EP4580589A1

EP4580589A1 - Use of a composition for boosting skin's night repair associated functions

Info

Publication number: EP4580589A1
Application number: EP23761914.3A
Authority: EP
Inventors: Anita DAMODARAN; Mruthyunjaya Swamy Mathapathi; Tanya Rachael THOMAS; Satish Kumar VENKATESH
Original assignee: Unilever Global IP Ltd; Unilever IP Holdings BV
Current assignee: Unilever Global IP Ltd; Unilever IP Holdings BV
Priority date: 2022-08-29
Filing date: 2023-08-28
Publication date: 2025-07-09
Also published as: CA3266388A1; JP2025527769A; CN119654130A; WO2024046943A1; MX2025002266A

Abstract

The present invention relates to use of a topical composition to boost skin's night repair associated functions. This is achieved through a vitamin B3 compound or a derivative thereof; or a combination of a vitamin B3 compound or a derivative thereof and an alkyl substituted dihydroxy benzene wherein the alkyl group comprises 2 to 10 carbon atoms.

Description

USE OF A COMPOSITION FOR BOOSTING SKIN’S NIGHT REPAIR ASSOCIATED FUNCTIONS

Field of the Invention

The present invention relates to use of a topical composition that boosts skin’s night repair associated functions.

Background of the Invention

Exposure of human skin to UV radiation produces a range of acute and chronic adverse effects on the skin. In addition, the current lifestyle especially of the younger generation with frequently delayed and poor sleep, excessive blue light exposure, as well as intrinsic stress/anxieties, are causes for concern. These factors impact multiple skin functions eventually affecting skin appearance including pigmentation, aging and glow. Skin processes are naturally regulated to provide increased protection during the day, while during the night skin focuses on repair. Because skin functions change from day to night, it would be advantageous if night-time cosmetic products worked to help in skin repair while daytime products worked to help skin to maximize protection.

The present inventors, in looking for a solution to the problem of providing enhanced level of night repair associated function to the skin, found that a vitamin B3 compound or a derivative thereof provided this benefit. They also found a combination of actives that synergistically interacted to deliver this benefit. They found that a combination of a vitamin B3 compound or a derivative thereof and an alkyl substituted dihydroxy benzene wherein the alkyl group comprises 2 to 10 carbon atoms, provided this synergy. They further found that the night repair functions of skin were boosted when a composition comprising a vitamin B3 compound was applied on to skin in the evening I night e.g. at the end of the day from about 5 pm to 12 am. Additionally, they found that the night repair functions of skin were boosted when a composition comprising a vitamin B3 compound or a derivative thereof and an alkyl (C2 to C10) substituted dihydroxy benzene was applied on to skin in the evening I night e.g. at the end of the day from about 5 pm to 12 am.

It is thus an object of the present invention to deliver enhanced night repair associated functions to skin. It is another object of the present invention to deliver this benefit though actives that interact synergistically thereby ensuring use of low concentration of actives which provides the consumer with a low cost product and one with minimal side effects.

Summary of the Invention

The first aspect of the present invention relates to use of a composition comprising a vitamin B3 compound or a derivative thereof and an alkyl substituted dihydroxy benzene wherein the alkyl group comprises 2 to 10 carbon atoms; for boosting the skin’s night repair function, wherein the composition is applied on to the skin in the evening or night.

A preferred aspect of the present invention relates to use of a composition of the first aspect additionally comprising a cosmetically acceptable carrier preferably in a lotion, cream, gel, serum or essence form.

Yet another aspect of the present invention relates to a method of boosting the skin’s night repair associated functions comprising the step of applying a composition of the invention on the desired skin surface, wherein the composition is applied on to the skin in the evening or night.

Yet another aspect of the present invention relates to use of a composition comprising a vitamin B3 compound or a derivative thereof; for boosting the skin’s night repair function, wherein the composition is applied on to the skin in the evening or night.

