improve the SPF of sunscreen compositions, thereby reducing the amount of sunscreen required to achieve a given SPF and improving the product's water resistance and aesthetics. An additional benefit of this crosspolymer is that it provides water resistance for up to 80 minutes, allowing the polymer to spread and form a uniform hydrophobic layer on the epidermis as the UV filter is absorbed. This serves the dual purpose of reducing UV filter loss and providing a unique texture on the skin. The ammonium acryloyldimethyl taurate / VP copolymer also improves the stability of the formulation.
[0036] Another unique aspect of this invention is the removal of the UV filter homosalate. By eliminating the homosalate molecule, this invention provides a low-oil / high-SPF sunscreen, making the composition aesthetically pleasing and comfortable for consumers while still providing long-lasting water resistance. For non-homosarene active ingredients (avobenzone, octocrylene, and / or octyl salicylate) to protect the epidermis by converting UV radiation into heat and light energy, these active ingredients must form a uniform layer on the epidermis. In some instances, acrylate / C10-30 alkanol acrylate crosspolymers and ammonium acryloyldimethyl taurate / VP copolymers can be used to capture and suspend microdroplets of the sunscreen active ingredients. During application, the polymer releases the sunscreen active ingredients onto the skin, forming a more uniform product film covering the epidermis. This provides the added benefit of achieving higher SPF values without the use of conventional emulsifiers. This method also prevents the sunscreen active ingredients from being washed away, thus improving water resistance.
[0037] The non-limiting aspects of the invention are described in more detail in the following subsections.
[0038] Some of the compositions disclosed herein are designed for use as sunscreen compositions. These compositions rely on any, any combination of, or a unique combination of chemical sunscreen filters, alkyl polymers such as acrylate / C10-30 alkanol acrylate crosspolymers, and thickening systems such as ammonium acryloyldimethyl taurate / VP copolymer (trade name Aristoflex A VC™). Non-limiting examples of such compositions are provided in formulations 1 through 6.
[0039] Some of the compositions disclosed herein can be applied to the skin or hair and remain on the skin or hair for a period of time (e.g., at least 1 minute, 2 minutes, 3 minutes, 4 minutes, 5 minutes, 10 minutes, 20 minutes, 30 minutes, or 60 minutes or longer). Afterward, if necessary, the composition can be rinsed off or peeled from the skin. Some of the compositions disclosed herein can be applied to the skin and immediately rinsed off. Some of the compositions disclosed herein can be applied to the skin and at least partially absorbed by the skin.
[0040] These and other non-limiting aspects of the invention are described in the following sections.
[0041] A. Active ingredients
[0042] Aspects of the invention include combinations of one or more active ingredients—chemical sunscreen filters, alkyl polymers, and thickening systems—that can be used to protect the skin from UV radiation while remaining water-resistant, non-greasy, and easy to apply.
[0043] High molecular weight acrylate copolymers can contain both hydrophilic and hydrophobic portions and can be used as gel-forming polymers. In some instances, this component is commercially available, for example from Lubrizol, which offers the copolymer under the trade name Pemulen™, including Pemulen™ TR-2 or Pemulen™ EZ-4U.
[0044] In some aspects, the composition comprises 0.001 wt% to 1.0 wt% of a high molecular weight acrylate copolymer. In a non-limiting aspect, for example, the composition in its final form may comprise, substantially constitute, or constitute, for example, at least, at most, exactly, between (including or excluding), or about 0.001 wt%, 0.002 wt%, 0.003 wt%, 0.004 wt%, 0.005 wt%, 0.006 wt%, 0.007 wt%, 0.008 wt%, 0.009 wt%, 0.01 wt%, 0.011 wt%, 0.012 wt%, 0.013 wt%, 0.014 wt%, 0.015 wt%, 0.016 wt%, 0.017 wt%, 0.018 wt%, 0.019 wt%, 0.02 wt%, 0. 0.021 wt%, 0.022 wt%, 0.023 wt%, 0.024 wt%, 0.025 wt%, 0.026 wt%, 0.027 wt%, 0.028 wt%, 0.029 wt%, 0.03 wt%, 0.031 wt%, 0.032 wt%, 0.033 wt%, 0.034 wt%, 0.035 wt%, 0.036 wt%, 0.037 wt%, 0.038 wt%, 0.039 wt%, 0.04 wt%, 0.041 wt%, 0.042 wt%, 0.043 wt%, 0.044 wt%, 0.045 wt%, 0.046 wt%, 0.047 wt%, 0 0.048 wt%, 0.049 wt%, 0.05 wt%, 0.051 wt%, 0.052 wt%, 0.053 wt%, 0.054 wt%, 0.055 wt%, 0.056 wt%, 0.057 wt%, 0.058 wt%, 0.059 wt%, 0.06 wt%, 0.061 wt%, 0.062 wt%, 0.063 wt%, 0.064 wt%, 0.065 wt%, 0.066 wt%, 0.067 wt%, 0.068 wt%, 0.069 wt%, 0.07 wt%, 0.071 wt%, 0.072 wt%, 0.073 wt%, 0.074 wt%, 0 0.075 wt%, 0.076 wt%, 0.077 wt%, 0.078 wt%, 0.079 wt%, 0.08 wt%, 0.081 wt%, 0.082 wt%, 0.083 wt%, 0.084 wt%, 0.085 wt%, 0.086 wt%, 0.087 wt%, 0.088 wt%, 0.089 wt%, 0.09 wt%, 0.091 wt%, 0.092 wt%, 0.093 wt%, 0.094 wt%, 0.095 wt%, 0.096 wt%, 0.097 wt%, 0.098 wt%, 0.099 wt%, 0.01 wt%, 0.02 wt%, 0.0.3 wt%, 0.04 wt%, 0.05 wt%, 0.06 wt%, 0.07 wt%, 0.08 wt%, 0.09 wt%, 0.1 wt%, 0.11 wt%, 0.12 wt%, 0.13 wt%, 0.14 wt%, 0.15 wt%, 0.16 wt%, 0.17 wt%, 0.18 wt%, 0.19 wt%, 0.2 wt%, 0.21 wt%, 0.22 wt%, 0.23 wt%, 0.24 wt%, 0.25 wt%, 0.26 wt%, 0.27 wt%, 0.28 wt%, 0.29 wt%, 0.3 wt%, 0.31 wt%, 0.32 wt%, 0.33 wt%, 0.34 wt% %, 0.35 wt%, 0.36 wt%, 0.37 wt%, 0.38 wt%, 0.39 wt%, 0.4 wt%, 0.41 wt%, 0.42 wt%, 0.43 wt%, 0.44 wt%, 0.45 wt%, 0.46 wt%, 0.47 wt%, 0.48 wt%, 0.49 wt%, 0.5 wt%, 0.51 wt%, 0.52 wt%, 0.53 wt%, 0.54 wt%, 0.55 wt%, 0.56 wt%, 0.57 wt%, 0.58 wt%, 0.59 wt%, 0.6 wt%, 0.61 wt%, 0.62 wt%, 0.63 wt%, 0.64 wt%, 0.65 wt%, 0. 66 wt%, 0.67 wt%, 0.68 wt%, 0.69 wt%, 0.7 wt%, 0.71 wt%, 0.72 wt%, 0.73 wt%, 0.74 wt%, 0.75 wt%, 0.76 wt%, 0.77 wt%, 0.78 wt%, 0.79 wt%, 0.8 wt%, 0.81 wt%, 0.82 wt%, 0.83 wt%, 0.84 wt%, 0.85 wt%, 0.86 wt%, 0.87 wt%, 0.88 wt%, 0.89 wt%, 0.91 wt%, 0.92 wt%, 0.93 wt%, 0.94 wt%, 0.95 wt%, 0.96 wt%, 0.97 wt% %, 0.98 wt%, 0.99 wt%, 1.00 wt%, 1.01 wt%, 1.02 wt%, 1.03 wt%, 1.04 wt%, 1.05 wt%, 1.06 wt%, 1.07 wt%, 1.08 wt%, 1.09 wt%, 1.1 wt%, 1.11 wt%, 1.12 wt%, 1.13 wt%, 1.14 wt%, 1.15 wt%, 1.16 wt%, 1.17 wt%, 1.18 wt%, 1.19 wt%, 1.2 wt%, 1.21 wt%, 1.22 wt%, 1.23 wt%, 1.24 wt%, 1.25 wt%, 1.26 wt%, 1.27 wt%, 1.28 wt%, 1.29% by weight, 1.3% by weight, 1.31% by weight, 1.32% by weight, 1.33% by weight, 1.34% by weight, 1.35% by weight, 1.36% by weight, 1.37% by weight, 1.38% by weight, 1.39% by weight, 1.4% by weight, 1.41% by weight, 1.42% by weight, 1.43% by weight, 1.44% by weight, 1.45% by weight, 1.46% by weight, 1.47% by weight, 1.48% by weight, 1.49% by weight, 1.5% by weight, 1.51% by weight, 1.52% by weight, 1.53% by weight, 1.54% by weight, 1.55% by weight, 1.56% by weight, 1.57% by weight, 1.58% by weight, 1.59% by weight, 1.6% by weight, 1.61% by weight, 1.62% by weight, 1.63% by weight, 1.64% by weight, 1.65% by weight 1.66 wt%, 1.67 wt%, 1.68 wt%, 1.69 wt%, 1.7 wt%, 1.71 wt%, 1.72 wt%, 1.73 wt%, 1.74 wt%, 1.75 wt%, 1.76 wt%, 1.77 wt%, 1.78 wt%, 1.79 wt%, 1.8 wt%, 1.81 wt%, 1.82 wt%, 1.83 wt%, 1.84 wt%, 1.85 wt%, 1.86 wt%, 1.87 wt%, 1.88 wt%, 1.89 wt%, 1.99 wt%, 1.91 wt%, 1.92 wt%, 1.93 wt%, 1.94 wt%, 1.95 wt%, 1.96 wt%, 1.97 wt%, 1.98 wt%, 1.99 wt%, or 2.00 wt% high molecular weight acrylate copolymers.
[0045] Ammonium acryloyldimethyl taurate / vinylpyrrolidone copolymer is a gelling agent that can be used to thicken certain compositions. In some instances, this component is commercially available, for example from Clariant, which offers the copolymer under the trade name Aristoflex AVC™.
[0046] In some aspects, the composition comprises 0.001% to 1.0% by weight of ammonium acryloyldimethyltaurate / vinylpyrrolidone copolymer. In a non-limiting aspect, for example, the composition in its final form may comprise, substantially constitute, or constitute, for example, at least, at most, exactly, between (including or excluding) or about 0.001% by weight, 0.002% by weight, 0.003% by weight, 0.004% by weight, 0.005% by weight, 0.006% by weight, 0.007% by weight, 0.008% by weight, 0.009% by weight, 0.01% by weight, 0.011% by weight, 0.012% by weight, 0.013% by weight, 0.014% by weight, 0.015% by weight, 0.016% by weight, 0.017% by weight, 0.018% by weight, 0.019% by weight, or 0.02% by weight. 0.021 wt%, 0.022 wt%, 0.023 wt%, 0.024 wt%, 0.025 wt%, 0.026 wt%, 0.027 wt%, 0.028 wt%, 0.029 wt%, 0.03 wt%, 0.031 wt%, 0.032 wt%, 0.033 wt%, 0.034 wt%, 0.035 wt%, 0.036 wt%, 0.037 wt%, 0.038 wt%, 0.039 wt%, 0.04 wt%, 0.041 wt%, 0.042 wt%, 0.043 wt%, 0.044 wt%, 0.045 wt%, 0.046 wt%, 0.047 wt% 0.048 wt%, 0.049 wt%, 0.05 wt%, 0.051 wt%, 0.052 wt%, 0.053 wt%, 0.054 wt%, 0.055 wt%, 0.056 wt%, 0.057 wt%, 0.058 wt%, 0.059 wt%, 0.06 wt%, 0.061 wt%, 0.062 wt%, 0.063 wt%, 0.064 wt%, 0.065 wt%, 0.066 wt%, 0.067 wt%, 0.068 wt%, 0.069 wt%, 0.07 wt%, 0.071 wt%, 0.072 wt%, 0.073 wt%, 0.07 4% by weight, 0.075% by weight, 0.076% by weight, 0.077% by weight, 0.078% by weight, 0.079% by weight, 0.08% by weight, 0.081% by weight, 0.082% by weight, 0.083% by weight, 0.084% by weight, 0.085% by weight, 0.086% by weight, 0.087% by weight, 0.088% by weight, 0.089% by weight, 0.09% by weight, 0.091% by weight, 0.092% by weight, 0.093% by weight, 0.094% by weight, 0.095% by weight, 0.096% by weight, 0.097% by weight, 0.098% by weight, 0.099% by weight, 0.01% by weight, 0.0.2 wt%, 0.03 wt%, 0.04 wt%, 0.05 wt%, 0.06 wt%, 0.07 wt%, 0.08 wt%, 0.09 wt%, 0.1 wt%, 0.11 wt%, 0.12 wt%, 0.13 wt%, 0.14 wt%, 0.15 wt%, 0.16 wt%, 0.17 wt%, 0.18 wt%, 0.19 wt%, 0.2 wt%, 0.21 wt%, 0.22 wt%, 0.23 wt%, 0.24 wt%, 0.25 wt%, 0.26 wt%, 0.27 wt%, 0.28 wt%, 0.29 wt%, 0.3 wt%, 0.31 wt%, 0.32 wt%, 0.33 wt% %, 0.34 wt%, 0.35 wt%, 0.36 wt%, 0.37 wt%, 0.38 wt%, 0.39 wt%, 0.4 wt%, 0.41 wt%, 0.42 wt%, 0.43 wt%, 0.44 wt%, 0.45 wt%, 0.46 wt%, 0.47 wt%, 0.48 wt%, 0.49 wt%, 0.5 wt%, 0.51 wt%, 0.52 wt%, 0.53 wt%, 0.54 wt%, 0.55 wt%, 0.56 wt%, 0.57 wt%, 0.58 wt%, 0.59 wt%, 0.6 wt%, 0.61 wt%, 0.62 wt%, 0.63 wt%, 0.64 wt%, 0. 65 wt%, 0.66 wt%, 0.67 wt%, 0.68 wt%, 0.69 wt%, 0.7 wt%, 0.71 wt%, 0.72 wt%, 0.73 wt%, 0.74 wt%, 0.75 wt%, 0.76 wt%, 0.77 wt%, 0.78 wt%, 0.79 wt%, 0.8 wt%, 0.81 wt%, 0.82 wt%, 0.83 wt%, 0.84 wt%, 0.85 wt%, 0.86 wt%, 0.87 wt%, 0.88 wt%, 0.89 wt%, 0.91 wt%, 0.92 wt%, 0.93 wt%, 0.94 wt%, 0.95 wt%, 0.96 wt% %, 0.97 wt%, 0.98 wt%, 0.99 wt%, 1.00 wt%, 1.01 wt%, 1.02 wt%, 1.03 wt%, 1.04 wt%, 1.05 wt%, 1.06 wt%, 1.07 wt%, 1.08 wt%, 1.09 wt%, 1.1 wt%, 1.11 wt%, 1.12 wt%, 1.13 wt%, 1.14 wt%, 1.15 wt%, 1.16 wt%, 1.17 wt%, 1.18 wt%, 1.19 wt%, 1.2 wt%, 1.21 wt%, 1.22 wt%, 1.23 wt%, 1.24 wt%, 1.25 wt%, 1.26 wt%, 1.27 wt%, 1.28% by weight, 1.29% by weight, 1.3% by weight, 1.31% by weight, 1.32% by weight, 1.33% by weight, 1.34% by weight, 1.35% by weight, 1.36% by weight, 1.37% by weight, 1.38% by weight, 1.39% by weight, 1.4% by weight, 1.41% by weight, 1.42% by weight, 1.43% by weight, 1.44% by weight, 1.45% by weight, 1.46% by weight, 1.47% by weight, 1.48% by weight, 1.49% by weight, 1.5% by weight, 1.51% by weight, 1.52% by weight, 1.53% by weight, 1.54% by weight, 1.55% by weight, 1.56% by weight, 1.57% by weight, 1.58% by weight, 1.59% by weight, 1.6% by weight, 1.61% by weight, 1.62% by weight, 1.63% by weight, 1.64% by weight, 1.65% by weight 1.66 wt%, 1.67 wt%, 1.68 wt%, 1.69 wt%, 1.7 wt%, 1.71 wt%, 1.72 wt%, 1.73 wt%, 1.74 wt%, 1.75 wt%, 1.76 wt%, 1.77 wt%, 1.78 wt%, 1.79 wt%, 1.8 wt%, 1.81 wt%, 1.82 wt%, 1.83 wt%, 1.84 wt%, 1.85 wt%, 1.86 wt%, 1.87 wt%, 1.88 wt%, 1.89 wt%, 1.99 wt%, 1.91 wt%, 1.92 wt%, 1.93 wt%, 1.94 wt%, 1.95 wt%, 1.96 wt%, 1.97 wt%, 1.98 wt%, 1.99 wt%, or 2.00 wt% of ammonium acryloyldimethyltaurate / vinylpyrrolidone copolymer.
