CN105168008A - Anti-wrinkle composition and external skin composition - Google Patents
Anti-wrinkle composition and external skin composition Download PDFInfo
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- CN105168008A CN105168008A CN201510427642.4A CN201510427642A CN105168008A CN 105168008 A CN105168008 A CN 105168008A CN 201510427642 A CN201510427642 A CN 201510427642A CN 105168008 A CN105168008 A CN 105168008A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/08—Anti-ageing preparations
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/31—Hydrocarbons
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
- A61K2800/52—Stabilizers
- A61K2800/522—Antioxidants; Radical scavengers
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Abstract
Provided is a novel composition containing a fullerene which has a strong anti-wrinkle effect. An anti-wrinkle composition characterized by containing a fullerene dissolved in an oil, i.e., a fullerene dissolved in squalane or the like. This composition inhibits double-strand cleavage of DNA by a lipid peroxide in human keratinocytes.
Description
The divisional application that the application is application number is " 200980108918.5 ", the applying date is on March 3rd, 2009, denomination of invention is the application of " crease-resistant compositions and composition for external application ".
Technical field
The present invention relates to crease-resistant compositions and composition for external application.
Background technology
Composition for external application has the various dosage form of emulsifiable paste, emulsion, astringent, wet goods, in any dosage form, is combined with UV absorbent or ultraviolet scattering diluent to defend ultraviolet.
On the other hand, application cosmetics of nanotechnology in large quantities are in recent years known wherein containing C
60, C
70cosmetics Deng fullerene show various skin Caring effect.Such as, patent documentation 1 describes the cosmetics display ultra-violet absorption effect obtained in oil content by Dissolving fullerene.In addition, patent documentation 2 also describes the product display health promoting effects fullerene suspended dispersed of the ultramicron as carbon burning residue obtained in squalane.
In addition, also developed the liquefiable technology of fullerene (with reference to patent documentation 3) making to be insoluble in water, and be actually used in the composition for external application such as cosmetics.
And, fullerene receives much concern as the material with active oxygen elimination ability, due to the safety in external coating also can be expected, therefore propose the composition for external application containing fullerene (with reference to patent documentation 4) for preventing free radical disease etc.
[advanced technology document]
[patent documentation 1] Japanese Unexamined Patent Publication 09-278625 publication
[patent documentation 2] Japanese Unexamined Patent Publication 2001-316251 publication
[patent documentation 3] Japanese Unexamined Patent Publication 2005-060380 publication
[patent documentation 4] Japanese Unexamined Patent Publication 2006-160664 publication
Summary of the invention
Technical problems that invention pre-solves
As mentioned above, expect the various application of fullerene in the composition for external application such as cosmetics, but for its function or effect, expect to also have a lot of unknown situation, can say that the exploitation of the application for fullerene is still in developmental stage.
Under this background, the present inventor is studied in detail the effect of Skin Cell for when being applicable to skin.One of problem of this research is " crease-resistant ".
The reason of saying so is all to wish to develop the technology more effectively playing " crease-resistant " and act on all the time.
The present invention completes in view of the foregoing, and its problem is to provide the new compositions that make use of fullerene with high crease-resistant function.
For the method for technical solution problem
The present invention derives according to reconstructing at human skin the brand-new discovery that obtains the exploratory development result of the detailed checking of " wrinkle " formation mechenism and the method for " crease-resistant " based on this in tissue by the present inventor and completes.
Namely, first the lipid peroxide 2 of inducement is formed as wrinkle, 4-nonadienal as the Skin Cell irradiated through ultraviolet (UV) glyceride 1, the peroxidating intermediate of 2-position fatty acid (mainly linoleic acid, arachidonic acid etc.) is comparatively stablized, is had anelasticity in skin, therefore becomes the essential factor that wrinkle is formed.In fact, when utilizing 2,4-nonadienal to carry out subcutaneous treatment, following 3 kinds of wrinkle related symptoms can be there are.
(1) concavo-convex fluctuating is formed at skin surface.(employing Fig. 1 (a) copying analysis of silicone rubber duplicating method from display to Fig. 1 (b) change)
(2) the scale stripping (changing from Fig. 2 (a) of reading scan type electron micrograph to Fig. 2 (b)) of multiple cutin is there is at skin surface
(3) multilamellar that corium occurs on skin section is separated and vertical atrophy (employing Fig. 3 (a) of the electron micrograph of DMSO Freeze-cracking Method from display to Fig. 3 (b) change)
It is shocking the wrinkle of these 3 kinds of (1) (2) (3), related indication any one is all suppressed by spreading upon in squalane the oil being dissolved with fullerene molten shape fullerene on a skin surface.Invalid when also confirming that squalane is independent on the other hand.
