CN110623949A - A composition containing azelaic acid monometal salt and Monoxazone for whitening and refining skin, and its preparation method - Google Patents

Abstract

The present invention provides a composition for whitening and thinning skin, which contains at least (a) azelaic acid or a salt thereof and (b) moenoxazone. Can be prepared into powder by mixing and grinding, or can be prepared into tablets, dispersion, emulsion, gel and paste for removing freckles, whitening and refining skin cosmetics, and meanwhile, the invention provides a method for treating rough skin caused by hyperpigmentation or acne of mammals (including human beings), which comprises applying a composition containing azelaic acid monometallic salt and moenobenzone on the skin surface of the mammals. The synergistic interaction of the azelaic acid metal salt and the morronizone overcomes the defects that azelaic acid is not easy to be compatible and the existing tyrosinase inhibitor is used for treating hyperpigmentation, and can achieve multiple effects of inhibiting bacteria, whitening, removing freckles, removing acne and refining skin.

Description

A composition containing azelaic acid monometal salt and Monoxazone for whitening and refining skin, and its preparation method

Technical Field

The invention relates to a composition containing azelaic acid and salts thereof and moenobenzone with skin whitening and refining effects and a preparation method thereof. More particularly, the present invention relates to compositions containing azelaic acid and its metal salts and monenzone having enhanced ability to whiten (light) and exfoliate mammalian skin.

Background

Pigmentation is a change in the pigmentation of human skin in different colors and shades in different areas for various reasons, and is directly related to the presence of melanogenesis, which is directly related to tyrosinase, and when tyrosinase activity is inhibited, the conversion of tyrosine and cysteine to melanin is reduced, with the end result that the skin becomes whitened.

Currently, tyrosinase inhibitors are increasingly regarded as being important in treating hyperpigmentation, clinically used hydroquinone is a tyrosinase substrate having antagonistic and competitive effects on tyrosine, but is unstable and irritant, and an etherification product, namely, the monenzone, is mild, but the cytotoxicity is increased when the dosage is large, and the skin becomes thin and the sensitivity is increased. Monoxazone is earlier applied to medicines for treating leukoplakia and leucoderma (such as Chinese patent 201410116500.1) and medicines for treating or preventing herpes virus infection (Chinese patent 201510675321.6), and the safety and treatment effect of the Monoxazone are confirmed. In the aspect of cosmetics, a series of Chinese patents (such as 201611099091.4, 201710039571.X and the like) apply the moenozonone and natural plant extract to various cosmetics for facial use, and do not take the main purposes of removing spots and acnes and whitening the skin. Chinese patent 201610552682.6 discloses a spot-removing whitening composition containing moenoxazone, which is used in large amounts and has no known effect on other skin lesions such as acne. Good skin needs to be fair, fine and smooth without roughness, and the moenozon cannot cope with various skin protrusions and has no function of thinning the skin. Azelaic acid is a prismatic crystal extracted from azalea and has an effect of inhibiting or killing anaerobic and aerobic bacteria in skin areas [ Journal of Applied bacteriology, 1998, 64: 497; drugs, 1991, 41 (5): 780.] in vitro are competitive inhibitors of tyrosinase [ practical skin disease therapy [ M ]. sheng yang: liaoning science and technology Press, 1992.555; supplement to medical prediction.1993, 20 (6): 19.], can be used for treating acne, rosacea, chloasma and the like, and the medical effect of the medicine is proved. However, the application of the emulsion is greatly limited due to insolubility and poor compatibility, and the utilization rate of some emulsion products is greatly reduced due to microcrystalline azelaic acid which can be seen in the emulsion products. The research shows that the water solubility of the azelaic acid monometallic salt, especially alkali metal salt, is good, the compatibility is stronger, and the utilization rate of the azelaic acid is ensured. The azelaic acid double metal salt is better in water solubility, but is converted into the azelaic acid single metal salt under the action of the pH regulator. Therefore, the invention relates to a tyrosinase inhibitor containing azelaic acid single metal salt and morronibenzone with better effect, which overcomes the defects that azelaic acid is not easy to be compatible and the existing tyrosinase inhibitor is used for treating hyperpigmentation and refining skin, and the synergy of the azelaic acid single metal salt and the morronibenzone can achieve multiple effects of bacteriostasis, whitening, freckle removing, acne removing and skin refining.

Disclosure of Invention

The present invention relates to cosmetic and dermatological whitening and thinning skin compositions for use in a method of treating hyperpigmentation or dermatological disorders associated with acne. More particularly, the present invention relates to a composition exhibiting enhanced ability to whiten skin color and effectively improving skin smoothness.

