CN102177150A

CN102177150A - Dithiolane compounds, composition including compounds and uses in protection of skin

Info

Publication number: CN102177150A
Application number: CN2009801406128A
Authority: CN
Inventors: X·马拉特
Original assignee: LOreal SA
Current assignee: LOreal SA
Priority date: 2008-10-10
Filing date: 2009-09-01
Publication date: 2011-09-07
Also published as: WO2010040603A1; FR2937035A1; FR2937035B1; EP2337780A1

Abstract

The present invention relates to novel dithiolane compounds of formula (I) below: formula (I), in which Y denotes 0, NR1 or S; R1 denotes a hydrogen atom; a saturated linear C1-C20 or branched C3-C20 or unsaturated C2-C20 alkyl hydrocarbon- based group; an aryl group optionally substituted with one or more hydroxyls and/or with one or more C1-C8 alkoxy radicals; R denotes a hydrogen atom; a saturated linear C1-C20 or branched C3-C20 or unsaturated C2-C20 alkyl hydrocarbon- based group; a radical having the following formula (Ia), in which n = 0, 1, 2, 3 or 4; x = 0, 1, 2 or 3 and R3, which may be identical or different, denote a hydrogen atom or a linear or branched C1-C4 alkyl such as methyl, ethyl or isopropyl; the radical 4-methyl dithiolane when Y denotes NH; when Y denotes NHR1 and R1 is other than hydrogen, R and Ri may form a ring. The invention also relates to the uses of these compounds for reinforcing the natural antioxidant protection of the skin against oxidative stress caused especially by UV radiation.

Description

The dithiolane compound, contain described compound compositions and purposes in the skin photo-protection

The present invention relates to new specific formula (I) the dithiolane compound, relate to cosmetic compositions or the pharmaceutical composition that contains described compound and finally relate to its illness that causes by oxidative stress in treatment or prevention, the purposes in the illness that especially causes by solar radiation.

Therefore skin is the outermost organ of our health, is the most especially by the target at first of the environmental stress factor of sunlight uv-radiation UVB and UVA representative.Say that exactly known acute the or chronic sunlight that is exposed to causes deleterious biological effect and clinical effect to health.

To having carried out extensive studies in the skin injury that UV-A or UV-B cause by chronic exposure (irradiation repeatedly) or acute exposure (strong irradiation); Especially known:

-UV-B ray (290-300nm; Total UV 5%), it has the wavelength of high energy, the most especially influences epidermic cell (keratinocyte) by acting on DNA;

-UV-A ray (320-400nm; Total UV 95%), it penetrates deeplyer, reaches dermal cell (for example inoblast), and plays indirect action by producing free radical;

-in addition, long-term exposure has the effect that stimulates collagenase, particularly 1 type matrix metalloproteinase (MMP-1) to express in uv-radiation.

At cell and molecular level, the influence of UVB and UVA radiating causes various reactions, comprises directly and causes dna damage indirectly.

In the dna damage that directly causes, there are some to be specific to the UV radiation, for example pyrimidine dimer and 6,4 photoproducts (photo-produced).If make mistakes during repairing by special enzyme system (nucleotide excision repairs NER or GER is repaired in excision of overall importance), just then they may cause sudden change, described sudden change itself is exactly the cause that causes forming the tumor progression of skin carcinoma.In addition, in deriving from the cell of these tumours, find that the incidence of the characteristic sudden change that sun UV influences is very high.These dna damages still induce epidermis to form the i.e. inducement of the apoptosis process of " sunburn cell " of characteristic cell.Should also be noted that UV is the reason that forms active oxygen on cell levels, described active oxygen itself is exactly the reason of many biological effects, for example causes O-DNA damage (8-oxo guanine) or induces several genes.

At last, except the effect to two kinds of main skin cells types (promptly forming the inoblast that the keratinocyte of epidermis of layering and differentiation and responsible corium extracellular matrix are synthetic and upgrade) of main description, the UV ray is also influential to the Langerhans cell with antigen presentation immunologic function.

The UV ray causes by the direct effect of UV ray to some cell chromophore (for example DNA) the deleterious effect (erythema, photocarcinogenesis, photoaging, light immunosuppression etc.) of skin, but also causes by indirect action.Say exactly, can be by relating to the photosensitized reaction of endogenous photosensitizers (for example riboflavin, bilirubin, brown pigments and derivatives of porphyrin) through the energy of UV ray transhipment, and the formation of initiating activity oxygen class (AOS) (for example singlet oxygen and superoxide anion).Singlet oxygen and superoxide anion experience reaction cascade cause the generation of other AOS (for example hydrogen peroxide and hydroxy radical qiao).AOS damage dna, cytolemma and some protein (enzyme, transcription factor etc.) that produces like this.

Cell is equipped with enzymatic anti-oxidative defense thing (Cu-Zn and Mn superoxide-dismutase, catalase, Selenoperoxidase etc.) and non-enzymatic anti-oxidative defense thing (vitamin-E and C, the thio-alcohol that comprises gsh, β-Hu Luobusu, trace elements etc.), its effect is to keep intracellular redox potential, but this defence capability may be transshipped when strong oxidative stress takes place.

Tripeptides gsh (γ-L-glutamyl-L-cysteinyl glycine or GSH) is the most extensive existence and the abundantest lower molecular weight nonprotein mercaptan.GSH exists with reduction form (GSH) in most of born of the same parents.Glutathione disulfide (GSSG) accounts for below 0.5% of total GSH.In most of zooblasts, the concentration of GSH is between 1mM and 10mM, and the concentration in blood plasma is then between about 0.5 μ M and 10 μ M.The mercapto functional group that is arranged on the cysteine residues is given it in the prevailing redox potential of redox metabolism phenomenon (approximately-230mV).Its reduction and nucleophilic character play a major role in the protection to fat, protein and nucleic acid oxidative damage.Under the situation of oxidative stress, its protection and detoxification mainly result from its function as the coenzyme of Selenoperoxidase and glutathione-S-transferase.It also with other component (for example vitamins C, vitamin-E and superoxide-dismutase) of anti-oxidation protection system experience cooperative interaction.

Therefore, the level of reduction gsh can influence the redox equilibrium of cell.Especially the known UV of being exposed to ray causes the loss of GSH level in the born of the same parents, thereby increases the susceptibility of cell to oxidative stress.

Use sun-screening agent can protect skin not to be subjected to UV radiating deleterious effect.These products contain the molecule of the harmful wavelength of absorption before harmful wavelength arrives skin and injured skin, thereby prevent to be exposed to the acute and chronic effect of UV ray.

Yet sun-screening agent does not have comprehensive effect.Though do not have the sun-screening agent that allows to absorb fully harmful wavelength (UVB, UVA and long UVA), be based on and induce the photo-protection strategy of endogenous anti-oxidative defense system that favourable prospect is provided.

Therefore, in this field, be starved of searching and be exposed to other solution of rebuilding and/or keep the endogenous glutathione level after the UV ray.This can be envisioned for, and stimulates natural endogenous cell defence and/or repair system with promoting agent after UV inductive stress event takes place.

Thioctic Acid (Lipoic/thioctic acid) (1,2-dithiolane-3-valeric acid) is endogenous two mercaptan that extensively are present in the plant and animal.It is the coenzyme of fat and carbohydrate metabolism in plastosome multienzyme complex (for example pyruvic oxidase and ketoglurate dehydrogenase).Thioctic Acid also improves the cell levels of gsh by the activity of regenerating oxidation type gsh (GSSG) and increase γ-Gu Anxianji halfcystine ligase enzyme (a kind of control GSH synthetic enzyme).