And, also confirm that the mechanism of the anti-wrinkle effect of oily molten shape fullerene is the DNA double chain interruption owing to inhibit with the cell membrane damage caused by lipid peroxide nonadienal in application on human skin keratinocyte.
Therefore, the present invention in order to solve above-mentioned problem, the compositions that to provide with following content be feature.
1st: a kind of crease-resistant compositions, it is characterized in that, it contains the molten shape fullerene of oil being dissolved with fullerene at squalane apoplexy due to endogenous wind.
2nd: the crease-resistant compositions described in above-mentioned 1, is characterized in that, fullerene contains and is selected from C
60, C
70with their salt or at least one of derivant.
3rd: the crease-resistant compositions described in above-mentioned 1 or 2, it is characterized in that, defend application on human skin keratinocyte and/or application on human skin fibrous bud cell and/or in comprising their skin histology due to the DNA damage comprising DNA double chain/single-strand break and/or the damage of DNA base that the oxidative stress containing lipid peroxide and/or active oxygen causes.
4th: a kind of composition for external application, is characterized in that, be made up of compositions described in above-mentioned 1st ~ 3rd any one.
Invention effect
According to the present invention, before can effectively being suppressed by the oil molten shape fullerene (can be called " fat fullerene (Lipo fullerene) ") being dissolved in spiny dogfish alkanes very unquenchable " wrinkle ".Thus, the uncharted field as the skin Caring effect brought as the fullerene of composition for external application cannot expected completely, predict in the past has been opened up.
Accompanying drawing explanation
[Fig. 1] Fig. 1 is the duplicating image of the 3 dimension skin histology model surfaces representing embodiment 1 and utilizes the figure of analysis result of its NIH-image.
[Fig. 2] Fig. 2 is the scanning electron microscope photo of 3 dimension skin histology model surface shapes of embodiment 1.
[Fig. 3] Fig. 3 is the scanning electron microscope photo of the cross section structure of 3 dimension skin histology models of embodiment 1.
[Fig. 4] Fig. 4 is the figure of the cell death inhibition of the application on human skin keratinocyte of display embodiment 2.
[Fig. 5] Fig. 5 is the scanning electron microscope photo of the application on human skin usual organize models surface configuration of embodiment 4.
[Fig. 6] Fig. 6 is the scanning electron microscope photo of the cross section structure of the usual organize models of application on human skin of embodiment 4.
[Fig. 7] Fig. 7 is the fluorescent microscopy images in the cross section of the application on human skin usual organize models section of embodiment 5.
[Fig. 8] Fig. 8 is the chart of the wrinkle area occupation ratio variable quantity evaluation result of the randomized, double-blind paired comparison test representing embodiment 6.
[Fig. 9] Fig. 9 is the scanning electron microscope photo of the application on human skin usual organize models surface configuration of embodiment 7.
[Figure 10] Figure 10 is the figure utilizing the analytic method of NIH-image of the surperficial SEM image of the usual organize models of application on human skin that embodiment 7 is described.
[Figure 11] Figure 11 is the figure utilizing the analysis result of NIH-image of the surperficial SEM image of the usual organize models of application on human skin representing embodiment 7.
[Figure 12] Figure 12 is the scanning electron microscope photo of the cross section structure of the usual organize models of application on human skin of embodiment 7.
[Figure 13] Figure 13 is the figure utilizing the analysis result of NIH-image of the cross-sectional SEM image of the usual organize models of application on human skin representing embodiment 7.
[Figure 14] Figure 14 is the duplicating image of the usual organize models of application on human skin of embodiment 7.
[Figure 15] Figure 15 is the figure utilizing the analysis result of NIH-image of the duplicating image of the usual organize models of application on human skin representing embodiment 7.
Detailed description of the invention
Below explain the present invention.
The molten shape fullerene of the oil used in this (being called for short: fat fullerene) is the material being dissolved with fullerene at squalane apoplexy due to endogenous wind.C can be used as fullerene
32, C
44, C
50, C
60, C
58, C
60, C
70, C
76, C
78, C
82, C
84, C
90, C
96and their salt or derivant etc., wherein preferably use C
60, C
70and salt or derivant.In addition, the mixture of more than two kinds in these fullerenes can also be used.
Spiny dogfish alkanes can be the mixture of any one or both of squalane and Squalene.Can be vegetalitas source or animal, fish origin any one.
When making fullerene be dissolved in spiny dogfish alkanes, as long as below the solubilized amount of fullerene, for its meltage, can thing combined according to the invention application mode determine.Can stir when dissolving, also can heat.Composition for external application can be made as compositions.
