CN101583691B

CN101583691B - Antioxidant

Info

Publication number: CN101583691B
Application number: CN2007800491088A
Authority: CN
Inventors: 阪口博之; 最上理映; 金辰也; 林克郎; 细野秀雄; 平野正浩
Original assignee: Fancl Corp; Tokyo Institute of Technology NUC
Current assignee: Fancl Corp; Tokyo Institute of Technology NUC
Priority date: 2007-01-18
Filing date: 2007-10-25
Publication date: 2012-11-14
Anticipated expiration: 2027-10-25
Also published as: HK1132758A1; WO2008087774A1; JP5213122B2; CN101583691A; KR20090109535A; KR101410636B1; CN102697665A; JPWO2008087774A1

Abstract

An antioxidant comprising as an active ingredient, a 12CaO7Al2O3 compound and/or a 12SrO7Al2O3 compound and a mixed crystal thereof, each of which contains a negative hydrogen ion (H-) at a concentration of 1x1018cm-3 or more.

Description

Inhibitor

Technical field

The present invention relates to contain the inhibitor of hydrogeneous anionic inorganic powder.

Background technology

Known mineral compound (the 12CaO7Al that contains hydride ion ₂O ₃Compound, 12SrO7Al ₂O ₃Compound or with 12 ((1-x) CaOxSrO) 7Al ₂O ₃The 12CaO7Al of expression is formed in (0＜x＜1) ₂O ₃And 12SrO7Al ₂O ₃The mixed grain effect compound) (patent documentation 1:WO2003/089373 communique).Known these compounds can show in atmosphere at room temperature through continued to be converted into the function of electroconductive after the rayed by isolator.But, do not know that still these compounds have excellent antioxidant effect.

In vivo, antioxygenation is being used for bringing into play important function aspect the health maintenance.Common inhibitor (free-radical scavengers) provides an electronics to make asymmetric electronic stability paired to radical.In this case, though inhibitor itself becomes radical, this radical is normally stable, and can be converted into the non-free radical class by all means.Compound with phenol skeleton, thiol group has anti-oxidant activity usually.Inhibitor is used as the antioxidant of food, grease etc., and then is applied in the pharmaceuticals.As naturally occurring inhibitor Viteolin (vitamin E), sesamin phenol (being present in the siritch), trans-resveratrol (being present in the red wine), catechin (being present in the tealeaves) etc. are arranged.

In addition, used inhibitor, in coating, grease, food, plastics etc., utilized as additive as the defence agent of corresponding oxygenizement.

Patent documentation 1WO2003/089373 communique

Patent documentation 2 TOHKEMY 2004-26608 communiques

No. the 3533648th, patent documentation 3 Japanese Patents

Summary of the invention

Novel antioxidant is provided.

Inhibitor and the application thereof of the powder of the mineral compound (the mixed grain effect compound of 12CaO7Al2O3 compound, 12SrO7Al2O3 compound or 12CaO7Al2O3 and 12SrO7Al2O3) that will contain hydride ion as effective constituent are provided.

The main composition of the application's invention is described below.

(1) inhibitor, its mixed crystal of 12CaO7Al2O3 compound and/or 12SrO7Al2O3 compound and these compounds of hydride ion (H-) that will contain the above concentration of 1 * 1018cm-3 is as effective constituent.

(2) external composition for skin, it contains (1) described inhibitor.

(3) cosmetic material, it contains (1) described inhibitor.

(4) whitening agent, it contains (1) described inhibitor.

(5) inhibitor is used in the plastics interpolation, and it contains (1) described inhibitor.

(6) inhibitor is used in the coating interpolation, and it contains (1) described inhibitor.

Novel antioxidant can be provided.

The mineral compound powder that contains hydride ion of the present invention is brought into play excellent function as inhibitor.The inhibitor that can be used as plastics, coating, cosmetic material, grease etc. uses.

Description of drawings

Fig. 1 representes through IR and SIMS method the hydride ion amount to be carried out quantitative results.

Fig. 2 representes to measure the result of the sample solution ESR collection of illustrative plates of pure water solvent.

Fig. 3 representes the radical scavenging activity of embodiment 3 Sample A-2～A-4.

