WO2015007146A1

WO2015007146A1 - Ultraviolet absorbent having better ultraviolet protection effect, and combination thereof

Info

Publication number: WO2015007146A1
Application number: PCT/CN2014/080941
Authority: WO
Inventors: 但飞君; 王振; 肖鹏
Original assignee: 北京北沃乐基生物医药科技有限公司
Priority date: 2013-07-17
Filing date: 2014-06-27
Publication date: 2015-01-22
Also published as: CN105408301B; CN105408301A

Abstract

The present invention provides a new UV-B ultraviolet absorbent and a combination containing the UV-B ultraviolet absorbent, especially a partial combination. The combination has good lipid solubility, a strong anti-UV radiation effect, simple formulation and convenient preparation method, and gives cool and comfortable feelings. Meanwhile, the combination has excellent chemical stability. The advantages enable it to be especially suitable for ultraviolet protection for skin and/or hair. Especially, the combination has a strong anti-ultraviolet effect, and has continuous cool and comfortable feature, thereby solving a defect of an existing ultraviolet absorbent.

Description

Ultraviolet absorber with better UV protection effect and composition thereof

Technical field

This invention relates to novel UV-B UV absorbers (sunscreens) and to compositions, particularly topical compositions, containing the above UV-B UV absorbers.

Background of the invention

Depending on the wavelength, UV rays are designated as UV-A rays (320-400 nm) and UV-B rays (280-320 nm). The damage of UV rays to human skin increases as the wavelength decreases and the duration of exposure increases, so UV rays can cause skin damage, and UV-B radiation can cause sunburn (erythema) to very severe skin burns. Sunlight's very frequent and unprotected exposure to the skin can also result in loss of skin elasticity and increased wrinkle formation, which can lead to premature aging of the skin and, in extreme cases, pathological skin changes to skin cancer. UV-A rays can penetrate deeper into the skin layer and accelerate the skin aging process, which can cause the skin to form pigments quickly and weakly, and also cause skin photosensitivity or photoallergic reactions, in UV-A irradiation and increased There is a definite link between skin cancer risks. UV absorbers for cosmetic and dermatological preparations are classified into UV-A absorbents and UV-B absorbents depending on their position of maximum absorption. Although there are a large number of safe and effective UV-B absorbers, there are few UV-A absorbers suitable for protecting human skin, and they are affected by major defects. To date, many compounds have been proposed for skin protection (UV-A and/or UV-B). Most of these compounds are aromatic compounds that absorb UV light in the 280-315 nm band, or the 315-400 nm band, or the entire two bands, which are often formulated in sunscreen compositions, which are water-based. An oil-in-oil emulsion (ie, a cosmetically acceptable carrier consisting of a continuously dispersed aqueous phase and a discontinuously dispersed oil phase), so that they contain different concentrations, are lipophilic and/or hydrophilic, and selectively absorb harmful UV light of one or more classical organic UV absorbers having an aromatic function, these UV absorbers (and amounts thereof) being selected according to the required protection index (protection index (IP) is used numerically The irradiation time necessary to reach the erythema generation threshold in the UV ultraviolet absorber is expressed as the ratio of the time required to reach the erythema generation threshold when no UV ultraviolet absorber is present.

In addition to their ability to protect their sunscreen, these compounds with UV activity should also have good cosmetic properties in compositions containing them, with good solubility in common solvents, especially in fatty materials such as oils and fats. This is especially true, as well as having good water and sweat resistance (stagnation) properties. Among any of the aromatic compounds recommended for this purpose, specifically, a P-aminobenzoic acid derivative, a methylene camphor derivative, a cinnamic acid derivative, and a benzotriazole derivative can be cited. However, some of these materials do not possess any of the properties required for use as a UV absorber in sunscreen compositions. In particular, their inherent sunscreen power may not be sufficient, and the solubility in various types of formulations for sunscreen applications is not always good enough (especially fat solubility), they may not have sufficient light stability (light stability) ), they may also have poor water and sweat resistance. In addition, it is desirable that these sunscreen materials do not penetrate into the skin.

In particular, whether it is UV-A or UV-B protectant, or a combination of both, even if it can play Description

