Personal care composition

Abstract

Disclosed is a personal care composition comprising: (a) rosemary extract and (b) retinoid, wherein the weight ratio of the rosemary extract to the retinoid is at least 1:1 and the retinoid is retinyl propionate.

Description

[0001] P0000932EP CPL

[0002] 1

[0003] PERSONAL CARE COMPOSITION

[0004] Field of the Invention

[0005] The present invention relates to a personal care composition comprising: (a) rosemary extract

[0006] 5 and (b) retinoid, wherein the weight ratio of the rosemary extract to the retinoid is at least 1 :1 and the retinoid is retinyl propionate. It was surprisingly found that such composition is capable of significantly upregulating the expression of filaggrin 2 (FLG2) gene.

[0007] Background of the Invention

[0008] 10 Skin is an organ that protects 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 barrier consists of different layers of stratified cells and the outermost layer consists of corneocytes embedded in a layer of lipids. The major constituents of corneocytes are proteins like keratin, filaggrin etc. These proteins are essential for the formation

[0009] 15 and maintenance of a healthy skin barrier. Any damage or dysfunction of these proteins lead to defective barrier and associated skin conditions like dryness, atopic dermatitis increased susceptibility to skin infections, inability to support a healthy microbiome etc.

[0010] Among the skin proteins, filaggrin play a pivotal role in maintaining healthy barrier. It is a structural

[0011] 20 protein involved in the terminal differentiation of keratinocytes. Proteolysis of filaggrin releases free amino acids and these free amino acids are the important constituents of natural moisturization factor (NMF) which imparts skin hydration. Filaggrin maintains barrier integrity thereby preventing entry of pathogens, and other irritants and allergens. Loss of filaggrin results in skin conditions like atopic dermatitis, an inflammatory skin condition manifested as dry, itchy

[0012] 25 and flaky skin. Filaggrin also helps in maintaining a healthy microbiome by protecting the skin from pathogens. One of the mechanisms by which moisturizers function is by boosting filaggrin in skin. Increasing filaggrin levels on skin is a well-accepted approach for maintaining or improving skin health. Upregulating the expression of filaggrin genes typically leads to an increase in filaggrin production.

[0013] 30

[0014] Therefore, the present inventors have recognized that there is a need to develop solution to enhance the expression of filaggrin 2 (FLG2). It was surprisingly found that by combining rosemary extract and retinoid in a specific ratio, the expression of FLG2 gene was significantly upregulated.

[0015] 35 P0000932EP CPL

[0016] 2

[0017] Summary of the Invention

[0018] In a first aspect, the present invention is directed to a personal care composition comprising: (a) rosemary extract and (b) retinoid, wherein the weight ratio of the rosemary extract to the retinoid is at least 1 :1 and the retinoid is retinyl propionate.

[0019] 5

[0020] In a second aspect, the present invention is directed to a method of providing the skin benefits selected from the group consisting of enhancing filaggrin production in the skin, improving skin barrier health, upregulating the expression of filaggrin 2 gene comprising a step of topically applying to the skin the composition of the composition of the present invention.

[0021] 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 enhancing filaggrin production in the skin, improving skin barrier health, upregulating the expression of filaggrin 2 gene.

[0022] 15

[0023] All other aspects of the present invention will more readily become apparent upon considering the detailed description and examples which follow.

[0024] Detailed Description of the Invention

[0025] 20 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”.

[0026] All amounts are by weight of the composition, unless otherwise specified.

[0027] 25

[0028] It should be noted that in specifying any range of values, any particular upper value can be associated with any particular lower value.

[0029] 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.

[0030] 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

[0031] 35 claims may be found without multiple dependency or redundancy. P0000932EP CPL

[0032] 3

[0033] 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.

[0034] 5

[0035] The retinoid is retinyl propionate. Preferably, retinoid is employed in the composition in an amount of 0.0001 to 20% by weight of the composition, more preferably in an amount of 0.005 to 15%, even more preferably in an amount of 0.2 to 12%, still even more preferably from 1 to 8%, and most preferably 2 to 6% by weight of the composition.