[0047] Avobenzone, also known as butylmethoxydibenzoylmethane or 4-tert-butyl-4'-methoxydibenzoylmethane, is an oil-soluble chemical agent with the following structural formula:
[0048] .
[0049] Avobenzone absorbs ultraviolet radiation from approximately 310 nm to 400 nm, covering the UVA range. Avobenzone is one of the few chemical sunscreens that effectively blocks the UVA spectrum, and is used in products to absorb the full spectrum of UVA rays. Avobenzone degrades in sunlight and loses its effectiveness over time. It is typically used in conjunction with stabilizers such as octocrylene or homosalate. It is a commercially available organic compound from a variety of sources.
[0050] In some aspects, the composition comprises 2% to 5% by weight of avobenzone. In a non-limiting aspect, for example, the composition in its final form may comprise, substantially constitute, or constitute, for example, at least, at most, exactly, between (including or excluding) or about 2% by weight, 2.01% by weight, 2.02% by weight, 2.03% by weight, 2.04% by weight, 2.05% by weight, 2.06% by weight, 2.07% by weight, 2.08% by weight, 2.09% by weight, 2.1% by weight, 2.11% by weight, 2.12% by weight, 2.13% by weight, 2.14% by weight, 2.15% by weight, 2.16% by weight, 2.17% by weight, 2.18% by weight, 2.19% by weight, 2.2% by weight, 2.21% by weight, 2.22% by weight, 2.23% by weight. 2.24 wt%, 2.25 wt%, 2.26 wt%, 2.27 wt%, 2.28 wt%, 2.29 wt%, 2.3 wt%, 2.31 wt%, 2.32 wt%, 2.33 wt%, 2.34 wt%, 2.35 wt%, 2.36 wt%, 2.37 wt%, 2.38 wt%, 2.39 wt%, 2.4 wt%, 2.41 wt%, 2.42 wt%, 2.43 wt%, 2.44 wt%, 2.45 wt%, 2.46 wt%, 2.47 wt%, 2.48 wt%, 2.49 wt%, 2.5 wt%, 2.51 wt%, 2.52 wt%, 2.53 wt%, 2.5 4 wt%, 2.55 wt%, 2.56 wt%, 2.57 wt%, 2.58 wt%, 2.59 wt%, 2.6 wt%, 2.61 wt%, 2.62 wt%, 2.63 wt%, 2.64 wt%, 2.65 wt%, 2.66 wt%, 2.67 wt%, 2.68 wt%, 2.69 wt%, 2.7 wt%, 2.71 wt%, 2.72 wt%, 2.73 wt%, 2.74 wt%, 2.75 wt%, 2.76 wt%, 2.77 wt%, 2.78 wt%, 2.79 wt%, 2.81 wt%, 2.82 wt%, 2.83 wt%, 2.84 wt%, 2 0.85 wt%, 2.86 wt%, 2.87 wt%, 2.88 wt%, 2.89 wt%, 2.9 wt%, 2.91 wt%, 2.92 wt%, 2.93 wt%, 2.94 wt%, 2.95 wt%, 2.96 wt%, 2.97 wt%, 2.98 wt%, 2.99 wt%, 3 wt%, 3.01 wt%, 3.02 wt%, 3.03 wt%, 3.04 wt%, 3.05 wt%, 3.06 wt%, 3.07 wt%, 3.08 wt%, 3.09 wt%, 3.1 wt%, 3.11 wt%, 3.12 wt%, 3.13 wt%, 3.14 wt%, 3.15 wt%, 3.16% by weight, 3.17% by weight, 3.18% by weight, 3.19% by weight, 3.2% by weight, 3.21% by weight, 3.22% by weight, 3.23% by weight, 3.24% by weight, 3.25% by weight, 3.26% by weight, 3.27% by weight, 3.28% by weight, 3.29% by weight, 3.3% by weight, 3.31% by weight, 3.32% by weight, 3.33% by weight, 3.34% by weight, 3.35% by weight, 3.36% by weight, 3.37% by weight, 3.38% by weight, 3.39% by weight, 3.4% by weight, 3.41% by weight, 3.42% by weight, 3.43% by weight, 3.44% by weight, 3.45% by weight, 3.46% by weight, 3.47% by weight 3.48 wt%, 3.49 wt%, 3.5 wt%, 3.51 wt%, 3.52 wt%, 3.53 wt%, 3.54 wt%, 3.55 wt%, 3.56 wt%, 3.57 wt%, 3.58 wt%, 3.59 wt%, 3.6 wt%, 3.61 wt%, 3.62 wt%, 3.63 wt%, 3.64 wt%, 3.65 wt%, 3.66 wt%, 3.67 wt%, 3.68 wt%, 3.69 wt%, 3.7 wt%, 3.71 wt%, 3.72 wt%, 3.73 wt%, 3.74 wt%, 3.75 wt%, 3.76 wt%, 3.77 wt%, 3.78 wt%, 3.79 3.8% by weight, 3.81% by weight, 3.82% by weight, 3.83% by weight, 3.84% by weight, 3.85% by weight, 3.86% by weight, 3.87% by weight, 3.88% by weight, 3.89% by weight, 3.9% by weight, 3.91% by weight, 3.92% by weight, 3.93% by weight, 3.94% by weight, 3.95% by weight, 3.96% by weight, 3.97% by weight, 3.98% by weight, 3.99% by weight, 4% by weight, 4.01% by weight, 4.02% by weight, 4.03% by weight, 4.04% by weight, 4.05% by weight, 4.06% by weight, 4.07% by weight, 4.08% by weight, 4.09% by weight, 4.1% by weight, 4.11% by weight. 4.12% by weight, 4.13% by weight, 4.14% by weight, 4.15% by weight, 4.16% by weight, 4.17% by weight, 4.18% by weight, 4.19% by weight, 4.2% by weight, 4.21% by weight, 4.22% by weight, 4.23% by weight, 4.24% by weight, 4.25% by weight, 4.26% by weight, 4.27% by weight, 4.28% by weight, 4.29% by weight, 4.3% by weight, 4.31% by weight, 4.32% by weight, 4.33% by weight, 4.34% by weight, 4.35% by weight, 4.36% by weight, 4.37% by weight, 4.38% by weight, 4.39% by weight, 4.4% by weight, 4.41% by weight, 4.42% by weight, 4.43% by weight, 4.44% by weight, 4.45% by weight, 4.46% by weight, 4.47% by weight, 4.48% by weight, 4.49% by weight, 4.5% by weight, 4.51% by weight, 4.52% by weight, 4.53% by weight, 4.54% by weight, 4.55% by weight, 4.56% by weight, 4.57% by weight, 4.58% by weight, 4.59% by weight, 4.6% by weight, 4.61% by weight, 4.62% by weight, 4.63% by weight, 4.64% by weight, 4.65% by weight, 4.66% by weight, 4.67% by weight, 4.68% by weight, 4.69% by weight, 4.7% by weight, 4.71% by weight. 72% by weight, 4.73% by weight, 4.74% by weight, 4.75% by weight, 4.76% by weight, 4.77% by weight, 4.78% by weight, 4.79% by weight, 4.8% by weight, 4.81% by weight, 4.82% by weight, 4.83% by weight, 4.84% by weight, 4.85% by weight, 4.86% by weight, 4.87% by weight, 4.88% by weight, 4.89% by weight, 4.99% by weight, 4.91% by weight, 4.92% by weight, 4.93% by weight, 4.94% by weight, 4.95% by weight, 4.96% by weight, 4.97% by weight, 4.98% by weight, 4.99% by weight, or 5% by weight of avobenzone.
[0051] Octocrylene is an oil-soluble, water-resistant chemical agent. It is an ester formed by the condensation of diphenyl cyanoacrylate and 2-ethylhexanol, and has the following structure:
[0052] .
[0053] Octocrylene is a clear, colorless, viscous, oily liquid. The extended conjugation of the acrylate moiety in this molecule absorbs ultraviolet radiation from approximately 280 nm to 350 nm, covering the UVB and short-wave UVA (also known as UVA-2) range, protecting the skin from direct DNA damage. Octocrylene is a stable but relatively weak sunscreen agent and is generally ineffective when used alone. It is capable of stabilizing other UV absorbers (such as avobenzone). The ethylhexanol moiety is a fatty alcohol, adding emollient and oily (water-resistant) properties. Octocrylene is commercially available from a variety of sources.
[0054] In some aspects, the composition contains 8% to 11% by weight of octocrylene. In a non-limiting aspect, for example, the composition in its final form may contain, substantially constitute, or constitute, for example, at least, at most, exactly, between (including or excluding) or about 8% by weight, 8.01% by weight, 8.02% by weight, 8.03% by weight, 8.04% by weight, 8.05% by weight, 8.06% by weight, 8.07% by weight, 8.08% by weight, 8.09% by weight, 8.1% by weight, 8.11% by weight, 8.12% by weight, 8.13% by weight, 8.14% by weight, 8.15% by weight, 8.16% by weight, 8.17% by weight, 8.18% by weight, 8.19% by weight, 8.2% by weight, 8.21% by weight, 8.22% by weight, 8.23% by weight. 8.24% by weight, 8.25% by weight, 8.26% by weight, 8.27% by weight, 8.28% by weight, 8.29% by weight, 8.3% by weight, 8.31% by weight, 8.32% by weight, 8.33% by weight, 8.34% by weight, 8.35% by weight, 8.36% by weight, 8.37% by weight, 8.38% by weight, 8.39% by weight, 8.4% by weight, 8.41% by weight, 8.42% by weight, 8.43% by weight, 8.44% by weight, 8.45% by weight, 8.46% by weight, 8.47% by weight, 8.48% by weight, 8.49% by weight, 8.5% by weight, 8.51% by weight, 8.52% by weight, 8.53% by weight, 8.5% by weight. 4% by weight, 8.55% by weight, 8.56% by weight, 8.57% by weight, 8.58% by weight, 8.59% by weight, 8.6% by weight, 8.61% by weight, 8.62% by weight, 8.63% by weight, 8.64% by weight, 8.65% by weight, 8.66% by weight, 8.67% by weight, 8.68% by weight, 8.69% by weight, 8.7% by weight, 8.71% by weight, 8.72% by weight, 8.73% by weight, 8.74% by weight, 8.75% by weight, 8.76% by weight, 8.77% by weight, 8.78% by weight, 8.79% by weight, 8.81% by weight, 8.82% by weight, 8.83% by weight, 8.84% by weight, 8 0.85 wt%, 8.86 wt%, 8.87 wt%, 8.88 wt%, 8.89 wt%, 8.9 wt%, 8.91 wt%, 8.92 wt%, 8.93 wt%, 8.94 wt%, 8.95 wt%, 8.96 wt%, 8.97 wt%, 8.98 wt%, 8.99 wt%, 9 wt%, 9.01 wt%, 9.02 wt%, 9.03 wt%, 9.04 wt%, 9.05 wt%, 9.06 wt%, 9.07 wt%, 9.08 wt%, 9.09 wt%, 9.1 wt%, 9.11 wt%, 9.12 wt%, 9.13 wt%, 9.14 wt%, 9.15 wt%, 9.16% by weight, 9.17% by weight, 9.18% by weight, 9.19% by weight, 9.2% by weight, 9.21% by weight, 9.22% by weight, 9.23% by weight, 9.24% by weight, 9.25% by weight, 9.26% by weight, 9.27% by weight, 9.28% by weight, 9.29% by weight, 9.3% by weight, 9.31% by weight, 9.32% by weight, 9.33% by weight, 9.34% by weight, 9.35% by weight, 9.36% by weight, 9.37% by weight, 9.38% by weight, 9.39% by weight, 9.4% by weight, 9.41% by weight, 9.42% by weight, 9.43% by weight, 9.44% by weight, 9.45% by weight, 9.46% by weight, 9.47% by weight 9.48 wt%, 9.49 wt%, 9.5 wt%, 9.51 wt%, 9.52 wt%, 9.53 wt%, 9.54 wt%, 9.55 wt%, 9.56 wt%, 9.57 wt%, 9.58 wt%, 9.59 wt%, 9.6 wt%, 9.61 wt%, 9.62 wt%, 9.63 wt%, 9.64 wt%, 9.65 wt%, 9.66 wt%, 9.67 wt%, 9.68 wt%, 9.69 wt%, 9.7 wt%, 9.71 wt%, 9.72 wt%, 9.73 wt%, 9.74 wt%, 9.75 wt%, 9.76 wt%, 9.77 wt%, 9.78 wt%, 9.79 wt%. % by weight, 9.8% by weight, 9.81% by weight, 9.82% by weight, 9.83% by weight, 9.84% by weight, 9.85% by weight, 9.86% by weight, 9.87% by weight, 9.88% by weight, 9.89% by weight, 9.9% by weight, 9.91% by weight, 9.92% by weight, 9.93% by weight, 9.94% by weight, 9.95% by weight, 9.96% by weight, 9.97% by weight, 9.98% by weight, 9.99% by weight, 10% by weight, 10.01% by weight, 10.02% by weight, 10.03% by weight, 10.04% by weight, 10.05% by weight, 10.06% by weight, 10.07% by weight, 10.08% by weight, 10.09% by weight, 1 0.1 wt%, 10.11 wt%, 10.12 wt%, 10.13 wt%, 10.14 wt%, 10.15 wt%, 10.16 wt%, 10.17 wt%, 10.18 wt%, 10.19 wt%, 10.2 wt%, 10.21 wt%, 10.22 wt%, 10.23 wt%, 10.24 wt%, 10.25 wt%, 10.26 wt%, 10.27 wt%, 10.28 wt%, 10.29 wt%, 10.3 wt%, 10.31 wt%, 10.32 wt%, 10.33 wt%, 10.34 wt%, 10.35 wt%, 10.36 wt%, 10.37 wt%, 10.38 wt%, 10.39 wt%, 10.4 wt%, 10.41 wt%, 10.42 wt%, 10.43 wt%, 10.44 wt%, 10.45 wt%, 10.46 wt%, 10.47 wt%, 10.48 wt%, 10.49 wt%, 10.5 wt%, 10.51 wt%, 10.52 wt%, 10.53 wt%, 10.54 wt%, 10.55 wt%, 10.56 wt%, 10.57 wt%, 10.58 wt%, 10.59 wt%, 10.6 wt%, 10.61 wt%, 10.62 wt%, 10.63 wt%, 10.64 wt%, 10.65 wt%, 10.66 wt%, 10.67 wt%, 10.68 wt%, 10.69 wt% 10.7% by weight, 10.71% by weight, 10.72% by weight, 10.73% by weight, 10.74% by weight, 10.75% by weight, 10.76% by weight, 10.77% by weight, 10.78% by weight, 10.79% by weight, 10.8% by weight, 10.81% by weight, 10.82% by weight, 10.83% by weight, 10.84% by weight, 10.85% by weight, 10.86% by weight, 10.87% by weight, 10.88% by weight, 10.89% by weight, 10.9% by weight, 10.91% by weight, 10.92% by weight, 10.93% by weight, 10.94% by weight, 10.95% by weight, 10.96% by weight, 10.97% by weight, 10.98% by weight, or 11% by weight of octocrylene.