Detailed Description of the Invention

These and other aspects, features and advantages will become apparent to those of ordinary skill in the art from a reading of the following detailed description and the appended claims. For the avoidance of doubt, any feature of one aspect of the present invention may be utilized in any other aspect of the invention. The word “comprising” is intended to mean “including” but not necessarily “consisting of” or “composed of.” In other words, the listed steps or options need not be exhaustive. It is noted that the examples given in the description below are intended to clarify the invention and are not intended to limit the invention to those examples per se. Similarly, all percentages are weight/weight percentages unless otherwise indicated. Except in the operating and comparative examples, or where otherwise explicitly indicated, all numbers in this description and claims indicating amounts of material or conditions of reaction, physical properties of materials and/or use are to be understood as modified by the word “about”. Numerical ranges expressed in the format “from x to y” are understood to include x and y. When for a specific feature multiple preferred ranges are described in the format “from x to y”, it is understood that all ranges combining the different endpoints are also contemplated.

The topical composition of the invention is meant to be used for personal care or for cosmetic use and could also be referred to as a personal care composition or a cosmetic composition. By a “personal care composition” as used herein, is meant to include a composition for topical application i.e external surfaces of the skin and/or hair of humans. Such a composition is generally of the leave-on type, and includes any product applied to a human body for improving appearance, odour control or general aesthetics. The composition of the present invention can be in the form of a lotion, cream, serum, essence or gel, preferably it is in the serum or essence form. Serums are normally considered to be high concentration/potent leave-on products with actives/skin beneficent ingredients. Essence on the other hand is a water-based composition containing active ingredients to hydrate and protect the skin. Both the formats are meant to be used for easy absorption and deep penetration of actives into skin layers.

“Skin” as used herein is meant to include skin on the face and body (e.g. neck, chest, back, arms, underarms, hands, legs and scalp) and especially to the exposed parts thereof.

By 'evening’ or ‘night’ as used in the context of the present invention, it is preferably meant that the composition is applied to skin at the end of the day preferably from about 5 pm to about 12 am, more preferably from about 6 pm to about 11 :30 pm, even more preferably from about 7 pm to about 11 :00 pm, further more preferably form about 8 pm to about 10:30 pm and yet more preferably from about 9 pm to about 10:00 pm.

In the context of the time of applying the composition at the end of the day as described above, the term ‘about’ is meant to include a modification of about 15 to 30 minutes, from the time range specified therein. For example, about 5 pm is meant to include 15 of 30 minutes earlier than 5 pm, i.e. 4:45 pm or 4:30 pm. Similarly, about 12 am is meant to include 12:15 am or 12:30 am.

The present invention relates to use of a composition comprising a vitamin B3 compound or a derivative thereof; for boosting the skin’s night repair function, wherein the composition is applied on to the skin in the evening or night. The present invention also relates to use of a composition comprising a vitamin B3 compound or a derivative thereof and an alkyl substituted dihydroxy benzene wherein the alkyl group comprises 2 to 10 carbon atoms; for boosting the skin’s night repair function, wherein the composition is applied on to the skin in the evening or night.

The vitamin B3 compound or derivative thereof is preferably chosen from one or more of niacin, niacinamide, picolinamide, isonicotinamide, methyl nicotinamides, cyclo-propyl niacinamide, and cyclo-pentyl niacinamide. More preferred is one or more chosen from niacinamide, picolinamide, and isonicotinamide. Most preferred is niacinamide. The composition preferably comprises 0.1 to 5%, more preferably 0.1 to 3%, further more preferably 0.1 to 1 % vitamin B3 compound or derivative thereof, by total weight of the composition.

Alkyl substituted dihydroxy benzene has the general chemical structure (I) as given below:

Wherein Ri is C2 to C10 alkyl group; and each of R2 to Re is either an OH group or H; and wherein at least two of R2 to Re is OH.

Structure of more preferred alkyl substituted dihydroxy benzene for use in the present invention is

Wherein R1 is a C2 to C10 alkyl group; R2 and R3 are OH.