The absorption protection of good ultraviolet radiation, however, we know that the high-energy ultraviolet light absorbed by the ultraviolet absorber does not completely disappear, but the ground state ultraviolet absorber is converted into a high-energy state, and some/all are in a high-energy state. Or return to the ground state by releasing lower energy radiation and/or heat. This process depends on the lightfastness of the protective agent. In fact, a large part of the people who apply UV absorbers are in a stronger time for a longer period of time. In the ultraviolet environment, although the ultraviolet absorber can effectively protect against skin damage caused by high-intensity ultraviolet radiation, the human skin is still in a high-heat environment and is extremely uncomfortable. For this defect of UV absorber products, some skin care products have added a proper amount of peppermint. Mint has a cooling effect, which can alleviate the feeling of high heat discomfort of the skin to some extent. However, peppermint has a distinct irritating smell. It has a certain stimulating effect on the skin. In addition, the mint has a strong volatility and a short-acting effect, especially when it is applied to the skin near the eyes, it will have significant irritation to the eyes. In order to overcome the above disadvantages, a new type of cooling agent such as an ester of menthol, an ether, a menthyl formamide and a ketal compound of menthol, especially a high-boiling mint, is obtained by modifying the molecular structure of the mint. Ester derivatives have better structural stability, greatly reduce the volatility and oxidizability of menthol, mild and long-lasting cooling effect, almost odorless products, and good compatibility with many surfactants in daily chemical formulations. It is particularly favored, such as the US FDA approval of menthyl anthranilate as an ultraviolet absorber. However, these modified and improved mint products have weak UV protection effects and require a large amount of use to effectively protect them, or as an additional additive to the protective agent product, resulting in complicated production, increased product quality control, and increased cost. . Therefore, it is necessary to find a novel compound which has both desired physical and chemical properties, a strong anti-violet effect, and a continuous, cool and refreshing property.

Summary of the invention

The first aspect of the present invention provides an anti-ultraviolet absorption compound, or a cis-trans isomer or a stereoisomer thereof, having the following structure:

The compound of the formula (1) is preferably a trans isomer thereof, that is, a compound having the following formula (2):

The compound of the formula (2) is preferably racemic or left-handed, that is, a compound having the following formulas (3) and (4):

, solved the above deficiencies.

The compounds of the invention have good improved properties, especially their good fat solubility (not easily eroded or eluted by water or sweat, and can be used in products with higher concentrations to achieve extremely high or desired protection indices), strong Effective anti-UV radiation effect, cool and refreshing feeling, simple formula and convenient preparation method, as well as excellent chemical stability (good hydrolysis resistance in both acidic and alkaline media) ) making it particularly suitable for UV protection of the skin and/or hair.

A second aspect of the invention relates to a cosmetic composition comprising the ultraviolet absorbers of formula (1)-(4). Such compositions may be in the form of emulsions, thickening lotions, creams, gels, solutions, dry powders, films, solid sticks and aerosols.

Additional one or more suitable UV-A and UV-B UV absorbers may be added to the cosmetic and/or skin care compositions of the present invention, and the different UV UV absorber combinations may also exhibit synergistic effects.

The total amount of UV UV absorber is not critical. A suitable amount may be from 0.5 to 20% by weight, preferably from 0.5 to 12% by weight, based on the total amount of the composition.

Suitable UV-B UV absorbers which may be added to the UV-A UV absorber of the present invention are the following organic or inorganic compounds:

An acrylate such as 2-ethylhexyl-2-cyano-3,3-diphenyl acrylate, 2-cyano-3,3-diphenyl acrylate or the like;

, camphor derivatives such as 4-methylbenzylidene camphor, 3-benzylidene camphor, camphor benzalkonium methyl sulfate, polyacrylamidomethylbenzylidene camphor, thiobenzylidene camphor, thioformate Lysobenzyl camphor, p-phenylidene camphorsulfonic acid, etc.;

• cinnamate derivatives such as octyl methoxycinnamate, ethoxyethyl methoxycinnamate, diethanolamine methoxycinnamate, isoamyl methoxycinnamate, etc., and attached to siloxanes a cinnamic acid derivative;

• p-aminobenzoic acid derivatives such as p-aminobenzoic acid, p-dimethylaminobenzoic acid-ethylhexyl ester, N-oxyally acrylated ethyl p-aminobenzoate, p-aminobenzoic acid;

• Benzophenones such as benzophenone-3, benzophenone-4, 2,2',4,4'-tetrahydroxy-benzophenone, 2,2'-dihydroxy-4,4-dimethoxy Benzophenone

• an ester of benzalmalonic acid such as 4-(2-ethylhexyl) 4-methoxybenzylidene malonate; Instruction manual

• An ester of 2-(4-ethoxy-anilinomethylidene)-malonic acid such as 2-(4-ethoxy-anilinomethylidene)-malonic acid diethyl ester;

• an organosilicon oxime compound containing a benzalmalonate group as described in European Patent Publication No. EP-BI-0358584, EP-BI-0538431 and P EP-AI-0709080;

• benzotriazole trisiloxane;

• Pigments such as particulate titanium dioxide, etc., the term "particulate" means a particle size of from about 5 nm to about 200 nm, especially from about 15 nm to about 100 nm, and the titanium dioxide particles may also be coated with a metal oxide such as alumina or zirconia, or coated Organic coatings such as polyols, methyl silicone oils, aluminum stearate, decyl silicon germanium, and the like. These coatings are well known in the art.

• Imidazole derivatives such as 2-phenylbenzimidazolesulfonic acid and salts thereof. The 2-phenyl benzimidazole sulfonate, for example, an alkali metal salt such as a sodium or potassium salt, an ammonium salt, a morpholine salt, a primary amine salt, a secondary amine salt and a tertiary amine salt such as a monoethanolamine salt, a diethanolamine salt or the like.