WO 2008/058999 discloses siloxanes or the silane dithiolane compound that is used for improving glutathione level after the loss of UV inductive, especially compound 5-(1,2-dithia ring penta-3-yl)-and N-[3-(trimethyl silyl) propyl group] valeramide and compound 5-(1,2-dithia ring penta-3-yl) valeric acid (trimethyl silyl) methyl esters.Yet the protection at the GSH loss of UVA sunlight-induced that these promoting agents provide still is not very satisfactory.

Applicant of the present invention has now found that: compare with the dithiolane compound of prior art, some dithiolane compound (hereinafter with specific definition) of specific formula (I) can significantly improve the level of gsh after the loss of UV inductive, thereby can strengthen and/or keep cutaneous acupuncture to especially by the protection of the natural anti-oxidation of the radiation-induced oxidative stress of UV.

Therefore, a theme of the present invention is the dithiolane compound (below will define in more detail) of new specific formula (I).

A theme of the present invention also is included in the beauty treatment or the pharmaceutical composition of the dithiolane compound of at least a formula (I) in the acceptable medium on the physiology.

Beautifying use in the composition of dithiolane compound acceptable medium on comprising physiology that a theme of the present invention still is an at least a formula (I), described composition are used to strengthen and/or keep cutaneous acupuncture to especially by natural anti-oxidation protection, the especially purpose of endogenous anti-oxidative defense system of the radiation-induced oxidative stress of UV.

Specifically, beautifying use in the composition of dithiolane compound acceptable medium on comprising physiology that a theme of the present invention is an at least a formula (I), described composition are used to strengthen and/or keep the purpose of the level of the endogenous born of the same parents glutathion inside that the protection of skin natural anti-oxidation is provided.

Therefore term " skin " means any skin surface of human body, comprises skin, mucous membrane and half mucous membrane, comprises lip, scalp and skin volume quilt, refers in particular to/toenail, chaeta and hair.

According to the present invention, " acceptable medium on the physiology " or with skin, mucous membrane, refer to/toenail and/or hair be at beauty treatment or pharmaceutically acceptable medium, or medium that can orally give.

Other theme of the present invention will describe in detail at the rest part of this specification sheets after a while.

Dithiolane compound of the present invention is corresponding to following formula (I):

Wherein Y represents O or NR ₁

R ₁The expression hydrogen atom; Saturated straight chain C ₁-C ₂₀Or side chain C ₃-C ₂₀Alkyl or undersaturated C ₂-C ₂₀Alkyl; By one or more hydroxyls and/or by one or more C ₁-C ₈The optional aryl that replaces of alkoxyl group;

R represents hydrogen atom; Saturated straight chain C ₁-C ₂₀Or side chain C ₃-C ₂₀Alkyl or undersaturated C ₂-C ₂₀Alkyl; Group with following formula:

N=0,1,2,3 or 4 wherein; X=0,1,2 or 3; And R ₃Can be identical or different, expression hydrogen atom or straight or branched C ₁-C ₄Alkyl, for example methyl, ethyl or sec.-propyl; Group 4-methyl dithiolane when Y represents NH;

When Y represents NR ₁And R ₁When being not hydrogen, R and R ₁Can form and be selected from following ring: tetramethyleneimine, pyrroline, piperidines, piperazine, morpholine, thiomorpholine and azepine

Described alkoxyl group is preferably straight chain C ₁-C ₄Group, more preferably methoxyl group, oxyethyl group, propoxy-or butoxy, also methoxyl group more preferably.

Described alkyl is preferably the straight or branched alkyl, and can be selected from: methyl, ethyl, propyl group, sec.-propyl, butyl, isobutyl-, the tertiary butyl, amyl group, hexyl, heptyl, octyl group, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl, octadecyl, nonadecyl, eicosyl.

Described aryl is preferably phenyl.

The straight or branched C that described alkyl is more preferably saturated ₁-C ₈Alkyl: methyl, ethyl, propyl group, sec.-propyl, butyl, isobutyl-, the tertiary butyl, amyl group, hexyl, heptyl, octyl group.

Preferred formula (I) compound is following compound, wherein:

R ₁Expression hydrogen or saturated straight chain C ₁-C ₆Or side chain C ₃-C ₆Alkyl,

R represents hydrogen or saturated straight chain C ₁-C ₁₂Or side chain C ₃-C ₁₂Alkyl; Saturated straight chain C ₁-C ₁₂Or side chain C ₃-C ₁₂Alkyl; Group with following formula:

N=0,1,2,3 or 4 wherein; X=0,1,2 or 3; And R ₃Can be identical or different, expression hydrogen, methyl, ethyl or sec.-propyl; Group 4-methyl dithiolane when Y represents NH;

In these compounds, more preferably the compound of Shi Yonging is following compound, wherein:

R represents hydrogen; Saturated straight chain C ₁-C ₁₀Or side chain C ₃-C ₁₀Alkyl; Following group

N=0,1 or 2 wherein; X=0,1 or 2, and R ₃Can be identical or different, expression hydrogen or methyl; Group 4-methyl dithiolane when Y represents NH;

In these compounds, the compound that also more preferably uses is that wherein Y is the compound of NH.

As formula (I) examples for compounds, mention following compounds especially:

Synthetic

Can obtain formula (I) compound according to the route of putting down in writing among described below and application EP 0 869 126 A1.

From the 4-methyl isophthalic acid, 2-dithiolane-4-formic acid (CAS:208243-72-5) or certainly corresponding methane amide are reset acquisition formula (I) compound by Curtius (Curtius) or Huffman (Hofmann).

Advantageously, can be according to route described below, (one-pot process) begins with the dichloro PIVALIC ACID CRUDE (25) according to one kettle way, finishes with precipitation, obtains compound 4-methyl isophthalic acid, 2-dithiolane-4-formic acid (CAS:208243-72-5).

Advantageously, can use isobutyl chlorocarbonate or oxalyl chloride, by the 4-methyl isophthalic acid, 2-dithiolane-4-formic acid obtains corresponding benzamide compound.

Can in the presence of trinitride ion source (sodiumazide, azide diphenyl phosphate, trimethyl azide base silane), for example in such as apolar aprotic solvents such as toluene or chloroforms or in, carry out Curtius reaction such as acetonitrile, dimethyl formamide or alcohol (tBuOH, MeOH, EtOH) isopolarity solvent.In case form the acylazide intermediate, just reacting by heating medium is so that along with extruding of phenodiazine reset.The isocyanic ester that forms is thus contacted with alcohol or amine to form carbamate or urea.

Can be in the presence of such as oxygenants such as multivalence iodine derivative (PIFA) or metal (sodium, calcium etc.) hypochlorites, carrying out hofmann rearrangement such as water or alcohol (tBuOH, MeOH, EtOH) isopolarity protonic solvent or in such as aprotic solvent such as dimethyl formamides.

Reference: L.Kurti and B.Czako, Strategic application of named reactions in organic synthesis (the famous tactic that is reflected in the organic synthesis is used), Elsevier Academic Press, 2005.

Applicant of the present invention is verified: (the stimulation of average UV daylight of UV daylight, L ' Or é al concept, Christiaens F.J. etc.: Standard ultraviolet daylight for non-extreme exposure conditions (the standard ultraviolet ray daylight of non-extreme exposure condition), Photochem.Photobiol., 2005) cause in the HaCaT cell (keratinocyte that obtains by the adult skin implant of external spontaneous immortalization) that the level of GSH reduces in the born of the same parents.Reach maximum (about 40% reduce) in exposure loss in back 6 hours, and got back to basal level in back 24 hours being exposed to UV daylight (UV-DL).

