CN101257847A

CN101257847A - Method of evaluating skin conditions and method of estimating skin thickness

Info

Publication number: CN101257847A
Application number: CNA2006800320215A
Authority: CN
Inventors: 宫前裕太; 山川弓香; 土屋顺子; 川畑真理绘
Original assignee: Pola Chemical Industries Inc
Current assignee: Pola Chemical Industries Inc
Priority date: 2005-09-02
Filing date: 2006-09-01
Publication date: 2008-09-03

Abstract

The aim of the invention is to evaluate at least one of the degree of skin injury caused by ultraviolet light and the degree of physiological aging of the skin and estimate at least one of the epidermal thickness and dermal thickness of the skin, the near infra-red absorption spectrum of the skin is used and the obtained data are employed in monitoring the skin conditions, evaluating a cosmetic and so on.

Description

The method of the method for evaluating skin situation and estimation skin thickness

Technical field

The present invention relates to determine method at least a in skin injury degree that UV light causes and the skin physiology aging degree, estimate method at least a in epiderm skin thickness and the dermis thickness and by using the result who obtains in the top method to monitor the method for skin condition and estimating the method etc. of cosmetics.

Background technology

Not only the women everyone wish to have beautiful skin.Therefore, in the present circumstance, most of women make to apply some make up etc. and make great efforts to make skin to be in good situation.Great changes have taken place with individuality for skin.Skin aging roughly is divided into physiological aging (original physiologic aging) and the pathology aging (damage that UV light causes or photoaging) (for example, referring to non-patent literature 1) that causes of UV light that betides everyone with ageing.

Since skin aging occur through the time for example change that loss of elasticity and wrinkle increase, this has a significant impact appearance and impression.This through the time change and to have reflected that the physiology in the skin changes, especially in the epidermis and corium that constitute skin, for example, it is very big that shallow wrinkle is influenced by epidermis and papillary layer, and deep wrinkle and sagging are subjected to corium to influence very big (for example, referring to non-patent literature 2).Therefore, in order to keep skin beauty, objective and judge situation such as epidermis and corium quantitatively thickness is extremely important separately that this makes it possible to select and uses suitable cosmetics and the medicine that is fit to skin or carry out Medical Treatment etc.

For measuring skin physiology or the old and feeble method that changes, disclose by (for example measuring method that wrinkle or sagging outward appearance estimate actual age, referring to patent documentation 1 and 2), the method of estimating the skin age according to the measurement result of skin surface form (for example, referring to patent documentation 3), according to the method at the vibration change calculations skin age that when making the contact skin vibrator, obtains (for example, referring to patent documentation 4), according to the method for estimating the age from the corium brightness of ultrasonic skin image (for example, referring to patent documentation 5), according to from method (for example, referring to patent documentation 6) of the skin thickness evaluating skin hardening effect of ultrasonic image etc.In addition, disclose and used method that horny layer of epidermis cell average area estimates the age as index (for example, referring to patent documentation 7), the method for the variation evaluating skin aging degree by measuring the power that fibroblast produces (for example, referring to patent documentation 8), use the method (for example, referring to patent documentation 9) of DNA evaluating skin aging degree etc.But, all openly do not measure the damage that UV light causes and the method for physiological aging in above-mentioned, and objective and estimate epidermis and the corium method of thickness separately quantitatively.

In recent years, measure people's tissue, skin and hair near-infrared absorption spectrum, at spectrum and particular value such as moisture and structural state carry out statistical procedures (multivariate analysis) as multiple regression analysis and principal component analysis and according to the non-infringement of its dependency relation illustrate the process known (for example, referring to patent documentation 10-13) of moisture of skin, mastitis, hair situation etc.In addition, quantize the dermis of skin collagen (for example, referring to patent documentation 14) of on-hand quantity.But these all openly do not measure the skin injury that UV light causes and the method for physiological aging, and objective and estimate epidermis and the corium method of thickness separately quantitatively.

In this case, the present inventor finds, when judging skin such as skin thickness, skin surface form, skin viscoelasticity or skin internal organizational structure, can judge the thickness of skin by the non-infringement of the multivariate analysis of using near-infrared absorption spectrum ground, and submit patent application (patent documentation 15) to.In order to select and use suitable cosmetics and the medicine that is fit to skin, need the further means of this technology that advance of exploitation to be not infringement and to measure the epidermis of formation skin and the thickness separately of corium objectively.

Patent documentation 1:JP 2002-330943A

Patent documentation 2:JP 2002-360544A

Patent documentation 3:JP 2005-095326A

Patent documentation 4:JP 2001-212087A

Patent documentation 5:JP 2000-083954A

Patent documentation 6:JP 11-290315A

Patent documentation 7:JP 11-299792A

Patent documentation 8:JP 2004-354159A

Patent documentation 9:JP 2001-161364A

Patent documentation 10:JP 2002-090298A

Patent documentation 11:JP 2003-344279A

Patent documentation 12:WO 01-075421A

Patent documentation 13:JP 2003-270138A

Patent documentation 14:JP 2005-083901A

Patent documentation 15:JP 2005-034350A

Non-patent literature 1: " Utility of Cosmetics ", Japanese cosmetic operator association edits, medicine thing day newspaper office, 51-52,2001

Non-patent literature 2: " Utility of Cosmetics ", Japanese cosmetic operator association edits, medicine thing day newspaper office, 163,178,2001

Summary of the invention

Carried out the present invention in this case, its objective is provide determine method at least a in skin injury degree that UV light causes and the skin physiology aging degree, estimate at least a method of epidermis skin thickness and corium skin thickness and use above the result of method monitor the method for skin condition and estimate the method for cosmetics.

In view of the foregoing, the present inventor furthers investigate.The result, at first, the present inventor is according to eigenvalue (the skin injury degree that UV light causes, the skin physiology aging degree, epidermal thickness and dermis thickness) analysis result of multivariate analysis of near-infrared absorption spectrum of known two or more skins obtains the dependency relation between skin characteristic value and its near-infrared absorption spectrum, then, obtain the near-infrared absorption spectrum of the skin of the eigenvalue the unknown that will be determined or estimate, discovery is according to above-mentioned dependency relation, can determine or estimate above-mentioned eigenvalue by the near-infrared absorption spectrum of the skin of eigenvalue the unknown, and therefore finish the present invention.More particularly, the present invention relates to following technology.

(1) a kind of near-infrared absorption spectrum by skin is determined skin injury degree that UV light causes and at least a method in the skin physiology aging degree, comprises step:

(X1) in skin injury degree that causes by UV light and the skin physiology aging degree at least a known two or more skins at 5990-5490cm ^-1And 5000-4480cm ^-1The measurement wavenumber region in the analysis result of multivariate analysis of near-infrared absorption spectrum of specific wavenumber region, obtain the dependency relation between at least a and near-infrared absorption spectrum of skin in specific wavenumber region in skin injury degree that UV light causes and the skin physiology aging degree;

(X2) in the skin injury degree that causes of the UV light that obtains being estimated and the skin physiology aging degree skin of at least a the unknown at the near-infrared absorption spectrum of specific wavenumber region; With

(X3) determine at least a in skin injury degree that UV light causes and the skin physiology aging degree according to the dependency relation that obtains in the step (X1) by the near-infrared absorption spectrum of the specific wavenumber region that obtains in the step (X2).

(2) according to (1) method, wherein determine skin injury degree and the skin physiology aging degree that UV light causes simultaneously.

(3) according to (1) or the method for (2), wherein multivariate analysis is principal component analysis (PCA) method, SIMCA method or KNN method.