Accordingly, the present invention provides a whitening and refining skin effect composition comprising at least (a) azelaic acid or a salt thereof and (b) moenobenzone. Azelaic acid or a metal salt thereof is present in an amount of 0.1 to 30% by weight, preferably 2 to 10% by weight, said weight being based on the total weight of the composition; the moenobenzone is present in an amount of 0.1 to 80% by weight, preferably 1 to 20% by weight, based on the total weight of the composition. The azelaic acid or the salt thereof is azelaic acid, azelaic acid monometallic salt and azelaic acid bimetallic salt, wherein the azelaic acid monometallic salt is metal potassium and sodium salt of carboxyl at one end of azelaic acid molecule, the other end is still carboxyl structure, and the azelaic acid monometallic salt has water solubility, can be prepared by reacting azelaic acid with alkali metal hydroxide according to a known method (US Patent 6392074, 2002-05-21), is prepared by neutralizing acid, is dissolved in water for use, and can be purchased as a product of azelaic acid monometallic salt on the market. The azelaic acid double metal salt is metal potassium and sodium salt of carboxyl at two ends of azelaic acid molecules. Experiments show that the water solubility of the azelaic acid monometallic salt is improved, and the synergistic function of the azelaic acid monometallic salt and the moenoxazone is not reduced, the comparison result of adding different contents of azelaic acid and azelaic acid monometallic salt in 10 wt% of the moenoxazone is shown in figure 1, and the result shows that, at low content, the same amount of azelaic acid and azelaic acid monometallic salt is added in the moenoxazone, the melanin inhibiting effect is close, but the effect of the azelaic acid is relatively poor when the content of the azelaic acid or the azelaic acid monometallic salt exceeds 10%. Bimetallic salts of azelaic acid, such as the potassium and sodium salts, are more water soluble but may be present as monometallic salts of azelaic acid in combination with the acidity regulator, and therefore do not perform better than monometallic salts of azelaic acid, but instead require the addition of more acidic regulator, as illustrated in the later examples.

The formulation of the whitening and skin-thinning composition is of any type, and examples thereof include emulsion type such as oil-in-water (O/W) type, water-in-oil (W/O) type, W/O/W type, O/W/O type, powder type, paste type, stick type, gel type, paste type, sheet type, and spray type, but are not limited thereto. The product form is also arbitrary, and may be cosmetics or medical supplies such as powder, dispersion, lotion, cream, pack, spray, gel, and sheet. The whitening and refining skin effect composition can be prepared into any form of semi-solid, liquid cosmetics by adding various liquid components, including water, alcohol, ether, oil, ester, amide or their mixed solution, in addition to powder, tablet, and pack. The alcohol may be a mono-, di-, or polyhydric alcohol such as ethanol, propanol, butanol, pentanol, octanol, dodecanol, hexadecanol, propylene glycol, butanediol, isoprene glycol, pentanediol, hexanediol, octanediol, nonanediol, decanediol, glycerol, ethylhexanediol, erythrulose, ozonized glycerol, glycol, (C15-18) diol, (C20-30) diol, diethylene glycol, diglycerol, dithiaoctanediol, DPG, dipropylene glycol, triethylene glycol, trimethylhydroxymethylcyclohexanol, phytantriol, phenoxypropylene glycol, butylethylpropylene glycol, methylpropanediol, menthanediol, lauranediol, polypropylene glycol, and the like; the ether is ethylene glycol butyl ether, ethylene glycol propyl ether, polyethylene glycol ether, anisole, etc.; the oil comprises liquid paraffin (mineral oil), heavy liquid isoparaffin, light liquid isoparaffin, alpha-olefin oligomer, coconut oil, palm kernel oil, safflower seed oil, olive oil, castor oil, avocado oil, sesame oil, tea oil, evening primrose oil, wheat germ oil, macadamia nut oil, shiqua nut oil, hazelnut nut oil, linseed oil, cottonseed oil, soybean oil, groundnut oil, rice bran oil, cocoa butter, rose hip oil, meadowfoam oil, peach kernel oil, tea tree oil, peppermint oil, corn oil, rapeseed oil, sunflower oil, wheat germ oil, shea butter, hydrogenated coconut oil, hydrogenated castor oil, jojoba oil, hydrogenated jojoba oil and other vegetable oils; lanolin such as liquid lanolin and modified lanolin; phospholipids such as lecithin, phosphatidylcholine, phosphatidylethanolamine, sphingomyelin, phosphatidic acid, and lysolecithin; phospholipid derivatives such as hydrogenated soybean phospholipid, partially hydrogenated soybean phospholipid, hydrogenated yolk phospholipid, and partially hydrogenated yolk phospholipid; sterols such as cholesterol, dihydrocholesterol, lanosterol, dihydrolanosterol, phytosterol, and cholic acid; the esters include cholesterol esters; a phytosterol; lipid complexes such as phospholipid cholesterol complexes and phospholipid/phytosterol complexes; alkyl esters, cetyl palmitate, hydroxy acid esters; glycerides, glycol esters, pentaerythritol esters, polyglycerol esters, and the like; the amides include fatty acid alkanolamides such as coconut oil fatty acid monoethanolamide (cobalaminide MEA), coconut oil fatty acid diethanolamide (cobalaminide DEA), lauric acid monoethanolamide (lauramide MEA), lauric acid diethanolamide (lauramide DEA), lauric acid monoisopropanolamide (lauramide MIPA), palmitic acid monoethanolamide (palmitamide MEA), palmitic acid diethanolamide (palmitamide DEA), and coconut oil fatty acid methyl ethanolamide (cobalaminide methyl MEA).

The composition of the present invention may contain, as necessary, any other additional component such as a therapeutic, moisturizing and/or cosmetic physiologically active substance and other functional substances, for example, oily moisturizer, humectant, surfactant, polymer thickener, antioxidant, antiseptic, antibacterial agent, bactericide, chelating agent, pH adjuster, acid, alkali, powder, inorganic salt, ultraviolet absorber, whitening agent, vitamins and derivatives thereof, blood circulation promoter, stimulant, hormone, anti-wrinkle agent, anti-aging agent, firming agent, cold-feeling agent, warm-feeling agent, irritation-reducing agent, cell activator, plant, animal, microorganism extract, antipruritic agent, keratolytic agent, antiperspirant, algefacient, astringent, enzyme, nucleic acid, perfume, colorant, skin permeation promoter, anti-inflammatory agent, anti-asthma, anti-chronic obstructive pulmonary agent, anti-inflammatory agent, anti-asthmatic agent, anti-chronic obstructive pulmonary agent, anti-inflammatory agent, anti-, Antiallergic agent, immunomodulator, anti-infectious agent, antifungal agent, etc.