Compound of the present invention can prevent and/or correct this loss of GSH, therefore can " promote " endogenous anti-oxidative defense system, so that skin stress prepare and help skin to carry out self-regeneration for bearing UV better.It is active suitable with the reference compound Thioctic Acid, and known Thioctic Acid improves the level of GSH.

Therefore, applicant of the present invention confirms: the ability of the level of compound raising GSH of the present invention is much larger than the ability (measuring under the same conditions) (seeing embodiment) of Thioctic Acid.

Specifically, a theme of the present invention is the beautifying use in the composition of at least a dithiolane compound acceptable medium on comprising physiology that is selected from formula (I) compound, and described composition is used to strengthen and/or keeps to be provided at especially by the purpose of the endogenous born of the same parents glutathion inside level of the skin natural anti-oxidation protection of the radiation-induced oxidative stress of UV.

Therefore, purposes of the present invention can strengthen and/or keep the anti-oxidative defense system of the anti-oxidative defense system, particularly skin cells of cell.Skin cells especially is inoblast, keratinocyte and Langerhans cell.

According to a favourable purposes of the present invention, the compound of general formula (I) can be used as the skin light protective agent.

Intensity is lower than minimum erythema dose (erythemal dose) and its effect does not produce the daylight of visible sign on skin no matter whether skin is through being exposed to, no matter perhaps as seen whether the UV RADI (for example rubescent by occurring on the skin), this purposes all can be useful.

Therefore, the scope of damage from simple discomfort (for example unique appreciable skin heat feel) to rubescent or even shouting pain.

Therefore, the compound of general formula (I) can be used for preventing and/or treating the UV that causes by solar radiation (particularly UVA and/or UVB) stress and/or heat feel.

The compound of general formula (I) also can be used for preparing the composition that comprises acceptable medium on the physiology, and its expection is used to prevent and/or treat the skin injury that is caused by solar radiation, for example skin rubefaction and stimulation.

The compound of general formula (I) also can be used for preparing the composition that comprises acceptable medium on the physiology, and it is used to prevent and/or treat the dna damage that is caused by solar radiation, thereby is used for the formation of preventing cancer (particularly skin carcinoma).

The compound of general formula (I) also can be used for preparing the composition that contains acceptable medium on the physiology, and its expection is used for the treatment of by by UVA and/or UVB radiation irradiation and the skin and/or the mucous membrane illness that cause.

Solar irradiation or expose by revealing cruelly to sunlight characterizes, and especially can be strong irradiation, its be equivalent to be exposed to zenith sun light (zenithal sunlight) or the solar radiation that changes along 30 ° of angles of this zenith position under, and/or when skin is subjected to causing the UV radiation of sun erythema (being commonly referred to the rubescent of " sunburn "), then define by minimum erythema dose (MED).This dosage is as light type (phototype) function of individuality and UVA/UVB ratio function and change.

The damage that the invention particularly relates to prevention or alleviate skin, mucous membrane and/or the body quilt of the Mammals (particularly human) that causes by the solar radiation that is exposed to erythema dose in short-term.

These sun exposed conditions comprise dosage about MED, particularly more than or equal to the UVA and/or the UVB ray of 1MED dosage.

As mentioned above, because it improves the ability of GSH level, formula of the present invention (I) compound can be for setting up skin antioxidant defense system.

Therefore, according to the present invention, the beautifying use in the composition of at least a dithiolane compound acceptable medium on containing physiology that is selected from formula (I) compound is specially adapted to prepare for skin is exposed to sunlight.

Specifically, can be by before being exposed to sunlight, described cosmetic compositions is applied to skin every day reaches a week, preferred two weeks, just come to prepare for skin is exposed to sunlight at least one day (between 6 hours and 18 hours) before being exposed to sunlight.

No matter it is endogenous source or exogenous source, free radical is especially at cytolemma (lipid oxidation cause membrane permeability descend), nucleus (destruction of DNA) with organize, particularly cause substantive oxidative damage in reticular tissue (degraded of elastin and collegen filament, and the depolymerization of polyuronic acid fiber (polyuronic fibre)).This damage especially causes xerosis cutis and loses firmness and elasticity (Grinwald etc., 1980; Agren etc., 1997).

At present, the expert thinks, a reason of cell senescence is to weaken to free radical and to the defence capability of the oxidative phenomena (the especially formation of superoxide ion) of its initiation.

Therefore, more briefly say, general formula of the present invention (I) compound can be used as and is used for preventing and/or the restraint of liberty base forms and/or be used to remove the indirect anti-oxidizing compounds of the free radical that cell exists, and can be used for any skin disorder of being caused by oxidative stress.

This activity of general formula (I) compound is strengthened by these compounds intrinsic antioxidation property relevant with its mercapto functional group.

Therefore, use The compounds of this invention that some clinical sign of skin aging is prevented and/or treated.

Aging is the physiological phenomenon of nature, and its clinical sign can be reflected on the skin usually, wrinkle and microgroove, skin and subcutis occur and relaxes, loses skin elasticity and texture shortage tension force.It is the reason that skin loses firmness and tension force (for example wrinkle and microgroove) that dermal atrophy and dermoepidermal junction are flattened to small part; Skin is more shaky, and is more lax, and epidermal thickness reduces.

Another clinical sign of aged is that the skin appearance drying is coarse, and this is by due to the more furfur in essence; By making the light diffraction, these scales of skin that peel offs also cause slightly grey of colour of skin outward appearance.

In these signs some are more specifically aging with inherency or physiological is aging, and (being that age related is aging) is relevant, and other sign more is specific to exogenous wearing out, and promptly generally is by wearing out that environment causes; More particularly be owing to be exposed to the situation of the photoaging that sunlight, light or any other radiation or pollutent cause.

Therefore, theme of the present invention is particularly suitable for the beautifying use of at least a general formula of the present invention (I) compound at the composition of firmness that is used for preventing and/or treating skin and/or elastic forfeiture, and described composition contains acceptable medium on the physiology.This class purposes especially can be recaptured uniform and smooth outward appearance for skin.

The present invention also is suitable at least a general formula of the present invention (I) compound at the beautifying use that can accept the composition of medium on the physiology that contains that is used for preventing and/or treating skin dehydration.

More briefly say, theme of the present invention also is suitable for being selected from least a compound of general formula of the present invention (I) compound, is being used for preventing and/or treating atrophy of epidermis and/or pachylosis and/or the xerodermatic beautifying use that can accept the composition of medium on the physiology that contains.

Another theme of the present invention relates to the compound of at least a general formula (I), is being used for preventing and/or treating contain the beautifying use that beauty treatment can accept the composition of medium of pollution to the deleterious effect of skin.

Known atmospheric polluting material, especially gaseous pollutant (for example sulfurous gas, ozone and oxynitride) are to skin component (fiber, cell and enzyme) and especially relevant with the activity of its radical initiator to the toxicity of the secreted sebum of skin, and described radical initiator is the source that causes the oxidative phenomena of life entity cell injury.

With outside atmosphere directly and the viable cell that contacts all the time (especially skin, scalp and some mucous membrane) responsive especially to these effects of gaseous pollutant, this especially is reflected in in the skin accelerated deterioration that wrinkle or microgroove form in early days, also is reflected in energy decline and the hair outward appearance dimness.

As previously mentioned, the undesirable action of the free radical that exists in the skin is that they cause lipid peroxidation.With age growth (more especially from 40 years old), the accumulation of these lipid peroxides is reason (Haze S. etc., J.Invest.Dermatol.2001,116 (4): 520-4) of causing body odour beastly (for example old flavor).

Theme of the present invention is suitable at least a general formula of the present invention (I) compound, be used for preventing and/or limit and/or eliminate skin lipid oxidation contain the beautifying use that can accept the composition of medium on the physiology.