(4) a kind of near-infrared absorption spectrum by skin is estimated at least a method in epiderm skin thickness and the dermis thickness, comprises step:

(Y1) by at least a known two or more skins in epiderm skin thickness and the dermis thickness at 6850-6620cm ^-1, 6540-5990cm ^-1, 5240-5180cm ^-1, 5030-4980cm ^-1, 4760-4720cm ^-1And 4650-4610cm ^-1, or 6940-6850cm ^-1, 6710-6540cm ^-1, 6250-6170cm ^-1, 5130-5080cm ^-1, 4950-4850cm ^-1, 4760-4690cm ^-1And 4670-4610cm ^-1Measure the analysis result of the multivariate analysis of the near-infrared absorption spectrum of specific wavenumber region in the wavenumber region, obtain at least a and dependency relation of skin between the near-infrared absorption spectrum of specific wavenumber region in epiderm skin thickness and the dermis thickness;

(Y2) obtain wanting the near-infrared absorption spectrum of the skin of at least a the unknown in estimative epiderm skin thickness and the dermis thickness in specific wavenumber region; With

(Y3) estimate at least a in epiderm skin thickness and the dermis thickness according to the dependency relation that obtains in the step (Y1) by the near-infrared absorption spectrum of the specific wavenumber region that obtains in the step (Y2).

(5) according to (3) method, wherein estimate epiderm skin thickness and dermis thickness simultaneously.

(6) according to (4) or the method for (5), wherein multivariate analysis is offset minimum binary (PLS) method or principal component regression (PCR) analytical method.

(7) a kind of method of selecting cosmetics comprises the step of the method selection cosmetics of any one in using (1)-(6).

(8) a kind of method of monitoring skin, the method seizure skin that comprises in using (1)-(6) any one be over time step in chronological order.

(9), comprise the step of confirmation to the skin treating effect according to (8) monitoring method.

(10) a kind of method of estimating cosmetics, the method that comprises in using (1)-(6) any one be relatively before the applied cosmetics and back skin condition or thickness, and with the step of variation as the index evaluation cosmetics.

(11), comprise and estimate the dermis thickness of cosmetics in skin thickness owing to have the step of wrinkle elimination function under the situation that applied cosmetics increases according to the method for (10) evaluation cosmetics.

According to the present invention, can provide non-infringement ground to estimate method at least a in method, non-infringement ground estimated statement skin thickness and the dermis thickness at least a in skin injury degree that UV light causes and the skin physiology aging degree and use the result of these methods to monitor the method for skin and estimate the method for cosmetics.

Description of drawings

Fig. 1 is the figure of load capacity (factor loading amount) feature of demonstration hairless mouse and people's near-infrared absorption spectrum.

Fig. 2 represents amido link (CONH) and amide (CONH for showing ₂) the figure of wavenumber region of near-infrared absorption spectrum of feature.

Fig. 3 is the figure of the measured value of the epidermis of the HE-dyeing image that shows the skin biopsy that hairless mouse is peeled off and skin samples group and corium.

Fig. 4 is for showing human arm upper arm and the ultrasonic image of forethiga skin samples group and the figure of epidermis and corium measured value.

Fig. 5 is for using the oval figure that concerns between degree of injury that the UV light as hairless mouse skin result shown in the embodiment 1 causes and the physiological aging degree that shows of scatter diagram and density.

Fig. 6 is for by determining the figure of hairless mouse skin result shown in the embodiment 2 that degree of injury that UV light causes and physiological aging degree obtain.

Fig. 7 is for using the oval figure that concerns between degree of injury that the UV light as application on human skin result shown in the embodiment 3 causes and the physiological aging degree that shows of scatter diagram and density.

Fig. 8 is for using the oval figure that concerns between degree of injury that the UV light as application on human skin result shown in the embodiment 3 causes and the physiological aging degree that shows of scatter diagram and density.

The figure of Fig. 9 for concerning between the degree of injury that uses scatter diagram and show that the result's of hairless mouse skin shown in 1 UV light as a comparative example causes and the physiological aging degree.

The figure of Figure 10 for concerning between the degree of injury that uses scatter diagram and show that the result's of hairless mouse skin shown in 2 UV light as a comparative example causes and the physiological aging degree.

The figure of Figure 11 for concerning between the degree of injury that uses scatter diagram and show that the result's of hairless mouse skin shown in 2 UV light as a comparative example causes and the physiological aging degree.

The figure of Figure 12 for concerning between the degree of injury that uses scatter diagram and show that the result's of application on human skin shown in 3 UV light as a comparative example causes and the physiological aging degree.

The figure of Figure 13 for concerning between the degree of injury that uses scatter diagram and show that as a comparative example the UV light of application on human skin result in 4 causes and the physiological aging degree.

The figure of Figure 14 for concerning between the degree of injury that uses scatter diagram and show that the result's of application on human skin shown in 4 UV light as a comparative example causes and the physiological aging degree.

The figure of Figure 15 for concerning between the degree of injury that uses scatter diagram and show that the result's of application on human skin shown in 4 UV light as a comparative example causes and the physiological aging degree.

The figure of Figure 16 for concerning between the degree of injury that uses scatter diagram and show that the result's of application on human skin shown in 4 UV light as a comparative example causes and the physiological aging degree.

Figure 17 is for showing the figure of the estimation model (calibration line) of skin (epidermis and corium) thickness in the set of hairless mouse skin sample.

Figure 18 gathers the figure of the estimation model (calibration line) of mesocuticle thickness for showing the hairless mouse skin sample.

Figure 19 is for showing the figure of the estimation model (calibration line) of dermis thickness in the set of hairless mouse skin sample.

Figure 20 is for showing the figure of the estimation model (calibration line) of skin (epidermis and corium) thickness in the set of application on human skin sample.

Figure 21 gathers the figure of the estimation model (calibration line) of mesocuticle thickness for showing the application on human skin sample.

Figure 22 is for showing the figure of the estimation model (calibration line) of dermis thickness in the set of application on human skin sample.

Figure 23 gathers the figure of the estimation model (calibration line) of mesocuticle thickness for showing the hairless mouse skin sample.

Figure 24 is for showing the figure of the estimation model (calibration line) of dermis thickness in the set of hairless mouse skin sample.

Figure 25 is for showing the figure of the estimation model (calibration line) of skin (epidermis and corium) thickness in the set of hairless mouse skin sample.

Figure 26 gathers the figure of the estimation model (calibration line) of mesocuticle thickness for showing the application on human skin sample.

Figure 27 is for showing the figure of the estimation model (calibration line) of dermis thickness in the set of application on human skin sample.

Figure 28 is for showing the figure of the estimation model (calibration line) of skin (epidermis and corium) thickness in the set of application on human skin sample.

The specific embodiment

Method feature of the present invention is: (1) obtains dependency relation between skin characteristic value and its near-infrared absorption spectrum by the analysis result of the multivariate analysis of the near-infrared absorption spectrum of known two or more skins of eigenvalue; (2) obtain the near-infrared absorption spectrum of the skin of the eigenvalue the unknown that will be determined or estimate; (3) determine or estimate eigenvalue according to above-mentioned dependency relation by the near-infrared absorption spectrum of the skin of eigenvalue the unknown.

Above-mentioned skin characteristic value is meant skin injury degree, skin physiology aging degree, epiderm skin thickness or the dermis of skin thickness that UV light causes.

The skin injury that UV light causes is divided into skin aging, skin carcinomas etc. such as speckle that acute reaction causes in UV light as long term exposure as sunburn and chronic reaction (it also is called as photoaging) and wrinkle." skin injury that UV light causes " among the application refers to that longer-term is exposed to the influence of UV light, and the near-infrared absorption spectrum of the skin of UV photic damage is at 5000-4480cm ^-1Wavenumber region change.The variation of this wavenumber region is considered to cause (see figure 1) by proteinic structural change.In addition, the influence that " physiological aging " among the application refer to naturally-aged is as the atrophy and the wrinkle of the skin that is not exposed to UV light, and the near-infrared absorption spectrum of skin with physiological aging is at 5990-5490cm ^-1Wavenumber region change.The variation of this wavenumber region is considered to cause (see figure 1) by the variation of collagen, elastin laminin, skin thickness, ceramide etc.