[0055] Octyl salicylate, also known as octyl salicylate or 2-ethylhexyl salicylate, is a colorless, oily liquid formed by the condensation of salicylic acid and 2-ethylhexanol, and has the following structure:
[0056] .
[0057] Octyl salicylate absorbs UVB (ultraviolet) rays from the sun. The salicylate portion of the molecule absorbs ultraviolet light, protecting the skin from the harmful effects of sun exposure. The ethylhexanol portion is a fatty alcohol, adding moisturizing and oily (water-resistant) properties. It also stabilizes avobenzone, resulting in longer-lasting sun protection. Octyl salicylate is commercially available from a variety of sources.
[0058] In some aspects, the composition comprises 2% to 5% by weight of octyl salicylate. In a non-limiting aspect, for example, the composition in its final form may comprise, substantially constitute, or constitute, for example, at least, at most, exactly, between (including or excluding) or about 2% by weight, 2.01% by weight, 2.02% by weight, 2.03% by weight, 2.04% by weight, 2.05% by weight, 2.06% by weight, 2.07% by weight, 2.08% by weight, 2.09% by weight, 2.1% by weight, 2.11% by weight, 2.12% by weight, 2.13% by weight, 2.14% by weight, 2.15% by weight, 2.16% by weight, 2.17% by weight, 2.18% by weight, 2.19% by weight, 2.2% by weight, 2.21% by weight, 2.22% by weight, 2%. 23% by weight, 2.24% by weight, 2.25% by weight, 2.26% by weight, 2.27% by weight, 2.28% by weight, 2.29% by weight, 2.3% by weight, 2.31% by weight, 2.32% by weight, 2.33% by weight, 2.34% by weight, 2.35% by weight, 2.36% by weight, 2.37% by weight, 2.38% by weight, 2.39% by weight, 2.4% by weight, 2.41% by weight, 2.42% by weight, 2.43% by weight, 2.44% by weight, 2.45% by weight, 2.46% by weight, 2.47% by weight, 2.48% by weight, 2.49% by weight, 2.5% by weight, 2.51% by weight, 2.52% by weight, 2.53% by weight 2.54 wt%, 2.55 wt%, 2.56 wt%, 2.57 wt%, 2.58 wt%, 2.59 wt%, 2.6 wt%, 2.61 wt%, 2.62 wt%, 2.63 wt%, 2.64 wt%, 2.65 wt%, 2.66 wt%, 2.67 wt%, 2.68 wt%, 2.69 wt%, 2.7 wt%, 2.71 wt%, 2.72 wt%, 2.73 wt%, 2.74 wt%, 2.75 wt%, 2.76 wt%, 2.77 wt%, 2.78 wt%, 2.79 wt%, 2.8 wt%, 2.81 wt%, 2.82 wt%, 2.83 wt%, 2.8 4% by weight, 2.85% by weight, 2.86% by weight, 2.87% by weight, 2.88% by weight, 2.89% by weight, 2.9% by weight, 2.91% by weight, 2.92% by weight, 2.93% by weight, 2.94% by weight, 2.95% by weight, 2.96% by weight, 2.97% by weight, 2.98% by weight, 2.99% by weight, 3% by weight, 3.01% by weight, 3.02% by weight, 3.03% by weight, 3.04% by weight, 3.05% by weight, 3.06% by weight, 3.07% by weight, 3.08% by weight, 3.09% by weight, 3.1% by weight, 3.11% by weight, 3.12% by weight, 3.13% by weight, 3.14% by weight, 3.15% by weight, 3.16% by weight, 3.17% by weight, 3.18% by weight, 3.19% by weight, 3.2% by weight, 3.21% by weight, 3.22% by weight, 3.23% by weight, 3.24% by weight, 3.25% by weight, 3.26% by weight, 3.27% by weight, 3.28% by weight, 3.29% by weight, 3.3% by weight, 3.31% by weight, 3.32% by weight, 3.33% by weight, 3.34% by weight, 3.35% by weight, 3.36% by weight, 3.37% by weight, 3.38% by weight, 3.39% by weight, 3.4% by weight, 3.41% by weight, 3.42% by weight, 3.43% by weight, 3.44% by weight, 3.45% by weight, 3.46% by weight 3.47 wt%, 3.48 wt%, 3.49 wt%, 3.5 wt%, 3.51 wt%, 3.52 wt%, 3.53 wt%, 3.54 wt%, 3.55 wt%, 3.56 wt%, 3.57 wt%, 3.58 wt%, 3.59 wt%, 3.6 wt%, 3.61 wt%, 3.62 wt%, 3.63 wt%, 3.64 wt%, 3.65 wt%, 3.66 wt%, 3.67 wt%, 3.68 wt%, 3.69 wt%, 3.7 wt%, 3.71 wt%, 3.72 wt%, 3.73 wt%, 3.74 wt%, 3.75 wt%, 3.76 wt%, 3.77 wt%, 3.78 % by weight, 3.79% by weight, 3.8% by weight, 3.81% by weight, 3.82% by weight, 3.83% by weight, 3.84% by weight, 3.85% by weight, 3.86% by weight, 3.87% by weight, 3.88% by weight, 3.89% by weight, 3.91% by weight, 3.92% by weight, 3.93% by weight, 3.94% by weight, 3.95% by weight, 3.96% by weight, 3.97% by weight, 3.98% by weight, 3.99% by weight, 4% by weight, 4.01% by weight, 4.02% by weight, 4.03% by weight, 4.04% by weight, 4.05% by weight, 4.06% by weight, 4.07% by weight, 4.08% by weight, 4.09% by weight, 4.1 4.11 wt%, 4.12 wt%, 4.13 wt%, 4.14 wt%, 4.15 wt%, 4.16 wt%, 4.17 wt%, 4.18 wt%, 4.19 wt%, 4.2 wt%, 4.21 wt%, 4.22 wt%, 4.23 wt%, 4.24 wt%, 4.25 wt%, 4.26 wt%, 4.27 wt%, 4.28 wt%, 4.29 wt%, 4.3 wt%, 4.31 wt%, 4.32 wt%, 4.33 wt%, 4.34 wt%, 4.35 wt%, 4.36 wt%, 4.37 wt%, 4.38 wt%, 4.39 wt%, 4.4 wt%, 4.41 wt%, 4.42% by weight, 4.43% by weight, 4.44% by weight, 4.45% by weight, 4.46% by weight, 4.47% by weight, 4.48% by weight, 4.49% by weight, 4.5% by weight, 4.51% by weight, 4.52% by weight, 4.53% by weight, 4.54% by weight, 4.55% by weight, 4.56% by weight, 4.57% by weight, 4.58% by weight, 4.59% by weight, 4.6% by weight, 4.61% by weight, 4.62% by weight, 4.63% by weight, 4.64% by weight, 4.65% by weight, 4.66% by weight, 4.67% by weight, 4.68% by weight, 4.69% by weight, 4.7% by weight, 4.71% by weight 4.72 wt%, 4.73 wt%, 4.74 wt%, 4.75 wt%, 4.76 wt%, 4.77 wt%, 4.78 wt%, 4.79 wt%, 4.8 wt%, 4.81 wt%, 4.82 wt%, 4.83 wt%, 4.84 wt%, 4.85 wt%, 4.86 wt%, 4.87 wt%, 4.88 wt%, 4.89 wt%, 4.99 wt%, 4.91 wt%, 4.92 wt%, 4.93 wt%, 4.94 wt%, 4.95 wt%, 4.96 wt%, 4.97 wt%, 4.98 wt%, 4.99 wt%, or 5 wt% octyl salicylate.
[0059] These combinations of ingredients can be used in different product forms to treat a variety of skin conditions. By way of non-limiting examples, these combinations of ingredients can be formulated into suspensions, emulsions (e.g., oil-in-water, water-in-oil), gels, serums, gel emulsions, gel serums, lotions, masks, scrubs, washes, creams, or body lotions.
[0060] The extracts described herein can be extracts prepared by extraction methods and combinations thereof known in the art. Non-limiting examples of extraction methods include liquid-liquid extraction, solid-phase extraction, solution extraction, extraction with ethyl acetate, alcohol, acetone, oil, supercritical carbon dioxide, heat, pressure, pressure drop extraction, ultrasonic extraction, etc. The extracts can be liquids, solids, dried liquids, resuspended solids, etc.
[0061] B. Component content
[0062] It is envisioned that the compositions of the present invention may include any amount of the ingredients discussed in this specification. The composition may also include combinations of any number of additional ingredients described throughout this specification (e.g., pigments, or additional cosmetic or pharmaceutical ingredients). The concentration of any ingredient in the composition may vary. In a non-limiting embodiment, for example, the composition in its final form may contain, substantially constitute, or consist of, for example, at least about 0.0001%, 0.0002%, 0.0003%, 0.0004%, 0.0005%, 0.0006%, 0.0007%, 0.0008%, 0.0009%, 0.0010%, 0.0011%, 0.0012%, 0.0013%, 0.0014%, 0.0015%, 0.0016%, 0.0017%, 0.0018%, 0.0019%, 0.0020%, 0.0021%, 0.0022%, 0.00 23%, 0.0024%, 0.0025%, 0.0026%, 0.0027%, 0.0028%, 0.0029%, 0.0030%, 0.0031%, 0.0032%, 0.0033%, 0.0034%, 0.0035%, 0.0036%, 0.0037%, 0.0038%, 0.0039%, 0.0040%, 0.0041%, 0.0042%, 0.0043%, 0.0044%, 0.0045%, 0.0046%, 0.0047%, 0.0048%, 0.0049%, 0.0050%, 0.0051 %, 0.0052%, 0.0053%, 0.0054%, 0.0055%, 0.0056%, 0.0057%, 0.0058%, 0.0059%, 0.0060%, 0.0061%, 0.0062%, 0.0063%, 0.0064%, 0.0065%, 0.0066%, 0.0067%, 0.0068%, 0.0069%, 0.0070%, 0.0071%, 0.0072%, 0.0073%, 0.0074%, 0.0075%, 0.0076%, 0.0077%, 0.0078%, 0.0079%, 0.0080%, 0.0081%, 0.0082%, 0.0083%, 0.0084%, 0.0085%, 0.0086%, 0.0087%, 0.0088%, 0.0089%, 0.0090%, 0.0091%, 0.0092%, 0.0093%, 0.0094%, 0.0095%, 0.0096%, 0.0097%, 0.0098%, 0.0099%, 0.0100%, 0.0200%, 0.0250%, 0.0275%, 0.0300%, 0.0325%, 0.0350%, 0.0375%, 0.0400%、0.0425%、0.0450%、0.0475%、0.0500%、0.0525%、0.0550%、0.0575%、0.0600%、0.0625%、0.0650%、0.0675%、0.0700%、0.0725%、0.0750%、0.0775%、0.0800%、0.0825%、0.0850%、0.0875%、0.0900%、0.0925%、0.0950%、0.0975%、0.1000%、0.1250%、0.1500%、0.1750%、0.2000%、0.2250%、0.2500%、0.2750%、0.3000%、0.3250%、0.3500%、0.3750%、0.4000%、0.4250%、0.4500%、0.4750%、0.5000%、0.5250%、0.5500%、0.5750%、0.6000%、0.6250%、0.6500%、0.6750%、0.7000%、0.7250%、0.7500%、0.7750%、0.8000%、0.8250%、0.8500%、0.8750%、0.9000%、0.9250%、0.9500%、0.9750%、1.0%、1.1%、1.2%、1.3%、1.4%、1.5%、1.6%、1.7%、1.8%、1.9%、2.0%、2.1%、2.2%、2.3%、2.4%、2.5%、2.6%、2.7%、2.8%、2.9%、3.0%、3.1%、3.2%、3.3%、3.4%、3.5%、3.6%、3.7%、3.8%、3.9%、4.0%、4.1%、4.2%、4.3%、4.4%、4.5%、4.6%、4.7%、4.8%、4.9%、5.0%、5.1%、5.2%、5.3%、5.4%、5.5%、5.6%、5.7%、5.8%、5.9%、6.0%、6.1%、6.2%、6.3%、6.4%、6.5%、6.6%、6.7%、6.8%、6.9%、7.0%、7.1%、7.2%、7.3%、7.4%、7.5%、7.6%、7.7%、7.8%、7.9%、8.0%、8.1%、8.2%、8.3%、8.4%、8.5%、8.6%、8.7%、8.8%、8.9%、9.0%、9.1%、9.2%、9.3%、9.4%、9.5%、9.6%、9.7%、9.8%、9.9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 35%, 40%, 45%, 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 99%, or any derivable range thereof, for at least one component mentioned throughout this specification and the claims. In a non-limiting respect, this percentage may be calculated by weight or volume of the total composition. Those skilled in the art will understand that the concentration can vary depending on the addition, substitution, and / or reduction of components in a given composition.
[0063] C. Carrier
[0064] The compositions of the present invention may include or be incorporated into all types of carriers and excipients. The carrier or excipient may be pharmaceutically or dermatologically acceptable. Non-limiting examples of carriers or excipients include water, glycerin, alcohol, oils, silicone-containing compounds, silicone compounds, and waxes. Variations and other suitable carriers will be apparent to those skilled in the art and are applicable to the present invention. In some aspects, the concentrations and combinations of compounds, ingredients, and reagents may be selected such that these combinations are chemically compatible and do not form complexes that precipitate from the final product.
[0065] D. Structure
[0066] The compositions of the present invention can be constructed or formulated into a variety of different forms. Non-limiting examples include suspensions, emulsions (e.g., emulsions of water-in-oil, water-in-oil, water-in-oil, water-in-silicone, silicone-in-water, oil-in-water-in-oil, and silicone-in-water-in-oil), creams, lotions, solutions (aqueous solutions and water-alcohol solutions), anhydrous bases (e.g., lipsticks and powders), gels, masks, scrubs, body lotions, peels, and ointments. Variations and other structures will be apparent to those skilled in the art and are applicable to the present invention.