Therefore, theme of the present invention also can be used for prevention and/or restriction and/or eliminates body odour beastly.

The present composition can expect be used for the beauty treatment and/or the dermatology purposes.They can be to be suitable for the composition that topical application, particularly external partial are applied to skin, mucous membrane and/or body quilt.

According to another embodiment, the present composition is suitable for oral route, and especially expection is used for oral cosmetic application.

The amount of compound obviously depends on needed effect used according to the present invention, therefore can change in a big scope.

In order to provide the order of magnitude, can be as formula (I) compound of preceding definition by the amount of the 0.001%-20% that accounts for composition total weight, preferably the amount by the 0.01%-10% that accounts for composition total weight is used for local approach, particularly the external partial approach.

For oral route, can use formula (I) compound as preceding definition, the amount that described compound exists is taken between dosage and the 100mg/ absorption dosage between 0.1mg/.

The preparation of composition

The present composition that comprises at least a formula (I) compound preferably is made of the beauty treatment acceptable medium, promptly has pleasant color, smell and sensation and does not cause the medium of any unacceptable discomfort.

Composition is preferably cosmetic compositions or cosmetics.Term " cosmetics " especially means to be desired contact with oral mucosa with the various surface portions of human body (epidermis, hair system, refer to/toenail, lip and vulva organ) or with tooth, with special or be mainly used in its cleaning, give its fragrance, modify its outward appearance and/or correction and savour and/or protect it or make its any material that maintains a good state or goods (the makeup standard of correction (Amended Cosmetic Directive) 76/768/EEC).

Composition of the present invention especially can be following form: the vesica dispersion of alcoholic solution agent, aqueous alcohol solutions agent or oily solution agent, suspensoid, dispersion, W/O, O/W or multiple emulsion, aqueous gels or anhydrous gel agent or ion or non-ionic type (vesicular dispersion).It can have liquid, semiliquid, pasty state or solid denseness.

For topical application, composition especially can be following form used according to the present invention: the dispersion of aqueous alcohol solutions agent or oily solution agent or washing lotion or slurry type, fat is scattered in water (O/W) or (W/O) newborn type liquid of obtaining or the emulsion or the multiple emulsion of semiliquid denseness conversely mutually, that treat to use or wait to mix the free or compacting pulvis of acceptable medium on the physiology with the unmodified form, the perhaps suspensoid or the emulsion of the soft denseness of water-based or anhydrous cream type or gel-type, perhaps microcapsule or microgranules, the perhaps vesica dispersion of ionic and/or non-ionic type.Therefore it can be following form: ointment, tincture, ointment, hair cream agent, powder, patch, impregnated pads (impregnated pad), solution, emulsion or vesica dispersion, lotion, gelifying agent, sprays, suspensoid, shampoo, aerosol or mousse.It can be not moisture or contains water.It also can be made up of soap or clean skin soap (cleansing bar) that solid articles constitutes.

Prepare these compositions according to common method.

According to another embodiment of the invention, composition is suitable for orally using, and particularly " beautifying oral " uses.

For orally using, composition especially can be following form or any other form well known by persons skilled in the art: glutinous rice capsule (wafer capsule), gel capsule, coated tablet, granule, plain sheet, chew paste (chewable paste), gelifying agent or drink syrup.

The amount of the various components of composition is the usual amounts in the field of the present invention used according to the present invention.

Combination

Composition of the present invention also can contain the active material that is useful on reinforcement or compensation type (I) compound, especially at least aly be selected from following compound: antioxidant, stainproofing agent, organic sunscreen agent and/or mineral sun-screening agent, and be used to the material that stimulates DNA to repair.

Formula of the present invention (I) compound also can be advantageously with the extract (total biomass, substratum, rrna part, cytolemma part, LPS part, lipid A etc.) of non-sporophore (non-fruiting), non-photosynthetic filamentous bacterium (for example linear Vitreoscilla (Vitreoscilla filiformis)) or 2-(ethanoyl (3-trifluoromethyl) amino]-3-methylbutyryl base amino acetate is combined.

Therefore, may use and for example be selected from following antioxidant:

-vitamin-E (tocopherol) and derivative thereof comprise acetate, linoleate or nicotinate derivative, and preferred concentration is about 0.1%-5%,

-γ-ferulic acid ester (0.1%-5%),

-Pidolic Acid Methionin (lysine pidolate) or Pidolic Acid arginine (arginine pidolate) (0.5%-10%),

-plant milk extract, for example melissa (balm) extract (0.01%-2%), Silymarin (silymarin) extract (0.01%-2%), ginkgo (Ginkgo biloba) extract (0.05%-2%), sage extract (0.05%-2%), kola nut extract (0.05%-2%), rutin extract (0.1%-2%) or Thymi Serpylli Herba extract (0.1%-2%), per-cent provides with dry matter

-carotenoid, for example (tomato puree for example, its Lyeopene titre reaches final lycopene concentration between 10 with pure form or with the α carotene of extract and beta carotene or Lyeopene ^-12Between the %-10%, more preferably 10 ^-7Between the %-0.1%),

-derive from proanthocyanidin alcohol (proanthocyanidol) oligopolymer (0.1%-2%) of pine tree, hawthorn or grape,

-di-t-butyl hydroxyl benzylidene camphor (di-tert-butylhydroxybenzylidenecamphor) (0.1%-2%),

-green tea (0.1%-2%),

-caffeine (0.1%-5%),

-glycerine (2%-30%),

-N.F,USP MANNITOL (2%-30%),

-carnosine (0.1%-2%),

-superoxide-dismutase (100-10 000IU/100g),

-guanosine (0.01%-1%),

-contain the microalgae of ethoxyquin (ethoxyquine), for example haematococcus (Haematococcus) (0.005%-1%),

-Amino Trimethylene Phosphonic Acid five sodium (0.001%-0.5%),

-lactoperoxidase (0.01%-0.1%),

-vitamins C and derivative thereof,

-lactoferrin (0.01%-0.1%),

-(benzyl 2-[benzyl (2-isopropoxy-2-oxo-ethyl) amino] and ethyl } amino) isopropyl acetate,

-Phloretin,

-Hesperidin,

-neohesperidin dihydrochalcone,

-forulic acid,

-Eukarions (comprising EUK-8, EUK-134 and EUK-189) by Proteome Systems exploitation,

-L-2-oxo-4-thiaproline,

-thioneine,

-coffic acid,

-Desferal (Desferal),

-4,4 '-(2,3-dimethylbutane-1,4-two bases) hexichol-1, the 2-glycol.

Can also use the mixture of some antioxidants.

Also can mention free-radical scavengers, particularly Vitamin P complex; Coenzyme Q10 99.0 or ubiquinone; Some enzyme, for example catalase, Selenoperoxidase and quinone reductase; Gsh; Benzylidene camphor; The benzyl naphthenone; Replace naphthalenone; Pidolic Acid salt; Phytantriol; Lignan; Melatonin; Hydroxylation phenyl styryl ketone, and reductive derivative.

Antioxidant is preferably selected from vitamins C, vitamin-E, (benzyl { 2-[benzyl (2-isopropoxy-2-oxoethyl) amino] ethyl } amino) isopropyl acetate, forulic acid, Phloretin, neohesperidin dihydrochalcone and SOD.

Term " stainproofing agent " means any compound that can catch ozone, monocycle or polynuclear aromatic compound (for example benzopyrene) and/or heavy metal (for example cobalt, mercury, cadmium and/or nickel).Term " free-radical scavengers " means any compound that can catch free radical.