[0036] The rosemary extract as used herein refers to an extract of rosemary (Rosmarinus officinalis). Preferably, the rosemary extract is extracted from leaf, stem, germ, flower, branch, root, and / or seed of rosemary, more preferably from leaf, stem, germ, flower, and / or branch of rosemary. Even more preferably the rosemary extract is rosemary leaf extract. Still even more preferably

[0037] 15 the rosemary extract has INCI (International Nomenclature of Cosmetic Ingredients) name of Rosmarinus Officinalis (Rosemary) Leaf Extract.

[0038] Preferably, the rosemary extract is an aqueous extract. The term “aqueous extract” means that the extract is obtained by using water, or water mixing with hydrophilic organic solvent as the solvent

[0039] 20 for extraction. The hydrophilic organic solvent may be selected from C1-C5 alcohol (including polyalcohol), C3-C6 aliphatic ketone; and C2-C5 polyalcohol. Preferably the hydrophilic organic solvent is selected from ethanol, acetone, ethyl acetate, glycerin, isoprene glycol, butylene glycol or a mixture thereof. Preferably the hydrophilic organic solvent is selected from ethanol, acetone, ethyl acetate, glycerin, isoprene glycol, butylene glycol or a mixture thereof. More preferably, the rosemary extract is obtainable by using water, ethanol, acetone, ethyl acetate, glycerin, butylene glycol or a mixture thereof. Even more preferably, the extraction of the rosemary extract comprises steps of using water, butylene glycol and / or glycerin as solvent for extraction.

[0040] Typically, the extraction of the rosemary extract may comprise solid-liquid extraction, liquid-liquid

[0041] 30 extraction, immersion, decoction, steam distillation, reflux extraction, sonication extraction, microwave extraction, homogenization, filtration, or combination thereof, preferably the extraction of the rosemary extract comprises solid-liquid extraction, steam distillation, reflux extraction, sonication extraction, microwave extraction, or homogenization, filtration, or combination thereof. P0000932EP CPL

[0042] 4

[0043] Preferably, the extraction of the rosemary extract comprises the step of extracting the leaves and / or stalks of rosemary by using water, and / or glycerin as solvent, preferably by microwave extraction.

[0044] 5 Preferably, the rosemary extract is present in amount of 0.00001 to 10% by weight of the composition, more preferably 0.0001 to 3%, even more preferably 0.001 to 1%, and still even more preferably 0.01 to 0.5% by weight of the composition. For sake of clarity, the weight of extract in the present invention refers to the weight of extract extracted from the plant. Thus, the extracting solvent is excluded.

[0045] Preferably the weight ratio of the rosemary extract to the retinoid is 1 : 1 to 1000: 1 , more preferably 2:1 to 300:1 , even more preferably 4:1 to 80:1 , and still even more preferably 5:1 to 20:1.

[0046] The present invention also provides a composition comprising (a) rosemary extract and (b) retinyl

[0047] 15 propionate, wherein the weight ratio of the rosemary extract to the retinyl propionate is at least 1 :1. Preferably, the retinyl propionate is present in an amount of 0.0001 to 20% by weight of the composition, more preferably in an amount of 0.005 to 15%, even more preferably in an amount of 0.2 to 12%, still even more preferably from 1 to 8%, and most preferably 2 to 6% by weight of the composition. Preferably the weight ratio of the rosemary extract to the retinyl propionate is

[0048] 20 1 : 1 to 1000: 1 , more preferably 2: 1 to 300: 1 , even more preferably 4: 1 to 80: 1 , and still even more preferably 5:1 to 20:1.

[0049] Preferably, the composition comprising (a) rosemary leaf extract and (b) retinyl propionate, wherein the weight ratio of the rosemary leaf extract to the retinyl propionate is at least 1 :1.

[0050] 25 Preferably the weight ratio of the rosemary leaf extract to the retinyl propionate is 1 :1 to 1000:1 , more preferably 2:1 to 300:1 , even more preferably 4:1 to 80:1 , and still even more preferably 5:1 to 20:1 . Preferably, the rosemary leaf extract is present in amount of 0.00001 to 10% by weight of the composition, more preferably 0.0001 to 3%, even more preferably 0.001 to 1%, and still even more preferably 0.01 to 0.5% by weight of the composition.

[0051] 30

[0052] 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 P0000932EP CPL

[0053] 5 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.

[0054] The composition may optionally comprise whitening pigment. Whitening pigments are typically

[0055] 5 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

[0056] 15 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.

