Method for estimating skin condition features

Abstract

To provide a simple method for estimating skin condition features by using the stratum corneum of a test subject's skin surface, which can be collected and used in a minimally invasive manner.SOLUTION: As a result of extensive studies, the present inventors have discovered that the contour features of the stratum corneum cells have a unique correlation with the skin condition features for each contour feature of the stratum corneum cells, and have completed the present invention.EFFECT: By using stratum corneum, which can be easily and minimally invasively collected from a subject's skin surface, and by analyzing contour features, the present invention can provide a simple method for estimating skin condition features without special staining. For example, it is possible to estimate various skin condition features by simply collecting the stratum corneum by applying tape to the face at home and sending it to an analysis organization, without having to perform measurements using specialized equipment.SELECTED DRAWING: Figure 1

Description

Technical Field

[0001] The present invention relates to a technique for estimating skin state characteristics by analyzing stratum corneum cells.

Background Art

[0002] The skin consists of three layers: the epidermis, dermis, and subcutaneous tissue, in order from the surface layer where the human body contacts the outside air. The epidermis consists of cells called keratinocytes, and is classified into the basal layer, spinous layer, granular layer, and stratum corneum (horny layer) from the deep part near the dermis. In the epidermis, keratinocytes are pushed upward from the basal layer toward the stratum corneum by division, and are shed as so-called dirt on the outermost surface of the stratum corneum.

[0003] Since the stratum corneum exists on the outermost surface of the skin and can be measured with low invasiveness, its use has been studied in the estimation of skin state. For example, techniques for estimating skin state from the degree of stratification or the rate of nucleated cells in the stratum corneum have been studied. In addition, an indirect estimation method for the amount of melanin and oxidized protein inside the skin by selectively staining and labeling melanin and oxidized protein in the stratum corneum and measuring them is known (Patent Documents 1 and 2).

[0004] There are individual differences and site differences in the size of the cells (stratum corneum cells) present in the stratum corneum, and it is known that the larger the stratum corneum cell area, the slower the turnover. Therefore, it may be used as an index for measuring the turnover rate. It is also known that the size and uniformity of the area of stratum corneum cells are related to the barrier function and water retention ability (Patent Documents 3 and 4). Thus, while indices related to area are often used in the estimation of skin state, the relationship between the shape of stratum corneum cells excluding area and skin state has not been known until now.

[0005] In addition, stratum corneum cells gradually flatten according to turnover and exist overlapping adjacent cells, but the relationship between these overlaps and skin state has not been known until now.

[0006] Skin condition encompasses a wide range of factors, including stratum corneum moisture content, transepidermal water loss, elasticity, pore condition, brightness, redness, and yellowness. However, it has been difficult to easily estimate these various skin conditions on subjects without using specialized measuring equipment. [Prior art documents] [Patent Documents]

[0007] [Patent Document 1] Japanese Patent Publication No. Hei 6-82443 [Patent Document 2] Japanese Patent Publication No. 2006-349372 [Patent Document 3] Japanese Patent Publication No. 2005-172481 [Patent Document 4] Japanese Patent Publication No. 2005-189011 [Overview of the Initiative] [Problems that the invention aims to solve]

[0008] The object of the present invention is to provide a simple method for estimating skin condition characteristics using the stratum corneum of a subject's skin surface, which can be collected and used in a minimally invasive manner. [Means for solving the problem]

[0009] As a result of diligent research, the inventors of the present invention discovered that the contour features of stratum corneum cells have a unique correlation with skin condition features for each contour feature of stratum corneum cells, and thus completed the present invention. [Effects of the Invention]

[0010] This invention provides a simple method for estimating skin condition features by analyzing contour features using stratum corneum that can be easily and minimally invasively collected from the skin surface of a subject, without the need for special staining. For example, it becomes possible to estimate various skin condition features simply by sending stratum corneum collected by attaching tape to the face at home to an analysis institution, without the need for measurements using specialized equipment. [Brief explanation of the drawing]

[0011] [Figure 1] This diagram shows a method for calculating the long and short diameters of stratum corneum cells. [Figure 2] This diagram shows a method for calculating the hexagonal ratio of stratum corneum cells. [Figure 3] This diagram shows a method for calculating the overlapping distance of stratum corneum cells. [Figure 4] This diagram illustrates a method for calculating the overlapping area and overlapping ratio of stratum corneum cells. [Modes for carrying out the invention]

[0012] An investigation into the relationship between contour features, which are features obtained from the contour information of stratum corneum cells, and skin condition features revealed that each contour feature of stratum corneum cells showed a unique correlation with the skin condition features, indicating a close relationship between the two. Since it is possible to estimate skin condition features from the contour features of stratum corneum cells by utilizing these discovered relationships, this invention was developed.

[0013] If there is a correlation between the contour features of stratum corneum cells and the skin condition features, then it can be said that if one changes, the other will also change. Based on this correlation, the skin condition features can be estimated by using the contour features of stratum corneum cells as an indicator. For example, in this invention, it has been found that there is a negative correlation between the roundness ratio, which is a contour feature of stratum corneum cells, and redness, which is a skin condition feature. Therefore, the measured value of the roundness ratio can be used as an indicator of redness, and it can be estimated that the higher the roundness ratio, the lower the redness.

[0014] Furthermore, in a well-fitting regression equation obtained based on the contour features of stratum corneum cells and skin condition features, the value calculated by substituting the contour features of stratum corneum cells collected from the skin of a specific subject as a variable corresponds to the subject's skin condition features. Therefore, it is possible to estimate the measured value of a subject's skin condition features by substituting the contour features of stratum corneum cells from a specific subject into a regression equation obtained using the contour features of stratum corneum cells collected from the skin of multiple subjects as explanatory variables and the measured value of the skin condition features as the dependent variable. In addition, by obtaining a multiple regression equation from the contour features of multiple stratum corneum cells that correlate with the estimated skin condition features, it is possible to estimate skin condition features with higher accuracy.