Examples of the above oily moisturizers include various alcohols, acids, oils, esters, amides and the like, such as higher (poly) alcohols including cetyl alcohol, myristyl alcohol, oleyl alcohol, lauryl alcohol, cetearyl alcohol, stearyl alcohol, arachidyl alcohol, behenyl alcohol, jojoba alcohol, chimyl alcohol, batyl alcohol, hexyldecyl alcohol, isostearyl alcohol, dimer diol and the like; aralkyl alcohols such as benzyl alcohol and derivatives thereof; higher fatty acids such as lauric acid, myristic acid, palmitic acid, stearic acid, isostearic acid, behenic acid, undecylenic acid, 12-hydroxystearic acid, palmitoleic acid, oleic acid, linoleic acid, linolenic acid, erucic acid, docosahexaenoic acid, eicosapentaenoic acid, isohexadecanoic acid, trans-heneicosanoic acid, long-chain branched fatty acids, dimer acids, and hydrogenated dimer acids, and metal soaps such as aluminum salts, calcium salts, magnesium salts, zinc salts, potassium salts, and sodium salts thereof, and nitrogen-containing derivatives such as amides; comprises the paraffin, natural oil, synthetic ester, synthetic alkane, amide and the like which are already mentioned and can be used as solvents, and comprises animal oil and fat such as natural tallow, butter fat, horse fat, egg yolk oil, mink oil, turtle oil and the like; animal waxes such as spermaceti, lanolin, and tilapia oil.

Examples of the humectant include polyhydric alcohols such as glycerin, propylene glycol, diglycerin, polyglycerin, and ethylene glycol-propylene glycol copolymer, and polymers thereof; glycol alkyl ethers such as diethylene glycol monoethyl ether and ethylene glycol monoethyl ether; water-soluble esters such as polyglyceryl (eicosanedioate/tetradecanedioate) -10 and polyglyceryl (tetradecanedioate-10); sugar alcohols such as sorbitol and xylitol; saccharides and derivatives thereof such as gluconic acid, glucuronic acid, cyclodextrins, beta-glucan, chitin, chitosan, heparin and derivatives thereof, pectin, arabinogalactan, dextrin, dextran, glycogen, ethylglucoside, polymers or copolymers of glucosylmethacrylate, and the like; hyaluronic acid, sodium hyaluronate; sodium chondroitin sulfate; mucin sulfate, caron sulfate, cutin sulfate, dermatan sulfate; tremella extract and tremella polysaccharide; algin; tuberose polysaccharide or natural polysaccharide; urea and its derivatives; 2-pyrrolidone-5-carboxylic acid and its sodium salt; amino acids such as betaine (trimethylglycine), proline, and taurine, and salts thereof; protein peptides such as collagen, fish-derived collagen, fat-denatured collagen, gelatin, elastin, collagen degradation peptide, hydrolyzed collagen, hydroxypropyl ammonium chloride hydrolyzed collagen, protein degradation peptide, and keratin degradation peptide, and derivatives thereof; acylated peptides such as palmitoyl oligopeptide; silylated peptides; lactobacillus culture solution, yeast extract, egg shell membrane protein, bovine submaxillary gland mucin, hypotaurine, sesame lignan glycoside, glutathione, albumin and whey; choline chloride, phosphorylcholine; preferable examples of the plant-derived material include animal or plant-derived components such as placenta extract, aloe extract, witch hazel water, luffa water, chamomile extract, licorice extract, daisy extract, silk extract, japanese cassia extract, yarrow extract, eucalyptus extract, and sweet clover extract, and ceramides such as natural ceramides, hydroxyceramides, suspected ceramides, sphingoglycolipids, ceramides, and ceramide-containing extracts.

The surfactant includes anionic surfactants, nonionic surfactants, cationic surfactants, amphoteric surfactants, and polymer surfactants, as preferable examples. Preferred examples of the surfactant include anionic surfactants such as fatty acid salts including potassium laurate and potassium myristate; alkyl sulfate ester salts such as sodium lauryl sulfate; sodium lauryl sulfate; polyoxyethylene alkyl sulfates; polyoxyethylene succinate salts; polyoxyethylene fatty amine sulfates; fatty acid alkanolamide sulfates; olefin sulfonates; a sulfosuccinate salt; alkyl benzene sulfonate; alkyl naphthalene sulfonates and the like; examples of the nonionic surfactant include various polyoxyethylene alkyl ethers such as laureth (polyoxyethylene lauryl ether) and ceteth (polyoxyethylene cetyl ether); polyoxyethylene alkylphenyl ethers; polyoxyethylene sorbitan fatty acid esters (tweens); sorbitan fatty acid esters (span); fatty alcohol polyoxyethylene ether (peregal); alkylphenol ethoxylates (APEO), and the like; examples of the cationic surfactant include silicone cationic surfactants such as trialkyl ammonium halides such as coco dimethyl ammonium chloride, fatty acid amides such as stearamide ethyl diethylamine and salts thereof, alkyl ether amines and salts thereof, fatty acid amide quaternary ammonium salts, polyoxyethylene alkylamines and salts or quaternary salts thereof, pyridinium salts, imidazolinium salts, alkylisoquinolinium salts, dialkylmorpholinium salts, polyamine fatty acid derivatives, amino-modified and polyether-modified silicones, and the like; examples of the amphoteric surfactant include various betaines such as lauryl betaine (lauryl dimethylaminoacetic acid betaine), phospholipids such as water-oxidized lecithin, silicone-based amphoteric surfactants, and the like; examples of the polymeric surfactant include polyvinyl alcohol, sodium alginate, starch derivatives, tragacanth gum, and acrylic acid/methacrylic acid alkyl copolymers.