" degree of injury that UV light causes " refers to UV rayed amount or the position difference to skin.Position difference refers to that exposure portion such as forearm Outboard Sections and face surface are exposed to UV light easily, but not exposure portion such as upper limb inside part and torso portion are difficult for being exposed to UV light.

In addition, " physiological aging degree " refers to the naturally-aged degree that UV light exposes does not take place, and refers to age (mice etc.) in week or actual age.

Skin for cover body surface and as with the organ on the border in the external world, form by epidermis, corium and three layers of hypodermis.The variation such as wrinkle of skin, sagging and the elasticity that have very big importance aspect beauty treatment have reflected the epidermis of formation skin or the physiological change of corium.Therefore, learn that the thickness separately of the epidermis that constitutes skin and corium is very useful aspect beauty treatment and cosmetics use." skin thickness " used herein refers to the thickness of epidermis and corium.

The method according to this invention can be used for determining at least a in skin injury degree that UV light causes and the skin physiology aging degree or is used for estimating at least a of epiderm skin thickness and dermis thickness.Skin used herein refers to the skin of animal such as people and mice.

Definite method of the present invention comprises step:

(X1) in skin injury degree that causes by UV light and the skin physiology aging degree at least a known two or more skins at 5990-5490cm ^-1And 5000-4480cm ^-1The measurement wavenumber region in the analysis result of multivariate analysis of near-infrared absorption spectrum of specific wavenumber region, obtain at least a and dependency relation of skin between the near-infrared absorption spectrum of specific wavenumber region in skin injury degree that UV light causes and the skin physiology aging degree;

(X3) determine in skin injury degree that UV light causes and the skin physiology aging degree at least a according to the dependency relation that obtains in the step (X1) by the near-infrared absorption spectrum of the specific wavenumber region that obtains in the step (X2).

Can obtain the near-infrared absorption spectrum of the skin in the step (X1) by any means.For example, can measure near-infrared absorption spectrum by using various types of near-infrared absorption spectrum measuring devices.More specifically, measure near-infrared absorption spectrum with decentralized measuring device that uses diffraction grating or use diode array as the measuring device of detector.In addition, can carry out Fourier transformation to the near-infrared absorption spectrum of the skin measured.

Multivariate analysis in the step (X1) refers to be used for wait the pattern recognition of illustrating relation between the sample (skin injury degree and skin physiology aging degree that the present invention causes for UV light) by calculating similarity according to a large amount of observed values (being the near-infrared absorption spectrum data here).Preferably suitably select the multivariable technique in the step (1) per sample.

Preferred steps (X1) may further comprise the steps (Xa)-(Xd).

(Xa) if desired, in skin injury degree that UV light is caused and the skin physiology aging degree near-infrared absorption spectrum of at least a known two or more skins (the measurement wavenumber region is 5990-5490cm ^-1And 5000-4480cm ^-1) carry out the step of date processing.

(Xb) by the step of near-infrared absorption spectrum or at least one the formation matrix in the spectral value of the wave number of respectively separating of the near-infrared absorption spectrum (hereinafter, will being called " spectrum " jointly) of date processing, UV irradiation dose, UV irradiated site, age (mice etc.) in week and actual age to skin.

(Xc) obtain two steps of suitable main constituent by the matrix that forms in (Xb) being carried out multivariate analysis.

(Xd) in two main constituents obtaining in (Xc) of supposition is that first and another one are second, obtain the relativeness of each sample, obtain the dependency relation of at least a and near-infrared absorption spectrum in skin injury degree that UV light causes and the skin physiology aging degree thus.

Near-infrared absorption spectrum or be 5990-5490cm in the step (Xa) through the wavenumber region of the near-infrared absorption spectrum of date processing ^-1And 5000-4480cm ^-1Think that the near-infrared absorption spectrum of these wavenumber region can accurately catch the variation of protein structure variation and collagen, elastin laminin, skin thickness, ceramide etc., and accurately reflect skin injury degree and the skin physiology aging degree (see figure 1) that UV light causes.Even embodiment described below shows that also the analysis result of the spectrographic multivariate analysis of the near-infrared absorption spectrum of above-mentioned wavenumber region or process date processing and skin injury degree and the skin physiology aging degree that UV light causes have sufficient dependency relation.

The date processing of near-infrared absorption spectrum comprises pre-treatment and conversion in the step (Xa).Pre-treatment comprises automatic conversion (autoscale), average center (mean center), range conversion (range scale), variance conversion (variance scale) etc.Conversion comprises single order differential, higher differentiation (comprising second-order differential), standard normal variable (SNV), polynary scatter correction (MSC), normalization (normalize), smoothing, subtraction, Log10, multiplication, baseline correction etc.

Date processing in the step (Xa) preferably includes second-order differential, more preferably standard normal variable (SNV) and second-order differential, most preferably average center, standard normal variable (SNV) and second-order differential.Because these are handled, proofreaied and correct the variation of individual variation, can abate the noise and the influence of exceptional value, thereby improve the quality of data.

Under any circumstance, all preferably carry out date processing, so that skin injury degree and skin physiology aging degree that two main constituents that obtained by the matrix that makes in the step described below (Xb) and UV light cause show more accurate dependency relation in step (Xc).

The spectral value of the wave number that the infrared absorption spectroscopy that the middle matrix column that forms of step (Xb) is every kind of skin separates.The differential value of the absorbance when absorbance during near-infrared absorption spectrum situation that spectral value refers to not to be transformed and differential smoothing situation.

Although preferably separate spectrum, wave number there is not particular restriction herein, with constant wave number.Usually with 2-16cm ^-1Wave number separate spectrum, preferred 4-8cm ^-1(4 or 8cm ^-1If separating degree (resolution) is 4cm ^-1), more preferably 4cm ^-1In addition, the spectrographic spectral value of the wave number of respectively separating can be set at separately meansigma methods.

The row of the matrix that makes in the step (Xb) be at the carrying out in the step (Xa) at least a in the skin injury that causes of the UV light of two or more skins of spectral measurement (at least a known skins in degree of injury that UV light causes and the physiological aging degree) and the physiological aging degree.Here, in the skin injury degree that causes of UV light and the skin physiology aging degree at least a available skin through being subject to processing degree of treatment and at least a difference of state show.Skin degree of treatment and at least a at least a difference of state all ages of referring to UV irradiation dose, UV irradiated site, live body, actual age etc. through being subject to processing.

That is to say, each spectrum that obtains at least a known two or more skins in skin injury degree that is caused by UV light and the physiological aging degree is by the spectral value of the wave number of respectively separating with about the data of at least one in UV irradiation dose, UV irradiated site, age (mice etc.) in week and the actual age of skin are formed matrix.For example, the matrix of formation as shown in following table 1.Sample number is preferably 20 or more, and more preferably 40 or more.

[table 1]

^*Each value in the table all is the absorbance (or second-order differential value) of near infrared spectrum.

^*The different samples of condition such as the age of data behaviour, mice etc., position and UV irradiation dose.

Algorithm for multivariate analysis in the step (Xc) preferably uses principal component analysis (PCA) method, soft independent modeling (SIMCA) method of analoglike or k-arest neighbors (KNN) method, more preferably principal component analytical method or SIMCA method.Except principal component analytical method, SIMCA method, KNN method etc., multivariate analysis can be used any known method, without any special restriction.