As the ozone trapping agent that can be used for the present composition, can mention vitamins C and derivative thereof especially, comprise ascorbic acid glucoside; Phenol and polyphenol, particularly tannin, ellagic acid and tannic acid; Epigallocatechin and the natural extract that contains it; The olive leaf extract; Tea, particularly green tea extract; Cyanidin(e); Rosemary extract; Phenol acids, particularly chlorogenic acid (chorogenic acid); Stilbene, particularly trans-resveratrol; Sulfur-containing amino acid derivative, particularly S-carboxyl-methyl halfcystine; Thioneine; The N-acetylcysteine; Sequestrant, N for example, one of N '-two (3,4,5-trimethoxy benzyl) quadrol or its salt, metal complex or ester; Carotenoid, for example crocin; And various starting material, for example by Laboratoires S é robiologiques with CPP LS 2633-12F

The mixture of the trade(brand)name arginine, Histidine ribonucleate, N.F,USP MANNITOL, adenosine triphosphate, pyridoxol, phenylalanine, tyrosine and the hydrolysis RNA that sell; By Solabia company with Phytovityl

The trade(brand)name water-soluble fraction of corn of selling; By Induchem company with Unicotrozon C-49

Corydalis (fumitory) extract sold of title and the mixture of citron extract; And by Provital company with Pronalen Bioprotect

The mixture of trade(brand)name Radix Ginseng extract, Fructus Mali pumilae extract, peach extract, wheat extract and the Fructus Hordei Vulgaris extract sold.

As can be used for the trapping agent present composition, that be used to catch monocycle or polynuclear aromatic compound, can mention tannin, for example ellagic acid especially; Indole derivatives, particularly 3-indole-alcohol; Tea, particularly green tea extract; Herba Eichhorniae (water hyacinth, Eichornia crassipes) extract; And by Solabia company with Phytovityl

The trade(brand)name water-soluble fraction of corn of selling.

At last, as the heavy metal trapping agent that can be used for the present composition, can mention sequestrant especially, the for example five sodium-salt of EDTA, ethylenediamine tetramethylene phosphonic acid and N, N '-two (3,4,5-trimethoxy benzyl) quadrol or one of its salt, metal complex or ester; Phytic acid; Chitosane derivatives; Tea, particularly green tea extract; Tannin, for example ellagic acid; Sulfur-containing amino acid, for example halfcystine; Herba Eichhorniae (Eichornia crassipes) extract; And by Solabia company with Phytovityl

The trade(brand)name water-soluble fraction of corn of selling.

Advantageously, the present composition contains and has activity (absorption agent) and be water-soluble, fat-soluble or be insoluble at least a organic light protective agent and/or at least a mineral light protective agent of beauty treatment commonly used with solvent in UVA and/or UVB scope.Preferably, the preferred system of sheltering UVA radiation and UVB radiation that uses.

Sun-screening agent is to absorb UV radiating molecule, thereby stops the UV radiation to arrive skin cells.Sun-screening agent or can mainly absorb UVB perhaps can mainly absorb UVA, and this depends on its character.Two kinds of main sun-screening agent classifications are arranged, i.e. organic sunscreen agent or mineral sun-screening agent (zinc oxide or titanium dioxide).Use them by combination and capacity ground in cosmetic compositions, it can block most UV radiation.

Yet, be recognized that for effectively, these preparations must be under good working conditions (capacity, often upgrade and evenly smear) uses.The user does not always observe these working conditionss, and this UV radiation that has just increased a great deal of reaches the risk of skin cells, therefore produces above-mentioned biological effect.In addition, in order to realize the absorption to UVB+UVA sun UV spectrographic all wavelengths, needing will be in the systemic some molecular combinations of complementary wavelength scope together.

Other organic sunscreen agent especially is selected from cinnamyl o-aminobenzoate; Cinnamic acid derivative; Salicyclic acid derivatives; Camphor derivatives; Benzophenone derivates; β, β-diphenylacrylate; Pyrrolotriazine derivatives; Benzotriazole derivatives; The toluenyl malonic ester derivative that toluenyl malonic ester derivative, especially patent US 5 624 663 mention; Benzimidizole derivatives; Imidazolines; Two-indyl the derivative that discloses among patent EP 669 323 and the US 2 463 264; Para-amino benzoic acid (PABA) derivative; Methylene-bis (hydroxy phenyl benzotriazole) derivative that discloses among patent application US 5 237 071, US 5 166 355, GB 2 303 549, DE 197 26 184 and the EP 893 119; The benzo that discloses among patent application EP 0 832 642, EP 1 027 883, EP 1 300 137 and the DE 101 62 844

Oxazole derivatives; Sun-proof polymkeric substance (screening polymer) and sun-proof silicone, for example described sun-screening agent that especially discloses among the patent application WO 93/04665; Based on the dimer of alpha-alkyl phenylethylene, the dimer that discloses among the patent application DE 198 55 649 for example based on alpha-alkyl phenylethylene; 4,4-diaryl divinyl, for example disclose among patent application EP 0 967 200, DE 197 46 654, DE 197 55 649, EP-A-1 008 586, EP 1 133 980 and the EP 133 981 4,4-diaryl divinyl; Merocyanine (merocyanin) derivative, for example Merocyanine derivatives that discloses among patent application WO 04/,006 878, WO 05/,058 269 and the WO 06/,032 741; And composition thereof.

As the example of other organic light protective agent, organic light protective agent of representing with its INCI name below can mentioning:

Cinnamic acid derivative:

Ethylhexyl methoxy cinnamate, particularly by DSM Nutritional Products, Inc. sells with the trade(brand)name of Parsol MCX,

The methoxy cinnamic acid isopropyl ester,

The methoxy cinnamic acid isopentyl ester is sold with the trade(brand)name of Neo Heliopan E 1000 by Symrise,

The DEA Methoxycinnamate,

The tolyl acrylic acid diisopropyl ester,

Glycerine ethylhexoate dimethoxy-cinnamic acid ester;

The para-amino benzoic acid derivative:

PABA，

The PABA ethyl ester,

PABA ethyl dihydroxyl propyl ester,

PABA ethylhexyl dimethyl ester is particularly sold with the title of Escalol 507 by ISP,

Glycerine PABA,

PEG-25 PABA is sold with the title of Uvinul P25 by BASF;

Salicyclic acid derivatives:

Homosalate is sold with the title of Eusolex HMS by Rona/EM Industries,

Ethylhexyl salicylate is sold with the title of Neo Heliopan OS by Symrise,

Dipropylene glycol salicylate is sold with the title of Dipsal by Scher,

The TEA salicylate is sold with the title of Neo Heliopan TS by Symrise;

β, β-diphenylacrylate:

Octocrilene is sold with the trade(brand)name of Uvinul N539 by BASF especially,

Viosorb 910 is particularly sold with the trade(brand)name of Uvinul N35 by BASF;

Benzophenone derivates:

Benzophenone-1 is sold with the trade(brand)name of Uvinul 400 by BASF,

Benzophenone-2 is sold with the trade(brand)name of Uvinul D50 by BASF,

Benzophenone-3 is sold with the trade(brand)name of Uvinul M40 by BASF,

Benzophenone-4 is sold with the trade(brand)name of Uvinul MS40 by BASF,

Benzophenone-5,

Benzophenone-6 is sold with the trade(brand)name of Helisorb 11 by Norquay,

Benzophenone-8 is sold with the trade(brand)name of Spectra-Sorb UV-24 by American Cyanamid,

Benzophenone 9 is sold with the trade(brand)name of Uvinul DS-49 by BASF,

Benzophenone-12,

The just own ester of 2-(4-diethylamino-2-hydroxy benzoyl) phenylformic acid is sold with the trade(brand)name of Uvinul A+ by BASF;

