Use of a composition for enhancing functions associated with nighttime skin repair

Abstract

The present invention relates to the use of a topical composition for enhancing the nocturnal repair-related functions of the skin, which is achieved by a combination of a vitamin B3 compound or a derivative thereof, or a vitamin B3 compound or a derivative thereof and an alkyl-substituted dihydroxybenzene, wherein the alkyl group contains 2 to 10 carbon atoms.

Description

[Technical Field]

[0001] The present invention relates to the use of topical compositions to enhance the nocturnal repair-related functions of the skin. [Background technology]

[0002] Exposure of human skin to ultraviolet radiation causes a variety of acute and chronic adverse effects on the skin. Furthermore, modern lifestyles, especially among younger generations, often involve late and insufficient sleep, excessive blue light exposure, and underlying stress / anxiety are also causes of concern. These factors affect multiple skin functions, ultimately affecting skin appearance, including pigmentation, aging, and radiance. Skin processes are naturally adjusted to enhance protection during the day, while at night, the skin focuses on repair. Because skin functions change from day to night, it would be advantageous if nighttime cosmetics could aid in skin repair and daytime cosmetics could function to maximize skin protection. Summary of the Invention [Problem to be solved by the invention]

[0003] In their search for a solution to the problem of providing high levels of skin repair-related functions at night, the inventors have found that vitamin B3 compounds or derivatives thereof provide this effect. The inventors have also discovered combinations of active substances that synergistically interact to provide this benefit. The inventors have found that the combination of vitamin B3 compounds or derivatives thereof with alkyl-substituted dihydroxybenzenes, in which the alkyl group contains 2 to 10 carbon atoms, provides this synergistic effect. The inventors have further found that applying a composition containing vitamin B3 compounds to the skin in the evening / night, for example, from about 5 PM to about 12 AM at the end of the day, enhances the skin's nighttime repair function. Furthermore, the inventors have found that applying a composition containing vitamin B3 compounds or derivatives thereof and alkyl (C2-C10)-substituted dihydroxybenzenes to the skin in the evening / night, for example, from about 5 PM to about 12 AM at the end of the day, enhances the skin's nighttime repair function.

[0004] It is therefore an object of the present invention to provide enhanced night-time repair-related functions to the skin.

[0005] Another object of the present invention is to provide this benefit through synergistically interacting active substances, thereby ensuring the use of low concentrations of active substances, thereby providing the consumer with a low-cost product and a product with minimal side effects. [Means for solving the problem]

[0006] A first aspect of the present invention relates to the use of a composition comprising a vitamin B3 compound or a derivative thereof and an alkyl-substituted dihydroxybenzene, wherein the alkyl group contains 2 to 10 carbon atoms, for enhancing the nocturnal repair function of the skin, wherein the composition is applied to the skin in the evening or at night.

[0007] A preferred embodiment of the present invention relates to the use of a composition according to the first embodiment, further comprising a cosmetically acceptable carrier, preferably in the form of a lotion, cream, gel, serum or essence.

[0008] Yet another aspect of the present invention relates to a method for enhancing the nighttime repair-related functions of the skin, comprising the step of applying the composition of the present invention to the desired skin surface, wherein the composition is applied to the skin in the evening or at night.

[0009] Yet another aspect of the present invention relates to the use of a composition comprising a vitamin B3 compound or a derivative thereof to enhance the nocturnal repair function of the skin, wherein said composition is applied to the skin in the evening or at night. DETAILED DESCRIPTION OF THE INVENTION

[0010] These and other aspects, features, and advantages will become apparent to those skilled in the art upon reading the following detailed description and the appended claims. For the avoidance of doubt, any feature of one aspect of the present invention can be utilized in any other aspect of the present invention. The term "comprising" is intended to mean "including," but not necessarily "consisting of" or "composed of." In other words, the steps or options described need not be all-inclusive. It should be noted that the examples described below are intended to clarify the invention and are not intended to limit the invention to those examples themselves. Similarly, unless otherwise indicated, all percentages are weight / weight percent. Except in the examples and comparative examples, or unless explicitly stated, all numbers in this "Detailed Description" and "Claims" describing amounts of materials or reaction conditions, physical properties of materials, and / or uses should be understood to be modified by the word "about." Numerical ranges expressed in the format "from x to y" are understood to include both x and y. When multiple preferred ranges for a particular feature are stated in the format "from x to y," it is understood that all ranges combining the different endpoints are also contemplated.

