Personal care composition based on carboxymethyl cysteine compound and acetyl methionine compound

Abstract

Disclosed is a personal care composition comprising carboxymethyl cysteine compound and acetyl methionine compound, wherein the molar ratio of the carboxymethyl cysteine compound to the acetyl methionine compound is 1:1.6 to 2:1.

Description

[0001] PERSONAL CARE COMPOSITION BASED ON CARBOXYMETHYL CYSTEINE COMPOUND AND ACETYL METHIONINE COMPOUND

[0002] Field of the Invention

[0003] The present invention relates to a personal care composition comprising carboxymethyl cysteine compound and acetyl methionine compound, wherein the molar ratio of the carboxymethyl cysteine compound to the acetyl methionine compound is 1:1.6 to 2:1. It was surprisingly found that such composition is capable of significantly upregulating the expression of aquaporin-3 (AQP3) gene.

[0004] Background of the Invention

[0005] The skin is a primary barrier of the human body. It protects the organs in the body from external stressors like heat, UV, pollutants, allergens, pathogens etc. It also prevents loss of moisture. The protective role of skin is carried out by epidermal or skin barrier. The skin is composed of three distinct layers: the hypodermis, the dermis, and the epidermis. The epidermis consists of a horny cell layer, a granulosa layer, a prickle cell layer and a basal layer. As the largest organ in human body, the skin requires proper hydration to maintain its elasticity, and skin barrier function.

[0006] Aquaporins (AQPs) play an important role in transporting small molecules such as water through the membrane. AQPs are expressed in many different cell types of the skin and contribute to several of the skin’s key functions including hydration, formation of waterpermeability barrier, and immune response. AQP3 is the most abundant aquaporin in the outer epithelial layer of the skin and has the function of keeping morphology and function of the skin normal.

[0007] Therefore, the present inventors have recognized that there is a need to develop solution to upregulate the expression of AQP3 gene and therefore boost the skin hydration, and thus skin barrier function. It was surprisingly found that by combining carboxymethyl cysteine compound and acetyl methionine compound in a specific ratio, the expression of AQP3 gene was significantly upregulated.

[0008] Summary of the Invention

[0009] In a first aspect, the present invention is directed to a personal care composition comprising carboxymethyl cysteine compound and acetyl methionine compound, wherein the molar ratio of the carboxymethyl cysteine compound to the acetyl methionine compound is 1:1.6 to 2:1. In a second aspect, the present invention is directed to a method of providing the skin benefits selected from the group consisting of improving skin barrier health, strengthening skin barrier, increasing skin hydration, and improving immune response comprising a step of topically applying to the skin the composition of the present invention.

[0010] In a third aspect, the present invention is directed to use of the composition of the present invention for providing the skin benefits selected from the group consisting of improving skin barrier health, strengthening skin barrier, increasing skin hydration, and improving immune response.

[0011] All other aspects of the present invention will more readily become apparent upon considering the detailed description and examples which follow.

[0012] Detailed Description of the Invention

[0013] 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”.

[0014] All amounts are by weight of the composition, unless otherwise specified.

[0015] It should be noted that in specifying any range of values, any particular upper value can be associated with any particular lower value.

[0016] For the avoidance of doubt, 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.

[0017] 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.

[0018] 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. The carboxymethyl cysteine compound refers to compound selected from carboxymethyl cysteine, salt of carboxymethyl cysteine, ester of carboxymethyl cysteine, amide of carboxymethyl cysteine or a mixture thereof. Preferably, the carboxymethyl cysteine compound comprises carboxymethyl cysteine, ester of carboxymethyl cysteine, and / or salt of carboxymethyl cysteine. More preferably, the carboxymethyl cysteine compound comprises carboxymethyl cysteine, and / or salt of carboxymethyl cysteine. Even more preferably, carboxymethyl cysteine compound comprises salt of carboxymethyl cysteine. Still even more preferably the carboxymethyl cysteine compound comprises lysine carboxymethyl cysteinate and most preferably, the carboxymethyl cysteine compound is lysine carboxymethyl cysteinate.

[0019] Preferably, the carboxymethyl cysteine compound is present in amount of at least 0.00001%, more preferably at least 0.0001%, even more preferably at least 0.001%, still even more preferably at least 0.01%, and most preferably at least 0.1% by weight of the composition. Preferably, the carboxymethyl cysteine compound is present in amount of no greater than 10%, more preferably no greater than 5%, even more preferably no greater than 3%, still even more preferably no greater than 1%, and most preferably no greater than 0.5% by weight of the composition.