Preferably R1 is an alkyl group comprising 2 to 6 carbon atoms, most preferably comprising 2, 4 or 6 carbon atoms. The two hydroxy groups are generally at the 1 and 3 position. Such compounds are often referred to as substituted resorcinols. Thus, the most preferred compounds are ethyl resorcinol, butyl resorcinol or hexyl resorcinol. The 4-substituted resorcinol is most preferred. Thus, the resorcinols which may be used 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 given below:

The compound is also known by its synonyms 4-hexylbenzene-1 ,3-diol, and 4-hexyl-1 ,3- benzenediol.

Hexylresorcinol is known to exhibit antiseptic and local anaesthetic properties. It has been used in topical applications for minor skin infections and in oral solutions for pain relief and as a first aid antiseptic. It has also been used as a skin-glow agent in skin care. The compound is also known to have antioxidant properties and so have been used in skin care compositions to provide skin with an even tone complexion or in anti-aging products.

The alkyl substituted dihydroxy benzene compound is preferably included in 0.01 to 1 wt%, more preferably 0.05 to 0.5 wt%, further more preferably 0.1 to 0.4 wt% of the composition.

Without wishing to be bound by theory, the present inventors believe that the technical effect, i.e. boost in the skin’s night repair function, occurs due to the following reason.

A vitamin B3 compound or a derivative thereof e.g. niacinamide, is the main precursor of nicotinamide adenine dinucleotide (NAD+), a coenzyme essential for DNA repair, glycolysis, autophagy, oxidative phosphorylation, cell energy etc. Niacinamide also increases the ratio of NAD+/NADH in skin cells and also activates SIRT1 and NAD+ dependent deacetylase that plays an important role in autophagy flux and circadian transcription of several core clock genes. NADH serves effectively as an energy storage component and donate high energy electrons to the mitochondrial electron transport chain when required. Niacinamide is also known to induce antioxidant system in skin cells by activating Nrf2 signaling, and this plays an important role in regulating oxidative stress in skin cells. Alkyl substituted dihydroxybenzene compound as claimed e.g. hexylresorcinol (HR) is known to function as a skin-brightening agent. It also functions as an antioxidant, that can contribute towards a more skin even tone benefits. As an antioxidant protection agent, hexylresorcinol can neutralize free radicals generated by UV, blue light, pollution etc., in skin cells. Besides, HR can also activate multiple other skin functions, including Nrf2 activation, antioxidant response element (ARE)-reporter activity and expression of ARE-dependent genes NAD(P)H dehydrogenase (NQO1) and heme oxygenase- 1 (HO-1).

Based on these insights, the inventors hypothesize that the effect of the combination of the ingredients claimed is attributable to the activation of NRF2 signaling, increasing the expression of NADPH dehydrogenase and other antioxidant enzymes by hexylresorcinol, and enhancing the ratio of NAD+/NADH and activating SIRT1 and NAD+ dependent deacetylase by niacinamide, thereby leading to the benefit observed.

The composition of the invention may be delivered in a lotion, cream, serum, essence or gel form, of which serum, essence or gel form is more preferred, the serum and essence form is most preferred. To enable this, the composition may comprise a cosmetically acceptable carrier. The cosmetically acceptable carrier is preferably chosen from water (which maybe thickened using polymers), or an emulsion which may be water-in-oil or an oil-in-water emulsion. Products in cream or lotion form are generally emulsions.

All of these product forms generally have a high content of water which may be in the range of 55 to 99%, preferably 70 to 95%, more preferably 85 to 95 % by weight of the composition.

Products in the gel form contain predominantly water in the range of 65 to 90 wt%, in serum in 60 to 90 wt% and in essence in 85 to 95 wt% of the composition.

The cosmetically acceptable carrier in the composition of the invention preferably comprises an an emulsifier, a thickener, a humectant, an emollient oil, or mixtures thereof.

