Multiband photoprotective compositions simultaneously targeting ahr and trpv1 antagonism and uses thereof

Abstract

This invention discloses a multi-band photoprotective composition that simultaneously targets AHR and TRPV1 antagonism and its applications, relating to the cosmetics field. The composition comprises an aqueous phase (A), an oil phase (B), a phase (C), and a phase (D), containing a compounded broad-spectrum sunscreen agent, an AHR antagonistic system composed of saffron extract, 7-dehydrocholesterol, and 5-hydroxyflavone, and a TRPV1 antagonistic system composed of palmitamide MEA and 4-tert-butylcyclohexanol. This composition not only effectively protects against ultraviolet, blue, and near-infrared light, but also inhibits photopollutation-induced AHR pathway activation at its source and soothes TRPV1-mediated skin nerve sensitivity, achieving multi-layered photoprotection. It is suitable for skincare products that improve skin photosensitivity and photodamage.

Description

Technical Field

[0001] This invention relates to the field of cosmetic technology, specifically to a multi-band photoprotective composition that simultaneously targets the antagonism of AHR and TRPV1 and its application. Background Technology

[0002] Sunscreen and photoprotection are crucial for skin health. Over the past 30 years, sunscreen technology has advanced rapidly. Consumers are increasingly aware of the importance of sun protection, and research into the biological mechanisms by which different wavelengths of light affect the skin has deepened. The development of innovative technologies and product applications continues unabated.

[0003] In recent years, with the advancement of scientific research, full-spectrum photoprotection has become the mainstream approach in the development of sunscreen products. In general, the biological mechanism of full-spectrum protection lies in: UVB, with a wavelength of 290-320nm, can penetrate the stratum corneum to reach the epidermis but cannot reach the dermis. UVB damage to the skin includes the generation of free radicals, causing DNA damage to epidermal keratinocytes, which can lead to sunburn and redness in a short time. UVB attacks DNA, producing DNA structural mutation products such as CPDs (cyclobutylpyrimidine dimers) and 6-4PP (6-4 photoproducts). UVB also induces epidermal cells to release various cytokines, resulting in an inflammatory response.

[0004] UVA, with a wavelength of 320-400nm, can penetrate most of the epidermis to reach the dermis. UVA damage to the skin is mainly manifested in skin darkening, dermal damage, and photoimmunosuppression. UVA induces fibroblasts to produce free radicals and matrix metalloproteinases (MMP-1), which degrade the dermal ECM, causing signs of photoaging.

[0005] Blue light, or visible light, has a wavelength of 400-500nm. Blue light around 460nm can regulate melatonin secretion through the sensing of opsin 3, participating in the circadian rhythm. Prolonged exposure to high doses of blue light can also induce free radicals, causing oxidative stress and resulting in long-lasting dullness of the skin.

[0006] Red light, with a wavelength of 620-1000nm, is near-red IRA. IRA induces a large amount of free radicals to be generated in mitochondria and upregulates MMPs and downregulates COL1A1, degrading collagen, reducing collagen renewal, and accelerating photoaging. Simultaneously, the transient receptor potential channel TRPV1 is also a major target for defending against photoaging and infrared-induced barrier damage. A specific number of TRPV1 cells exist in the cell membrane of normal skin, and calcium ion mobility is regulated by TRPV1. This invention finds that existing technologies do not consider the importance of product regulation of TRPV1. In sensitive skin, due to the fragile barrier, it is more easily affected by external heat stimulation and osmotic pressure stimulation, activating more TRPV1 nerve receptors. Calcium flux increases due to loss of regulation, causing the skin to be in a state of neuroreactivity, resulting in skin irritation and inflammation. For people with sensitive skin, the "Chinese Expert Consensus on the Diagnosis and Treatment of Sensitive Skin" already provides recommendations, which is to follow the twelve-character principle: gentle cleansing, soothing moisturizing, and strict sun protection. Environmental factors, including air temperature and humidity, seasonal changes, and ultraviolet radiation intensity, are the main triggers for skin sensitivity.

[0007] Meanwhile, sunscreen products also address skin problems caused by urban pollution and solar radiation. CN114557940A discloses an anti-pollution sunscreen skincare composition, whose components include extracellular polysaccharides, thiotaurine, aloe vera extract, scutellaria baicalensis extract, and polyols. The product's anti-pollution effect is explained by verifying skin inflammation and spots caused by environmental pollution. However, it does not fundamentally verify the product's targeting of skin problems caused by pollution mechanisms. This is because ultraviolet radiation, combined with pollution particles, activates the AhR receptor channel on skin cells. Specifically, tryptophan undergoes UVB photosynthesis to produce FICZ, which binds to the aryl hydrocarbon receptor AhR, thereby promoting downstream gene expression, increasing MMPs, immunosuppression, oxidative stress, and thus leading to inflammatory aging, collagen degradation, pigment synthesis, and even skin cancer. Literature reports that active metabolites of vitamin D3 (such as 1,25(OH)2D3) can contribute to aging (Georgeta Bocheva et al., DOI:10.3390 / ijms22169097). Therefore, products need to be designed to competitively inhibit the binding of pollutant particles to AHR receptors in order to effectively regulate the target of ultraviolet radiation and pollutant particles, and solve skin problems caused by pollution through products.