• Salicylate derivatives such as isopropyl benzyl salicylate, benzyl salicylate, butyl salicylate, octyl salicylate, isooctyl salicylate or high maleuryl salicylate.

• Triazinone derivatives such as octyltriazinone, dioctylbutyrylaminotriazinone and the like.

Suitable conventional UV-A UV absorbers which may be added to the UV-A UV absorber of the present invention are the following organic and inorganic compounds:

• Dibenzoylformamidine derivatives such as 4-tert-butyl-4'-methoxydibenzoylformamidine, dimethoxydibenzoylformamidine, isopropyldibenzoylformamidine, etc. ;

• Benzotriazole derivatives such as 2,2'-methylene-bis(6-(2H-benzotriazol)-2-yl)-4-(1,1,3,3-tetramethylbutyl) ) - phenol, etc.;

• a phenylene-1,4-dibenzimidazole sulfonic acid or salt such as 2,2-(1,4-phenylene)-di-(IH-benzimidazole-4,6-disulfonic acid);

An amino-substituted hydroxybenzophenone such as 2-(4diethylamino-2-hydroxy-benzoyl)-benzoic acid ethyl ester as described in European Patent Publication EP1046391;

• Pigments such as particulate zinc oxide. The term "particulate" means a particle size of from about 5 nm to about 200 nm, especially from about 15 nm to about 100 nm, and the titanium dioxide particles may also be coated with a metal oxide such as alumina or zirconia, or coated with an organic coating such as a polyol, A Base silicone oil, aluminum stearate, fluorenyl silicon germanium, and the like. These coatings are well known in the art.

Since the dibenzoylformamidine derivative is a photolabile UV-A ultraviolet absorber, it is desirable to stabilize the light. The compositions of the present invention may also contain conventional cosmetic auxiliaries and additives such as preservatives/antioxidants, fatty substances/oils, water, organic solvents, silicones, thickeners, softeners, emulsifiers, defoaming agents. Agent, humectant, perfume, surfactant, filler, chelating agent, anionic polymer, cationic polymer, nonionic polymer or amphoteric polymer or mixture thereof, propellant, acidifier or alkalizing agent, dye, colorant , pigments or nanopigments, especially those suitable for providing additional photoprotection by physical shielding of ultraviolet radiation, or any other ingredient usually formulated with cosmetics, especially Description

Those used to prepare sunscreen/communication compositions.

The skilled person can easily select the necessary amount of cosmetic and dermatological auxiliaries and additives depending on the desired product. Particularly preferred antioxidants are those selected from the group consisting of amino acids (eg, glycine, histidine, tyrosine, tryptophan) and derivatives thereof; peptides such as DL-carnosine, D-carnosine, L - carnosine and derivatives (eg goose carnosine); carotenoids, carotenes (eg P-carotene, Y-carotene, lycopene) and derivatives; chlorogenic acids and derivatives; fatty acides and derivatives (eg dihydroaliphatic acid); glucosinolate, propylthiouracil and other thiols (eg glutathione, cysteine, cystine, cystine and its glycosyl-, N-acetyl) -, methyl-, ethyl-, propyl-, pentyl-, butyl- and lauryl-, palmitic acid-, oleyl-, Y-linoleyl-, cholesteryl and glyceryl esters and a salt thereof; dilauryl thiodipropionate, distearyl thiodipropionate, thiodipropionic acid and derivatives thereof (esters, ethers, peptides, lipids, nucleotides, nucleosides and Salts) and very low compatible doses (eg from p mol-μ mol/kg) of sulfoxide amine compounds (eg butyl sulfoxide sulfoxide amine, high semi-dead) Acid sulfoxide amine; additional (metal) chelating agents (eg -hydroxy fatty acids, palmitic acid, phytic acid, lactoferrin); a-hydroxy acids (eg citric acid, lactic acid, malic acid), gallic acid, Gallop extract, bilirubin, biliverdin, EDTA, EGTA and its derivatives; unsaturated fatty acids and their derivatives (eg Y-linoleic acid, linoleic acid, oleic acid); folic acid and its derivatives; pan Bismuth and panthenol and their derivatives; vitamin C and its derivatives, such as ascorbyl acetate; tocopherols and derivatives (such as vitamin E acetate); vitamin A and derivatives (vitamin A palmitate) and coniferyl benzene Formate, musk acid and derivatives, a-glycosyl rutin, ferulic acid, decyl glucosamine, carnosine, butylated hydroxytoluene, butylated hydroxy anisole, trihydroxypropyl phenyl ketone, selenium and Derivatives (eg selenium methionine).

The preservative and/or antioxidant may be present in an amount of from about 0.01% to about 10% by weight based on the total weight of the composition. Preferably, the preservative and/or antioxidant are present in an amount from about 0.1% to about 1% by weight.

The composition according to the present invention may further contain an emulsifier which can uniformly mix two or more immiscible liquids while increasing the viscosity of the composition. In addition, the emulsifier acts to stabilize the composition.