[0011] The topical compositions of the present invention are intended for use in personal care or cosmetic applications and may also be referred to as personal care compositions or cosmetic compositions. As used herein, "personal care composition" is intended to include compositions for topical application, i.e., application to the external surface of human skin and / or hair. Such compositions are leave-on, including products applied to the human body for appearance improvement, odor control, or general beauty. The compositions of the present invention can be in the form of a lotion, cream, serum, essence, or gel, and preferably are in the form of a serum or essence. Solutions are typically considered to be highly concentrated / potent leave-on products containing active ingredients / skin benefit ingredients. Essences, on the other hand, are aqueous compositions containing active ingredients that hydrate and protect the skin. Both forms are intended to be used so that the active substances are easily absorbed into the skin layers and penetrate deeply.

[0012] As used herein, "skin" includes the skin of the face and body (eg, neck, chest, back, arms, underarms, hands, feet, and scalp), particularly exposed areas thereof.

[0013] "Evening" or "night" as used in the context of the present invention preferably means that the composition is applied to the skin at the end of the day, preferably between about 5 PM and 12 AM, more preferably between about 6 PM and 11:30 PM, even more preferably between about 7 PM and 11 PM, even more preferably between about 8 PM and 10:30 PM, and even more preferably between about 9 PM and 10 PM.

[0014] In the context of applying the composition at the end of the day as described above, the term "about" is meant to include about a 15-30 minute variation from the specified time range. For example, "about 5:00 PM" is intended to include 15 or 30 minutes earlier than 5:00 PM, i.e., 4:45 PM or 4:30 PM. Similarly, "about 12:00 AM" is intended to include 12:15 AM or 12:30 AM.

[0015] The present invention relates to the use of a composition comprising a vitamin B3 compound or a derivative thereof for enhancing the nocturnal repair function of the skin, the composition being applied to the skin in the evening or at night.

[0016] The present invention also relates to the use of a composition comprising a vitamin B3 compound or a derivative thereof and an alkyl-substituted dihydroxybenzene, wherein the alkyl group contains 2 to 10 carbon atoms, for enhancing nighttime skin repair, the composition being applied to the skin in the evening or at night.

[0017] The vitamin B3 compound or derivative thereof is preferably selected from one or more of niacin, niacinamide, picolinamide, isonicotinamide, methylnicotinamide, cyclopropylniacinamide, and cyclopentylniacinamide. More preferably, it is selected from one or more of niacinamide, picolinamide, and isonicotinamide. Most preferably, it is niacinamide. The composition preferably contains 0.1 to 5%, more preferably 0.1 to 3%, and even more preferably 0.1 to 1% of the vitamin B3 compound or derivative thereof based on the total weight of the composition.

[0018] Alkyl-substituted dihydroxybenzenes have the general chemical structure (I) provided below. [ka]

[0019] In the formula, R1 is C2 to C 10 is an alkyl group, and R2 to R6 are each an OH group or H; At least two of R2 to R6 are OH.

[0020] The structures of the more preferred alkyl-substituted dihydroxybenzenes for use in the present invention are as follows: [ka]

[0021] In the formula, R1 is C2 to C 10 is an alkyl group, and R2 and R3 are OH.

[0022] Preferably, R1 is an alkyl group containing 2 to 6 carbon atoms, most preferably 2, 4, or 6 carbon atoms. The two hydroxy groups are usually located at the 1- and 3-positions. Such compounds are often referred to as substituted resorcinols. Therefore, the most preferred compounds are ethyl resorcinol, butyl resorcinol, or hexyl resorcinol. 4-Substituted resorcinols are most preferred. Therefore, usable resorcinols are 4-ethyl resorcinol (4-ER), 4-butyl resorcinol (4-BR), or 4-hexyl resorcinol (4-HR). The most preferred compound for use in the present invention is 4-hexyl resorcinol. This compound has the structure shown below. [ka]

[0023] The compound is also known by the synonyms 4-hexylbenzene-1,3-diol and 4-hexyl-1,3-benzenediol.