[0008] Based on the complex mechanisms of multi-band photodamage and the synergistic effects of pollution, the concept of "Penta-antagonist (Pentagonist) five-fold antagonistic photoprotection technology" emerged. This technology aims to transcend traditional single-UV protection by simultaneously targeting and antagonizing five key photodamage pathways, achieving full-spectrum, multi-dimensional skin defense. These "five antagonisms" specifically include: 1) antagonism against UVB-induced sunburn and DNA damage; 2) antagonism against UVA-induced photoaging and pigmentation; 3) antagonism against blue light-induced oxidative stress and pigmentation disorders; 4) antagonism against inflammation and barrier damage caused by near-infrared light (red light) and heat stimulation through activation of the TRPV1 channel; and 5) antagonism against the chain reaction of inflammatory aging caused by environmental pollutants activating AhR receptors. Most existing sunscreens only cover the first two or three layers of protection, lacking a systematic intervention plan for TRPV1-mediated heat damage and AhR-mediated pollution damage.

[0009] Therefore, guided by the technical concept of "Penta-antagonist (Pentagonist)," this invention aims to provide an innovative composition that not only possesses broad-spectrum physical light shielding capabilities but also integrates active ingredients that can specifically antagonize TRPV1 and AHR receptors, thereby truly achieving a leap from "ultraviolet protection" to "full-spectrum and multi-dimensional protection against environmental damage." Summary of the Invention

[0010] To address the shortcomings of existing technologies, this invention provides a multi-band photoprotective composition that simultaneously targets AHR and TRPV1 antagonism and its application. The aim is to provide broad-spectrum physical photoprotection through specific component combinations and phase separation processes, and to inhibit pollution-induced AHR pathway activation and antagonize the neurosensitive TRPV1 channel at the molecular biological level. This provides comprehensive protection against ultraviolet, blue, and near-infrared light, alleviates skin damage caused by light pollution, and improves skin photosensitivity.

[0011] To achieve the above objectives, the present invention is implemented through the following technical solution: a multi-band light protection composition that simultaneously targets the antagonism of AHR and TRPV1, characterized in that: the composition is composed of phase A, phase B, phase C and phase D, wherein: phase A is an aqueous phase; phase B is an oil phase; phase C contains water and a water-dispersible sunscreen agent; and phase D contains powder and a powder dispersion component.

[0012] Preferably, by mass percentage, phase A comprises: water, 1-2% phenylbenzimidazole sulfonic acid, 1.5-3% disodium phenyldibenzimidazole tetrasulfonate, 0.2-2.0% carnosine, 2% glycerol, and 2% a stabilizer mixture composed of hydroxyethyl acrylate / sodium acryloyldimethyl taurate copolymer, polysorbate-60, and sorbitan isostearate. Preferably, phase A further comprises 0.5% 1,2-hexanediol, 0.5% p-hydroxyacetophenone, 2.0% 1,2-pentanediol, and 2.2% arginine.

[0013] Preferably, by mass percentage, phase B comprises: 2-5% ethylhexyl triazine, 3-6% isoamyl p-methoxycinnamate, 1-3% hexyl diethylaminohydroxybenzoylbenzoate, 2-4% bis-ethylhexyloxyphenol methoxyphenyl triazine, 0.1-5.0% saffron flower extract, 0.01-0.1% 7-dehydrocholesterol, 0.1-1.0% palmitamide MEA, and 3.0% a mixture of C20-22 phosphate and C20-22 alcohol, 3.0% dibutyl adipate, 2.0% cetearyl alcohol, 0.5% behenol, and 0.05% tocopherol.

[0014] Preferably, phase B further comprises 0.075% 4-tert-butylcyclohexanol and 4.0% C9-12 alkyl.

[0015] Preferably, the mass ratio of saffron flower extract to 7-dehydrocholesterol in phase B is 10-100:1, and the mass ratio of palmitamide MEA to 4-tert-butylcyclohexanol is 2-4:1.

[0016] Preferably, the C phase comprises 5.0% water and 2-4% methylenebis-benzotriazolyltetramethylbutylphenol by mass percentage.

[0017] Preferably, the D phase comprises, by mass percentage, 0.01-1.0% 5-hydroxyflavone, 2.0% corn starch and 1.5% silica.