[0015] By using the skin condition feature estimation method described above, it becomes possible to determine changes in skin condition features by measuring the contour features of stratum corneum cells over time, and to screen for agents that improve skin condition features. For example, in this invention, it has been found that there is a negative correlation between the roundness ratio, which is a contour feature of stratum corneum cells, and redness, which is a skin condition feature. If skin condition features are estimated based on this correlation, it becomes possible to measure the roundness ratio of the area where the test substance is applied, and if the roundness ratio increases after a certain amount of time, it can be determined that the agent is capable of improving redness.

[0016] In this invention, the contour features of stratum corneum cells used as indicators refer to features other than area that can be read from the contour information of stratum corneum cells, and include diameter features, external shape features, overlap features, and the degree of irregularity features of each of the diameter features, external shape features, and overlap features.

[0017] The diameter feature amount, which is a contour feature amount of stratum corneum cells, is a feature amount of the length of a line segment that passes through the center (center of gravity, incenter, or circumcenter) of the stratum corneum cell and has both ends on the contour of the stratum corneum cell, or when the stratum corneum cell is approximated by an ellipse, a line segment that passes through the center of the ellipse and has both ends on the ellipse contour. The longest diameter is the major axis, and the shortest diameter is the minor axis. The method for measuring the major axis and minor axis of the stratum corneum cells used as indicators in the present invention is not particularly limited. For example, as shown in FIG. 1, when the stratum corneum cell is sandwiched between two concentric circles from the inside and outside, the diameters of the circumscribed circle and the inscribed circle where the distance between the two concentric circles is minimized are measured, and they are respectively taken as the major axis and the minor axis. Or, as shown in FIG. 1, the stratum corneum cell is approximated by an ellipse, and the major axis and minor axis of the ellipse can be grasped as the major axis and minor axis of the stratum corneum cell.

[0018] The outer shape feature amount, which is a contour feature amount of stratum corneum cells, is a feature amount related to the shape excluding the area that can be read from the contour information of the stratum corneum cells, and includes the circularity, roundness, and regular hexagon ratio. The circularity is a numerical value representing the complexity of the contour shape of the stratum corneum cell, and the measurement method is not particularly limited. Generally, circularity = 4π×S÷L2 (S is the area of the stratum corneum cell, L is the perimeter of the stratum corneum cell). The higher the value, the less complex the shape, that is, the higher the circularity is grasped. The roundness is a numerical value representing the degree of deviation from a geometrically correct circle, and the measurement method is not particularly limited. For example, it can be grasped that the higher the roundness, the smaller the ratio and difference between the major axis and minor axis of the stratum corneum cell obtained in paragraph 0017. The regular hexagon ratio indicates the approximation rate when the stratum corneum cell is approximated by a regular hexagon, and the measurement method is not particularly limited. For example, as shown in FIG. 2, the centers of gravity of regular hexagons having the same area as the stratum corneum cell are aligned and overlapped, and when rotated so that the overlapping area is the widest, the overlapping rate can be grasped as the regular hexagon ratio. The overlapping rate can be calculated by dividing the area of the common part indicated by the shaded area in FIG. 2 by the area surrounded by the stratum corneum cell contour indicated by the thick line or the regular hexagon indicated by the broken line.

[0019] The overlapping feature amount, which is a contour feature amount of stratum corneum cells, refers to a feature amount related to the degree of overlap between adjacent cells when the skin surface side is regarded as the top. This overlapping feature amount is different from the feature amount related to the degree of multi-layered stratum corneum cells that are peeled off together during tape stripping and the amount of multi-layered peeling, which is caused by the failure of separation between cells in the vertical relationship and is almost single-layered peeling that has been used so far. Even when three or more cells overlap, it can be considered that there are multiple pairs of overlapping two cells, and it can be determined that there is an overlap for each combination. The overlapping feature amount includes an overlapping distance, an overlapping area, and an overlapping rate. The overlapping distance is the distance representing the width of the part where a certain stratum corneum cell overlaps with another adjacent stratum corneum cell. Specifically, for example, as shown in FIG. 3, when a straight line (the line shown by the broken line in the figure) connecting two points (A and B in the figure) where the contours of two stratum corneum cells overlap is drawn, it is the distance between two parallel straight lines (C and D in the figure) that are parallel to the straight line and pass through the two farthest overlapping parts in the direction perpendicular to the straight line. In the case of three or more points overlapping, the two farthest points are regarded as the two points where the contours overlap. The overlapping area is the area of the range where a stratum corneum cell overlaps with another adjacent stratum corneum cell. The overlapping area and the overlapping rate are illustrated in FIG. 4. First, when calculating the overlapping area of the stratum corneum cells in FIG. 4, for example, the area of the overlapping part shown by the shaded area can be grasped as the overlapping area from the contours of the two overlapping cells. Next, regarding the overlapping rate, the overlapping rate is the ratio of the area of the part where a stratum corneum cell overlaps with another adjacent stratum corneum cell to the area of the stratum corneum cell. When calculating the overlapping rate of the stratum corneum cells based on FIG. 4, for example, the ratio of the area of the overlapping part shown by the shaded area to the area of the stratum corneum cell can be calculated. At this time, since there is one overlapping part while there are two stratum corneum cells (A and B), two overlapping rates can be obtained for each combination of one pair of overlaps as the overlapping rate based on the area of each stratum corneum cell. Or, by dividing the area of the overlapping part by the average value of the areas of the two stratum corneum cells, it can also be grasped as one overlapping rate for one combination of overlaps (see FIG. 4).

[0020] The irregularity features of each of the stratum corneum cell contour features—diameter, external shape, and overlap—represent the variability that occurs when multiple measurements of these features are taken within the same test range. These features can be selected from the coefficient of variation, standard deviation, or standard error. The irregularity features of each of the diameter, external shape, and overlap features include variability in major axis, variability in minor axis, variability in circularity, variability in perfect circularity, variability in regular hexagonal ratio, variability in overlap distance, and variability in overlap rate. When calculating the irregularity features of each of the diameter, external shape, and overlap features, for example, one can calculate the diameter, external shape, and overlap features of 10 or more stratum corneum cells within the same test range and determine the coefficient of variation, standard deviation, and standard error for each to obtain the irregularity features of each of the diameter, external shape, and overlap features.