[0020] Preferably, the lysine carboxymethyl cysteinate is present in amount of no greater than 10%, more preferably no greater than 5%, even more preferably no greater than 3%, still even more preferably no greater than 1%, and most preferably no greater than 0.5% by weight of the composition. Preferably, the lysine carboxymethyl cysteinate is present in amount of at least 0.00001%, more preferably at least 0.0001%, even more preferably at least 0.001%, still even more preferably at least 0.01 %, and most preferably at least 0.1 % by weight of the composition.

[0021] The acetyl methionine compound refers to compound selected from acetyl methionine, salt of acetyl methionine, ester of acetyl methionine, amide of acetyl methionine, salt of ester of acetyl methionine, or salt of amide of acetyl methionine, or a mixture thereof. Preferably, the acetyl methionine compound is selected from acetyl methionine, salt of acetyl methionine, ester of acetyl methionine, salt of ester of acetyl methionine, or a mixture thereof. More preferably, the acetyl methionine compound is selected from acetyl methionine, salt of acetyl methionine, or a mixture thereof. The particularly preferred acetyl methionine compound is acetyl methionine. Preferably, the acetyl methionine compound is Acetyl-DL-methionine, N-Acetyl-L-methionine, Acetyl-D-methionine, or a combination thereof. In a further aspect, the acetyl methionine compound may be present in any of its isomeric forms and in combinations thereof. “Isomers”, as used herein, is meant to include D-isomers, L-isomers, and / or DL-isomers for a particular compound. Thus, the acetyl methionine compound comprises its D-isomer form, L-isomer form, DL-isomer form, ora combination thereof. For example, N-acetyl methionine may be present in any of its isomeric forms and in combinations thereof. For example, N-acetyl-DL-methionine (i.e., is in its DL-isomer form), N-acetyl-D-methionine (i.e., is in its D-isomer form) and N-acetyl-L-methionine (i.e., is in its L-isomer form).

[0022] Typically, the acetyl methionine compound is present in the composition disclosed herein in an amount of from 0.0001 to 10%, or from 0.0005 to 8%, or from 0.001 to 6%, or from 0.005 to 5%, or from 0.01 to 4%, or from 0.02 to 3.5%, or from 0.025 to 3%, or from 0.05 to 2.5%, or from 0.1 to 2.5%, or from 0.1 to 2%, or from 0.2 to 1.5% by weight of the composition. In another aspect, the acetyl methionine compound is present in the composition in an amount from 0.001 to 5%, or from 0.005 to 4%, or from 0.01 to 3%, or from 0.05 to 3%, or from 0.1 to 3%, or from 0.25 to 2% by weight of the composition.

[0023] Where the composition comprises acetyl methionine, acetyl methionine (or N-acetyl methionine) has the following structural formula (which is available from numerous suppliers, including Sigma-Aldrich):

[0024]

[0025] In one aspect, at least 50%, or at least 70%, or at least 80%, or at least 90%, or 100% by weight of the acetyl methionine compound is acetyl methionine. In one aspect, from 50 to 100%, or from 60 to 100%, or from 70 to 100%, or from 80 to 100%, or from 90 to 100%, or from 80 to 95%, or from 85 to 95%, by weight, of the acetyl methionine compound is acetyl methionine.

[0026] Preferably, the molar ratio of the carboxymethyl cysteine compound to the acetyl methionine compound is 1:1.6 to 1.8:1, more preferably 1:1.4 to 1.6:1, and even more preferably 1:1.3 to 1.4:1. Preferably, the molar ratio of the carboxymethyl cysteine compound to the total acetyl methionine and salt of acetyl methionine is 1 : 1.6 to 1.8: 1 , more preferably 1 : 1.4 to 1.6:1, and even more preferably 1:1.3 to 1.4:1. Preferably, the molar ratio of the lysine carboxymethyl cysteinate to the total acetyl methionine and salt of acetyl methionine is 1:1.6 to 1.8:1, more preferably 1:1.4 to 1.6:1, and even more preferably 1:1.3 to 1.4:1. Preferably, the molar ratio of the lysine carboxymethyl cysteinate to the acetyl methionine is 1:1.6 to 1.8:1, more preferably 1 : 1.4 to 1.6: 1 , and even more preferably 1 : 1.3 to 1.4: 1.