In composition for external application now, normally used various composition in cosmetics, medical portion exterior-applied article, medicine etc. can be engaged in, macromolecule, viscosifier, powder constituents, UV absorbent, screening uv-ray agent, wetting agent, spice, the pH adjusting agents etc. such as such as water, oils, hydro carbons, higher fatty acids, higher alcohol, silicone, anion surfactant, cationic surfactant, amphoteric surfactant, non-ionic surface active agent, antiseptic, saccharide, metal ion end-capping reagent, water soluble polymer in the scope not damaging its effect.In addition, other the active ingredient, physiologically active ingredient etc. such as vitamins, skin activating agent, blood circulation accelerant, active oxygen eliminating agent, antiinflammatory, whitening agent, antibacterial can also be coordinated.
Object lesson as oils can enumerate the liquid fat such as Camellia oil, Radix Oenotherae erythrosepalae oil, macadimia nut oil, olive oil, Oleum Brassicae campestris, Semen Maydis oil, Oleum sesami, Jojoba oil, germ oil, Semen Tritici aestivi germ oil, tricaprylin; cocoa butter, Oleum Cocois, solidification Oleum Cocois, Petiolus Trachycarpi oil, palm kernel oil, haze tallow, haze tallow kernel oil, solidified oil, solidification Semen Ricini wet goods solid grease, the wax class etc. such as Apis cerana Fabricius, candelilla wax, continuous wax, bran wax, lanoline, Acetylated lanolin alcohols., aqueous lanoline, sugarcane wax.
As the object lesson of hydro carbons, liquid paraffin, Squalene, squalane, microwax etc. can be enumerated.
As the object lesson of higher fatty acids, lauric acid, myristic acid, Palmic acid, stearic acid, oleic acid, linoleic acid, linolenic acid, docosahexenoic acid (DHA), eicosapentaenoic acid (EPA) etc. can be enumerated.
As the object lesson of higher alcohol, the branched-chain alcohos etc. such as the straight chain alcohols such as lauryl alcohol, stearyl alcohol, spermol, palmityl alcohol, single monostearoyl glyceride ether, lanolin alcohol, cholesterol, plant sterol, octyldodecanol can be enumerated.
As the object lesson of silicone, the decamethylcyclopentaandoxane etc. of the dimethyl polysiloxane of chain polysiloxanes, methyl phenyl silicone, cyclic polysiloxanes can be enumerated.
As the object lesson of anion surfactant, the alkyl ether sulphate salts such as the high alkyl sulfate such as soap, sodium lauryl sulphate salt, POE dodecyltriethanolamine sulfate such as sodium laurate, N-acyl group sarcosine, sulfosuccinate, N-acyl amino hydrochlorate etc. can be enumerated.
As the object lesson of cationic surfactant, the alkyl trimethyl ammonium salts such as stearyl trimethyl ammonium chloride, benzalkonium chloride, benzethonium chloride etc. can be enumerated.
As the object lesson of amphoteric surfactant, the betaine series surfactants such as alkyl betaine, amide betaine etc. can be enumerated.
As the object lesson of non-ionic surface active agent, the sorbitan aliphatic ester classes such as sorbitan monooleates, solidification castor oil derivative etc. can be enumerated.
As the object lesson of antiseptic, methyl hydroxybenzoate, ethyl hydroxybenzoate etc. can be enumerated.
As the object lesson of metal ion end-capping reagent, the edetates etc. such as disodiumedetate, ethylenediaminetetraacetic acid, disodium edta can be enumerated.
As high molecular object lesson, the ethylene system macromolecule etc. such as arabic gum, Tragacanth, galactan, guar gum, carrageenin, pectin, Qiong Zhi, Fructus cydoniae oblongae seed extract (Network イ Application ス シ mono-De), dextran, pulullan polysaccharide, carboxymethyl starch, collagen, casein, gelatin, methylcellulose, methylhydroxypropylcellulose, hydroxyethyl-cellulose, sodium carboxymethyl cellulose (CMC), sodium alginate, carboxyl ethylene polymer can be enumerated.
As the object lesson of viscosifier, carrageenin, Tragacanth, Fructus cydoniae oblongae seed extract, casein, dextrin, gelatin, CMC, hydroxyethyl-cellulose, hydroxypropyl cellulose, carboxyl ethylene polymer, guar gum, xanthan gum, bentonite etc. can be enumerated.