[0021] The method for identifying and quantifying the contour features of stratum corneum cells used as indicators in this invention is not particularly limited. For example, stratum corneum cells can be collected from the test area by tape stripping, their contour features can be clarified by staining, and then identified by observation and photography under a microscope. For quantification, the contour features of stratum corneum cells can be quantified by manually tracing the contour of each cell in the acquired stratum corneum image, or by using an algorithm that automatically extracts the contours of stratum corneum cells.

[0022] Regarding the number of stratum corneum cells required for analysis, since there is some variation in the contour features of stratum corneum cells even within the same person and the same body part, it is desirable to analyze multiple stratum corneum cells within the same test area when understanding the contour features of stratum corneum cells. It is even more desirable to analyze 10 or more cells, preferably 50 or more, and even 100 or more stratum corneum cells.

[0023] It is desirable that the stratum corneum cells to be analyzed have accurately measurable contours. Stratum corneum cells that are torn, bent, or otherwise whose contours cannot be accurately captured immediately after they appear on the skin surface due to turnover should be excluded from the analysis. Furthermore, when the stratum corneum is collected by tape stripping, if multiple layers of stratum corneum cells overlap in the depth direction and are collected in a state of multi-layered exfoliation, and it is not possible to selectively measure the outermost stratum corneum cells, it is desirable to exclude them from the analysis.

[0024] Skin condition features refer to features that describe the state of the skin, including its physical state, optical state, and component presence. These features include moisturizing features, skin surface image features, and internal skin state features. In estimating skin condition features according to the present invention, the features may be estimated using the contour features of stratum corneum cells as an indicator based on correlation. Alternatively, the contour features of stratum corneum cells collected from the skin of multiple subjects may be used as explanatory variables, and the measured values ​​of skin condition features may be used as the objective variable. The numerical value obtained by substituting the contour features of stratum corneum cells of a specific subject into this regression equation may be estimated as the measured value of the subject's skin condition features. For estimation, criteria may be established to create a ranking system divided into multiple stages, or the values ​​may be estimated as high or low based on comparison with other comparison targets. Furthermore, while skin condition features are primarily the target of estimation in this invention, when calculating the correlation coefficient with the contour features of stratum corneum cells, or when creating a regression equation for calculating the measured value of skin condition features, it is possible to actually measure the skin condition features and compare them with the contour features of stratum corneum cells.

[0025] Skin condition characteristics, specifically moisturizing characteristics, refer to the moisture content of the stratum corneum and the ability to maintain that moisture content; in other words, they are characteristics related to moisturizing. Moisturizing characteristics include stratum corneum moisture content and transepidermal water loss. Stratum corneum moisture content refers to the amount of water contained in the stratum corneum. There are no specific requirements for the measurement method; for example, it can be measured using electrical indicators such as electrical conductivity, capacitance, and dielectric constant, or optical methods such as near-infrared light and Raman scattering. Transepidermal water loss (TEWL) is the amount of water that evaporates from the body through the stratum corneum. It is expressed as the weight of water per unit area and per unit time. There are no specific requirements for the measurement method; for example, it can be measured with a water evaporation measurement probe.

[0026] Skin surface image features, which are skin condition features, refer to features related to the skin condition that can be determined when the skin surface condition is grasped visually or as an image by photography. Skin surface image features include image color features that can be calculated from the color tone of an image of the skin surface, such as the amount of blemishes, porphyrin amount, saturation, and redness, as well as the outward tendency of sagging. The amount of blemishes refers to the amount per test area of ​​blemishes where the skin becomes partially brown or black due to the accumulation of melanin, mainly senile lentigines that increase with age and inflammatory hyperpigmentation associated with acne. There are no specific requirements for the measurement method; for example, areas that are darker or blacker than a set standard relative to the average skin color and brightness of the subject can be judged as blemishes, and the area ratio of blemishes can be defined as the amount of blemishes. The amount of porphyrin is the amount per test area of ​​porphyrin, a metabolite of acne bacteria and known as a source of reactive oxygen species. There are no specific requirements for the measurement method; for example, it can be measured by utilizing the property of fluorescing in response to UV light. Saturation refers to the vividness of the skin surface, and redness refers to the chromaticity in the red direction. There are no particular restrictions on the measurement method; for example, the degree to which vividness and redness are perceived can be quantified by establishing a standard through observation with the naked eye or a microscope, or a* and b* in the L*a*b* color system (L*: lightness, a*: red-direction hue, b*: yellow-direction hue) can be estimated in the test area, and the square root of the sum of the squares of a* and b* can be used to determine saturation, with a* representing redness. The direction of sagging refers to the direction in which the cheeks move inward (towards the center) or outward when they sag downwards due to sagging, and the degree of outward sagging estimated in this invention is the degree to which the direction of sagging is outward. If the degree of outward sagging is high, it can be said that there is a so-called bulldog-type sagging, where the skin sags outwards. On the other hand, if the degree of outward sagging is low, it can be said that there is a so-called sunken or hollow-faced look, where the skin sags inwards. Furthermore, since the direction of sagging is not affected by the size of the sagging, it can be used to distinguish between subtle differences in sagging types that are difficult to discern by visual inspection. The method for measuring the degree of outward sagging in this invention is not particularly limited; for example, it can be determined by measuring the degree to which a point or circle marked on the cheek moves outwards when the posture changes from a supine position to a sitting position.