Emulsifiers which can be used in accordance with the invention to form 0/W, W/O and/or 0/W/0 formulations include sorbitan oleate, sorbitan sesquioleate, iso-hard Sorbitan acid sorbitan ester, sorbitan trioleate, polyglyceryl-diisostearate, polyglycerol ester of oleic acid isostearic acid, polyglyceryl-6-hexaparale Acid ester, polyglyceryl-4-oleate, polyglyceryl-4-oleate/PEG-8 propylene glycol cocoate, oleamide DEA, TEA myristate, TEA stearate, stearic acid Magnesium, sodium stearate, potassium laurate, potassium ricinoleate, sodium covate, sodium tauroate, potassium betulinate, sodium oleate and mixtures thereof. Other suitable emulsifiers are phosphates and salts thereof, such as cetyl phosphate, DEA cetyl phosphate, potassium hexadecanoate, sodium oleate, hydrogenated plant glyceride phosphates and Its mixture. In addition, one or more synthetic polymers can be used as emulsifiers, for example, PVP eicosene copolymer, acrylate/acrylic acid C10-C30 decyl ester crosspolymer, acrylate/stearyl methacrylate Copolymer, PEG-2?/dodecyl glycol copolymer, PEG-4 dodecyl glycol copolymer and mixtures thereof. Preferred emulsifiers are PVP eicosene copolymer, acrylate/C10-C30 decyl crosspolymer, PEG-20 sorbitan isostearate, sorbitan isostearate Esters and mixtures thereof.

The emulsifier is present in a total amount of from about 0.01% by weight to about 45% by weight, preferably from about 0.1% to about 3% by weight based on the total weight of the composition. Instruction manual

The fat/oil phase is advantageously selected from:

• mineral oil and mineral wax;

, oil, such as triglyceride of citric acid or octanoic acid, preferably castor oil;

a natural or synthetic oil, preferably an ester of carbonic acid or a fatty acid with an alcohol such as isopropanol, propylene glycol or glycerol; • a decyl benzoate;

• Polysiloxanes such as dimethylpolysiloxane, dihexylpolysiloxane, diphenylpolysiloxane and mixtures thereof. The fatty substance which may be added to the oil phase of the composition of the invention is advantageously selected from the group consisting of saturated and/or unsaturated linear or branched hydrocarbyl acids having from 3 to 30 carbon atoms and saturated with from 3 to 30 carbon atoms. An ester of an unsaturated linear and/or branched alcohol, and an ester of an aromatic acid and a saturated and/or unsaturated linear or branched alcohol having from 3 to 30 carbon atoms. These esters may advantageously be selected from the group consisting of: isostearyl neopentanoate, diethylene glycol monostearate, isobutyl p-hydroxybenzoate, acrylate C10-C30 mercapto acrylate, octyl palmitate, coconut Octyl oleate, decyl cocoate, octyl isostearate, octyldodecanyl myristate, cetyl isononate, isopropyl myristate, isopropyl palmitate, stearic acid Isopropyl ester, isopropyl oleate, n-butyl stearate, n-hexyl laurate, n-decyl oleate, isooctyl stearate, isodecyl stearate, isodecyl isononanoate, brown 2-ethylhexyl acid release, 2-ethylhexyl laurate, 2-hexyl decyl stearate, 2-octyldodecanyl palmitate, stearyl heptanoate, oleic acid base Esters, oleic acid oleyl esters, oleic acid heart starch esters, erucic acid lysine core esters, tridecyl stearate, tridecyl trimellitate, and synthetic mixtures selected from these esters, semi-synthetic Mixtures and natural mixtures such as jojoba oil.

Other fatty components suitable for use in the compositions of the present invention include polar oils such as lecithin and fatty acid triglycerides, i.e., saturated and/or unsaturated straight chains of 8 to 24 carbon atoms, preferably 12 to 18 carbon atoms. Branched carbonic acid triglyceride, however fatty acid triglyceride is preferably selected from the group consisting of synthetic oils, semi-synthetic oils and natural oils (eg cocoglycerides, olive oil, sunflower oil, soybean oil, peanut oil, vegetable oil, almond oil, palm oil) , coconut oil, castor oil, hydrogenated castor oil, wheat oil, grape oil and other oils); non-polar oils such as linear and / or branched diameter and wax, such as mineral oil, petrolatum (petrolatum); paraffin, horn Shark and squalene, polyolefin (favorable polydecene), hydrogenated polyisobutylene and isohexadecane; dimercapto acid such as dioctanoyl ether; linear or cyclic silicone oil such as cyclomethicone, Octamethylcyclotetrasiloxane, hexadecanyl dimethicone, hexamethylcyclotrisiloxane, polydimethylsiloxane, poly(methylphenylsiloxane) and mixtures thereof. Other fatty components which may be advantageously added to the compositions of the invention are isodecahedon; neopentyl glycol heptanoate; propylene glycol diacrylate/dicaprate; octyl succinate/decyl acrylate/diglyceride; octanoic acid /butylene citrate; C12-13 decyl lactate; di C12-13 decyl tartrate; isoglyceryl tristearate; hexacyanoic acid / dipentaerythritol hexarate; propylene glycol monoisostearate ; Trioctyl glycerate; Dimethyl isosorbate. Particular preference is given to using a mixture of C12-15 decyl benzoate and 2-ethylhexyl isostearate, a mixture of C12-15 decyl benzoate and isodecyl isononanoate and C12-15 benzoic acid. A mixture of a base ester, 2-ethylhexyl isostearate and isodecyl isononanoate. The oil phase of the compositions of the present invention may also contain natural vegetable waxes or animal waxes such as beeswax, Chinese wax, rhubarb and other insect waxes, and shea butter.

