WO2018193565A1 - Procédé d'évaluation de l'impact d'une substance ou d'un produit d'essai sur la peau - Google Patents

Procédé d'évaluation de l'impact d'une substance ou d'un produit d'essai sur la peau Download PDF

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Publication number
WO2018193565A1
WO2018193565A1 PCT/JP2017/015796 JP2017015796W WO2018193565A1 WO 2018193565 A1 WO2018193565 A1 WO 2018193565A1 JP 2017015796 W JP2017015796 W JP 2017015796W WO 2018193565 A1 WO2018193565 A1 WO 2018193565A1
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Prior art keywords
skin
article
test substance
moisture
contact
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PCT/JP2017/015796
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English (en)
Japanese (ja)
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千絵 布施
尚子 森崎
恭子 志摩
俊希 市橋
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花王株式会社
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Priority to JP2017547588A priority Critical patent/JP6326557B1/ja
Priority to PCT/JP2017/015796 priority patent/WO2018193565A1/fr
Publication of WO2018193565A1 publication Critical patent/WO2018193565A1/fr

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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/65—Raman scattering
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/15—Medicinal preparations ; Physical properties thereof, e.g. dissolubility
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing

Definitions

  • the present invention relates to a method for evaluating the influence of a test substance or article on skin.
  • Skin has the function of preventing the loss of moisture and biological components from the inside of the body and the entry of foreign substances from the outside. Such a function is generally called a “skin barrier function”.
  • the barrier function of the skin is mainly borne by the stratum corneum present in the outermost layer of the skin.
  • the water content of the stratum corneum is about 20% to 30% on the skin surface.
  • the water content gradually increases as it goes in the depth direction, and the water content reaches about 70% in the epidermis.
  • stratum corneum is a part that is touched by human eyes, when a foreign substance such as a chemical substance enters the skin, skin troubles such as inflammation are recognized at a glance.
  • skin troubles may occur when the skin is covered or brought into contact with absorbent articles such as diapers and sanitary products, wound protection materials, masks, rubber gloves and the like.
  • absorbent articles such as diapers and sanitary products, wound protection materials, masks, rubber gloves and the like.
  • many women suffer from skin problems such as itching and rash during use of sanitary products. Baby diaper rash is also frequently observed.
  • the permeability of a substance to the stratum corneum is one of the very important factors in the medical field and the beauty field.
  • Non-Patent Document 1 a method of applying methyl nicotinate to the skin and evaluating it as a method for evaluating the barrier function of the skin is widely used (for example, see Non-Patent Documents 1 to 3). In this method, the barrier function of the skin is evaluated based on erythema induced by the vasodilatory action of methyl nicotinate.
  • erythema is also affected by factors other than skin function, such as blood flow, outside air temperature, increased body temperature, decreased body temperature, body movement, sweating, and subject skin color. Therefore, in the above-described method, the evaluation result of the barrier function may be influenced by various factors (excluding the controlled environment and situation). Moreover, since methyl nicotinate has a vasodilatory effect, it may be a burden itself to apply methyl nicotinate to the skin of a subject.
  • a test substance or article is brought into contact with human skin, and the amount of change in the moisture content or distribution of the skin before and after contact is compared with a reference value.
  • a method for evaluating a test substance or article for evaluating an influence on a function The water content or distribution of the skin, measured by the water load test on the skin with different water loads, is related to the skin barrier function, and the skin water content or water distribution and the skin barrier function Therefore, the present invention relates to a method for evaluating a test substance or article, in which the moisture content or moisture distribution of the skin when a change in the barrier function of the skin is confirmed is set as the reference value.
  • the present invention also provides a test substance by measuring the amount of water for each depth of human skin after contacting the test substance or article with human skin, and obtaining the moisture distribution after contact with the test substance or article.
  • a test substance or article evaluation method for evaluating the influence of a test substance or article on the barrier function of human skin by comparing the moisture distribution after contact of the article with a reference moisture distribution, Before applying water or aqueous solution to human skin, measure the amount of water at each depth of human skin to obtain the initial moisture distribution, and immediately after loading water or aqueous solution to human skin, Obtain water distribution after loading water or aqueous solution by measuring the amount of water at each skin depth, apply the indicator substance to the skin, measure the permeability of the indicator substance, and determine the water or aqueous solution from the initial moisture distribution.
  • the present invention relates to a test substance or article evaluation method in which the moisture distribution after loading with water or an aqueous solution at each depth is used as the reference moisture distribution.
  • the present invention is a method for evaluating the effect of a test substance or article on the barrier function of human skin, Obtain the moisture distribution by measuring the amount of moisture at each skin depth before and after contact of the test substance or article with human skin, and the initial angle before contact in the moisture distribution before and after contact.
  • the present invention relates to a test substance or article evaluation method for evaluating the influence of a test substance or article on the barrier function of human skin using as an index the difference in moisture content deeper than the layer thickness.
  • FIG. 2 (a) is a graph showing the moisture distribution when the moisture load on the skin is 0 mL / cm 2
  • FIG. 2 (b) shows that the moisture load on the skin is 0.02 mL / cm 2
  • 2 (c) is a graph showing the moisture distribution when the moisture load on the skin is 0.04 mL / cm 2
  • FIG. 2 (d) shows the moisture distribution on the skin. It is a graph which shows a moisture distribution in case water load amount of is 0.20 mL / cm ⁇ 2 >. It is a graph which shows the moisture distribution in the skin of the depth direction measured using the confocal Raman spectroscopic microscope before and behind sticking of two types of absorbent articles.
  • the present invention provides a test substance or article evaluation method that evaluates the influence of a test substance or article on the skin barrier function in a non-invasive manner, with less burden on the subject, safe, simple, and in a short time.
  • the swelling state (hydration state) of the stratum corneum located on the outermost layer of the skin affects the barrier function of the skin, and the permeability of the substance to the skin changes accordingly. Therefore, if it is possible to grasp the hydration state of the stratum corneum caused by the test substance or article coming into contact with the skin, the test substance or article has less burden on the subject as to how the test substance or article affects the barrier function of the skin, It is expected to be evaluated without being affected by various factors. However, it has not been elucidated in detail about the relationship between the change in substance permeability to the skin and the increase / decrease of the moisture content of the skin and the moisture distribution in the depth direction of the skin.
  • the present inventors examined the relationship between the permeability of a substance in living human skin and the moisture content of the stratum corneum located on the outermost surface of the skin and the moisture distribution in the depth direction. As a result, we found for the first time in living humans that there is a high correlation between the moisture content of the stratum corneum and the moisture distribution in the depth direction and the permeability of substances to the skin. Then, the test substance or article becomes a skin barrier from the change in the skin moisture content or the moisture distribution in the depth direction in a living human measured non-invasively before and after the test substance or article is brought into contact with the human skin. It was found that the effect on the function can be evaluated. The present invention has been completed based on these findings.
  • the skin barrier function is evaluated from the moisture content and moisture distribution of the skin before and after contact with the test substance or article based on the relationship between the moisture content and moisture distribution of the skin and the barrier function of the skin. Therefore, according to the present invention, the influence of the test substance or article on the skin can be known safely, simply and in a short time.