[0027] Skin condition features, specifically internal skin condition features, refer to features related to the composition and physical properties of the skin's interior, which are difficult to visually grasp from the skin's surface. These internal skin condition features include collagen content, stratum corneum thickness, and elasticity. Collagen content refers to the amount of collagen present in the dermis. There are no specific requirements for measuring collagen content; for example, it can be estimated from the intensity of the reflection of ultrasound emitted into the skin. Stratum corneum thickness refers to the thickness of the stratum corneum present in the epidermis. There are no specific requirements for measuring it; for example, a confocal laser microscope can be used to irradiate infrared light and estimate the stratum corneum thickness from the reflected image, or confocal Raman spectroscopy can be used to measure the mass water content gradient in the depth direction and estimate the stratum corneum thickness by finding the inflection point of the mass water content gradient. Elasticity refers to the force in the skin that tries to repel external forces that cause strain, or the force that tries to return to its original state after deformation caused by external forces. The measurement method is not particularly restricted; for example, a probe with an opening at its tip can be placed on the skin, and negative pressure can be used to suction the skin surface through the opening for a certain period of time. After releasing the pressure, the degree of displacement of the skin surface due to the suction and the speed at which it returns to its original state after release can be used to estimate the value.

[0028] In this invention, we investigated the relationship between contour features, which are features obtained from the contour information of stratum corneum cells, and skin condition features. As a result, as shown in the examples described later, the contour features of stratum corneum cells correlate with skin condition features in the combinations listed below, and it was found that for each contour feature of stratum corneum cells used as an indicator, the corresponding skin condition features can be estimated. [1] By using the longest diameter, which is a contour feature of stratum corneum cells, as an indicator, the transepidermal water loss, which is a characteristic feature of skin condition, can be estimated. [2] By using the short axis, which is a contour feature of stratum corneum cells, as an indicator, the transepidermal water loss, which is a characteristic feature of skin condition, can be estimated. [3] By using the roundness ratio, which is a contour feature of stratum corneum cells, as an indicator, the transepidermal water loss, which is a characteristic feature of skin condition, can be estimated. [4] By using the roundness ratio, which is a contour feature of stratum corneum cells, as an indicator, the transepidermal water loss, which is a characteristic feature of skin condition, can be estimated. [5] By using the hexagonal ratio, which is a contour feature of stratum corneum cells, as an indicator, the transepidermal water loss, which is a characteristic feature of skin condition, can be estimated. [6] By using the overlapping area, which is a contour feature of stratum corneum cells, as an indicator, the transepidermal water loss, which is a characteristic of skin condition, can be estimated. [7] By using the variability of the roundness ratio, which is a contour feature of stratum corneum cells, as an indicator, the transepidermal water loss, which is a characteristic feature of skin condition, can be estimated. [8] By using the variability of the roundness ratio, which is a contour feature of stratum corneum cells, as an indicator, the transepidermal water loss, which is a characteristic feature of skin condition, can be estimated. [9] By using the variability of the hexagonal ratio, which is a contour feature of stratum corneum cells, as an indicator, the transepidermal water loss, which is a characteristic feature of skin condition, can be estimated.

[10] By using the roundness ratio, which is a contour feature of stratum corneum cells, as an indicator, the stratum corneum water content, which is a feature of skin condition, can be estimated.

[11] By using the roundness ratio, which is a contour feature of stratum corneum cells, as an indicator, the stratum corneum moisture content, which is a feature of skin condition, can be estimated.

[12] By using the ratio of regular hexagons, which is a contour feature of stratum corneum cells, as an indicator, the amount of stratum corneum water, which is a feature of skin condition, can be estimated.

[13] By using the overlapping distance, which is a contour feature of stratum corneum cells, as an indicator, the amount of collagen, which is a characteristic of skin condition, can be estimated.

[14] By using the variation in the longest axis, which is a contour feature of stratum corneum cells, as an indicator, the amount of collagen, which is a characteristic of skin condition, can be estimated.

[15] By using the roundness ratio, which is a contour feature of stratum corneum cells, as an indicator, the amount of porphyrin, which is a feature of skin condition, can be estimated.

[16] By using the hexagonal ratio, which is a contour feature of stratum corneum cells, as an indicator, the amount of porphyrin, which is a feature of skin condition, can be estimated.

[17] By using the variability of the roundness ratio, which is a contour feature of stratum corneum cells, as an indicator, the amount of porphyrin, which is a feature of skin condition, can be estimated.

[18] By using the variability of the overlapping distance, which is a contour feature of stratum corneum cells, as an indicator, the amount of blemishes, which is a skin condition feature, can be estimated.

[19] By using the variability of the overlap rate, which is a contour feature of stratum corneum cells, as an indicator, the amount of blemishes, which is a skin condition feature, can be estimated.

[20] By using the roundness ratio, which is a contour feature of stratum corneum cells, as an indicator, the saturation, which is a feature of skin condition, can be estimated.

[21] By using the roundness ratio, which is a contour feature of stratum corneum cells, as an indicator, the saturation, which is a feature of skin condition, can be estimated.

[22] By using the hexagonal ratio, which is a contour feature of stratum corneum cells, as an indicator, the saturation, which is a feature of skin condition, can be estimated.

[23] By using the roundness ratio, which is a contour feature of stratum corneum cells, as an indicator, it is possible to estimate redness, which is a feature of skin condition.

[24] By using the roundness ratio, which is a contour feature of stratum corneum cells, as an indicator, it is possible to estimate redness, which is a feature of skin condition.

[25] By using the ratio of regular hexagons, which is a contour feature of stratum corneum cells, as an indicator, it is possible to estimate redness, which is a feature of skin condition.

[26] By using the variability of the roundness ratio, which is a contour feature of stratum corneum cells, as an indicator, the redness, which is a skin condition feature, can be estimated.

[27] By using the variability of the roundness ratio, which is a contour feature of stratum corneum cells, as an indicator, it is possible to estimate redness, which is a skin condition feature.

[28] By using the variability of the hexagonal ratio, which is a contour feature of stratum corneum cells, as an indicator, the skin condition feature of redness can be estimated.

[29] By using the variability of the overlap rate, which is a contour feature of stratum corneum cells, as an indicator, the elasticity, which is a feature of skin condition, can be estimated.

