JP5398055B2 - How to identify “dullness” and “stain” - Google Patents

How to identify “dullness” and “stain” Download PDF

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JP5398055B2
JP5398055B2 JP2008211822A JP2008211822A JP5398055B2 JP 5398055 B2 JP5398055 B2 JP 5398055B2 JP 2008211822 A JP2008211822 A JP 2008211822A JP 2008211822 A JP2008211822 A JP 2008211822A JP 5398055 B2 JP5398055 B2 JP 5398055B2
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skin
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dullness
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JP2010048611A (en
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川口勝浩
平尾直靖
山南春奈
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Shiseido Co Ltd
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Description

本発明は、血小板数の測定値を利用する客観的なすみとシミとの識別方法に関する。 The present invention relates to a method of identifying an objective Ku corner and stains utilizing the measurements of platelet count.

今日のコスメティックビジネスにおいては、顧客の1人1人の肌のコンディションにあわせて最適な化粧品を提案したり、最適な美容ケアソリューションを提供するというような、顧客へのきめ細かな個別対応が求められている。肌のトラブルの評価には視診、専用の肌測定用機器等の手法を利用することが一般的である。しかしこれらの手法は、既に発生した肌のトラブルを評価することはできるが、肌のトラブルが将来発生するリスクを評価することはできない。   In today's cosmetics business, there is a need for meticulous individual response to customers, such as proposing optimal cosmetics according to the skin condition of each customer and providing optimal beauty care solutions. ing. For the evaluation of skin troubles, it is common to use techniques such as visual inspection and dedicated skin measuring equipment. However, these methods can evaluate skin problems that have already occurred, but cannot evaluate the risk of future skin problems.

肌のトラブルが発生する要因のうち、気温、湿度又は紫外線のような環境要因や、精神的ストレスのような心理的要因は顧客が自覚している。しかし生理学的要因は顧客が直接自覚するものではないため、別途評価を行う意義がある。肌のトラブルの生理学的要因の候補としては、皮膚の血流の物理・化学的特性(組織血流量、組織酸素飽和度等)、ホルモン(プロゲステロン、プロラクチン等)、生体内の抗酸化力(ビタミンA、C等)等の生化学的特性、女性ホルモン(エストラジオール等)、細胞外マトリクス等に関連する生化学的特性が考えられる。これらの特性を含む各種の生理学的指標を用いて肌のトラブルのリスクを評価する試みが行われた例はほとんどない。   Among the factors that cause skin problems, customers are aware of environmental factors such as temperature, humidity, and ultraviolet rays, and psychological factors such as mental stress. However, since physiological factors are not directly perceived by customers, it is worthwhile to evaluate them separately. Possible physiological factors for skin problems include physical and chemical characteristics of skin blood flow (tissue blood flow, tissue oxygen saturation, etc.), hormones (progesterone, prolactin, etc.), and antioxidant power (vitamins in vivo) A, C, etc.), biochemical characteristics related to female hormones (estradiol, etc.), extracellular matrix, etc. are conceivable. There have been few examples of attempts to evaluate the risk of skin trouble using various physiological indicators including these characteristics.

そこで、肌のトラブルに関する大規模な調査を行って肌のトラブルと各種生理学的指標との関連の有無及びその程度を明らかにし、統計的な裏づけのある客観的な証拠すなわちエビデンスに基づいて、肌のトラブルのリスクを評価する方法を開発する必要がある。   Therefore, a large-scale survey on skin troubles was conducted to clarify the existence and extent of the relationship between skin troubles and various physiological indicators, and based on objective evidence with statistical support, that is, evidence. There is a need to develop a method to assess the risk of trouble.

本発明は、くすみ及び/又はシミのリスク評価方法を提供する。本発明の評価方法は、被験者の血小板数の測定値を指標として被験者の肌におけるくすみ及び/又はシミのリスクを評価するステップとを含む。   The present invention provides a risk assessment method for dullness and / or spots. The evaluation method of the present invention includes the step of evaluating the risk of dullness and / or spots on the skin of the subject using the measured value of the platelet count of the subject as an index.

本発明は、くすみとシミとの識別方法を提供する。本発明の識別方法は、被験者の血小板数の測定値を指標として被験者の肌におけるくすみとシミとを識別するステップとを含む。   The present invention provides a method for discriminating between dullness and spots. The identification method of the present invention includes the step of identifying dullness and spots on the skin of the subject using the measured value of the platelet count of the subject as an index.

本明細書において「肌のトラブル」とは、肌の外観状態が正常でない状態を指し、シミ、くすみ、しわ、たるみ等を含む。   As used herein, “skin trouble” refers to a condition in which the appearance of the skin is not normal, and includes spots, dullness, wrinkles, sagging, and the like.

本明細書において「シミ」とは、肌のトラブルの一種であって、肌に色素が沈着することにより生じ、肌上の色素が沈着した部位と沈着していない部位との境界が明瞭である程度に色素が沈着した状態を指す。本明細書における「シミ」は、日光性黒子、脂漏性角化症等のようなケラチノサイトの異常によるシミと、肝斑、雀卵斑、紫外線照射後の光線性花弁状色素斑等のようなメラノサイトの異常によるシミと、色素沈着性接触皮膚炎、固定薬疹、外傷後色素沈着等のような炎症後色素沈着症とを含む。本明細書における「シミ」は、後天性真皮メラノサイトーシス、扁平母斑、太田母斑等のような、シミに似たメラノサイトが多いあざも含む場合がある。   In this specification, “stain” is a kind of skin trouble, which occurs when pigment is deposited on the skin, and the boundary between the pigment deposited site and the non-deposited site on the skin is clear to some extent. Refers to the state of pigmentation. As used herein, “stain” refers to spots caused by abnormal keratinocytes such as sunlight melanoma, seborrheic keratosis, liver spots, sparrow egg spots, and light petal-like pigment spots after UV irradiation. Stains due to abnormal melanocytes and post-inflammation pigmentation such as pigmented contact dermatitis, fixed drug eruption, post-traumatic pigmentation and the like. As used herein, “stain” may also include bruises with many melanocytes resembling spots, such as acquired dermal melanocytosis, flat nevus, Ota nevus and the like.

本明細書において「くすみ」とは、肌のトラブルの一種であって、肌への色素の沈着、血流の低下、肌表面の凹凸、皮膚の汚れ等により肌が暗く見える部位が生じ、該肌が暗く見える部位は弥漫(びまん)しており、該暗く見える部位と暗く見えない部位との境界が不明瞭である状態を指す。   In the present specification, “dullness” is a kind of skin trouble, and a site where the skin appears dark due to pigmentation on the skin, a decrease in blood flow, unevenness on the skin surface, dirt on the skin, etc. The part where the skin appears dark is diffuse, and the boundary between the part that appears dark and the part that does not appear dark is unclear.

本明細書において「しわ」とは、肌のトラブルの一種であって、加齢により生じる皮表の線状陥没が作り出す紋様が、特定の領域に集中して、かつ、大きさ及び配列の不規則性をもって存在する状態を指す。   In this specification, “wrinkle” is a kind of skin trouble, and the pattern created by the linear depression of the skin surface caused by aging is concentrated in a specific area, and the size and arrangement are not correct. A state that exists with regularity.

本明細書において「たるみ」とは、肌のトラブルの一種であって、加齢に伴い皮膚の張りが失われて、眼又は口の周囲、頬下等に皮膚の膨らみが観察される状態を指す。   In this specification, “sagging” is a kind of skin trouble, which is a state in which skin tension is lost with aging, and swelling of the skin is observed around the eyes or mouth, under the cheeks, etc. Point to.