[0067] E. Additional ingredients
[0068] In addition to the ingredient combinations disclosed by the inventors, the composition may also include additional ingredients, such as cosmetic ingredients and pharmaceutical active ingredients. Non-limiting examples of these additional ingredients are described in the following subsections.
[0069] 1. Cosmetic ingredients
[0070] The CTFA International Dictionary and Handbook of Cosmetic Ingredients (2004 and 2008) describes a variety of non-restricted cosmetic ingredients that may be used in the context of this document. Examples of these ingredient categories include: fragrances (artificial and natural; e.g., gluconic acid, phenoxyethanol, and triethanolamine), dyes and coloring agents (e.g., Blue 1, Blue 1 Lake, Red 40, titanium dioxide, D&C Blue 4, D&C Green 5, D&C Orange 4, D&C Red 17, D&C Red 33, D&C Purple 2, D&C Yellow 10, D&C Yellow 11), flavorings / fragrances (e.g., stevia). Rebaudiana (sweet leaf) extract and menthol), adsorbents, lubricants, solvents, humectants (including emollients, humectants, film-forming agents, occlusive agents, and agents that affect the skin's natural moisturizing mechanisms), waterproofing agents, UV absorbers (physical and chemical absorbers, such as para-aminobenzoic acid (“PABA” and corresponding PABA derivatives, titanium dioxide, zinc oxide, etc.), essential oils, vitamins (such as vitamin A, vitamin B, vitamin C, vitamin D, vitamin E, and vitamin K), trace metals (such as zinc, calcium, and selenium), anti-irritants (such as steroidal and nonsteroidal anti-inflammatory drugs), plant extracts (such as aloe vera (Aloe vera)). Vera, chamomile, cucumber extract, ginkgo biloba, ginseng and rosemary), antibacterial agents, antioxidants (e.g., BHT and tocopherol), chelating agents (e.g., disodium EDTA and tetrasodium EDTA), preservatives (e.g., methylparaben and propylparaben), pH adjusters (e.g., sodium hydroxide and citric acid), absorbents (e.g., aluminum octenyl succinate, kaolin, corn starch, oat starch, cyclodextrin, lubricant). The ingredients include: stone powder and zeolite; skin whitening and spot-fading agents (e.g., hydroquinone and niacinamide lactate / ester); humectants (e.g., sorbitol, urea, methyl gluceth-20, saccharide isomers, and mannitol); exfoliants; waterproofing agents (e.g., magnesium hydroxide / aluminum stearate); and skin conditioning agents (e.g., aloe vera extract, allantoin, bisabolol, ceramide, dimethicone, hyaluronic acid, biosaccharide gum-1, ethylhexylglycerin, pentylene glycol, hydrogenated polydecene, octyl dodecyl oleate, and dipotassium glycyrrhizate). Non-limiting examples of some of these ingredients are provided in the following subsections.
[0071] a. Ultraviolet absorbers and / or reflectors
[0072] Ultraviolet absorbing and / or reflecting agents that can be used in conjunction with the compositions of the present invention include chemical and physical sunscreens. Non-limiting examples of chemical sunscreens that may be used include para-aminobenzoic acid (PABA), PABA esters (glycerol PABA, dimethyl PABA pentyl ester, and dimethyl PABA octyl ester), butyl PABA, ethyl PABA, ethyl dihydroxypropyl PABA, benzophenone (hydroxybenzophenone, sulphone, benzophenone, and benzophenone-1 to benzophenone-12), cinnamic acid esters (octinoxate, isoamyl para-methoxycinnamic acid, octyl para-methoxycinnamic acid, cinoxate, diisopropyl methyl cinnamic acid ester, DEA salt of methoxycinnamic acid, ethyl diisopropyl cinnamic acid, etc.). Octyl oleate, dimethoxycinnamate and ethyl methoxycinnamate), cinnamate esters, salicylates (homomethylsalicylate, benzyl salicylate, ethylene glycol salicylate, isopropyl benzyl salicylate, etc.), anthranilates, ethyl urocarboxylate, homomethylsalicylate, dibenzoylmethane derivatives (e.g., avobenzone), octocrylene, octyl triazine, galloyl gallate trioleate, glyceryl aminobenzoate, 2-hydroxy-1,4-naphthoquinone (lawsone) and dihydroxyacetone, ethylhexyl triazine, dioctylbutyramide triazine, benzyl malonic acid polysiloxane (benzylidene) Malonate polysiloxane, terephthalimide dicamphor sulfonic acid, disodium phenyl dibenzimidazole tetrasulfonate, diethylaminohydroxybenzoylhexylbenzoate, bis(diethylaminohydroxybenzoyl)benzoate, bis(benzoxazolyl)phenylethylhexyliminotriazine, cresoltrazol trisiloxane, methylene bis-benzotriazolyl tetramethylbutylphenol, and bis(ethylhexyl)phenol methoxyphenyltriazine, 4-methylbenzyl camphor, and isoamyl 4-methoxycinnamate. Non-limiting examples of physical sunscreens include kaolin, talc, petrolatum, and metal oxides (e.g., titanium dioxide and zinc oxide). Certain UV absorbers and / or reflectors, including one or more agents disclosed herein, are also contemplated and may be excluded from the compositions of the invention. Homosalate is specifically excluded from certain compositions disclosed herein.
[0073] b. Moisturizer
[0074] Non-limiting examples of moisturizers that can be used in conjunction with the compositions of the present invention include amino acids, chondroitin sulfate, diglycerides, erythritol, fructose, glucose, glycerol, glycerol polymers, ethylene glycol, 1,2,6-hexanetriol, honey, hyaluronic acid, hydrogenated honey, hydrogenated starch hydrolysate, inositol, lactitol, maltitol, maltose, mannitol, natural moisturizing factors, PEG-15 butylene glycol, polyglycerol sorbitol, pyrrolidone carboxylate, potassium PCA, propylene glycol, sugar isomers, sodium gluconate, sodium PCA, sorbitol, sucrose, trehalose, urea, and xylitol.
[0075] Other examples include acetylated lanolin, acetylated lanolin alcohol, alanine, algae extracts, Aloe barbadensis, Aloe barbadensis extract, Aloe barbadensis gel, Althea officinalis extract, Prunus armeniaca kernel oil, arginine, arginine aspartate / ester, Arnicamontana extract, aspartic acid, Persea gratissima oil, barrier sphingolipids, butanol, beeswax, behenol, β-sitosterol, Betula alba bark extract, Borago officinalis extract, Ruscus aculeatus extract, butylene glycol, Calendula officinalis extract, calendula oil, and Euphorbia milii. Cetifera wax, rapeseed oil, caprylic / capric triglycerides, cardamom (Elettaria cardamomum) oil, copal (Copernica cerifera) wax, carrot (Daucus carota sativa) oil, castor (Ricinus communis) oil, ceramides, ceresin, cetearyl alcohol polyether-5, cetearyl alcohol polyether-12, cetearyl alcohol polyether-20, cetearyl alcohol caprylate, cetearyl alcohol polyether-20, cetearyl alcohol polyether-24, cetearyl acetate, cetearyl caprylate, cetearyl palmitate, chamomile (Anthemis nobilis) oil, cholesterol, cholesterol esters, cholesterol hydroxystearate, citric acid, clary sage (Salvia sclarea) oil, cocoa (Theobroma cacao) butter, cocoyl caprylate / capric acid ester, coconut (Cocos nucifera) oil, collagen, collagen amino acids, corn (Zea Mays oil, fatty acids, decyl oleate, polydimethylsiloxane copolyol, polydimethylsiloxane alcohol, dioctyl adipate, dioctyl succinate, pentaerythritol hexacaprylate / hexacaprylate, DNA, erythritol, ethoxydiethylene glycol, ethyl linoleate, Eucalyptus globulus oil, Oenothera biennis oil, fatty acids, Geranium maculatum oil, glucosamine, glucosamine glutamate / ester.glutamate, glutamic acid, glyceryl polyether-26, glycerin, glycerol, glyceryl distearate, glyceryl hydroxystearate, glyceryl laurate, glyceryl linoleate, glyceryl myristate, glyceryl oleate, glyceryl stearate, glyceryl stearate SE, glycine, ethylene glycol stearate, ethylene glycol stearate SE, glycosaminoglycans, grape (Vitis vinifera) seed oil, hazelnut (American hazelnut, Corylus americana) nut oil, hazelnut (European hazelnut, Corylus avellana) nut oil, hexanediol, hyaluronic acid, safflower (Carthamus tinctorius) Tinctorius oil, hydrogenated castor oil, hydrogenated coconut oil glycerides, hydrogenated coconut oil, hydrogenated lanolin, hydrogenated lecithin, hydrogenated palm oil glycerides, hydrogenated palm kernel oil, hydrogenated soybean oil, hydrogenated tallow glycerides, hydrogenated vegetable oil, hydrolyzed collagen, hydrolyzed elastin, hydrolyzed glycosaminoglycans, hydrolyzed keratin, hydrolyzed soybean protein, hydroxylated lanolin, hydroxyproline, isocetyl stearate, isocetyl stearoyl stearate, isodecanyl oleate, isopropyl isostearate, isopropyl lanolinate, isopropyl myristate, isopropyl palmitate, isopropyl stearate, isostearamide DEA, isostearic acid, isostearyl lactate, isostearyl neopentanoate, jasmine (Jasminum officinale) oil, jojoba (Buxus chinensis) oil, giant seaweed (kelp), kelp (Aleurites) Moluccana oil, lactamide MEA, lanolin alcohol polyether-16, lanolin alcohol polyether-10 acetate, lanolin, lanolin acid, lanolin alcohol, lanolin oil, lanolin wax, lavender (Lavandula angustifolia) oil, lecithin, lemon (Citrus medicalimonum) oil, linoleic acid, linolenic acid, macadamia (Macadamia ternifolia) oil, maltitol, chamomile (Chamomilla recutita) oil, methyl glucosesquistearate, methylsilanol PCA ester, mineral oil, mink oil, Mortierella oil Oil), Myristyl lactate, Myristyl myristate, Myristyl propionate, Neopentyl glycol dicaprylate / dicaprylate, Octyl dodecyl alcohol, Octyl dodecyl myristate, Octyl dodecyl stearate, Octyl hydroxystearate, Octyl palmitate, Octyl salicylate, Octyl stearate, Oleic acid, Olive oil, Sweet orange oil, Palm oil, Palmitic acid, Panthenol, Panthenol ethyl ether, Paraffin wax, PCA, Peach oilPeanut kernel oil (Arachis hypogaea) oil, PEG-8 C12-18 ester, PEG-15 cocoamine, PEG-150 distearate, PEG-60 glyceryl isostearate, PEG-5 glyceryl stearate, PEG-30 glyceryl stearate, PEG-7 hydrogenated castor oil, PEG-40 hydrogenated castor oil, PEG-60 hydrogenated castor oil, PEG-20 methylglucose sesquistearate, PEG-40 sorbitan full oleate, PEG-5 soybean sterol, PEG-10 soybean sterol, PEG-2 stearate, PEG-8 stearate, PEG-20 stearate, PEG-32 stearate, PEG-40 stearate, PEG-50 stearate, PEG-100 Stearates, PEG-150 stearates, pentadecyl lactone, peppermint (Menthapiperita) oil, petrolatum, phospholipids, plankton extracts, polyaminosaccharide condensates, polyglycerol-3 diisostearate, polyquaternium-24, polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80, polysorbate 85, potassium myristate, potassium palmitate, propylene glycol, propylene glycol dicaprylate / dicaprate, propylene glycol dicaprylate, propylene glycol dinonanoate, propylene glycol laurate, propylene glycol stearate, propylene glycol stearate SE, PVP, pyridoxine dipalmitate, retinol, retinyl palmitate, rice (Oryza) Saturated soybean oil, RNA, rosemary (Rosmarinus officinalis) oil, rose oil, safflower (Carthamus tinctorius) oil, sage (Salvia officinalis) oil, sandalwood (Santalumalbum) oil, serine, serum albumin, sesame (Sesamum indicum) oil, shea butter (Butyrospermum parkii), silk powder, sodium chondroitin sulfate, sodium hyaluronate, sodium lactate, sodium palmitate, sodium PCA, sodium polyglutamate, soluble collagen, sorbitan laurate, sorbitan oleate, sorbitan palmitate, sorbitan sesquioleate, sorbitan stearate, sorbitol, soybean (Glycine) Soja oil, sphingolipids, squalane, squalene, stearamide MEA-stearate, stearic acid, stearoxydimethylsiloxane, stearoxytrimethylsilane, stearyl alcohol, stearyl glycyrrhetinate, stearyl heptanoate, stearyl stearate, sunflower (Helianthus annuus) seed oil, sweet almond (Prunus amygdalus)The ingredients include: dulcis oil, synthetic beeswax, tocopherol, tocopheryl acetate, tocopheryl linoleate, trimethylolpropionate, tridecyl pentoate, tridecyl stearate, triethanolamine, tristearin, urea, vegetable oil, water, wax, wheat (Triticum vulgare) germ oil, and ylang-ylang (Cananga odorata) oil. Certain humectants, including one or more agents disclosed herein, are also contemplated to be excluded from the compositions of the invention.
[0076] c. Antioxidants
[0077] Non-limiting examples of antioxidants that can be used in combination with the compositions of the present invention include acetylcysteine, ascorbic acid peptides, ascorbate dipalmitate, ascorbate methylsilanol pectate, ascorbate palmitate, ascorbate stearate, BHA, BHT, tert-butylhydroquinone, cysteine, cysteine HCl, dipentylhydroquinone, ditert-butylhydroquinone, diceryl thiodipropionate, dioleenyl tocopherol methylsilanol, disodium ascorbate sulfate, distearate thiodipropionate, ditridecyl thiodipropionate, dodecyl gallate, isoascorbic acid, ascorbate ester, ethyl ferulic acid, ferulic acid, gallate, and hydrogen. Quinones, isooctyl mercaptoacetate, kojic acid, magnesium ascorbate, magnesium ascorbate phosphate, methylsilanol ascorbate, natural plant antioxidants such as green tea or grape seed extract, nordihydroguaiac acid, octyl gallate, phenyl mercaptoacetic acid, potassium ascorbate tocopheryl phosphate, potassium sulfite, propyl gallate, quinones, rosmarinic acid, sodium ascorbate, sodium bisulfite, sodium isoascorbate, sodium metabisulfite, sodium sulfite, superoxide dismutase, sodium mercaptoacetate, sorbitol furfural, thiodiglycol, thiodiglycolamide, thiodiglycolic acid The compositions contain, but are not limited to, tocopherol, thiolactic acid, thiosalicylic acid, tocopherol ethyl ether-5, tocopherol ethyl ether-10, tocopherol ethyl ether-12, tocopherol ethyl ether-18, tocopherol ethyl ether-50, tocopherol, tocophersolan, tocopherol acetate, tocopherol linoleate, tocopherol nicotinate, tocopherol succinate, and tris(nonylphenyl) phosphite. Certain antioxidants, including one or more disclosed herein, are also contemplated to be excluded from the compositions of the invention.
[0078] d. Structuring agents
[0079] In other non-limiting aspects, the compositions of the present invention may include structuring agents. In some aspects, structuring agents contribute to providing rheological properties to the composition, thereby contributing to the stability of the composition. In other aspects, structuring agents may also act as emulsifiers or surfactants. Non-limiting examples of structuring agents include stearic acid, palmitic acid, stearyl alcohol, cetyl alcohol, behenyl alcohol, stearic acid, palmitic acid, stearyl alcohol polyethylene glycol ether having an average of about 1 to about 21 ethylene oxide units, cetyl alcohol polyethylene glycol ether having an average of about 1 to about 5 ethylene oxide units, and mixtures thereof. Certain structuring agents, including one or more agents disclosed herein, are also contemplated to be excluded from the compositions of the present invention.