The benzylidene camphor derivative:

The 3-benzylidene camphor, by the title manufacturing of Chimex with Mexoryl SD,

4 methyl benzylidene camphor is sold with the title of Eusolex 6300 by Merck,

Benzylidene camphor sulfonic acid, by the title manufacturing of Chimex with Mexoryl SL,

Camphor alkyl dimethyl benzyl methylsulfuric acid ammonium (Camphor benzalkonium methosulfate), by the title manufacturing of Chimex with Mexoryl SO,

The Terephthalidene Dicamphor Sulfonic Acid, by the title manufacturing of Chimex with Mexoryl SX,

Polyacrylamide amino methyl benzylidene camphor is by the title manufacturing of Chimex with Mexoryl SW;

The phenyl benzimidizole derivatives:

Phenylbenzimidazolesulfonic acid is sold with the trade(brand)name of Eusolex 232 by Merck especially,

Phenyl bisbenzimidazole tetrasulfonic acid disodium is sold with the trade(brand)name of Neo Heliopan AP by Symrise;

The phenyl benzotriazole derivatives:

The drometrizole trisiloxanes is sold with the title of Silatrizole by Rhodia Chimie,

Methylene-bis (benzotriazole base) tetramethyl butyl phenol, sell with solid form with the trade(brand)name of MIXXIM BB/100 by Fairmount Chemical, perhaps sell with the micronization form as aqueous dispersion with the trade(brand)name of Tinosorb M by Ciba Specialty Chemicals;

Pyrrolotriazine derivatives:

Two (ethyl hexyl oxy phenol) p-methoxy-phenyl triazine is sold with the trade(brand)name of Tinosorb S by Ciba Geigy,

The ethylhexyl triazone is sold with the trade(brand)name of Uvinul T150 by BASF especially,

Diethylhexyl butyrylamino triazone is sold with the trade(brand)name of Uvasorb HEB by Sigma 3V,

2,4,6-three (4 '-amino benzylidene malonic acid diisobutyl ester)-s-triazine,

2,4,6-three (4 '-amino benzylidene malonic acid two peopentyl esters)-s-triazine,

2,4-pair (4 '-the positive butyl ester of benzaminic acid)-6-(aminopropyl trisiloxanes)-s-triazine,

2, two (4 '-amino benzylidene malonic acid two peopentyl esters)-6-(the positive butyl ester of 4 '-benzaminic acid)-s-triazine of 4-,

Patent US 6 225 467, patent application WO 20,04/,085 412 (referring to compound 6 and 9) or document Symmetrical Triazine Derivatives IP.COM Journal, IP.COM INC West Henrietta, NY, US has disclosed symmetric triazine sun-screening agent in (on September 20th, 2004), especially 2,4,6-three (biphenyl)-1,3, the 5-triazine (particularly 2,4,6-three (biphenyl-4-base-1,3, the 5-triazine) and also at patent application WO 06/035000, WO 06/,034 982, WO 06/,034 991, WO 06/,035 007, mention among WO 20,06/,034 992 and the WO 20,06/,034 985 2,4,6-three (terphenyl)-1,3, the 5-triazine;

Anthranilic acid derivative:

Anthranilic acid

Ester is sold with the trade(brand)name of Neo Heliopan MA by Haarmann and Reimer;

Imidazolidine derivatives:

Ethylhexyl dimethoxybenzylidenegroup group dioxo tetrahydroglyoxaline propionic ester;

The toluenyl malonic ester derivative:

The organopolysiloxane that contains toluenyl malonic ester functional group, for example by DSM Nutritional Products, the polysiloxane-15 that Inc. sells with the trade(brand)name of Parsol SLX;

4,4-diaryl butadiene derivatives:

1,1-dicarboxyl (2,2 '-dimethyl propyl)-4,4-phenylbenzene-divinyl;

2, two [5-(1-dimethyl propyl) benzos of 4-

Azoles-2-base (4-phenyl) imino-]-6-(2-ethylhexyl) imino--1,3,5-triazines, sell with the title of Uvasorb K2A by Sigma 3V;

Merocyanine derivatives

5-N, N-diethylamino-2-benzenesulfonyl-2,4-pentadienoic acid monooctyl ester;

And composition thereof.

Preferred organic sunscreen agent is selected from:

Ethylhexyl methoxy cinnamate,

Ethylhexyl salicylate,

Homosalate,

Octocrilene,

Phenylbenzimidazolesulfonic acid,

Benzophenone-3,

Benzophenone-4,

Benzophenone-5,

The just own ester of 2-(4-diethylamino-2-hydroxy benzoyl) phenylformic acid,

4 methyl benzylidene camphor,

The Terephthalidene Dicamphor Sulfonic Acid,

Phenyl bisbenzimidazole tetrasulfonic acid disodium,

Methylene-bis (benzotriazole base) tetramethyl butyl phenol,

Two (ethyl hexyl oxy phenol) p-methoxy-phenyl triazine,

The ethylhexyl triazone,

Diethylhexyl butyrylamino triazone,

2,4,6-three (4 '-amino benzylidene malonic acid diisobutyl ester)-s-triazine,

2, two (the positive butyl ester of 4 '-benzaminic acid)-6-(aminopropyl trisiloxanes) of 4--s-triazine,

2,4,6-three (biphenyl-4-yl)-1,3,5-triazines,

2,4,6-three (terphenyl)-1,3,5-triazines,

The drometrizole trisiloxanes,

Polysiloxane-15,

1,1-dicarboxyl (2,2 '-dimethyl propyl)-4, the 4-diphenyl diethylene,

2, two [5-1 (dimethyl propyl) benzos of 4-

Azoles-2-base (4-phenyl) imino-]-6-(2-ethylhexyl) imino--1,3,5-triazines,

5-N, N-diethylamino-2-benzenesulfonyl-2,4-pentadienoic acid monooctyl ester,

And composition thereof.

Organic sunscreen agent of the present invention generally accounts for the 0.1%-30% of composition total weight, preferred 1%-25%.

Other used according to the present invention mineral UV sun-screening agent is a metal oxide pigment.Mineral UV sun-screening agent of the present invention is metal oxide particle more preferably, and its averaging unit granular size is less than or equal to 500nm, more preferably between 5nm and 500nm, also more preferably between 10nm and 100nm, preferably between 15nm and 50nm.

They especially can be selected from titanium oxide, zinc oxide, ferriferous oxide, Zirconium oxide or cerium oxide or its mixture, more particularly titanium oxide.

Disclose this class bag nuclear among the patent application EP-A-0 518 773 especially or do not wrapped the nuclear metal oxide pigment.The commercially available pigment that can mention comprises Kemira, Tayca, Merck and Degussa company product sold.

Metal oxide pigment can be that bag is examined or bag is examined.

Core pigment is the surface-treated pigment that has carried out one or more chemistry, electronics, mechanochemistry and/or mechanical properties with following compound: for example sodium of amino acid, beeswax, lipid acid, Fatty Alcohol(C12-C14 and C12-C18), anion surfactant, Yelkin TTS, lipid acid, potassium, zinc, iron or aluminium salt, metal alkoxide (titanium or aluminium-alcohol salt), polyethylene, silicone, protein (collagen, elastin), alkanolamine, Si oxide, metal oxide or Sodium hexametaphosphate 99.