[0018] This invention also discloses a method for preparing a multi-band photoprotective composition that simultaneously targets AHR and TRPV1 antagonism, comprising the following steps: Preparation of phase A: Water is heated, phenylbenzimidazole sulfonic acid is dissolved in part of the water and neutralized with an alkaline substance, the remaining components of phase A are added, and the mixture is heated and stirred to dissolve, resulting in a homogeneous aqueous phase; (2) Preparation of phase B: Mix all oil-soluble components of phase B and heat to melt evenly to obtain the oil phase; (3) Emulsification: Under stirring or homogenization conditions, the oil phase is added to the aqueous phase for emulsification to form an emulsion matrix; (4) Adding phase C and phase D: Add the pre-dispersed phase C to the emulsion matrix, homogenize it, cool it down and add phase D, and stir until homogeneous to obtain the final product.

[0019] A cosmetic product comprising a multi-band photoprotective composition that simultaneously targets AHR and TRPV1 antagonism.

[0020] Application of a multi-band photoprotective composition that simultaneously targets AHR and TRPV1 antagonism in the preparation of skin care products for protecting against ultraviolet light, blue light, near-infrared light, alleviating skin damage caused by light pollution, and improving skin photosensitivity.

[0021] This invention provides a multi-band optical protection composition that simultaneously targets AHR and TRPV1 antagonism and its application. Compared with the prior art, it has the following advantages: This composition, by combining multiple sunscreen agents, achieves broad-spectrum and highly effective physical protection against UVB, UVA, blue light, and near-infrared light.

[0022] This composition, by adding ingredients such as saffron extract, vitamin D3 precursor and 5-hydroxyflavone, can competitively inhibit pollutants from activating AhR receptors, thereby reducing inflammatory aging and pigmentation caused by light pollution at its source.

[0023] This composition, by containing palmitamide MEA and 4-tert-butylcyclohexanol, effectively antagonizes TRPV1 receptors and reduces calcium ion influx, thereby soothing skin nerve hyperresponsiveness and is especially suitable for photoprotection of sensitive skin.

[0024] (4) This composition combines physical protection with biological targeted intervention, providing a multi-level, multi-mechanism light protection solution with more comprehensive and in-depth effects. Attached Figure Description

[0025] Figure 1 This is a schematic diagram illustrating the prediction of the minimum amount of blue light blackening in a subject according to the present invention. Figure 2 A schematic diagram showing the blue light irradiation of the test area and control skin area in this invention; Figure 3 This is a schematic diagram of the test product and negative control of the present invention; Figure 4 This is a schematic diagram of the test product and negative control of the present invention; Figure 5 These are three schematic diagrams showing the test product and negative control of this invention; Figure 6 This is a schematic diagram showing the skin area division and pigmentation comparison for the blue light protection efficacy test of this invention. Figure 7This is a comparative diagram showing the effect of capsaicin-induced intracellular calcium ion fluorescence intensity on HaCaT cells according to the present invention. Figure 8 This is a schematic diagram of the SPF value calculation formula of the present invention; Figure 9 This is a schematic diagram illustrating the differences in skin brightness index (CIE-L*) between the comparative test product and the negative control of this invention; Figure 10 This is a schematic diagram illustrating the differences in skin ITA° index between the comparative test product and the negative control of this invention; Figure 11 This is a schematic diagram illustrating the differences in skin melanin index between the comparative test product and the negative control of this invention; Figure 12 This is a schematic diagram of the AHR docking test (AhR domain / binding pocket diagram) of the experimental product of this invention; Figure 13 This is a schematic diagram of the molecular docking results of the AHR docking test of the experimental product of this invention. Detailed Implementation

[0026] The technical solutions in the embodiments of the present invention have been clearly and completely described. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0027] Example 1: Preparation of a multi-band light protection composition (sunscreen) A multi-band photoprotective composition that simultaneously targets AHR and TRPV1 antagonism has the specific formulation shown in the table below: Phase A water Add to 100 Phenylenoidimidazolium sulfonic acid 1.5 Sodium phenyl dibenzimidazole tetrasulfonate 2.0 Hydroxyethyl acrylate / sodium acryloyldimethyl taurate copolymer, polysorbate-60, sorbitan isostearate (mixture) 1.8 glycerin 2.0 1,2-Hexanediol 0.5 p-Hydroxyacetophenone 0.5 1,2-Pentanediol 2.0 Carnosine 0.5 Arginine 2.2 Phase B C20-22 alcohol phosphates, C20-22 alcohols (mixtures) 3.0 Ethylhexyltriazine 3.0 Dibutyl adipic acid 3.0 Diethylaminohydroxybenzoyl benzoate 2.0 bis-ethylhexyloxyphenol methoxyphenyl triazine 3.0 Isoamyl p-methoxycinnamate 4.0 Cetearyl alcohol 2.0 Betaine alcohol 0.5 Palmitamide MEA 0.3 4-tert-butylcyclohexanol 0.075 Tocopherol (Vitamin E) 0.05 Saffron (Crocus sativus) flower extract 2.0 7-Dehydrocholesterol 0.05 C9-12 alkyl 4.0 C phase water 5.0 Methylenebis-benzotriazolyltetramethylbutylphenol 3.0 D phase Corn (ZEA MAYS) starch 2.0 silica 1.5 5-hydroxyflavone 0.1 Based on the technical solution disclosed in this invention, the composition of each phase in the composition can be adjusted within a wide range without departing from the core concept of simultaneously targeting AHR and TRPV1 to provide multi-band optical protection.