The compositions of the present invention may additionally contain one or more emollients. An emollient that softens or smoothes the surface of the skin Description

Used and generally considered safe for topical use. The emollient also helps to control the rate of evaporation and the viscosity of the composition. Preferred emollients include mineral oil, lanolin oil, coconut oil, cocoa butter, olive oil, aloe extract, jojoba oil, castor oil, fatty acids such as oleic acid and stearic acid, fatty alcohols such as cetyl alcohol or sixteen Mercapto alcohol, diisopropyl adipate, benzoate and hydroxybenzoate of C9-C15 alcohol, isodecyl isononanoate, C15-C50 anthraquinone, mineral oil, siloxane such as Methyl polysiloxane, ethers such as polyoxypropylene butyl ether and polyoxypropylene cetyl ether, and C2-C15 decyl benzoate and mixtures thereof. The most preferred emollients are hydroxybenzoate, aloe vera, C12-C15 decyl benzoate and mixtures thereof.

The emollient is present in an amount from about 1% to about 20% by weight based on the total weight of the composition, preferably from about 2% to about 15% by weight, most preferably from about 4% to about 10% by weight. The aqueous phase of the preparation of the invention may contain customary cosmetic additives such as alcohols, especially lower alcohols, preferably ethanol and/or isopropanol, lower mercapto diols or polyols and ethers thereof, preferably propylene glycol, glycerol, ethylene Alcohol, ethylene glycol monoethyl ether or ethylene glycol monobutyl ether, propylene glycol monomethyl ether, propylene glycol monoethyl ether or propylene glycol monobutyl ether, diethylene glycol monomethyl ether or monoethyl ether and similar products, polymer, foam stabilizer; electrolyte And especially one or more thickeners.

Thickeners which can be used in the formulations of the present invention include silicas, magnesium silicates and/or aluminum silicates, polysaccharides and derivatives thereof such as hyaluronic acid, xanthan gum, hydroxypropyl cellulose, acrylate copolymers. Preferred are carbomer polyacrylates such as carbomers of the 980, 981, 1382, 2984, 5984 type.

A humectant, such as a humectant, can be added to the compositions of the present invention to reduce transepidermal water loss (TEWL) in the stratum corneum of the skin. Suitable humectants include glycerin, lactic acid, pyrrolidone, carbonic acid, urea, polyethylene glycol, polypropylene glycol, sorbitan, PEG-4, and mixtures thereof. Further suitable humectants are water-soluble polymeric humectants and/or hydrogelatinized polysaccharides such as hyaluronic acid, chitosan and/or trehalose-rich polysaccharides obtainable from SOLABIAS, such as Fucogel 1000 (CAS) -Nr. 178463-23-5) ₀ The amount of humectant optionally present is from about 0.5% to about 8% by weight, preferably from about 1% by weight to about 5% by weight based on the total weight of the composition. Suitable neutralizing agents can also be included in the compositions of the invention, such as emulsifiers, foam buliders and stabilizers. Suitable neutralizing agents include alkali metal hydroxides such as sodium hydroxide or potassium hydroxide; organic bases such as diethanolamine, triethanolamine, aminomethylpropanol or mercaptophosphates of these alkanolamines, such as diethanolamine Mercaptophosphate, trisodium ethylenediaminetetraacetate; basic amino acids such as arginine and lysine; and any combination of any of the foregoing. The amount of neutralizing agent optionally present is from about 0.01% to about 8% by weight, preferably from about 1% to about 5% by weight based on the total weight of the composition. It is preferred to add an electrolyte to the composition of the invention to modify the properties of the hydrophobic emulsifier. Accordingly, the microemulsion of the present invention preferably contains an electrolyte having one or more salts of anions including, but not limited to, hydrochlorides, sulfates, carbonates, borates, and lead salts. Other suitable electrolytes may be based on organic anions such as, but not limited to, lactate, acetate, benzoate, propionate, tartrate, and citrate. Preferred cations are ammonium ion, guanyl ammonium ion, alkali metal ion, magnesium ion, iron ion and zinc ion. Particularly preferred salts are potassium chloride and sodium chloride, magnesium sulfate, zinc sulfate and mixtures thereof. The electrolyte is present in an amount of about 0.01% by weight to 48% by weight based on the total weight of the composition.