Fig. 4 representes the radical scavenging activity of embodiment 3 sample B-2～B-4.

Fig. 5 representes that embodiment 4 uses the radical scavenging activity of the sample C-2～C-4 of solvent C.

Fig. 6 representes that embodiment 4 uses the radical scavenging activity of sample D-2～D-4 of solvent D.

Fig. 7 representes the removing ability from the hydroxyl radical free radical of rayed titanium oxide that embodiment 10 measures through the ESR method of using sample B.

Embodiment

In the present invention as starting substance; Can be pure 12CaO7Al2O3 compound (the following C12A7 that is designated as sometimes); As long as in treating processes, do not destroy the distinctive mayenite of C12A7 (Mayenite) type crystalline texture, also can be a part of of calcium and aluminium or whole having and the mixed crystal of the equal crystalline texture of C12A7 compound, sosoloid (following these materials slightly are called coordinator matter) by other element substitution.

As the material that has with the equal crystalline texture of C12A7 compound, now known have a 12SrO7Al2O3, and the ratio of mixture of Ca and Sr can freely change.That is: also can be the mixed grain effect compound of 12CaO7Al2O3 and 12SrO7Al2O3.In addition, the anionic kind of initial stage inclusion, quantity do not produce big influence to the importing effect of hydride ion.And then form can be in powder, film, polycrystal, the monocrystalline any.

As the C12A7 of starting substance, the atom equivalence ratio that contains calcium (Ca) and aluminium (Al) through use is the raw material of 12: 14 ratios, in sintering temperature more than 1200 ℃ and be lower than and carry out solid state reaction under 1415 ℃ and synthesize.Representative raw material is the mixture of lime carbonate and aluminum oxide.

Can obtain monocrystalline through zone melting method (FZ method) with the C12A7 sintered compact that obtains in the solid state reaction as precursor.The cultivation of C12A7 monocrystalline, through with infrared rays optically focused on bar-shaped ceramic precursor, lift precursor rods simultaneously, the melting zone is moved, on the interface of melting zone-solidify portion, make the monocrystalline continuous growth.The present inventor discloses the C12A7 compound monocrystal that contains the high density active oxygen and the method for manufacture of bubble-free C12A7 monocrystalline in patent documentation 3 (No. the 3533648th, Japanese Patent).

In starting substance C12A7 and the environment of equal material more than hydrogeneous 1000ppm; Preferably in the ambient windstream more than the hydrogeneous 20 volume % of oxygen-free, moisture; More than 800 ℃, preferred more than 1000 ℃ and be lower than 1350 ℃; More preferably under about 1300 ℃ temperature,, keep cooling off after several minutes to several hours according to the form of starting substance.In order to obtain ambient containing hydrogen, can in the container of can high temperature resistant heat treated material processing as silica glass, tantalum, fill hydrogen, starting substance is enclosed wherein.At this moment, also can the material that can generate hydrogen through chemical reaction together be enclosed wherein, to replace filling hydrogen.Pure C12A7 fuses when being heated to more than 1350 ℃ in ambient containing hydrogen, loses crystalline texture.

Implement hydrogen concentration in the heat treated environment and be 1000ppm when following, the amount that imports the hydride ion in C12A7 and the equal material is below 1 * 1018cm-3, is difficult to obtain excellent antioxidant effect in vivo.In addition, when thermal treatment temp is low more, import the easy more hydroxyl ion (OH-) that is replaced into of hydrogen ion in C12A7 and the equal material, when being lower than 800 ℃, because the amount of hydride ion is lower than 1 * 1018cm-3, so be difficult to obtain excellent anti-oxidant function equally.

Speed of cooling can be put coldly for electric furnace common naturally, but is preferably cool quickly, and it is more than 1 * 1018cm-3 that thermal treatment temp can make the quantitative change of hydride ion through cool quickly when low.

Through this material of above pyroprocessing, if pure C12A7 be raw material then be water white transparency, if powder then is white in color.When utilizing the condition of hydrogen reducing strong, import electronics, be light green in the part of cage structure.At this moment,, under the situation of the amount that does not reduce hydride ion, electronics is disappeared, form transparent or white states through keeping about 10 minutes under the temperature between 300 ℃ to 450 ℃.