[0080] e. Emulsifiers
[0081] In some aspects of the invention, the composition does not include an emulsifier. However, in other aspects, the composition may include one or more emulsifiers. Emulsifiers can reduce interfacial tension between phases and improve the formulation and stability of the emulsion. Emulsifiers may be nonionic, cationic, anionic, and zwitterionic emulsifiers (see U.S. Patent Nos. 5,011,681, 4,421,769, and 3,755,560). Non-limiting examples include esters of glycerol, esters of propylene glycol, fatty acid esters of polyethylene glycol, fatty acid esters of polypropylene glycol, esters of sorbitol, esters of dehydrated sorbitan anhydride, carboxylic acid copolymers, glucose esters and ethers, ethoxylated ethers, ethoxylated alcohols, alkyl phosphates, polyoxyethylene fatty alcohol ether phosphates, fatty acid amides, acyl lactates, soaps, TEA stearate, oleyl alcohol polyether-3 phosphate DEA salt, polyethylene glycol 20 dehydrated sorbitan monolaurate (polysorbate 20), polyethylene glycol 5 soybean sterol, stearyl alcohol polyether-2, stearyl alcohol polyether-20 Cetearyl alcohol polyether-21, cetearyl alcohol polyether-20, cetearyl glucoside, cetearyl alcohol, C12-13 alkyl polyether-3, PPG-2 methyl glucoether distearate, PPG-5-cetearyl alcohol polyether-20, bisPEG / PPG-20 / 20 polydimethylsiloxane, cetearyl alcohol polyether-10, polysorbate 80, cetearyl phosphate, cetearyl potassium phosphate, cetearyl diethanolamine phosphate, polysorbate 60, glyceryl stearate, PEG-100 stearate, arachidyl alcohol, arachidyl glucoside, and mixtures thereof. Certain emulsifiers, including one or more agents disclosed herein, are also contemplated for exclusion from the compositions of the invention. Certain compositions specifically exclude emulsifiers conventionally present in sunscreen compositions. Certain compositions specifically exclude cationic emulsifiers such as behenyltrimethylammonium chloride, dimethylcocoylammonium chloride, imidazolines (e.g., 1-hydroxyethyl-2-heptadecenylimidazoline), ethoxylated amines, and distearate dimethylammonium chloride.
[0082] f. Silicone-containing compounds
[0083] In a non-limiting sense, silicone compounds include any member of the polymer product family whose molecular backbone consists of alternating silicon and oxygen atoms with side groups attached to silicon atoms. By varying the -Si-O- chain length, side groups, and crosslinking, silicones can be synthesized into a wide variety of materials. Their consistency can range from liquid to gel to solid.
[0084] Silicone-containing compounds that can be used in the context of this invention include those described herein or known to those skilled in the art. Non-limiting examples include silicone oils (e.g., volatile and non-volatile oils), gels, and solids. In some aspects, silicone-containing compounds include silicone oils, such as polyorganosiloxanes. Non-limiting examples of polyorganosiloxanes include polydimethylsiloxane, cyclodimethylsiloxane, polysiloxane-11, phenyltrimethylsiloxane, trimethylsilyl-terminated trimethylsiloxane, stearoxytrimethylsilane, or mixtures of these and other organosiloxane materials in any given proportion to achieve the desired consistency and application characteristics according to the intended application (e.g., application to a specific area such as skin, hair, or eyes). "Volatile silicone oil" includes silicone oils with low heat of vaporization, i.e., typically less than about 50 calories per gram of silicone oil. Non-limiting examples of volatile silicone oils include: cyclic polydimethylsiloxanes, such as Dow Corning 344 fluid, Dow Corning 345 fluid, Dow Corning 244 fluid, and Dow Corning 245 fluid, Volatile Silicon 7207 (Union Carbide Corp., Danbury, Conn.); and low-viscosity polydimethylsiloxanes, i.e., polydimethylsiloxanes with a viscosity of approximately 50 cst or less (e.g., Dow Corning 200-0.5 cst fluid). Dow Corning fluids are available from Dow Corning Corporation in Midland, Michigan. Cyclic polydimethylsiloxanes and polydimethylsiloxanes are described in the 3rd edition of the CTFA Dictionary of Cosmetic Ingredients as mixtures of cyclic dimethyl polysiloxane compounds and fully methylated linear siloxane polymers capped with trimethylsiloxy units. Other non-limiting volatile silicone oils that may be used in the context of this invention include those available from General Electric Co., Silicone Products Div., Waterford, NY, and SWS Silicones Div., Stauffer Chemical Co., Adrian, Michigan. Certain silicone-containing compounds, including one or more agents disclosed herein, are also contemplated for exclusion from the compositions of this invention.
[0085] g. Exfoliating agents
[0086] Exfoliating agents comprise components that remove dead skin cells from the outermost layer of the skin. These agents can act by mechanical, chemical, and / or other means. Non-limiting examples of mechanical exfoliating agents include abrasives such as pumice, silica, cloth, paper, shells, beads, solid crystals, solid polymers, etc. Non-limiting examples of chemical exfoliating agents include acid and enzymatic exfoliating agents. Acids that can be used as exfoliating agents include, but are not limited to, glycolic acid, lactic acid, citric acid, α-hydroxy acids, β-hydroxy acids, etc. Other exfoliating agents known to those skilled in the art are also considered useful in the context of this invention. Certain exfoliating agents, including one or more agents disclosed herein, are also contemplated to be excluded from the compositions of this invention.
[0087] h. Essential oils
[0088] Essential oils comprise oils derived from herbs, flowers, trees, and other plants. These oils typically exist as tiny droplets between plant cells and can be extracted using several methods known to those skilled in the art, such as steam distillation, enfleurage (extraction using fats), maceration, solvent extraction, or mechanical pressing. When exposed to air, these oils tend to evaporate (i.e., are volatile oils). Therefore, many essential oils are colorless, but they may oxidize and darken over time. Essential oils are insoluble in water but soluble in alcohols, ethers, (plant) fixed oils, and other organic solvents. Typical physical properties of essential oils include a boiling point of about 160°C to 240°C and a density of about 0.759 to about 1.096.
[0089] Essential oils are typically named after the plant from which the oil is found. For example, rose oil or peppermint oil comes from the plant of rose or peppermint, respectively. Non-limiting examples of essential oils that can be used in the context of this invention include sesame oil, macadamia oil, tea tree oil, evening primrose oil, Spanish sage oil, Spanish rosemary oil, coriander oil, thyme oil, allspice oil, rose oil, fennel oil, balsam oil, bergamot oil, rosewood oil, cypress oil, chamomile oil, sage oil, clary sage oil, clove oil, cypress oil, eucalyptus oil, fennel oil, sea fennel oil, frankincense oil, geranium oil, ginger oil, grapefruit oil, jasmine oil, juniper berry oil, lavender oil, lemon oil, lemongrass oil, lime oil, citrus oil, marjoram oil, myrrh oil, neroli oil, orange oil, patchouli oil, pepper oil, black pepper oil, petitgrain oil, pine oil, and rose of Otto. Otto oil, rosemary oil, sandalwood oil, spearmint oil, spikenard oil, vetiver oil, wintergreen oil, or ylang-ylang oil. Other essential oils known to those skilled in the art are also considered useful in the context of this invention. Certain essential oils, including one or more agents disclosed herein, are also contemplated to be excluded from the compositions of this invention.
[0090] i. Thickener
[0091] Thickeners, including thickeners or gelling agents, include substances that can increase the viscosity of a composition. Thickeners include those that can increase the viscosity of a composition without substantially altering the efficacy of the active ingredient within the composition. Thickeners can also improve the stability of the compositions of the present invention. In some aspects of the invention, thickeners include hydrogenated polyisobutylene, trihydroxystearin, ammonium acryloyldimethyl taurate / VP copolymer, or mixtures thereof.
[0092] Non-limiting examples of additional thickeners that may be used in the context of this invention include carboxylic acid polymers, crosslinked polyacrylate polymers, polyacrylamide polymers, polysaccharides, and gums. Examples of carboxylic acid polymers include crosslinked compounds comprising one or more monomers derived from acrylic acid, substituted acrylic acid, and salts and esters of such acrylic and substituted acrylic acids, wherein the crosslinker contains two or more carbon-carbon double bonds and is derived from a polyol (see U.S. Patent Nos. 5,087,445, 4,509,949, and 2,798,053; CTFA International Dictionary of Cosmetic Ingredients, 4th Edition, 1991, pp. 12 and 80). Examples of commercially available carboxylic acid polymers include carbomer, which is a homopolymer of acrylic acid crosslinked with an allyl ether of sucrose or pentaerythritol (e.g., CARBOPOL™ 900 series from BF GOODRICH).
[0093] Non-limiting examples of crosslinked polyacrylate polymers include cationic and nonionic polymers. Examples are described in U.S. Patent Nos. 5,100,660, 4,849,484, 4,835,206, 4,628,078, and 4,599,379.
[0094] Non-limiting examples of polyacrylamide polymers (including nonionic polyacrylamide polymers, which include substituted branched or unbranched polymers) include polyacrylamide, isoparaffins and lauryl ether-7, and acrylamide and multiblock copolymers of substituted acrylamide with acrylic acid and substituted acrylic acid.
[0095] Non-limiting examples of polysaccharides include cellulose, carboxymethyl hydroxyethyl cellulose, cellulose acetate propionate carboxylate, hydroxyethyl cellulose, hydroxyethyl ethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, methyl hydroxyethyl cellulose, microcrystalline cellulose, sodium cellulose sulfate, and mixtures thereof. Another example is alkyl-substituted cellulose, wherein the hydroxyl groups of the cellulose polymer are hydroxyalkylated (preferably hydroxyethylated or hydroxypropylated) to form hydroxyalkylated cellulose, and then further modified by C10-C30 straight-chain or branched alkyl groups via ether bonds. Typically, these polymers are ethers of C10-C30 straight-chain or branched alcohols with hydroxyalkyl cellulose. Other useful polysaccharides include stearin, which comprises a straight chain containing (1 to 3) linked glucose units, with one (1 to 6) linked glucose units for every three units.
[0096] Non-limiting examples of gums that can be used with the present invention include gum arabic, agar, alginic acid, ammonium alginate, amylopectin, calcium alginate, calcium carrageenan, carnitine, carrageenan, dextrin, gelatin, gellan gum, guar gum, guar gum hydroxypropyltrimethylammonium chloride, lithium montmorillonite, hyaluronic acid, hydrated silica, hydroxypropyl chitosan, hydroxypropyl guar gum, karaya gum, giant seaweed, locust bean gum, natto gum, potassium alginate, potassium carrageenan, propylene glycol alginate, sclerotium gum, sodium carboxymethyl dextrin, sodium carrageenan, astragalus gum, xanthan gum, and mixtures thereof.
[0097] It is also envisioned that certain thickeners, including one or more agents disclosed herein, may be excluded from the compositions of the present invention.
[0098] j. Preservatives
[0099] Non-limiting examples of preservatives that may be used in the context of this invention include quaternary ammonium salts such as polyquaternium-1 and benzalkonium halides (e.g., benzalkonium chloride ("BAC") and benzalkonium bromide), parabens (e.g., methylparaben and propylparaben), phenoxyethanol, benzyl alcohol, chlorobutanol, phenol, sorbic acid, thimerosal, or combinations thereof. Certain preservatives, including one or more agents disclosed herein, are also contemplated that may be excluded from the compositions of this invention.
[0100] 2. Drug components
[0101] Pharmaceutical active agents are also considered suitable for use with the compositions of the present invention. Non-limiting examples of pharmaceutical active agents include anti-acne agents, agents for treating rosacea, analgesics, anesthetics, anorectal agents, antihistamines, anti-inflammatory agents including nonsteroidal anti-inflammatory drugs, antibiotics, antifungal agents, antiviral agents, antimicrobial agents, anticancer active agents, anti-scabies agents, antilice agents, antitumor agents, antiperspirants, antipruritic agents, antipsoriatic agents, antiseborrheic agents, bioactive proteins and peptides, burn treatment agents, and cauterizing agents. Agents, depigmenting agents, depilatory agents, diaper rash treatment agents, enzymes, hair growth stimulants, hair growth retardants including DFMO and its salts and analogues, hemostatic agents, kerolytic agents, oral ulcer treatment agents, cold sore treatment agents, dental and periodontal treatment agents, photosensitizing agents, skin protectants / barrier agents, steroids including hormones and corticosteroids, sunburn treatment agents, sunscreens, transdermal agents, nasal agents, vaginal agents, wart treatment agents, wound treatment agents, wound healing agents, etc. Certain pharmaceutical ingredients, including one or more agents disclosed herein, are also contemplated to be excluded from the compositions of the present invention.
[0102] F. Reagent kit
[0103] Kits that can be used for certain aspects of the invention are also envisioned. For example, the compositions of the invention may be included in a kit. The kit may include a container. The container may include a bottle, metal tube, laminated tube, plastic tube, dispenser, pressurized container, barrier container, packaging, compartment, lipstick container, compacted container, cosmetic tray capable of containing a cosmetic composition, or other types of containers, such as injection or blow-molded plastic containers, wherein the dispersion or composition or the desired bottle, dispenser, or packaging is stored. The surface of the kit and / or container may contain markings. The markings may, for example, be text, phrases, abbreviations, pictures, or symbols.
[0104] The container can dispense a predetermined amount of the composition. In other embodiments, the container (e.g., metal, laminated material, or plastic tube) can be squeezed to dispense the desired amount of composition. The composition can be dispensed in the form of a spray, aerosol, liquid, fluid, or semi-solid. The container can have a spray mechanism, a pump mechanism, or a squeeze mechanism. The kit may also include instructions on using any other compositions in the container and on using the kit components. The instructions may include explanations on how to apply, use, and maintain the composition. Example
[0105] The following embodiments are intended to illustrate preferred embodiments of the present invention. Those skilled in the art will understand that the techniques disclosed in the following embodiments represent techniques discovered by the inventors that have proven effective in implementing the present invention, and therefore can be considered preferred modes of practice. However, based on this disclosure, those skilled in the art will understand that many changes can be made to the specific embodiments disclosed without departing from the spirit and scope of the invention, and similar or related results can still be obtained.
[0106] All compositions and / or methods disclosed and claimed herein can be manufactured and performed based on this disclosure without excessive experimentation. While the compositions and methods of the present invention have been described according to preferred embodiments, it will be apparent to those skilled in the art that changes can be made to the compositions and / or methods described herein, as well as the steps or sequence of steps within the methods, without departing from the concept, spirit, and scope of the invention. More specifically, it will be apparent that certain chemically and physiologically relevant reagents can be substituted for the reagents described herein, while yielding the same or similar results. All such similar substitutions and modifications that will be apparent to those skilled in the art are considered to be within the spirit, scope, and concept defined by the appended claims.
[0107] Example 1
[0108] (Materials used)
[0109] The active ingredients in Table 1 were used to obtain the following in vitro data.