The composition of the present invention can be used to photoprotect human skin or hair against the damaging effects of ultraviolet radiation, which can be used as a light/sun protection composition or cosmetic. These compositions may in particular be lotions, thickening lotions, gels, pastes, Instruction manual

It is provided in the form of a milk, ointment, powder or solid tube stick and may optionally be packaged as an aerosol and may be provided in the form of a mousse, foam or propellant. They may be in the form of a suspension or dispersion in a solvent or in the form of a fatty substance; or alternatively in the form of an emulsion (preferably a 0/W type such as a cream or a milk, a foaming dispersion), an ointment, a gel, a solid tube Rod or aerosol mousse form. The emulsion may also contain anionic, nonionic, cationic or amphoteric surfactants.

A third aspect of the invention relates to the use of a cosmetic composition for protecting human skin, head, and ultraviolet light.

When the cosmetic composition of the present invention is used for protecting hair, the composition may be in the form of shampoo, lotion, gel, that is, before, during or after shampooing, before or after dyeing or bleaching, perm or curling. A composition for application, combing or treating a lotion or gel, combing or wavy a lotion or gel, hair styling, perming or straightening the hair, hair dyeing or discoloring composition.

When the cosmetic composition of the present invention is used as a cosmetic for eyelashes, eyebrows, skin or hair, such as skin treatment cream, face oil or cream for makeup, lipstick, eye cream, face cream, eyeliner (referred to as 'eye circle') Color liquid), mascara, dyed gel, the cosmetic composition may be in the form of an anhydrous or aqueous solid or paste and such as an oil-in-water or water-in-oil emulsion, suspension or gel.

A fourth aspect of the invention relates to a method of using the cosmetic composition of the invention to protect the skin and hair from ultraviolet radiation, in particular against sunlight, by a cosmetic composition as defined above or a chemical formula as defined above ( The compound is applied to the skin or hair.

detailed description

The following examples illustrate the invention without limiting its scope:

Figure 1 shows the ultraviolet absorption spectrum of the compound (3);

Figure 2 is an ultraviolet absorption spectrum of the compound (4);

Figure 3 UV absorption spectrum of OMC

Example

Instruments and reagents

Instrument: 400M Fourier transform NMR spectrometer (Bmker, Germany), CDCI3 as solvent, TMS as internal standard; Ion 肼 mass spectrometer (Bmker, Germany); UV-3100PC UV-visible spectrophotometer (Shanghai Mapada) ;

WRS-1A Digital Melting Point Instrument (Shanghai Suoguang Optoelectronic Technology Co., Ltd.).

Reagents: p-methoxybenzaldehyde and thionyl chloride (re-distilled before use); malonic acid, L-menthol, pyridine, piperidine, triethylamine, toluene, petroleum ether, etc. are all AR; TLC chromatography Plate, column chromatography silica gel, Qingdao Ocean Chemical Plant. Example 1 Instruction manual

This example illustrates a general method for preparing compounds of the invention having formulas (1)-(4):

Synthesis of 1.1 p-methoxycinnamic acid

In a three-necked flask equipped with a thermometer and a reflux condenser, p-methoxybenzaldehyde (13.60 g, 0.1 mol), malonic acid (14.60 g, 0.14 mol), pyridine (7.90 g, O.10 mol) were sequentially added. Piperidine (0.08 g, 1 mmol), stirred, and reacted at 85 ° C for 6 h. After cooling to room temperature, cold water (80 ml) was added under stirring, and the solid was precipitated, suction filtered, washed twice with cold water, dried, and recrystallized from ethanol to give the title compound 14.49 g, yield 87.8%, melting point 172 174. ~175 ° C, see Lu Lianying et al, the synthesis of sunscreen octyl methoxycinnamate, Chemical World, 2006, 11: 672-675: ).

The trans isomer can be partially or completely obtained by high temperature or light, for example, referring to Yang Xiaolong, the conversion of trans-cinnamic acid to cis β-bromo styrene, Chinese Journal of Pharmaceutical Industry, 2001, 07 .

Synthesis of 1.2 p-methoxy cinnamate menthyl ester

To a 100 ml single-mouth bottle, p-methoxycinnamic acid (5.00 g, 0.028 mol), thionyl chloride (16.75 g, 0.14 mol) was added, and a reflux condenser with a drying tube was placed, and the mixture was stirred for 3 hours, and then removed under reduced pressure. Excess thionyl chloride gave solid (3). 50 ml of toluene, L-menthol (4.4 g, 0.028 mol), triethylamine (2.8 g, 0.028 mol), stirred under reflux for 1 h, quenched the reaction, suction filtered, filtrate concentrated, column chromatography [V ( petroleum ether): V (ethyl acetate) = 25: 1] gave a pale yellow oily solid which solidified to afford (1) 7.49 g. ^NMRiCDC ), δ: 0·789(3Η, d, J=6.8Hz), 0.902~0.928(7H , m), 0.993~1.118(2H , m), 1.410~1.483(1H , m), 1.886~1.969 (1H , m), 1.582(1H , s), 1.671~1.730(2H , m), 2.049(1H, s), 3.840(3H, s), 4.814(1H, d, J=4Hz), 6.305(1H , d, J=16Hz), 6.901(2H , d, J=8.8Hz), 7.482(2H, d, J=8.8Hz), 7.629(1H, d, J=16Hz); ES Bu MSm/z:315 { [ M- H ] }

Determination of the ultraviolet absorption properties of the compound of Example 2

0.1003 g of the compound (1) was weighed, dissolved in absolute ethanol and diluted to 100 ml; 1 ml of the solution was pipetted into a 100 ml volumetric flask; and diluted to the mark to prepare a compound (1) solution having a mass concentration of 10 g/ml. Absolute ethanol was used as a blank calibration, and scanned by an ultraviolet-visible spectrophotometer, and scanned in the range of 200 nm to 400 nm.