Contain hydride ion or imported the state of hydride ion, be meant the hydride ion inclusion in C12A7 crystalline cage structure space.The lattice parameter of known C12A7 crystalline unit cell is about 1.2nm, representes with the composition of [Ca24Al28O64] 4+.When the importing through hydride ion came 4 positive charges of whole compensation per unit lattices, the quantity of the hydride ion that the C12A7 crystallization contains predicted that per 1 cubic centimetre is 2.3 * 1021 at most.

The inorganic powder that contains hydride ion is as the excellent function of inhibitor performance.The inhibitor that can be used as plastics, coating or make up material, medicine, grease etc. uses.

Embodiment

Embodiment 1

To be processed into the polished plate of minute surface of thickness 300 μ m through the C12A7 monocrystalline that zone melting method (FZ) is made.With its in oxygen in 1350 ℃ of thermal treatments 6 hours (Sample A).Then in the mixed gas air-flow of 20% volume hydrogen-80% volume nitrogen, after 2 hours, in equivalent environment, cool off fast, in the C12A7 crystallization, import hydride ion (sample B) 1300 ℃ of maintenances.

Then, cool off after in air, being warming up to 800 ℃, or remove or make it to become hydroxyl (OH-) (sample C) hydride ion.Utilize the intensity of 3560cm-1 place ir absorption to obtain the hydroxyl concentration in each sample.In addition, through secondary ion mass spectrometry (SIMS) the total amount concentration of the hydrogen that contains in each sample is carried out quantitatively.

In Sample A, C, hydrogen has almost all formed hydroxyl as proton.In sample B, the hydrogen proton free also exists as hydride ion outward.Utilize the quantitative values of ir absorption and the SIMS of Sample A, C to make the calibration curve of proton concentration, can infer the concentration that the hydride ion in the sample B thus.These method of calculation are shown in the 1st figure.The hydrogen concentration that becomes hydride ion in the sample B infers to be 2 * 1020cm-3.

With reference to Fig. 5, the C12A7 sintered compact of density about 80% is carried out the thermal treatment with sample B the same terms, import hydride ion.Because be the condition identical, be 2 * 1020cm-3 so hydride ion concentration is inferred with sample B.It is that dispersion medium, alumina balls are the planetary type ball-milling of crushing medium that this sintered compact is implemented with ethanol, processes powder.The specific surface area of powder infers to be about 2m2/g through the BET method.

Embodiment 2

The DPPH radical scavenging activity is measured

(1) preparation of DPPH solution

(1.1-phenylbenzene picryl phenylhydrazine (1,1 '-diphenyl-2-picrylhydrazyl) already make with the pure pharmaceutical worker of light) is dissolved in 100% ethanol, preparation 0.00394w/v% solution to make DPPH.

(2) preparation of sample solution

Make solvent with pure water, the 0.1w/v% dispersion liquid of the sample B of preparation among the preparation embodiment 1.With ultrasonic echography handle agglutinator pulverized in 5 minutes after, with whisking appliance stir about 1 hour.Because powder is easily sedimentation in pure water, so also will stir before soon mixing with whisking appliance with DPPH solution.Use the contrast of pure water as the sample solution of pure water solvent.

(3) mensuration of ESR collection of illustrative plates

(device ESR-JES-TE200:JEOL)

Resonant frequency: 9.43GHz, output: 4.0mW, magnetic field modulation: 100kHz; Observation magnetic field: 338.5 ± 5mT, minute: 1min, modulation amplitude: 0.1mT; Amplification factor: 500 (when DPPH radical and lipid peroxidation can be measured), answering time: 0.03sec.

Plate reader with in dull and stereotyped with sample solution (with 0.1w/v% is benchmark, dilutes 1/2,1/4,1/10 respectively) the 100 μ l mixing of DPPH solution 100 μ l and pure water solvent, with free radical reaction after about 2 minutes, mensuration ESR collection of illustrative plates.Mensuration result is as shown in Figure 2.

The sample solution of pure water solvent

(pure water) observed radical and had peculiar collection of illustrative plates in the contrast.After mixing 0.1w/v% sample B dispersion liquid, the peak disappears, and can confirm to have removed radical.When using pure water that 0.1w/v% powder dispersion dilution is also carried out same mensuration as the solution of 0.01w/v% (1/10 dilution), 0.025w/v% (1/4 dilution), 0.05w/v% (1/2 dilution), confirm that radical scavenging activity has the powder concentration dependency.Utilize following formula to obtain radical scavenging activity.