[30] By using the variation in the longest diameter, which is a contour feature of stratum corneum cells, as an indicator, the transepidermal water loss, which is a characteristic feature of skin condition, can be estimated.

[31] By using the variation in the short axis, which is a contour feature of stratum corneum cells, as an indicator, the transepidermal water loss, which is a characteristic feature of skin condition, can be estimated.

[32] By using the roundness ratio, which is a contour feature of stratum corneum cells, as an indicator, the stratum corneum thickness, which is a feature of skin condition, can be estimated.

[33] By using the roundness ratio, which is a contour feature of stratum corneum cells, as an indicator, the amount of blemishes, which is a feature of skin condition, can be estimated.

[34] By using the variation in the short axis, which is a contour feature of stratum corneum cells, as an indicator, the skin condition feature of redness can be estimated.

[35] By using the variation in the short axis, which is a contour feature of stratum corneum cells, as an indicator, it is possible to estimate redness, which is a characteristic of skin condition.

[36] By using the roundness of the stratum corneum cells, which is a contour feature, as an indicator, the degree of outward sagging, which is a skin condition feature, can be estimated.

[0029] Furthermore, based on the correlation obtained in this invention, as shown in the examples described later (see Tables 1 and 2), the contour features of stratum corneum cells from multiple individuals can be used as indicators to compare and estimate the corresponding skin condition features as follows. [1] Using the longest diameter, which is a contour feature of stratum corneum cells, as an indicator, a higher value can be estimated to indicate lower transepidermal water loss, which is a characteristic of skin condition. [2] Using the short axis, which is a contour feature of stratum corneum cells, as an indicator, a higher value can be estimated to indicate a lower transepidermal water loss, which is a skin condition feature. [3] Using the roundness ratio, which is a contour feature of stratum corneum cells, as an indicator, a higher value can be estimated to indicate a lower transepidermal water loss, which is a skin condition feature. [4] Using the roundness ratio, which is a contour feature of stratum corneum cells, as an indicator, a higher value can be estimated to indicate a lower transepidermal water loss, which is a skin condition feature. [5] Using the hexagonal ratio, a characteristic feature of the stratum corneum cells, as an indicator, a higher value can be estimated to indicate a lower transepidermal water loss, a characteristic feature of skin condition. [6] Using the overlapping area, which is a contour feature of stratum corneum cells, as an indicator, a higher value can be estimated to indicate a lower transepidermal water loss, which is a skin condition feature. [7] Using the variability of the roundness ratio, which is a contour feature of stratum corneum cells, as an indicator, a higher value can be estimated to indicate a higher transepidermal water loss, which is a skin condition feature. [8] Using the variability of the roundness ratio, which is a contour feature of stratum corneum cells, as an indicator, a higher value can be estimated to indicate a higher transepidermal water loss, which is a skin condition feature. [9] Using the variability of the hexagonal ratio, which is a contour feature of stratum corneum cells, as an indicator, a higher value can be estimated to indicate a higher transepidermal water loss, which is a skin condition feature.

[10] Using the roundness ratio, which is a contour feature of stratum corneum cells, as an indicator, a higher value can be estimated to indicate a lower stratum corneum moisture content, which is a skin condition feature.

[11] Using the roundness ratio, which is a contour feature of stratum corneum cells, as an indicator, a higher value can be estimated to indicate a lower stratum corneum moisture content, which is a skin condition feature.

[12] Using the hexagonal ratio, which is a contour feature of stratum corneum cells, as an indicator, a higher value can be estimated to indicate a lower stratum corneum moisture content, which is a skin condition feature.

[13] Using the overlap distance, which is a contour feature of stratum corneum cells, as an indicator, a higher value can be estimated to indicate a lower amount of collagen, which is a skin condition feature.

[14] Using the variation in the longest axis, which is a contour feature of stratum corneum cells, as an indicator, a higher value can be estimated to indicate a higher amount of collagen, which is a skin condition feature.

[15] Using the roundness ratio, which is a contour feature of stratum corneum cells, as an indicator, a higher value can be estimated to indicate a lower amount of porphyrin, which is a skin condition feature.

[16] Using the hexagonal ratio, which is a contour feature of stratum corneum cells, as an indicator, a higher value can be estimated to indicate a lower amount of porphyrin, which is a skin condition feature.

[17] Using the variability of the roundness ratio, which is a contour feature of stratum corneum cells, as an indicator, a higher value can be estimated to indicate a higher amount of porphyrin, which is a skin condition feature.

[18] Using the variability of the overlapping distance, which is a contour feature of stratum corneum cells, as an indicator, a higher value can be estimated to indicate a higher amount of blemishes, which is a skin condition feature.

[19] Using the variability of the overlap rate, which is a contour feature of stratum corneum cells, as an indicator, a higher value can be estimated to indicate a higher amount of blemishes, which is a skin condition feature.

[20] Using the roundness ratio, which is a contour feature of stratum corneum cells, as an indicator, a higher value can be estimated to indicate a lower saturation, which is a skin condition feature.

[21] Using the roundness ratio, which is a contour feature of stratum corneum cells, as an indicator, a higher value can be estimated to indicate a lower saturation, which is a skin condition feature.

[22] Using the hexagonal ratio, which is a contour feature of stratum corneum cells, as an indicator, a higher value can be estimated to indicate a lower saturation, which is a skin condition feature.

[23] Using the roundness ratio, which is a contour feature of stratum corneum cells, as an indicator, a higher value can be estimated to indicate a lower redness, which is a skin condition feature.

[24] Using the roundness ratio, which is a contour feature of stratum corneum cells, as an indicator, a higher value can be estimated to indicate a lower redness, which is a skin condition feature.

[25] Using the hexagonal ratio, which is a contour feature of stratum corneum cells, as an indicator, a higher value can be estimated to indicate a lower redness, which is a skin condition feature.

[26] Using the variability of the roundness ratio, which is a contour feature of stratum corneum cells, as an indicator, a higher value can be estimated to indicate a higher level of redness, which is a skin condition feature.