  • the test substance or article is brought into contact with human skin (S1), the amount of change in the moisture content or moisture distribution of the skin measured before and after contact with the test substance or article, Compare the moisture distribution of the skin with the reference value or reference moisture distribution (S2), and evaluate the effect of the test substance or article on the skin barrier function from the comparison result with the reference value or reference moisture distribution (S3) .
  • analysis and evaluation of the influence on the skin barrier function are performed based on the relationship between the amount of moisture in the skin or the distribution of moisture distribution and the barrier function of the skin.
  • carrier function refers to the permeability of a substance from the outside to the inside of the skin.
  • the “test substance” means a substance (for example, a compound, a chemical substance, a pigment, a secretion or excrement derived from a living body, a moisturizing agent, or the like that penetrates into the skin by contact with the skin or application to the skin. External preparations, cosmetics).
  • the “test substance” and the “indicator substance” described later include water-soluble components and hydrophobic components.
  • substances include water or water vapor, physiological saline, phosphate buffered saline, methyl nicotinate, hexyl nicotinate, lactic acid, yellow No. 4 (tartrazine), red No. 215 (rhodamine B stearate), cafe In, ubinal, carotenoids, retinol, urine, sweat, menstrual blood, feces, simulated urine, simulated menstrual blood, simulated feces, and active ingredients contained in skin moisturizers, topical skin preparations, skin cosmetics or steam heating devices Medicinal ingredients are listed.
  • the skin moisture content or moisture distribution at the site where the barrier function is evaluated is measured.
  • the measurement of the skin moisture content or moisture distribution is preferably performed noninvasively. In this case, the burden on the subject is small, and the skin barrier function can be safely evaluated.
  • the method for noninvasively measuring the moisture content or moisture distribution in the stratum corneum can be appropriately selected from conventional methods. Examples thereof include a method using Raman spectroscopy, skin capacitance measurement means, high-frequency current measurement means, infrared spectroscopy, or near infrared spectroscopy.
  • an apparatus capable of measuring skin moisture content or moisture distribution in accordance with Raman spectroscopy, skin capacitance measuring means, etc., when the test substance or article is loaded on the skin. Use to measure. Then, the influence of the substance or article on the skin barrier function is evaluated from the amount of change. As shown in Examples described later, when excessive moisture is applied to human skin, the substance permeability is enhanced and the skin barrier function is lowered. In response to such findings, the present inventors evaluated the skin barrier function based on the skin moisture content or the change in the moisture distribution when the test substance or article is loaded on the skin or the reference moisture distribution. I found what I could do for the first time.
  • the substance permeability does not increase until the skin moisture content reaches a certain value. However, when the moisture content of the skin increases above a certain value, the substance permeability increases.
  • the permeability of methyl nicotinate which is a water-soluble substance, was evaluated as a representative example of the indicator substance. A water-soluble substance is likely to be distributed into the skin as the amount of moisture in the skin increases, and may penetrate into the skin.
  • the reference value and the reference moisture distribution for evaluating the influence of the test substance or article on the skin barrier function can be set as appropriate.
  • the setting method of the reference value and the reference moisture distribution in the present invention will be described based on specific examples.
  • the present invention is not limited to this.
  • the water load test is performed on the skin by changing the water load, and the moisture content or moisture distribution of the skin at each water load is measured by a conventional method.
  • the measured moisture content or moisture distribution of the skin is associated with the barrier function of the skin.
  • the association between the moisture content or moisture distribution of the skin and the barrier function of the skin is defined as “the reference value of the moisture content or moisture distribution of the skin when a change is confirmed in the skin barrier function. ”Is set.
  • the method for setting the “reference value” include a method for setting from the permeability of the indicator substance from the outside to the inside of the skin. Following the water load test on the skin described above, the load test of the index substance to the skin was conducted to measure the permeability of the index substance by a conventional method, and the moisture of the skin when the change in the permeability of the index substance was observed The amount or moisture distribution can be a “reference value”. In this embodiment, when a change is confirmed in relation between the amount of moisture loaded and the permeability of the indicator substance, or when the permeability of the indicator substance reaches a certain state, can do.
  • the association between the moisture content or moisture distribution of the skin and the barrier function of the skin is the human when the association between the permeability of the indicator substance and the load of water or aqueous solution is changed.
  • the water distribution after loading with water or an aqueous solution at each skin depth is set as the “reference water distribution”.
  • the amount of water at each depth of the human skin is measured to obtain an initial moisture distribution.
  • water or an aqueous solution is loaded onto the human skin for a certain period of time, and immediately after the end of the loading, the moisture content at each depth of the human skin is measured to obtain the moisture distribution after loading with the water or aqueous solution.
  • the indicator substance is applied to the skin and the penetration degree of the indicator substance is measured. Then, the measurement is repeated while increasing or decreasing the load of water or aqueous solution until the relationship between the permeability of the indicator substance and the load of water or aqueous solution changes. Based on the measurement results, the water distribution after loading of water or aqueous solution at each depth of human skin when the relationship between the permeability of the indicator substance and the load of water or aqueous solution changes is determined as the reference water content. It can be a distribution.
  • the indicator substance for evaluating the permeability to the skin can be appropriately selected.
  • the moisture content deeper than the initial stratum corneum thickness is associated with the skin barrier function.
  • the moisture distribution is obtained by measuring the amount of moisture at each skin depth before and after the test substance or article is brought into contact with human skin. Then, the moisture distribution before and after contact is compared, and the test substance or article is evaluated using as an index the difference in moisture content deeper than the initial stratum corneum thickness before contact.
  • the amount of moisture or the moisture distribution in any region or part from the stratum corneum surface layer to the granular layer may be measured.
  • the characteristics of the moisture content or moisture distribution measuring device used in the present invention for example, the intensity of Raman scattering due to the excitation wavelength applied to the inside of the skin, the moisture content or moisture in the region from the skin surface to a predetermined depth You may measure distribution or the moisture content of the site
  • the “initial stratum corneum thickness” refers to the thickness of the stratum corneum before moisture, a test substance or an article is loaded.
  • the initial stratum corneum thickness from the Raman spectrum can be measured according to the method described in IFSCC Magazine, 2009, vol. 12 (1), p. 9-15. Calculate the moisture content at each depth from the Raman spectrum measured according to the usual method, and create a graph plotting the numerical value of the moisture content approximately calculated for each fixed distance (eg 1 ⁇ m) in the depth direction. Get distribution profile. Then, the obtained moisture profile is approximated by two straight lines, and the depth to the intersection can be defined as the stratum corneum thickness from the stratum corneum surface layer.
  • the signal intensity derived from the CH stretching vibration of the protein shows a maximum value on the skin side slightly from the boundary between the window material of the objective lens and the skin, and then goes deeper. Signal strength decreases. This is because, in the skin, the signal is attenuated by the diffusion of light as it goes deeper. Since there is no signal derived from protein CH stretching vibration in the window material, the signal intensity derived from CH stretching vibration is 0 when the focal point of the laser is within the window material. On the other hand, when the signal intensity derived from the CH stretching vibration when the laser is focused in the skin is 100, the signal intensity derived from the CH stretching vibration is 50 when the focus comes to the interface between the window material and the skin.
  • the point where the signal intensity derived from the CH stretching vibration shows the maximum half value is defined as the boundary between the skin and the window material.