Multivariate analysis is a kind ofly to handle chemical feature such as spectroscopic data is relevant with occurrence such as physical property and analysis concerns process by meterological.

Principal component analytical method is a kind of like this method, during concerning in analyzing concrete sample etc. between the appearance spectrogram of variable such as absorbance and the occurrence in the continuous variation of sample in the factor such as wave number, from the main constituent that causes fluctuation, select as target two compositions of (referring to the damage that physiological aging and UV light cause in this case), analysis is compared in patterns of change in the coordinate that is formed by two main constituent axles and the estimation physical property with respect to the vertical Second principal component, axle of first principal component axle.

SIMCA method and KNN method for except analytic function, also have to unknown sample estimate, the method for classification feature.In recent years, some principal component analytical methods have assessment function.Can use commercial software to carry out statistical disposition such as principal component analytical method or SIMCA method and KNN method.For this class software that is used for statistical disposition, for example, can mention software as " Pirouette " (registered trade mark) that can obtain from GL Sciences Inc., can be from CYBERNET SYSTEMS CO., " MATLAB " (registered trade mark) that LTD. obtains, " the Unscrumbler II " that can obtain from Yokogawa Electric Corporation, " SIMCA " that can obtain from SEPANOVA.

Multivariate analysis shows that uncorrelated each other by two main constituents that matrix obtains, promptly vector is perpendicular to one another.Skin injury degree and skin physiology aging degree that two main constituents and UV light cause have dependency relation.

In addition, obtain ternary words if desired, the faulted condition of diagnosable skin also degree of injury that causes except UV light and the physiological aging degree.The degree of injury that causes except UV light and the example of the skin injury state the physiological aging degree comprise paramophia, the conversion of connective tissue composition etc.

Step (Xd) for at least two main constituents obtaining in the step (Xc) as axle, obtain the step of the relativeness of each sample.

For example, set up the plane scatter diagram of two main constituents as axle, and by the relativeness that obtains each sample corresponding to the position relation of the curve (plot) of each sample.By obtaining the relativeness of each sample, can obtain in skin injury degree that UV light causes and the skin physiology aging degree dependency relation of the near-infrared absorption spectrum of at least one and skin.In addition, the relativeness grouping of at least one each sample that will obtain like this in skin injury degree that can cause according to UV light and the skin physiology aging degree.For example can using, the algorithm of SIMCA method divides into groups.

Specifically, in the analysis result of multivariate analysis, one at least two main constituents that obtain like this (for example, with one in two main constituents is composition A) show the dependency relation of the skin injury degree that causes with UV light, the another one main constituent (for example, with the another one in two main constituents is composition B) show the dependency relation (for example, seeing Fig. 5) with the skin physiology degree of injury.That is to say that the main constituent axle of composition A shows the degree of injury that UV light causes, the main constituent axle of composition B shows the physiological aging degree.By observing damaged skin (promptly not using the light-struck skin of UV) not and with the relativeness of the light-struck skin of UV on the axle of composition A, can obtain degree of injury that UV light causes and the dependency relation between the spectrum.Similarly, by between the skin of observing not damaged skin (being new skin) and physiological aging about the relativeness of the axle of composition B, can obtain the dependency relation between physics aging degree and the spectrum.

In addition, from understand the degree (see figure 1) that each wavenumber region spectral value of variable effect shown in the main constituent axle changes about the spectrographic curve of load of various wavenumber region (loading plot) (utilizing the factor loading discharge curve of multivariate analysis).Therefore, the skin injury degree that causes of UV light and at least one in the skin physiology aging degree can be regarded as concrete chemical change (peak variation).

On the other hand, method of estimation of the present invention comprises step:

(Y1) by at least a known two or more skins in epiderm skin thickness and the dermis thickness at 6850-6620cm ^-1, 6540-5990cm ^-1, 5240-5180cm ^-1, 5030-4980cm ^-1, 4760-4720cm ^-1And 4650-4610cm ^-1, or 6940-6850cm ^-1, 6710-6540cm ^-1, 6250-6170cm ^-1, 5130-5080cm ^-1, 4950-4850cm ^-1, 4760-4690cm ^-1And 4670-4610cm ^-1Measure the analysis result of the multivariate analysis of the near-infrared absorption spectrum of specific wavenumber region in the wavenumber region, obtain in epiderm skin thickness and the dermis thickness at least a and skin in the dependency relation of the near-infrared absorption spectrum of specific wavenumber region;

Can obtain the near-infrared absorption spectrum of skin in the step (Y1) by the mode identical with step (X1) by any suitable method.

In addition, multivariate analysis in the step (Y1) refer to by by with step (X1) same way as according to a large amount of observed values (here, be the near-infrared absorption spectrum data) calculate similarity etc. with the structure of illustrating the model (being estimation model or calibration line here) that concerns between the sample (among the present invention be in epiderm skin thickness and the dermis thickness at least one actual measured value and estimated value) etc.Preferably suitably select the multivariable technique in the step (Y1) per sample.

Preferred steps (Y1) may further comprise the steps (Ya)～(Yd).

(Ya) if desired, (the measurement wavenumber region is 6850-6620cm to the near-infrared absorption spectrum of at least a known two or more skins in epidermal thickness and the dermis thickness ^-1, 6540-5990cm ^-1, 5240-5180cm ^-1, 5030-4980cm ^-1, 4760-4720cm ^-1And 4650-4610cm ^-1, or 6940-6850cm ^-1, 6710-6540cm ^-1, 6250-6170cm ^-1, 5130-5080cm ^-1, 4950-4850cm ^-1, 4760-4690cm ^-1And 4670-4610cm ^-1) carry out the step of date processing.

(Yb) by the step of above-mentioned near-infrared absorption spectrum or at least one the formation matrix in UV irradiation dose, UV irradiated site, age (mice etc.) in week and the actual age of the thickness of the spectral value of the wave number that the above-mentioned spectrum (hereinafter, will being called " spectrum " jointly) of date processing respectively separates and skin (at least a in epidermis and the corium), skin.

(Yc) by the matrix that makes in (Yb) being carried out the step that multivariate analysis obtains skin (at least a in epidermis and the corium) thickness estimation value.

(Yd) actual measured value with at least one known two or more skin in epiderm skin thickness and the dermis thickness is first, the estimated value of skin (in epidermis and the corium at least one) thickness is second, obtain the relativeness (calibration line) of each sample, obtain in epiderm skin thickness and the dermis thickness dependency relation of the near-infrared absorption spectrum of at least one and skin thus.

Near-infrared absorption spectrum or be 6850-6620cm in the step (Ya) through the wavenumber region of the near-infrared absorption spectrum of date processing ^-1, 6540-5990cm ^-1, 5240-5180cm ^-1, 5030-4980cm ^-1, 4760-4720cm ^-1And 4650-4610cm ^-1, or 6940-6850cm ^-1, 6710-6540cm ^-1, 6250-6170cm ^-1, 5130-5080cm ^-1, 4950-4850cm ^-1, 4760-4690cm ^-1And 4670-4610cm ^-1(see figure 2).

Presumably to count the near-infrared absorption spectrum reflection amido link feature in zone be amido link (CONH) or amide (CONH to ground roll ₁) architectural feature, and infer that this feature is relevant with the thickness of skin (at least a in epidermis and the corium).That is to say, under the situation of amido link (CONH), infer above-mentioned wavenumber region show first partials (harmonictone) under the free situation, hydrogen bond first partials, second partials of amide I, NH is flexible and amide II in conjunction with sound, NH is flexible and amide III in conjunction with the partials of sound and amide I and amide III in conjunction with sound.In addition, at amide (CONH ₂) situation under, infer that wavenumber region shows NH ₂First partials of antisymmetric stretching vibration, NH ₂First partials of separately first partials of symmetrical stretching vibration and intramolecular hydrogen bond, intermolecular hydrogen bonding, NH is flexible and second partials of amide II in conjunction with sound, amide I, NH is flexible and amide II in conjunction with sound, NH is flexible and amide III in conjunction with the partials of sound and amide I and amide III in conjunction with sound.This also obtains embodiment (hereinafter describing) and supports, wherein use among the regression analysis result of offset minimum binary (PLS) method at above-mentioned wavenumber region spectrum, the actual measured value of skin (at least a in epidermis and the corium) thickness and the correlation coefficient of estimated value (calibration line) are very big.

