Use of starch for delivering autophagy related benefits to skin

Abstract

The present invention relates to delivering autophagy benefits to skin through personal care compositions, especially through wash off compositions like a soap, body wash, or shampoo. This is achieved through use of specific starch especially by including it in such compositions.

Description

[0001] P0001072 CPL

[0002] 1

[0003] USE OF STARCH FOR DELIVERING AUTOPHAGY RELATED BENEFITS TO SKIN

[0004] Field of the Invention

[0005] The present invention relates to delivering autophagy benefits to skin through personal care

[0006] 5 compositions, especially through wash off compositions like a soap, body wash, or shampoo.

[0007] Background of the Invention

[0008] Skin is the primary line of defense that protects the human body from invading pathogens, like viruses and bacteria. As a primary defense organ, the skin tissue always remains in constant

[0009] 10 contact with the environment and therefore it has to face and resolve threats and challenges from invading pathogens and environmental allergens. The exposed skin surface is not only challenged by such foreign bodies, but it also remains in contact and interacts with the resident commensal bacteria.

[0010] 15 Autophagy is one of the mechanisms by which the cells in the body, including skin cells, retain their normal function. Autophagy is a process by which the old and broken parts of cells are regenerated thereby making the cells operate more efficiently. It is also believed that the process of autophagy has a part in destroying pathogens in a cell. It is believed that lysosomes are responsible for consuming the broken cell parts and converting them into new and reusable parts.

[0011] 20

[0012] The present inventors who have worked extensively in the area of personal care and cleansing, have of late been working on delivering health benefits to skin through the use of commonly used ingredients. Personal care and cleansing products like cosmetic creams, lotions and gels that are applied on skin deliver benefits to skin like moisturization, sunscreen benefits, and skin tone

[0013] 25 benefits. Of late, health benefits that are non-therapeutic in nature have been sought to be delivered through personal care and cleansing compositions. Such health benefits include antimicrobial, antiacne, antiaging, improving immunity etc. The present inventors have been looking to deliver such benefits through commonly used materials in personal care and cleansing compositions.

[0014] 30

[0015] Starch is one such material the present inventors have been using in skin cleansing compositions like soap e.g. soap bars for various benefits. During the course of their research, they have found that starch helps in a skin benefit which they believe is heretofore not known. They found that starch helps in delivering autophagy benefits by upregulating expression levels of LC3B or ATG5

[0016] 35 which is a known autophagy marker of skin. P0001072 CPL

[0017] 2

[0018] It is thus an object of the present invention to deliver autophagy benefits to skin cells though commonly known and used ingredient in personal care or cleansing compositions.

[0019] Summary of the Invention

[0020] 5 The first aspect of the present invention relates to use of starch comprising native starch selected from potato starch, tapioca starch, maize starch, corn starch, or sweet potato starch for upregulating expression levels of LC3B or ATG5 autophagy marker on skin for providing benefit like modulating barrier repair response, giving anti-pigmentation response, exposome protection response against UV radiation on skin, or mental well-being response against stress hormone.

[0021] Another preferred aspect refers to use of the first aspect wherein the starch is present in a personal care composition.

[0022] Detailed Description of the Invention

[0023] 15 Except in the examples, or where otherwise explicitly indicated, all numbers in this description indicating amounts of material or conditions of reaction, physical properties of materials and / or use may optionally be understood as modified by the word “about”.

[0024] All amounts are by weight of the composition, unless otherwise specified.

[0025] 20

[0026] It should be noted that in specifying any range of values, any particular upper value can be associated with any particular lower value.

[0027] For the avoidance of doubt, the word “comprising” is intended to mean “including” but not

[0028] 25 necessarily “consisting of” or “composed of”. In other words, the listed steps or options need not be exhaustive.

[0029] The disclosure of the invention as found herein is to be considered to cover all embodiments as found in the claims as being multiply dependent upon each other irrespective of the fact that claims may be found without multiple dependency or redundancy.

[0030] Where a feature is disclosed with respect to a particular aspect of the invention (for example a composition of the invention), such disclosure is also to be considered to apply to any other aspect of the invention (for example a method of the invention) mutatis mutandis.

[0031] 35 P0001072 CPL

[0032] 3

[0033] The present invention relates to use of starch for upregulating expression levels of LC3B or ATG5 autophagy marker on skin. This leads to various benefits as given below:

[0034] Modulating barrier repair response: Keratinocytes in the skin act as the first barrier protecting it

[0035] 5 from external hazards such as UV radiation and infection due to attack by microorganisms. Activating autophagy (and lysosomes) can regulate keratinocyte differentiation thereby enhancing skin barrier function.