  • the window material may be detected even though the signal intensity derived from the CH stretching vibration is weak. Therefore, when the moisture content is calculated and analyzed according to the method described in JP2012-50739A, the moisture content will be high, and the interface between the skin and the window material, that is, the moisture content on the outermost surface of the skin is not appropriate. It is theoretically clear that there is no data. Further, the spatial resolution in the depth direction of the confocal Raman spectroscopic device used in this condition is 2 ⁇ m, and the water amount for each 1 ⁇ m is interpolated and calculated in the analysis.
  • the data analysis when determining the moisture content on the skin surface, the data from the actual skin surface to at least 5 ⁇ m is omitted, and the skin surface is not less than 5 ⁇ m.
  • the part of the skin is the “skin surface” in the data analysis, the data of at least 2 ⁇ m from the actual skin surface is omitted, and the part of 2 ⁇ m or more from the skin surface is the “skin surface” in the data analysis More preferably, it is more preferable to omit the data from the actual skin surface to 2 ⁇ m, and to set the portion of 2 ⁇ m from the skin surface as the “skin surface” in the data analysis.
  • a method for approximately calculating the amount of water from a Raman spectrum obtained by measurement using a confocal Raman spectroscopic microscope can be performed with reference to the method described in JP 2012-50739 A.
  • the initial stratum corneum thickness measured by Raman spectroscopy is usually about 10 ⁇ m to 20 ⁇ m and an average of about 13 ⁇ m. Therefore, in the present invention, the moisture content of the skin is from 2 to 40 ⁇ m deep from the actual skin surface, preferably from 2 to 35 ⁇ m deep from the skin surface, more preferably from the skin surface. It is preferable to measure and analyze up to a depth of 2 to 20 ⁇ m, more preferably a depth of 9 to 15 ⁇ m from the skin surface, more preferably a depth of about 13 ⁇ m from the skin surface.
  • the skin moisture amount or moisture distribution measured by Raman spectroscopy, skin capacitance measuring means, or the like has a strong relationship with the skin barrier function. Specifically, when the amount of change in the amount of moisture in the skin increases by a certain value or more due to contact with the test substance or article, the permeability of substances such as methyl nicotinate to the skin is enhanced.
  • the test substance or article is obtained from the amount of change in the moisture content or moisture distribution measured noninvasively. Evaluate the effects on skin barrier function.
  • the barrier function is reduced (for example, the permeability of the substance from the outside to the inside of the skin) Can be evaluated).
  • the amount of moisture in the skin after contact with the test substance or article changes with an amount of change smaller than the reference value, it can be evaluated that the barrier function has not changed.
  • the skin capacitance measuring device (calculating the relative value (AU) of moisture calculated from the capacitance) for the skin inside the forearm of a healthy person after washing the skin and acclimatizing for at least 20 minutes
  • the reference value for the amount of change in the moisture content of the skin before and after contact with the test substance or article is set to 8 (AU), preferably 12 (AU), more preferably 16 (AU). To do.
  • the amount of moisture in the skin after contact with the test substance or article actually measured increases more than the reference value, the permeability of the substance from the outside to the inside of the skin is enhanced, and contact with the test substance or article It can be evaluated that the barrier function is lowered.
  • the amount of change in the amount of water is smaller than the reference value, it can be evaluated that the barrier function is not changed by contact with the test substance or article.
  • the moisture distribution of the skin before and after contact with the test substance or article is compared. Based on the initial stratum corneum thickness, the amount of skin moisture deeper than the initial stratum corneum due to the test substance or article contact When it increases, it becomes easy to enhance the permeability of the substance from the outside to the inside of the skin, and it can be evaluated that the barrier function is lowered.
  • the skin on the inner side of the forearm of a healthy person after washing the skin and acclimatizing for at least 20 minutes is the target, from the actual skin surface to a predetermined depth (preferably a depth of 40 ⁇ m from the skin surface).
  • the moisture distribution of the skin before and after contact with the test substance or article is measured by Raman spectroscopy. To do. Then, the moisture distribution in the skin before and after contact with the test substance or article is compared, and when the skin moisture content in the deep part is deeper than the initial stratum corneum thickness due to contact with the test substance or article, It can be evaluated that the permeability of the substance is enhanced and the barrier function is lowered by contact with the test substance or article.
  • the moisture content on the skin surface before and after contact with the test substance or article can be measured, and the influence on the barrier function can be evaluated from the amount of change in the moisture content on the skin surface due to contact with the test substance or article.
  • the skin inside the forearm of a healthy person after washing the skin and acclimatizing for at least 20 minutes is targeted, and the moisture content of the skin before and after contact with the test substance or article on the skin surface is determined by Raman spectroscopy. Measure and compare the moisture content of the skin before and after contact with the test substance or article.
  • the reference value of the amount of change in the moisture content on the skin surface obtained by Raman spectroscopy before and after contact with the test substance or article is 2.0 times, more preferably 2.5 times, and even more preferably 3. Set to 0 times.
  • the surface moisture content of the skin after contact with the actually measured test substance or article increases above the reference value, the permeability of the substance from the outside of the skin to the inside increases, and the test substance or article It can be evaluated that the barrier function is lowered by the contact.
  • the amount of change in the surface moisture content of the skin is smaller than the reference value, it can be evaluated that the barrier function is not changed by contact with the test substance or article.
  • the moisture content at the depth corresponding to the initial stratum corneum thickness before and after contact with the test substance or article is measured, and the change in the moisture content at the depth corresponding to the initial stratum corneum due to the contact with the test substance or article.
  • the effect on the barrier function can also be evaluated from the amount. Specifically, the skin on the inner side of the forearm of a healthy person after washing the skin and acclimatizing for at least 20 minutes is targeted, and the skin before and after contact with the test substance or article at the site corresponding to the initial stratum corneum thickness The moisture content is measured by Raman spectroscopy, and the moisture content of the skin before and after contact with the test substance or article is compared.
  • the reference value of the amount of change before and after the contact of the test substance or article with the water content at the site corresponding to the initial stratum corneum thickness obtained by Raman spectroscopy is 8%, preferably 11%, more preferably Is set to 14%. Then, when the amount of water at the site corresponding to the initial stratum corneum thickness after contact with the actually measured test substance or article increases more than the reference value, the permeability of the substance from outside the skin to the inside is enhanced. It can be evaluated that the barrier function has decreased due to contact with the test substance or article. On the other hand, when the amount of change in the amount of water at the site corresponding to the initial stratum corneum thickness is smaller than the reference value, it can be evaluated that the barrier function is not changed by contact with the test substance or article.
  • the skin inside the forearm of a healthy person after washing and acclimatization for at least 20 minutes is used as a target, and is measured by Raman spectroscopy to a predetermined depth from the skin surface (preferably a depth from the skin surface).
  • the reference value of the amount of change in the area under the curve before and after contact of the test substance or article obtained by Raman spectroscopy is 1.4 times, preferably 1.6 times, more preferably 1.8. Set to double. Then, when the area under the curve from the skin surface to the predetermined depth after contact with the actually measured test substance or article increases beyond the reference value, the permeability of the substance from outside the skin to the inside increases. It can be evaluated that the barrier function has decreased due to contact with the test substance or article. On the other hand, when the amount of change in the area under the curve is smaller than the reference value, it can be evaluated that the barrier function is not changed by contact with the test substance or article.