Examples of the polymer thickener or gelling agent include guar gum, locust bean gum, cedar seed, carrageenan, galactan, gum arabic, tara gum, tamarind seed, furcellaran, karaya gum, cotton rose, agarwood gum, tragacanth gum, pectin, salts such as pectic acid and sodium salt, salts such as alginic acid and sodium salt, and mannan; starch and modified starch, cellulose and modified cellulose; xanthan gum, dextran, succinoglucan, curdlan, hyaluronic acid and its salts, gellan gum, chitin, polysaccharide, agar, brown algae extract, chondroitin sulfate, casein, collagen, gelatin, albumin, polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA), vinylpyrrolidone-vinyl alcohol copolymer, polyvinyl methyl ether, polyethylene glycol, polypropylene glycol, polyoxyethylene-polyoxypropylene copolymer and other copolymers, silicic anhydride, fumed silica (ultra-fine silicic anhydride), aluminum magnesium silicate, sodium magnesium silicate, metal soap, metal dialkyl phosphate, bentonite, hectorite, organically modified clay minerals, sucrose fatty acid esters, fructooligosaccharide fatty acid esters as preferred species.

Examples of the antioxidant include tocopherol derivatives such as tocopherol (vitamin E) and tocopherol acetate; BHT, BHA; gallic acid derivatives such as propyl gallate; vitamin C (ascorbic acid) and/or derivatives thereof; erythorbic acid and derivatives thereof; sulfites such as sodium sulfite; a metabisulfite salt; bisulfite such as sodium bisulfite; thiosulfate salts such as sodium thiosulfate; thiotaurine, hypotaurine; thioglycerol, thiourea, thioglycolic acid, cystine hydrochloride as preferred species.

As preservative/antiseptic/bactericide azelaic acid has antimicrobial preservative properties by itself, but additional preservatives/antiseptics/bactericides may be added, which may be listed as: hydroxybenzoic acids such as methyl parahydroxybenzoate, ethyl parahydroxybenzoate, propyl parahydroxybenzoate and butyl parahydroxybenzoate, and their salts and esters; salicylic acid; sodium benzoate; phenoxyethanol; 1, 2-diols such as 1, 2-pentanediol and 1, 2-hexanediol; isothiazolinone derivatives such as methylchloroisothiazolinone and methylisothiazolinone; an imidazoline urea; dehydroacetic acid and salts thereof; phenols; halogenated bisphenols such as triclosan, acid amides, and quaternary ammonium salts; triclocarban, zinc pyrithione, benzalkonium chloride, benzethonium chloride, sorbic acid, chlorhexidine gluconate, halocarban, hexachlorophene, 4-isopropylcycloheptadiene phenol ketone; phenyl ethanol, photoreceptors, antibacterial zeolite, and silver ions are preferred examples.

Examples of the chelating agent include EDTA and EDTA₂Na、EDTA₃Na、EDTA₄Ethylenediaminetetraacetate such as Na; HEDTA₃Hydroxyethyl ethylenediamine triacetate such as Na; pentetate (diethylenetriaminepentaacetate); phytic acid; phosphonic acids such as etidronic acid and salts such as sodium salts thereof; sodium oxalate; polyamino acids such as polyaspartic acid and polyglutamic acid; sodium polyphosphate, sodium metaphosphate, phosphoric acid; sodium citrate, citric acid, alanine, dihydroxyethylglycine, gluconic acid, ascorbic acid, succinic acid, tartaric acid as preferred examples.

The pH adjuster is an inorganic or organic compound optionally having an acid-base property, and includes an organic acid/base or an inorganic/acid/base added to the composition for use as another function, and examples thereof include citric acid, sodium citrate, lactic acid, sodium lactate, potassium lactate, glycolic acid, succinic acid, acetic acid, sodium acetate, malic acid, tartaric acid, fumaric acid, phosphoric acid, hydrochloric acid, sulfuric acid, monoethanolamine, diethanolamine, triethanolamine, isopropanolamine, triisopropanolamine, aminoalcohols, arginine, sodium hydroxide, potassium hydroxide, sodium carbonate, sodium bicarbonate, aqueous ammonia, guanidine carbonate, and ammonium carbonate, as preferable examples.

Examples of the powder include inorganic powders having various sizes and shapes such as mica, talc, kaolin, sericite, montmorillonite, kaolinite, mica, muscovite, phlogopite, synthetic mica, lepidolite, biotite, vermiculite, magnesium carbonate, calcium carbonate, aluminum silicate, barium silicate, calcium silicate, magnesium silicate, strontium silicate, tungstic acid metal salt, magnesium, zeolite, barium sulfate, calcined calcium sulfate, calcium phosphate, fluorapatite, hydroxyapatite, ceramic powder, bentonite, smectite, clay, mud, metal soap (e.g., zinc myristate, calcium palmitate, aluminum stearate), calcium carbonate, red iron oxide, yellow iron oxide, black iron oxide, ultramarine, berlin blue, carbon black, titanium oxide, zinc oxide, aluminum oxide, silica, mica titanium, fish scale foil, boron nitride, photochromic pigment, synthetic fluorophlogopite, fine composite powder, gold, aluminum, and the like, and various resin powders such as starch, cellulose, nylon powder, polyethylene powder, and polymethyl methacrylate, organic powders and surface-treated powders having various sizes and shapes such as silicone powder and Teflon (registered trademark) powder, and organic-inorganic composite powders are preferable examples.