As the object lesson of powder constituents, the organic pigments etc. such as the pearl pigment such as Talcum, Kaolin, Muscovitum, silicon dioxide, zeolite, polyethylene powders, Polystyrene powder, cellulose powder, inorganic white pigment, inorganic red series pigments, titanium oxide coated mica, titanium-oxide-coated Talcum, painted titanium oxide coated mica, No. 201, redness, No. 202, redness can be enumerated.
As the object lesson of UV absorbent, para-amino benzoic acid, phenyl salicytate, p-methoxycinnamate isopropyl ester, p-methoxycinnamate monooctyl ester, 2,4-DihydroxyBenzophenone etc. can be enumerated.
As the object lesson of screening uv-ray agent, titanium oxide, Talcum, carmine, bentonite, Kaolin, zinc oxide etc. can be enumerated.
As the object lesson of wetting agent, Polyethylene Glycol, propylene glycol, dipropylene glycol, 1 can be enumerated, 3-butanediol, 1,2-pentanediol, glycerol, two glycerol, polyglycereol, xylitol, maltose alcohol, maltose, Sorbitol, glucose, sodium chondroitin sulfate, hyaluronate sodium, sodium lactate, 2-pyrrolidone-5-carboxylic acid, cyclodextrin etc.
Compositions of the present invention such as can with liquors such as aqueous solution, oil preparation, emulsion, suspensions, and the form of the solid agents such as half solid agent such as gel, emulsifiable paste, solid uses.Utilize known method to be modulated into these forms, lotion, Emulsion, gel, ointment, ointment, plaster, patch, aerosol etc. can be made various.Utilization is smeared, paste, spraying etc. by them for health.Particularly in these dosage forms, lotion, Emulsion, ointment, ointment, plaster, patch, aerosol etc. are suitable for composition for external application.
Compositions of the present invention, by being scattered in the water solvents such as the mixture of water or aqueous solvent, such as alcohol etc. and water, makes the external preparation etc. headed by cosmetics, as practicality technology effective launch.
Dispersion in water solvent is such as made O/W latex etc. and is specific, but in the manufacture of this water system dispersion, by utilizing the process of hyperacoustic irradiation or vortex mixer, refiner etc. more effective.
And non-ionic surface active agent is also effectively for the dispersion of fullerene liposoluble body in this water solvent.Such as, based on the non-ionic surface active agent of polyoxyethylene ether structure.The interpolation use amount of these non-ionic surface active agents is preferably the scope of 0.01 ~ 2 quality % of total scale of construction.
Preferably think Potter type refiner as refiner, its by with glass cylinder, the combination being fit to the fluororesin rotating rod of tube inner chamber, the rotation of both utilizations and the break-in of piston movement, by particle micronize.Owing to being difficult to be involved in air, therefore effective to micronize.
Utilize the dispersion treatment of these methods, preferably carry out subtracting under bubble condition, more preferably aqueous dispersion can be used as external preparation and uses, and thinks as described below to its mode.
1. use amount
The concentration of the fullerene in composition for external application is such as 0.00001 ~ 30 quality %, considers that the side of use sense etc. is preferably below 5 quality %.When being applicable to skin, the amount of topical composition to be such as every 1 square metre of skin area is liquid 0.001 ~ 20ml, be preferably 0.01 ~ 5.0ml, preferably utilize external to be coated with, wet cloth or spraying etc. use.
2. occupation mode
Example as the form of composition for external application is not particularly limited, such as can adopt the form of all external preparations such as aqueous solvent, ointment, emulsion, emulsifiable paste, gel, facial film, bath agent, detergent, application, dispersion liquid, its dosage form is also not particularly limited, can be made into pasty state, butyrous, gel, Powdered, solution system, solubilized system, emulsion type.Particularly for aqueous solution, Emulsion, ointment, gel, water-soluble agents, beautifying liquid, face film agent, by using humidification introducer, vibration introducer, iontophoresis device, sound wave introducer, electromagnetic wave introducer after these preparations of external, fullerene infiltration in skin can be promoted, larger effect can be played.
Coating process, when for liquor, can use all method that spraying, patch, wet cloth, dipping, face shield etc. are physically possible.
When using compositions of the present invention as cosmetics, can be made into the cosmetics for skin such as astringent, emulsion, emulsifiable paste, facial film, the cream base of makeup substrate astringent, makeup emulsifiable paste, emulsion form, emulsifiable paste shape or ointment type, the healths such as hands frost, restructuring compound for the neck, body lotions apply some make up.
[embodiment]
Below, utilize embodiment in further detail the present invention to be described, but the present invention is not defined in these embodiments.Wherein, following middle % unless otherwise specified, then represents quality %.
< embodiment 1>
Use 3 dimension skin histology models (TestskinLSE-high, Japan's weaving), according to the sequentially built test specimen of following table 1, carry out the crease-resistant test utilizing fat fullerene.
