KR102260252B1 - Method of analyzing circadian rhythm through skin cells, method of normalizing circadian rhythm disorder, and information providing system using circadian rhythm information - Google Patents

Abstract

The present invention provides a method for analyzing a circadian rhythm by measuring a user's protein from skin cells, a method and composition for normalizing the circadian rhythm by determining whether there is a disorder, and a physiologically active ingredient at a specific time based on the normalized circadian rhythm It relates to a method of optimizing the efficacy of a bioactive ingredient by injecting

Description

TECHNICAL FIELD The present invention relates to a method of analyzing circadian rhythm through skin cells, a method of normalizing circadian rhythm disorder, and information providing system using circadian rhythm information. circadian rhythm information}

The present invention analyzes proteins related to circadian rhythm collected from the skin cell layer to analyze whether the circadian rhythm is disrupted, and uses a component that activates autophagy to normalize the disorder of the circadian rhythm, , to a method for determining the optimal time of injection of a bioactive ingredient based on a normalized circadian rhythm.

Circadian Rhythm (CR) is a concept that encompasses all biological rhythms that appear every 24 hours, and the sleep-wake cycle and its activity, body temperature changes, and hormone secretion patterns are representative life phenomena that show circadianity. The biological clock can be defined as an endogenous mechanism that induces all biological rhythms in a comprehensive sense, but as circadian genes have recently been identified, the circadian biological clock is sometimes defined as a narrow biological clock.

The biological clock is composed of a transcription-translation feedback loop (TTL) of specific biological clock proteins at the molecular level. Among the main biological clock proteins, clock and droplet 1 (Bmal1) form a form of heterodimer and induce the expression of biological clock-related genes Per, Cry, Ppar, Rev-Erb, and the like. Expression-induced Per and Cry form a heterodimerization form, and by inhibiting the activity of Clark/droplet 1 again, a negative feedback loop is formed. Through the transcription-translational negative feedback loop structure of the biological clock protein, a periodic rhythm phenomenon of biological clock-related gene expression is shown. In addition, through post-translational modification of the protein, it is possible to show an expression rhythm of about 24 hours by controlling an appropriate time delay and pulling phenomenon.

The biological clock protein is expressed and activated at a specific time of the day, and regulates the expression and activity of genes and proteins involved in various physiological processes in a cycle of about 24 hours. Through this, the biological clock regulates the activity of physiological responses according to the external environment.

On the other hand, an independent biological clock system exists in skin cells such as keratinocytes, melanocytes, and fibroblasts. The biological clock protein is expressed not only in cultured human skin cells but also in human skin tissues, affecting skin functions. The skin is easily exposed to external environmental factors such as light, temperature, humidity, ultraviolet rays, and pathogens, and these external environmental factors change every day. In order to adapt to this environment, the skin activates the biological clock existing in the skin to regulate various physiological functions. According to the report, it is known that skin cell proliferation and differentiation, hydration and transepidermal water loss (TEWL), capillary blood flow, sebum production, temperature, surface pH, and wrinkle formation change every 24 hours.

For example, skin cell proliferation and differentiation occur through a series of processes in a daily cycle. Skin cell differentiation mainly occurs between late night and early morning, and during the daytime, which is easy to be exposed to UV rays, DNA damage protection mechanism is mainly made, followed by cell division. By temporally separating these series of processes, it is possible to protect skin cells from harmful environments. When the rhythm of this process is broken, the physiological response required at the appropriate time cannot be generated, the homeostasis of the skin is broken, and skin damage is promoted.

Accordingly, the present inventors tried to find a means to understand the circadian rhythm of an individual by analyzing the circadian rhythm-related proteins present in skin cells, and to normalize the circadian rhythm in response to the destruction of the circadian rhythm.

It was discovered that a component having an autophagy activating effect had an excellent effect in normalizing the circadian rhythm disturbed from external stress, and using this, the present invention was completed.

It is an object of the present invention to provide a method for analyzing circadian rhythm, by measuring the amount of CR-related protein collected from the user's skin cells, without going through a complex analysis such as continuously measuring the skin surface temperature. It is intended to provide a method for analyzing

Another object of the present invention is to determine whether the circadian rhythm is impaired through the user's CR curve analyzed above, and to provide a method of normalizing CR from the disorder using an active ingredient having an autophagy activation effect. will be.