[0027] Preferably, the present invention provides a personal care composition comprising carboxymethyl cysteine compound and acetyl methionine, wherein the molar ratio of the carboxymethyl cysteine compound to the total acetyl methionine and salt of acetyl methionine is 1:1.6 to 2:1. More preferably, the present invention provides a personal care composition comprising lysine carboxymethyl cysteinate and acetyl methionine, wherein the molar ratio of the lysine carboxymethyl cysteinate to the acetyl methionine is 1:1.6 to 2:1.

[0028] The composition may comprise substituted resorcinol. Substituted resorcinol typically refers to that at least one hydrogen on the ring structure and / or on a hydroxy group of the resorcinol replaced with an alkyl group, phenyl alkyl group, or heterocyclic group. Preferably, the substituted resorcinol is 4-substituted resorcinol. Preferably, the substituted resorcinol is selected from 4-ethyl resorcinol, 4-butyl resorcinol, 4-hexyl resorcinol, phenylethyl resorcinol, thiamidol, or a mixture thereof, more preferably, the substituted resorcinol is selected from 4-ethyl resorcinol, 4-butyl resorcinol, 4-hexyl resorcinol, or a mixture thereof and even more preferably, the substituted resorcinol comprises 4-hexyl resorcinol. The amount of the substituted resorcinol is preferably in the range of 0.00001 to 10%, more preferably from 0.001 to 5% and most preferably from 0.1 to 0.6% by weight of the total amount of the composition.

[0029] Preferably, the composition comprises Vitamin B3 compounds (including derivatives of vitamin B3). The vitamin B3 compounds comprises niacin, nicotinic acid, niacinamide or a mixture thereof. The most preferred vitamin B3 compound is niacinamide. Amount of Vitamin B3 compounds may be 0.1 to 10%, preferably 0.5 to 5% by weight of the composition. 2-mercaptonicotinoyl glycine may also be included in the composition. Amount of 2-mercaptonicotinoyl glycine may be 0.0001 to 10%, preferably 0.01 to 1% by weight of the composition.

[0030] Preferably, the composition comprises a glutamate source selected from the group consisting of glutamine, glutamine ester, glutamic acid, pyroglutamic acid, salts, and mixtures thereof. More preferably, the composition comprises pyroglutamic acid and / or salt of pyroglutamic acid. Even more preferably, the composition comprises sodium salt of pyroglutamic acid. Preferably, the glutamate source is present in amount of 0.0001 to 10% by weight of the composition, more preferably 0.001 to 6%, even more preferably 0.01 to 3% by weight of the composition.

[0031] The composition may optionally comprise whitening pigment. Whitening pigments are typically particles of high refractive index materials. For example, the whitening pigment may have a refractive index of greater than 1.3, more preferably greater than 1.8 and most preferably from 2.0 to 2.7. Examples of such whitening pigment are those comprising bismuth oxy-chloride, boron nitride, barium sulfate, mica, silica, titanium dioxide, zirconium oxide, aluminium oxide, zinc oxide or combinations thereof. More preferred whitening pigment are particles comprising titanium dioxide, zinc oxide, zirconium oxide, mica, iron oxide or a combination thereof. Even more preferred whitening pigment are particles comprising zinc oxide, zirconium oxide, titanium dioxide or a combination thereof as these materials have especially high refractive index. Still even more preferably the whitening pigment is selected from titanium dioxide, zinc oxide or a mixture thereof and most preferred whitening pigment is titanium dioxide. The average diameter of whitening pigment is typical from 15 nm to 1 micron, more preferably from 35 nm to 800 nm, even more preferably from 50 nm to 500 nm and still even more preferably from 100 to 300 nm. Amount of whitening pigment may be 0.1 to 15%, preferably 0.5 to 5% by weight of the composition.

[0032] Preferably, the composition comprises polyhydric alcohol. Polyhydric alcohols may be selected from group of glycerin, propylyene glycol, dipropylene glycol, polypropylene glycol, polyethylene glycol, sorbitol, hydroxypropyl sorbitol, hexylene glycol, 1,3-butylene glycol, isoprene glycol, ethoxylated glycerol, propoxylated glycerol or a mixture thereof. Most preferred polyhydric alcohol is glycerol known also as glycerin. The amount of polyhydric alcohol may range anywhere from 0.1 to 20%, preferably 0.5 to 15% and more preferably 2 and 10% by weight of the composition.

[0033] Preferably, the composition comprises emollient materials. Suitable emollient materials include silicones, hydrocarbons, triglycerides or a mixture thereof. These silicones may be organic, silicone-containing or fluorine-containing, volatile or non-volatile, polar or non-polar.