[0036] Anti-pigmentation response: By activating autophagy it is possible to regulate melanogenesis in melanocytes and melanosome degradation in keratinocytes thereby leading to improved antipigmentation response.

[0037] Exposome protection response on skin: Exposome, like ultra-violet radiation exposure, impairs autophagic function in skin, which in turn can led to compromised barrier function. Stimulating

[0038] 15 autophagy activity in skin is therefore considered as an important route to help skin against stress.

[0039] Mental well-being response against stress hormone: Studies have suggest that autophagy function is linked to stress hormone system and its related problem, like depression although the conclusion on the involvement of autophagy in the pathology and treatment of depression is still

[0040] 20 limited. In general, homeostatic maintenance of physiological function is fundamental to organismal well-being. Synaptic components like synaptic proteins, organelles, neurotransmitters and receptors can be selectively degraded by autophagy, which can be the mode of action for autophagy for mental wellbeing.

[0041] The invention relates to the use of starch comprising native starch selected from potato starch, tapioca starch, maize starch, corn starch, or sweet potato starch or its microbial metabolite for upregulating expression levels of LC3B or ATG5 autophagy marker on skin. This use provides one or more benefit selected from: modulating barrier repair response, giving anti-pigmentation response, exposome protection response against UV radiation on skin, or mental well-being

[0042] 30 response against stress hormone.

[0043] Starch as used herein refers to component selected from the group consisting of native starch, modified starch and combinations thereof. The term “native starch” as used herein refers to a starch that has been isolated from a natural plant source and that has not been hydrolyzed or P0001072 CPL

[0044] 4 chemically modified. The term “modified starch” as used herein refers to a starch that has been chemically modified, preferably by esterification.

[0045] Preferably the starch comprises native starch and more preferably is native starch. Preferably,

[0046] 5 the native starch is selected from potato starch, tapioca starch, maize starch, corn starch, or sweet potato starch. More preferably the native starch is maize starch which is also known as corn starch.

[0047] Preferably the modified starch comprises hydroxyalkylated starch, carboxyalkylated starch, succinated starch, or a mixture thereof. More preferably the modified starch comprises hydroxypropylated starch, hydroxyethylated starch, carboxymethylated starch, octenylsuccinated starches, dodecylsuccinated starch or a mixture thereof.

[0048] Preferably, the starch of the present invention has a molar ratio of amylose to amylopectin of from

[0049] 15 1 :99 to 99:1 , more preferably 20:80 to 80:20, even more preferably 20:80 to 30:70. Preferably, the native starch of the present invention has a molar ratio of amylose to amylopectin is from 1 :99 to 99:1 , more preferably 20:80 to 80:20, even more preferably 20:80 to 30:70.

[0050] Preferably, the starch has a bulk density of 200 to 1000 g / L, more preferably 300 to 800 g / L and

[0051] 20 even more preferably 400 to 600 g / L. Preferably, the native starch has a bulk density of 200 to 1000 g / L, more preferably 300 to 800 g / L and even more preferably 400 to 600 g / L.

[0052] Preferably, the starch has a weight average molecular weight of at least 1 KDa, more preferably at least 10 KDa and even more preferably at least 100 KDa. Preferably, the starch has a weight

[0053] 25 average molecular weight of no greater than 100,000,000 KDa, more preferably no greater than 10,000,000 KDa and even more preferably no greater than 1 ,000,000 KDa. Preferably, the native starch has a weight average molecular weight of at least 1 KDa, more preferably at least 10 KDa and even more preferably at least 100 KDa. Preferably, the starch has a weight average molecular weight of no greater than 100,000,000 KDa, more preferably no greater than 10,000,000 KDa and even more preferably no greater than 1 ,000,000 KDa.

[0054] The starch is preferably included in a personal care composition. The composition of the present invention may be a skin cleansing composition, a skin care composition, a hair care composition, an oral care composition, or a deodorant composition. The composition may be in the form of a

[0055] 35 solid, soft solid, liquid, emulsion, microemulsion, lotion, cream, gel, or aerosol forms. P0001072 CPL

[0056] 5

[0057] Preferably, the starch is present in an amount of 0.0001 to 45% by weight of the composition. More preferably, the starch is present in amount of 0.001 to 30% by weight of the composition.