Another object of the present invention is to provide a composition comprising an active ingredient for normalizing the CR disorder.

Another object of the present invention is to provide a method or system for providing information about the injection timing of a physiologically active ingredient to a user by normalizing the user's CR and specifying the optimal time of absorption for each physiologically active ingredient required by the human body.

In order to achieve the above object, the CR analysis method according to the present invention is a method of analyzing circadian rhythm (CR), and a method of analyzing circadian rhythm (CR), which is collected at regular time intervals. determining the amount of a CR-related protein from a biological sample of a user; realizing a circadian rhythm curve by converting the measured amount of protein into time-series data; comparing the circadian rhythm curve with a circadian rhythm curve of a normal person; and determining as a circadian rhythm disorder when the circadian rhythm curve is 25% or more longer than the circadian rhythm of a normal person or the circadian rhythm curve is 25% or more shorter than the circadian rhythm of a normal person; It is characterized in that it includes.

The CR-related protein according to an embodiment of the present invention may be any one or more selected from the group consisting of CLOCK (Circadian Locomoter Output Cycles protein Kaput), melatonin, cortisol, PER, BMAL, and CRE (cAMP Response Element). .

The present invention provides a measurement unit 110 for measuring the amount of CR (Circadian Rhythm; circadian rhythm) related protein from a user's biological sample taken at regular time intervals; a CR curve implementation unit 120 that implements a circadian rhythm curve by converting the measured amount of protein into time-series data; a comparator 130 for comparing the circadian rhythm curve with a circadian rhythm curve of a normal person; and a determination unit 140 that determines a circadian rhythm disorder when the circadian rhythm curve is 25% or more longer than the circadian rhythm of a normal person or when the circadian rhythm curve is 25% or more shorter than the circadian rhythm of a normal person It provides an information providing system for analyzing a circadian rhythm curve, characterized in that.

The present invention is characterized in that it is a method for normalizing CR disorders using a composition comprising an active ingredient having an autophagy activation effect.

The component according to an embodiment of the present invention may be any one or more selected from the group consisting of Phloretin (PHL), Nothofagin (NOF), and Aspalathin (APS).

The method according to an embodiment of the present invention may be to apply the active ingredient to the skin.

In addition, the present invention relates to a cosmetic composition for preventing or improving circadian rhythm disorder comprising a component having an autophagy activation effect as an active ingredient.

According to an embodiment of the present invention, measuring the amount of CR-related protein from a user's biological sample taken at regular time intervals; realizing a circadian rhythm curve by converting the measured amount of protein into time-series data; comparing the circadian rhythm curve with a circadian rhythm curve of a normal person; and judging a circadian rhythm disorder when the circadian rhythm curve is 25% or more longer than the circadian rhythm of a normal person or when the circadian rhythm curve is 25% or more shorter than the circadian rhythm of a normal person; Accordingly, when determining the circadian rhythm disorder, the component having the autophagy activation effect may be applied to the skin.

The present invention relates to a pharmaceutical composition for preventing, improving or treating circadian rhythm disorder, comprising a component having an autophagy activation effect as an active ingredient.

The present invention relates to a health functional food for preventing or improving circadian rhythm disorder, comprising a component having an autophagy activating effect as an active ingredient.

The present invention relates to a method for providing information using circadian rhythm information, comprising the steps of: a) analyzing skin data from a sample taken from a user's skin; b) securing the user's circadian rhythm based on the skin data; c) specifying an optimal time for maximizing absorption of a physiologically active ingredient according to the user's circadian rhythm; and d) providing the specified optimal time and physiologically active ingredient information to the user; It is characterized in that it includes.

The physiologically active component according to an embodiment of the present invention may be any one or more of an anti-aging component, a whitening component, an anti-inflammatory component, and an immune modulating component.

According to an embodiment of the present invention, the method comprising: determining suitable cosmetic information based on the optimal time information specified after step c); It may further include.