[0057] Preferably, the composition comprises polyhydric alcohol. Polyhydric alcohols may be selected

[0058] 20 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.

[0059] 25

[0060] 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. Hydrocarbons may include mineral oil, petrolatum and polyalpha-olefins. Examples of preferred volatile hydrocarbons include polydecanes such as isododecane and isodecane (e.g. 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

[0061] 35 preferable are glyceryl monostearate and glyceryl distearate. P0000932EP CPL

[0062] 6

[0063] 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

[0064] 5 and / or its precursor N-acetyl glucosamine, or a mixture thereof.

[0065] 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.

[0066] 15

[0067] 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

[0068] 20 properties of the product.

[0069] 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.

[0070] 25

[0071] 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.

[0072] 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.

[0073] Preferably, the composition is an emulsion, more preferably an oil-in-water emulsion. Preferably, the personal care composition is a skin care composition. The skin care composition refers to a

[0074] 35 composition suitable for topical application to human skin, including leave-on and wash-off P0000932EP CPL

[0075] 7 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

[0076] 5 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.

[0077] 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.

[0078] 15

[0079] Preferably, the composition is capable of upregulating the expression of filaggrin 2 gene by at least 1.2 fold change, more preferably 1.4 to 12 and most preferably 2 to 10 and most preferably 3 to 8 fold change, typically in comparison to personal care composition comprising rosemary extract or retinoid alone, or in comparison to personal care composition comprising rosemary

[0080] 20 extract and retinoid with a weight ratio less than 1 :1 , for example 0.05:1 to 0.08:1.

[0081] 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.

[0082] 25 The following examples are provided to facilitate an understanding of the invention. The examples are not intended to limit the scope of the claims.

[0083] P0000932EP CPL

[0084] 8

[0085] Examples

[0086] Example 1

[0087] This Example demonstrates the synergistic upregulation of FLG2 gene expression by combining rosemary extract and retinyl propionate in a specific weight ratio.

[0088] 5

[0089] Living skin equivalent (EpiKutis®) is a 3D reconstructed human epidermis model was supplied by Biocell Biotech Gudong, China (Lot: ES240703). Squalene monohydroperoxide (SQOOH), a stress surrogate, was prepared in house, by subjecting squalene to solar irradiation in the presence of a sensitizer. Skin models of non-treatment (control) group were incubated for six days with daily culture medium refreshment. For SQOOH treatment group, skin models were cultured for four days with daily culture medium refreshment till treatment. On Day 5, skin models were treated with 10pL of 1 wt% of SQOOH topically and incubated for another 24 hours before sample collection. In the three treatment groups, the testing samples (individuals or combinations, 5pL for each) were applied on the top of skin models before SQOOH application on Day 5. After

[0090] 15 treatment, the skin models were also incubated for another 24 hours till harvest.

[0091] Upon collection, samples were homogenized in AG RNAex Pro Reagent (Accurate Biotechnology, AG21102, China) with T 10 basic ULTRA-TURRAX® (IKA, Germany) and total RNA was extracted with chloroform. The extracted RNA was quantified using Nanodrop spectrometer

[0092] 20 (Thermo Fisher Scientific, Waltham, US) and reverse transcribed to generate the template cDNA using the Evo M-MLV (Accurate Biotechnology, AG11728, China) according to manufacturer’s protocol. Gene expression of FLG2 gene was analyzed by PCR using SYBR Green Premix Pro Taq HS qPCR Kit, the beta-actin gene was selected as the housekeeping gene. The relative expression of the target genes was normalized to housekeeping gene. The fold changes of active

[0093] 25 treated samples relative to the control were calculated (2(-AACt)) and used for comparison between treatments. All tests were conducted at least three times and Table 1 shows the fold changes in expression of FLG2 gene. P0000932EP CPL

[0094] 9

[0095] Table 1

[0096] 5 *The levels of the ingredients refer to the level of listed ingredient based on the medium. a: Phytexcell rosemary supplied by Croda, containing 5-8% of rosemary extract by weight of the Phytexcell rosemary. The rosemary for making rosemary extract is from China. b: Retinyl propionate, cat no.: sc-236667, supplied by Santa Cruz Biotechnology (USA). c: Significantly better (p<0.01) than either of single active at same level.