Examples of the inorganic salts include sodium chloride, potassium chloride, aluminum chloride, calcium chloride, magnesium chloride, bittern, zinc chloride, and ammonium chloride; sodium sulfate, aluminum potassium sulfate (alum), aluminum ammonium sulfate, barium sulfate, calcium sulfate, potassium sulfate, magnesium sulfate, zinc sulfate, ferric sulfate, and copper sulfate; disodium phosphate, sodium phosphate, potassium phosphate, calcium phosphate, and magnesium phosphate are preferred examples.

Examples of the ultraviolet absorber include benzoic acid-based ultraviolet absorbers such as p-aminobenzoic acid, monoglyceride of p-aminobenzoic acid, and homopentanol N-acetyl anthranilate; salicylic acid-based ultraviolet absorbers such as salicylic acid and sodium salts thereof, amyl salicylate, and the like; cinnamic acid-based ultraviolet absorbers such as octyl cinnamate, ferulic acid and derivatives thereof; benzophenone-based ultraviolet absorbers such as 2, 4-dihydroxybenzophenone and 4-hydroxy-3-carboxybenzophenone; hydroxyphenyl benzotriazole; dibenzylazine; a diantimoyl methane; a dibenzoylmethane derivative; octyl triazone; urocanic acid derivatives such as urocanic acid and ethyl urocanic acid; hydantoin derivatives, phenylbenzimidazole sulfonic acid, terephthalylidene dicamphor sulfonic acid, benzotriazolylmethylphenol trisiloxane, methyl anthranilate, rutin and derivatives thereof, and oryzanol and derivatives thereof are preferable examples.

As whitening agents, it is possible to assist in increasing the function of the composition of the present invention, and there may be mentioned hydroquinone glycosides such as arbutin and α -arbutin, and esters thereof; ascorbic acid phosphate ester salts such as ascorbic acid, sodium ascorbyl phosphate, and magnesium ascorbyl phosphate, ascorbic acid fatty acid esters such as ascorbyl tetraisopalmitate, ascorbic acid alkyl ethers such as ascorbyl ethyl ether, ascorbyl glucosides such as ascorbic acid-2-glucoside, and ascorbic acid derivatives such as fatty acid esters thereof, ascorbyl sulfate, and tocopheryl ascorbyl phosphate; plant extracts such as kojic acid, ellagic acid, tranexamic acid and derivatives thereof, ferulic acid and derivatives thereof, placenta extract, glutathione, oryzanol, butylresorcinol, oil-soluble chamomile extract, oil-soluble licorice extract, cacumen Tamaricis extract, and Saxifraga stolonifera extract are preferable examples.

Examples of the vitamins and derivatives thereof include vitamin a compounds such as retinol, retinyl acetate, and retinyl palmitate; nicotinic acids such as thiamine hydrochloride, thiamine sulfate, riboflavin acetate, pyridoxine hydrochloride, pyridoxine dicaprylate, pyridoxine dipalmitate, flavin adenine dinucleotide, cyanocobalamin, folic acid, nicotinamide, and benzyl nicotinate, and vitamin B group such as choline; ascorbic acids and salts thereof such as sodium ascorbate; vitamin D; vitamin E compounds such as alpha, beta, gamma, delta-tocopherol; other vitamins such as pantothenic acid and biotin; ascorbic acid phosphate ester salts such as sodium ascorbyl phosphate and magnesium ascorbyl phosphate, ascorbic acid fatty acid esters such as ascorbyl tetraisopalmitate, ascorbic acid alkyl ethers such as ascorbic acid ethyl ether, ascorbyl glucosides such as ascorbic acid-2-glucoside, fatty acid esters thereof, and ascorbic acid derivatives such as tocopheryl ascorbyl phosphate; vitamin derivatives such as tocopherol nicotinate, tocopherol acetate, tocopherol linoleate, tocopherol ferulate, tocopherol phosphate and the like, tocotrienols, and other various vitamin derivatives are preferable examples.

The animal, plant and microorganism extracts include various animal, plant and microorganism extracts having skin improving function, including the aforementioned various animal and plant extracts having nourishing function, skin moisturizing function and skin whitening function.

As a fragrance, vanillin, sage, origanum, parsley oil, spearmint oil, cinnamon oil, oil of wintergreen (methyl salicylate), peppermint oil, clove oil, bay oil, anise oil, eucalyptus oil, citrus oils, fruit oils, and lemon, orange, lime, grapefruit, apricot, banana, grape, apple, strawberry, cherry, pineapple flavors are included, with one or more fragrances being optional.

As colorants, including pigments, dyes, lakes, and agents imparting a particular sheen or reflectivity, in various embodiments the colorant is controlled to be from 0 to 20 weight percent of the total composition and the appearance-improving colorants include one of talc, mica, calcium carbonate, magnesium silicate, magnesium aluminum silicate, silica, titanium dioxide, zinc oxide, yellow iron oxide, red iron oxide, FD & C dyes (food colors), and mixtures thereof.