本明細書における用語「肌のトラブルのリスク」は、既に発生している肌のトラブルが継続し、あるいは、増悪する蓋然性と、肌のトラブルが発生する潜在的な蓋然性とを含む。本明細書における用語「肌のトラブルのリスク評価」は、肌のトラブルのリスクの有無についての定性的な評価と、リスクの蓋然性についての定量的な評価とを含む。   The term “risk of skin trouble” in this specification includes a probability that a skin trouble that has already occurred continues or worsens, and a potential probability that a skin trouble occurs. The term “skin trouble risk assessment” in this specification includes qualitative assessment of the presence or absence of skin trouble risk and quantitative assessment of risk probability.

本明細書において「血小板数」は、血液の単位体積当たりの血小板の数である。血小板は、血液中に存在する無核の細胞である。血小板は巨核球の細胞質の断片であり、傷害された血管内皮細胞に接触するとそこで粘着・凝集反応を起こすことにより、止血機序に重要な役割を果たすことが知られる。   As used herein, “platelet count” is the number of platelets per unit volume of blood. Platelets are anuclear cells that are present in the blood. It is known that platelets are cytoplasmic fragments of megakaryocytes and play an important role in the hemostasis mechanism by causing adhesion / aggregation when they contact damaged vascular endothelial cells.

以下の実施例で詳しく説明するとおり、本発明は、被験者の血中血小板数のの測定値が高いほど、当該被験者がくすみを有する蓋然性が低く、逆に、シミを有する蓋然性は高いという発明者らの調査結果に基づいて完成された。   As will be described in detail in the following examples, the present invention is that the higher the measured value of the blood platelet count of a subject, the lower the probability that the subject will have dullness, and the higher the probability that the subject will have stains. It was completed based on these survey results.

本発明の評価方法又は識別方法の血小板数の測定は、臨床検査の分野の当業者に周知のいかなる検定方法を使用して実施されてもかまわない。好ましくは、電気抵抗方式や光学的方式による自動血球測定装置を使用する方法、位相差顕微鏡を使用して目視で計測する直接法、赤血球数と赤血球単位個数当たりの血小板数とを計測し血液中の血小板数を算出する間接法等により実施される場合がある。また、血小板数の測定は、通常の医療機関における血液検査の一項目として実施される場合がある。   The platelet count measurement of the evaluation method or identification method of the present invention may be performed using any assay method well known to those skilled in the clinical laboratory field. Preferably, a method using an automatic blood cell measuring device using an electric resistance method or an optical method, a direct method using a phase-contrast microscope to visually measure, a red blood cell count and a platelet count per unit red blood cell count, In some cases, an indirect method for calculating the number of platelets is used. In addition, the measurement of the platelet count may be performed as one item of blood test in a normal medical institution.

被験者の血小板数の測定値を指標として被験者の肌におけるくすみ及び/又はシミのリスクを評価し、あるいは、被験者の肌におけるくすみとシミとを識別するための判断基準は、統計学的な手法により設定される場合がある。統計学的な手法により設定される判断基準は、例えば被験者の血小板数の測定値とくすみ及び/又はシミの有無とを関連づける判別関数の場合がある。前記判断基準は、血小板数と被験者の肌におけるくすみ及び/又はシミの有無とを関連付ける判別関数をも併用するステップワイズ判別分析の場合がある。   Evaluation of the risk of dullness and / or spots on the subject's skin using the measured value of the platelet count of the subject as an index, or the judgment criteria for distinguishing between dullness and spots on the subject's skin are based on statistical methods. May be set. The determination criterion set by a statistical method may be, for example, a discriminant function that correlates the measured value of the platelet count of the subject with the presence or absence of dullness and / or spots. The determination criterion may be a stepwise discriminant analysis that also uses a discriminant function that associates the platelet count with dullness and / or the presence or absence of spots on the subject's skin.

以下の実施例は例示のために説明するのであり、本発明の特許請求の範囲はこれらの実施例により何ら限定されるものではない。   The following examples are set forth for purposes of illustration, and the claims of the present invention are not limited in any way by these examples.

1.くすみ、シミ又はしわ・たるみの有無及びその程度と、肌及び全身の所見との関連性の解析
1−1.方法
(被験者の選定)
健康な成人女性150名を対象として、後述の皮膚科医による視診、生理学的・医学的測定、肌・身体測定(以下、「視診等」という。)の被験者を選定するためのアンケート調査を実施した。アンケート調査の前に、前記150名の成人女性には試験の概要が説明され、アンケート調査への協力について自由意志に基づく書面による同意を得た。このアンケート調査における主な質問項目を表1に示す。アンケート調査の結果から、現在の顔の肌の状態(顔の肌のトラブルを有すること)及び体質(顔の肌のトラブルを発生しやすいこと)についての自覚の有無及び程度を基準として、皮膚科医による視診の対象とする被験者を選定した。顔の肌のトラブルは、くすみ、シミ及びしわ・たるみに分類した。選定の際に、被験者が、くすみ、シミ又はしわ・たるみのうち少なくとも1種類の肌のトラブルのみ自覚があること、並びに、顔の肌の状態及び体質に影響を与える可能性がある他の生活習慣、健康状態等について特に自覚がないことを確認した。
1. 1. Analysis of the relationship between the presence and extent of dullness, spots, wrinkles and sagging, and findings on the skin and the whole body 1-1. Method (Selection of subjects)
A questionnaire survey was conducted on 150 healthy adult women to select subjects to be examined by dermatologists described below, physiological and medical measurements, and skin and body measurements (hereinafter referred to as “inspection etc.”). did. Prior to the questionnaire survey, the 150 adult women were given an overview of the study and written consent was obtained based on their free will to cooperate in the questionnaire survey. Table 1 shows the main question items in this questionnaire survey. Based on the results of the questionnaire survey, dermatology based on the presence and degree of awareness of the current facial skin condition (having facial skin trouble) and constitution (prone to face skin trouble) Subjects were selected for medical examination. Facial skin problems were classified into dullness, spots and wrinkles / sagging. At the time of selection, the subject is aware of at least one type of skin trouble among dullness, spots, wrinkles and sagging, and other life that may affect the condition and constitution of the facial skin It was confirmed that there was no particular awareness of habits and health conditions.

アンケート調査の結果、前記150名の成人女性から、くすみに関する顔の肌の状態及び体質について顕著な自覚を有する者17名と、くすみに関する顔の肌の状態又は体質について自覚をほとんど有しない者8名と、シミに関する顔の肌の状態及び体質について顕著な自覚を有する者17名と、シミに関する顔の肌の状態又は体質について自覚をほとんど有しない者8名と、しわ・たるみに関する顔の肌の状態及び体質について顕著な自覚を有する者17名と、しわ・たるみに関する顔の肌の状態又は体質について自覚をほとんど有しない者8名との計75名の被験者を選定した。   As a result of the questionnaire survey, from the 150 adult women, 17 people who have a remarkable awareness of facial skin condition and constitution related to dullness, and 8 who have little awareness of facial skin condition or constitution related to dullness 8 17 people who have a remarkable awareness of the name, facial skin condition and constitution related to the stain, 8 people who have little awareness of the facial skin condition or constitution related to the stain, and facial skin related to wrinkles and sagging A total of 75 subjects were selected, including 17 persons who had a remarkable awareness of the condition and constitution, and 8 persons who had little awareness of the facial skin condition or constitution regarding wrinkles and sagging.

