KR20190085455A - Composition comprising banana peel extract for regulating expressions of tph1 gene, ddc gene and/or aanat gene - Google Patents

Abstract

A composition for increasing the expression of TPH1 genes, DDC genes and/or AANAT genes is provided, wherein the composition contains an effective amount of a banana peel extract. The composition can be used for treating, preventing, or adjusting diseases or physiological functions related to TPH1, DDC and/or AANAT genes.

Description

Technical Field [0001] The present invention relates to a composition comprising a banana peel extract for controlling the expression of a TPH1 gene, a DDC gene and / or an AANAT gene.

This application claims priority from U.S. Provisional Application No. 62 / 457,457, filed February 10, 2017, and U.S. Patent Application No. 10710371, filed on January 29, 2018, with the Taiwan Patent Office, , Incorporated herein by reference.

The present invention relates to the use of TPH1 ( Tryptophan hydroxylase 1 ), DDC ( DOPA decarboxylase ) and / or an aralkylamine N- acetyltransferase ( AANAT ) gene for use in the treatment, prevention or control of a disease or a physiological function. The present invention relates in particular to the use of banana peel extracts in the treatment of insomnia and / or sleep disorders by increasing the expression of melatonin.

Melatonin, a hormone secreted from the pineal gland, functions to regulate the biological clock. Because melatonin secretion is suppressed by exposure to light, people can stay awake during the day. On the other hand, the secretion of melatonin will increase at night, so people can fall asleep. Night or irregular shifts If you maintain a lifestyle that uses electronics for long periods of work, tension, and melatonin secretion is insufficient for night time. Inadequate secretion of melatonin leads to a decrease in the quality of sleep and / or serious problems in daily life (for example, insomnia) and / or problems (such as feeling fatigue during the day and disturbing the biological clock and weakening the immune system) .

Medications commonly used in clinics to treat sleep disorders include sedative-hypnotic drugs (such as benzodiazepines and barbiturates) and antidepressants (such as chlamipramine and imipramine). However, the above-mentioned drugs are prone to poisoning, and may cause hypersomnia, nausea, headache, vomiting, gastrointestinal disorders, memory disorders, rebound insomnia, unconsciousness, ataxia, dyspnea and / There can be the same side effect. Currently, melatonin extracted and / or chemically synthesized in bovine pineal gland is commercially available, but such melatonin is strictly controlled or prohibited in countries concerned about the uncertain safety dose of mad cow disease and / or melatonin. Thus, there is a need and urgency to continuously develop drugs or methods for effectively treating insomnia and / or improving sleep disorders without addiction and side effects.

In this study, melatonin expression was regulated by genes such as TPH1 gene, DDC gene and AANAT gene, and increased expression of TPH1 gene, DDC gene and / or AANAT gene increased melatonin expression and melatonin secretion And helping to promote it. Thus, if the expression of the TPH1 gene, DDC gene and / or AANAT gene can be increased, insomnia and / or sleep disorders can be effectively treated or ameliorated. The present inventors have found that the banana bark extract is effective for increasing the expression of genes such as the TPH1 gene, the DDC gene and the AANAT gene, and thus can be used not only for the treatment of insomnia and / . ≪ / RTI >

It is an object of the present invention to provide a method for increasing the expression of TPH1 (tryptophan hydroxylase 1) gene, DDC (DOPA dicarboxylase) gene and / or AANAT (aralkylamine N-acetyltransferase) gene Comprising administering to a subject in need thereof an effective amount of banana peel extract. The method can be used for the prevention and treatment of diseases related to neuro-metabolic disorders, prevention of diseases related to neuro-metabolic disorders, improvement of sleep disorders, appetite regulation, sleep control, mood regulation, vasoconstriction regulation, control of hemostatic function and melatonin secretion, melatonin secretion promotion, insomnia treatment, For at least one of the modulation of the immune response. Preferably, the method is for treating insomnia and / or improving sleep disorders. In the method according to the present invention, the composition is administered to a patient by oral administration, transdermal administration or a combination thereof.

Another object of the present invention is to provide the use of a banana peel extract in the manufacture of a composition wherein said composition is used in at least one of increasing TPH1 gene expression, increasing DDC gene expression, and increasing AANAT gene expression. The composition is a pharmaceutical composition or a food composition. Preferably, the composition is used to increase the expression of melatonin and / or promote secretion of melatonin.

Another object of the present invention is to provide a composition used for increasing the expression of TPH1 gene, DDC gene and / or AANAT gene. The composition is a pharmaceutical composition or food composition and comprises an effective amount of banana peel extract. Preferably, the composition is used to increase the expression of melatonin and / or promote secretion of melatonin.