(formula 1) radical scavenging activity (%)=(1-beta/alpha) * 100

At this, the peak height of the ESR collection of illustrative plates of β=sample B dispersion liquid+DPPH solution

The peak height of the ESR collection of illustrative plates of α=contrast (pure water)+DPPH solution

(4) result

The radical scavenging activity of 0.05w/v%, 0.025w/v%, 0.01w/v% concentrations samples B dispersion liquid is 83%, 43%, 8%.Show that radical scavenging activity has linear concentration dependent.Confirm that in addition IC50 is 0.021w/v%.Can confirm the anti-oxidant ability (DPPH radical scavenging activity) of sample B according to this result.

Embodiment 3

Oxidation about lipid suppresses effect (utilizing the Supraene of ESR, oleic anti-oxidant can the evaluation)

(1) solvent

Use Supraene (this special liver oil system purity 99.5% oxygen-freeization of bank prevents agent), oleic acid (with the pure pharmaceutical worker's industry of light one-level).

(2) spin trapping agent preparation

Make spin trapping agent α-Phenyl-N-tert-butylnitrone (α-phenyl-N-4-butyl nitrone) (below be called α-PBN) be dissolved in three (caprylic/capric) glyceryl ester (utilizing UW), process 400mM solution.

(3) measure specimen preparation

(solution of α-PBN) according to the use level preparation of table 1, is processed ESR mensuration sample for the sample B that in the solvent sample, adds embodiment 1 and spin trapping agent.The weight percent of the concentration of sample B for calculating with (sample B weight)/(weight of solvent) * 100.

Table 1

(4) ESR measures

To each sample irradiation UV-A ripple, the free-radical generating amount when making finish generation oxidation with ESR mensuration.The UV irradiation time is as shown in table 1.

Utilize following formula to obtain radical scavenging activity.A-2～A-4 is as shown in Figure 3, and B-2～B-4 is as shown in Figure 4.

(formula 2) radical scavenging activity (%)=(1-beta/alpha) * 100

β=sample B dispersion liquid (the peak height of the ESR collection of illustrative plates of A-2～A-4 or B-2～B-4)

The peak height of the ESR collection of illustrative plates of α=contrast (A-1 (when β is A-2～A-4) or B-1 (when β is B-2～B-4))

(5) result

In Supraene, add the result of the powder (sample B of embodiment 1) of 5w/w%, 2.5w/w%, 1.25w/w%, radical scavenging activity is 55%, 35%, 15%.Depend on powder concentration, demonstrate significant antioxidant effect.Confirm that in addition IC50 is 4.2w/w%.In oleic acid, add the result of the powder (sample B of embodiment 1) of 5w/w%, 2.5w/w%, 1.25w/w%, radical scavenging activity is 50%, 41%, 33%.Depend on powder concentration, demonstrate significant antioxidant effect.Confirm that in addition IC50 is 4.9w/w%.

Embodiment 4

About the oxidation of lipid suppress effect (utilize ESR sfas+unsaturated fatty acids (oleic acid, Supraene) anti-oxidant can the evaluation)

Oleic acid+three (caprylic/capric) glyceryl ester

Supraene+three (caprylic/capric) glyceryl ester

(1) solvent preparation

Carry out the preparation that ESR measures sample, following 3 kinds of finishes are mixed and use.The solvent of preparation is described below.

Solvent C a: c=5: 5 (weight ratio) solvent D b: c=5: 5 (weight ratios)

A Supraene (with the superfine 99% antioxidant alpha-tocopherol 0.05% of the pure pharmaceutical worker's industry of light)

B oleic acid (with the pure pharmaceutical worker's industry of light one-level)

C three (caprylic/capric) glyceryl ester (Myritol 318, Cognis)

(2) measure the sample preparation

For solvent C, D, add sample B, the α-PBN of embodiment 1 according to the use level of table 2, process ESR and measure sample (C-1～C-4, D-1～D-4).The weight percent of the concentration of sample B for calculating with (sample B weight)/(weight of solvent) * 100.