(被験者による同意)
前記アンケート調査の結果として選定された75名の被験者を対象として、文書に基づいて試験内容等について説明した。その上で、皮膚科医による視診等への参加について被験者の自由意志に基づく文書による同意を得た。
(Consent by subject)
The test contents and the like were explained based on documents for 75 subjects selected as a result of the questionnaire survey. In addition, written consent based on the subject's free will was obtained for participation in a visual examination by a dermatologist.

(皮膚科医による視診)
前記アンケート調査の結果として選定された75名の被験者を対象として、後述の生理学的・医学的測定及び肌・身体測定の被験者を選定するための皮膚科医による視診を実施した。この視診では、資生堂ビューティーソリューション開発センターにおいて肌の状態の視感評価に使用される基準を示した「視感評価マニュアル」に基づき、くすみ、シミ又はしわ・たるみの度合いを評価した。この評価結果を基準として、顕著なくすみ、シミ又はしわ・たるみを有する者と、くすみ、シミ又はしわ・たるみをほとんど有しない者とを、前記皮膚科医の判断で選定した。また視診当日には、体調、精神的ストレス、制限事項の遵守状態等についてアンケート調査を実施し、視診結果に影響を与える可能性のある項目への回答が特異な傾向を示さないことを確認した。この結果として、前記75名の被験者から、以下に示す計6群、計30名の被験者を選定した。
・くすみに関する顔の肌の状態及び体質について顕著な自覚を有し、かつ、顕著なくすみを有する被験者(第1群の被験者)7名
・くすみに関する顔の肌の状態又は体質について自覚をほとんど有さず、かつ、くすみをほとんど有しない被験者(第2群の被験者)3名
・シミに関する顔の肌の状態及び体質について顕著な自覚を有し、かつ、顕著なシミを有する被験者(第3群の被験者)7名
・シミに関する顔の肌の状態又は体質について自覚をほとんど有さず、かつ、シミをほとんど有しない被験者(第4群の被験者)3名
・しわ・たるみに関する顔の肌の状態及び体質について顕著な自覚を有し、かつ、顕著なしわ・たるみを有する被験者(第5群の被験者)7名
・しわ・たるみに関する顔の肌の状態又は体質について自覚をほとんど有さず、かつ、しわ・たるみをほとんど有しない被験者(第6群の被験者)3名
前記30名の被験者を選定する過程で、以下に示す除外基準に抵触する者は除外した。
(Visit by a dermatologist)
For 75 subjects selected as a result of the questionnaire survey, a dermatologist was inspected to select subjects for physiological / medical measurement and skin / body measurement described later. In this inspection, the Shiseido Beauty Solution Development Center evaluated the degree of dullness, spots, wrinkles and sagging based on the “Visual Evaluation Manual” which shows the criteria used for visual evaluation of skin condition. Based on this evaluation result, a person having notable dullness, spots or wrinkles / sag and a person having little dullness, spots or wrinkles / sag were selected at the judgment of the dermatologist. In addition, on the day of the visit, a questionnaire survey was conducted on physical condition, mental stress, compliance with restrictions, etc., and it was confirmed that responses to items that might affect the result of the inspection do not show a unique tendency. . As a result, a total of 30 subjects were selected from the 75 subjects, for a total of 6 groups shown below.
・ 7 subjects with significant awareness of facial skin condition and constitution related to dullness and 7 subjects with significant dullness (subjects of group 1) ・ Almost aware of facial skin condition or constitution related to dullness Three subjects who have almost no dullness (subjects of the second group). Subjects who have a remarkable awareness of the skin condition and constitution of the face related to the stains, and have a noticeable spot (the third group) No. of subjects) 7 people ・ Facial skin condition regarding wrinkles and sagging 3 subjects (subjects of the fourth group) who have little awareness of facial skin condition or constitution related to spots and almost no spots (subjects of the fourth group) 7 subjects with significant wrinkles and sagging (5th group subjects), and almost no awareness of facial skin condition or constitution related to wrinkles and sagging Not, and, in the process of selecting almost no subjects (Group 6 subjects) of three the 30 subjects wrinkles sagging were excluded who violate the exclusion criteria listed below.

除外基準
a.現在治療目的に通院し、医薬品を服用(使用)している者
b.妊娠している者、授乳中の者、妊娠の予定のある者
c.他の臨床試験に参加中の者
d.その他、試験責任医師あるいは試験担当医師が不適当と判断した者
(生理学的・医学的測定及び肌・身体測定)
前記30名の被験者を対象として、生理学的・医学的測定及び肌・身体測定を実施した。これらの測定は、測定データの再現性を確認するために、同一の被験者に対し同一の測定項目について冬季(2007年3月)及び春季(2007年5−6月)の2回繰り返して実施した。生理学的・医学的測定における測定内容は、血液検査、尿検査、血管硬化度測定、頸動脈内膜中膜複合体肥厚(IMT)測定、筋力測定、体組織測定、呼吸機能検査、循環検査、心臓超音波検査、聴力検査、平衡機能検査、声の老化検査、認知症検査及び自律神経バランス検査である。肌・身体測定における測定内容は、角層水分量測定、経表皮水分蒸散量測定、皮脂量測定、肌拡大画像撮影、顔写真撮影、肌粘弾性測定、肌色測定、肌血流測定、肌表面温度測定、総合肌診断、基礎代謝測定及び体温測定であった。また測定当日には、体調、精神的ストレス、制限事項の遵守状態等についてアンケート調査を実施し、測定結果に影響を与える可能性のある項目への回答が特異な傾向を示さないことを確認した。
Exclusion criteria a. Those who are currently in the hospital for treatment purposes and are taking (using) medicinal products b. Pregnant, breastfeeding, or planning to become pregnant c. Participants in other clinical trials d. Others who are judged inappropriate by the investigator or the investigator (physiological / medical measurement and skin / body measurement)
Physiological and medical measurements and skin and body measurements were performed on the 30 subjects. In order to confirm the reproducibility of the measurement data, these measurements were repeated twice for the same subject on the same measurement item in winter (March 2007) and spring (May-June 2007). . Physiological and medical measurements include blood tests, urinalysis, vascular sclerosis measurement, carotid intima-media complex thickness (IMT) measurement, muscle strength measurement, body tissue measurement, respiratory function test, circulation test, These are cardiac ultrasonography, hearing test, balance function test, voice aging test, dementia test, and autonomic nerve balance test. Measurement content in skin / body measurement includes stratum corneum moisture measurement, transepidermal moisture transpiration measurement, sebum measurement, enlarged skin image photography, facial photography, skin viscoelasticity measurement, skin color measurement, skin blood flow measurement, skin surface These were temperature measurement, comprehensive skin diagnosis, basal metabolism measurement, and body temperature measurement. In addition, on the day of the measurement, a questionnaire survey was conducted on physical condition, mental stress, compliance with restrictions, etc., and it was confirmed that responses to items that might affect the measurement results did not show a unique tendency .