The present invention relates to an information providing system using circadian rhythm information, comprising: a skin data receiving unit for receiving and outputting skin data of a user; a CR information processing unit that implements and outputs a user's circadian rhythm (CR) based on the skin data; Active ingredient DB for storing information on maximizing absorption of physiologically active ingredients according to circadian rhythm; an injection determining unit that compares the user's circadian rhythm information derived from the CR information processing unit with the active ingredient DB to determine an optimal time for injecting the user's physiologically active ingredient; and a transmitter providing the determined optimal time to a user. It is characterized in that it includes.

Since the method for analyzing a circadian rhythm according to the present invention collects a protein from a user's skin cells, it is non-invasive and does not react sensitively to external changes, enabling more accurate circadian rhythm analysis.

Through the method of analyzing circadian rhythm according to the present invention, it is possible to normalize the circadian rhythm by determining whether the circadian rhythm is impaired and applying an active ingredient having an autophagy activation effect to the skin.

1 is a graph measuring the amount of CLOCK protein collected from the stratum corneum of a subject.
Figure 2 shows a schematic diagram of a CR analysis method according to an embodiment of the present invention.
3 is a block diagram of an information providing system for analyzing a circadian rhythm curve according to an embodiment of the present invention.
4 is a flowchart illustrating a method of providing information on an optimal time of injection of a bioactive ingredient to a user according to an embodiment.
5 is a diagram showing a configuration diagram of a system for providing information about an optimal time of injection of a physiologically active ingredient to a user according to an embodiment.
6 is a graph showing CR curves obtained by extracting CR-related proteins from the skin through a non-invasive method.

Hereinafter, the present invention will be described in detail. Unless otherwise defined, terms used in this specification should be interpreted as content commonly understood by those of ordinary skill in the art. The drawings and embodiments of the present specification are for those of ordinary skill in the art to easily understand and practice the present invention, and content that may obscure the gist of the present invention may be omitted in the drawings and embodiments, and the present invention is not limited to the drawings and embodiments. is not limited to

The present invention provides a method for analyzing circadian rhythm (CR), comprising: measuring the amount of a CR-related protein from a user's biological sample taken at regular time intervals; realizing a circadian rhythm curve by converting the measured amount of protein into time-series data; comparing the circadian rhythm curve with a circadian rhythm curve of a normal person; and determining as a circadian rhythm disorder when the circadian rhythm curve is 25% or more longer than the circadian rhythm of a normal person or the circadian rhythm curve is 25% or more shorter than the circadian rhythm of a normal person; includes

As the CR analysis method of the present invention, the user's skin cells may be melanocytes, keratinocytes, or fibroblasts, and are not particularly limited as long as they are cells capable of isolating CR-related proteins. As a specific example, in the stratum corneum of the skin, CR-related proteins may be collected at intervals of several hours. If the amount of CR-related protein is measured at regular time intervals, a graph of about 24 hours in the form of a sinusoid can be obtained in a normal circadian rhythm. This is because the molecular rhythm of each cell generates a constant cycle of about 24 hours through the regulatory steps after transcription, translation, and translation in the cell.

Specifically, the present invention can measure the amount of the CR-related protein by collecting a biological sample from a user's skin cells at regular time intervals for a predetermined period in which the circadian rhythm pattern can be determined. When the amount of CR-related protein is time-series data, a circadian rhythm curve is realized, and by analyzing the pattern, it is possible to determine whether a circadian rhythm disorder is present.

More specifically, for example, if a graph of about 24 hours is viewed as a normal circadian rhythm, it is 25% or more, i.e., 6 hours or more, or 6 hours or more, and the circadian cycle is 30 hours or more or 18 hours or less. When analyzed, it may be difficult to see the circadian rhythm of a normal person. Therefore, in this case, it can be determined that there is a circadian rhythm disorder.

The CR-related protein is any one or more selected from the group consisting of CLOCK (Circadian Locomoter Output Cycles protein Kaput), melatonin, cortisol, PER, Bmal, CRE (cAMP Response Element), CRY, REV-ERB, and ROR. can

When CR-related proteins such as CLOCK and PER are subjected to environmental stress, gene expression becomes less, which may lead to a decrease in autophagy. Therefore, the cell cycle rhythm is disrupted while the damaged cells that should be killed survive and divide.