[0058] When the composition is formulated as a personal cleansing composition, the composition

[0059] 5 preferably comprises a cleansing surfactant, preferably in 1 to 80% by weight of the composition. More than one cleansing surfactant may be included in the composition. The cleaning surfactant may be chosen from soap, non-soap anionic, cationic, non-ionic, amphoteric surfactant and mixtures thereof. Many suitable surface-active compounds are available and are fully described in the literature, for example, in "Surface-Active Agents and Detergents", Volumes I and II, by Schwartz, Perry and Berch. The preferred surface-active compounds that can be used are soaps, non-soap anionic, non-ionic surfactant, amphoteric surfactant or a mixture thereof.

[0060] Suitable non-soap anionic surfactants include linear alkylbenzene sulphonate, primary and secondary alkyl sulphates, particularly Cs to C15 primary alkyl sulphates; alkyl ether sulphates;

[0061] 15 olefin sulphonates; alkyl xylene sulphonates; dialkyl sulphosuccinates; fatty acid ester sulphonates; or a mixture thereof. Sodium salts are generally preferred.

[0062] Most preferred non-soap anionic surfactant are linear alkylbenzene sulphonate, particularly linear alkylbenzene sulphonates having an alkyl chain length of from Cs to C15. It is preferred if the level

[0063] 20 of linear alkylbenzene sulphonate is from 0 wt% to 30 wt%, more preferably from 1 wt% to 25 wt%, most preferably from 2 wt% to 15 wt%, by weight of the total composition.

[0064] Nonionic surfactants that may be used include the primary and secondary alcohol ethoxylates, especially the Cs to C20 aliphatic alcohols ethoxylated with an average of from 1 to 20 moles of ethylene oxide per mole of alcohol, and more especially the C10 to C15 primary and secondary aliphatic alcohols ethoxylated with an average of from 1 to 10 moles of ethylene oxide per mole of alcohol. Non ethoxylated nonionic surfactants include alkylpolyglycosides, glycerol monoethers, and polyhydroxyamides (glucamide). It is preferred if the level of non-ionic surfactant is from 0 wt% to 30 wt%, preferably from 1 wt% to 25 wt%, most preferably from 2 wt%

[0065] 30 to 15 wt%, by weight of the composition.

[0066] Suitable amphoteric surfactants preferably are betaine surfactants. Examples of suitable amphoteric surfactants include, but are not limited to, alkyl betaines, alkylamido betaines, alkyl sulfobetaines, alkyl sultaines and alkylamido sultaines; preferably, those having 8 to 18 carbons P0001072 CPL

[0067] 6 in the alkyl and acyl group. It is preferred that the amount of the amphoteric surfactant is 0 to 20 wt%, more preferably from 1 to 10 wt%, by weight of the composition.

[0068] It is also possible to include certain mono-alkyl cationic surfactants. Cationic surfactants that may

[0069] 5 be used include quaternary ammonium salts of the general formula R1R2R3R4N+X- wherein the R groups are long or short hydrocarbon chains, typically alkyl, hydroxyalkyl or ethoxylated alkyl groups, and X is a counter-ion (for example, compounds in which R1is a C8-C22 alkyl group, preferably a Cs-C or C12-C14 alkyl group, R2is a methyl group, and R3and R4, which may be the same or different, are methyl or hydroxyethyl groups); and cationic esters (for example, choline esters).

[0070] The composition may comprise soap. The soap is preferably a C8-C24 soap, more preferably C10- C20 soap and most preferably C12-C18 soap. The cation of the soap can be alkali metal, alkaline earth metal or ammonium. Preferably, the cation of the soap is selected from sodium, potassium

[0071] 15 or ammonium. More preferably the cation of the soap is sodium or potassium. Fatty acids derived from other suitable oils / fats such as groundnut, soybean, tallow, palm, palm kernel, etc. may also be used in other desired proportions. Soap is preferably present in an amount of 1 to 90%, preferably from 10 to 85%, more preferably 25 to 75% by weight of the composition. The composition is preferably in the form of a solid or semi solid form, more preferably in a solid form.

[0072] 20 Even more preferably the composition is a soap bar. Preferably, the composition is a skin cleansing composition. When water is present, it is preferably present in an amount of at least 1%, more preferably at least 2%, even more preferably at least 5% by weight of the composition. When water is the carrier, a preferred composition comprises 10 to 50%, more preferably 12 to 40% by weight water. Starch or native starch may be present from 5 to 45%, more preferably from 8 to 40% and most preferably from 10 to 35% by weight of the composition.