血液検査は、試験担当医師が被験者の両肘の内側の静脈より真空採血管を用いて採取した血液試料(被験者1人当たり25mL)を使用して行った。血液試料は採取後直ちに冷蔵保管した。その後血液試料についてグルタミン酸オキサロ酢酸トランスアミナーゼ(GOT)活性、グルタミン酸ピルビン酸トランスアミナーゼ(GPT)活性、γ−グルタミルトランスペプチダーゼ(γ−GTP)活性、乳酸デヒドロゲナーゼ(LDH)活性、コリンエステラーゼ活性、蛋白分画、アルブミン/グロブリン比、アルブミン濃度、クレアチニン濃度、尿酸値、総コレステロール量、LDLコレステロール量、SD−LDLコレステロール量、HDL2コレステロール(HDL2)量、HDL3コレステロール(HDL3)量、中性脂肪量、遊離脂肪酸量、リポ蛋白a量、レムナント様リポ蛋白c量、血糖値、ヘモグロビンA1c量、フルクトサミン濃度、Cペプチド濃度、成長ホルモン(インスリン様成長因子−1(IGF−1))濃度、甲状腺ホルモン濃度、副腎皮質ホルモン濃度、デヒドロエピアンドロステロンサルフェート(DHEA−s)濃度、フリーテストステロン濃度、プロゲステロン濃度、プロラクチン濃度、エストラジオール濃度、NK細胞活性、グラニュライシン濃度、インターロイキン−6濃度、インターロイキン−10濃度、白血球数、赤血球数、ヘモグロビン量、ヘマトクリット値、血小板数、フェリチン量、血清過酸化脂質(血清LPO)量、鉄濃度、銅濃度、血清総抗酸化能(STAS)、ビタミンC濃度、葉酸濃度、ビタミンB12濃度、ルテイン量+ゼアキサンチン量、β−クリプトキサンチン濃度、リコピン濃度、α−カロテン濃度、β−カロテン濃度、ビタミンA濃度、α−トコフェロール濃度、δ−トコフェロール濃度、γ−トコフェロール濃度、α−トコフェロール/総トコフェロール比、ユビキノール濃度、ビタミンB濃度、ビタミンB濃度、ビタミンB濃度、高感度検査によるC反応性タンパク質(高感度CRP)量、総ホモシステイン量、アディポネクチン量、フィブリノゲン量、総プラスミノーゲンアクティベーターインヒビター(総PAI−1)量、細胞間接着分子−1(ICAM−1)量、P−セレクチン量、非対称性ジメチルアルギニン(ADMA)量、単球走化性タンパク質−1(MCP−1)量、マトリックスメタロプロテイナーゼ−9(MMP−9)量、アポEフェノタイプ及び脳性ナトリウム利尿ペプチド(BNP)量を定法により分析した。 The blood test was performed using a blood sample (25 mL per subject) collected by the test doctor using a vacuum blood collection tube from the veins inside the elbows of the subjects. Blood samples were stored refrigerated immediately after collection. Thereafter, glutamate oxaloacetate transaminase (GOT) activity, glutamate pyruvate transaminase (GPT) activity, γ-glutamyl transpeptidase (γ-GTP) activity, lactate dehydrogenase (LDH) activity, cholinesterase activity, protein fraction, albumin / Globulin ratio, albumin concentration, creatinine concentration, uric acid level, total cholesterol level, LDL cholesterol level, SD-LDL cholesterol level, HDL2 cholesterol (HDL2) level, HDL3 cholesterol (HDL3) level, neutral fat level, free fatty acid level, lipo Protein a amount, remnant-like lipoprotein c amount, blood glucose level, hemoglobin A1c amount, fructosamine concentration, C peptide concentration, growth hormone (insulin-like growth factor-1 (IGF-1)) concentration , Thyroid hormone concentration, corticosteroid concentration, dehydroepiandrosterone sulfate (DHEA-s) concentration, free testosterone concentration, progesterone concentration, prolactin concentration, estradiol concentration, NK cell activity, granulysin concentration, interleukin-6 concentration, interleukin-6 concentration Leukine-10 concentration, white blood cell count, red blood cell count, hemoglobin content, hematocrit value, platelet count, ferritin content, serum lipid peroxide (serum LPO) content, iron concentration, copper concentration, serum total antioxidant capacity (STAS), vitamin C Concentration, folic acid concentration, vitamin B 12 concentration, lutein amount + zeaxanthin amount, β-cryptoxanthin concentration, lycopene concentration, α-carotene concentration, β-carotene concentration, vitamin A concentration, α-tocopherol concentration, δ-tocopherol concentration, γ -Toco Fellow Concentration, α-tocopherol / total tocopherol ratio, ubiquinol concentration, vitamin B 1 concentration, vitamin B 2 concentration, vitamin B 6 concentration, C-reactive protein (high-sensitivity CRP) amount by high-sensitivity test, total homocysteine amount, adiponectin Amount, fibrinogen amount, total plasminogen activator inhibitor (total PAI-1) amount, intercellular adhesion molecule-1 (ICAM-1) amount, P-selectin amount, asymmetric dimethylarginine (ADMA) amount, monocyte chemotaxis The amount of sex protein-1 (MCP-1), matrix metalloproteinase-9 (MMP-9), apoE phenotype and brain natriuretic peptide (BNP) were analyzed by a conventional method.

尿検査は、被験者が各自で適当量採取した尿試料を使用して行った。採取した尿試料について、尿中アルブミン濃度、尿中シスタチンC濃度、尿中シスタチンC/クレアチニン比、尿デオキシピリジノリン量、8−ヒドロキシ−デオキシグアノシン(8OHdG)生成速度、イソプラスタン生成速度及びコエンザイムQ10(CoQ10)酸化率を定法により分析した。   The urine test was performed using a urine sample collected by the subject in an appropriate amount. About collected urine samples, urinary albumin concentration, urinary cystatin C concentration, urinary cystatin C / creatinine ratio, urine deoxypyridinoline amount, 8-hydroxy-deoxyguanosine (8OHdG) production rate, isoplastane production rate and Coenzyme Q10 (CoQ10) oxidation rate was analyzed by a conventional method.

血管硬化度測定としては、血圧の測定と、動脈硬化度の測定と、血管硬化度の測定と、加速度波の測定と、眼底検査とを実施した。血圧の測定は、自動血圧計BP203RV−11(日本コーリン株式会社)を使用して収縮期血圧及び拡張期血圧の測定を実施した。動脈硬化度の測定は、フォルムPWV(日本コーリン株式会社)及びVS−1000(フクダ電子株式会社)を使用して脈波伝導速度(PWV)を測定することにより実施した。血管硬化度の測定は、CVMS2000(株式会社オサチ)を使用して足首上腕血圧指数(ABI=下肢血圧/上肢血圧)を測定することにより実施した。加速度波の測定は、アルテット(株式会社ユメディカ)を使用して実施した。眼底検査は、CR5(キャノン株式会社)を使用して眼底画像を撮影することにより実施した。   As blood vessel sclerosis measurement, blood pressure measurement, arteriosclerosis measurement, vascular sclerosis measurement, acceleration wave measurement, and fundus examination were performed. Measurement of blood pressure was performed by measuring systolic blood pressure and diastolic blood pressure using an automatic sphygmomanometer BP203RV-11 (Nippon Chorin Co., Ltd.). The degree of arteriosclerosis was measured by measuring the pulse wave conduction velocity (PWV) using form PWV (Nippon Chorin Co., Ltd.) and VS-1000 (Fukuda Electronics Co., Ltd.). The degree of vascular sclerosis was measured by measuring an ankle upper arm blood pressure index (ABI = lower limb blood pressure / upper limb blood pressure) using CVMS2000 (Osachi Co., Ltd.). The acceleration wave was measured using Artet (Yumedika Inc.). The fundus examination was performed by taking a fundus image using CR5 (Canon Inc.).

頸動脈内膜中膜複合体肥厚(IMT)測定としては、nemio550(東芝社)を使用して、被験者の頸部にプローブをあて超音波によるIMTの測定を実施した。   As the carotid intima-media complex thickening (IMT) measurement, nemio 550 (Toshiba Corp.) was used to measure IMT by ultrasound by applying a probe to the neck of the subject.