The thickener is preferably selected from one or more of an acrylate/ alkyl acrylate cross polymer, carbomer, ammonium acryloyldimethyltaurate/beheneth-25 methacrylate cross-polymer, and ammonium acryloyldimethyltaurate/VP copolymer. The most preferred thickener is an acrylate I alkyl acrylate cross polymer. These are sold under the brand names Pemulene TR-1 , Pemulene TR-2, llltrez 20, llltrez 21. Other polymers which may be included are crosslinked acrylates (e.g. Carbopol 982), hydrophobically-modfied acrylates (e.g. carbopol 1382), carbomer and ammonium acryloyldimethyltaurate/beheneth-25 methacrylate crosspolymer, ammonium acryloyldimethyltaurate/VP copolymer, cellulosic derivatives and natural gums. Among useful cellulosic derivatives are sodium carboxymethylcellulose, hydroxypropyl methylcellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, ethyl cellulose and hydroxymethyl cellulose. Natural gums suitable for the present invention include guar, xanthan, sclerotium, carrageenan, pectin and combinations of these gums. The most preferred thickener is selected from one or more of acrylate/ alkyl acrylate cross polymer, carbomer, ammonium acryloyldimethyltaurate/beheneth-25 methacrylate crosspolymer, and ammonium acryloyldimethyltaurate/VP copolymer. Concentration of the thickener in the composition may range from 0.0001 to 5%, usually from 0.001 to 1 %, optimally from 0.01 to 0.5% by weight.

The composition of the invention may include a humectant which is generally 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 glycerine, 1 ,3-butylene glycol, propylene glycol, 1 ,3 propanediol, pentylene glycol, hexylene glycol, and sorbitol. Glycerol is the most preferred humectant. It is preferred that the amount of humectant is 1 to 10 %, more preferably 2 to 8% by weight of the composition.

The composition may optionally include a skin brightening compound. Illustrative substances are placental extract, lactic acid, arbutin, kojic acid, ferulic acid, hydroquinone, hydroxystearic acid (HSA) preferably 12-HSA, pyridoxine hydrochloride, alpha hydroxyacid (AHA) , beta hydroxyacid (BHA), polyhydroxy acid (PHA) or natural skin brightening extracts like honey or lemon extracts and combinations thereof. More preferably, such skin brightening compound is selected from one or more of hydroxystearic acid, pyridoxine hydrochloride, AHA, BHA, PHA or natural skin brightening extracts like honey or lemon extracts. Amounts of these skin brightening compounds may range from 0.01 to 10 %, preferably from 0.1 to 2 % by weight of the composition.

A preferred format for the solid form of the composition is a cream, further more preferably one which has a vanishing cream base. Vanishing cream base is one which comprises 3 to 25 wt% fatty acid. Optionally, the composition may comprise 0.1 to 10 wt% soap. When included, the fatty acid is preferably a C10 to C22 fatty acid, more preferably a C16 to C18 fatty acid. Most preferably the fatty acids are stearic acid or palmitic acid or a mixture thereof and the soap is preferably the potassium salt of the fatty acid mixture. The fatty acid is often hystric acid which is substantially (generally about 90 to 95 %) a mixture of 45 % stearic acid and 55 % palmitic acid.

Preferably, the composition comprises emollients. Examples of emollients that may be used in the leave-on composition include stearyl alcohol, glyceryl monoricinoleate, mink oil, isopropyl isostearate, isobutyl palmitate, isocetyl stearate, oleyl alcohol, isopropyl laurate, hexyl laurate, decyl oleate, octadecan-2-ol, isocetyl alcohol, eicosanyl alcohol, behenyl alcohol, cetyl palmitate, silicone oils such as dimethylpolysiloxane, din-butyl sebacate, isopropyl myristate, isopropyl palmitate, isopropyl stearate, butyl stearate, polyethylene glycol, triethylene glycol, lanolin, cocoa butter, corn oil, cotton seed oil, olive oil, palm kernel oil, rape seed oil, safflower seed oil, evening primrose oil, soybean oil, sunflower seed oil, avocado oil, sesame seed oil, coconut oil, arachis oil, castor oil, acetylated lanolin alcohols, petroleum jelly, mineral oil, butyl myristate, isopropyl linoleate, lauryl lactate, myristyl lactate, decyl oleate, myristyl myristate and mixtures thereof.

Preferably, the composition comprises solvents. Examples of solvents that may be used in the composition include ethyl alcohol, isopropanol, acetone, ethylene glycol ono ethyl ether, diethylene glycol mono butyl ether, diethylene glycol mono ethyl ether and mixtures thereof.