[27] Using the variability of the roundness ratio, which is a contour feature of stratum corneum cells, as an indicator, a higher value can be estimated to indicate a higher level of redness, which is a skin condition feature.

[28] Using the variability of the hexagonal ratio, which is a contour feature of stratum corneum cells, as an indicator, a higher value can be estimated to indicate a higher level of redness, which is a skin condition feature.

[29] Using the variability of the overlap rate, which is a contour feature of stratum corneum cells, as an indicator, a higher value can be estimated to indicate lower elasticity, which is a skin condition feature.

[30] Using the variation in the longest diameter, which is a contour feature of stratum corneum cells, as an indicator, a higher value can be estimated to indicate a higher transepidermal water loss, which is a skin condition feature.

[31] Using the variation in the short axis, which is a contour feature of stratum corneum cells, as an indicator, a higher value can be estimated to indicate a higher transepidermal water loss, which is a skin condition feature.

[32] Using the roundness ratio, which is a contour feature of stratum corneum cells, as an indicator, a higher value can be estimated to indicate a higher stratum corneum thickness, which is a skin condition feature.

[33] Using the roundness ratio, which is a contour feature of stratum corneum cells, as an indicator, a higher value can be estimated to indicate a lower amount of blemishes, which is a skin condition feature.

[34] Using the variation in the short axis, which is a contour feature of stratum corneum cells, as an indicator, a higher value can be estimated to indicate a higher level of redness, which is a skin condition feature.

[35] Using the variation in the short axis, which is a contour feature of stratum corneum cells, as an indicator, a higher value can be estimated to indicate a higher level of redness, which is a skin condition feature.

[36] Using the roundness of the stratum corneum cells as an indicator, a higher value can be estimated to indicate a higher degree of outward sagging, which is a characteristic of skin condition.

[0030] In this invention, the contour features of stratum corneum cells collected from the skin of multiple subjects are used as explanatory variables, and the measured values ​​of the measured skin condition features are used as the objective variable. By substituting the contour features of the stratum corneum cells of a specific subject into this regression equation, the numerical value calculated can be estimated as the measured value of the subject's skin condition features. Preferred combinations of explanatory and objective variables are listed below. [1] Explanatory variable: Longest axis, Dependent variable: Transepidermal water loss [2] Explanatory variable: Short axis, Dependent variable: Transepidermal water loss [3] Explanatory variable: roundness, dependent variable: transepidermal water loss [4] Explanatory variable: roundness, dependent variable: transepidermal water loss [5] Explanatory variable: Hexagonal ratio, Dependent variable: Transepidermal water loss [6] Explanatory variable: overlapping area, dependent variable: transepidermal water loss [7] Explanatory variable: Variability of roundness, dependent variable: Transepidermal water loss [8] Explanatory variable: Variation in roundness, dependent variable: Transepidermal water loss [9] Explanatory variable: Variability of the hexagonal ratio, dependent variable: Transepidermal water loss

[10] Explanatory variable: roundness, dependent variable: stratum corneum water content

[11] Explanatory variable: roundness, dependent variable: stratum corneum water content

[12] Explanatory variable: Hexagonal ratio, Dependent variable: Stratum corneum water content

[13] Explanatory variable: overlap distance, dependent variable: collagen amount

[14] Explanatory variable: Variation in major axis, dependent variable: Collagen amount

[15] Explanatory variable: roundness, dependent variable: porphyrin amount

[16] Explanatory variable: Hexagonal ratio, Dependent variable: Porphyrin amount

[17] Explanatory variable: Variability of circularity, Dependent variable: Porphyrin amount

[18] Explanatory variable: Variation in overlap distance, dependent variable: Amount of stains

[19] Explanatory variable: Variation in overlap rate, dependent variable: Amount of stains

[20] Explanatory variable: Circularity, Dependent variable: Saturation

[21] Explanatory variable: roundness, dependent variable: saturation

[22] Explanatory variable: Hexagonal ratio, Dependent variable: Saturation

[23] Explanatory variable: Circularity, Dependent variable: Redness

[24] Explanatory variable: roundness, dependent variable: redness

[25] Explanatory variable: Hexagonal ratio, Dependent variable: Redness

[26] Explanatory variable: Variation in circularity, dependent variable: Redness

[27] Explanatory variable: Variation in roundness, dependent variable: Redness

[28] Explanatory variable: Variation in the ratio of regular hexagons, dependent variable: Redness

[29] Explanatory variable: Variation in overlap rate, dependent variable: Elasticity

[30] Explanatory variable: roundness, dependent variable: outward sagging

[0031] The embodiments disclosed herein should be considered in all respects to be illustrative and not restrictive. The scope of the present invention is indicated by the claims, not in the sense described above, and all modifications within the sense and scope equivalent to the claims are intended.

[0032] The present invention includes a method for extracting stratum corneum cells from the human body, but is a method for the purpose of skin cosmetic purposes and does not include medical procedures, that is, it does not include methods of performing surgery, treatment, or diagnosis on a human being, and more specifically, it does not include methods of performing surgery, treatment, or diagnosis on a human being by a physician or a person under the direction of a physician. [Examples]

[0033] The present invention will be specifically described below based on examples.

[0034] [Measurement of skin condition characteristics] For measuring skin condition characteristics, the cheek condition of 79 people (ages: 20s to 60s, gender: female and male) was measured. First, the face was washed, and then it was acclimatized for 15 minutes in a constant temperature and humidity room at 22°C and 50%. Stratum corneum moisture content was measured using the THz-ATR method (Japanese Patent Publication No. 2017-201254). Transepidermal water loss was measured using Tewameter (Courage+Khazaka). The amount of blemishes and porphyrin was measured using VISIA (Canfield Scientific). Saturation and redness were measured using a colorimeter (Konica Minolta). Stratum corneum thickness was measured using a stratum corneum thickness moisture meter (Asahi Biomed). Collagen content was measured using DermaLab (Cortex Technology). Elasticity was measured using Cutometer (Courage+Khazaka). The degree of outward movement of sagging was measured by measuring the angle at which a point marked on the cheek moved outward when the patient changed position from supine to sitting (using the method described in paragraph 0031 of Japanese Patent Application Publication No. 2020-157013).