[0073] Water-soluble skin benefit agents may optionally be formulated into the compositions of the invention. A variety of water-soluble skin benefit agents can be used, and the level can be from 0.1 to 50% but preferably from 1 to 30% by weight of the composition. These materials include,

[0074] 30 but are not limited to, polyhydroxy alcohols. Preferred water-soluble skin benefit agents are glycerin, sorbitol and polyethylene glycol.

[0075] Water-insoluble skin benefit agents may also be formulated into the compositions as conditioners and moisturizers. Examples include silicone oils; hydrocarbons such as liquid paraffins, P0001072 CPL

[0076] 7 petrolatum, microcrystalline wax, and mineral oil; and vegetable triglycerides such as sunflower seed and cottonseed oils.

[0077] Some compositions may include thickeners. These may be selected from cellulosics, natural

[0078] 5 gums and acrylic polymers but not limited by this thickening agent types. Among the cellulosics are sodium carboxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl methylcellulose and combinations thereof. Suitable gums include xanthan, pectin, karaya, agar, alginate gums and combinations thereof. Among the acrylic thickeners are homopolymers and copolymers of acrylic and methacrylic acids including carbomers such as Carbopol 1382, Carbopol 982, llltrez, Aqua SF-1 and Aqua SF-2 available from the Lubrizol Corporation. Amounts of thickener may range from 0.01 to 3% by weight of the active polymer (outside of solvent or water) in the compositions.

[0079] Preservatives can desirably be incorporated into the compositions of this invention to protect against the growth of potentially harmful microorganisms. Particularly preferred preservatives

[0080] 15 are phenoxyethanol, methyl paraben, propyl paraben, imidazolidinyl urea, sodium dehydroacetate and benzyl alcohol. The preservatives should be selected having regard for the use of the composition and possible incompatibilities between the preservatives and other ingredients. Preservatives are preferably employed in amounts ranging from 0.01 % to 2% by weight of the composition.

[0081] 20

[0082] Preferably the composition comprises water in an amount of at least 5% by weight of the composition, more preferably at least 25%, even more preferably 40 to 90% and still even more preferably at least 60 to 85% by weight of the composition.

[0083] The cosmetic composition refers to a composition suitable for topical application to human skin, preferably is a rinse-off product. The term "rinse-off" as used with reference to compositions herein means a composition that is applied to or rubbed on the skin, and then washed off. Typically, the use is on desired skin surface. The term "skin" as used herein may include the skin on the face, scalp, neck, chest, abdomen, back, arms, under arms, hands, oral cavity, body and / or

[0084] 30 legs.

[0085] For sake of clarity, the composition comprises starch which typically provides a greater benefit selected from modulating barrier repair response, giving anti-pigmentation response, exposome protection response against UV radiation on skin, or mental well-being response against stress P0001072 CPL

[0086] 8 hormone by way of upregulating expression levels of LC3B or ATG5 autophagy marker on skin as compared to same composition which comprises no starch.

[0087] The present invention also provides starch or a personal care composition comprising starch

[0088] 5 comprising native starch selected from potato starch, tapioca starch, maize starch, corn starch, or sweet potato starch for use in providing benefit like modulating barrier repair response, giving anti-pigmentation response, exposome protection response against UV radiation on skin, or mental well-being response against stress hormone by way of upregulating expression levels of LC3B or ATG5 autophagy marker on skin.

[0089] The present invention also provides use of starch comprising native starch selected from potato starch, tapioca starch, maize starch, corn starch, or sweet potato starch for the manufacture of a medicament for providing benefit like modulating barrier repair response, giving anti-pigmentation response, exposome protection response against UV radiation on skin, or mental well-being

[0090] 15 response against stress hormone by way of upregulating expression levels of LC3B or ATG5 autophagy marker on skin comprising a step of topically applying to skin a composition comprising starch.

[0091] The present invention also relates to a method for providing benefit like modulating barrier repair

[0092] 20 response, giving anti-pigmentation response, exposome protection response against UV radiation on skin, or mental well-being response against stress hormone by way of upregulating expression levels of LC3B or ATG5 autophagy marker on skin comprising a step of topically applying to skin a composition comprising starch comprising native starch selected from potato starch, tapioca starch, maize starch, corn starch, or sweet potato starch.

[0093] The invention is especially useful for providing benefits like modulating barrier repair response or mental well-being response against stress hormone.

[0094] Preferably the use is non-therapeutic. Preferably the method is non-therapeutic. The term non- therapeutic typically means for cosmetic purposes and not curative or therapeutic purposes.