[0034] Hydrocarbons may include mineral oil, petrolatum and polyalpha-olefins. Examples of preferred volatile hydrocarbons include polydecanes such as isododecane and isodecane (e.g.

[0035] Permethyl-99A which is available from Presperse Inc.) and the C7-C8 through C12-C15 isoparaffins (such as the Isopar Series available from Exxon Chemicals). Illustrative triglycerides but not limiting are sunflower seed oil, cotton oil, canola oil, soybean oil, castor oil, borage oil, olive oil, shea butter, jojoba oil and mixtures thereof. Mono- and di- glycerides may also be useful. Particularly preferable are glyceryl monostearate and glyceryl distearate.

[0036] Preferably, the composition comprises moisturizing agents. Particularly preferred moisturizing agents includes, petrolatum, aquaporin manipulating actives, oat kernel flour, substituted urea like hydroxyethyl urea, hyaluronic acid and / or its precursor N-acetyl glucosamine, hyaluronic acid and / or its precursor N-acetyl glucosamine, or a mixture thereof.

[0037] Some compositions may include thickeners. These may be selected from cellulosics, natural 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.

[0038] In addition, the compositions of the invention may further include 0.5 to 10% by weight of sequestering agents, such as tetra sodium ethylenediaminetetraacetate (EDTA), EHDP or mixtures; opacifiers and pearlizers such as ethylene glycol distearate, titanium dioxide or Lytron 621 (Styrene / Acrylate copolymer); all of which are useful in enhancing the appearance or properties of the product.

[0039] The composition may comprise water in amount of 10 to 96% by weight of the composition, more preferably from 25 to 92%, even more preferably from 42 to 88%, most preferably from 55 to 82% by weight of the composition.

[0040] Preferably, the composition has a viscosity of at least 10 mPa s, more preferably in the range 30 to 10000 mPa s, even more preferably 50 to 5000 mPa s, and most preferably 100 to 2000 mPa s, when measured at 20 degrees C at a relatively high shear rate of about 20 s'1.

[0041] Preferably, the composition is an emulsion, more preferably an oil-in-water emulsion. Preferably the composition is a fluid liquid at 25 °C and atmospheric pressure. Preferably, the composition is an emulsion, more preferably an oil-in-water emulsion.

[0042] Preferably, the personal care composition is a skin care composition. The skin care composition refers to a composition suitable for topical application to human skin, including leave-on and wash-off products but preferably leave-on compositions. The term “leave-on” as used with reference to compositions herein means a composition that is applied to or rubbed on the skin and left thereon. The term “wash-off” as used with reference to compositions herein means a skin cleanser that is applied to or rubbed on the skin and rinsed off substantially immediately subsequent to application. Preferably the composition is a fluid liquid, and particularly a moisturizer rather than a make-up product. The term "skin" as used herein includes the skin on the face, neck, chest, abdomen, back, arms, under arms, hands, and legs. Preferably “skin” means includes the skin on the face and under arms, more preferably skin means skin on the face other than lips and eyelids.

[0043] Preferably, the composition is a topical composition. Preferably, the composition may be in the form of cream, lotion, ointment, solution, suspension, emulsion, paste, gel, powder, powder foundation, emulsion foundation, wax foundation, or spray. More preferably, the composition may be formulated in the form of cream, lotion, ointment, emulsion, gel, or a spray.

[0044] Preferably, the composition is capable of upregulating the expression of AQP3 gene by at least 1.5 folds change, more preferably 2 to 30, and even more preferably 5 to 25 folds change, and still even more preferably 9 to 17 folds change, typically in comparison to personal care composition comprising neither carboxymethyl cysteine compound nor acetyl methionine compound, or blank control.

[0045] 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.

[0046] The following examples are provided to facilitate an understanding of the invention. The examples are not intended to limit the scope of the claims. Example 1

[0047] This example demonstrates upregulation of gene expression by combining lysine carboxymethyl cysteinate and acetyl methionine in specific ratio.

[0048] The normal human epidermal keratinocytes (NHEKs) (Biocell, Xi’an, China, LOT: Ep23073102) 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, and then challenged skin cells with blue light (10J / cm2) except the control group, after 24 hours incubation, the total RNA for NHEKs was extracted using RNAex Pro reagent (Accurate Biotechnology, Cat: AG21102) according to manufacturer’s protocol.