Preferably, the composition comprises powders. Examples of powders that may be used in the composition include chalk, talc, fullers earth, kaolin, starch, gums, colloidal silica sodium polyacrylate, tetra alkyl and/or trialkyl aryl ammonium smectites, chemically modified magnesium aluminium silicate, organically modified montmorillonite clay, hydrated aluminium silicate, fumed silica, carboxyvinyl polymer, sodium carboxymethyl cellulose, ethylene glycol monostearate and mixtures thereof.

Preferably, the composition comprises preservatives to protect against the growth of potentially harmful microorganisms. Examples of ingredients that may be used as preservatives in the composition include alkyl esters of para-hydroxybenzoic acid, hydantoin derivatives, propionate salts, and a variety of quaternary ammonium compounds. More preferably, ingredients that may be used as preservative in the composition are sodium benzoate, iodopropynyl butyl carbamate, methylisothiazolinone, iodopropynylbutylcarbamate, phenoxyethanol, methyl paraben, propyl paraben, imidazolidinyl urea, sodium dehydroacetate, ethylhexylglycerin, benzyl alcohol, alkane diols and mixtures thereof. The alkane diols that are suitable for use as preservative are C6-C12 alkanes that are vicinally substituted with hydroxy groups. Illustrative examples include 1 ,2-octane diol (caprylyl glycol), 2,3-octane diol, 1 ,2-nonane diol, 1 ,2-decane diol, 1 ,2-hexane diol, 3,4-octane diol, mixtures thereof or the like where caprylyl glycol is typically the most preferred. When present in the composition, preservatives are added preferably in an amount 0.001 to 5 wt%, more preferably 0.01 to 3 wt% and most preferably 0.02 to 2 wt%, even most preferably 0.25 to 1.5%.

Preferably, the composition comprises a range of other optional ingredients that include antioxidants, binders, buffering agents, colorants, astringents, fragrance, opacifying agents, conditioners, exfoliating agents, pH adjusters, skin sensates, skin soothing agents, and skin healing agents.

Another aspect of the present invention relates to a method of boosting the skin’s night repair function comprising the step of applying a composition of the invention on the desired skin surface. The composition is preferably applied on to the skin in the evening or night. In other words, the composition is applied on skin at the end of the day from about 5 pm to about 12 am.

Another aspect of the present invention relates to use of a composition comprising a vitamin B3 compound or a derivative thereof; for boosting the skin’s night repair function, wherein the composition is applied on to the skin in the evening or night.

The invention will now be illustrated with the help of the following non-limiting examples.

Examples

A study was carried out for two consecutive days (day 1 and day 2) for assessing gene expression of skin repair markers associated with night. The study was carried out for genes: skin circadian rhythm gene (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/Cyclin D1 ; NCBI database accession number NM_053056), in human epidermal primary keratinocytes (NHEK; Cascade Biologies, USA) using RT-PCR. The results obtained were as shown in table 1 below. Table 1

The data in table 1 above showed that expression levels of BMAL1, LC3B, XPA and Cyclin D1 genes were upregulated at night as compared to their levels during the day. Importantly, these upregulated expression levels of these genes were in absence of any actives, i.e. the cells were not treated with any actives. Effect of vitamin B3 compound or a derivative thereof for boosting the skin’s night repair function:

Here, NHEK cells were treated with niacinamide (10 mM) in the evening around 7.30 pm ± 30 min, for 12 hours ± 30 min; and gene expression study was carried out as described earlier. The results obtained were as shown in table 2 below:

Table 2

Effect of vitamin B3 compound or a derivative thereof for boosting/restoring the skin’s circadian rhythm and night repair function despite under stress conditions:

Here, NHEK cells were treated with niacinamide in the evening around 7.30 pm ± 30 min for 12 hours ± 30 min as shown in table 3 below, after being exposed to cortisol (a known stress inducer) for 12 hours ± 30 min; and gene expression study was carried out as described earlier. The results obtained were as shown in table 3 below:

Table 3

Benefits of the composition of the invention without blue light stress.