[0024] Hexylresorcinol is known to have antiseptic and local anesthetic properties. It has been used topically for minor skin infections, in oral solutions for pain relief, and as a first-aid antiseptic. It has also been used in skin care as a skin lightening agent. This compound is also known to have antioxidant properties, which is why it has been used in skin care ingredients to even out skin tone and in anti-aging products.

[0025] The alkyl-substituted dihydroxybenzene compound is contained in an amount of preferably 0.01 to 1% by weight, more preferably 0.05 to 0.5% by weight, and even more preferably 0.1 to 0.4% by weight of the composition.

[0026] Without wishing to be bound by theory, the inventors believe that the technical effect, namely, the improvement of the skin's nighttime repair function, occurs for the following reasons.

[0027] Vitamin B3 compounds and their derivatives, such as niacinamide, are the primary precursors of nicotinamide adenine dinucleotide (NAD+), a coenzyme essential for DNA repair, glycolysis, autophagy, oxidative phosphorylation, and cellular energy. Niacinamide also increases the NAD+ / NADH ratio in skin cells and activates SIRT1 and NAD+-dependent deacetylases, which play important roles in autophagic flux and the circadian transcription of several core clock genes. NADH effectively functions as an energy storage component, donating high-energy electrons to the mitochondrial electron transport chain when needed. Niacinamide is also known to induce the antioxidant system in skin cells by activating Nrf2 signaling, which plays an important role in regulating oxidative stress in skin cells.

[0028] The claimed alkyl-substituted dihydroxybenzene compounds, such as hexylresorcinol (HR), are known to function as skin lightening agents. They also function as antioxidants, potentially contributing to a more even skin tone. As an antioxidant protectant, hexylresorcinol can neutralize free radicals generated in skin cells by UV, blue light, pollution, and other factors. Furthermore, HR can also activate multiple other skin functions, including Nrf2 activation, antioxidant response element (ARE) reporter activity, and the expression of the ARE-dependent genes NAD(P)H dehydrogenase (NQO1) and heme oxygenase-1 (HO-1).

[0029] Based on these insights, the inventors hypothesize that the effects of the claimed ingredient combination are due to activation of NRF2 signaling, increased expression of NADPH dehydrogenase and other antioxidant enzymes by hexylresorcinol, and improved NAD / NADH ratio and activation of SIRT1 and NAD-dependent deacetylases by niacinamide, thereby resulting in the observed benefits.

[0030] The composition of the present invention can be provided in the form of a lotion, cream, serum, essence, or gel, of which the form of serum, essence, or gel is more preferred, and the form of serum and essence is most preferred.To make this possible, the composition can contain a cosmetically acceptable carrier.The cosmetically acceptable carrier is preferably selected from water (which may be thickened using a polymer) or an emulsion, such as a water-in-oil or oil-in-water emulsion.Products in the form of a cream or lotion are generally emulsions.

[0031] All of these product forms generally have a high moisture content, which may range from 55 to 99% by weight of the composition, preferably from 70 to 95% by weight, more preferably from 85 to 95% by weight.

[0032] Gel-type products contain mainly water in the range of 65 to 90% by weight, serums in the range of 60 to 90% by weight, and essences in the range of 85 to 95% by weight.

[0033] The cosmetically acceptable carrier in the compositions of the present invention preferably comprises an emulsifier, a thickener, a humectant, an emollient oil or mixtures thereof.

[0034] The thickener is preferably selected from one or more of acrylate / alkyl acrylate crosspolymer, carbomer, ammonium acryloyldimethyl taurate / beheneth-25 methacrylate crosspolymer, and ammonium acryloyldimethyl taurate / VP copolymer. The most preferred thickener is acrylate / alkyl acrylate crosspolymer. These are sold under the trade names Pemulene TR-1, Pemulene TR-2, Ultrez 20, and Ultrez 21. Other polymers that may be included are crosslinked acrylates (e.g., Carbopol 982), hydrophobically modified acrylates (e.g., Carbopol 1382), carbomer, ammonium acryloyldimethyl taurate / beheneth-25 methacrylate crosspolymer, ammonium acryloyldimethyl taurate / VP copolymer, cellulose derivatives, and natural gums. Useful cellulose derivatives include sodium carboxymethylcellulose, hydroxypropylmethylcellulose, hydroxypropylcellulose, hydroxyethylcellulose, ethylcellulose, and hydroxymethylcellulose. Natural gums suitable for the present invention include guar, xanthan, sclerotium, carrageenan, pectin, and combinations of these gums. Most preferred thickeners are selected from one or more of acrylate / alkyl acrylate crosspolymer, carbomer, ammonium acryloyldimethyl taurate / beheneth-25 methacrylate crosspolymer, and ammonium acryloyldimethyl taurate / VP copolymer. Concentration of the thickener in the composition may range from 0.0001 to 5% by weight, usually from 0.001 to 1%, optimally from 0.01 to 0.5%.