Autophagy refers to the activity of a cell self-degrading its own components, which selectively decomposes depleted or damaged components within the cell to maintain cellular functional homeostasis. Autophagy can be influenced by environmental factors that threaten the survival of cells.

In addition, the present invention is a measurement unit 110 for measuring the amount of CR (Circadian Rhythm; circadian rhythm) related protein from the user's biological sample taken at regular time intervals; a CR curve implementation unit 120 that implements a circadian rhythm curve by converting the measured amount of protein into time-series data; a comparator 130 for comparing the circadian rhythm curve with a circadian rhythm curve of a normal person; and a determination unit 140 that determines a circadian rhythm disorder when the circadian rhythm curve is 25% or more longer than the circadian rhythm of a normal person or when the circadian rhythm curve is 25% or more shorter than the circadian rhythm of a normal person It provides an information providing system for analyzing a circadian rhythm curve, characterized in that.

The present invention provides a method for normalizing CR disorders using a composition comprising an active ingredient having an autophagy activation effect.

SIRT1, known as one of the orthologs of the sirtuin gene in yeast, is a deacetylating enzyme that uses NAD as a coenzyme. It reflects the circadian rhythm of the clock. In addition, it is involved in the deacetylation of a number of autophagy-related genes in a famine situation, affecting the regulation of autophagy protein activity. Considering the correlation between SIRT1-mediated autophagy and circadian rhythm regulation, induction of autophagy activation can lead to normalization of circadian rhythm disturbances.

The active ingredient having an autophagy activation effect may be any one or more selected from the group consisting of Phloretin (PHL), Nothofagin (NOF) and Aspalathin (APS). In addition, in the following specification, the active ingredient may be any one or two or more selected from the active ingredients.

In addition, the present invention comprises the steps of measuring the amount of CR-related protein from a user's biological sample taken at regular time intervals; realizing a circadian rhythm curve by converting the measured amount of protein into time-series data; comparing the circadian rhythm curve with a circadian rhythm curve of a normal person; and judging a circadian rhythm disorder when the circadian rhythm curve is 25% or more longer than the circadian rhythm of a normal person or when the circadian rhythm curve is 25% or more shorter than the circadian rhythm of a normal person; Accordingly, there is provided a cosmetic composition for preventing or improving circadian rhythm disorder, characterized in that the component having the autophagy activation effect is applied to the skin when the circadian rhythm disorder is determined.

By applying any one or more of the above active ingredients to the skin, it is possible to normalize the CR disorder as the absorbed active ingredients regulate the activity of the SIRT1 protein.

The method of application to the skin is not particularly limited whether it is applied locally or sprayed in a spray formulation as long as it is absorbed into the skin.

The cosmetic composition is an external skin ointment, cream, softening lotion, nutrient lotion, pack, essence, hair tonic, shampoo, conditioner, hair conditioner, hair treatment, gel, skin lotion, skin softener, skin toner, astringent, lotion, Milk lotion, moisture lotion, nourishing lotion, massage cream, nourishing cream, moisture cream, hand cream, foundation, nourishing essence, sunscreen, soap, cleansing foam, cleansing lotion, cleansing cream, body lotion and body cleanser It may be prepared in a dosage form, but is not limited thereto. The cosmetic composition comprising each of these dosage forms may contain various bases and additives necessary and appropriate for the formulation of the dosage form.

The present invention provides a pharmaceutical composition for preventing, improving or treating circadian rhythm disorder, comprising a component having an autophagy activation effect as an active ingredient.

In addition, the present invention comprises the steps of measuring the amount of CR-related protein from a user's biological sample taken at regular time intervals; realizing a circadian rhythm curve by converting the measured amount of protein into time-series data; comparing the circadian rhythm curve with a circadian rhythm curve of a normal person; and judging a circadian rhythm disorder when the circadian rhythm curve is 25% or more longer than the circadian rhythm of a normal person or when the circadian rhythm curve is 25% or more shorter than the circadian rhythm of a normal person; Accordingly, when determining the circadian rhythm disorder, it may be a pharmaceutical composition for preventing, improving or treating circadian rhythm disorder, characterized in that the component having the autophagy activation effect is administered orally or parenterally.