The titanium oxide that core pigment has more especially been examined with following compound bag:

-silicon-dioxide for example derives from the product Sunveil of Ikeda company,

-silicon-dioxide and ferriferous oxide for example derive from the product Sunveil F of Ikeda company,

-silicon-dioxide and aluminum oxide for example derive from product Microtitanium Dioxide MT 500 SA and Microtitanium Dioxide MT 100 SA of Tayca company, derive from the Tioveil of Tioxide company,

-aluminum oxide, the UVT 14/4 that for example derives from the product Tipaque TTO-55 (B) of Ishihara company and Tipaque TTO-55 (A) and derive from Kemira company,

-aluminum oxide and aluminum stearate, for example derive from product Microtitanium Dioxide MT 100 TV, MT 100 TX, MT 100 Z and the MT-01 of Tayca company, with the product Solaveil CT-10 W and the Solaveil CT 100 that derive from Uniqema company, and the product E usolex T-AVO that derives from Merck company

-silicon-dioxide, aluminum oxide and alginic acid for example derive from the product MT-100 AQ of Tayca company,

-aluminum oxide and Aluminum trilaurate for example derive from product Microtitanium Dioxide MT 100 S of Tayca company,

-ferriferous oxide and iron stearate for example derive from product Microtitanium Dioxide MT 100 F of Tayca company,

-zinc oxide and Zinic stearas for example derive from the product B R 351 of Tayca company,

-silicon-dioxide and aluminum oxide, and use silicone-treated, for example derive from product Microtitanium Dioxide MT 600 SAS, Microtitanium Dioxide MT 500 SAS or Microtitanium Dioxide MT 100 SAS of Tayca company,

-silicon-dioxide, aluminum oxide and aluminum stearate, and use silicone-treated, for example derive from the product STT-30-DS of Titan Kogyo company,

-silicon-dioxide, and use silicone-treated, for example derive from the product UV-Titan X 195 of Kemira company,

-aluminum oxide, and use silicone-treated for example derives from the product Tipaque TTO-55 (S) of Ishihara company or derives from the UV Titan M 262 of Kemira company,

-trolamine for example derives from the product STT-65-S of Titan Kogyo company,

-stearic acid for example derives from the product Tipaque TTO-55 (C) of Ishihara company,

-Sodium hexametaphosphate 99 for example derives from product Microtitanium Dioxide MT 150 W of Tayca company,

The TiO that-usefulness octyl group trimethyl silane is handled ₂, sell with the trade(brand)name of T 805 by Degussa Silices company,

-the TiO that handles with polydimethylsiloxane ₂, sell with the trade(brand)name of 70250 Cardre UF TiO2SI3 by Cardre company,

-anatase/rutile the TiO that handles with polydimethylhydrogenosiloxane ₂, sell with the trade(brand)name of Microtitanium Dioxide USP Grade Hydrophobic by Color Techniques company.

Bag nuclear titanium oxide pigment is not for example sold with the trade(brand)name of Microtitanium Dioxide MT 500 B or Microtitanium Dioxide MT 600 B by Tayca company, sell with the title of P 25 by Degussa company, sell with the title of Transparent titanium oxide PW by Wackher company, sell with the title of UFTR by Miyoshi Kasei company, sell with the title of ITS by Tomen company, with sell with the title of Tioveil AQ by Tioxide company.

Bag nuclear zinc oxide pigment is for for example:

-by the not bag nuclear zinc oxide pigment of Sunsmart company with the title sale of Z-Cote;

-by the not bag nuclear zinc oxide pigment of Elementis company with the title sale of Nanox;

-by the not bag nuclear zinc oxide pigment of Nanophase Technologies company with the title sale of Nanogard WCD 2025.

Bag nuclear zinc oxide pigment is for for example:

-by the bag nuclear zinc oxide pigment (with the ZnO of polydimethylhydrogenosiloxane bag nuclear) of Toshibi company with the title sale of Zinc Oxide CS-5;

-sell with the title of Nanogard Zinc Oxide FN by Nanophase Technologies company bag nuclear zinc oxide pigment (as Finsolv TN, phenylformic acid C ₁₂-C ₁₅40% dispersion in the alkyl ester);

-bag nuclear the zinc oxide pigment (containing the dispersion in the cyclopolymethyl siloxane/oxyethylation polydimethylsiloxane of the nano zine oxide that 30% or 50% usefulness silicon-dioxide and polymethylhydrogenosiloxane bag examines) sold with the title of Daitopersion ZN-30 and Daitopersion ZN-50 by Daito company;

-by the bag nuclear zinc oxide pigment (as the ZnO that use phosphoric acid perfluoroalkyl ester and based on the multipolymer bag of perfluor alkyl ethide examine of the dispersion of encircling penta siloxanes) of Daikin company with the title sale of NFD Ultrafine ZnO;

-by the bag nuclear zinc oxide pigment (with the ZnO of the silicone graft acrylate copolymer bag nuclear that is scattered in ring dimethyl siloxane) of Shin-Etsu company with the title sale of SPD-Z1;

-by the bag nuclear zinc oxide pigment (be scattered in the ZnO of alumina treatment in ethylhexyl methoxy cinnamate/PVP-cetene/polydimethylsiloxane (methicone) copolymer mixture) of ISP company with the title sale of Escalol Z100;

-by the bag nuclear zinc oxide pigment (with the ZnO of silicon-dioxide and poly methyl silsesquioxane bag nuclear) of Fuji Pigment company with the title sale of Fuji ZnO-SMS-10;

-(concentration with 55% is scattered in phenylformic acid C to examine zinc oxide pigment by Elementis company with the bag of the title sale of Nanox Gel TN ₁₂-C ₁₅ZnO in alkyl ester and the oxystearic acid polycondensate).

Bag nuclear cerium oxide pigment is not sold with the title of Colloidal Cerium Oxide by Rhone-Poulenc company.

Bag nuclear iron oxide pigments is not for example sold with the title of Nanogard WCD 2002 (FE 45B), Nanogard Iron FE 45 BL AQ, Nanogard FE 45R AQ and Nanogard WCD 2006 (FE 45R) by Arnaud company, is perhaps sold with the title of TY-220 by Mitsubishi company.

Bag nuclear iron oxide pigments is for example sold with the title of Nanogard WCD 2008 (FE 45B FN), Nanogard WCD 2009 (FE 45B 556), Nanogard FE 45 BL 345 and Nanogard FE 45 BL by Arnaud company, is perhaps sold with the title of Transparent Iron Oxide by BASF AG.

Can also mention the mixture of metal oxide, especially titanium dioxide and cerium dioxide, comprise titanium dioxide and cerium dioxide silicon-dioxide bag nuclear etc. reblending thing (selling with the title of Sunveil A) by Ikeda company, and the mixture (for example by the product sold M of Kemira company 261) of the aluminum oxide of titanium dioxide and zinc oxide (zinc dioxide), silicon-dioxide and silicone bag nuclear, the perhaps mixture of the aluminum oxide of titanium dioxide and zinc oxide, silicon-dioxide and glycerine bag nuclear, for example the product sold M of Kemira company 211.

According to the present invention, the titanium oxide pigment of nuclear is examined or wrapped to special preferred package.

Mineral sun-screening agent of the present invention generally accounts for the 0.5%-40% of composition total weight, preferred 1%-30%.

Can with the mineral sun-screening agent with its natural form or with the form of pigment paste (promptly as with the mixture of dispersion agent, for example referring to document GB-A-2 206 339) introduce in the present composition.

Especially operable vitamin e derivative is a tocopherol acetate.

The material that is used to stimulate DNA to repair especially is the enzyme that promotes that DNA repairs, for example photolyase and/or T4 endonuclease.

Composition also can contain moistening agent, NO synthase inhibitor, free-radical scavengers or be used to stimulate the epidermis macromole to synthesize and/or be used to prevent the material of its degraded.

Those skilled in the art can change the amount of these different componentss.

The following examples are used for illustrating the present invention.In example of formulations, the amount of composition components provides with the weight percent of comparing with composition total weight.