[0028] Specifically, the types and contents of the functional components in phase A, which serve as moisturizers, preservatives, and pH adjusters, can be adapted to the product formulation (e.g., lotion, cream, gel) and skin feel requirements. For example, glycerin can be replaced or compounded with other polyols (e.g., propylene glycol, butylene glycol, dipropylene glycol, polyethylene glycol, etc.) in equal or similar amounts; the specific component ratio of the preservative and moisturizing system composed of 1,2-hexanediol, 1,2-pentanediol, and p-hydroxyacetophenone can be optimized while ensuring the safety and stability of the system, or partially replaced with other cosmetically acceptable, highly effective, and mild preservatives (e.g., caprylyl glycol, ethylhexylglycerin, etc.); arginine can also be replaced with other basic amino acids (e.g., lysine, histidine) or inorganic bases (e.g., sodium hydroxide, potassium hydroxide) to achieve effective neutralization of phenylbenzimidazole sulfonic acid and precise pH adjustment of the system.

[0029] Similarly, non-core functional components in phases B, C, and D (such as emollient esters, thickeners, stabilizers, and skin-feeling powders) can be replaced with equivalent components. For example, dibutyl adipic acid can be replaced with other light synthetic esters or plant-derived oils; corn starch and silica can be adjusted in proportion or replaced with other inorganic powders (such as mica or boron nitride) or organic powders (such as nylon powder or polymethyl methacrylate powder) according to different requirements for product texture (matte, soft-focus, oil-absorbing).

[0030] The substitution, addition, reduction, and proportion adjustment of the above-mentioned components, as long as they do not impair the overall stability of the composition, its sun protection efficacy, or its synergistic antagonistic effect on the AHR and TRPV1 targets, shall be considered to be within the scope of the technical concept of this invention.

[0031] Detailed preparation process This process is carried out in a stirred tank equipped with a homogenizer and precise temperature control, and all operations must comply with Good Manufacturing Practices (GMP) for cosmetics.

[0032] Preparation of phase A (aqueous phase): Add approximately 80% of the total water volume of deionized water to the main emulsification vessel, heat to 80±2℃, and keep warm.

[0033] In another container, add the remaining water (approximately 5% of the total volume) and heat to 50±2℃. Slowly add phenylbenzimidazole sulfonic acid and stir until completely dissolved.

[0034] While stirring, slowly add arginine to the above solution to neutralize it until the solution becomes clear and transparent, with a pH of approximately 7.0-7.5. This step is crucial to ensure that the sunscreen agent is stable and non-irritating.

[0035] The neutralized solution, disodium phenyl dibenzimidazole tetrasulfonate, and all other components of phase A (glycerol, 1,2-hexanediol, p-hydroxyacetophenone, 1,2-pentanediol, carnosine, hydroxyethyl acrylate / sodium acryloyl dimethyl taurate copolymer, polysorbate-60, sorbitan isostearate) were sequentially added to the 80°C hot water in the main emulsifying vessel.

[0036] Continue stirring at a medium speed (approximately 300-500 rpm) until all solids are completely dissolved and the system is homogeneous and transparent. Maintain the temperature at 80±2℃ and set aside.

[0037] Preparation of phase B (oil phase): In another oil phase pot, accurately weigh out and add C20-22 alcohol phosphate, C20-22 alcohol, cetearyl alcohol, behenol, ethylhexyl triazine, dibutyl adipate, hexyl diethylamino hydroxybenzoyl benzoate, bis-ethylhexyloxyphenol methoxyphenyl triazine, isoamyl p-methoxycinnamate, tocopherol acetate, and C9-12 alkyl in sequence.

[0038] Heat to 85±2℃ and stir at a moderate speed (about 200-400 rpm) at this temperature until all solid components are completely melted and the system is a homogeneous, transparent oily liquid.

[0039] Adjust the temperature of the oil phase reactor to 80±2℃, consistent with the temperature of phase A. While stirring, add palmitamide MEA, 4-tert-butylcyclohexanol, saffron flower extract, and 7-dehydrocholesterol to the oil phase, and stir until evenly dispersed. Note that adding the active ingredients later can prevent inactivation due to prolonged high temperatures.