Date processing in the step (Ya) comprise with step (Xa) in identical pre-treatment and conversion.In addition, the date processing in the preferred steps (Ya) comprise with step (Xa) in same second-order differential.

Under any circumstance, all preferably carry out date processing so that the estimated value table of skin (at least a in epidermis and the corium) thickness that is obtained by the matrix that makes in the step described below (Yb) reveals the high dependency relation with actual measured value in step (Yc).

In the matrix that in step (Yb), makes, use with (Xb) in the spectral value and skin (at least a in epidermis and the corium) thickness of the wave number of separating of infrared absorption spectroscopy of same every kind of skin.For the epidermis and the dermis thickness of skin, can use the actual measured value of the various skin samples of preparation by the following method.

For example, under the hairless mouse situation, peel off the skin biopsy that skin prepares 5mm * 5mm from the back.Then, with 10% neutral buffered formalin fixedly skin biopsy use the optical microscope measuring skin thickness with preparation HE painted tissue specimen.Fig. 3 has shown the painted image of the HE that peels off skin, and the example of the thickness measurements of epidermis, corium and skin (epidermis and corium).Fig. 3 shows that in not irradiation group of UV, age in week is very little to the influence of epidermis and dermis thickness, and the thickness of UV irradiation group mesocuticle and corium shows the 1-5 different value doubly into not irradiation group of UV.Therefore, think when carrying out the application's method, can preferably use the epidermis and the dermis thickness value that obtain by HE dyeing image etc.

In addition, for example, under people's situation, (for example carry out ultrasonic measurement by whether being exposed to the torso portion (upper arm inboard, back, abdominal part etc.) that UV light promptly covers and the position difference of exposure portion (the forearm outside, face etc.), the supersonic diagnostic appts UX-02 that Rion company makes etc.), can use skin (at least a in epidermis and the corium) one-tenth-value thickness 1/10 that obtains by this ultrasonic image.Fig. 4 has shown ultrasonic image, and upper arm Outboard Sections and the forearm inside part example of the thickness measurements of epidermis and corium separately.From Fig. 4, obtain the dermis thickness variation that various values such as aging cause.According to the application's invention, think and preferably to use the skin thickness value that obtains by ultrasonic image etc.

In the matrix that in step (Yb), makes, can use UV irradiation dose, UV irradiated site, all ages (mice etc.) of live body and at least one in the actual age of two or more skins of having carried out spectral measurement in the step (Ya) (epidermis with corium at least a different skin of thickness).

That is to say, for each spectrum that obtains by at least a two or more different skins of thickness in epidermis and the corium, form matrix by thickness at least a in the spectral value of the wave number of respectively separating and epidermis and the corium and UV irradiation dose, UV irradiated site, all ages (mice etc.) of live body and at least one in the actual age of skin.For example, form the matrix shown in the following table 2.Sample number is preferably 20 or more, and preferred 40 or more.

[table 2]

^*Data relate to the different samples of condition such as age, position and UV irradiation dose of people, mice etc.

Algorithm for multivariate analysis (regression analysis) in the step (Yc) preferably uses offset minimum binary (PLS) method or principal component regression (PCR) analytical method.The reason of doing like this is as follows.The final goal of regression analysis is to make up the estimation model that is used to estimate relevant particular value (being thickness at least a in epiderm skin and the corium here).In this model, use the measured value obtain by spectrophotometer as an illustration variable so that estimate under the situation of continuous particular value, compare with multiple regression analysis (MRA) with the simple linear regression analysis, PLS or PCR are highly beneficial at aspects such as high estimated accuracy and accuracy, exceptional value identification, model optimizations.In addition, by increase skin samples more new database (DB) estimation model can be optimized to model with high estimated accuracy.

Can use commercial software to carry out PLS or PCR regression analysis.The example of this class software comprise " Pirouette " (registered trade mark) that can obtain from GL Sciences Inc., can be from CYBERNET SYSTEMS CO., " MATLAB " (registered trade mark) that LTD. obtains, " the Unscrumbler II " that can obtain from Yokogawa Electric Corporation etc.

Step (Yd) for make up estimation model (calibration line) by the skin thickness estimated value that obtains in the step (Yc) and obtain in epiderm skin thickness and the dermis thickness at least one and skin near-infrared absorption spectrum value between the step of dependency relation.More particularly, by the actual measured value with at least one known two or more skin in epiderm skin thickness and the dermis thickness is first, the estimated value of at least one is second in this epiderm skin thickness and the dermis thickness, obtain the relativeness of each sample, can obtain in epiderm skin thickness and the dermis thickness dependency relation (calibration line) between the near-infrared absorption spectrum of at least one and skin.

For example, if form by at least one actual measured value and the plane scatter diagram formed of two axles of estimated value in epiderm skin thickness and the dermis thickness, the suitable estimated value of at least one, precision, skin samples feature (for example UV irradiation dose, position, all ages or actual age) etc. in position relation that then can be by each sample curve chart (plot) and correlation coefficient supposition epiderm skin thickness and the dermis thickness.

Step (X2) and (Y2) comprise the step of the near-infrared absorption spectrum that obtains following skin: at least one unknown skin in skin injury degree that determined UV light causes and the skin physiology aging degree; Or want at least one unknown skin in estimative epiderm skin thickness and the dermis thickness.

Near-infrared absorption spectrum among preferred steps (X2) and (Y2) is measured identical method or measurement device by near-infrared absorption spectrum with step (X1) and (Y1) and is obtained.In addition, preferably to the near-infrared absorption spectrum that obtains by with step (X1) and (Y1) identical mode carry out date processing.Hereinafter, step (X2) and (Y2) can be called as step (2) jointly.

Step (X3) comprises the step of being determined in skin injury degree that UV light causes and the skin physiology aging degree at least one according to the dependency relation that obtains in the step (X1) by the near-infrared absorption spectrum that obtains in the step (X2).In addition, step (Y3) comprises the step of being estimated in epiderm skin thickness and the dermis thickness at least one according to the dependency relation that obtains in the step (Y1) by the near-infrared absorption spectrum that obtains in the step (Y2).Hereinafter, step (X3) and step (Y3) can be called as step (3) jointly.

Step (3) is represented with following [A] or [B].

[A] adds the spectroscopic data that obtains in the step (X2) in step (X1) and obtains in the matrix of dependency relation, and carry out multivariate analysis by the mode identical with step (X1), determine skin injury degree that the UV light of the skin that will be determined causes and at least one (principal component analytical method) in the skin physiology aging degree whereby.

Perhaps, the spectroscopic data that obtains in the step (X2) is applied on the model that is obtained by the dependency relation that obtains in the step (X1), determines skin injury degree that the UV light of the skin that will be determined causes and at least one (SIMCA or the KNN method) in the skin physiology aging degree whereby.That is to say, use is checked the analysis result of the skin of the analysis result of degree of injury that UV light causes and the known skin of physiological aging degree and degree of injury that UV light causes and the unknown of physiological aging degree about the dependency relation of two main constituent axles, so can determine skin injury degree that the UV light of unknown skin causes and at least one in the physiological aging degree.Can for example have first principal component and Second principal component, as the plane scatter diagram of axle on the expression two main constituent axles relativeness.