Table 2

(3) ESR measures

To each sample irradiation UV-A ripple, the free-radical generating amount when making finish generation oxidation with ESR mensuration.The UV irradiation time is shown in above-mentioned table 2.

Utilize following formula to obtain radical scavenging activity, use the sample C-2～C-4 of solvent C as shown in Figure 5, use sample D-2～D-4 of solvent D as shown in Figure 6.

(formula 3) radical scavenging activity (%)=(1-beta/alpha) * 100

β=sample B dispersion liquid (the peak height of the ESR collection of illustrative plates of C-2～C-4 or D-2～D-4)

The peak height of the ESR collection of illustrative plates of α=contrast (C-1 (when β is C-2～C-4) or D-1 (when β is D-2～D-4))

(4) result

(Supraene: the result of the sample B of the embodiment 1 of interpolation 2.0w/w%, 1.0w/w%, 0.5w/w% three (caprylic/capric) glyceryl ester=5: 5), radical scavenging activity is 40%, 27%, 9% in solvent C.Depend on powder concentration, demonstrate significant antioxidant effect.Confirm that in addition IC50 is 2.9w/w%.(oleic acid: add powder (sample B of the embodiment 1) result of 2.0w/w%, 1.0w/w%, 0.5w/w% three (caprylic/capric) glyceryl ester=5: 5), radical scavenging activity is 66%, 42%, 26% at solvent D.Depend on powder concentration, demonstrate significant antioxidant effect.Confirm that in addition IC50 is 1.2w/w%.

Use TG (three (caprylic/capric) glyceryl ester) to be diluted to respectively at 50% o'clock Supraene, oleic acid, same with embodiment 3, Supraene, radical concentration dependent under the powder effect of sample B that oleic acid oxidation produced are eliminated.

Embodiment 5

The preparation of plastic grain

(quality %)

(1) ABS resin 96

(2) calcium stearate 1

(3) sample B 3 of embodiment 1

(method for making) 200 ℃ of extrusion processinges, made particle with above-mentioned (1)～(3).

Embodiment 6

The preparation of liquid foundation

(quality %)

(1) sweet oil 2

(2) capryiin 7

(3) trimethyl silicane alcoxyl base silicon ester 1

(4) silicon-dioxide 6

(5) decamethylcyclopentaandoxane 15

(6) octamethylcyclotetrasiloxane 15

(7) pure water remainder amount

(8) 1,3 butylene glycol 4

(9) titanium oxide 12.5

(10) mica 3

(11) sample B 1 of embodiment 1

(12) spices 0.1

(13) sanitas 0.1

(method for making)

Mentioned component (1), (2), (12) and (13) are mixed and heating for dissolving (A phase).Composition (7) and (8) are mixed and dissolving (B phase).With pulverizing (C phase) behind composition (4), (9), (10) and (11) uniform mixing.(D phase) mixed in composition (3), (5) and (6).After A reached D mutually and mix mutually, add C and mix mutually, add above-mentioned B again and carry out emulsification mutually.

Embodiment 7

The preparation of sunscreen

(quality %)

(1) titanium dioxide fine particles 5

(2) zinc oxide fine particles 15

(3) cerium oxide 5

(4) sample B 1 of embodiment 1

(5) octamethylcyclotetrasiloxane

20 (5) amino modified polyethers ZGK 51

(6) PIVALIC ACID CRUDE (25) isooctadecanol ester 10

(7) behenyl alcohol 3

(8) Rizinsan K2 A2 0.1

(9) pure water remainder

(method for making) with above-mentioned (5)～(7) composition in 80 ℃ of heating for dissolving (A phase).Add composition (1)～(4) to A and mix (B phase) in mutually.Behind (8), (9) uniform mixing, add it to B and carry out emulsification in mutually and mix.

Embodiment 8

The preparation of powdery foundation cream

(quality %)

(1) silicon is handled mica 20

(2) silicon is handled talcum 22.4

(3) fluorine is handled titanium oxide 10

(4) amino acid is handled sericite 25

(5) silicon is handled yellow oxide of iron 5

(6) silicon is handled red iron oxide 2.5

(7) silicon is handled iron oxide black 0.1

(8) sample B 1 of embodiment 1

(9) methyl polysiloxane (100cst) 11

(10) oxysuccinic acid two isooctadecanol esters 3

(method for making) slowly added well-mixed (9)～(10) after with Henschel mixer (Henschel mixer) (1)～(8) being stirred 5 minutes, pulverizes with hammer mill.Be pressed into then in the foundation cream dish.