[0035] The compositions of the present invention may contain a humectant, typically a polyhydric alcohol. Preferably, the humectant is at least one of propylene glycol, dipropylene glycol, polypropylene glycol, polyethylene glycol, sorbitol, hydroxypropyl sorbitol, hexylene glycol, 1,3-butylene glycol, isoprene glycol, 1,3-propanediol, pentylene glycol, hexylene glycol, 1,2,6-hexanetriol, glycerol, ethoxylated glycerol, and propoxylated glycerol. Preferred humectants are selected from one or more of glycerin, 1,3-butylene glycol, propylene glycol, 1,3-propanediol, pentylene glycol, hexylene glycol, and sorbitol. Glycerol is the most preferred humectant. The amount of humectant is preferably 1 to 10% by weight of the composition, more preferably 2 to 8% by weight.

[0036] The composition may optionally contain a skin-lightening compound. Exemplary substances are placenta extract, lactic acid, arbutin, kojic acid, ferulic acid, hydroquinone, hydroxystearic acid (HSA), preferably 12-HSA, pyridoxine hydrochloride, alpha hydroxy acids (AHA), beta hydroxy acids (BHA), polyhydroxy acids (PHA), or natural skin-lightening extracts such as honey or lemon extract, and combinations thereof. More preferably, such skin-lightening compounds are selected from one or more of hydroxystearic acid, pyridoxine hydrochloride, AHA, BHA, PHA, or natural skin-lightening extracts such as honey or lemon extract. The amount of these skin-lightening compounds can range from 0.01 to 10% by weight of the composition, preferably from 0.1 to 2% by weight.

[0037] A preferred solid form of the composition is a cream, more preferably one having a vanishing cream base. The vanishing cream base contains 3 to 25% by weight of a fatty acid. Optionally, the composition may contain 0.1 to 10% by weight of a soap. When a fatty acid is included, it is preferably a C10 to C22 fatty acid, more preferably a C16 to C18 fatty acid. Most preferably, the fatty acid is stearic acid or palmitic acid, or a mixture thereof, and the soap is preferably a potassium salt of the fatty acid mixture. The fatty acid is often substantially (generally about 90 to 95%) hystric acid, which is a mixture of 45% stearic acid and 55% palmitic acid.

[0038] Preferably, the composition comprises an emollient. Examples of emollients that can be used in leave-on compositions include stearyl alcohol, glyceryl monoricinoleate, mink oil, isopropyl isostearate, isobutyl palmitate, isocetyl stearate, oleyl alcohol, isopropyl laurate, hexyl laurate, decyl oleate, octadecane-2-ol, isocetyl alcohol, eicosanyl alcohol, behenyl alcohol, cetyl palmitate, silicone oils such as dimethylpolysiloxane, dibutyl sebacate, isopropyl myristate, palmitic acid, methylparaben ... Examples of suitable oils include isopropyl phosphate, isopropyl stearate, butyl stearate, polyethylene glycol, triethylene glycol, lanolin, cocoa butter, corn oil, cottonseed oil, olive oil, palm kernel oil, rapeseed oil, safflower seed oil, evening primrose oil, soybean oil, sunflower seed oil, avocado oil, sesame oil, coconut oil, peanut oil, castor oil, acetylated lanolin alcohol, petrolatum, mineral oil, butyl myristate, isopropyl linoleate, lauryl lactate, myristyl lactate, decyl oleate, myristyl myristate, and mixtures thereof.