Scanning both OMC and Compounds 3 and 4 (concentration of 10 g/ml) in the range of 200-400 nm showed that the latter had strong UV absorption in the 280-330 nm band and the maximum absorption at 310 nm. The maximum absorption wavelength is 310.50 nm, the absorbance is 1.054, the molar absorption coefficient is 3.36 X 10 ⁴ L/(mol X cm), see Figures 1 and 2; and the maximum absorption wavelength of OMC is 309.50 nm, and the absorbance is 0.461, Molar The absorption coefficient is 1.36 X 10 ⁴ L/(mol X cm), as shown in Figure 3, indicating that compounds 3 and 4 have significantly higher UV absorption than OMC, and cover a wider range of UV wavelengths, which can be used as a potential UVB UV. Use as an absorbent. Example 3: Solubility test

Method: The solubility of this product was investigated by referring to the methods prescribed in the Chinese Pharmacopoeia 2010 edition. Weigh a certain amount of the test powder into a fine powder, place it in a certain amount of container at 25 ° C ± 2 ° C, shake vigorously for 5 seconds every 5 minutes; observe the dissolution within 30 minutes, If the solute particles are not visible, they are considered to be completely dissolved.

The solubility of this product in the following solvents was examined: ethanol, water, 0.1 mol/L HCI, O.lmol/L NaOH aqueous solution, and the solubility results of compounds 3 and 4 are shown in the table below. Instruction manual

Solubility test results for compounds 3 and 4

Weight (g) solvent phenomenon conclusion

0.1 Ethanol Easy to dissolve >10%

Cocoate octanoate phthalate soluble >10%

0.1

(CETIOLLC)

Diisopropyl adipate soluble >10%

0.1

(crodamolDA)

0.01 water insoluble <0.01%

<0.01%

0.01 O.lmol/LHCI insoluble

<0.01%

0.01 O.lmol/L NaOH insoluble

Conclusion This product is easily soluble in ethanol, cocoate decanoate (CETIOLLC), diisopropyl adipate (crodamolDA); insoluble in water, 0.1mol/L HCI, O.lmol/L NaOH aqueous solution, indicating the invention Compounds 3 and 4 have good cosmetic properties, good solubility in common fat solvents, and good water and sweat resistance (stagnation) properties, and have excellent sunscreen cosmetic potential. Example 4: Evaluation of cooling sensation of menthyl p-methoxycinnamate

Test solution: menthol and compound (3), (4) p-methoxy cinnamic acid menthol ester, respectively, were prepared into a lmg / ml ethanol solution;

Subjects: 10 subjects aged 19-21, 5 males and 5 females;

Test method: Take a small amount of the above two ethanol solutions with absorbent cotton and apply them to the inside of the left and right forearms of the subject respectively to observe the reaction and skin irritation of the subject after use. All subjects were coated with a menthyl ester solution on their left hand and a p-methoxycinnamate menthol ester compound of the formula (3), (4). (3) Test again 2 hours after the test is completed (4).

Record of test results: According to the duration of coolness and refreshing sensation, the three compounds were respectively in accordance with the cooling sensation: no cooling sensation (-); weak cooling sensation (+); strong cooling sensation (++); strong coolness : (+++). Cooling duration: 30 minutes, 60 minutes, 120 minutes and 120 minutes.

test results:

Cooling effect of the compound

Note: No cool feeling: -; Weak cool feeling: +; Strong cool feeling: ++; Strong cool feeling: +++ Instruction manual

Analysis: After coating lmg/ml menthol, p-menthyl p-aminobenzoate and ethanol solution of p-methoxycinnamate menthol, menthol produced a significant stimulating effect in a short time, but the refreshing feeling was very fast. It disappeared, but the menthyl anthranilate and the compounds 3 and 4 produced a long-lasting cooling effect, and the effect was mild, but the cooling sensation of the compounds 3 and 4 was longer than that of the menthyl anthranilate.