筋力測定としては、一般的な握力計により握力を測定した。   For measuring muscle strength, grip strength was measured with a general grip strength meter.

体組織測定としては、骨量及び骨密度の測定と、体脂肪率及び四肢筋肉量の評価と、身長及び体重の測定とを実施した。骨量及び骨密度の測定は、AS−100(アロカ株式会社)を使用してインピーダンス法により、また、PRODIGY(GE横河メディカルシステム株式会社)を使用してDXA法(二重X線評価法)により実施した。体脂肪率及び四肢筋肉量の評価は、In Body(株式会社タニタ)及びTBF202(株式会社タニタ)を使用してインピーダンス法により実施した。身長及び体重の測定は、通常の身長計及び体重計を使用して実施した。身長及び体重の測定結果からボディマス指数(BMI)を算出した。   As body tissue measurements, bone mass and bone density, body fat percentage and limb muscle mass, and height and weight were measured. Bone mass and bone density are measured by impedance method using AS-100 (Aloka Co., Ltd.), and DXA method (double X-ray evaluation method) using PRODIGI (GE Yokogawa Medical System Co., Ltd.). ). The body fat percentage and the limb muscle mass were evaluated by the impedance method using In Body (TANITA) and TBF202 (TANITA). Measurement of height and weight was carried out using a normal height meter and weight scale. The body mass index (BMI) was calculated from the measurement results of height and weight.

呼吸機能検査としては、肺活量の測定と、酸素飽和度の測定とを実施した。肺活量の測定は、スパイロメーターHI−701(日本光電工業株式会社)を使用して実施した。酸素飽和度の測定は、パルスオキシメーター(カシオ計算機株式会社)を使用して実施した。   As a respiratory function test, a vital capacity measurement and an oxygen saturation measurement were performed. The vital capacity was measured using a spirometer HI-701 (Nihon Kohden Co., Ltd.). The oxygen saturation was measured using a pulse oximeter (Casio Computer Co., Ltd.).

循環検査としては、生体アンプECG9321(日本光電工業株式会社)を使用して四肢に装着した電極により心電図を測定した。   As a circulation test, an electrocardiogram was measured with an electrode attached to the extremities using a biological amplifier ECG9321 (Nihon Kohden Co., Ltd.).

心臓超音波検査としては、超音波検査装置nemio550(株式会社東芝)を使用して心臓の超音波画像を取得し、開放速度、後退速度、中隔厚、心拍出量、収縮率、大動脈径等を定量的に評価した。   As a cardiac ultrasound examination, an ultrasound image of the heart is acquired using an ultrasound examination apparatus nemio550 (Toshiba Corporation), and the opening speed, retraction speed, septal thickness, cardiac output, contraction rate, aortic diameter Etc. were evaluated quantitatively.

聴力検査としては、一般的な健康診断に用いる機器を使用して、高音域及び低音域それぞれの一般聴力検査を実施した。   As a hearing test, a general hearing test was performed for each of the high sound range and the low sound range by using a device used for a general medical examination.

平衡機能検査としては、平衡機能検査装置G10(アニマ株式会社)を使用して、開眼及び閉眼状態並びに立位状態での身体の重心の動揺を時系列的に記録し平衡機能を評価した。   As the balance function test, balance function test apparatus G10 (Anima Co., Ltd.) was used to record the sway of the center of gravity of the body in the open and closed eye states and the standing state in time series to evaluate the balance function.

声の老化検査としては、SUGI Speech Analyzer(株式会社アニモ)を使用して、マイクより取り込んだ音声データを解析し、発声音の周波数帯域のスペクトルより老化度を評価した。   As a voice aging test, SUGI Speech Analyzer (Animo Co., Ltd.) was used to analyze voice data captured from a microphone and evaluate the degree of aging from the spectrum of the frequency band of the uttered sound.

認知症検査としては、CogHealth(コンピュータ上でのカード判別課題における反応速度を測定し判定するシステム、株式会社ヘルス・ソリューション)を使用して認知症傾向の検査を実施した。   As a test for dementia, a test for dementia was performed using CogHealth (a system for measuring and judging a reaction speed in a card discrimination task on a computer, Health Solution Co., Ltd.).

自律神経バランス検査としては、アイリスメーター(アイリステック株式会社)を使用して、光に対する瞳孔反応速度を測定した。   As an autonomic nerve balance test, an iris meter (Iris Tech Co., Ltd.) was used to measure the pupillary reaction speed to light.

角層水分量測定としては、頬の角層水分量の測定を実施した。被験者を、洗顔後恒温恒湿室内にて45分間安静にさせた後、頬の角層水分量をcorneometer(Courage+Khazaka electronic GmbH,Germany)を用いて測定した。5回測定し平均値を算出した。   As the measurement of the stratum corneum moisture content, the measurement of the stratum corneum moisture content of the cheek was performed. The subject was allowed to rest for 45 minutes in a constant temperature and humidity room after washing the face, and then the moisture content of the horny layer of the cheek was measured using a corneometer (Courage + Khazaka electronic GmbH, Germany). The average value was calculated by measuring 5 times.

経表皮水分蒸散量測定としては、頬の経表皮水分蒸散量の測定を実施した。被験者を、洗顔後恒温恒湿室内にて45分間安静にさせた後、頬の経表皮水分蒸散量をvapometer(Delfin Technologies Ltd,Kuopio,Finland)を用いて測定した。3回測定し平均値を算出した。   For transepidermal water transpiration, measurement of cheek transepidermal water transpiration was performed. The subject was allowed to rest for 45 minutes in a constant temperature and humidity room after washing the face, and then the transepidermal water transpiration amount on the cheek was measured using a vaporometer (Delfin Technologies Ltd, Kuopio, Finland). The average value was calculated by measuring three times.

皮脂量測定としては、頬及び額の皮脂量の測定を実施した。被験者を、洗顔後恒温恒湿室内にて45分間安静にさせた後、頬及び額の皮脂量をSebumeter(Courage+Khazaka electronic GmbH,Germany)を用いて測定した。   As the sebum amount measurement, the amount of sebum on the cheek and forehead was measured. The subject was allowed to rest for 45 minutes in a constant temperature and humidity room after washing the face, and then the amount of sebum on the cheeks and forehead was measured using Sebumeter (Courage + Khazaka electronic GmbH, Germany).

肌拡大画像撮影としては、頬の肌拡大画像を撮影した。マイクロスコープ、照明装置及び記録装置から構成される独自開発の機器を使用して、8×6.2mm角の肌の拡大画像を取得し、キメの状態、角層の剥離状態等の評価を実施した。   As the skin enlargement image photographing, the skin enlarged image of the cheek was photographed. Using an independently developed device consisting of a microscope, lighting device, and recording device, obtain an enlarged image of 8 x 6.2 mm square skin, and evaluate the texture, exfoliation of the stratum corneum, etc. did.

顔写真撮影としては、全顔の正面及び左右側面の顔画像を撮影し、顔全体の肌のトラブルの評価を実施した。   As face photography, face images of the front and left and right sides of the entire face were taken to evaluate skin problems on the entire face.