[B] is applied to the spectroscopic data that obtains in the step (Y2) on the model that is obtained by the dependency relation that obtains in the step (Y1), and at least one in estimative epiderm skin thickness and the dermis thickness wanted in estimation whereby.The spectroscopic data that obtains in the spectroscopic data (matrix) that will obtain dependency relation in step (Y1) and the step (Y2) combines, and press the mode identical with step (Y1) and carry out regression analysis, at least one in estimative epiderm skin thickness and the dermis thickness wanted in estimation whereby.That is to say, in epiderm skin thickness and dermis thickness at least one known skin estimation model (calibration line), check the analysis result of at least one unknown skin in epiderm skin thickness and the dermis thickness relatively, can estimate the epidermal thickness of unknown skin and at least one in the dermis thickness whereby.In above-mentioned estimation, can show estimated value and estimated accuracy according to the dependency relation in the estimation model.Can use regression analysis software to carry out step (Y3).

In step (X3), the relativeness of composition A (one of two main constituents) that the analysis result of at least one known skin obtains in degree of injury that use is caused by UV light and the physiological aging degree and composition B (two another one in main constituent) axle is checked the analysis result of unknown skin, can estimate degree of injury that the UV light of unknown skin causes and at least one in the physiological aging degree whereby.Can for example have composition A and B as the plane scatter diagram of axle on the relativeness of axle of expression composition A and B.

In addition, in step (Y3), in epiderm skin thickness and dermis thickness, in the estimation model of at least one known skin (calibration line), check the relativeness of the analysis result of unknown skin, estimate the epidermal thickness of unknown skin and at least one in the dermis thickness whereby.In estimation, can show estimated value and estimated accuracy according to the dependency relation in the estimation model.

Can use method of the present invention to estimate skin injury degree and skin physiology aging degree that UV light causes in time.Therefore, determine that the result can be used for determining applying some make up, the necessity of treatment such as medicine, operation or beauty treatment and nursing skin.In addition, evaluation result also can be used for determining treatment and effect of nursing.In addition, determine the result according to these, can select required cosmetics etc. and offer suggestions, for example, when the degree of injury that causes at UV light is high, the cosmetics that are mixed with UV inhibitor and skin lightening agent can be used, when the physiological aging degree is high, the cosmetics that are mixed with wetting agent and anti-aging dose can be used.

Whether in addition, can use method of the present invention to monitor skin in time and change, promptly whether the thickness of epidermis and corium changes, and change increase or minimizing.The necessity of treatments such as in addition, monitoring result can be used for determining applying some make up, medicine, operation, beauty treatment and nursing skin, determine treatment or nursing efficacy or select required cosmetics and offer suggestions etc.For example, compared with the meansigma methods at actual age and position by the thickness of evaluating skin (epidermis and one of corium) when statistically deviation being arranged, the epidermis that supposition is caused by the skin histology dysfunction is loose and occurred by the defective mode that causes such as unusual of extracellular matrix (collagen etc.), so determine that above-mentioned treatment and nursing are essential.In addition, when the thickness of being differentiated skin (one of epidermis and corium) changes in time, determine that treatment and nursing produce effect to it.

In addition, before applied cosmetics, compare skin (one of epidermis and corium) thickness with the back, can use the effect of variation as index evaluation cosmetics and beauty treatment with the back or before improving looks.For example, little in dermis thickness, and dermis thickness is owing to using the cosmetics be mixed with collagen synthesis promoter, collagenous fiber bundle rebuild agent etc. to increase, can estimate cosmetics and beauty treatment and have wrinkle and eliminate effect.In addition, big and utilize and be mixed with that turnover adjusts that the cosmetics of agent etc. have suppressed that epidermis increases and epidermal thickness when reducing at epidermal thickness, can estimate cosmetics and have epidermis hypertrophy inhibitory action.

Method of the present invention does not have treatment or diagnosis people's purpose, and does not comprise the medical science behavior.

Hereinafter, will utilize embodiment to wait and describe the present invention in detail.It should be noted that embodiment etc. does not limit the scope of the invention.

Embodiment

The preparation of＜animal skin sample 〉

Use hairless mouse to be used for the set of animal skin sample, and set UV irradiation group and not irradiation group of UV, preparation has the sample set of various skin conditions and skin thickness whereby.For not irradiation group of UV, 30 mices altogether are set, wherein (hereinafter at 6 all age groups, it can be represented as CT6W or UV and not shine the #6W group), 10 all age groups (hereinafter, it can be represented as CT10W or UV and not shine the #10W group), 14 all age groups (hereinafter, it can be represented as CT14W or UV and not shine the #14W group), 16 all age groups (hereinafter, it can be represented as CT16W or UV and not shine the #16W group) and 27 all age groups (hereinafter, its can be represented as CT27W or UV do not shine #27W and organize) in each in all comprise 6 mices.In addition, for UV irradiation group, 24 mices altogether are set, wherein (hereinafter at 8 all age groups, it can be represented as UV8W or UV irradiation #8W group), 10 all age groups (hereinafter, it can be represented as UV10W or UV irradiation #10W group), all comprise 6 mices in 14 all age groups (hereinafter, it can be represented as UV14W or UV irradiation #14W group) and the 16 all age groups (hereinafter, its can be represented as UV16W or UV irradiation #16W organizes) each.

＜UV illuminate condition 〉

About the UV irradiation, after hairless mouse reached for 6 ages in week, give each 0.1 dosage (J/cm to every hairless mouse ²), Ci energy exposure on every Wendesdays.Therefore, 10 all age groups of UV irradiation group are meant mice and reach the skin that carries out 4 all UV irradiations after 6 ages in week that accumulative total is subjected to 1.2 dosage (J/cm 12 times during 4 weeks ²) the UV rayed.

The preparation of＜application on human skin sample 〉

Do not having more than 20 year old of the arm dermatosis-60 female subject (15 of each generations) over fifty years old in setting comprise and three parts of forearm Outboard Sections, forearm inside part and upper arm inside part this three part left standstill after washing 20 minutes.This condition is determined in set to the application on human skin sample.

The measurement of the near-infrared absorption spectrum of＜skin samples 〉

The near-infrared absorption spectrum of the skin samples that under certain environment, prepares by skin samples 20 ℃ of measurements.Here, consider to handle the probability that changes with skin site, measure the near-infrared absorption spectrum at the position of selecting at random, three places.Use Fourier transform near infrared spectrometer VECTOR 22/N (Bruker Optics manufacturing) to measure near-infrared absorption spectrum.For measuring condition, use the scattered reflection method of utilizing fiber probe, separating degree is 8cm ^-1, the measurement wave number is 8000-4000cm ^-1

＜embodiment 1 〉

In the near-infrared absorption spectrum of the skin samples set that obtains by hairless mouse skin, to 5990-5490cm ^-1And 5000-4480cm ^-1Wavenumber region carry out date processing.Specifically, average center and standard normal variable (SNV), carry out second dervative (secondderivation) then.

Will be through the every 4cm of the spectrum of date processing ^-1Separately, calculate the spectrographic spectral value (the second-order differential value of absorbance) that respectively separates.By the second-order differential value of the spectral value of each wave number of calculating and skin treatment content (the UV irradiation have/do not have and irradiation dose difference and all ages difference) form matrix.The matrix that forms is carried out principal component analysis.By the analysis result that obtains, form the plane scatter diagram, suppose Second principal component, as first and the 3rd main constituent as second (two compositions of the damage that aging of option table open-birth reason and UV light cause, and be set at first and second respectively).Use multivariate analysis software (Pirouette (registered trade mark) 3.11 editions; GL Sciences Inc.) carries out date processing and principal component analysis.