[0035] [Measurement of contour features of stratum corneum cells] After measuring skin condition characteristics from the subjects described in paragraph 0034, stratum corneum was collected by attaching and removing a skin checker (promo tool) from the cheek. The skin checkers with the collected stratum corneum attached were immersed in a staining solution (0.1% amide black, 9% acetic acid, 0.9% sodium acetate, 90% water) for 24 hours, and then washed with tap water. Using a microscope (BZ-X700, KEYENCE), 48 stratum corneum images were acquired for each skin checker, and more than 100 stratum corneum cells were selected from each skin checker. The contour of each selected stratum corneum cell was extracted from the obtained stratum corneum cell images, and the contour characteristics of the stratum corneum cells were measured from the contour information. The mean value and coefficient of variation of each index of the stratum corneum cells of the subjects were then determined.

[0036] The entire process, from selecting stratum corneum cells to be targeted for contour extraction to measuring contour features, was carried out using the information processing method described in Japanese Patent Application No. 2021-118198. The method for calculating contour features from the contour information of stratum corneum cells in this information processing is as follows.

[0037] The major and minor axes were determined by approximating the stratum corneum cells as ellipses, and then determining the major and minor axes of the ellipses as the major and minor axes of the stratum corneum cells.

[0038] The circularity ratio was calculated by applying the values ​​to formula 1 below. The perfect circularity ratio was obtained by dividing the value of the minor axis by the value of the major axis. The hexagonal ratio was determined by aligning the centroids of regular hexagons with the same area as stratum corneum cells and rotating the hexagons to maximize the overlapping area.

[0039]

number

[0040] In measuring overlap features, even when three or more cells overlapped, we considered it as multiple pairs of overlapping cells, and determined that overlap existed for each combination. Measurements were then performed for each pair of overlapping cells. The overlap distance was determined by measuring the distance between two parallel lines that pass through the two furthest overlapping points, drawn parallel to and perpendicular to a line connecting two points (A and B in the figure) where two stratum corneum cells begin to overlap, as shown in Figure 3. The overlap area was determined by measuring the area of ​​the overlapping portion from the contours of the two overlapping cells. The overlap rate was calculated as the ratio of the overlapping area to the area of ​​the stratum corneum cells.

[0041] The degree of irregularity features for diameter, outline, and overlap were obtained by calculating the coefficient of variation for each contour feature for all stratum corneum cells selected from the same skin checker.

[0042] Table 1 shows the correlation coefficients obtained by Pearson's correlation analysis for some combinations of measurement results for stratum corneum cell contour features and skin condition features, and Table 2 shows the correlation coefficients obtained by Spearman's correlation analysis. For example, when correlation analysis was performed using the measured values ​​of the major axis, which is a contour feature of stratum corneum cells, and transepidermal water loss, which is a skin condition feature, for all subjects, a correlation coefficient of -0.429 was obtained. If a correlation is found as a result of the correlation analysis (in this invention, a correlation is recognized if the absolute value of the correlation coefficient is 0.3 or higher), it becomes possible to estimate the skin condition features using the stratum corneum cell contour features as an indicator based on that correlation. Furthermore, if a correlation is found in Pearson's correlation analysis, it can be said that the corresponding stratum corneum cell contour features and skin condition features have a nearly linear relationship. Therefore, by creating a regression equation from the stratum corneum cell contour features and the actual skin condition features, the skin condition features of a new subject can be estimated numerically.

[0043] [Table 1]

[0044] [Table 2]

[0045] [Estimation of skin condition characteristics] The redness of the cheeks of 76 individuals (ages: 20s to 60s, gender: female and male) was measured using a colorimeter (Konica Minolta). Stratum corneum samples were collected from the subjects' cheeks using a skin checker (Promotool). The skin checkers were immersed in a staining solution (0.1% amide black, 9% acetic acid, 0.9% sodium acetate, 90% water) for 24 hours and then washed with tap water. Using a microscope (BZ-X700, KEYENCE), 48 stratum corneum images were acquired per skin checker, and more than 100 stratum corneum cells were selected. From the obtained stratum corneum cell images, the contour of each selected stratum corneum cell was extracted, and the roundness, a contour feature of the stratum corneum cell, was measured from the contour information, and the average value was calculated. The entire process, from selecting stratum corneum cells for contour extraction to measuring contour features, was carried out using the information processing method described in Japanese Patent Application No. 2021-118198. In this information processing, the method for calculating the roundness from the contour information of stratum corneum cells involved first approximating the stratum corneum cells as ellipses, determining the major and minor axes of the ellipse as the major and minor axes of the stratum corneum cells, and then dividing the value of the minor axis by the value of the major axis to obtain the roundness.

[0046] In this measurement, when selecting two subjects from all subjects (76 subjects x 75 subjects / 2 combinations), the relationship between roundness and redness was examined, and in 63% of all combinations, it was found that in association with higher roundness, the subject had lower redness. Thus, it was possible to estimate which subject had higher redness with 63% accuracy from the difference in roundness, demonstrating that roundness can be used as an indicator, with a higher value indicating lower redness. Furthermore, if there is a correlation between the contour features of stratum corneum cells and skin condition features, the skin condition features can be similarly estimated by utilizing the contour features of stratum corneum cells.

[0047] Next, the equation of the regression curve was obtained from the scatter plot of roundness and redness measurements. When the difference between the estimated redness obtained by substituting roundness into the regression curve equation and the actual redness was calculated, it was found that for 83% of subjects, the redness was within ±2.1 of the estimated value of the regression curve. From this result, for example, if the roundness is 75, when applied to the regression curve, the redness becomes 11.523, and it can be determined with 83% probability that the redness is 11.523 ± 2.1. It was found that the value calculated by substituting the roundness obtained from the measurement of the subject's stratum corneum cells into the regression equation obtained with roundness as the explanatory variable and redness as the dependent variable can be used to estimate the subject's redness. Furthermore, if there is a correlation between the contour features of stratum corneum cells and skin condition features, the skin condition features can be similarly estimated by using the contour features of stratum corneum cells.