  • the “lower area curve” indicates the moisture content in the stratum corneum, and is obtained by integrating the moisture content for each depth in the depth direction.
  • Measurement of the moisture content of the skin by Raman spectroscopy can be performed with reference to the method described in JP2012-50739A.
  • This method approximates a skin sample with a ternary system of protein, water, and lipid, creates a corrected Raman spectrum by subtracting the contribution from the lipid-derived Raman spectrum from the measured Raman spectrum of the skin, and generates a protein-derived CH
  • This is a method of measuring the amount of skin moisture based on the ratio of the signal intensity derived from the OH stretching vibration of water to the stretching signal intensity.
  • a method for measuring the moisture content of the skin by Raman spectroscopy will be described in detail. However, the present invention is not limited to this.
  • the baseline fluorescence is corrected. Since the Raman spectrum of the measured skin to eliminate the distortion of baseline by fluorescence, from the data of the wavenumber region of 2000 ⁇ 2800 cm -1 and 3800 ⁇ 4200cm -1, a baseline based on cubic function approximation using the least square method Predict and subtract this.
  • the corrected skin spectrum excluding the influence of fluorescence is superimposed on four Raman spectra of degreased and dried stratum corneum, model sebum, model intercellular lipid and water using equation (4) described in JP2012-50739A. Approximate together. That is, the coefficients C 1 to C 4 in the equation (4) are determined by the least square method.
  • C 2 I SEB ( ⁇ ) is the contribution of sebum
  • C 3 I CER ( ⁇ ) is the contribution of the intercellular lipid.
  • the contribution amount of the model lipid in the Raman spectrum of the model lipid shown below is estimated by the least square method.
  • a corrected Raman spectrum represented by the formula (5) described in JP 2012-50739 A is obtained by subtracting the contribution of sebum and the contribution of intercellular lipids.
  • CH stretch signal (wavenumber region: 2800 ⁇ 3030cm -1) in the correction Raman spectra of the formula (5) OH stretching vibration peak area (wavenumber region: 3100 ⁇ 3750cm -1) to the peak area ratio of Is calculated.
  • the moisture content (mass%) of the skin is calculated based on a line (for example, see FIG. 5 of JP2012-50739A).
  • a horny layer piece is excised with a knife from the heel of a degreased and dried horny layer healthy male (40's), and then immersed in chloroform-methanol (1: 1) overnight. Thereafter, a sample of the stratum corneum is taken out and naturally dried to prepare a degreased and dried stratum corneum from which oil-soluble components such as lipids and water-soluble components such as amino acids have been removed.
  • Model sebum The following components are mixed to prepare model sebum.
  • Examples of articles used in the present invention include absorbent articles (absorbent cotton, sanitary napkins, paper diapers, cloth diapers, training pants, adult diapers, sweat pads, urine pads, puerperium pads, panty liners, absorbent pads, etc.) , Steam heaters, wound protection materials (such as bandages, gauze, bandages, etc.), masks, and rubber gloves.
  • Examples of the test substance include water or water vapor, cosmetics, humectants or external preparations, active ingredients and medicinal ingredients contained in steam heating devices, physiological saline, phosphate buffered saline, and biologically derived secretions. And urine such as urine, sweat, menstrual blood, and feces.
  • simulated urine, simulated sweat, simulated menstrual blood, simulated stool, etc. are included in living body-derived secretions and excretion.
  • the contact time of the test substance or article with the skin can also be set as appropriate.
  • the time for contacting the test substance or article with human skin is 1 hour or more and 6 hours or less, preferably 2 hours or more and 4 hours or less, more preferably 2.5 hours or more and 3.5 hours or less, and further preferably About 3 hours.
  • the evaluation method of the present invention measures the skin moisture content or moisture distribution noninvasively, and relates the relationship between the amount of change in skin moisture content or moisture distribution due to contact with an article or test substance and the skin barrier function. Based on the sex, the barrier function of the skin, in particular the permeability of the substance, is evaluated from the measured amount of change in the skin water content.
  • the amount of change in skin moisture or moisture distribution measured non-invasively is also described.
  • the state of the stratum corneum can be evaluated. For example, the amount of moisture in the skin before and after loading of the test substance or article, measured using a skin capacitance measuring device, for the skin inside the forearm of a healthy subject after washing the skin and acclimatizing for at least 20 minutes
  • the reference value of the change amount is set to 8 (AU), preferably 12 (AU), more preferably 16 (AU).
  • the barrier function of the stratum corneum is lowered when the moisture content of the skin after loading the actually measured test substance or article increases by more than the reference value.
  • the skin on the inner side of the forearm of a healthy person after washing the skin and acclimatizing for at least 20 minutes is the target, and from the skin surface to a predetermined depth (preferably to a depth of 40 ⁇ m from the skin surface, more preferably The water distribution of the skin before and after contact with the test substance or article at a depth of 35 ⁇ m from the skin surface, more preferably to a depth of 20 ⁇ m from the skin surface) is measured by Raman spectroscopy.
  • the moisture distribution in the skin before and after contact with the test substance or article is compared, and when the skin moisture content in the deeper part than the initial stratum corneum thickness is increased by contact with the test substance or article, the barrier function of the stratum corneum is It can be evaluated that it has decreased.
  • the skin moisture before and after contact with the test substance or article at a depth of 2 ⁇ m from the skin surface was examined for the skin inside the forearm of a healthy person after the skin was washed and acclimatized for at least 20 minutes. Measure by spectroscopy. Then, the surface moisture content of the skin before and after contact with the test substance or article is compared.
  • the reference value of the amount of change of the obtained skin surface moisture before and after contact with the test substance or article is set to 2.0 times, more preferably 2.5 times, and even more preferably 3.0 times. And it can be evaluated that the barrier function of the stratum corneum is reduced when the surface moisture content of the skin after contact with the test substance or article actually measured increases above the reference value.
  • the amount of moisture in the skin before and after contact with the test substance or article at the site corresponding to the initial stratum corneum thickness is measured for the skin inside the forearm of a healthy person after washing the skin and acclimatizing for at least 20 minutes. Measured by Raman spectroscopy. Then, the moisture content of the skin before and after contact with the test substance or article is compared.
  • the reference value of the amount of change before and after the contact of the test substance or article with the moisture content at the site corresponding to the initial stratum corneum thickness obtained by Raman spectroscopy is 8%, preferably 11%, more preferably 14%. Set. And when the moisture content of the site
  • the skin inside the forearm of a healthy person after washing and acclimatization for at least 20 minutes is used as a target, and is measured by Raman spectroscopy to a predetermined depth from the skin surface (preferably a depth from the skin surface).
  • the area under the curve of water profile is determined at a depth of 15 ⁇ m, more preferably a depth of about 13 ⁇ m from the skin surface.
  • the reference value of the amount of change in the area under the curve of the moisture content of the skin after contact with the test substance or article for a certain period of time relative to the area under the curve of the moisture content of the skin before contact with the test substance or article is preferably 1.4 times, preferably It is set to 1.6 times, more preferably 1.8 times.
  • the barrier function of the stratum corneum is reduced. Can be evaluated.