[0049] The extracted RNA was quantified 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 qPCR (Accurate Biotechnology, Cat: AG11706) according to manufacturer’s protocol. Gene expression of AQP3 gene was analyzed by polymerase chain reaction (PCR) using SYBR® Green Premix Pro Taq HS qPCR Kit (Accurate Biotechnology, AG11701). The actin beta (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 for AQP3. Table 1

[0050] Ingredient (pM) * Fold changes Molar ratio of

[0051] Sample of AQP3 gene LCCaAceMetbLCC to AceMet

[0052] Expression A (Control) - 1.00 B (Blue light exposure) - 0.74 C 25 0.95 D 50 6.68 E 100 5.84 F - 10 8.93 G 25 10 2.5:1 1.76cH 50 10 5:1 6.51cI 100 10 10:1 6.03cJ - 100 - 3.31 K 25 100 1:4 1.22cL 50 100 1:2 4.57c

[0053]

[0054] 1 100 100 1:1 13.37d

[0055] *The level of the ingredients refers the level of active based on the medium.

[0056] a: LCC means Lysine carboxymethyl cysteinate, Hair App, supplied by Sinerga.

[0057] b: AceMet means Acetyl Methionine, supplied by Sigma.

[0058] c: Significantly lower than at least one single active (p < 0.05).

[0059] d: Significantly higher than either of single actives (p < 0.05).

[0060] It was evident from Table 1 that only when combining lysine carboxymethyl cysteinate and acetyl methionine in specific ratio of the present invention, the expression AQP3 gene was significantly upregulated (sample 1). In contrast, the combination of lysine carboxymethyl cysteinate and acetyl methionine with ratio outside of the present did not evaluate the AQP3 gene expression (sample G, H, I, K, or L).

Claims

Claims1. A personal care composition comprising carboxymethyl cysteine compound and acetyl methionine compound, wherein the molar ratio of the carboxymethyl cysteine compound to the acetyl methionine compound is 1:1.6 to 2:1, the carboxymethyl cysteine is selected from carboxymethyl cysteine, salt of carboxymethyl cysteine, ester of carboxymethyl cysteine, amide of carboxymethyl cysteine or a mixture thereof, and the acetyl methionine compound is selected from acetyl methionine, salt of acetyl methionine, ester of acetyl methionine, amide of acetyl methionine, salt of ester of acetyl methionine, or salt of amide of acetyl methionine, or a mixture thereof.

2. The composition according to claim 1 wherein the carboxymethyl cysteine compound comprises carboxymethyl cysteine, ester of carboxymethyl cysteine, and / or salt of carboxymethyl cysteine.

3. The composition according to claim 2 wherein the carboxymethyl cysteine compound comprises salt of carboxymethyl cysteine and preferably the carboxymethyl cysteine compound comprises lysine carboxymethyl cysteinate.

4. The composition according to any one of the preceding claims wherein the carboxymethyl cysteine compound is present in amount of at least 0.00001% and no greater than 10% by weight of the composition, preferably carboxymethyl cysteine compound is present in amount of at least 0.01 % and no greater than 3% by weight of the composition.

5. The composition according to any one of the preceding claims wherein the acetyl methionine compound is selected from acetyl methionine, salt of acetyl methionine, ester of acetyl methionine, salt of ester of acetyl methionine, or a mixture thereof, preferably the acetyl methionine compound is acetyl methionine.

6. The composition according to any one of the preceding claims wherein the acetyl methionine compound is present in the composition in an amount of from 0.0001 to 10%, preferably 0.05 to 2.5% by weight of the composition.

7. The composition according to any one of the preceding claims wherein the molar ratio of the carboxymethyl cysteine compound to the acetyl methionine compound is 1:1.6 to 1.8:1 preferably 1:1.3 to 1.4:1.

8. The composition according to any one of the preceding claims wherein the composition is an emulsion, preferably an oil-in-water emulsion.

9. The composition according to any one of the preceding claims wherein the composition comprises water in amount of 10 to 96% by weight of the composition, preferably from 42 to 88% by weight of the composition.

10. A method of providing the skin benefits selected from the group consisting of improving skin barrier health, strengthening skin barrier, increasing skin hydration, and improving immune response comprising a step of topically applying to the skin the composition of any one of the preceding claims.

11. Use of the composition of any one of the preceding claims 1 to 10 for providing the skin benefits selected from the group consisting of improving skin barrier health, strengthening skin barrier, increasing skin hydration, and improving immune response.

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