肌粘弾性測定としては、頬の肌粘弾性の測定を実施した。被験者を、洗顔後恒温恒湿室内にて40分間安静にさせた後、頬の肌粘弾性をcutometer(Courage+Khazaka electronic GmbH,Germany)を用いて測定した。cutometerは、頬の肌を吸引(500mb、2秒間)した後1秒間開放するサイクルを5回繰り返すよう設定し、表皮の柔軟性と真皮の粘弾性とを評価した。   As the skin viscoelasticity measurement, the skin viscoelasticity of the cheek was measured. The subject was allowed to rest for 40 minutes in a constant temperature and humidity room after washing the face, and then the skin viscoelasticity of the cheeks was measured using a cutometer (Courage + Khazaka electronic GmbH, Germany). The cutometer was set to repeat the cycle of suctioning the skin of the cheek (500 mb, 2 seconds) and then releasing for 1 second, and evaluated the flexibility of the epidermis and the viscoelasticity of the dermis.

肌色測定としては、頬の肌色と、眼の下の肌色との測定を実施した。被験者を、洗顔後恒温恒湿室内にて40分間安静にさせた後、頬の肌色と眼の下約3.5cm部分の肌色とをCM−2600d(コニカミノルタセンシング株式会社)を用いて測定した。3回測定し平均値を算出した。   As skin color measurement, the skin color of the cheek and the skin color under the eyes were measured. The subject was allowed to rest for 40 minutes in a constant temperature and humidity room after washing the face, and then the cheek skin color and the skin color of the approximately 3.5 cm portion under the eyes were measured using CM-2600d (Konica Minolta Sensing Co., Ltd.). . The average value was calculated by measuring three times.

肌血流測定としては、頬の肌血流をオメガモニターTR BOM−L1TR SF(オメガウエーブ株式会社)を用いて測定した。   As the skin blood flow measurement, the skin blood flow of the cheek was measured using an omega monitor TR BOM-L1TR SF (Omega Wave Co., Ltd.).

肌表面温度測定としては、全顔の表面温度を測定した。被験者を、洗顔後恒温恒湿室内にて45分間安静にさせた後、全顔の表面温度をサーモグラフィーTVS−8502(日本アビオニクス株式会社)を用いて測定した。   As the skin surface temperature measurement, the surface temperature of the whole face was measured. The subject was allowed to rest in a constant temperature and humidity room for 45 minutes after face washing, and then the surface temperature of the entire face was measured using a thermography TVS-8502 (Nippon Avionics Co., Ltd.).

総合肌診断は、スキンビジオムII(株式会社資生堂)を使用して実施した。   The comprehensive skin diagnosis was performed using Skin Visionum II (Shiseido Co., Ltd.).

基礎代謝測定は、携帯用カロリーメーターMETAVINE model VMB−005N(株式会社ヴァイン)を使用して実施した。安静にさせた被験者の3分間の呼気量と呼気中の酸素濃度とを測定し、単位時間当たりの酸素摂取量から消費カロリーを推定した。   The basal metabolism measurement was performed using a portable calorimeter METAVINE model VMB-005N (Vine Co., Ltd.). The exhaled amount for 3 minutes and the oxygen concentration in the exhaled air of the subject who was made to rest were measured, and the calorie consumption was estimated from the oxygen intake per unit time.

体温測定は、仁丹平型体温計(森下仁丹株式会社)を使用して実施した。   The body temperature was measured using a Nitandaira type thermometer (Morishita Nitan Co., Ltd.).

上述の一連のアンケート調査、皮膚科医による視診、生理学的・医学的測定及び肌・身体測定は、ヘルシンキ宣言及び疫学研究に関する疫学指針の精神に則り、事前に作成した試験実施計画書を遵守して実施した。   The above series of questionnaire surveys, inspection by dermatologists, physiological and medical measurements, and skin and body measurements are in accordance with the spirit of the Declaration of Helsinki and epidemiological guidelines on epidemiological studies, and comply with pre-prepared test plans. Carried out.

(生理学的・医学的測定及び肌・身体測定の結果の解析)
上述の計6群、計30名の被験者に対して実施した生理学的・医学的測定及び肌・身体測定により取得された測定データを使用して、顔の肌のトラブル(くすみ、シミ又はしわ・たるみ)の有無と、生理学的・医学的測定及び肌・身体測定の測定値との関連性の解析を行った。先ず、測定項目ごとに、かつ、顔の肌のトラブルごとに、測定値及び解析結果をグラフ化し、視覚的にデータの傾向を把握した。次いで、測定値の再現性を評価するために、各測定項目ごとに、冬季の測定の測定値と春季の測定の測定値との間の積率相関係数を算出した。また、顔の肌のトラブルの有無と、生理学的・医学的測定及び肌・身体測定の測定値との関連性を評価するために、各測定項目ごとに、測定時期(冬季/春季)×くすみの有無(第1群/第2群)と、測定時期(冬季/春季)×シミの有無(第3群/第4群)と、測定時期(冬季/春季)×しわ・たるみの有無(第5群/第6群)とについてそれぞれ2要因の分散分析を実施し、肌のトラブルの有無の要因に関する帰無仮説に対する危険率(p)を算出した。
(Analysis of the results of physiological and medical measurements and skin and body measurements)
Using the measurement data obtained from the physiological and medical measurements and skin and body measurements conducted on a total of 30 subjects in a total of 6 groups as described above, facial skin troubles (dullness, spots or wrinkles) We analyzed the relationship between the presence or absence of sagging and the measured values of physiological and medical measurements and skin and body measurements. First, the measured values and analysis results were graphed for each measurement item and for each facial skin trouble, and the tendency of the data was grasped visually. Subsequently, in order to evaluate the reproducibility of the measurement value, the product moment correlation coefficient between the measurement value of the winter measurement and the measurement value of the spring measurement was calculated for each measurement item. In addition, in order to evaluate the relationship between the presence or absence of facial skin problems and physiological / medical and skin / body measurements, the measurement period (winter / spring) x dullness for each measurement item. Presence / absence (group 1 / group 2), measurement period (winter / spring) x presence / absence of stain (group 3 / group 4), measurement period (winter / spring) x wrinkle / sag (no. A variance analysis of two factors was performed for each of the 5th group and the 6th group), and a risk rate (p) for the null hypothesis regarding the factor of the presence or absence of skin trouble was calculated.

1−2.結果
上述のアンケート調査と皮膚科医による視診との結果として選定された計6群、計30名の被験者に対して生理学的・医学的測定及び肌・身体測定を実施し、測定データを得た。第6群の被験者3名のうち1名については試験期間途中で試験を中止したため、この1名を除く29名の被験者の測定結果に基づき結果の解析を実施した。
1-2. Results Physiological / medical measurements and skin / body measurements were performed on a total of 30 subjects, selected as a result of the above-mentioned questionnaire survey and inspection by a dermatologist, and measurement data were obtained. . Since one of the three subjects in the sixth group was discontinued during the test period, the results were analyzed based on the measurement results of 29 subjects excluding this one.