The pharmaceutical composition may include a pharmaceutically effective amount of the active ingredient alone or may further include one or more pharmaceutically acceptable carriers. In the above, the pharmaceutically effective amount refers to an amount showing a response higher than that of the negative control group, and preferably refers to an amount sufficient to prevent, improve or treat circadian rhythm disorder. This may be appropriately changed according to various factors such as the disease and its severity, the user's age, health status, administration route, and treatment period.

Diseases to which the pharmaceutical composition of the present invention can be applied are circadian diseases, such as sleep disorders, emotional disorders, metabolic diseases, cardiovascular diseases, and neoplastic diseases. It is not limited as long as it is a disease that is evaluated to be compound-related. Specifically, emotional disorders may include various types of emotional disorders such as depression, bipolar disorder, anxiety disorder, and seasonal mood disorder.

The present invention provides a health functional food for preventing or improving circadian rhythm disorder, comprising a component having an autophagy activation effect as an active ingredient.

In addition, the present invention comprises the steps of measuring the amount of CR-related protein from a user's biological sample taken at regular time intervals; realizing a circadian rhythm curve by converting the measured amount of protein into time-series data; comparing the circadian rhythm curve with a circadian rhythm curve of a normal person; and judging a circadian rhythm disorder when the circadian rhythm curve is 25% or more longer than the circadian rhythm of a normal person or when the circadian rhythm curve is 25% or more shorter than the circadian rhythm of a normal person; Accordingly, it may be a health functional food for preventing or improving circadian rhythm disorder, characterized in that the component having the autophagy activation effect is consumed when the circadian rhythm disorder is determined.

The health functional food of the present invention can be manufactured by a method commonly used in the art, and during the manufacture, it can be prepared by adding raw materials and components commonly added in the art. In addition, as long as the formulation of the above 　 health functional food is also recognized as a health functional food, it can be manufactured without limitation. The health functional food of the present invention has the advantage that there are no side effects that may occur during long-term administration of the drug as a raw material, unlike general drugs, and is excellent in portability and can be consumed as an adjuvant to enhance the effect of activating autophagy. It is possible.

An information providing method using circadian rhythm information according to the present invention comprises the steps of: a) analyzing skin data from a sample taken from a user's skin; b) securing the user's circadian rhythm based on the skin data; c) specifying an optimal time for maximizing absorption of a physiologically active ingredient according to the user's circadian rhythm; and d) providing the specified optimal time and physiologically active ingredient information to the user; It is characterized in that it includes.

The method of collecting the user's skin cells corresponding to S210 of FIG. 2 during step a) is not particularly limited, but tape is attached to the user's forehead, cheek, chin, arm, etc. and then removed by tape stripping ( tape stripping). As corresponding to S220 of FIG. 2 , it is possible to obtain data on the amount of change in protein extracted from skin cells according to a conventional method known in the art. In step b) corresponding to S230 of FIG. 2 , the user's circadian rhythm may be identified and secured according to the amount of change in the protein. As corresponding to S240 of FIG. 4 , the optimal time for maximizing absorption of the physiologically active component in the user's circadian rhythm curve through step c) is specified.

The physiologically active component is characterized in that any one or two or more of an anti-aging component, a whitening component, an anti-inflammatory component and an immune modulating component.

determining suitable cosmetic information based on the optimal time information specified after step c); may further include.

Through the above steps, it is possible to provide information on cosmetics customized for each user. Through this, the user can efficiently manage the skin through information on the type and injection timing of the physiologically active ingredient required based on the skin data.

An information providing system using circadian rhythm information according to the present invention includes: a skin data receiving unit 310 for receiving and outputting a user's skin data; CR information processing unit 320 to implement and output a user's circadian rhythm (CR) based on the skin data; Active ingredient DB (330) for storing information on maximizing absorption of physiologically active ingredients according to circadian rhythm; an injection determining unit 340 comparing the user's circadian rhythm information derived from the CR information processing unit with the active ingredient DB to determine an optimal time for injecting the user's physiologically active ingredient; and a transmitter 350 providing the determined optimal time to the user. It is characterized in that it includes.