[0110]
[0111] Example 2
[0112] (Exemplary formulation)
[0113] Topical skin or hair compositions were prepared using formulations of the ingredients in Example 1. Formulations 1 to 7 are examples of topical skin compositions prepared as sunscreens.
[0114]
[0115]
[0116]
[0117]
[0118]
[0119]
[0120]
[0121]
[0122]
[0123] *The formulation can be prepared by mixing the components in a beaker at 70°C to 75°C until homogeneous. The formulation can then be cooled to room temperature (20°C to 25°C). Further, and if desired, additional components can be added, for example, to adjust the rheological properties of the composition.
[0124] **A carrier may be added, for example, to adjust the rheological properties of the composition. Alternatively, the amount of water may be varied, provided that the water content in the composition is at least 60 wt%, and preferably between 60 wt% and 85 wt%.
[0125] Example 3
[0126] (Sunscreen activity)
[0127] The sunscreen compositions of formulations 1 through 7 have been determined to block ultraviolet radiation, even after contact with water. A summary of the results is shown in Table 2, and the methods used to determine the properties of the components are described below.
[0128]
[0129] SPF values are calculated using the in vivo SPF measurement method based on standard in vivo measurements.
[0130] Example 4
[0131] (Additional measurements)
[0132] Determinations that can be used to determine the efficacy of any single ingredient or any combination of ingredients disclosed throughout the specification and claims, or a composition having a combination of said ingredients, can be determined by methods known to those skilled in the art. The following are non-limiting determinations that can be used and / or have already been used in the context of this invention. It should be recognized that other testing procedures can be used, including, for example, objective and subjective procedures.
[0133] B16 Pigmentation Assay: Melanogenesis is the process by which melanocytes produce melanin, a naturally occurring pigment that gives skin, hair, and eyes color. Inhibiting melanin production helps prevent skin darkening and reduce age-related dark spots. This bioassay uses immortalized mouse melanoma cell line B16-F1 melanocytes (ATCC) to analyze the effect of compounds on melanogenesis. The endpoint of this assay is the spectrophotometric determination of melanogenesis and cell viability. B16-F1 melanocytes can be cultured in standard DMEM growth medium at 37°C and 10% CO2 using 10% fetal bovine serum (MEDIATECH), and then treated for 6 days with the active ingredient, combination of ingredients, or composition containing said combination as disclosed in the instructions. After incubation, melanin secretion is measured by absorbance at 405 nm, and cell viability is quantified.
[0134] Collagen Stimulation Assay: Collagen is an extracellular matrix protein essential for skin structure. Increased collagen synthesis contributes to improved skin firmness and elasticity. This bioassay can be used to detect the effect of any of the active ingredients, combinations of ingredients, or compositions having said combinations disclosed in the product information on the production of procollagen peptides (precursors to collagen) in human epidermal fibroblasts. The endpoint of this assay is a spectrophotometric measurement reflecting the presence of procollagen peptides and cell viability. This assay employs a quantitative sandwich enzyme immunoassay technique, in which a procollagen peptide-specific monoclonal antibody has been pre-coated onto a microplate. Standards and samples can be pipetted into the wells, and any present procollagen peptides are bound by the immobilized antibody. After washing away any unbound material, an enzyme-linked polyclonal antibody against the procollagen peptide can be added to the wells. After washing to remove any unbound antibody-enzyme reagent, a substrate solution can be added to the wells, which will develop color proportionally to the amount of procollagen peptide bound in the initial step and be detected using a microplate reader at 450 nm. It can stop color development and measure color intensity.
[0135] For the preparation of samples and controls, subconfluent normal adult epidermal fibroblasts (Cascade Biologics) cultured at 37°C in 10% CO2 in standard DMEM growth medium containing 10% fetal bovine serum (MEDIATECH) were treated for 3 days with a combination of each component disclosed in the instructions or a composition having said combinations. After incubation, the cell culture medium was collected, and the amount of precollagen peptide secretion was quantified using a sandwich enzyme-linked immunosorbent assay (ELISA) from TAKARA (#MK101).
[0136] Elastin Stimulation Assay: Elastin is a connective tissue protein that helps the skin regain its shape after stretching or contraction. Elastin is also an important load-bearing protein, used in areas where mechanical energy needs to be stored. Elastin is produced through a reaction catalyzed by lysyl oxidase, by linking numerous soluble proelastin molecules. Elastin secretion and elastin fibers can be monitored in cultured human fibroblasts by staining them with an immunofluorescent antibody targeting elastin.
[0137] Laminin and Fibronectin Stimulation Assay: Laminin and fibronectin are major proteins of the dermal-epidermal junction (DEJ), also known as the basement membrane. The DEJ lies between the dermis and epidermis, forming finger-like projections called reteridges. Epidermal cells obtain nutrients from blood vessels in the dermis. The reteridges increase the surface area of the epidermis exposed to these vessels and the necessary nutrients. The DEJ provides adhesion between the two tissue compartments and controls the structural integrity of the skin. Laminin and fibronectin are two structural glycoproteins located in the DEJ. Laminin and fibronectin are considered adhesives that bind cells together; they are secreted by dermal fibroblasts and contribute to promoting intracellular and intercellular adhesion of epidermal cells to the DEJ. The secretion of laminin and fibronectin can be monitored by quantifying laminin and fibronectin in the cell supernatant of cultured human fibroblasts treated for 3 days with a medium containing or without 1.0% of one or more test components at a final concentration. Following incubation, the levels of laminin and fibronectin can be measured using an enzyme-linked immunosorbent assay (ELISA) using immunofluorescent antibodies targeting laminin and antibodies targeting fibronectin directly. Measurements of cellular metabolic activity are standardized, for example, by biotransformation with 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazonium (MTS).
[0138] Tumor necrosis factor-α (TNF-α) assay: TNF-α, the prototype ligand of the TNF superfamily, is a pleiotropic cytokine that plays an important role in inflammation. Increased expression of TNF-α is associated with upregulation of pro-inflammatory activity. This bioassay can be used to analyze the effect of any of the active ingredients, combinations of ingredients, or compositions having said combinations disclosed in the product specification on the production of TNF-α by human epidermal keratinocytes. The endpoint of this assay can be a spectrophotometric measurement reflecting TNF-α and cell viability. This assay employs a quantitative sandwich enzyme immunoassay technique, in which a monoclonal antibody specifically targeting TNF-α has been pre-coated onto a microplate. Standards and samples can be pipetted into the wells, and any present TNF-α is bound by the immobilized antibody. After washing away any unbound material, a TNF-α-specific enzyme-linked polyclonal antibody can be added to the wells. After washing to remove any unbound antibody-enzyme reagent, a substrate solution can be added to the wells, and color development is performed proportionally to the amount of TNF-α bound in the initial step, and detection is performed using a microplate reader at 450 nm. It can stop color development and measure color intensity. It was tested at 37°C in 5% CO2 using EPILIFE. TM Submerged normal adult keratinocytes cultured in standard growth medium (Cascade Biologics) can be treated for 6 hours with phorbol 12-tetradecanoate 13-acetate (PMA, 10 ng / ml, SIGMA CHEMICAL, #P1585-1MG) and any of the active ingredients, combinations of ingredients, or compositions having said combinations disclosed in the instructions. PMA has been shown to induce a significant increase in TNF-α secretion, which peaks at 6 hours post-treatment. After incubation, the cell culture medium can be collected, and TNF-α secretion can be quantified using a sandwich enzyme-linked immunosorbent assay (ELISA) (#DTA00C) from R&D Systems.
[0139] Antioxidant (AO) assay: An in vitro bioassay used to measure the total antioxidant capacity of any one of the ingredients, combinations of ingredients, or compositions having said combinations disclosed in the product specification. This assay relies on the antioxidants in the sample inhibiting metmyoglobin from releasing ABTS. ® (2,2'-Azido-bis-[3-ethylbenzothiazoline sulfonate]) oxidized to ABTS ®•+ Capacity. The antioxidant system of living organisms includes enzymes such as superoxide dismutase, catalase, and glutathione peroxidase; macromolecules such as albumin, ceruloplasmin, and ferritin; and a range of small molecules including ascorbic acid, α-tocopherol, β-carotene, reduced glutathione, uric acid, and bilirubin. The sum of endogenous and food-derived antioxidants represents the total antioxidant activity in extracellular fluid. The synergistic effect of all the different antioxidants provides stronger protection against reactive oxygen species or nitrogen free radical attacks than any single compound acting alone. Therefore, total antioxidant capacity provides more relevant biological information than information obtained by measuring individual components, as it takes into account the cumulative effect of all antioxidants present in plasma and body fluids. The ability of antioxidants in a sample to prevent ABTS® oxidation is compared to the ability of the water-soluble tocopherol analog Trolox and quantified as molar equivalents of Trolox. The Antioxidant Capacity Kit #709001 from CAYMAN CHEMICAL (Ann Arbor, Michigan, USA) can be used as an in vitro bioassay to measure the total antioxidant capacity of any one of the active ingredients, combinations of ingredients, or compositions having said combinations disclosed in the product information. The protocol can be performed according to the manufacturer's recommendations.
[0140] ORAC assay: The oxygen radical absorption (or absorbance) capacity (ORAC) of any of the active ingredients, combinations of ingredients, or compositions having said combinations disclosed in the product specification can also be determined by measuring the antioxidant activity of these ingredients or compositions. Antioxidant activity indicates the ability to reduce oxidants (oxidants). This assay quantifies the time and extent required to inhibit the action of oxidants such as oxygen radicals, which are known to damage cells (e.g., skin cells). The ORAC value of any of the ingredients, combinations of ingredients, or compositions having said combinations disclosed in the product specification can be determined by methods known to those skilled in the art (see U.S. Publications 2004 / 0109905 and 2005 / 0163880; and commercially available kits, such as the Zen-Bio ORAC Antioxidant Assay Kit (#AOX-2)). The Zen-Bio ORAC Antioxidant Assay Kit measures the loss of fluorescein fluorescence over time due to the formation of peroxide radicals from the decomposition of AAPH (2,2'-azobis-2-methylpropylammonium dihydrochloride). The water-soluble vitamin E analog Trolox was used as a positive control in a dose-dependent manner to inhibit fluorescein decay.
[0141] Mushroom Tyrosinase Activity Assay: In mammalian cells, tyrosinase catalyzes two steps in the multi-step biosynthesis of melanin from tyrosine (and from the polymerization of dopachrome). Tyrosinase is located in melanocytes and produces melanin (an aromatic quinone compound), which gives skin, hair, and eye color. Purified mushroom tyrosinase (from SIGMA) can be incubated with its substrate L-Dopa (from FISHER) in the presence or absence of any of each active ingredient, combination of ingredients, or composition having said combinations disclosed in the specification. Pigment formation can be assessed by a microplate reader reading at 490 nm. The percentage of inhibition of mushroom tyrosinase activity can be calculated and compared with an untreated control to determine the ability of the test ingredient or combination thereof to inhibit the activity of the purified enzyme. The inhibitory effect of the test extract is compared with the inhibitory effect of kojic acid (SIGMA).
[0142] Matrix metalloproteinase 3 and matrix metalloproteinase 9 (MMP3; MMP9) activity assays: In vitro assays of matrix metalloproteinase (MMP) inhibition. MMPs are extracellular proteases that function in many normal and disease states due to their broad substrate specificity. MMP3 substrates include collagen, fibronectin, and laminin; while MMP9 substrates include collagen VII, fibronectin, and laminin. Using the Colorimetric Drug Discovery kits for MMP3 (AK-400) and MMP-9 (AK-410) from BioMol International, this assay aims to measure the protease activity of MMPs using a thiopeptide as the chromogenic substrate (Ac-PLG-[2-mercapto-4-methyl-valeryl]-LG-OC2H5)5,6. The peptide bonds at the MMP cleavage site are replaced by thioester bonds in the thiopeptide. MMP hydrolyzes this bond to generate a thiol group, which reacts with DTNB [5,5'-dithiobis(2-nitrobenzoic acid), Ellman's reagent] to form 2-nitro-5-thiobenzoic acid, which can be detected by its absorbance at 412 nm (ε=13600 M). -1 cm -1 (pH 6.0 and above 7). It can determine the active ingredients disclosed in the product specification, any combination of ingredients, or compositions having said combinations.
[0143] Matrix metalloproteinase 1 (MMP1) activity assay: An in vitro assay for the inhibition of matrix metalloproteinases (MMPs). MMPs are extracellular proteases that function in many normal and disease states due to their broad substrate specificity. MMP1 substrates include type IV collagen. The ENZ / CHEK gelatinase / collagenase assay kit (#E12055) utilizes a fluorescent gelatin substrate to detect MMP1 protease activity. A bright green fluorescence is observed during proteolytic cleavage, and the enzyme activity can be monitored using a fluorescent microplate reader.
[0144] The ENZ / CHEK Gelatinase / Collagenase Assay Kit (#E12055) from Invitrogen is designed for the in vitro assay of MMP1 enzyme activity. It can measure the active ingredient disclosed in the instructions, any combination of ingredients, or a combination containing said combinations. This assay relies on the ability of purified MMP1 enzyme to degrade fluorescent gelatin substrates. Once the substrate is specifically cleaved by MMP1, bright green fluorescence appears and can be monitored using a fluorescent microplate reader. Test materials are incubated in the presence or absence of purified enzyme and substrate to determine their protease inhibitory activity.
[0145] Cyclooxygenase (COX) Assay: In vitro inhibition assay of cyclooxygenase-1 and cyclooxygenase-2 (COX-1, COX-2). COX is a bifunctional enzyme with both cyclooxygenase and peroxidase activities. Cyclooxygenase activity converts arachidonic acid into hydroperoxides (prostaglandin G2; PGG2), while the peroxidase component reduces these hydroperoxides (prostaglandin H2; PGH2) into their corresponding alcohols, namely precursors to prostaglandins, thromboxanes, and prostacyclin. This COX inhibitor screening assay measures the peroxidase component of cyclooxygenase. Peroxidase activity is determined colorimetrically by monitoring the presence of oxidized N,N,N',N'-tetramethyl-p-phenylenediamine (TMPD). This inhibitor screening assay includes both COX-1 and COX-2 enzymes to screen for isoenzyme-specific inhibitors. Colorimetric COX (Sheep) Inhibitor Screening Assay (#760111, CAYMAN CHEMICAL) can be used to analyze the effect of each active ingredient, any combination of ingredients, or a combination of said ingredients disclosed in the product information on the activity of purified cyclooxygenase (COX-1 or COX-2). Following the manufacturer's instructions, the purified enzyme, heme, and test extract are mixed in a detection buffer and incubated with shaking at room temperature for 15 minutes. After incubation, arachidonic acid and the colorimetric substrate can be added to initiate the reaction. Colorimetric development can be assessed by reading the microplate reader at 590 nm. The percentage of COX-1 or COX-2 activity inhibition can be calculated and compared to an untreated control to determine the ability of the test extract to inhibit the activity of the purified enzyme.