Claims

1. A method for estimating the measured value of skin condition features, wherein the contour features of stratum corneum cells collected from the skin of multiple subjects are used as explanatory variables, and the measured value of the measured skin condition features is used as the dependent variable in a regression equation, and the contour features of the stratum corneum cells of a specific subject are substituted into the regression equation to estimate the measured value of the subject's skin condition features. As contour features of stratum corneum cells, one or more variables selected from the following are used as explanatory variables: major axis, minor axis, circularity, perfect circularity, regular hexagonal ratio, overlap distance, variability of circularity, variability of perfect circularity, variability of regular hexagonal ratio, variability of major axis, and variability of minor axis. A method for estimating the measured value of a skin condition feature, with transepidermal water loss as the dependent variable (excluding medical procedures).

2. A method for estimating the measured value of skin condition features, wherein the contour features of stratum corneum cells collected from the skin of multiple subjects are used as explanatory variables, and the measured value of the measured skin condition features is used as the dependent variable in a regression equation, and the contour features of the stratum corneum cells of a specific subject are substituted into the regression equation to estimate the measured value of the subject's skin condition features. As contour features of stratum corneum cells, one or more variables selected from circularity, perfect roundness, and regular hexagonal ratio are used as explanatory variables. A method for estimating the measured values ​​of skin condition features, with stratum corneum moisture content as the dependent variable (excluding medical procedures).

3. A method for estimating the measured value of skin condition features, wherein the contour features of stratum corneum cells collected from the skin of multiple subjects are used as explanatory variables, and the measured value of the measured skin condition features is used as the dependent variable in a regression equation, and the contour features of the stratum corneum cells of a specific subject are substituted into the regression equation to estimate the measured value of the subject's skin condition features. As contour features of stratum corneum cells, one or more variables selected from overlap distance and variation in major axis are used as explanatory variables. A method for estimating the measured value of a skin condition feature, with collagen content as the dependent variable (excluding medical procedures).

4. A method for estimating the measured value of skin condition features, wherein the contour features of stratum corneum cells collected from the skin of multiple subjects are used as explanatory variables, and the measured value of the measured skin condition features is used as the dependent variable in a regression equation, and the contour features of the stratum corneum cells of a specific subject are substituted into the regression equation to estimate the measured value of the subject's skin condition features. As contour features of stratum corneum cells, one or more variables selected from the roundness ratio, hexagonal ratio, and variability of the roundness ratio are used as explanatory variables. A method for estimating the measured value of a skin condition feature, with porphyrin content as the dependent variable (excluding medical procedures).

5. A method for estimating the measured value of skin condition features, wherein the contour features of stratum corneum cells collected from the skin of multiple subjects are used as explanatory variables, and the measured value of the measured skin condition features is used as the dependent variable in a regression equation, and the contour features of the stratum corneum cells of a specific subject are substituted into the regression equation to estimate the measured value of the subject's skin condition features. As contour features of stratum corneum cells, one or more variables selected from the variability of overlapping distance and the variability of overlapping rate are used as explanatory variables. A method for estimating the measured value of a skin condition feature, with the amount of blemishes as the dependent variable (excluding medical procedures).

6. A method for estimating the measured value of skin condition features, wherein the contour features of stratum corneum cells collected from the skin of multiple subjects are used as explanatory variables, and the measured value of the measured skin condition features is used as the dependent variable in a regression equation, and the contour features of the stratum corneum cells of a specific subject are substituted into the regression equation to estimate the measured value of the subject's skin condition features. As contour features of stratum corneum cells, one or more variables selected from circularity, perfect roundness, and regular hexagonal ratio are used as explanatory variables. A method for estimating the measured value of a skin condition feature, with saturation as the dependent variable (excluding medical procedures).

7. A method for estimating the measured value of skin condition features, wherein the contour features of stratum corneum cells collected from the skin of multiple subjects are used as explanatory variables, and the measured value of the measured skin condition features is used as the dependent variable in a regression equation, and the contour features of the stratum corneum cells of a specific subject are substituted into the regression equation to estimate the measured value of the subject's skin condition features. As contour features of stratum corneum cells, one or more variables selected from circularity, perfect roundness, regular hexagonal ratio, variability of circularity, variability of perfect roundness, and variability of regular hexagonal ratio are used as explanatory variables. A method for estimating the measured value of a skin condition feature, with redness as the dependent variable (excluding medical procedures).

8. A method for estimating the measured value of skin condition features, wherein the contour features of stratum corneum cells collected from the skin of multiple subjects are used as explanatory variables, and the measured value of the measured skin condition features is used as the dependent variable in a regression equation, and the contour features of the stratum corneum cells of a specific subject are substituted into the regression equation to estimate the measured value of the subject's skin condition features. As a contour feature of stratum corneum cells, the variability of the overlap rate is used as an explanatory variable. A method for estimating the measured value of a skin condition feature, with elasticity as the dependent variable (excluding medical procedures).

9. A method for estimating the measured value of skin condition features, wherein the contour features of stratum corneum cells collected from the skin of multiple subjects are used as explanatory variables, and the measured value of the measured skin condition features is used as the dependent variable in a regression equation, and the contour features of the stratum corneum cells of a specific subject are substituted into the regression equation to estimate the measured value of the subject's skin condition features. As a contour feature of stratum corneum cells, roundness is used as the explanatory variable. A method for estimating the measured value of a skin condition feature, with the degree of outward sagging as the dependent variable (excluding medical procedures).

10. A method for screening agents that improve skin condition features using a method for estimating the measured value of skin condition features according to any of Claims 1 to 9.

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