The above test shows that the compound of the present invention has a mild cooling feeling, a small irritancy, and a long duration of cooling sensation, and is an ideal ultraviolet absorbing agent. Example 5

This embodiment specifically discloses a formula of a cosmetic composition

Component composition

Part A:

Compound

Avobenzone

Cetyl alcohol

Coconut octanoate (CETIOLLC)

Isostearyl pivalate

Diethylene glycol monostearate

Isobutyl p-hydroxybenzoate

EDTA-sodium salt

Diethanolamine hexadecanoyl phosphate B part

Acrylate C10-C30 mercapto acrylate

Deionized water

1,2-propanediol

Potassium Hydroxide (10%) Heat part A to 85 °C in the reactor, then slowly add Part B over 10 minutes, then add potassium hydroxide, then cool and degas the obtained emulsion to get 0/W type. UV-A and UV-B compound sunscreen lotion.

Claims

claims

1. Compounds with the following structures including cis-trans isomers or stereoisomers (1):

.Compounds with the following structures including stereoisomers

(2) :

3. Racemic compounds with the following structure of formula (3) and optical compounds with the structure of formula (4):

4. A cosmetic composition containing a certain amount of a compound of any one of the formulas (1) to (4) as an ultraviolet absorber.

5. The composition of claim 4 is an emulsion, thickened emulsion, cream, gel, solution, dry powder, film, solid rod, aerosol and mousse.

6. The amount of the compound of formula (1)-(4) described in claim 4 is 0.5-20wt%.

7. The composition of claim 4, which may include one or more other UV-A and UV-B ultraviolet absorbers.

8. Other UV absorbers described in claim 7 include:

The following organic or inorganic UV-A:

, acrylates, including 2-ethylhexyl-2-cyano-3,3-diphenylacrylate and ethyl 2-cyano-3,3-diphenylacrylate;

•Camphor derivatives, including 4-methylbenzylidene camphor, 3-benzylidene camphor, camphor benzylidene methyl sulfate, polyacrylamidomethylbenzylidene camphor, thiobenzylidene camphor, thio Methyl benzylidene camphor and p-phenylidene camphorsulfonic acid; cinnamate derivatives, including octyl methoxycinnamate, ethoxyethyl methoxycinnamate, and methoxycinnamic acid Claims

Diethanolamine ester and isoamyl methoxycinnamate;

, p-aminobenzoic acid derivatives, including p-aminobenzoic acid, 2-ethylhexyl p-dimethylaminobenzoate, N-oxypropylated ethyl p-aminobenzoate, and glyceryl p-aminobenzoate;

*Benzophenones, including benzophenone-3, benzophenone-4, 2,2',4,4'-tetrahydroxy-benzophenone, 2,2'-dihydroxy-4,4-dimethoxy benzophenone;

• Benzylidene malonates, including 4-methoxybenzylidene malonate di(2-ethylhexyl) ester;

•2-(4-ethoxy-anilinomethylene)-malonate, including 2-(4-ethoxy-anilinomethylene)-malonate diethyl ester; organosiloxane Compounds including benzylidene malonates as described in European patent publications EP-BI-0358584, EP-BI-0538431 and EP-AI-0709080;

•Benzotriazole trisiloxane;

, pigments with a diameter of about 5nm to about 200nm, including titanium dioxide particles, which can be further coated with metal oxides of aluminum oxide or zirconium oxide, or coated with polyols, methyl silicone oil, aluminum stearate, and alkyl silane;

•Imidazole derivatives, including 2-phenylbenzimidazole sulfonic acid and its salts;

•Salicylate derivatives, including isopropyl benzyl salicylate, benzyl salicylate, butyl salicylate, octyl salicylate, isooctyl salicylate or homomontethyl salicylate;

•Triazone derivatives, including octyltriazone, dioctylbutylamidotriazone, etc.;

and/or the following organic or inorganic UV-B:

•Dibenzoylformate derivatives, including 4-tert-butyl-4'-methoxydibenzoylformane, dimethoxydibenzoylformane, and isopropyldibenzoylformane ;

•Benzotriazole derivatives, including 2,2'-methylene-bis-(6-(2H-benzotriazole)-2-yl)-4-(1,1,3,3-tetramethyl Butyl) - phenol;

•Phenylene-1,4-dibenzimidazole sulfonic acid or salt, including 2,2-(1,4-phenylene)-bis-(IH-benzimidazole-4,6-disulfonic acid) ;

, amino-substituted hydroxybenzophenones, including ethyl 2-(4-diethylamino-2-hydroxy-benzoyl)-benzoate as described in European Patent Publication EP1046391;

, pigments with a diameter of about 5 nm to about 200 nm, including zinc oxide particles, which can be further coated with metal oxides of aluminum oxide or zirconium oxide, or coated with polyol, methyl silicone oil, aluminum stearate, or alkyl silane.

9. The composition according to claims 4-7 may additionally contain preservatives/antioxidants, fatty substances/oils, water, organic solvents, silicones, thickeners, softeners, emulsifiers, defoaming agents, Humectants, fragrances, surfactants, fillers, chelating agents, anionic polymers, cationic polymers, nonionic polymers or amphoteric polymers or mixtures thereof, propellants, acidulants or alkalizing agents, dyes, colorants, pigments Or nanopigments.

10. Application of the compound or composition described in claims 1-3 and 4-7 in the preparation of sunscreen agents for protecting human skin and hair.