[0146] Lipoxygenase (LO) Assay: An in vitro assay for lipoxygenase (LO) inhibition. LO is a non-heme iron-containing dioxygenase that catalyzes the addition of molecular oxygen to fatty acids. Linoleic acid and arachidonic acid are the main substrates of LO in plants and animals. Arachidonic acid can then be converted into hydroxyeicosatetrienic acid (HETE) derivatives, which are subsequently converted into leukotrienes, a potent inflammatory mediator. This assay provides an accurate and convenient method for screening lipoxygenase inhibitors by measuring the hydroperoxides produced during incubation of lipoxygenases (5-LO, 12-LO, or 15-LO) with arachidonic acid. The Colorimetric LO Inhibitor Screening Kit (#760700, CAYMAN CHEMICAL) can be used to determine the ability of each active ingredient, any combination of ingredients, or a combination having the combinations disclosed in the instructions to inhibit enzyme activity. Purified 15-lipoxygenase and the test ingredient can be mixed in assay buffer and incubated with shaking at room temperature for 10 minutes. After incubation, arachidonic acid can be added to initiate the reaction, and the mixture can be incubated again at room temperature for 10 minutes. The catalysis can be terminated by adding a colorimetric substrate, and the colorimetric progress can be assessed by fluorescence plate readings at 490 nm. The percentage inhibition of lipoxygenase activity can be calculated compared to an untreated control to determine the ability of each active ingredient, any combination of ingredients, or a composition having the combinations disclosed in the specification to inhibit the activity of the purified enzyme.
[0147] Elastase Assay: The ENZCHEK® Elastase Assay (Kit #E-12056) from MOLECULAR PROBES (Eugene, Oregon USA) can be used as an in vitro enzyme inhibition assay to measure the inhibition of elastase activity of each active ingredient, any combination of ingredients, or a combination of said ingredients disclosed in the instructions. The ENZCHEK kit contains soluble bovine cervical ligament elastin, which can be labeled with a dye so that the fluorescence of the conjugate can be quenched. Non-fluorescent substrates can be digested with elastase or other proteases to produce highly fluorescent fragments. The resulting increase in fluorescence can be monitored using a fluorescence microplate reader. The digestion product of the elastin substrate has maximum absorption at approximately 505 nm and maximum fluorescence emission at approximately 515 nm. When screening for elastase inhibitors using the ENZCHEK ELASTASE ASSAY KIT, the peptide N-methoxysuccinyl-Ala-Ala-Pro-Val-chloromethyl ketone can be used as a selective, co-elastase inhibitor of elastase.
[0148] Ceramide formation: Ceramide in cell or tissue samples can be labeled at room temperature using a mouse monoclonal antibody against ceramide (ENZO LIFE SCIENCE, reference number ALX-804-196, clone MID15B4) diluted to 1 / 50 with a magnification system (Biotin / Streptavidin) for 2 hours. Ceramide can be observed using a video microscope (pink staining).
[0149] Oil Control Assay: Measurements of reduced sebum secretion and / or reduced sebum production can be performed using standard techniques known to those skilled in the art. In one case, the forehead may be used. Each active ingredient, any combination of ingredients, or composition having said combination disclosed in the specification may be applied once or twice daily to a portion of the forehead for a set number of days (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or more than 14 days), while another portion of the forehead remains untreated. After the set number of days has elapsed, sebum secretion can be measured by applying fine blotting paper to the treated and untreated forehead skin. First, all sebum is removed from the treated and untreated areas with a damp and then dry cloth. Then, blotting paper can be applied to the treated and untreated areas of the forehead, and an elastic band can be placed around the forehead to gently press the blotting paper onto the skin. After 2 hours, the blotting paper can be removed, allowed to dry, and then transmitted through the light. Darker blotting paper is associated with more sebum production (or lighter blotting paper is associated with less sebum production).
[0150] Erythema Assay: A MINOLTA colorimeter can be used to assess the reduction of skin redness. Applying a 0.2% sodium lauryl sulfate solution to the subject's forearm induces skin erythema. The area is protected with an occlusive patch for 24 hours. After 24 hours, the patch is removed, and the irritation-induced redness is assessed using the a* value of the MINOLTA colorimeter. The a* value measures the change in skin color in the red area. Immediately after taking the reading, the area is treated with the active ingredient, any combination of ingredients, or a composition having the combination disclosed in the instructions. Repeat measurements can be performed periodically to determine the formulation's ability to reduce redness and irritation.
[0151] Skin Moisture / Hydration Measurement: Skin moisture / hydration can be measured using impedance measurement with the Nova dermal phase meter. The impedance meter measures changes in skin moisture content. The outer layer of skin has unique electrical properties. When skin is dry, its conductivity is poor. As skin moisture content increases, its conductivity increases. Therefore, changes in skin impedance (related to conductivity) can be used to assess changes in skin hydration. The device can be calibrated according to the instrument instructions each test day. Temperature and relative humidity can also be recorded. Subjects can be evaluated by equilibrating them in a room with specified humidity (e.g., 30% to 50%) and temperature (e.g., 68°C to 72°C) before measurement. Three individual impedance readings can be read on each side of the face, recorded, and averaged. A T5 setting can be used for the impedance meter, which averages the impedance applied to the face every five seconds. Changes can be reported using statistical variance and significance. Each active ingredient, any combination of ingredients, or composition having said combinations disclosed in the instructions can be determined according to the method.
[0152] Determination of Skin Clarity and Reduction of Freckles and Age Spots: Skin clarity and reduction of freckles and age spots can be assessed using a Minolta colorimeter. Using the a* value of the Minolta colorimeter, changes in skin color can be assessed to identify potential irritation caused by product treatment. The a* value measures changes in skin color in red areas. This is used to determine whether each active ingredient, any combination of ingredients, or a composition having said combinations disclosed in the instructions will cause irritation. Measurements can be taken on each side of the face, and the average value is taken as the left and right face value. Skin clarity can also be measured using a Minolta meter. This measurement is a combination of the a*, b, and L values of the Minolta meter, related to skin brightness and closely related to skin smoothness and hydration. Readings are taken from the skin as described above. In a non-limiting aspect, skin clarity can be described as L / C, where C is chromaticity and is defined as (a... 2 +b 2 ) 1 / 2 .
[0153] Skin dryness, fine lines, skin smoothness, and skin color assessment: Skin dryness, fine lines, skin smoothness, and skin color can be assessed using clinical grading techniques. For example, the clinical grading of dry skin can be determined using the five-point Kligman scale: (0) Skin is soft and moist; (1) Skin appears normal with no visible dryness; (2) Skin feels slightly dry with no visible peeling; (3) Skin feels dry, firm, and has a whitish appearance with some scaling; and (4) Skin feels very dry, rough, and has a whitish appearance with scaling. Assessments can be performed independently by two clinicians, and the average value is taken.
[0154] Clinical grading of skin color: Clinical grading of skin color can be performed using a ten-point analog number scale: (10) Smooth, uniform pinkish-brown skin. No dark, red, or scaly patches are visible when examined with a handheld magnifying glass. The microscopic texture of the skin is very uniform when touched; (7) Uniform skin color is observed without magnification. No scaly areas, but slight discoloration due to pigmentation or erythema. No discoloration exceeding 1 cm in diameter; (4) Skin discoloration and uneven texture are easily noticeable. Slight scaling. Some areas of skin feel rough to the touch; and (1) Uneven skin color and texture. Numerous areas of scaling and discoloration, either due to hypopigmentation or erythema or melanosis. Large areas of uneven color exceeding 1 cm in diameter. The assessment is performed independently by two clinicians and the average is taken.
[0155] Clinical grading of skin smoothness: Clinical grading of skin smoothness can be determined using a ten-point analog number scale: (10) smooth, moist and glossy, with no resistance when dragged with a finger; (7) slightly smooth, with slight resistance; (4) rough, with significantly altered friction when rubbed; and (1) rough, flaky, and uneven surface. Assessments were performed independently by two clinicians, and the average value was taken.
[0156] Skin smoothness and wrinkle reduction were assessed using the method disclosed by Packman et al. (1978): Skin smoothness and wrinkle reduction can also be visually assessed using the method disclosed by Packman et al. (1978). For example, at each subject visit, the depth, shallowness, and total number of superficial facial lines (SFLs) for each subject can be carefully scored and recorded. Numerical scores are obtained by multiplying a numerical factor by a depth / width / length factor. Scores for the eye and mouth regions (left and right sides) are obtained and summed to obtain the total wrinkle score.
[0157] Skin firmness can be measured using the Hargens Ballistometer: The Hargens Ballistometer assesses skin elasticity and firmness by dropping a ball onto the skin and recording its first two rebound peaks. Ballistometry uses a small, lightweight probe with a relatively blunt probe (4 square millimeters contact area). The probe slightly penetrates the skin and produces measurements dependent on the properties of the outer layers of the skin, which include the stratum corneum and epidermis, as well as some of the dermis.
[0158] Skin softness / flexibility determination using the Gas Bearing Electrodynamometer: Skin softness / flexibility can be assessed using the Gas Bearing Electrodynamometer, an instrument for measuring the stress / strain properties of the skin. Skin viscoelasticity is related to skin hydration. Measurements can be obtained at predetermined locations on the cheek area by attaching a probe to the skin surface with double-sided tape. A force of approximately 3.5 gm can be applied parallel to the skin surface, and the skin displacement can be accurately measured. Skin flexibility can then be calculated and expressed as DSR (Dynamic Elasticity Coefficient in gm / mm).
[0159] Determination of the appearance of lines and wrinkles using replicas: The appearance of lines and wrinkles on the skin can be evaluated using replicas, which are impressions of the skin surface. Materials similar to silicone rubber can be used. Replicas can be analyzed through image analysis. By obtaining a silicone replica from the subject's face and analyzing the replica image using a computer image analysis system, changes in the visibility of lines and wrinkles can be objectively quantified. Replicas can be photographed from the eye and neck areas using a digital camera with low-angle incident light. Digital images can be analyzed using image processing programs to identify replicas covered by wrinkles or fine lines.
[0160] Skin surface profile determination using a surface photometer / stylus method: The surface profile of the skin can be measured using a surface photometer / stylus method. This involves shining light on the surface of a replica or dragging a stylus across it. The vertical displacement of the stylus is input into a computer via a distance sensor, and after scanning a replica of a fixed length, a cross-sectional analysis of the skin profile can be generated as a two-dimensional surface. This scan can be repeated an arbitrary number of times along a fixed axis to produce a simulated 3-D image of the skin. Ten random portions of the replica can be obtained using the stylus technique and combined to produce an average value. Values of interest include Ra, which is the arithmetic mean of all roughness (height) values, calculated by integrating the profile height relative to the average profile height. Rt is the maximum vertical distance between the highest peak and the lowest valley, and Rz is the average peak amplitude minus the average peak height. These values are calibration values in mm. Before each use, the device should be standardized by scanning a metal standard with known values. The Ra value can be calculated using the following equation: R a =Standardized roughness; l m = Horizontal (scanning) length; y = Absolute value of the profile position relative to the average profile height (x-axis).
[0161] MELANODERM TMAssay: In other non-limiting respects, the efficacy of each active ingredient, any combination of ingredients, or composition having said combination disclosed in the specification can be determined by the use of a dermal analogue, such as MELANODERM. TM To assess. Melanocytes are a type of cell found in skin analogs that stain positively when exposed to L-dihydroxyphenylalanine (L-DOPA), a precursor to melanin. Skin analog MELANODERM TM Various matrices containing each active ingredient, any combination of ingredients, or compositions having the combinations disclosed in the specification, or the matrix alone, can be used as controls. Alternatively, an untreated sample of the skin mimic can be used as a control.
[0162] Filament production: Changes in filaggrin production in keratinocytes can be measured due to each active ingredient, any combination of ingredients, or a composition having said combinations disclosed in the product specification. Filament is a precursor to natural moisturizing factor (NMF) in the skin. Increased NMF increases skin hydration. The yield of filaggrin in treated and untreated keratinocytes can be determined using a bioassay that measures the concentration of filaggrin in keratinocyte lysates. A non-limiting example of a bioassay that can be used to quantify intermediate filament-associated protein production is the PROTEINSIMPLE® SIMON™ Western blot protocol. For each sample, normal human epidermal keratinocytes (NHEK) were grown in calcium-containing EPI-200–MATTEK EPILIFE® growth medium from Life Technologies (M-EP-500-CA). Prior to treatment, the NHEK were incubated overnight at 37°C in growth medium with 5% CO2. NHEK was then incubated for 24 to 36 hours in growth medium containing 1% of the test compound / extract or without the compound / extract (negative control). The NHEK was then washed, collected, and stored on ice or colder until lysed on ice using lysis buffer and sonication. The protein concentration of the sample could be determined and used for sample standardization. The lysate could be stored at -80°C until used for quantification.
[0163] PROTEINSIMPLE® SIMON™ Protein Blot Bioassay employs quantitative protein blot immunoassay technology, using a polyfilamentin-specific antibody to quantitatively detect polyfilamentin in the test sample. Cell samples are lysed, and protein concentrations are standardized. The standardized sample and molecular weight standards are then loaded onto a denaturing protein separation gel for analysis using capillary electrophoresis. The proteins in the gel are immobilized, and immunoprobe detection is performed using a polyfilamentin-specific primary antibody. Immunoplasmic detection of the immobilized proteins can then be performed using an enzyme-linked immunosorbent assay (ELISA) antibody bound to the primary antibody. A chemiluminescent substrate solution can then be added to the immobilized proteins, ensuring that chemiluminescent development is proportional to the amount of intermediate filament-associated proteins bound in the immobilization. Chemiluminescent development is stopped at a specific time, allowing measurement of the chemiluminescent signal intensity and comparison with positive and negative controls.
[0164] Closure protein production: Changes in closure protein production in keratinocytes can be measured due to each active ingredient, any combination of ingredients, or a composition having said combinations disclosed in the product specification. Closure proteins are proteins essential for the formation of tight junctions and the skin's moisture barrier function. A non-limiting example of how to determine closure protein production in treated and untreated keratinocytes is by using a bioassay to determine the concentration of closure proteins in keratinocyte lysates. Bioanalysis can be performed using the PROTEINSIMPLE® SIMON™ protein blotting protocol. For the sample, adult epidermal keratinocytes (HEKa) from Life Technologies (C-005-5C) can be blotted at EPILIFE. TM EPILIFE was grown in the growth medium at 37°C in 5% CO2 for 24 hours. TM The growth medium was supplemented with calcium (M-EP-500-CA) from Life Technologies and keratinocyte growth supplement (HKGS) (S-101-5) from Life Technologies. HEKa samples were then incubated for 24 to 48 hours in growth medium containing the test compound / extract, growth medium without the compound / extract as a negative control, or growth medium containing 1 mM CaCl2 as a positive control. The HEKa samples were then washed, collected, and stored on ice or colder until lysed on ice using lysis buffer and sonication. The protein concentration of the sample can be determined and used for sample standardization. Lysates were stored at -80°C until used for bioassays.
[0165] PROTEINSIMPLE® SIMON™ Protein Blot Bioassay employs quantitative protein blot immunoassay technology, using antibodies specific to closure proteins to quantitatively detect closure proteins in test samples. Cell samples are lysed, and protein concentrations are standardized. The standardized sample and molecular weight standards are then loaded onto a denaturing protein separation gel and analyzed using capillary electrophoresis. The proteins in the gel are then fixed and detected using an immunoprobe with a primary antibody specific to the closure protein. Immunoplasmic detection is performed on the fixed proteins using an enzyme-linked immunosorbent assay (ELISA) antibody bound to the primary antibody. A chemiluminescent substrate solution is then added to the fixed proteins, ensuring that chemiluminescent development is proportional to the amount of closure protein bound in the fixation. Chemiluminescent development can be stopped at specific times, and the intensity of the chemiluminescent signal can be measured and compared with positive and negative controls.