[0040] Emulsification and Main Matrix Formation: Start the homogenizer in the main emulsification vessel (speed approximately 2000-3000 rpm). Under homogenization conditions, slowly and uniformly add phase B (oil phase) with the adjusted temperature to phase A (aqueous phase) through a filter screen.

[0041] After all phase B is added, continue homogenization at 80±2℃ for 10-15 minutes until a uniform, fine, and stable O / W (oil-in-water) emulsion matrix is ​​formed.

[0042] Stop homogenizing, switch to anchor or scraper stirring, and begin slow cooling (cooling rate approximately 1-2℃ / minute).

[0043] C phase addition: Methylenebis-benzotriazolyltetramethylbutylphenol (Tinosorb® M) was pre-dispersed with 5.0% deionized water (C phase water) in a disperser at high speed to form a uniform slurry.

[0044] When the emulsion temperature in the main reactor drops to 60±2℃, add the pre-dispersed C-phase slurry while stirring (about 300-500 rpm).

[0045] After adding the ingredients, restart the homogenizer (1500-2000 rpm) and homogenize for 5-10 minutes to ensure that the poorly soluble sunscreen agent is evenly dispersed throughout the system without any grainy texture.

[0046] Once homogenization is complete, resume stirring and continue cooling.

[0047] D-phase addition and final treatment: When the system temperature drops to 40±2℃, slowly sieve in corn starch and silica in sequence. Turn on the homogenizer for short-term homogenization (about 1000-1500 rpm, 1-2 minutes) to break up any possible lumps, then switch to stirring to ensure that the powder is completely dispersed and wetted.

[0048] Finally, add the ultrafine powdered or cyclodextrin-coated 5-hydroxyflavone powder, and stir at low speed (about 100-200 rpm) for 20-30 minutes until it is completely and evenly dispersed, and the system is smooth, uniform, free of bubbles and lumps.

[0049] Samples were taken for testing of pH value, heat and cold resistance stability, and sensory indicators. After passing the tests, the material was discharged, allowed to stand to defoam, and then ready for filling.

[0050] Key Points of Formula Design The sun protection system employs a composite system consisting of a water-soluble UVA absorber (disodium phenyl dibenzimidazole tetrasulfonate), an oil-soluble UVB / UVA absorber (ethylhexyl triazine, isoamyl p-methoxycinnamate, etc.), a broad-spectrum oil-soluble absorber (bis-ethylhexyloxyphenol methoxyphenyl triazine), and a broad-spectrum water-dispersible absorber (methylene bis-benzotriazolyl tetramethylbutylphenol). This system, through the combination of sunscreens with different solubilities and action spectra, achieves broad-spectrum, high SPF and PA protection from UVB to UVA, extending to parts of the visible / infrared light region, while reducing the amount of a single sunscreen agent required and improving safety.

[0051] The AHR targeted antagonistic system employs a synergistic combination of saffron extract (rich in crocin and crocinic acid) + vitamin D3 precursor (7-dehydrocholesterol) + 5-hydroxyflavone. The saffron extract and 7-dehydrocholesterol are combined in a specific ratio (40:1 in this example) to mimic the effects of vitamin D active metabolites reported in the literature. By competitively binding to AHR at multiple targets or interfering with its dimerization with ARNT, it blocks the upstream activation of the AHR pathway induced by pollutant particles / UV. 5-hydroxyflavone, as a potent antioxidant and a reported AHR modulator, is added later in the formulation to protect its activity and as a supplement.

[0052] TRPV1 Targeted Antagonistic System: Employs the classic soothing combination of "palmitamide MEA + 4-tert-butylcyclohexanol". The two work synergistically in a specific ratio (4:1 in this example) to effectively inhibit the activation of TRPV1 receptors by stimuli such as heat and osmotic pressure, reducing calcium ion influx. This provides immediate relief from burning and stinging sensations and offers long-term benefits for skin barrier repair and reduced nerve sensitivity, making it especially suitable for sensitive skin sun protection.

[0053] Supporting active ingredients: Carnosine is added to combat oxidative and glycation damage during photoaging; the antioxidant tocopheryl acetate is added to protect oils and active ingredients.

[0054] Skin feel and stability system: C9-12 alkyl provides a refreshing, non-greasy volatile skin feel; the combination of corn starch and silica effectively absorbs excess oil, increases the smoothness and matte finish of the formula, and helps enhance the stability of the sunscreen film. A precise phase separation process (A / B / C / D phases) ensures that various chemically different components can coexist stably within a single system.

[0055] Test Example 1: UV protection efficacy of photoprotective compositions (Sunscreen SPF standard test) The SPF value of the sunscreen prepared in Example 1 was determined according to the human body method specified in the Chinese Cosmetic Safety Technical Specifications (2015 edition).

[0056] Materials and methods The sample tested was the sunscreen prepared in Example 1.

[0057] 1. Test substance: Prepared according to Example 1.