[0095] 30

[0096] The invention will now be illustrated with the help of the following non-limiting examples: P0001072 CPL

[0097] 9

[0098] Examples

[0099] Examples A,1: Effect of inclusion of starch on upregulation of autophagy marker genes

[0100] Materials

[0101] 5 Starch (Beaute by Roguette ST 005, ROQUETTE) was extracted from corn farmed in Lianyungang, China.

[0102] Experimental method and results

[0103] The normal human epidermal keratinocytes (NHEKs) (Biocell, Xi’an, China, LOT: Ep25011503) were cultured in keratinocyte culture medium (KcGrowth, Biocell, Xi’an, China) and plated in 6- well plates. When the cell confluency reached 40% to 60%, the culture medium was replaced with medium together with or without actives for 24 hours, the total RNA for NHEKs was extracted using RNAex Pro reagent (Accurate Biotechnology, Cat: AG21102) according to manufacturer’s protocol.

[0104] 15

[0105] The extracted RNA was guantified using Nanodrop spectrometer (Thermo Fisher Scientific, Waltham, MA, US) and reverse transcribed to generate the template cDNA using the Evo M-MLV RT Premix for gPCR (Accurate Biotechnology, Cat: AG11706) according to manufacturer’s protocol. Gene expression levels of ATG5 and LC3B were analyzed by polymerase chain

[0106] 20 reaction (PCR) using SYBR® Green Premix Pro Tag HS gPCR Kit (Accurate Biotechnology, AG11701). The beta actin (ACTB) gene was selected as the housekeeping gene and all data on relative expression of the target genes was normalized to ACTB gene. The fold changes in expression were calculated relative to the blank control (medium having no active). All tests were conducted at least three times and Table 1 shows the fold change of the gene expression.

[0107] Table 1

[0108] #: indicates that the data is significantly better (p<0.05) than Example A with no treatment)

[0109] 30 The data in Table 1 above indicates that starch at 0.00001 % significantly activated two autophagy-related gene expression levels, ATG5 and LC3B, respectively. P0001072 CPL

[0110] 10

[0111] It is to be understood that the experiments described above were conducted in an in vitro assay to evaluate the upregulation of genes. These were carried out at concentrations much lower than that used in a composition used on skin for the following reasons. E.g. in the case of skin cleansing composition, firstly the composition as bought by the consumer is diluted with water

[0112] 5 before application on to the skin. Further it is expected that the concentration of the active e.g. starch in the bulk solution would be many times (if not orders of magnitude higher) as compared to that at the cellular level where it comes in contact with the skin cells due to partitioning of the actives in the oil phase and in the water phase. Further other resistances like diffusional rates, convective transport rates, rheological properties etc. would ensure that the concentration of the 10 actives at the cellular level is further reduced compared to that in the bulk.

[0113] Therefore, the concentration of an active used in experiments carried out at the cellular level is many orders of magnitude lower than that used in formulating a composition to be sold to the consumer.

Claims

P0001072 CPL11Claims1. Use of starch comprising native starch selected from potato starch, tapioca starch, maize starch, corn starch, or sweet potato starch for upregulating expression levels of LC3B or ATG5 autophagy marker on skin for providing benefit like modulating barrier repair response, giving anti-pigmentation response, exposome protection response against UV radiation on skin, or mental well-being response against stress hormone.

2. Use as claimed in claim 1 wherein the use is non-therapeutic.

3. Use as claimed in claims 1 or 2 wherein the starch is native starch.

4. Use as claimed in any one of the preceding claims wherein the starch is present in a personal care composition.

5. Use as claimed in claim 4 wherein the starch is present in amount of 0.0001 to 45% by weight of the composition, preferably 0.001 to 30% by weight of the composition.

6. Use as claimed in claim 4 or 5 wherein the personal cleansing composition additionally comprises 1 to 80 wt% surfactant7. Starch, or a personal care composition comprising starch, comprising native starch selected from potato starch, tapioca starch, maize starch, corn starch, or sweet potato starch for use in providing benefit like modulating barrier repair response, giving anti-pigmentation response, exposome protection response against UV radiation on skin, or mental well-being response against stress hormone by way of upregulating expression levels of LC3B or ATG5 autophagy marker on skin.

8. A method of providing benefit like modulating barrier repair response, giving antipigmentation response, exposome protection response against UV radiation on skin, or mental well-being response against stress hormone by way of upregulating expression levels of LC3B or ATG5 autophagy marker on skin comprising a step of topically applying to skin a composition comprising starch comprising native starch selected from potato starch, tapioca starch, maize starch, corn starch, or sweet potato starch.

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