[0166] Keratinocyte monolayer permeability: Changes in keratinocyte monolayer permeability caused by each active ingredient, any combination of ingredients, or a composition having said combinations, as disclosed in the product information can be measured. Keratinocyte monolayer permeability is a measure of skin barrier integrity. As a non-limiting example, the in vitro vascular permeability assay of MILLIPORE (ECM642) can be used to determine the keratinocyte monolayer permeability in treated and untreated keratinocytes. This assay analyzes the adsorption, transport, and permeability of endothelial cells. Briefly, adult epidermal keratinocytes (C-005-5C) from Life Technologies can be seeded onto a porous collagen-coated membrane within collection wells. The keratinocytes are then subjected to EPILIFE... TM The culture medium was incubated at 37°C in 5% CO2 for 24 hours, containing EPILIFE. TMThe growth medium was supplemented with calcium (M-EP-500-CA) from LIFE TECHNOLOGIES and keratinocyte growth supplement (HKGS) (S-101-5) from LIFE TECHNOLOGIES. This culture time allowed cells to form a monolayer and close the membrane pores. The keratinocytes were then cultured for another 48 hours at 37°C in 5% CO2 after replacing the medium with either fresh medium containing the test compound / extract (test sample) or fresh medium without the test compound / extract (untreated control). To determine the permeability of the keratinocyte monolayer after culture with / without the test compound / extract, the medium was replaced with fresh medium containing high molecular weight fluorescein isothiocyanate (FITC)-glucan, and the keratinocytes were cultured for 4 hours at 37°C in 5% CO2. During the 4-hour incubation, FITC could pass through the keratinocyte monolayer and porous membrane at a rate proportional to the monolayer permeability into the collection wells. After 4 hours of incubation, cell viability and FITC content in the collection wells could be measured. For FITC content, the culture medium in the collection wells was used to measure fluorescence at 480 nm (Em) when excited at 520 nm. Permeability percentage and percentage change compared to the untreated control could be determined by the following equations: Permeability percentage = ((average Ex / Em of test sample) / average Ex / Em of untreated control) * 100; Permeability change percentage = Permeability percentage of test sample – Permeability percentage of untreated control.
[0167] Hyaluronic acid production: Changes in hyaluronic acid production in human skin fibroblasts can be measured by each active ingredient disclosed in the product specification, any combination of ingredients, or a composition having said combinations. HA is a polysaccharide associated with the stability of the matrix structure and is involved in providing turgor pressure to tissues and cells.
[0168] As a non-limiting example, the production of HA in treated and untreated adult dermal fibroblasts (HDFa) can be determined using the R&DSystems Hyaluronic Acid DuoSet ELISA Kit (DY3614). In this assay, to produce samples, sub-convergent HDFa cells (C-13-5C) from Cascade Biologics were cultured for 72 hours at 37°C in 10% CO2 in starvation medium (Dulbecco modified Eagle medium containing 0.15% fetal bovine serum and 1% penicillin-streptomycin solution) prior to treatment. The cells were then incubated for 24 hours with fresh starvation medium containing the test compound, positive controls (phorbol 12-tetradecanoate 13-acetate from SIGMA-ALDRICH and platelet-derived growth factor from SIGMA-ALDRICH (P3201)) or no additives. The medium was then collected and frozen at -80°C until used for the ELISA assay.
[0169] In short, the ELISA assay employs a quantitative sandwich enzyme immunoassay technique, whereby HA-specific capture antibodies are pre-coated onto a microplate. Standards and culture medium from treated and untreated cells are pipetted into the wells of the microplate to allow any present HA to bind to the immobilized antibodies. After washing away any unbound material, HA-specific enzyme-linked detection antibodies are added to the wells. After washing to remove any unbound antibody-enzyme reagent, substrate solution is added to the wells to allow color development proportional to the amount of HA bound in the initial step. Color development is terminated at a specific time, and the color intensity at 450 nm is measured using a microplate reader.
[0170] As another non-limiting example, human skin explants can be cultured in a viable explant medium at 37°C in humid air supplemented with 5% CO2. Explant treatment can be performed by topical application of the sample product (n=3) on days D0, D2, D3, D6, D8, and D9. Control explants (n=3) are treated without any changes except for replacement of the viable explant medium. On days D3, D6, and D8, half the volume of viable medium can be replaced. On D9, three explants from each condition can be removed and cut in half. One half of the explant is fixed in buffered formalin, and the other half is frozen at -80°C.
[0171] After fixation in plain Bouin for 48 hours and in formalin for 24 hours, the samples were dried and immersed in paraffin using an automated tissue processor, Leica TP 1020. Sections of 5 micrometers were prepared using a microtome (LEICA RM2125 Minota) and mounted on SUPERFROST™ histological slides. Microscopic observation was performed using an optical microscope with a LEICA ORTHOPLAN or LEICA DM LB microscope. Images were taken using an OLYMPUS DP72 camera and CELL^D software. General morphology could be examined on paraffin sections stained with Masson's trichrome Goldner variant. Hyaluronic acid staining was performed at room temperature with a 1 / 100 dilution of anti-hyaluronic acid biotinylated protein (HABP) (SEIKAGAKU, catalog number 400763-1A) and a magnification system of biotin / streptavidin (VECTOR, VECTASTAIN PK-7200) for 1 hour.
[0172] Inhibition of hyaluronidase activity: Changes in hyaluronidase activity caused by each active ingredient, any combination of ingredients, or a composition having said combinations, as disclosed in the product specification can be measured. Hyaluronidase is an enzyme that degrades hyaluronic acid. HA is a polysaccharide associated with the stability of the matrix structure and is related to providing turgor pressure for tissues and cells. As a non-limiting example, hyaluronidase activity can be determined using an in vitro protocol modified from SIGMA-ALDRICH protocol #EC 3.2.1.35. Briefly, 1-S type hyaluronidase (H3506) from SIGMA-ALDRICH is added to microplate reaction wells containing the test compound or a control. Tannins can be used as a positive control inhibitor, the control enzyme can be without the test compound, and wells containing the test compound or a positive control but without hyaluronidase can be used as a background negative control. The wells are incubated at 37°C for 10 minutes before adding the substrate (HA). The substrate is added, and the reaction is incubated at 37°C for 45 minutes. A portion of each reaction solution was then transferred to a solution of sodium acetate and acetic acid at pH 3.75 and gently mixed to terminate that portion of the reaction (terminus well). After adding a portion of the reaction solution to the terminus well, both the terminus well and the reaction well should contain the same volume of solution. Both the reaction well and the terminus well were incubated at room temperature for 10 minutes. The absorbance of the reaction well and the terminus well at 600 nm was then measured. Inhibition can be calculated using the following formulas: Inhibitor (or control) activity = (Absorbance of inhibitor terminus well at 600 nm - Absorbance of inhibitor reaction well at 600 nm); Initial activity = Absorbance of control enzyme at 600 nm; Inhibition percentage = [(Initial activity / Inhibitor activity) * 100] - 100.
[0173] Peroxisome proliferator-activated receptor γ (PPAR-γ) activity: Changes in PPAR-γ activity caused by each active ingredient, any combination of ingredients, or a composition having said combinations, as disclosed in the specification can be measured. PPAR-γ is a key receptor for sebum production. As a non-limiting example, PPAR-γ activity can be determined using a bioassay that analyzes the ability of a test compound or composition to inhibit ligand binding. Briefly, the fluorescent small molecule pan-PPAR ligand, FLUORMONE™ Pan-PPAR Green, available from Life Technologies (PV4894), can be used to determine whether a test compound or composition can inhibit the binding of a ligand to PPAR-γ. Sample wells include PPAR-γ and the fluorescent ligand, and: the test compound or composition (test); the reference inhibitor rosiglitazone (positive control); or no test compound (negative control). The wells are incubated for a set time to allow the ligand to bind to PPAR-γ. The fluorescence polarization of each sample well can then be measured and compared with the negative control wells to determine the percentage inhibition by the test compound or composition.
[0174] Cytokine array: Human epidermal keratinocytes were cultured to 70%-80% confluence. The culture medium was aspirated from the plates, and 0.025% trypsin / EDTA was added. When the cells became rounded, the culture dish was gently tapped to release the cells. The trypsin / EDTA containing the cells was removed from the culture dish and neutralized. The cells were centrifuged at 180xg for 5 minutes to form a cell pellet. The supernatant was aspirated. The resulting pellet was resuspended in EPILIFE. TM In Cascade Biologics culture medium. Seed cells at approximately 10% to 20% confluence in 6-well plates. Once cell confluence reaches approximately 80%, aspirate the culture medium and add 1.0 ml of EPILIFE. TM Phorbolol 13-tetradecanoate 12-acetate (“PMA”) (a known inflammatory inducer) and test composition diluent were added to two replicate wells (i.e., 1.0% (100 μL of 100X stock solution) and 0.1% (10 μL of 100X stock solution) of the test composition were diluted to a final volume of 1 ml of EPILIFE. TM (In the growth medium). Gently stir the medium to ensure thorough mixing. Additionally, add 1.0 ml of EPILIFE to the control wells. TM With and without additional PMA. After administration, the culture plates were incubated at 37±1℃ and 5.0%±1% CO2 for approximately 5 hours. After 5 hours of incubation, all culture media were collected in conical tubes and frozen at -70℃.
[0175] For analysis, 16-well hybridization chambers were attached to 16-well fast slides, arranged in triplicate with 16 anti-cytokine antibodies and experimental controls (WHATMAN BIOSCIENCES), and the slides were placed in a FASTFrame (4 slides per frame) for processing. The array was blocked for 15 minutes. 70 ml of S&S protein array blocking buffer (WHATMAN SCHLEICHER AND SCHEULL) was used at room temperature. The blocking buffer was removed, and 70 ml of each supernatant sample was added to each array. The array was incubated with gentle stirring at room temperature for 3 hours. The array was washed three times with TBS-T. The array was then treated with 70 ml of an antibody mixture containing one biotinylated antibody corresponding to the capture antibody for each arrangement. The array was incubated with gentle stirring at room temperature for 1 hour. The array was washed three times with TBS-T. The array was then incubated with 70 ml of a solution containing streptavidin-Cy5 conjugates with gentle stirring at room temperature for 1 hour. The array was washed three times with TBS-T, rapidly rinsed in deionized water, and dried.
[0176] The slides can be imaged using the PERKIN-ELMER SCANARRAY 4000 confocal fluorescence imaging system. Array images can be saved and analyzed using the imaging research software ARRAYVISION. In short, spot intensity is determined by subtracting the background signal. Spotting replicates under each sample condition can be averaged and then compared with appropriate controls.
[0177] Endothelial tube formation: Endothelial tube formation involves angiogenesis and microvascular capillary formation. Capillary formation and angiogenesis can lead to skin redness and rosacea. In the presence or absence of test extracts and compounds, the ability of endothelial cells to form tubes can be determined using a capillary disruption assay, which utilizes pre-formed primary human umbilical vein endothelial cells (HUVECs) in a cell culture system.
[0178] In short, culturing HUVECs in vitro on the extracellular matrix stimulates endothelial cell attachment and tubular morphogenesis, forming capillary-like luminal structures. These in vitro-formed capillaries are similar to human vascular capillaries in many ways. Capillary assays are based on this phenomenon and are used to evaluate potential vascular targets.
[0179] HUVEC cultures were grown in a 5% CO2, 37°C cell culture incubator. The complete growth medium for HUVECs was endothelial cell basal medium (EBM) supplemented with 2% fetal bovine serum (FBS), 12 μg / ml bovine brain extract, 1 μg / ml hydrocortisone, and 1 μg / ml GA-1000 (gentamicin-amphotericidal). HUVEC cultures between passage 3 and passage 8 were used for all assays.
[0180] HUVECs were pre-labeled with the fluorescent agent calcein AM and seeded in 96-well culture plates coated with extracellular matrix containing their complete growth medium. Endothelial capillaries should form approximately four hours after morphogenesis. Then, a 50 µl volume of the designed test reagent was applied as a treatment to the formed capillary culture. An untreated control could be added with a carrier of the test reagent. The FDA-approved anti-angiogenic drug SUTENT was used. ® Its concentration can be used as a performance control for the assay. Approximately six hours after treatment, the morphology of the endothelial tubules in each well is examined under a microscope for imaging, allowing for quantitative analysis of capillary destructive activity under the treatment conditions. Each test condition can be performed in duplicate wells, including controls.
[0181] * * * * * * * * * * * * * *
[0182] Based on this disclosure, all compositions and / or methods disclosed and claimed herein can be manufactured and performed without excessive experimentation. Although the compositions and methods of the invention have been described according to preferred embodiments, it will be apparent to those skilled in the art that changes can be made to the compositions and / or methods described herein, as well as the steps or sequence of steps, without departing from the concept, spirit, and scope of the invention. More specifically, it will be apparent that certain chemically and physiologically relevant reagents can be substituted for the reagents described herein while achieving the same or similar results. All such similar substitutions and modifications that are apparent to those skilled in the art are considered to fall within the spirit, scope, and concept of the invention as defined by the appended claims.
Claims
1. A sunscreen composition comprising at least one high molecular weight acrylate copolymer, ammonium acryloyldimethyl taurate / vinylpyrrolidone copolymer, and at least one ultraviolet filter.
2. The sunscreen composition according to claim 1, wherein the high molecular weight acrylate copolymer comprises an acrylate / C10-30 alkanol acrylate crosspolymer.
3. The sunscreen composition according to claim 1, wherein the ultraviolet filter comprises avobenzone, octocrylene, and / or octyl salicylate.
4. The sunscreen composition according to claim 1, wherein the sunscreen composition does not contain homosalate.
5. The sunscreen composition according to claim 1, wherein the sunscreen composition does not contain vinylpyrrolidone / eicosane copolymer.
6. The sunscreen agent of claim 1, wherein the sunscreen agent does not contain additional emulsifiers.
7. The sunscreen composition of claim 1, wherein the sunscreen composition further comprises cetearyl alcohol.
8. The sunscreen composition according to claim 1, wherein the sunscreen composition comprises 0.01% to 1% by weight of one or more high molecular weight acrylate copolymers.
9. The sunscreen composition of claim 1, wherein the sunscreen composition comprises 0.01% to 1% by weight of ammonium acryloyldimethyltaurate / vinylpyrrolidone copolymer.
10. The sunscreen composition of claim 1, wherein the sunscreen composition comprises 3% to 20% by weight of one or more ultraviolet filters.
11. The sunscreen composition according to claim 1, wherein the sunscreen composition has a sun protection factor greater than 30.
12. The sunscreen composition according to claim 1, wherein the sunscreen composition has a sun protection factor greater than 50.
13. The sunscreen composition according to claim 1, wherein the sunscreen composition has a sun protection factor greater than 30 after exposure to water for 80 minutes.
14. The sunscreen composition of claim 1, wherein the sunscreen composition has a sun protection factor greater than 50 after exposure to water for 80 minutes.
15. The sunscreen composition according to claim 1, wherein the sunscreen composition is a polymer suspension.
16. A method for protecting an individual's skin from ultraviolet radiation, the method comprising applying an effective amount of the sunscreen composition according to claim 1 to the skin.
17. The method of claim 16, wherein the sunscreen composition is applied before the skin is exposed to water.
18. The method of claim 16, wherein the application of the sunscreen agent forms a uniform hydrophobic layer.
19. The method of claim 16, wherein the skin of the individual includes facial skin.
20. The method of claim 19, wherein the sunscreen composition does not contain vinylpyrrolidone / eicosane copolymer.
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