[0058] 2. Reference standard: SPF standard reference standard (prepared according to the standard formula in Appendix P2 of the "Cosmetic Safety Technical Specifications" (2015 edition), with a labeled SPF value of 16.1±2.4.

[0059] 3. Subjects: A total of 3 female subjects, aged 31 to 37 years, with a mean age of 34.3 ± 3.1 years, all with skin type III, and meeting the subject voluntary inclusion criteria.

[0060] 4. Light source: Xenon arc lamp from a daylight simulator, with all performance indicators meeting the requirements of the testing specifications.

[0061] 5. Test Method: The test shall be conducted in accordance with the specific requirements of the currently effective technical specifications. The subject shall be in a forward-leaning position, and their back shall be irradiated. The minimum erythema dose (MED) of the subject's skin to ultraviolet radiation shall be predicted 24 hours prior to the test, and the ultraviolet radiation dose shall be adjusted according to the prediction result for testing the analyte. On the day of the test, a normal skin area of ​​not less than 30 cm² shall be selected on the subject's back. The analyte or control shall be evenly applied to this area at a dosage of (2.00 ± 0.05) mg / cm². Then, the irradiation dose shall be selected according to the specifications, and irradiation shall be carried out under three conditions: ① no analyte applied to the subject's skin; ② control applied; ③ analyte applied. The experimental results shall be observed 24 hours later, and the MED values ​​under each of the three conditions shall be recorded.

[0062] 6. SPF Calculation Method: The SPF value of the analyte or control for protecting a single subject is expressed by the following formula: Figure 8 As shown.

[0063] Individual SPF values ​​must be accurate to one decimal place. Calculate the arithmetic mean of the SPF values ​​of all subjects tested, and take the integer part as the SPF value of that sample. The sampling error of estimating the mean can be calculated by calculating the standard deviation and standard error of the data set.

[0064] II. Test Results SPF value determination results of reference standard and analyte

[0065]

[0066] Conclusion: Based on the results of human testing, the SPF value of the sunscreen sample prepared in Example 1 is 69.

[0067] Test Example 2: Skin Blue Light Protection Efficacy Test of Photoprotective Composition I. Testing Methods According to the "Evaluation Standard for Blue Light Protection Efficacy of Human Skin" (T / CAPA 13-2024), test and control areas were pre-marked on the backs of the subjects. A skin analyzer was used to measure the melanin index (M), lightness index (L), and individual skin type angle (ITA°) values ​​of each area at baseline (see diagram of area division). Figure 1 ).

[0068] 2. Predicting the minimum blue light induced pigment darkening dose (MPD-BL): Two hours before the test, six points on the test site were irradiated with different doses of blue light. Two hours after irradiation, the lowest irradiation dose at which dark spots appeared was observed to determine the MPD-BL. Subsequent blue light irradiation doses were set at 0.75 times the MPD-BL.

[0069] 3. Sample dosage and coating method: Weigh the sample (Example 1) at a dosage of (2.00±0.05) mg / cm2. Use a latex finger cot to evenly coat the sample onto the test area and wait 15-30 minutes. The coated area should be no less than 2 cm2.

[0070] 4. Blue light irradiation and continuous protection: Blue light irradiation was applied to the test area and control skin area for 4 consecutive days. After the irradiation was completed, the test sample was applied again.

[0071] 5. Index Measurement: Before applying the product daily, subjects were tested for melanin index (M), lightness index (L), and skin type angle (ITA°) for 5 consecutive days. Comparisons were made using Antera 3D imaging (e.g., ...). Figure 2 (As shown).

[0072] II. Test Results 1. At baseline, there were no significant differences in skin parameters (M, L, ITA°) between the test and control areas.

[0073] 2. Product intervention stage: 2.1 Comparison of the test product and the negative control (blank control, without any treatment, such as...) Figure 3 As shown), the differences in skin brightness index (CIE-L*) (e.g.) Figure 9 (as shown) 2.2 Comparison of test product and negative control (blank control, without any treatment, such as...) Figure 4 As shown), the differences in skin ITA° index (e.g.) Figure 10 (as shown) 2.3 Comparison of test product and negative control (blank control, without any treatment, such as...) Figure 5 As shown), the differences in skin melanin indicators (such as...) Figure 11 (as shown) 2.4 Use the Antera 3D Skin Imaging Analyzer to photograph the treated areas on the back. Observe the pigmentation of the treated and control areas after blue light irradiation in color and pigmentation modes (e.g., Figure 6 (As shown).

[0074] Test Example 3: Targeted molecular docking of the Pentagonist active component to the aryl hydrocarbon receptor (AHR) Testing Methods: Based on computational biology-based molecular docking methods, modeling was performed to evaluate the binding energy between the active component of the multi-band photoprotective composition Pentagonist and the aromatic hydrocarbon receptor (AHR). The inhibitory effect of the component on AhR was assessed by analyzing the binding energy scores and the binding mode between the component and the protein (see reference: Molecular Docking of Natural Compounds for Potential Inhibition of AhR). (https: / / doi.org / 10.3390 / foods12101953), thereby assessing the blocking intervention of components on pollutant receptors.