図1に、測定値及び解析結果の表示例として、第1群及び第2群の被験者における一部の測定項目(コリンエステラーゼ活性、クレアチニン濃度、血糖値、ヘモグロビン量及びCペプチド濃度)についての測定値及び解析結果を示したグラフを示す。それぞれのグラフの横軸は各測定項目の測定値を示す。それぞれのグラフにおけるそれぞれの段は、上から、第1群の被験者の冬季の測定の測定値(1段目)、第1群の被験者の春季の測定の測定値(2段目)、医学的な標準範囲を示す上限値及び下限値(3段目)、第2群の被験者の冬季の測定の測定値(4段目)、第2群の被験者の春季の測定の測定値(5段目)を示す。1、2、4、5段目には、被験者ごとにマーク(×、▲、○等)を対応させて示す。各測定項目名の下に記載される小数点以下4桁の数値は、冬季の測定の測定値と春季の測定の測定値との間の積率相関係数を示す。グラフの右側に百分率で示される数値は、2要因の分散分析により算出された肌のトラブルの有無の要因に関する帰無仮説に対する危険率(p)である。図1では、4種類の測定項目のうちCペプチドのみについての分散分析の結果を示し、危険率(p)は3.0%と算出されたことを示す。このようにして測定項目ごとに、かつ、顔の肌のトラブルごとに、測定値及び解析結果をグラフ化し視覚的にデータの傾向を把握した。その後、測定値の再現性、測定値に影響を及ぼす肌のトラブルの有無の要因等について検討した。   As a display example of measured values and analysis results, FIG. 1 shows measured values for some measurement items (cholinesterase activity, creatinine concentration, blood glucose level, hemoglobin amount, and C peptide concentration) in subjects of the first group and the second group. And the graph which showed the analysis result is shown. The horizontal axis of each graph shows the measured value of each measurement item. Each graph in each graph shows, from the top, the measured value of the first group of subjects in the winter (first tier), the measured value of the first group of subjects in the spring (second tier), medical Upper and lower limits (3rd stage) indicating the standard range, measured values of the second group of subjects in winter (4th stage), measured values of the second group of subjects in spring (5th stage) ). In the first, second, fourth, and fifth tiers, marks (×, ▲, ○, etc.) are shown corresponding to each subject. The numerical value of four digits after the decimal point described under each measurement item name indicates the product moment correlation coefficient between the measurement value of the winter measurement and the measurement value of the spring measurement. The numerical value shown as a percentage on the right side of the graph is the risk factor (p) for the null hypothesis regarding the factor of the presence or absence of skin troubles calculated by a two-factor analysis of variance. FIG. 1 shows the results of analysis of variance for only the C peptide among the four types of measurement items, and shows that the risk factor (p) was calculated to be 3.0%. In this way, the measured values and analysis results were graphed for each measurement item and for each facial skin trouble, and the tendency of the data was grasped visually. After that, the reproducibility of the measured values, the factors of the presence or absence of skin troubles affecting the measured values, etc. were examined.

図2−1ないし2−4に、上述の方法により分析した測定項目のうち101項目についての、冬季の測定の測定値と春季の測定の測定値との間の積率相関係数と、分散分析により取得した肌のトラブルの有無の要因に関する帰無仮説に対する危険率(p)とを示す。図2−1ないし2−4では、101個の測定項目を、血管の老化度に関連する指標と考えられる11項目と、血液の老化度に関連する指標と考えられる22項目と、ホルモンバランスに関連する指標と考えられる5項目と、免疫バランスに関連する指標と考えられる4項目と、一般的な血液検査の項目15項目と、身体の構成に関連する指標と考えられる11項目と、酸化ストレスに関連する指標と考えられる27項目と、その他の6項目とを、1項目に1行を与える形で表示する。各測定項目ごとに、項目の名称と、単位と、基準値(上限値及び下限値)と、29名の被験者の測定結果から算出された積率相関係数と、分散分析により算出された肌のトラブルの有無の要因に関する危険率(p)とを表示する。危険率(p)については、測定項目ごとの測定値及び解析結果のグラフの検討から肌のトラブルの有無の要因の測定値への影響がありそうだと考えられた項目と、生理学的な仮説等から興味深いと考えられた項目とについての算出結果を表示した。しわ・たるみの有無の要因に関する危険率は、第6群の被験者3名のうち1名については試験を途中で中止したことにより測定データ数が2個となったため、参考値として表示した(図2−1ないし2−4)。   FIGS. 2-1 to 2-4 show the product-moment correlation coefficient and the variance between the measurement value of the winter measurement and the measurement value of the spring measurement for 101 items among the measurement items analyzed by the above method. The risk rate (p) with respect to the null hypothesis about the factor of the presence or absence of the skin trouble acquired by analysis is shown. In FIGS. 2-1 to 2-4, 101 measurement items are classified into 11 items that are considered to be indicators related to the degree of aging of blood vessels, 22 items that are considered to be indicators related to the degree of aging of blood, and hormone balance. 5 items considered as related indicators, 4 items considered as indicators related to immune balance, 15 items of general blood tests, 11 items considered as indicators related to body composition, oxidative stress 27 items that are considered to be indices related to, and the other 6 items are displayed in a form that gives one line to one item. For each measurement item, the item name, unit, reference value (upper limit and lower limit), product moment correlation coefficient calculated from the measurement results of 29 subjects, and skin calculated by analysis of variance And the risk factor (p) regarding the cause of the presence or absence of trouble. As for the risk factor (p), items that are considered likely to have an effect on the measured values of factors related to the presence or absence of skin problems from the examination of measured values and analysis results graphs for each measurement item, physiological hypotheses, etc. The calculation result about the item considered to be interesting from was displayed. The risk factors related to the presence or absence of wrinkles and sagging were displayed as reference values for one of the three subjects in Group 6 because the number of measurement data was 2 because the test was stopped halfway (Fig. 2-1 to 2-4).

前記101個の測定項目のうち、積率相関係数が0.7を超えるものは57個あり、これらは、冬季の測定の測定値と春季の測定の測定値とを比較したときの測定の再現性が高い測定項目であると考えられた(図2−1ないし2−4)。   Among the 101 measurement items, there are 57 items whose product moment correlation coefficient exceeds 0.7, and these are the measurement values obtained by comparing the measurement values in winter and the measurements in spring. It was considered to be a measurement item with high reproducibility (FIGS. 2-1 to 2-4).

有意水準を5%としたときに肌のトラブルの有無の要因による効果が有意であった測定項目は、くすみについては、血小板数(p=1.8%)、ヘモグロビン量(2.2%)、ヘマトクリット値(2.8%)及びクレアチニン濃度(3.2%)であった。シミについては、右上腕足首脈波伝導速度(RbaPWV)(2.8%)、左上腕足首脈波伝導速度(LbaPWV)(3.7%)、収縮期血圧(2.2%)、拡張期血圧(0.8%)、フィブリノゲン量(3.8%)、血小板数(3.9%)、NK細胞活性(1.1%)、Cペプチド濃度(3.0%)、基礎代謝量(4.4%)、BMI(4.1%)、体脂肪率(2.2%)、鉄濃度(1.8%)であった。   When the significance level was set to 5%, the measurement items that had significant effects due to the presence or absence of skin trouble were the platelet count (p = 1.8%) and hemoglobin content (2.2%) for dullness. , Hematocrit value (2.8%) and creatinine concentration (3.2%). For stains, upper right ankle pulse wave conduction velocity (RbaPWV) (2.8%), left upper ankle pulse wave conduction velocity (LbaPWV) (3.7%), systolic blood pressure (2.2%), diastolic phase Blood pressure (0.8%), fibrinogen content (3.8%), platelet count (3.9%), NK cell activity (1.1%), C peptide concentration (3.0%), basal metabolism ( 4.4%), BMI (4.1%), body fat percentage (2.2%), and iron concentration (1.8%).