[table 1]
As test specimen, prepare contrast (only casting PBS (-)), cast lipid peroxide 2,4-nonadienal (NDA) 500 μMs, cast NDA500 μM and squalane and cast 3 dimension skin histology model samples of NDA500 μM and fat fullerene, utilize the embodiment microscope employing the copy of silicone rubber duplicating method to carry out the evaluations such as the parsing of image photography and wrinkle rating.Fat fullerene has dissolved fullerene (containing C in vegetalitas squalane (Uniquema)
60, C
70) and according to as C
60concentration contains 500ppm and is prepared.
The results are shown in Fig. 1.Wherein, for experimental verification, in containing the culture medium of 2,4-nonadienal (NDA) 500 μMs, cultivate application on human skin tissue sample 42 hours, fat fullerene casts in culture medium before casting NDA5 hour.Represent (a) in Fig. 1 be contrast (PBS (-)), (b) be only cast NDA (500 μMs), (c) be the comparative result of replacement fat fullerene when casting vegetalitas squalane.As shown in same figure, fat fullerene administration sample is compared with NDA administration sample and then with contrast with squalane administration sample, inhibits the wrinkle of skin surface to be formed.That is, as shown in Fig. 1 (c), when squalane is independent, substantially can not improve concave-convex surface, but substantially improve concave-convex surface when casting fat fullerene as shown in Fig. 1 (d).
In addition, for test specimen same as described above, utilize the surface configuration (Fig. 2) of scanning electron microscope observation 3 dimension skin histology models, use DMSO Freeze-cracking Method electron microscope observation 3 to tie up the cross section structure (Fig. 3) of skin histology model.Represent in Fig. 2 and Fig. 3 that (a) is contrast (PBS (-)), (b) is that when only casting NDA (500 μMs), (c) for replacing fat fullerene to cast vegetalitas squalane, (d) is for casting result during fat fullerene.
As shown in Fig. 2 (d), during for fat fullerene, the most scutellums controlling to produce at skin surface are peeled off, and as shown in Fig. 3 (d), prevent the multilamellar of the corium at skin section place to be separated and atrophy.As shown in Fig. 2 (c), Fig. 3 (c), when squalane is independent, these effects are very weak.
< embodiment 2>
Use the fullerene, i.e. the fat fullerene that are dissolved in squalane, utilize TUNRL to dye and verify the effect that the cell death (apoptosis) of the application on human skin keratinocyte (HaCaT) that NDA causes suppresses.
Fig. 4 shows its result, represents contrast successively, only casts NDA (30 μMs), replaces fat fullerene to cast the situation of vegetalitas squalane, cast the situation of fat fullerene from left.For fat fullerene (4%: as C
60for 20ppm), inhibit DNA double chain interruption significantly.And squalane independent time substantially invalid.
< embodiment 3>
By C
60the C of the ratio about 95% of fullerene
60standard substance are dissolved in vegetalitas squalane, then utilize Potter type refiner (to utilize getter to carry out reducing pressure, reducing bubble) under bubble condition to make its aqueous dispersion subtracting, form O/W latex.
This latex is made an addition to application on human skin keratinocyte respectively: in HaCaTCell cultivating system, cells survival rate is evaluated.Results verification improves greatly.
< embodiment 4>
Make the usual organize models of application on human skin with corium, basement membrane, epidermis and cuticular diameter 24mm in the following order.
Collagen gel cultivation test kit (new field gelatin (strain)) is used to carry out the cultivation of collagen gel according to the rule of operation (with reference to http://www.nitta-gelatin.co.jp/products/labo/column_1.html) in new field gelatin (strain).Containing through fibrous bud cell OUMS-365 × 10 of centrifugal recovery
5add chilled type i collagen gel mixed solution in the bead in/hole to carry out mixing until evenly.Type i collagen mixed solution containing this fibrous bud cell OUMS-36 is injected culture dish, in incubator, at 37 DEG C, leaves standstill 30 minutes, carry out gelation.
Then, in culture medium (DMEM/10%FCS), carry out fermentation to type i collagen gel, after the 5th day, gel shrinks.
And then, the overlapping basement membrane formation gel containing IV Collagen Type VI, laminin，LN and entactin on type i collagen gel.
Then, application on human skin keratinocyte (HaCaT) 5 × 10 inoculated by basement membrane formation gel
5/ hole, to its fermentation 1 day in culture medium (DMEM/Ham ' sF12 (1: 1)+5%FBS+15%Knockoutserumreplacement (SR, IntrogenInc.)).