[0075] The literature mentions that a key step in the classic AhR activation process is the formation of a heterodimer between AhR and ARNT. In exploring the potential AhR inhibitory activity of specific natural components, an AhR model incorporating bHLH, PAS A, and PAS B domains was constructed. Furthermore, blind docking and focused docking simulations revealed the existence of other binding pockets (Pocket ADs) besides the known classic binding pocket in the PAS B domain. These binding pockets are crucial for AhR inhibition, preventing the formation of a heterodimer between AhR and ARNT: firstly, by preventing conformational changes in AhR, and secondly, by masking key sites required for protein-protein interactions (such as...). Figure 12 (As shown).

[0076] 1.1 Name of the molecular docking calculation software AutoDock Vina 1.1.2 1.2 Dock Box Parameters The relevant parameters are set as follows: center_x=30.175, center_y=-4.537, center_z =-25.979; search space: size_x=100, size_y=100, size_z=100, exhaustiveness = 100, and the remaining parameters are set to default.

[0077] 1.3 Protein processing methods Pymol 2.3.0 was used to remove the protein's water of crystallization and original ligands. The protein structure was then imported into AutoDocktools (v1.5.6) for hydrogenation, charge calculation, charge assignment, atom type specification, and saved as a "pdbqt" file.

[0078] 1.4 Small molecule treatment methods Small molecules were modeled using GaussView, and their structures were then optimized using the M062X / LAN2LDZ method in Gaussian 16 software. The optimized small molecules were then imported into AutodockTools-1.5.6 for hydrogenation, charge calculation, charge distribution, and setting of rotatable bonds before being saved as "pdbqt" format.

[0079] 1.5 Results Analysis: The interaction modes of the docking results were analyzed using PyMol 2.3.0.

[0080] 1.6 Molecular docking results (e.g.) Figure 13 (As shown) The results show that crocin, crocin, crocinin, crocinaldehyde, stigma-hydroxyflavone, and vitamin D3 are all potential candidates, with varying degrees of potential. Crocinin exhibits an ideal binding energy of -11.9. Crocinin and vitamin D3 show high selectivity for pocket D, which is responsible for inhibiting the heterodimerization of AhR with ARNT. Crocinin also directly interacts with three residues (ASN-95, LYS-244, GLN-240) that actively bind ARNT, and its presence undoubtedly creates steric hindrance for ARNT binding.

[0081] Test Example 4: Study on the inhibitory effect of active ingredients on TRPV1 channel activation.

[0082] Effects of capsaicin on intracellular Ca2+ flux 4.1 HACAT cells (human immortalized epidermal cells) were purchased from Shanghai Fuheng Biotechnology Co., Ltd.

[0083] 4.2 Cell Culture Related Reagents DMEM medium (Gibco, 11966025); fetal bovine serum (FBS) (Gibco, 16140071); penicillin-streptomycin Pyrimethamine PS (gibco, 15140122); Hank's balanced salt solution (HBSS) (Adamas Life, C8025); Trypsin EDTA (0.05%) (gibco, 25300062); Fluo-4, AM fluorescent probe (Yeasen, HB220823) 4.3 Experimental Drugs Blank control, capsaicin (1 μM), sample group (palmitamide MEA 0.1%, 4-tert-butylcyclohexanol 0.025%) 4.4 Experimental Methods 1. Resuscitate HACAT cells in DMEM medium containing 10% fetal bovine serum and 1% PS by water bath at 37°C.

[0084] 2. Collect cells in the exponential growth phase, count them, and seed HACAT cells in 6 wells at a ratio of 1E6 / well and 2ml / well. In the middle of the board; 3. After culturing for 24 hours, the samples to be tested were added and processed. The sample concentration and fluorescent probe concentration are shown in the table below. Capsaicin 1uM, 2uM Fluo-4, AM 2uM, 5uM 4. Remove the culture medium and wash three times with PBS; 5. Add the prepared capsaicin and incubate at 37°C for 24 hours; 6. Remove the culture medium and wash three times with HBSS; 7. Add the prepared Fluo-4, AM fluorescent probe and incubate at 37°C for 40 min; 8. Remove the culture medium, wash 3 times with HBSS, add 1 ml / well of HBSS, and observe under a fluorescence microscope.