Fig. 5 has shown the plane scatter diagram of the analysis result generation that is obtained by multivariate analysis.As shown in Figure 5, recognize can according to the difference of the having/does not have of UV irradiation, irradiation dose and all ages difference most clearly the result is classified.Specifically, recognize towards the left of first (transverse axis) higher to the skin physiology aging degree.In addition, recognize that the skin injury degree that causes towards second (longitudinal axis) below UV light is higher.Recognize that towards the lower left skin injury degree and skin physiology aging degree that UV light causes are all higher.Therefore, recognize that skin injury degree that UV light causes and skin physiology aging degree have clear and definite dependency relation with the analysis result of skin near-infrared absorption spectrum multivariate analysis independently.

＜embodiment 2 〉

In embodiment 1, increase the near-infrared absorption spectrum of the hairless mouse skin sample of skin injury degree that UV light causes and the unknown of skin physiology aging degree, and carry out date processing by the process identical and form matrix with embodiment 1, carry out principal component analysis whereby.Fig. 6 scatter diagram that the result that obtains forms of serving as reasons.As shown in Figure 6, each sample sets classification that clearly will have the different disposal content, and the result's of the skin samples of the degree of injury that is caused by UV light and the unknown of physiological aging degree curve chart position determines that this skin is equivalent to UV non-irradiated 27 all age groups most.

＜embodiment 3 〉

By with embodiment 1 in identical mode above-mentioned application on human skin sample set is measured and is analyzed.The analysis result that is obtained by multivariate analysis forms the plane scatter diagram, suppose first principal component as first and Second principal component, as second.The plane scatter diagram that forms is presented in Fig. 7 and 8.In Fig. 7, obtain 95% density ellipse, the 95% density ellipse of in Fig. 8, by age being classified by the position classification.As shown in Fig. 7 or 8, recognize according to arm position or age and most clearly the result is classified.Specifically, to higher, the degree of injury that UV light causes is higher towards Second principal component, axle (longitudinal axis) below towards first principal component axle (transverse axis) left for the physiological aging degree.Therefore, recognize from Fig. 7 that the degree of injury that UV light causes is high in exposing more forearm Outboard Sections, the degree of injury that UV light causes is low in exposing less upper arm inside part.In addition, recognize from Fig. 8 that classification direction left moves, the physiological aging degree was carried out from 20 years old to 50 years old.Therefore, can separately determine application on human skin degree of injury and the physiological aging degree that UV light causes.

＜comparative example 1 〉

By among the embodiment 1 at 8000-4000cm ^-1Wavenumber region is carried out the scatter diagram that result that date processing and principal component analysis obtain forms and is presented among Fig. 9.As shown in Figure 9, recognize that the skin of hairless mouse can not wait and classify according to the having/does not have of UV irradiation, irradiation dose difference, all ages difference, be difficult to distinguish the degree of injury that physiological aging degree and UV light cause in this wavenumber region.

＜comparative example 2 〉

By among the embodiment 1 at 8000-6000cm ^-1And 5490-5000cm ^-1Wavenumber region is carried out the scatter diagram that result that date processing and principal component analysis obtain forms and is presented at (8000-6000cm among Figure 10 ^-1And 5490-5000cm ^-1Wavenumber region) and Figure 11 (4480-4000cm ^-1Wavenumber region).As shown in Figure 10 and 11, recognize that the skin of hairless mouse can not wait and classify according to the having/does not have of UV irradiation, irradiation dose difference, all ages difference, be difficult to distinguish the degree of injury that physiological aging degree and UV light cause in this wavenumber region.

＜comparative example 3 〉

By among the embodiment 3 at 8000-4000cm ^-1Wavenumber region is carried out the scatter diagram that result that date processing and principal component analysis obtain forms and is presented among Figure 12.As shown in Figure 12, recognize that application on human skin can not classify according to the age, in this wavenumber region, be difficult to distinguish the degree of injury that physiological aging degree and UV light cause.

＜comparative example 4 〉

By among the embodiment 3 at 8000-6000cm ^-1And 4480-4000cm ^-1Wavenumber region is carried out the scatter diagram that result that date processing and principal component analysis obtain forms and is presented at (8000-6000cm among Figure 13 ^-1Wavenumber region), (4480-4000cm among Figure 14 ^-1Wavenumber region), (8000-6000cm among Figure 15 ^-1Wavenumber region) and Figure 16 in (4480-4000cm ^-1Wavenumber region).As shown in Figure 13-16, recognize that application on human skin can not classify according to age and position, be difficult to distinguish the degree of injury that physiological aging degree and UV light cause in this wavenumber region.

＜embodiment 4 〉

In the near-infrared absorption spectrum of the skin samples set that obtains by hairless mouse skin, to the wavenumber region 6850-6620cm of amido link (CONH) ^-1, 6540-5990cm ^-1, 5240-5180cm ^-1, 5030-4980cm ^-1, 4760-4720cm ^-1And 4650-4610cm ^-1Carry out date processing.Specifically, average center and standard normal variable (SNV), carry out second-order differential then.

Will be through the every 4cm of the spectrum of date processing ^-1Separately, calculate the spectrographic spectral value (the second-order differential value of absorbance) that respectively separates.With the spectral value that calculates and skin (in epidermis and the corium at least one) thickness as row and skin treatment content (the having/does not have of UV irradiation, irradiation dose difference and age in week difference) as going the formation matrix.Use PLS that the matrix that forms is carried out regression analysis.Be presented among Figure 17-19 as the epiderm skin thickness of the analysis result that obtains and the estimation model of dermis thickness (calibration line, correlation coefficient).From Figure 17-19, recognize, in hairless mouse, can estimate epiderm skin thickness and dermis thickness accurately.Use multivariate analysis software (Pirouette (registered trade mark) 3.11 editions; GL Sciences Inc.) carries out date processing and PLS.

＜embodiment 5 〉

Use the Figure 17-19 that obtains among the embodiment 4, each thickness (seeing Table 3) of the 14 all age groups of estimation UV irradiation and hairless mouse skin (epidermis and corium), epidermis and the corium of the non-irradiated 14 all age groups of UV.Recognize that from table 1 high accuracy of the relative standard deviation with about 10% has been estimated each thickness.

[table 3]

The estimation of mouse skin thickness	UV irradiation group is average ± SD (μ m)	Not irradiation group of UV is average ± SD (μ m)
The estimation of mouse skin thickness	UV irradiation group is average ± SD (μ m)	Not irradiation group of UV is average ± SD (μ m)	Epidermis	58.9±10.4	18.0±5.8
Corium	222.9±27.7	131.4±13.4	Epidermis	58.9±10.4	18.0±5.8
Corium	222.9±27.7	131.4±13.4	Skin	281.8±34.8	149.3±13.1

＜embodiment 6 〉

Replace the hairless mouse skin among the embodiment 4 to carry out the PLS regression analysis by the female subject skin that shows in the personnel selection skin samples by identical process.Be presented among Figure 20-22 as the epiderm skin thickness of the analysis result that obtains and the estimation model of dermis thickness (calibration line and correlation coefficient).From Figure 20-22, recognize, even in the people, also can estimate epiderm skin thickness and dermis thickness accurately.

＜embodiment 7 〉

Use the Figure 20-22 that obtains among the embodiment 6, estimate each thickness (seeing Table 4) of more than 40 year old female subject upper arm medial part skin (epidermis and corium), epidermis and corium.From table 4, recognize, can estimate relative standard deviation (coefficient of variation) with about 10% high accuracy.