Examples of the skin permeation enhancer include oils and fats such as the above alcohols, the above fatty acids, the above surfactants, azepinone, dimethyl sulfoxide derivatives, eucalyptus oil, and peppermint oil.

The composition of the present invention may be a powder, dispersion, emulsion, cream, mask, spray, gel, tablet, or like cosmetic or medical product.

The whitening and thinning skin composition of the present invention may be prepared by any means known in the art. For example, the preparation method of the powder is as follows: azelaic acid or its salt is ground together with the moenobenzone to obtain a very homogeneous powder which can be dispersed in other cosmetic products or in medical preparations for medical purposes, such as topical treatment of skin diseases like acne, scars, etc. For example, the mixed powder is directly added into a commercial emulsion in the following examples, and the mixed powder plays the role of the invention. The preparation method of the whitening and refining skin composition dispersion or emulsion may employ well-known techniques (e.g., wopelnkun eds., skin care cosmetic preparation methods, chemical industry press, 2007-09), and in general, azelaic acid or its salt, moroxydine, other water-soluble raw materials (e.g., alcohol, glycerin, salicylic acid, hyaluronic acid, disodium edetate, emulsifiers, thickeners, etc.) are dissolved in water in a conventional mixer with stirring to form an aqueous phase; dissolving oil soluble materials (such as lanolin, refined animal oil, fatty acid, cetyl alcohol, perfume, etc.) in liquid oil (such as paraffin, vegetable oil, etc.) to form oil phase; then the water phase and the oil phase are fully mixed to form an oil-in-water or water-in-oil emulsion (according to the different dosage of water and oil). It should be noted that, in the preparation of the raw material having both water-solubility and oil-solubility, such as the emulsifier, the raw material may be dissolved in the water phase, the oil phase, or the raw material may be separated into two parts to be added to the water phase and the oil phase, which is a well-known preparation method.

The method for preparing the whitening and refining skin composition gel is to add a macromolecular thickening agent in the process of preparing the emulsion, wherein the macromolecular thickening agent is used as a gelling agent, and the macromolecular thickening agent is preferably carboxyl vinyl polymer, carboxymethyl cellulose, gellan gum or xanthan gum. The concentration of the carboxyvinyl polymer is 0.025 to 0.05 wt% when the polymeric thickener is a carboxyvinyl polymer, the concentration of the carboxymethylcellulose is 0.05 to 0.1 wt% when the polymeric thickener is carboxymethylcellulose, the concentration of the gellan gum is 0.05 to 0.1 wt% when the polymeric thickener is gellan gum, and the concentration of the xanthan gum is 0.05 to 0.1 wt% when the polymeric thickener is xanthan gum. The general preparation method is to add the macromolecular thickener into the water phase or the emulsion after mixing the water phase and the oil phase, and stir the obtained mixture until a homogeneous gel phase is formed. The polymer thickener may be added directly to the polymer thickener powder, or may be a polymer thickener dispersion or solution dispersed in advance with a solvent (e.g., water).

The preparation method of the whitening and thinning skin composition paste can further add any filler mentioned above or any other thickening auxiliary agent such as higher alcohol, animal fat, fatty acid, pigment and the like on the basis of emulsion and gel until a homogeneous phase is obtained. Further mixing with common equipment such as high speed stirrer, colloid mill grinding, three-roller grinding, homogenizing disperser, etc. to obtain homogeneous and semi-solid paste product.

The composition in any form obtained by the preparation method is dissolved in a high polymer system for the facial mask, so that a facial mask product with the same whitening and thinning skin can be obtained, wherein the high polymer system comprises all the high polymer thickening agents. Tablets are prepared by mixing the monometallic salt of azelaic acid with the monenzone, wetting with any solvent (water, alcohol, ester), adding various fillers and tabletting. The filler comprises the polymer thickening agent and/or powder, preferably modified starch and modified cellulose with disintegrating effect.

The invention has the technical effects that:

1. azelaic acid, especially single metal salt thereof and Monoxazone are used as main active ingredients, the complementation of the two in whitening effect is utilized, the three effects of bacteriostasis, spot removal and whitening are integrated, harmful preservatives are not required to be added, the whitening and spot removal effects are good, the azelaic acid composition is safe and non-irritant, and the azelaic acid composition can be used for treating skin diseases such as chloasma and other pigmented dermatosis, whelk, rosacea, seborrheic dermatitis and the like.

2. The azelaic acid monometallic salt has good water solubility, does not precipitate in emulsion products, and has excellent storage and service performance.

3. Due to the synergistic effect of the azelaic acid single metal salt, the dosage of the moenozonone is reduced, the safety is greatly increased, the production cost is reduced, and the resources are saved.

4. The composition has simple preparation process, low cost and energy saving.

DETAILED DESCRIPTION OF EMBODIMENT (S) OF INVENTION

The present invention will be described more specifically by the following examples and comparative examples, but the present invention is not limited to the following examples.

Example 1

The composition with the skin whitening and refining effects prepared according to the preparation method provided by the invention comprises the following raw materials in parts by weight (based on 100 parts by weight):

azelaic acid monosodium salt 60 parts

40 parts of Monoxazone

The preparation method of the composition with the skin whitening and refining effects comprises the following steps: mixing the monosodium azelaic acid and the moenozonone, and grinding to obtain a powder product.

The application comprises the following steps: respectively adding 1g of the above powder product into 10g of commercially available cosmetic lotion and 10g of vitamin A acid ointment, heating to 75 deg.C under stirring, and dissolving completely to obtain emulsion cosmetic containing the composition and enhanced vitamin A acid ointment, which can be applied on skin surface.