[0097] 10

[0098] It was evident from Table 1 that only when combining rosemary extract and retinyl propionate in a specific weight ratio of the present invention, the expression of FLG2 gene was synergistically upregulated (1, 2 and 3). In contrast, when combining rosemary extract and retinyl propionate in 15 a weight ratio not within the range of the present invention, the expression of FLG2 gene was not upregulated (I, J, and K). P0000932EP CPL

[0099] Example 2

[0100] This Example demonstrates the comparison of rosemary extract with different retinoid.

[0101] The normal human epidermal keratinocytes (NHEKs) (Biocell, Xi’an, China, LOT: Ep23073102)

[0102] 5 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.

[0103] 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. The expression of FLG2 gene was analyzed by polymerase chain reaction (PCR) using

[0104] 15 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 2 shows the fold change of the gene expression for FLG2.

[0105] 20

[0106] Table 2

[0107] *The levels of the ingredients refer to the level of listed ingredient based on the medium. a: Phytexcell rosemary supplied by Croda, containing 5-8% of rosemary extract by weight of the Phytexcell rosemary. The rosemary for making rosemary extract is from China. b: Retinyl propionate, cat no.: sc-236667, supplied by Santa Cruz Biotechnology (USA). c: Retinyl palmitate, Cat: PHR1235, supplied by MERCK. d: Retinyl acetate, Cat: PHR1236, supplied by MERCK. e: Significantly better (p<0.01) than either of single active at same level.

[0108] 30 P0000932EP CPL

[0109] 11

[0110] As shown in Table 2, when combining rosemary extract with retinyl propionate, the fold change of FLG2 gene expression was higher than the fold change either by rosemary extract alone, or retinyl propionate alone (2.09 > 1.29*1.36), indicating synergistic upregulation. In contrast, when combining rosemary extract with retinyl palmitate, or retinyl acetate, it was not capable of

[0111] 5 providing synergistic upregulation of FLG2 gene expression.

Claims

P0000932EP CPL12Claims1. A personal care composition comprising:(a) rosemary extract; and(b) retinoid, wherein the weight ratio of the rosemary extract to the retinoid is at least 1 :1 and the retinoid is retinyl propionate.

2. The composition according to claim 1 wherein the retinoid is employed in the composition in an amount of 0.0001 to 20% by weight of the composition, preferably in an amount of 0.2 to 12% by weight of the composition.

3. The composition according to any one of the preceding claims wherein the rosemary extract is rosemary leaf extract.

4. The composition according to any one of the preceding claims wherein the rosemary extract is obtainable by using water, ethanol, acetone, ethyl acetate, glycerin, butylene glycol or a mixture thereof.

5. The composition according to any one of the preceding claims wherein the rosemary extract is present in amount of 0.00001 to 10% by weight of the composition, preferably 0.001 to 1 % by weight of the composition.

6. The composition according to any one of the preceding claims wherein the weight ratio of the rosemary extract to the retinoid is 1 :1 to 1000:1 , preferably 4:1 to 80:1.

7. A composition comprising (a) rosemary extract and (b) retinyl propionate, wherein the weight ratio of the rosemary extract to the retinyl propionate is at least 1 :1.

8. The composition according to claim 7 wherein the retinyl propionate is present in an amount of 0.005 to 15%, preferably in an amount of 0.2 to 12% by weight of the composition.

9. The composition according to claim 8 wherein the weight ratio of the rosemary extract to the retinyl propionate is 1 :1 to 1000:1 , preferably 4:1 to 80:1.P0000932EP CPL1310. The composition according to any one of the preceding claims wherein the composition is an emulsion, preferably an oil-in-water emulsion.

11. The composition according to any one of the preceding claims wherein the composition is a fluid liquid at 25 °C and atmospheric pressure.

12. 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.

13. A method of providing benefit selected from the group consisting of enhancing filaggrin production in the skin, improving skin barrier health, upregulating the expression of filaggrin 2 gene comprising the steps of topically applying to the skin the composition of any one of the preceding claims 1 to 12.

14. Use of the composition of any one of the preceding claims 1 to 12 for providing benefits selected from the group consisting of enhancing filaggrin production in the skin, improving skin barrier health, upregulating the expression of filaggrin 2 gene.

Images