Embodiment 9

The preparation of eye shadow

(quality %)

(1) silicon is handled mica 10

(2) silicon is handled talcum 19

(3) amino acid is handled titanium oxide 7

(4) amino acid is handled sericite 10

(5) nylon powder 10

(6) Si powder 10

(7) fluorine is handled yellow oxide of iron 5

(8) fluorine is handled red iron oxide 10

(9) silicon is handled ultramarine 3

(10) sample B 1 of embodiment 1

(11) methyl phenyl silicone 8

(12) the Tego Alkanol 16 2-ethylhexanoate 7

(method for making) slowly added well-mixed (11)～(12) after with Henschel mixer (Henschel mixer) (1)～(10) being stirred 5 minutes, pulverizes with hammer mill.Be pressed into then in the foundation cream dish.

Embodiment 10

Utilize the ESR method to estimate removing ability from the hydroxyl radical free radical of rayed titanium oxide

During with the rayed anatase titanium dioxide below the wavelength 380nm, produce radical through light-catalyzed reaction.Whether the sample B of preparation removes the radical that produces through rayed titanium dioxide fine particles aqueous dispersions among the embodiment 1, and (ESR) estimates with ESR spectrum.Through (coexistence of 5-N-oxide compound (5,5-Dimethyl-1-Pyrroline-N-Oxide)) prolongs life-span of radical and measures with spin trapping agent DMPO.

(TP)

Anatase titanium dioxide particulate (median size 180nm) dispersion liquid 0.5% (w/v) 20 μ L, sample solution 180 μ L, the 10mM DMPO aqueous solution 200 μ L are mixed (adding up to 400 μ L), passed through the extra-high-pressure mercury vapour lamp irradiation ultraviolet radiation 1 minute when stirring with whisking appliance.Will through the mixed dispersion liquid of uviolizing pack into the solution of ESR with sample pool in, measure the ESR collection of illustrative plates of DMPO-OH.

As sample solution, use ion exchanged water (contrast), sample B dispersion liquid.The sample B dispersion liquid is to be used for immediately after being dispersed in sample B in the water measuring.The concentration that makes the sample B dispersion liquid is 1.22% (w/v), 1.67% (w/v), 2.22% (w/v), 10% (w/v), and the concentration that makes the sample B in the mixed dispersion liquid is 0.5% (w/v), 0.75% (w/v), 1.0% (w/v), 4.5% (w/v).

Using appts EMX8/2.7 type (BurkerBiospin) when ESR measures.With self-tuning (Autotune) decision condition determination.

Obtain radical scavenging activity with following formula.

(formula 3) free radical scavenging activity (%)=(1-beta/alpha) * 100

Second peak height that begins from downfield in the ESR collection of illustrative plates of the mixed dispersion liquid after the uviolizing of β=when using the sample B dispersion liquid as sample solution.

Second peak height that begins from downfield in the ESR collection of illustrative plates of the mixed dispersion liquid after the uviolizing of α=when using ion exchanged water (contrast) as sample solution.

(result)

Do not find radical scavenging activity when the concentration of the sample B in the mixed dispersion liquid is 0.5% (w/v), 0.75% (w/v), demonstrated 38% radical scavenging activity when being 1.0% (w/v), demonstrated 86% removing ability when being 4.5% (w/v).The result is as shown in Figure 7.

The inorganic powder that contains hydride ion that the present invention relates to is as the excellent function of inhibitor performance.

In plastics, coating or the fields such as material, medicine part outer article of making up, can cooperate, use and as the corresponding any amount of the purpose of inhibitor.

Claims

1. contain 1 * 10 ¹⁸Cm ^-3Hydride ion (the H of above concentration ^-) 12CaO7Al ₂O ₃Compound and/or 12SrO7Al ₂O ₃The application of the mixed crystal of compound and these compounds in the preparation inhibitor.