The skin data obtained by analyzing the amount of protein collected from the user's skin cells is received through the skin data receiving unit 310 , and the user's circadian rhythm is derived from the CR information processing unit 320 . In this case, the data obtained from the skin cells is not limited to the amount of protein and may include other biological signals. Specifically, for example, it may include continuously sensed blood pressure, heart rate, body temperature, and the like.

The CR information processing unit 320 may derive the user's circadian rhythm curve through the skin data, and determine whether there is a disorder in the user's circadian rhythm.

The type of component stored in the active ingredient DB 330 is not particularly limited as long as it is a component that can be injected into the skin, such as an anti-aging component, a whitening component, an anti-inflammatory component, or an immune modulating component. Information on conditions or states for these ingredients to function efficiently in the body is stored in the active ingredient DB.

It is the injection decision unit 340 that derives the optimal time for the user to inject the active ingredient through the CR information processing unit and the active ingredient DB. The information derived through this may be transmitted to the user through the transmitter 350 . Specifically, as a means to be transmitted to the user, direct transmission through the display unit inside the information providing system, indirect transmission through the user terminal, or direct transmission through the display unit and indirect transmission through the user terminal may be simultaneously performed.

In this case, the user terminal may be a wearable device, a portable terminal, or the like.

According to one embodiment of the present invention, it may further include a determining unit for determining suitable cosmetic information based on the specified optimal time information. Specifically, by specifying that the time when collagen synthesis is activated in the user's skin according to the user's CR information is, for example, 1:00 pm to 2:00 pm, the time to use cosmetics including active ingredients related to collagen synthesis is specified Thus, it is possible to maximize the absorption of the active ingredient. That is, it is possible to provide customized cosmetic information according to the CR information of each user.

The examples described above may be implemented with a hardware component, a software component, and/or a combination of a hardware component and a software component.

Hereinafter, the present invention will be described by way of examples. However, the following examples are for explaining the present invention in detail, and the scope of the present invention is not limited to the following examples, and those of ordinary skill in the art may A modified form may be implemented.

Experimental Example 1. Setting criteria for circadian rhythm disorder

In order to determine whether the circadian rhythm is disturbed, 50 patients with insomnia (group 1) and 50 patients with hypersomnia (group 2) complaining of symptoms due to lack of sleep were subjected to the same method as described in Example 1 below. circadian rhythm was measured.

As a result, it was confirmed that more than 60% of each test group had a circadian cycle of 30 hours or more, 20% of group 1 had about 18 hours, and 20% of group 2 had about 17 hours. Based on these experimental results, when 24 hours was a normal circadian cycle, it was judged that the circadian phase of sleep and wakefulness was abnormal when it was 30 hours or more or 18 hours or less.

Example 1. Method for measuring the circadian cycle of the skin

A test to measure the skin circadian rhythm was conducted on two subjects each in the test group (sleep disorder test group) and the test group (normal test group) in which the circadian rhythm was disturbed through sleep disturbance.

The stratum corneum was collected from the inside of the subject's upper arm using D-Squame tape (Clinical and Derm LLC., Dallas, TX, USA), and the collected D-Squame tape was used with PBS buffer (pH 7.4). , the protein was extracted by sonication at 4℃ for 20 minutes, and the amount of CLOCK (Circadian Locomotor Output Cycles Kaput) protein, a circadian indicator protein, from the extracted protein was measured with an ELISA kit (MyBioSource Inc., San Diego, CA, USA) ) was used for measurement.

As a result of analyzing the stratum corneum collected at the same time (10 am) from the subject, there was no significant difference in the amount of protein in the sleep disorder test group, with an average of 0.972 mg/ml and 0.937 mg/ml. It can be seen from FIG. 1 that it shows a significant difference with the amount (0.663 mg/ml).

Figure 6 shows the amount of change in the amounts of CLOCK and Per1 extracted from the stratum corneum of the subjects by time. It can be seen that the CR curve obtained from 4 subjects is repeated every 24 hours. This leads to the conclusion that the circadian cycle can be identified by analyzing the amount of protein change in keratinocytes non-invasively collected from the skin.

In addition, in the case of the sleep disorder test group, a circadian cycle was observed for 30 hours or more, 18 hours or less, or a curve without regularity compared to the normal test group.