Then, culture medium (DMEM/Ham ' sF12 (1: 1)+1%FBS+15%Knockoutserumreplacement) is replaced with, fermentation 4 days.
Then, overlap had the gel of application on human skin keratinocyte to be placed on to impregnated of culture medium (DMEM/Ham ' sF12 (1: 1)+15%Knockoutserumreplacement filter paper on, application on human skin keratinocyte is exposed to air, cultivates 14 days.Thus, basement membrane forms epidermis and horny layer.
Use the usual organize models of application on human skin so obtained, according to the sequentially built test specimen of following table 2, carry out the evaluation test of the NDA protection effect that fat fullerene brings.
[table 2]
Prepare contrast (only casting PBS (-)) as test specimen, cast NDA450 μM, cast NDA450 μM+squalane and cast NDA450 μM+fat fullerene (as C
60for 2-500ppm) application on human skin usual organize models sample, utilize scanning electron microscope to observe its surface configuration (Fig. 5), use DMSO Freeze-cracking Method to utilize electron microscope observation cross section structure (Fig. 6).As shown in Figure 5,6, NDA administration sample, NDA+ squalane administration sample have injured the structure of skin due to NDA, and by the administration of fat fullerene, inhibit the skin damage that NDA causes, its inhibition depends on fullerene content and increases.
< embodiment 5>
Use the sample identical with embodiment 4, utilize the fluorescence microscope employing Hoechst33342 nuclear staining to measure the NDA protection effect (nucleus maintenance effect) studied fat fullerene and produce.Using squalane or fat fullerene (as C
60be 2,50,200ppm) 150 μ L/ holes cast the usual organize models of application on human skin (
) carry out cultivating (5hr, 37 DEG C).Then, the culture medium be replaced with containing 450 μMs of NDA/ holes carries out cultivating (42hr, 37 DEG C, 5%CO
2).Utilize PBS (-) 200 μ L to rinse 3 times, freezingly rear Hoechst33342 nuclear staining is carried out to skin biopsy (thickness 5mm), utilize fluorescence microscope to observe.
Carry out the nuclear staining of the usual organize models of application on human skin in the following order.
[table 3]
The fluorescent microscopy images in the cross section of usual for application on human skin organize models's section (thickness 5 μm) is shown in Fig. 7.In contrast, nucleus is health status.In NDA administration sample, NDA+ squalane administration sample, due to NDA, there occurs and distortion condensing as the DNA break of one of apoptosis symptom, core at epidermis cell.And pass through the administration of fat fullerene, C
60inhibit the injury that NDA causes nucleus concentration dependant.
< embodiment 6>
Cosmetics are coordinated for fat fullerene, carries out the test of randomized, double-blind paired comparison.Be called object with tester 23, smear the cosmetics (emulsifiable paste, a left side: tested product, fullerene 1.8 μ g/ day, the right side: placebo, fuller olefinic carbon 60 .0 μ g/ day) of prescription shown in following table 4.I group (11) will be spread upon right side face by the product of testing, placebo spread upon left side face, and II group (12) placebo is spread upon right side face, will be spread upon left side face by the product of testing.
[table 4]
The choice criteria of tester to be wrinkle degree be 2 ~ 3 adult female's (left and right same levels).Cosmetics are every day 2 times sooner or later, after clean, after utilizing the skin care formulation skin protection of specifying, are applied in half face of specified side before cosmetic.Make to apply some make up get mutually commensurability (every half facial about 0.3g) according to specification at every turn, be placed in 4 positions (forehead, cheek, lower jaw, the tail of the eye) of face after make it fully ooze in half face.The tail of the eye by well affine, permeate fully.Service time is 8 weeks.
With wrinkle area occupation ratio for assessment item, evaluation methodology is according to cosmetics functional assessment method guide (Japanese fragrant make-up product association 2006).The tail of the eye before obtaining the use of cosmetics and after using and the copy of wrinkle under the tail of the eye, irradiate directional light by certain orientation (distance horizontal plane 30 °), produced shade is carried out image procossing.By length, the degree of depth of its computational shadowgraph area.Similarly, by standard size computational shadowgraph area and length thereof, production standard curve, corrects the numerical value that tail of the eye wrinkle copies.
The evaluation result of wrinkle area occupation ratio, wrinkle area occupation ratio variable quantity is shown in table 5, Fig. 8.
[table 5]
Wrinkle area occupation ratio is compared with before use, and product of being tested reduced at the 4th week, the 8th week.Placebo all increased at the 4th week, the 8th week.And for wrinkle area occupation ratio variable quantity, carried out corresponding t between product and placebo and check being tested, result is visible significantly (p=0.021) difference at the 8th week.In addition, do not find at the problematic adverse condition of safety.