  • Absorbent articles absorbent cotton, sanitary napkins, disposable diapers, cloth diapers, training pants, adult diapers, sweat pads, urine pads, puerperium pads, panty liners, absorbent pads, etc.
  • products such as skin cosmetics or external preparations, wound protection materials (such as bandages, gauze, bandages, etc.), masks or rubber gloves, and steam heaters.
  • the performance of these products e.g., by evaluating the barrier function of the skin before and after wearing using the evaluation method of the present invention
  • the ability to absorb moisture (wet), the ability of water vapor (steaming) to spread to the outside, and the likelihood of skin problems) can be evaluated safely and simply in a short time.
  • an absorbent article containing physiological saline, simulated urine, or the like may be used for the evaluation. If the moisture content or moisture distribution of the skin after the wearing or application of the article is evaluated according to the present invention, the permeability of the substance is evaluated without the need to apply a substance such as methyl nicotinate used in this example to human skin.
  • the substance permeability can be estimated from the moisture content or moisture distribution of the skin before and after wearing when comparing the current product with the improved product. it can. If it does in this way, development of an absorptive article etc. can be performed efficiently.
  • active ingredients contained in cosmetics, external preparations and the like can be permeated into the skin using the hydration state of the skin (for example, J. Invest. Dermatol., 1963, vol. 41, p. 307-311).
  • the active ingredient contained in these products can be evaluated by using the evaluation method of the present invention to evaluate the barrier function of the skin before and after application, application, or wearing on the skin of cosmetics, external preparations, steam heaters, etc.
  • the permeability to the skin such as can be evaluated safely and simply in a short time.
  • the system for evaluating the influence of the test substance or article on the skin barrier function relates to the relationship between the amount of change in the moisture content or distribution of the skin due to the contact of the test substance or article and the skin barrier function. Information on sex is stored, and the influence is evaluated from the amount of change in the moisture content or moisture distribution of the skin due to contact with the test substance or article based on the information on the relevance.
  • the system of the present invention is a so-called computer and includes, for example, a CPU (Central Processing Unit), a memory, an input / output interface, and the like that are connected to each other via a bus.
  • a CPU Central Processing Unit
  • the memory is a RAM (Random Access Memory), a ROM (Read Only Memory), a hard disk, a portable storage medium, or the like.
  • the input / output interface is connected to a user interface device such as a display device or an input device.
  • the input / output interface may be connected to a communication device or the like that communicates with another computer via a network.
  • the evaluation method and the evaluation system of the present invention target human skin, preferably human (healthy person) skin having a normal barrier function in a state in which no test substance or article is loaded.
  • the present invention further discloses the following evaluation method and evaluation system.
  • a test substance or article is brought into contact with human skin, Compare the amount of moisture or moisture distribution in the skin before and after contact with the reference value, From the comparison results, the effect of the test substance or article on the skin barrier function is evaluated.
  • a method for evaluating a test substance or article The water content or distribution of the skin, measured by a water load test on the skin with different water loads, is associated with the barrier function of the skin, From the relationship between the moisture content or moisture distribution of the skin and the barrier function of the skin, the moisture content or moisture distribution of the skin when the change is confirmed in the skin barrier function is set as the reference value. Evaluation method of test substance or article.
  • ⁇ 2> In order to confirm the change in the barrier function of the skin, the permeability of the indicator substance from the outside to the inside of the skin is further measured, and the reference value is set from the result of the permeability of the indicator substance.
  • ⁇ 3> When the amount of skin moisture after contact with the test substance or article increases with a change amount greater than or equal to a reference value, the barrier function is reduced, preferably the permeability of the substance from the outside of the skin to the inside is increased, The method according to ⁇ 1> or ⁇ 2>, wherein ⁇ 4> When the amount of change in skin moisture after contact with the test substance or article is smaller than the reference value, the barrier function is not changed, preferably the permeability of the substance from the outside to the inside is enhanced. The method according to any one of ⁇ 1> to ⁇ 3>, wherein the method is evaluated as having no.
  • ⁇ 5> Measure the moisture content for each depth of human skin after contacting the test substance or article with human skin, and obtain the moisture distribution after contact of the test substance or article, A test substance or article evaluation method for evaluating the influence of a test substance or article on the barrier function of human skin by comparing the moisture distribution after contact of the test substance or article with a reference moisture distribution.
  • the indicator Measure the permeability of the substance, From the initial moisture distribution to the moisture distribution immediately after the end of the load of water or aqueous solution, and the permeability of the indicator substance, determine the relationship between the permeability of the indicator substance and the load of water or aqueous solution, The water distribution after loading with water or an aqueous solution at every depth of the human skin when the relevance is changed as the reference water distribution, Evaluation method of test substance or article.
  • ⁇ 6> Measure the moisture content at a predetermined depth position of the human skin before and after contact with the test substance or article, and obtain the difference between the moisture content before contact and the moisture content after contact; The evaluation method according to ⁇ 5>, wherein the influence on the skin barrier function is evaluated based on the obtained difference in water amount and the reference water distribution.
  • the indicator substance is methyl nicotinate, hexyl nicotinate, lactic acid, yellow No. 4, red No. 215, caffeine, ubinal, carotenoid, retinol, and skin moisturizer, skin external preparation, skin cosmetic, or steam
  • ⁇ 8> The method according to any one of ⁇ 1> to ⁇ 7>, wherein the moisture content of the skin is measured and analyzed by a skin capacitance measuring unit.
  • ⁇ 9> Skin of healthy subject is evaluated, skin moisture after contact with test substance or article is measured by skin capacitance measuring means, and skin moisture after contact with test substance or article is tested.
  • the barrier function decreases.
  • ⁇ 11> Up to a depth of 2 to 40 ⁇ m from the skin surface, preferably up to a depth of 2 to 35 ⁇ m from the skin surface, more preferably up to a depth of 2 to 20 ⁇ m from the skin surface, more preferably The water content or water distribution up to a depth of 9 to 15 ⁇ m from the skin surface, more preferably a depth of about 13 ⁇ m from the skin surface is measured and analyzed by Raman spectroscopy, ⁇ 1> to ⁇ 7. The method according to any one of 7>.
  • the skin of a healthy person is the subject of evaluation, up to a predetermined depth from the skin surface, preferably up to a depth of 40 ⁇ m from the skin surface, more preferably up to a depth of 35 ⁇ m from the skin surface, more preferably
  • the skin moisture distribution before and after contact with the test substance or article up to a depth of 20 ⁇ m from the skin surface is measured by Raman spectroscopy, and the skin moisture distribution before and after contact with the test substance or article is compared.
  • the barrier function is lowered, preferably the permeability of the substance from the outside to the inside of the skin is increased.
  • Skin surface moisture after contact with a test substance or article obtained by Raman spectroscopy is 2 with respect to the skin surface moisture before contact with the test substance or article.
  • the barrier function is lowered, preferably the permeability of the substance from the outside of the skin to the inside is increased,
  • the skin surface moisture after contact of the test substance or article obtained by Raman spectroscopy is 3 with respect to the skin surface moisture before contact of the test substance or article.
  • the barrier function is not changed, preferably the permeability of the substance from outside the skin to the inside is The method according to ⁇ 11>, wherein the method is evaluated as not enhanced.