Synthetic embodiment:

Embodiment 1: compound N, N '-two (4-methyl isophthalic acid, 2-dithia ring penta-4-yl) urea (compound Synthesizing 2)

1.1 equivalent triethylamines (306 μ l) and the adding of 1.2 equivalents (520 μ l) azide diphenyl phosphate are contained 2mmol (330mg) 4-methyl isophthalic acid, among the 10ml tBuOH of 2-dithiolane-4-formic acid.In 20 ℃ of stirrings 10 minutes, refluxing then stopped to emit up to gas with reaction medium.Behind the vacuum concentration, crude product is carried out purifying (elutriant: the 100/0-90/10 methylene chloride) on silica column, then required flow point is concentrated (P=100mbar, T=40 ℃) in Rotary Evaporators, obtain light yellow solid corresponding to the expection product.

NMR is consistent with the expection product with mass spectrum.

Embodiment 2: compound 4-methyl isophthalic acid, 2-dithia ring penta-4-aminocarbamic acid tert-butyl ester (is changed Synthesizing compound 3)

Synthesis condition is identical with embodiment 1, uses anhydrous tBuOH, carries out in nitrogen atmosphere and in the presence of molecular sieve.Obtain yellow wax corresponding to described t-butyl carbamate.

NMR is consistent with the expection product with mass spectrum.

Embodiment 3: compound N-benzyl-N '-(4-methyl isophthalic acid, 2-dithia ring penta-4-yl) urea (chemical combination Synthesizing thing 1)

Condition is identical with embodiment 2, but uses toluene to be solvent, and adds 218 μ l benzylamines in room temperature after gas stops to emit.Reaction medium is diluted with basic solution, then organic phase is washed with acidic solution.The organic phase of vacuum concentration drying obtains mashed prod then, and it is dissolved in the ether, obtains orange solids, is accredited as N-benzyl-N '-(4-methyl isophthalic acid, 2-dithia ring penta-4-yl) urea.

NMR is consistent with the expection product with mass spectrum.

Embodiment 4: The compounds of this invention is to improving the active mensuration of GSH level

This research is to estimate the protective effect of the sad and of the present invention lipoic acid derivatives of reference molecular sulfur for GSH loss in the UV-DL inductive born of the same parents on cell levels.

For this reason, with the HaCaT cellular exposure in UV daylight (UV-DL).Measure intracellular GSH level then, thus can be for estimating by may protecting of providing in the substratum is provided lipoic acid derivatives of the present invention.

UV daylight is equivalent to the radiation and the average spectral irradiance of non-zenith sun light: its simulation individual's skin during one day in the radiation of reception, and not only be equivalent to be exposed to the radiation of zenith sun light.Be used to reproduce this radiating device referring to FR 2 863 356.Evaluation technique adopts fluorescent probe monochlorobimane (MCB).(for example monobromobimane) is different with other bimane compound, and MCB has has the more special property of multi-selection reaction to gsh: the blue-fluorescence compound of being measured (GSH-monochlorobimane) is by producing via the catalytic enzymatic reaction of glutathione-S-transferase.Confirmed that before MCB is to the specificity of GSH in the keratinocyte model (HaCaT system) at us.With the sad pair cell pre-treatment of 1mM reference molecular sulfur 24 hours, obtain about 100% of UV-DL inductive GSH loss is protected (referring to Fig. 1, be presented in the MCB assay method 1mM Thioctic Acid to the evaluation of the protective effect of HaCaT: with or not pretreated and be exposed in the keratinocyte of UV-DL with the 1mM Thioctic Acid, after being exposed to UV-DL, carry out the mensuration of GSH level in the cell when t=0, t=6 hour and t=24 hour); This protection is about 83% under 500 μ M, is about 10% under 100 μ M.

Tested The compounds of this invention N, N '-two (4-methyl isophthalic acid, 2-dithia ring penta-4-yl) urea (compound 2).In the MCB assay method; protective effect to 2 couples of HaCaT of 30 μ M compounds is estimated: also in the MCB assay method; following silyl dithiolane compound to 100 μ M patent application WO 20,08/,058 999 is estimated the protective effect of HaCaT: compound 5-(1; 2-dithia ring penta-3-yl)-and N-[3-(trimethyl silyl) propyl group] valeramide and compound 5-(1,2-dithia ring penta-3-yl) valeric acid (trimethyl silyl) methyl esters.With or not pretreated and be exposed in the keratinocyte of UV-DL with promoting agent, after being exposed to UV-DL, carry out the mensuration of GSH level in the cell t=6 hour the time).The results are shown in Figure 2 and the histogram of Fig. 3.

The provide protection of the compound of the provide protection at the GSH loss of UV sunlight-induced of observing that promoting agent of the present invention provides and prior art sad greater than 100 μ M reference molecular sulfur, this superiority just produces (referring to Fig. 2 and Fig. 3) when being low to moderate 30 μ M.

Embodiment 5: anti-sun light (antisun) composition (oil-in-water emulsion)

The fat that will contain described compound heats down up to melting fully at about 70-80 ℃.Then under 80 ℃, disposablely in vigorous stirring add entry.Continue to stir 10-15 minute, under appropriateness stirs, make mixture be cooled to about 40 ℃ then, add sanitas then.

Embodiment 6: anti-sun light composition (oil-in-water emulsion)

This emulsifiable paste is prepared as follows according to the standard technique of preparation emulsion: by sun-screening agent being dissolved in the fatty phase that contains emulsifying agent, should the fat heat phase to 70-80 ℃, in vigorous stirring, add the water that has been heated to uniform temp then.Continue to stir 10-15 minute, when appropriateness stirs, make the mixture cooling then, add perfume compound and sanitas down at 40 ℃ at last.

Claims

1. the dithiolane compound of following formula (I):

Wherein Y represents O or NR1;

When Y represents NHR ₁And R ₁When being not hydrogen, R and R ₁Can form and be selected from following ring: tetramethyleneimine, pyrroline, piperidines, piperazine, morpholine, thiomorpholine and azepine

2. the dithiolane compound of claim 1, wherein:

3. the dithiolane compound of claim 2, wherein:

N=0,1 or 2 wherein; X=0,1 or 2; And R ₃Can be identical or different, expression hydrogen or methyl; Group 4-methyl dithiolane when Y represents NH;

4. the dithiolane compound of claim 3, wherein Y is NH.

5. each dithiolane compound among the claim 1-4, it is selected from following compounds:

6. cosmetic compositions or pharmaceutical composition, it comprises among at least a claim 1-5 each formula (I) dithiolane compound in acceptable medium on physiology.

7. each formula (I) dithiolane compound among at least a claim 1-5, be used for strengthening and/or keep cutaneous acupuncture to especially by the beautifying use of the composition of the purpose of the natural anti-oxidation protection of the radiation-induced oxidative stress of UV, described composition comprises acceptable medium on the physiology.

8. the purposes of claim 7, described composition is used to skin to be exposed to the purpose that sunlight is prepared.

9. claim 7 or 8 purposes, described composition is used to prevent and/or treat the purpose of skin aging, especially following sign:

(i) firmness of skin and/or elasticity and/or tensile forfeiture;

(ii) dry coarse skin appearance;

(iii) skin dehydration;

(iv) atrophy of epidermis and/or pachylosis and/or xerosis cutis.

10. each purposes among the claim 7-9, described composition is used to prevent and/or treat the purpose of pollution to the deleterious effect of skin.

11. each purposes among the claim 7-10 is characterized in that described composition is used for external partial and uses or orally use.

12. be used to make skin to receiving the beauty method that sunlight is prepared, described method comprises at least one step that gives each compound among at least a claim 1-5.