[0085] 4.5. Experimental Results To investigate whether capsaicin can inhibit calcium influx, we first used Fluo-4 AM ester as a fluorescent indicator of Ca2+ to measure the accumulation of [Ca2+] cells in HaCaT cells. The results showed that capsaicin significantly increased the accumulation of [Ca2+] cyt (e.g., ...). Figure 7 (As shown). Next, a 1 μM capsaicin concentration was selected to induce calcium influx into HaCaT cells. The inhibitory effect of PEA&1609 on TRPV1 channels was investigated by assessing changes in intracellular free Ca2+ concentration. Fluo-4 AM ester was used as a fluorophore to observe Ca2+ accumulation in HaCaT cells. Compared with the control group (Fig. a), the fluorescence intensity of capsaicin-treated cells was significantly enhanced (Fig. b). In contrast, the green fluorescence was weakened after the product was added (Fig. c). Further quantitative analysis of fluorescence intensity folding revealed that the fluorescence intensity of capsaicin was 90.74% higher than that of the blank group, indicating that capsaicin can significantly promote Ca2+ accumulation (***p<0.001). After the product was added, the fluorescence intensity decreased by 16.38% compared with cells treated with capsaicin alone, indicating that the product significantly reduced Ca2+ accumulation (p<0.001).

[0086] It should be noted that, in this document, relational terms such as "first" and "second" are used only to distinguish one entity or operation from another, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Furthermore, the terms "comprising," "including," or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such process, method, article, or apparatus.

[0087] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. A multi-band photoprotective composition that simultaneously targets AHR and TRPV1 antagonism, characterized in that: The composition comprises phase A, phase B, phase C, and phase D, wherein: Phase A is an aqueous phase; Phase B is an oil phase; Phase C contains water and a water-dispersible sunscreen agent; The D phase comprises powder and powder dispersion components.

2. The multi-band optical protection composition that simultaneously targets AHR and TRPV1 antagonism according to claim 1, characterized in that: By mass percentage, phase A comprises: water, 1-2% phenylbenzimidazole sulfonic acid, 1.5-3% disodium phenyl dibenzimidazole tetrasulfonate, 0.2-2.0% carnosine, 1-10% glycerol, and 0.5-1.8% a stabilizer mixture consisting of hydroxyethyl acrylate / sodium acryloyl dimethyl taurate copolymer, polysorbate-60, and sorbitan isostearate.

3. The multi-band optical protection composition that simultaneously targets AHR and TRPV1 antagonism according to claim 2, characterized in that: Phase A further comprises 0.5-2.0% of 1,2-hexanediol, 0.5-1.0% of p-hydroxyacetophenone, 0.5-2.0% of 1,2-pentanediol and 0.5-2.5% of arginine.

4. The multi-band optical protection composition that simultaneously targets AHR and TRPV1 antagonism according to claim 1, characterized in that: By mass percentage, phase B comprises: 2-5% ethylhexyl triazine, 3-6% isoamyl p-methoxycinnamate, 1-3% hexyl diethylamino hydroxybenzoyl benzoate, 2-4% bis-ethylhexyloxyphenol methoxyphenyl triazine, 0.1-5.0% saffron flower extract, 0.01-0.1% 7-dehydrocholesterol, 0.1-1.0% palmitamide MEA, and 1.0-3.0% a mixture of C20-22 phosphate and C20-22 alcohol, 1.0-3.0% dibutyl adipate, 1.0-2.0% cetearyl alcohol, 0.5-2.0% behenol, and 0.05-1.0% tocopherol.

5. The multi-band photoprotective composition that simultaneously targets AHR and TRPV1 antagonism according to claim 4, characterized in that: Phase B also contains 0.05-0.075% of 4-tert-butylcyclohexanol and 4.0-8.0% of C9-12 alkyl groups.

6. The multi-band optical protection composition that simultaneously targets AHR and TRPV1 antagonism according to claim 5, characterized in that: In phase B, the mass ratio of saffron flower extract to 7-dehydrocholesterol is 10-100:1, and the mass ratio of palmitamide MEA to 4-tert-butylcyclohexanol is 2-4:

1.

7. The multi-band optical protection composition that simultaneously targets AHR and TRPV1 antagonism according to claim 1, characterized in that: The C phase comprises 1.0-10.0% water and 2-4% methylenebis-benzotriazolyltetramethylbutylphenol by mass percentage.

8. The multi-band optical protection composition that simultaneously targets AHR and TRPV1 antagonism according to claim 1, characterized in that: The D phase comprises, by mass percentage, 0.01-1.0% quinacrine, 2.0-5.0% corn starch and 1.0-3.0% silica.

9. A cosmetic product, characterized in that, The multi-band light protection composition comprising the simultaneous targeting of AHR and TRPV1 antagonism as described in any one of claims 1-7.

10. The use of a multi-band photoprotective composition that simultaneously targets AHR and TRPV1 antagonism as described in any one of claims 1-8 in the preparation of skin care products for protecting against ultraviolet light, blue light, near-infrared light, alleviating skin damage caused by light pollution, and improving skin photosensitivity.

Images