  • the skin of a healthy person is the subject of evaluation, and the water content of the site corresponding to the initial stratum corneum thickness after contact with the test substance or article obtained by Raman spectroscopy is the value before contact with the test substance or article.
  • the barrier function is lowered, preferably from the outside of the skin to the inside.
  • the method according to ⁇ 11> wherein the permeability of the substance is evaluated to be enhanced.
  • the moisture content of the site corresponding to the initial stratum corneum thickness after contact with the test substance or article obtained by Raman spectroscopy is the value before contact with the test substance or article. If the amount of water in the region corresponding to the initial stratum corneum thickness is less than 14% increase, preferably less than 11% increase, more preferably less than 8% increase, the barrier function is not changed, Preferably, the method according to ⁇ 11> above, wherein it is evaluated that the permeability of the substance from the outside to the inside of the skin is not enhanced.
  • the skin of a healthy person is evaluated, and is obtained by Raman spectroscopy up to a predetermined depth from the skin surface, preferably a depth of 2 to 40 ⁇ m from the skin surface, more preferably from the skin surface.
  • a depth of 2 to 35 ⁇ m more to a depth of 2 to 20 ⁇ m from the skin surface, more preferably to a depth of 9 to 15 ⁇ m from the skin surface, more preferably to a depth of 13 ⁇ m from the skin surface.
  • the area under the curve of the moisture content of the skin after contact with the test substance or article up to a certain depth is obtained, and the area under the curve of the skin moisture amount after contact with the test substance or article is the contact of the test substance or article
  • the barrier function is lowered, preferably skin From outside to inside
  • the skin of a healthy person is evaluated, and obtained by Raman spectroscopy, to a predetermined depth from the skin surface, preferably to a depth of 2 to 40 ⁇ m from the skin surface, more preferably from the skin surface.
  • a depth of 2 to 35 ⁇ m more to a depth of 2 to 20 ⁇ m from the skin surface, more preferably to a depth of 9 to 15 ⁇ m from the skin surface, more preferably to a depth of 13 ⁇ m from the skin surface.
  • the area under the curve of the moisture content of the skin after contact with the test substance or article up to a certain depth is obtained, and the area under the curve of the skin moisture amount after contact with the test substance or article is the contact of the test substance or article If the area under the curve of water content of the previous skin is less than 1.8 times, preferably less than 1.6 times, more preferably less than 1.4 times, the barrier function is not changed, Like Alternatively, the method according to ⁇ 11> above, wherein it is evaluated that the permeability of the substance from the outside to the inside of the skin is not enhanced.
  • a method for evaluating the influence of a test substance or article on the barrier function of human skin Obtain water distribution by measuring the amount of water at each skin depth before and after contact of the test substance or article with human skin, Evaluate the effect of the test substance or article on the barrier function of human skin, using the difference in water content deeper than the initial stratum corneum thickness before contact in the moisture distribution before and after contact, Evaluation method of test substance or article.
  • ⁇ 20> to a depth of 2 to 40 ⁇ m from the skin surface, preferably to a depth of 2 to 35 ⁇ m from the skin surface, more preferably to a depth of 2 to 20 ⁇ m from the skin surface, more preferably The method according to ⁇ 19>, wherein the moisture content is measured and analyzed by Raman spectroscopy up to a depth of 9 to 15 ⁇ m from the skin surface, more preferably a depth of about 13 ⁇ m from the skin surface.
  • ⁇ 21> Skin of a healthy subject is evaluated by measuring the moisture distribution of the skin before and after contact with the test substance or article from the skin surface to a predetermined depth by Raman spectroscopy, and before and after contact with the test substance or article
  • the barrier function decreases, preferably the permeability of the substance from the outside to the inside of the skin
  • ⁇ 22> The method according to any one of ⁇ 1> to ⁇ 21>, wherein the skin moisture content or moisture distribution is noninvasively measured.
  • ⁇ 23> The method according to any one of ⁇ 1> to ⁇ 22>, wherein the evaluation is performed on the skin of a human (healthy person) having a normal barrier function in a state in which no test substance or article is loaded.
  • the moisture content of the skin is measured according to at least one selected from the group consisting of Raman spectroscopy, skin capacitance measurement means, high-frequency current measurement means, infrared spectroscopy, and near-infrared spectroscopy, The method according to any one of 1> to ⁇ 7>, ⁇ 19>, ⁇ 22> and ⁇ 23>.
  • the test substance is water or water vapor, skin cosmetics, skin moisturizer or external preparation for skin, active ingredient or medicinal ingredient contained in steam heating device, physiological saline, phosphate buffered saline, and biological origin
  • the method according to any one of ⁇ 1> to ⁇ 24>, wherein the method is at least one selected from the group consisting of secretions and excrements of ⁇ 26>
  • the article is an absorbent article (preferably absorbent cotton, a sanitary napkin, a paper diaper, a cloth diaper, a training pant, an adult diaper, a sweat pad, a urine pad, a postpartum pad, a panty liner, or an absorbent pad),
  • the method according to any one of ⁇ 1> to ⁇ 24>, wherein the method is a steam heating device, a wound protection material (preferably a bandage, a gauze, or a bandage), a mask, or a rubber glove.
  • Time for contacting the test substance or article with human skin is 1 hour or more and 6 hours or less, preferably 2 hours or more and 4 hours or less, more preferably 2.5 hours or more and 3.5 hours or less, and further preferably The method according to any one of ⁇ 1> to ⁇ 27>, wherein is about 3 hours.
  • ⁇ 29> Stores information on the relationship between the amount of change in the moisture content or distribution of skin due to contact of the test substance or article with human skin, and the barrier function of the skin.
  • Test Example 1 Measurement of change in permeability of methyl nicotinate and moisture content of skin before and after water load
  • Measurement of erythema score Healthy males and 10 females (20s to 40s) were subjects. A different amount of water was loaded on the inner side of the forearm, and the permeability of methyl nicotinate after the water load was evaluated. The measurement was carried out after acclimatization for 20 minutes in an environment variable room at 24 to 25 ° C. and a relative humidity of 40 to 50%.
  • Moisture load per cm 2 of absorbent cotton is 0 mL (0 mL / cm 2 ), 0.02 mL (0.02 mL / cm 2 ), 0 on 2.5 cm ⁇ 2.5 cm member cut cotton (manufactured by White Cross)
  • Add distilled water to make 0.04 mL (0.04 mL / cm 2 ), 0.20 mL (0.20 mL / cm 2 ), place this on the inner side of the forearm, and use a moisture-permeable adhesive bandage (trade name: Skinnagate) to surround it. Fixed and affixed for 3 hours.
  • the surface of the member cut cotton that does not come into contact with the skin is covered with a dressing material (trade name: Tegaderm TM Transparent Dressing), and the dressing material is used to prevent the skin from stuffy during application. Made 8 holes per 1 cm 2 with a needle 29G (TERUMO, Japan). While applying the member cut cotton, the participants were prohibited from exercising or working outdoors for a long time.