[table 4]

The estimation of application on human skin thickness	Women's upper arm medial part is average ± SD (μ m)
The estimation of application on human skin thickness	Women's upper arm medial part is average ± SD (μ m)	Epidermis	157.6±23.4
Corium	743.7±71.9	Epidermis	157.6±23.4
Corium	743.7±71.9	Skin	901.3±80.7

＜embodiment 8 〉

Use is by being used as amide (CONH ₂) 6940-6850cm of architectural feature ^-1, 6710-6540cm ^-1, 6250-6170cm ^-1, 5130-5080cm ^-1, 4950-4850cm ^-1, 4760-4690cm ^-1And 4670-4610cm ^-1The wavenumber region that replaces near-infrared absorption spectrum among the embodiment 4 and 6 is carried out each thickness (seeing Table 5) that estimation model (calibration line) that the PLS regression analysis obtains is estimated skin (epidermis and corium), epidermis and the corium of more than 40 year old female subject upper arm inside part by identical process.From table 5, recognize, can estimate relative standard deviation (coefficient of variation) with about 15% high accuracy.

[table 5]

The estimation of application on human skin thickness	Women's upper arm inside part is average ± SD (μ m)
The estimation of application on human skin thickness	Women's upper arm inside part is average ± SD (μ m)	Epidermis	157.6±25.3
Corium	743.7±97.7	Epidermis	157.6±25.3
Corium	743.7±97.7	Skin	901.3±98.2

＜comparative example 5 〉

Use is by using 8000-4000cm ^-1The wavenumber region that replaces near-infrared absorption spectrum among the embodiment 4 and 6 is carried out each thickness that estimation model (calibration line) that the PLS regression analysis obtains is estimated skin (epidermis and corium), epidermis and the corium of more than 40 year old female subject upper arm inside part by identical process.Recognize that relative standard deviation (coefficient of variation) is 20-30% or bigger, and can not as application of the present invention, estimate each thickness effectively aspect skin (epidermis and corium), each thickness measure of epidermis and corium.

＜comparative example 6 〉

With methyl key (CH ₃) wavenumber region 7380-7330cm ^-1, 5850-5780cm ^-1, 5650-5600cm ^-1And 4400-4380cm ^-1Replace the wavenumber region of amido link (CONH) among the embodiment 4 to carry out the PLS regression analysis by identical process.The estimation model (calibration line) of each thickness of the epidermis that obtains, corium and skin (epidermis and corium) is presented among Figure 23-25.Recognize that from Figure 23-25 correlation coefficient of estimation model is 0.71-0.74, can not the same each thickness of estimating epidermis, corium and skin (epidermis and corium) accurately with the wavenumber region situation of amido link in the hairless mouse (CONH).Use Figure 23-25, each thickness (seeing Table 6) of skin (epidermis and corium), epidermis and the corium of hairless mouse in 14 all age groups of estimation UV irradiation and the UV non-irradiated 14 all age groups.Recognize that from table 6 relative standard deviation (coefficient of variation) improves about 20-30%, can not equally with the application's invention estimate each thickness of skin (epidermis and corium), epidermis and corium effectively.

[table 6]

The estimation of mouse skin thickness	UV irradiation group is average ± SD (μ m)	Not irradiation group of UV is average ± SD (μ m)
The estimation of mouse skin thickness	UV irradiation group is average ± SD (μ m)	Not irradiation group of UV is average ± SD (μ m)	Epidermis	58.9±12.7	18.0±6.7
Corium	222.9±35.4	131.4±21.8	Epidermis	58.9±12.7	18.0±6.7
Corium	222.9±35.4	131.4±21.8	Skin	281.8±49.6	149.3±30.9

＜comparative example 7 〉

With methyl key (CH ₃) wavenumber region 7380-7330cm ^-1, 5850-5780cm ^-1, 5650-5600cm ^-1And 4400-4380cm ^-1Replace the wavenumber region of amido link (CONH) among the embodiment 6 to carry out the PLS regression analysis by identical process.The estimation model (calibration line) of each thickness of the epidermis that obtains, corium and skin (epidermis and corium) is presented among Figure 26-28.Recognize that from Figure 26-28 correlation coefficient of estimation model is 0.68-0.73, can not the same each thickness of estimating epidermis, corium and skin (epidermis and corium) accurately with the wavenumber region situation of philtrum amido link (CONH).Use Figure 26-28, estimate each thickness (seeing Table 7) of skin (epidermis and corium), epidermis and the corium of more than 40 year old female subject upper arm inside part.Recognize that from table 7 it is about 20% that relative standard deviation (coefficient of variation) improves, can not equally with the application's invention estimate each thickness of skin (epidermis and corium), epidermis and corium effectively.

[table 7]

The estimation of application on human skin thickness	Women's upper arm medial part is average ± SD (μ m)
The estimation of application on human skin thickness	Women's upper arm medial part is average ± SD (μ m)	Epidermis	157.6±25.9
Corium	743.7±151.5	Epidermis	157.6±25.9
Corium	743.7±151.5	Skin	901.3±177.3

The application requires the rights and interests of the 2005-279292 of the Japanese patent application 2005-254324 of JIUYUE in 2005 submission on the 2nd, the 2005-254326 of JIUYUE in 2005 submission on the 2nd, JIUYUE in 2005 submission on the 27th, and this paper introduces them as a reference in full.

Industrial applicability

According to the present invention, can non-infringement and estimate quantitatively at least a in people that UV light causes and mouse skin degree of injury and the skin physiology aging degree. In addition, according to the present invention, can non-infringement and estimate quantitatively at least a in epiderm skin thickness and the dermis thickness. Determine and evaluation result by using, can monitor in time at least a in skin injury degree that UV light causes and at least one and epiderm skin thickness and the dermis thickness in the skin physiology aging degree. Therefore, at department store, shop or consumer's family, the ordinary people can be easily and suggestion and the consulting of enjoying fully cosmetic evaluation for skin, skin evaluation and selecting and estimating about cosmetics.

Claims

1. determine skin injury degree that UV light causes and at least a method in the skin physiology aging degree by the near-infrared absorption spectrum of skin, comprise step:

(X1) in skin injury degree that causes by UV light and the skin physiology aging degree at least a known two or more skins at 5990-5490cm ^-1And 5000-4480cm ^-1The measurement wavenumber region in the analysis result of multivariate analysis of near-infrared absorption spectrum of specific wavenumber region, obtain in skin injury degree that UV light causes and the skin physiology aging degree at least a and skin in the dependency relation of the near-infrared absorption spectrum of specific wavenumber region;

2. the described method of claim 1 is wherein determined skin injury degree and the skin physiology aging degree that UV light causes simultaneously.

3. claim 1 or 2 described methods, wherein multivariate analysis is principal component analysis (PCA) method, SIMCA method or KNN method.

4. estimate at least a method in epiderm skin thickness and the dermis thickness by the near-infrared absorption spectrum of skin, comprise step:

5. the described method of claim 4 is wherein estimated epiderm skin thickness and dermis thickness simultaneously.

6. claim 4 or 5 described methods, wherein multivariate analysis is offset minimum binary (PLS) method or principal component regression (PCR) analytical method.

7. select the method for cosmetics, comprise the step of using the method selection cosmetics of any one among the claim 1-6.

8. the method for monitoring skin condition comprises and uses the method for any one among the claim 1-6 to catch skin over time step in chronological order.

9. the described monitoring method of claim 8 comprises the step of confirmation to the skin treating effect.

10. estimate the method for cosmetics, comprise that the method for any one is also used the step that changes as the index evaluation cosmetics with back skin condition or thickness before comparing applied cosmetics among the use claim 1-6.

11. the method for the described evaluation cosmetics of claim 10, comprise estimate cosmetics in skin thickness dermis thickness owing to have the step of wrinkle elimination function under the situation that applied cosmetics increases.