The effect is as follows: the melanin inhibition of a commercially available emulsion was increased by 64% as analyzed by the melanin inhibition test after addition of the powder product of the present invention. Through skin tests of more than 30 patients, the tretinoin soft cream enhanced by the composition has obvious effects of removing freckles, whitening and refining skin, and has obvious treatment effects on skin diseases such as whelk, rosacea, seborrheic dermatitis and the like.

Examples 2 to 6

The composition with the skin whitening and refining effects prepared according to the preparation method provided by the invention comprises the following raw materials in parts by weight (based on 100 parts by weight):

wherein X is respectively 5, 10, 15, 20 and 30, Y is respectively 15, 10, 15 and 5, and the preparation method of the composition with the effects of whitening and thinning the skin comprises the following steps:

(1) adding olive oil, lanolin and moenobenzone into a container, heating to 75 deg.C, dissolving all the components to obtain oil phase component liquid, and keeping the temperature for later use; (2) adding monosodium azelate, sodium oleate, tween 60, nonylphenol polyoxyethylene ether (0P-10), disodium ethylene diamine tetraacetate, glycerol and deionized water into another container, and heating to 60 ℃ to form a solution to obtain a water-phase component liquid; (3) gradually adding the water phase component liquid prepared in the step (2) into the oil phase component liquid prepared in the step (1) under stirring, stirring for 1 hour, cooling, and discharging to obtain a homogeneous emulsion product.

Example 7

The monosodium salt of azelaic acid from example 3 above was replaced with the equivalent of disodium salt of azelaic acid and the pH of the emulsion was adjusted with salicylic acid to the same pH as in example 3 to provide an emulsion product. The inhibition rate test shows that the product has the same effect as the product in the example 3.

Example 8

Taking 20g of the emulsion obtained in the example 3, adding 1g of gelatin and 5g of bentonite, and mixing for 15min in a high-speed shearing emulsifying machine to obtain the cream of the composition with the effects of whitening and refining the skin.

Example 9

Mixing 10g of monosodium azelate and 5g of Mornoxazone, sequentially adding 2mL of ethanol and 2mL of water for wetting, grinding while adding 0.5g of crosslinked carboxymethyl starch and 0.1g of polyethylene glycol (molecular weight 800), fully grinding, and tabletting with a tabletting machine. The performance test shows that the tablet has good water solubility and fast disintegration when in use, and can be directly applied to the surface of the skin after being dissolved.

Drawings

FIG. 1 is a graph showing the effect of the addition of monosodium azelaic acid and azelaic acid to the melanogenesis yield of an equivalent formulation of moenobenzone, in a low dosage range, which is comparable, but at high dosages, monosodium azelaic acid works better.

FIG. 2 shows the comparison results of skin tests of products of examples 2 to 6 of the composition of the present invention and commercially available whitening and spot-removing cosmetics of certain brands.

The product effects and novel features of the present invention will become apparent from the following detailed description of the preferred embodiments, including the drawings.

For the product, the storage properties directly affected the practical application, and for comparison with the compatibility of the azelaic acid salt, an emulsion containing azelaic acid was prepared according to the formulation of example 1, replacing the monosodium salt of azelaic acid with an equivalent amount of azelaic acid. In the static storage process, a small amount of azelaic acid is crystallized and separated out after 6 days, the separated-out amount is obviously increased after 10 days, and the products prepared by the above examples have no precipitation phenomenon in the 6-month storage process, which shows that the azelaic acid has good compatibility with other components after being prepared into single metal salt.

Moenobenzone is a catechol oxidase inhibitor that prevents oxidation of dopa to dopamine and thus melanin formation. In order to compare the effects before and after adding the azelaic acid salt, the inhibition effect on the oxidation process of the dopa is experimentally researched, the effect of the combination of the azelaic acid monosodium salt with different concentrations and the fixed amount of the moenobenzone on the yield (absorbance method) of the dopa pigment is examined within a certain oxidation time according to the oxidation reaction (oxidation into the dopa pigment) of the dopa in a tyrosinase solution with the concentration of 1.5mmol/L, and the result is shown in the attached figure 1. Figure 1 shows that the inhibition effect on the oxidation reaction is gradually enhanced along with the increase of the content of the azelaic acid monometallic salt, the yield of the dopachrome is reduced fastest when the content of the azelaic acid reaches 10 percent, the inhibition effect on the oxidation reaction reaches the maximum when the content of the azelaic acid reaches about 25 percent, and then the dosage of the azelaic acid salt is increased, so that the inhibition effect is not changed greatly. It can be seen that the addition of the monosodium salt of azelaic acid has a significant synergistic effect on the inhibition of dopachrome formation by moenobenzone.

In order to further verify the action effect of the whitening and thinning skin composition, clinical research of skin test is carried out.

Test samples: test samples of examples 2-6 were prepared according to the preparation method of the present invention.

The test method comprises the following steps: 120 volunteers aged 20 to 65 years in Tianjin are selected, 60 men and 60 women.

The main symptoms of the volunteers are: freckle, chloasma, sunburn, dark skin color, and acne. Volunteers were randomly divided into 6 groups of trial 1-5 and control (6), 20 persons each.

Runs 1-5 groups: after daily cleansing, the cosmetics prepared in examples 2-6 were applied to the face before sleep, and rubbed slightly to apply, without applying other skin care products. The test period was one month.