  • a dressing material trade name: Tegaderm TM Transparent Dressing
  • a filter paper (trade name: Advantec No. 2) hollowed out to a diameter of 5 mm containing 5.0 ⁇ L of 0.007 mass% methyl nicotinate aqueous solution was loaded on the test site for 15 seconds. After 30 minutes from the load of methyl nicotinate, the resulting erythema was visually determined according to the following evaluation criteria. From the erythema score obtained by visual determination, the permeability of methyl nicotinate at each water load was evaluated. IBM SPSS version 23 software was used for statistical analysis. The results are shown in Table 1. (Evaluation criteria) Score 0: No response. Score 0.5: Slightly red.
  • Score 1 More than half of the area of the filter paper is red.
  • Score 2 The area on which the filter paper is applied is clearly red.
  • Score 3 larger than the area of the filter paper.
  • Score 4 Red area is larger than the area of the filter paper and swollen.
  • the load amount of water as compared with the case of 0.00mL / cm 2 or 0.02 mL / cm 2, to load a moisture 0.04 mL / cm 2 or 0.20 mL / cm 2
  • the erythema score due to methyl nicotinate was significantly increased. That is, the permeation of methyl nicotinate into the skin was significantly enhanced by applying a certain amount or more of moisture to the skin.
  • the skin barrier function is lowered when the water load is at least 0.04 mL / cm 2 . Therefore, the state of the skin when the moisture load is 0.04 mL / cm 2 can be set as a reference state for evaluating the barrier function of the skin.
  • Erythema is observed on the skin when the loaded methyl nicotinate penetrates or passes through the skin and acts on the peripheral blood vessels to exert a vasodilating action. As shown in Table 1, erythema is hardly observed on the skin before water load (water load: 0 mL / cm 2 ) even when methyl nicotinate is loaded. This is probably because methyl nicotinate is difficult to penetrate into the skin and cannot reach the peripheral blood vessels. That is, it can be inferred that the barrier function is maintained in the skin before moisture loading. On the other hand, erythema is observed in the skin after a certain amount of water load due to the load of methyl nicotinate. From this result, it can be determined that loading with moisture caused methyl nicotinate to penetrate or pass through the skin, that is, the barrier function of the skin was reduced.
  • a moisture load per cm 2 of absorbent cotton is 0 mL (0 mL / 0) on a 2.5 cm ⁇ 2.5 cm member cut cotton (manufactured by White Cross).
  • cm 2 0.01mL (0.01mL / cm 2), 0.02mL (0.02mL / cm 2), 0.03mL (0.03mL / cm 2), 0.04mL (0.04mL / cm 2 ), 0.06 mL (0.06 mL / cm 2 ), 0.10 mL (0.10 mL / cm 2 ), and 0.20 mL (0.20 mL / cm 2 ) in distilled water,
  • the circumference was fixed with a moisture-permeable adhesive plaster (trade name: Skinnagate) on the inner side of the subject's forearm and applied for 3 hours.
  • the surface of the member cut cotton that does not come into contact with the skin is covered with a dressing material (trade name: Tegaderm TM Transparent Dressing), and the dressing material is used to prevent the skin from stuffy during application. Made 8 holes per 1 cm 2 with a needle 29G (TERUMO, Japan). While applying the member cut cotton, the participants were prohibited from exercising or working outdoors for a long time.
  • a dressing material trade name: Tegaderm TM Transparent Dressing
  • Skin capacitance measuring device (trade name: Corneometer CM-825, Courage +) before and after removing the member cut cotton, and measuring the moisture content of the skin where the member cut cotton is applied. Measured by Khazaka Germany). Then, a value obtained by subtracting the value before application of the member cut cotton from the value immediately after the removal of the member cut cotton was calculated, and the amount of change in the stratum corneum moisture content was measured. IBM SPSS version 23 software was used for statistical analysis. The results are shown in Table 2.
  • the load amount of water of at least 0.04 mL / cm 2 when the load amount of water of at least 0.04 mL / cm 2 can be determined that the skin barrier function is impaired, the state of the skin when the water loading amount of 0.04 mL / cm 2 A reference state for evaluating the skin barrier function was used. Therefore, the amount of change in the amount of skin moisture in this reference state can be used as the reference value in the evaluation method of the present invention.
  • the surface of the member cut cotton that does not come into contact with the skin is covered with a dressing material (trade name: Tegaderm TM Transparent Dressing), and the dressing material is used to prevent the skin from stuffy during application. Made 8 holes per 1 cm 2 with a needle 29G (TERUMO, Japan). While applying the member cut cotton, the participants were prohibited from exercising or working outdoors for a long time.
  • a dressing material trade name: Tegaderm TM Transparent Dressing
  • a method of approximately calculating the amount of water from the Raman spectrum obtained by measurement using a confocal Raman spectroscopic microscope was performed by referring to the method described in JP2012-50739A. Furthermore, according to the method described in IFSCC Magazine, 2009, vol. 12 (1), p. 9-15, the moisture profile obtained by Raman spectroscopy is approximated by two linear lines, The depth was defined as the initial stratum corneum thickness (the stratum corneum thickness prior to the application of the member cut cotton).
  • FIGS. 2 (a) to (d) The results are shown in FIGS. 2 (a) to (d).
  • the X-axis indicates the skin depth ( ⁇ m)
  • the Y-axis indicates the water content (%).
  • the average thickness of the stratum corneum before the water load determined from the graph shown in FIG. 2A was 13 ⁇ m.
  • FIG. 2 (b) when the moisture load is 0.02 mL / cm 2 , the skin has an area up to 13 ⁇ m corresponding to the stratum corneum thickness before moisture load compared to before moisture load.
  • the amount of change ( ⁇ surface water content) of the surface water content was calculated.
  • a signal derived from CH stretching vibration of protein contained in the skin was used as a guide. Details will be described below.
  • the signal intensity derived from the CH stretching vibration of the protein of the Raman spectrum shows a maximum value on the skin side slightly from the boundary between the window material of the objective lens and the skin, and then the signal intensity decreases as it goes deeper.
  • the signal intensity derived from CH stretching vibration is 0 when the focal point of the laser is within the window material.
  • the signal intensity derived from the CH stretching vibration when the laser is focused in the skin is 100
  • the signal intensity derived from the CH stretching vibration is 50 when the focus comes to the interface between the window material and the skin.
  • the window material may be detected even though the signal intensity derived from the CH stretching vibration is weak. Therefore, in consideration of the spatial resolution of the nano finder, which is the confocal Raman spectroscopic apparatus used for the measurement in the present invention, the water content at a portion 2 ⁇ m deep from the surface, which is the actual measurement value, is defined as “surface water content”. .
  • the results are shown in Table 3.
  • the surface moisture content before and after the water load changed. Specifically, when the water load was 0.02 mL / cm 2 , the surface water content (%) after the water load increased 1.39 times compared to that before the water load. Similarly, in the case where the moisture load amount is 0.04 mL / cm 2 in the above-described reference state, the surface moisture amount (%) after the moisture load increases 2.40 times compared to before the moisture load, When the water load was 0.20 mL / cm 2 , it increased 2.99 times. Therefore, the moisture content on the skin surface can also be used as the reference value in the evaluation method of the present invention.
  • the amount of water at a depth of 13 ⁇ m corresponding to the thickness of the stratum corneum before the water load changed according to the amount of water to be loaded.