T o establish the night repair benefit of a vitamin B3 compound or a derivative thereof and an alkyl substituted dihydroxy benzene wherein the alkyl group comprises 2 to 10 carbon atoms e.g. niacinamide + 4-HR, human epidermal primary keratinocytes were treated with 1 iM 4-HR + 10 mM niacinamide in the evening (8 pm +/-30min), for 12 ± 30 min and the gene expression study was carried out in NHEK cells for night repair associated markers of autophagy (LC3B); DNA repair (XPA) and cell proliferation (CCND1/Cyclin D1) using RT PCR. The data is summarized in the table - 4 below.

Table -4

The gene expression levels obtained for control (no treatment) were taken to be 1 (no change); and the fold changes shown in table 4 above were calculated over and above the expression levels obtained for the control.

The data in the table -4 above indicates that 4-HR + niacinamide upregulated night repair associated gene expression by more than 2-fold.

Benefits of the composition of the invention with blue light stress.

Experiment similar to the one above was carried out with blue light exposure (445 nm, 5.7J/cm²) as shown in table 5 below; and the gene expression study was carried out in NHEK cells for skin circadian rhythm gene (BMAL1) and for night repair markers of autophagy (LC3B); DNA repair (XPA) and cell proliferation (CCND1/Cyclin D1) using RT PCR. The data is summarized in the table - 5 below.

Table - 5

The data in the table -5 above indicates that the composition of the invention is capable of reversing the ill effects of blue light on night repair function.

Claims

1. Use of a composition comprising a vitamin B3 compound or a derivative thereof and an alkyl substituted dihydroxy benzene wherein the alkyl group comprises 2 to 10 carbon atoms; for boosting the skin’s night repair function, wherein the composition is applied on to the skin in the evening or night.

2. Use as claimed in claim 1 wherein the vitamin B3 compound or derivative thereof is selected from one or more of niacin, niacinamide, picolinamide, isonicotinamide, methyl nicotinamide, cyclo-propyl niacinamide, and cyclo-pentyl niacinamide.

3. Use as claimed in claim 2 wherein the vitamin B3 compound or derivative thereof is niacinamide.

4. Use as claimed in any one of the preceding claims wherein the alkyl substituted dihydroxybenzene is selected from one or more of 4-ethyl resorcinol, 4-butyl resorcinol and 4-hexyl resorcinol.

5. Use as claimed in any one of the preceding claims wherein the composition additionally comprises a cosmetically acceptable carrier.

6. Use of the composition as claimed in claim 5 in lotion, cream, gel, serum or essence form.

7. Use of the composition as claimed in claim 5 or 6 comprising 55 to 99% water.

8. Use as claimed in any one of the preceding claims wherein said vitamin B3 compound or a derivative thereof is included in 0.1 to 5 wt% of the composition.

9. Use as claimed in any one of the preceding claims wherein said alkyl substituted dihydroxy benzene is included in 0.01 to 1 wt% of the composition.

10. Use of the composition as claimed in any one of the preceding claims 5 to 9 wherein the cosmetically acceptable carrier comprises an emulsifier, a thickener, a humectant, an emollient oil, or mixtures thereof. Use of the composition as claimed in claim 10 wherein the thickener is selected from one or more of an acrylate/ alkyl acrylate cross polymer, carbomer, ammonium acryloyldimethyltaurate/beheneth-25 methacrylate cross-polymer, and ammonium acryloyldimethyltaurate/VP copolymer. Use of the composition as claimed in claim 10 or 11 wherein the humectant is a polyhydric alcohol selected form one or more of glycerine, 1,3-butylene glycol, propylene glycol, 1,3- propanediol, pentylene glycol, hexylene glycol, and sorbitol. A method of boosting the skin’s night repair function comprising the step of applying a composition as claimed in any one of the preceding claims on the desired skin surface, wherein the composition is applied on to the skin in the evening or night. Use of a composition comprising a vitamin B3 compound or a derivative thereof; for boosting the skin’s night repair function, wherein the composition is applied on to the skin in the evening or night.