As from the foregoing, fat fullerene coordinates emulsifiable paste to have the anti-wrinkle effect reducing wrinkle.
< embodiment 7>
Identical with embodiment 4, make and there is corium, basement membrane, epidermis and the usual organize models of cuticular application on human skin.
Use the usual organize models of this application on human skin, according to the sequentially built test specimen of following table 6, compare fat fullerene and (use 10% polyvinylpyrrolidone by RadicalSponge (R), vitamin C 60 biological study (strain) with free radical sponge, mix fullerene (C
60, C
70) after enclose, the product be dissolved in the water, C
60more than 200ppm) anti-wrinkle effect.
[table 6]
Prepare contrast (only casting PBS (-)) as test specimen, cast NDA500 μM, cast NDA500 μM+free radical sponge (as C
60for 4ppm, 30ppm), cast NDA500 μM+fat fullerene (as C
60for 4ppm, 30ppm) application on human skin usual organize models sample, utilize scanning electron microscope to observe its surface configuration (Fig. 9).In addition, as shown in Figure 10, the SEM image of application on human skin usual organize models surface configuration is utilized to the parsing of NIH-image.Specifically, for 3 regions of SEM image, utilize NIH-image1.6.3 make linear histogram, in concavo-convex middle leads, add and upper and lower area, calculating mean value, as each treatment region wrinkle rating (μm
2/ area).The results are shown in Figure 11.
From Fig. 9 ~ Figure 11, fat fullerene, compared with the free radical sponge of equivalent, decreases the skin irritation that excitor substance (NDA) causes,
In addition, DMSO Freeze-cracking Method is used to utilize scanning electron microscope to observe cross section structure (Figure 12), carry out the parsing (Figure 13) of the SEM imagery exploitation NIH-image of application on human skin usual organize models cross sectional shape for same application on human skin usual organize models sample.
From Figure 12, Figure 13, fat fullerene, compared with the free radical sponge of equivalent, decreases the skin irritation that excitor substance (NDA) causes,
In addition, the solid fibrous footpath of copying employing silicone rubber duplicating method is utilized to carry out image taking (Figure 14), carry out the parsing (Figure 15) utilizing NIH-image of duplicating image for same application on human skin usual organize models sample.
From Figure 14, Figure 15, fat fullerene, compared with the free radical sponge of equivalent, inhibits the wrinkle of skin surface to be formed,
As from the foregoing, contain preparation as fullerene, fat fullerene, compared with free radical sponge, is anti-wrinkle agent more likely.
Claims (9)
1. compositions is for preventing the multilamellar of corium to be separated and/or the purposes of vertical atrophy, described compositions contain spiny dogfish alkanes and this squalane apoplexy due to endogenous wind dissolve with C
60meter concentration is the fullerene of 2-500ppm.
2. purposes according to claim 1, the dosage form of described compositions is emulsion type.
3. for preventing the compositions of the multilamellar separation of corium and/or vertically atrophy, it is characterized in that, the compositions described in claim 1 or 2 being coordinated and forms.
4. compositions is for improving the concavo-convex purposes of skin surface, described compositions contain spiny dogfish alkanes and this squalane apoplexy due to endogenous wind dissolve with C
60meter concentration is the fullerene of 2-500ppm.
5. purposes according to claim 4, the dosage form of described compositions is emulsion type.
6., for improving the concavo-convex compositions of skin surface, it is characterized in that the compositions described in claim 4 or 5 to coordinate to form.
7. compositions for control cutin scale peel off a purposes, described compositions contain spiny dogfish alkanes and this squalane apoplexy due to endogenous wind dissolve with C
60meter concentration is the fullerene of 2-500ppm.
8. purposes according to claim 7, the dosage form of described compositions is emulsion type.