  • the water load increases after the water load of 0.04 mL / cm 2 where the substance permeability is increased, that is, the water at the depth corresponding to the initial stratum corneum thickness. It was found that the amount increased. Therefore, as the reference value in the evaluation method of the present invention, it is also possible to use the amount of change in the water content at the depth corresponding to the initial stratum corneum thickness.
  • the area under the curve of the water content at a depth of 1 ⁇ m to 13 ⁇ m from the skin surface before and after the water load changed. Specifically, when the water load was 0.02 mL / cm 2 , the area under the curve of the water amount after the water load increased 1.20 times compared with that before the water load. Similarly, in the case where the moisture load amount is 0.04 mL / cm 2 in the above-described reference state, the area under the curve of the moisture amount after the moisture load increases 1.59 times compared to before the moisture load, When the water load was 0.20 mL / cm 2 , it increased 1.83 times. Therefore, the area under the curve of the moisture content of the skin up to a predetermined depth from the skin surface can also be used as the reference value in the evaluation method of the present invention.
  • the permeability of the substance increases when the water load increases beyond a certain value. That is, the permeability of the substance, that is, the barrier function of the skin, is compared with the skin moisture content or moisture distribution in the reference state from the skin moisture content or moisture distribution measured non-invasively by a corneometer or Raman spectroscopy. Can be evaluated.
  • Test Example 2 Performance Comparison Test of Absorbent Article (1) Moisture load on skin One healthy woman (30's) was the subject, and the effect of the absorbent article on the skin on the inner side of the forearm was evaluated. The measurement was performed after acclimatization for 20 to 30 minutes in an environment variable room at 24 to 25 ° C. and a relative humidity of 40 to 50%.
  • the amount of skin moisture was increased when the absorbent article B was affixed.
  • the absorbent article B is affixed, the amount of water deeper than the initial stratum corneum thickness before the moisture load is increased as compared with the case where the absorbent article A is affixed. Therefore, the barrier function does not change even if the absorbent article A is pasted from the difference in the moisture content deeper than the initial stratum corneum thickness using the moisture distribution, whereas the barrier function when the absorbent article B is pasted Can be evaluated as decreasing.
  • the surface moisture content (%) before and after the water load increased 1.19 times after application of the absorbent article A compared to before application. On the other hand, it increased 2.86 times after sticking of the absorbent article B compared with before sticking. Further, the surface moisture content when the absorbent article A was applied was the reference value in Test Example 1, and the increase in the surface moisture content when the moisture load was 0.04 mL / cm 2 (2.40 times). Was smaller than. Therefore, even if the absorbent article A is pasted, it can be evaluated that the barrier function is not changed. On the other hand, since the increase in the amount of surface moisture when the absorbent article B is affixed is greater than the reference value, it can be evaluated that the barrier function decreases when the absorptive article B is affixed.
  • the absorbent article B when the absorbent article B was affixed, the water content at a depth of 13 ⁇ m was greatly increased as compared to the case where the absorbent article A was affixed.
  • the amount of change in the water content at the depth corresponding to the initial stratum corneum thickness is the reference value in Test Example 1, and the water load is 0.04 mL / cm 2 It was less than the amount of change in water content at the depth corresponding to the initial stratum corneum thickness (9.21 ⁇ 9.2 (%)). Therefore, even if the absorbent article A is pasted, it can be evaluated that the barrier function is not changed.
  • the barrier function decreases when the absorptive article B is affixed. it can.
  • the area under the curve of the water content at a depth of 1 ⁇ m to 13 ⁇ m from the skin surface before and after water load is 1.08 after the application of the absorbent article A and before the application. Doubled.
  • the increase was 1.89 times as compared with before application.
  • the amount of change in the area under the curve when the absorbent article A was applied was the reference value in Test Example 1, and the increase in the area under the curve when the moisture load was 0.04 mL / cm 2 (1. 59 times). Therefore, even if the absorbent article A is pasted, it can be evaluated that the barrier function is not changed.
  • the increase in the area under the curve when the absorbent article B is pasted is larger than the reference value, it can be evaluated that the barrier function is lowered when the absorbent article B is pasted.
  • the absorbent article A When the absorbent article A was applied and the permeability of the water-soluble substance was actually judged, the permeability of the water-soluble substance from the outside to the inside of the skin was low. That is, from the above results, it can be said that the absorbent article A is an absorbent article that does not increase the permeability of the water-soluble substance to the skin and hardly causes skin troubles.
  • the absorbent article B When the absorbent article B was affixed and the permeability of the water-soluble substance was actually judged, it was surprisingly found that the permeability of the water-soluble substance from the outside to the inside of the skin was increased. That is, it can be said that the absorbent article B is an absorbent article in which the permeability of the water-soluble substance to the skin is enhanced and skin trouble may occur.
  • test substance or article is brought into contact with human skin according to the method of the present invention, and the effect of the test substance or article on the skin barrier function is determined from the result of measuring the moisture content or moisture distribution of the skin before and after contact. It was confirmed that it is effective as a method for evaluating

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  • Measuring And Recording Apparatus For Diagnosis (AREA)

Abstract

La présente invention concerne un procédé d'évaluation de substance ou de produit d'essai qui met en œuvre la mise en contact de peau humaine avec une substance ou un produit d'essai, la comparaison de la quantité de changement de la teneur en eau ou de la distribution d'eau de la peau avant et après le contact à une valeur de référence et, sur la base des résultats de la comparaison, l'évaluation de l'impact que la substance ou le produit d'essai a sur la fonction de barrière cutanée, la fonction de barrière cutanée étant associée à la teneur en eau ou la distribution d'eau de la peau mesurée en soumettant la peau à un test de chargement d'eau en modifiant la quantité de chargement d'eau, et la teneur en eau ou la distribution d'eau de la peau lorsqu'un changement de la fonction de barrière cutanée est confirmé est définie en tant que valeur de référence sur la base de l'association entre la fonction de barrière cutanée et la teneur en eau ou la distribution d'eau de la peau.
PCT/JP2017/015796 2017-04-19 2017-04-19 Procédé d'évaluation de l'impact d'une substance ou d'un produit d'essai sur la peau WO2018193565A1 (fr)

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JP2017547588A JP6326557B1 (ja) 2017-04-19 2017-04-19 被験物質又は物品が皮膚に与える影響を評価する方法
PCT/JP2017/015796 WO2018193565A1 (fr) 2017-04-19 2017-04-19 Procédé d'évaluation de l'impact d'une substance ou d'un produit d'essai sur la peau

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JP2020193915A (ja) * 2019-05-29 2020-12-03 花王株式会社 乳幼児の皮膚状態の評価方法
WO2024000232A1 (fr) * 2022-06-29 2024-01-04 L'oreal Procédé et dispositif informatique permettant d'évaluer l'effet de protection d'une composition protectrice à appliquer sur la matière kératinique d'un utilisateur

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JP2020176977A (ja) * 2019-04-22 2020-10-29 花王株式会社 皮膚バリア機能に与える影響の評価方法

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JP2020193915A (ja) * 2019-05-29 2020-12-03 花王株式会社 乳幼児の皮膚状態の評価方法
WO2024000232A1 (fr) * 2022-06-29 2024-01-04 L'oreal Procédé et dispositif informatique permettant d'évaluer l'effet de protection d'une composition protectrice à appliquer sur la matière kératinique d'un utilisateur

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