[0039] Preferably, the composition includes a solvent. Examples of solvents that can be used in the composition include ethyl alcohol, isopropanol, acetone, ethylene glycol monoethyl ether, diethylene glycol monobutyl ether, diethylene glycol monoethyl ether, and mixtures thereof.

[0040] Preferably, the composition comprises a powder. Examples of powders that can be used in the composition include chalk, talc, fuller's earth, kaolin, starch, gum, colloidal silica, sodium polyacrylate, tetraalkyl and / or trialkylarylammonium smectite, chemically modified magnesium aluminum silicate, organically modified montmorillonite clay, hydrated aluminum silicate, fumed silica, carboxyvinyl polymer, sodium carboxymethylcellulose, ethylene glycol monostearate, and mixtures thereof.

[0041] Preferably, the composition contains a preservative to prevent the growth of potentially harmful microorganisms. Examples of ingredients that can be used as preservatives in the composition include alkyl esters of para-hydroxybenzoic acid, hydantoin derivatives, propionate salts, and various quaternary ammonium compounds. More preferably, ingredients that can be used as preservatives in the composition are sodium benzoate, iodopropynyl butylcarbamate, methylisothiazolinone, iodopropynyl butylcarbamate, phenoxyethanol, methylparaben, propylparaben, imidazolidinyl urea, sodium dehydroacetate, ethylhexylglycerin, benzyl alcohol, alkanediols, and mixtures thereof. Alkanediols suitable for use as preservatives include C6-C alkanediols vicinal substituted with hydroxy groups. 12Alkanes. Specific examples include 1,2-octanediol (caprylyl glycol), 2,3-octanediol, 1,2-nonanediol, 1,2-decanediol, 1,2-hexanediol, 3,4-octanediol, and mixtures thereof, with caprylyl glycol being typically the most preferred. When present in the composition, preservatives are preferably added in an amount of 0.001 to 5% by weight, more preferably 0.01 to 3% by weight, most preferably 0.02 to 2% by weight, and even more preferably 0.25 to 1.5% by weight.

[0042] Preferably, the composition includes various other optional ingredients such as antioxidants, binders, buffers, colorants, astringents, fragrances, opacifiers, conditioners, exfoliants, pH adjusters, skin feel agents, skin emollients, and skin healing agents.

[0043] Another aspect of the present invention relates to a method for enhancing skin's nighttime repair function, comprising applying the composition of the present invention to the desired skin surface. The composition is preferably applied to the skin in the evening or at night. In other words, the composition is applied to the skin at the end of the day, between about 5:00 PM and about 12:00 PM.

[0044] Another aspect of the present invention relates to the use of a composition comprising a vitamin B3 compound or a derivative thereof to enhance the nocturnal repair function of the skin, wherein the composition is applied to the skin in the evening or at night.

[0045] The invention will now be illustrated by the following non-limiting examples. [Example]

[0046] To evaluate the gene expression of nighttime-related skin repair markers, a study was conducted on two consecutive days (days 1 and 2). This study was performed using RT-PCR on genes involved in skin circadian rhythm (BMAL1; NCBI database accession number NM_001297719), autophagy (LC3B; NCBI database accession number NG_029030), DNA repair (XPA; NCBI database accession number NM_000380), and cell proliferation (CCND1 / CyclinD1; NCBI database accession number NM_053056) in primary human epidermal keratinocytes (NHEK; Cascade Biologics, USA). The results are shown in Table 1. [Table 1]

[0047] The data in Table 1 above show that the expression levels of the BMAL1, LC3B, XPA, and CyclinD1 genes were elevated at night compared to daytime levels. Importantly, the elevated expression levels of these genes were in the absence of active substances, i.e., the cells were not treated with active substances.