Example 2. CR disorder normalization efficacy test

(1) Preparation of a cosmetic composition containing PHL (phloretin) as an active ingredient

A cosmetic composition containing PHL having the composition shown in Table 1 as an active ingredient was prepared.

(2) Observation of changes in skin moisture content and circadian rhythm curve when applied daily to the skin of the sleep disorder test group

PHL (phloretin (phloretin) according to the formulation example in Table 1 above for each of 10 subjects in the test group (sleep disorder test group) and the test group (normal test group) in which the circadian rhythm was disturbed through sleep disturbance ) containing a cosmetic composition and a cosmetic composition not containing PHL (phloretin) (except PHL in Table 1 above) were applied to a designated area before bedtime to apply. In the case of the sleep disorder test group, sleep disorder was induced by waking up at 3 am, and this was continued for 7 days. After 7 days, the skin moisture content of the sleep disorder test group and the normal test group was measured, and the normalization of the circadian rhythm curve was observed.

As a result, as shown in Table 2 below, in the sleep disorder test group, the skin moisture content was reduced by 13% in the group applying the cosmetic composition containing no PHL, and in the group applying the cosmetic composition containing PHL according to the present invention, clinical trials It can be confirmed that the skin moisture content before the test has improved.

In the case of the normal test group, the skin moisture content increased by about 5% in both the group that applied the cosmetic composition containing PHL and the cosmetic composition that did not contain PHL, but there was no significant difference between the two groups. From these results, it was confirmed that the efficacy of PHL was not significantly marked in the case of the normal test group.

After completion of the clinical trial, the subjects' circadian cycles were measured according to the method described in Example 1, and two subjects showed recovery of the circadian rhythm curve in the sleep disorder test group. Through this, it can be confirmed that when the cosmetic composition comprising the CR-related protein according to the present invention is used as an active ingredient, it can contribute to normalizing the circadian rhythm disorder.

110: measurement unit
120: CR curve implementation unit
130: comparison unit
140: judgment unit
S110: Determination of the amount of CR-related protein from a biological sample
S120: Dataization of CR-related protein amount and implementation of CR curve
S130: Comparison of normal CR and user CR
S140: Determination of CR failure
S210: Sample collection step from the user's skin
S220: skin data analysis step from the collected sample
S230: Step of securing the user's circadian rhythm from the skin data
S240: according to the user's circadian rhythm, the optimal time for absorption of the bioactive ingredient specific stage
S250: Optimal time and bioactive ingredient information provision step
310: skin data receiving unit
320: CR information processing unit
330: active ingredient DB
340: injection decision unit
350: transmitter

Claims (11)

As a method of analyzing circadian rhythm (CR),
measuring the amount of CR-related protein from the user's stratum corneum skin cells collected at regular time intervals;
realizing a circadian rhythm curve by converting the measured amount of protein into time-series data;
comparing the circadian rhythm curve with a circadian rhythm curve of a normal person; and
determining a circadian rhythm disorder when the circadian rhythm curve is 25% or more longer than the circadian rhythm of a normal person or the circadian rhythm curve is 25% or more shorter than the circadian rhythm of a normal person; including,
The CR-related protein is at least one selected from the group consisting of CLOCK (Circadian Locomoter Output Cycles protein Kaput), melatonin, cortisol, PER, BMAL and CRE (cAMP Response Element), CR analysis method. delete a measuring unit measuring the amount of CR (Circadian Rhythm; circadian rhythm) related protein from the user's stratum corneum skin cells collected at regular time intervals;
a CR curve implementation unit for implementing a circadian rhythm curve by converting the measured protein amount into time-series data;
a comparator for comparing the circadian rhythm curve with a circadian rhythm curve of a normal person; and
and a judging unit that determines a circadian rhythm disorder when the circadian rhythm curve is 25% or more longer than the circadian rhythm of a normal person or when the circadian rhythm curve is 25% or more shorter than the circadian rhythm of a normal person and,
The CR-related protein is any one or more selected from the group consisting of CLOCK (Circadian Locomoter Output Cycles protein Kaput), melatonin, cortisol, PER, BMAL and CRE (cAMP Response Element), information analyzing a circadian rhythm curve delivery system. delete delete delete delete delete delete delete delete

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