血小板数の測定値に対するくすみの有無の要因による効果と、シミの有無の要因による効果との両方が統計学的に有意であったことに着目し、血小板数の測定値と、くすみ又はシミの有無との関係について詳細な解析を実施した。血小板数の測定値及び解析結果を図3に示す。くすみの有無との関係では、くすみを有しない被験者(第2群の被験者)と比較してくすみを有する被験者(第1群の被験者)の方が、血小板数の測定値が小さい傾向が見出された。それに対して、シミの有無との関係では、シミを有しない被験者(第4群の被験者)と比較してシミを有する被験者(第3群の被験者)の方が、血小板数の測定値が大きい傾向が見出された。測定項目ごとに算出した積率相関係数は、血小板数についてはr=0.94であり、測定の再現性が非常に高いことが示された。また、上述の傾向はともに、分散分析の結果有意水準5%で有意であった。以上より、血小板数の測定値とくすみの有無との間には、被験者におけるその測定値が大きいほどその被験者はくすみを有する可能性が低いという傾向が存在する一方で、血小板数の測定値とシミの有無との間には、被験者におけるその測定値が大きいほどその被験者はシミを有する可能性が高いという傾向が存在し、くすみとシミとで相異なる傾向が存在することが分かった。   Focusing on the fact that both the effect of dullness on the measured platelet count and the effect of the presence of stain were statistically significant, the platelet count and dullness or A detailed analysis was conducted on the relationship between presence and absence. The measured values and analysis results of the platelet count are shown in FIG. In relation to the presence or absence of dullness, it was found that subjects with dullness (subjects in the first group) compared to subjects without dullness (subjects in the second group) tended to have smaller platelet count measurements. It was done. On the other hand, in relation to the presence or absence of a stain, the measured value of the platelet count is larger in the subject having the stain (subject in the third group) than in the subject having no stain (subject in the fourth group). A trend was found. The product moment correlation coefficient calculated for each measurement item was r = 0.94 for the platelet count, indicating that the measurement reproducibility was very high. In addition, both of the above trends were significant at the significance level of 5% as a result of analysis of variance. From the above, between the measured platelet count and the presence or absence of dullness, the greater the measured value in the subject, the less likely the subject has dullness, while the measured platelet count It was found that there is a tendency that the greater the measured value in the subject, the higher the possibility that the subject has a stain, and there is a different tendency between dullness and the stain.

血小板は身体の炎症部位に集まり止血する働きを有する。シミは色素沈着性接触皮膚炎、固定薬疹、外傷後色素沈着等のような炎症後色素沈着症を含む。くすみの発生の要因には色素沈着も含まれる。これらのことから、今回の解析の結果として見出された血小板数の測定値とくすみ又はシミの有無との間の関係は、炎症との関係で説明される可能性があると考えられた。そこで、高感度で信頼性の高い炎症性マーカーであるC反応性タンパク質(CRP)量の測定値と、くすみ又はシミの有無との関係について詳細な解析を実施した。血小板数及びCRP量の測定値及び解析結果を図4に示す。その結果、CRP量の測定値については、第2群の被験者と第1群の被験者との間にも、第4群の被験者と第3群の被験者との間にも、明確な差異は見出されず、CRP量とくすみ又はシミの有無との間には特別な関係は認められなかった(図4)。以上より、今回の解析から血小板数の測定値とくすみ及びシミの有無との間に見出された傾向は、炎症との関係で説明することは困難な、血小板数に特有の傾向であり
、くすみ又はシミの発生機構に関係する既存の概念から当業者が容易に導き出すことができない知見であるといえる。
Platelets have a function of collecting blood and stopping hemorrhage in the body. Spots include post-inflammatory pigmentation such as pigmented contact dermatitis, fixed drug eruption, post-traumatic pigmentation and the like. Factors that cause dullness include pigmentation. From these, it was considered that the relationship between the measured platelet count found as a result of this analysis and the presence or absence of dullness or spots may be explained by the relationship with inflammation. Therefore, a detailed analysis was performed on the relationship between the measured value of C-reactive protein (CRP), which is a highly sensitive and reliable inflammatory marker, and the presence or absence of dullness or spots. The measured values and analysis results of the platelet count and CRP amount are shown in FIG. As a result, no clear difference was found between the second group subjects and the first group subjects as well as between the fourth group subjects and the third group subjects regarding the measured CRP amount. As a result, no special relationship was observed between the amount of CRP and the presence or absence of dullness or spots (FIG. 4). From the above, the trend found between the platelet count measurement and the presence or absence of dullness and stains from this analysis is a tendency specific to platelet count that is difficult to explain in relation to inflammation, It can be said that this is a knowledge that a person skilled in the art cannot easily derive from an existing concept related to the generation mechanism of dullness or spots.

測定値及び解析結果の表示例として、第1群及び第2群の被験者における一部の測定項目についての測定値及び解析結果を示したグラフ。The graph which showed the measured value and analysis result about a part of measurement item in the test subject of a 1st group and a 2nd group as a display example of a measured value and an analysis result. 11個の測定項目についての、冬季の測定の測定値と春季の測定の測定値との間の積率相関係数と、分散分析により取得した肌のトラブルの有無の要因に関する帰無仮説に対する危険率(p)とを示した表。Risk for the null hypothesis on the product moment correlation coefficient between the measured value of the winter measurement and the measured value of the spring for the 11 measurement items and the factor of the presence or absence of skin trouble obtained by analysis of variance Table showing rate (p). 22個の測定項目についての、冬季の測定の測定値と春季の測定の測定値との間の積率相関係数と、分散分析により取得した肌のトラブルの有無の要因に関する帰無仮説に対する危険率(p)とを示した表。Risks for the null hypothesis on the product moment correlation coefficient between the measured values of the winter measurement and the measured value of the spring for the 22 measurement items and the cause of the presence or absence of skin troubles obtained by analysis of variance. Table showing rate (p). 24個の測定項目についての、冬季の測定の測定値と春季の測定の測定値との間の積率相関係数と、分散分析により取得した肌のトラブルの有無の要因に関する帰無仮説に対する危険率(p)とを示した表。Risks for the null hypothesis on the factor of the product moment correlation between the measured values of the winter measurement and the measured value of the spring for the 24 measurement items and the factor of the presence or absence of skin trouble obtained by analysis of variance Table showing rate (p). 17個の測定項目についての、冬季の測定の測定値と春季の測定の測定値との間の積率相関係数と、分散分析により取得した肌のトラブルの有無の要因に関する帰無仮説に対する危険率(p)とを示した表。Risks for the null hypothesis on the product moment correlation coefficient between the measured values of the winter measurement and the measured value of the spring for the 17 measurement items and the factor of the presence or absence of skin trouble obtained by analysis of variance. Table showing rate (p). 27個の測定項目についての、冬季の測定の測定値と春季の測定の測定値との間の積率相関係数と、分散分析により取得した肌のトラブルの有無の要因に関する帰無仮説に対する危険率(p)とを示した表。Risks for the null hypothesis on the factor of the product moment correlation between the measured values of the winter measurement and the measured value of the spring for the 27 measurement items, and the factor of the presence or absence of skin trouble obtained by analysis of variance Table showing rate (p). 血小板数の測定値及び解析結果を示したグラフ。The graph which showed the measured value of platelet count, and the analysis result. 血小板数及びCRP量の測定値及び解析結果を示したグラフ。The graph which showed the measured value of platelet count and the amount of CRP, and the analysis result.

Claims (1)

被験者の血小板数の測定値を指標として被験者の肌におけるくすみとシミとを識別するステップを含み、前記測定値が高いほどその被験者の肌のトラブルはくすみである蓋然性が低い、及び/又は、前記測定値が高いほどその被験者の肌のトラブルはシミである蓋然性が高いと判定することを特徴とする、くすみとシミとの識別方法。   Identifying the dullness and spots in the subject's skin using the measured value of the subject's platelet count as an index, and the higher the measured value, the lower the probability that the subject's skin trouble is dull and / or A method for discriminating between dullness and spots, characterized in that the higher the measured value, the higher the probability that the subject's skin trouble is a spot.
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