[0048] The effect of vitamin B3 compounds or their derivatives on enhancing skin repair function at night: Here, NHEK cells were treated with niacinamide (10 mM) for 12 hours ± 30 minutes starting from approximately 7:30 pm in the evening, and gene expression assays were performed according to the method described above. The results are shown in Table 2 below. [Table 2]

[0049] The effect of vitamin B3 compounds or their derivatives on promoting / restoring the skin's circadian rhythm and nighttime repair function even under stress: Here, NHEK cells were exposed to cortisol (a known stress inducer) for 12 hours ± 30 minutes, and then treated with niacinamide for 12 hours ± 30 minutes at approximately 7:30 pm ± 30 minutes, as shown in Table 3 below. Gene expression assays were then performed according to the method described above. The results are shown in Table 3 below. [Table 3]

[0050] Advantages of the composition of the present invention without blue light stress To establish the nighttime repair effects of vitamin B3 compounds or their derivatives with alkyl-substituted dihydroxybenzenes containing 2–10 carbon atoms (e.g., niacinamide + 4-HR), primary human epidermal keratinocytes were treated with 1 μM 4-HR + 10 mM niacinamide in the evening (8:00 PM ± 30 min) for 12 ± 30 min. Gene expression studies were performed in NHEK cells using real-time PCR for nighttime repair-related markers of autophagy (LC3B), DNA repair (XPA), and cell proliferation (CCND1 / cyclin D1). The data are summarized in Table 4. [Table 4]

[0051] The gene expression level obtained in the control (no treatment) was set to 1 (no change) and the fold change shown in Table 4 above was calculated as being higher than the expression level obtained in the control.

[0052] The data in Table 4 above show that 4-HR plus niacinamide increased nighttime repair-related gene expression by more than two-fold.

[0053] Advantages of the compositions of the present invention in blue light stress The same test as above was performed using blue light exposure (445 nm, 5.7 J / cm ) as shown in Table 5 below. 2) and gene expression studies were performed in NHEK cells using RT-PCR for skin circadian rhythm genes (BMAL1) and nocturnal repair markers of autophagy (LC3B); DNA repair (XPA) and cell proliferation (CCND1 / cyclin D1). The data are summarized in Table 5 below. [Table 5]

[0054] The data in Table 5 above demonstrate that the compositions of the present invention can reverse the adverse effects of blue light on nighttime repair function.

Claims

1. The use of a composition comprising a vitamin B3 compound or a derivative thereof and an alkyl-substituted dihydroxybenzene having an alkyl group containing 2 to 10 carbon atoms, for the purpose of enhancing the skin's nocturnal repair function, The composition is used by applying it to the skin in the evening or at night.

2. The use according to claim 1, wherein the vitamin B3 compound or its derivative is selected from one or more of niacin, niacinamide, picolineamide, isonicotinamide, methylnicotinamide, cyclopropylniacinamide, and cyclopentylniacinamide.

3. The use according to claim 2, wherein the vitamin B3 compound or derivative thereof is niacinamide.

4. The use according to claim 1, wherein the alkyl-substituted dihydroxybenzene is selected from one or more of 4-ethyl resorcinol, 4-butyl resorcinol, and 4-hexyl resorcinol.

5. The use according to claim 1, wherein the composition further comprises a carrier that is acceptable as a cosmetic.

6. Use of the composition according to claim 5 in the form of a lotion, cream, gel, serum, or essence.

7. Use of the composition according to claim 5, which contains 55 to 99% water.

8. The use according to claim 1, wherein the vitamin B3 compound or a derivative thereof is contained in the composition in an amount of 0.1 to 5% by weight.

9. The use according to claim 1, wherein the alkyl-substituted dihydroxybenzene is contained in the composition in an amount of 0.01 to 1% by weight.

10. Use of the composition according to claim 5, wherein the carrier acceptable as a cosmetic comprises an emulsifier, a thickener, a humectant, a skin softening oil, or a mixture thereof.

11. Use of the composition according to claim 10, wherein the thickening agent is selected from one or more of acrylate / alkyl acrylate crosspolymer, carbomer, ammonium acryloyldimethyltaurate / beheneth-25 methacrylate crosspolymer, and ammonium acryloyldimethyltaurate / VP copolymer.

12. Use of the composition according to claim 10 or 11, wherein the humectant is a polyhydric alcohol selected from one or more of glycerin, 1,3-butylene glycol, propylene glycol, 1,3-propanediol, pentylene glycol, hexylene glycol, and sorbitol.

13. A method for enhancing the nocturnal repair function of the skin, comprising the step of applying the composition described in claim 1 to a desired skin surface, A method of applying the aforementioned composition to the skin in the evening or at night.

14. Use of a composition containing a vitamin B3 compound or a derivative thereof to enhance the skin's nocturnal repair function, wherein the composition is applied to the skin in the evening or at night.