Control group 6: after the face is cleaned every day, certain brand of commercially available whitening and freckle-removing cosmetics are coated on the skin of the face before sleeping, and other skin care products are not coated. The test period was one month.

Evaluation criteria: the skin color whitening degree and the color spot fading degree are identified by the patient's self-describing feeling and the computer comparison of the skin texture map. Significant effect (Excellent): the skin color becomes white, the color of the color spots is obviously reduced, the skin is fine and smooth, and the acne disappears; effective (Effective): whitening skin color, reducing color of mottle, thinning skin, and reducing acne; invalid (Ineffective): the skin color and the color spots have no change before the test, and the skin texture has no obvious change.

The test results are shown in figure 2. As shown in fig. 2, compared with the control group 6, the effectiveness (including significant effect) rate of each experimental group except the 5 th group is 100%, while the non-effectiveness rate of the control group is as high as 45%.

These results show that the whitening composition of the present invention is directly applied to human skin, and is significantly superior to the commercial products in whitening, spot-removing and skin-thinning effects.

Claims (7)

1. A composition for whitening and thinning skin, characterized by comprising at least (a) azelaic acid or a salt thereof and (b) moenobenzone.

2. The composition for whitening and thinning skin as claimed in claim 1, wherein said azelaic acid or the salt thereof is azelaic acid, monometallic salt of azelaic acid, bimetallic salt of azelaic acid.

3. The whitening and refining skin effect composition according to claim 1 and claim 2, characterized in that the mono-metal salt of azelaic acid, the bi-metal salt of azelaic acid is potassium or sodium salt of azelaic acid molecule.

4. The whitening and refining skin effect composition according to claim 1, which is prepared by mixing (a) azelaic acid or its salt and (b) moenobenzone to obtain a powder product, and the powder can be dispersed in a commercially available cosmetic or medical preparation under heating and stirring for use.

5. The composition for whitening and refining skin according to claim 1, which is prepared by adding solvent and functional additives such as therapeutic, moisturizing and/or beautifying physiologically active substances and other functional substances, and preparing into semisolid and liquid cosmetics in any form according to known cosmetic production technology, such as preparing cosmetic or medical products in the form of dispersion, emulsion, cream, facial mask, spray, gel, tablet, etc.

6. The method according to claim 5, wherein the solvent is water, alcohol, ether, oil, ester, amide or a mixture thereof, and comprises ethanol, propanol, butanol, pentanol, octanol, dodecanol, hexadecanol, propylene glycol, butanediol, isoprene glycol, pentanediol, hexanediol, octanediol, nonanediol, decanediol, glycerol, ethylhexanediol, erythrulose, ozonized glycerol, glycol, (C15-18) diol, (C20-30) diol, diethylene glycol, diglycerol, dithiaoctanediol, DPG, dipropylene glycol, triethylene glycol, trimethylmethylol cyclohexanol, phytantriol, phenoxypropylene glycol, butylethylpropylene glycol, methylpropylene glycol, menthanediol, laurylene glycol and polypropylene glycol, ethylene glycol butyl ether, ethylene glycol propyl ether, polyethylene glycol ether, anisole, liquid paraffin (mineral oil), ethylene glycol, propylene glycol ether, heavy liquid isoparaffins, light liquid isoparaffins, α -olefin oligomers, coconut oil, palm kernel oil, safflower seed oil, olive oil, castor oil, avocado oil, sesame oil, tea oil, evening primrose oil, wheat germ oil, macadamia nut oil, shiqua nut oil, hazelnut nut oil, linseed oil, cottonseed oil, soybean oil, groundnut oil, rice bran oil, cocoa butter, rose hip oil, meadowfoam oil, peach kernel oil, tea tree oil, peppermint oil, corn oil, rapeseed oil, sunflower oil, wheat germ oil, shea butter, hydrogenated coconut oil, hydrogenated castor oil, jojoba oil, hydrogenated jojoba oil, and other vegetable oils; lanolin such as liquid lanolin and modified lanolin; phospholipids such as lecithin, phosphatidylcholine, phosphatidylethanolamine, sphingomyelin, phosphatidic acid, and lysolecithin; phospholipid derivatives such as hydrogenated soybean phospholipid, partially hydrogenated soybean phospholipid, hydrogenated yolk phospholipid, and partially hydrogenated yolk phospholipid; sterols such as cholesterol, dihydrocholesterol, lanosterol, dihydrolanosterol, phytosterol, and cholic acid; the esters include cholesterol esters; a phytosterol; lipid complexes such as phospholipid cholesterol complexes and phospholipid/phytosterol complexes; alkyl esters, cetyl palmitate, hydroxy acid esters; glycerides, glycol esters, pentaerythritol esters, polyglycerol esters, and the like; the amides include fatty acid alkanolamides such as coconut oil fatty acid monoethanolamide (cobalaminide MEA), coconut oil fatty acid diethanolamide (cobalaminide DEA), lauric acid monoethanolamide (lauramide MEA), lauric acid diethanolamide (lauramide DEA), lauric acid monoisopropanolamide (lauramide MIPA), palmitic acid monoethanolamide (palmitamide MEA), palmitic acid diethanolamide (palmitamide DEA), and coconut oil fatty acid methyl ethanolamide (cobalaminide methyl MEA).

7. The composition for skin whitening and thinning according to claim 1, which is used in a cosmetic for skin thinning, whitening and spot removal, and a medical application for treating skin diseases such as pigmented dermatosis such as chloasma, acne, rosacea and seborrheic dermatitis.