9., for the compositions that the scale controlling cutin is peeled off, it is characterized in that the compositions described in claim 7 or 8 to coordinate to form.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2008066374 | 2008-03-14 | ||
| JP2008-066374 | 2008-03-14 | ||
| CN2009801089185A CN101969917A (en) | 2008-03-14 | 2009-03-03 | Anti-wrinkle composition and external skin composition |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2009801089185A Division CN101969917A (en) | 2008-03-14 | 2009-03-03 | Anti-wrinkle composition and external skin composition |
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| CN105168008A true CN105168008A (en) | 2015-12-23 |
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ID=41065094
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2009801089185A Pending CN101969917A (en) | 2008-03-14 | 2009-03-03 | Anti-wrinkle composition and external skin composition |
| CN201510427642.4A Pending CN105168008A (en) | 2008-03-14 | 2009-03-03 | Anti-wrinkle composition and external skin composition |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2009801089185A Pending CN101969917A (en) | 2008-03-14 | 2009-03-03 | Anti-wrinkle composition and external skin composition |
Country Status (4)
| Country | Link |
|---|---|
| JP (1) | JP5284345B2 (en) |
| KR (1) | KR20100135703A (en) |
| CN (2) | CN101969917A (en) |
| WO (1) | WO2009113426A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108324646A (en) * | 2018-04-16 | 2018-07-27 | 广州雷诺生物科技有限公司 | A kind of moisturizer containing fullerene |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104997646A (en) * | 2015-07-09 | 2015-10-28 | 北京福纳康生物技术有限公司 | Oil-soluble fullerene solution and preparation method thereof |
| CN105342904B (en) * | 2015-11-02 | 2018-04-10 | 嘉文丽（福建）化妆品有限公司 | A kind of Essence with skin wrinkle resisting effect |
| CN105434182A (en) * | 2015-12-23 | 2016-03-30 | 豌豆之本(北京)科技有限公司 | Fullerene composition applied to daily chemicals |
| WO2017125080A1 (en) * | 2016-01-21 | 2017-07-27 | 北京福纳康生物技术有限公司 | Application of fullerene/metal-fullerene for preparing pharmaceutical product |
| JP6883534B2 (en) * | 2017-03-30 | 2021-06-09 | ビタミンＣ６０バイオリサーチ株式会社 | Fullerene-containing cosmetic composition |
| JP2018203630A (en) * | 2017-05-30 | 2018-12-27 | ビタミンＣ６０バイオリサーチ株式会社 | Cosmetic fullerene-containing composition and cosmetic prepared therewith |
| CN108403549A (en) * | 2018-04-23 | 2018-08-17 | 广州雷诺生物科技有限公司 | A kind of face cleaning mousse containing fullerene |
| CN108852865A (en) * | 2018-07-16 | 2018-11-23 | 北京福纳康生物技术有限公司 | A kind of fullerene topical composition |
| US20210308266A1 (en) * | 2018-08-20 | 2021-10-07 | LivePet, LLC | Lipofullerene conjugates and their use for promotion of hair growth and prevention of hair loss |
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| CN1404382A (en) * | 2000-02-24 | 2003-03-19 | 法伊鲁特股份有限公司 | Squalane containing ultra fine particles of burning residue of carbon and method for producing the same |
| CN1753968A (en) * | 2003-01-27 | 2006-03-29 | 三菱商事株式会社 | Antioxidative composition and composition for external use |
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| JPH09157150A (en) * | 1995-12-05 | 1997-06-17 | Mitsushieru:Kk | Dermal cosmetic |
| JP3506349B2 (en) * | 1996-04-11 | 2004-03-15 | 株式会社資生堂 | Sun care cosmetic composition |
| JP4360925B2 (en) * | 2003-01-27 | 2009-11-11 | ビタミンＣ６０バイオリサーチ株式会社 | Composition for external use |
| JP2004269523A (en) * | 2003-02-20 | 2004-09-30 | Shinobu Ito | Fullerene composition for external use |
| JP4474225B2 (en) * | 2003-07-29 | 2010-06-02 | ビタミンＣ６０バイオリサーチ株式会社 | Cosmetic composition |
-
2009
- 2009-03-03 WO PCT/JP2009/053991 patent/WO2009113426A1/en active Application Filing
- 2009-03-03 JP JP2010502776A patent/JP5284345B2/en active Active
- 2009-03-03 KR KR1020107014546A patent/KR20100135703A/en not_active Application Discontinuation
- 2009-03-03 CN CN2009801089185A patent/CN101969917A/en active Pending
- 2009-03-03 CN CN201510427642.4A patent/CN105168008A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1404382A (en) * | 2000-02-24 | 2003-03-19 | 法伊鲁特股份有限公司 | Squalane containing ultra fine particles of burning residue of carbon and method for producing the same |
| CN1753968A (en) * | 2003-01-27 | 2006-03-29 | 三菱商事株式会社 | Antioxidative composition and composition for external use |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108324646A (en) * | 2018-04-16 | 2018-07-27 | 广州雷诺生物科技有限公司 | A kind of moisturizer containing fullerene |
Also Published As
| Publication number | Publication date |
|---|---|
| KR20100135703A (en) | 2010-12-27 |
| WO2009113426A1 (en) | 2009-09-17 |
| JP5284345B2 (en) | 2013-09-11 |
| JPWO2009113426A1 (en) | 2011-07-21 |
| CN101969917A (en) | 2011-02-09 |
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