The pharmaceutical compositions provided according to the present invention are used for at least one of the treatment of insomnia, the treatment of diseases associated with neuro-metabolic disorders, and the prevention of diseases associated with neuro-metabolic disorders. Preferably, the pharmaceutical composition is used in the treatment of insomnia. The pharmaceutical composition is provided in a form for oral administration or transdermal administration.

The food composition provided according to the present invention is used for at least one of sleep disorder, appetite control, sleep control, mood control, vasoconstriction control, hemostatic function regulation and immune response control. Preferably, the food composition is used to ameliorate sleep disorders. The food composition is a health food, a nutritional supplement, a functional food, a nutritional supplement or a special nutritional food. Preferably, the food composition is provided as a dairy, a meat product, a bread ingredient, a pasta, a cookie, a troche, a capsule, a fruit juice, a tea, a sports drink or a nutritional drink.

The detailed description and preferred embodiments of implementing the invention are set forth in the following paragraphs which accompany the accompanying drawings to those skilled in the art in order to better understand the features of the invention.

1 shows the expression levels of TPH1 gene, DDC gene and AANAT gene in human neuroblastoma cells of an extract group in comparison with the control group, wherein the cells of the "control group " were cultured in a medium containing no banana bark extract For 6 hours, and the "extract group" cells were cultured in a medium containing banana bark extract for 6 hours.
Figure 2 shows the scores of group I to III sleep disorder scores on day 0 (i.e., score before drinking banana peel extract) and day 7 (score after drinking banana peel extract for 7 consecutive days) I were subjects with severe sleep disturbances, subjects in Group II were those with potential sleep disorders, and those in Group III were those without sleep disturbances.
FIG. 3 is a graph showing the melatonin contents in saliva of Groups I to III in comparison with the control group on days 0 and 7. FIG.
Fig. 4 shows the expression levels of the TPH1 gene and the AANAT gene in the peripheral blood mononuclear cells of Groups I to III of days 0 and 7 as compared with the control group.

Hereinafter, some embodiments of the present invention will be described in detail. However, without departing from the spirit of the invention, the invention may be embodied in various forms and should not be construed as limited to the embodiments set forth in the specification or defined in the appended claims.

Unless otherwise indicated herein, the expressions recited in the specification (particularly in the claims) of the present invention are intended to include both singular and plural forms. The term " treating "or" treating "as used herein is intended to refer to maintaining the progression or symptom of a substantially static condition, which should not be construed as treating the patient until the patient is fully recovered, Reducing the severity of the condition or improving the quality of life of the patient. As used herein, the term " prevent "or" prevent "refers to inhibiting or preventing a particular condition of a disease from collapsing or maintaining health to endure a disease in a susceptible subject. The term " modulate "or" modulate " as used herein refers to upregulating (including inducing, stimulating and enhancing) or downregulating (including suppressing and attenuating) a subject's physiological function to a normal state. The term "subject" referred to herein means a mammal, including human and non-human animals.

Bananas are perennial herbs derived from tropical and subtropical Asia. In Taiwan, bananas are planted mainly in Kaohsiung, Tainan, Pingdong, and Taitung. In general, the edible part of the banana is the flesh part and the shell is discarded. Therefore, if the banana peel can be utilized, the economic value of the banana will increase.

The TPH1 gene is known to be involved mainly in the synthesis of serotonin related to physiological functions such as appetite, sleep, mood, vasoconstriction, hemostatic function and immune response. Thus, decreased expression of the TPH1 gene affects the physiology associated with the serotonin. The above-mentioned facts can be seen from the "Peter Zill et al., 2007, Analysis of tryptophan hydroxylase I and II mRNA expression in the human bone: a post-mortem study", which is fully incorporated herein by reference. Therefore, if the expression of the TPH1 gene can be increased, the physiological function associated with the serotonin can be controlled.

The DDC gene is involved in the synthesis of melatonin, and deletion of the DDC gene is also known to induce neuro-metabolic disorders. The above-mentioned fact can be seen from Riccardo Montioli et al., 2014, which is hereby incorporated by reference in its entirety, with a summary picture of the associations with aromatic amino acid decarboxylase deficiency: from molecular mechanisms to therapy implications. Therefore, if the expression of the DDC gene can be increased, it is possible to treat or prevent diseases associated with neurodegenerative disorders, and to regulate physiological functions associated with melatonin synthesis.

The AANAT gene is known to play an important role in the synthesis of melatonin. The above-mentioned facts can be seen in reference to "Jimo Borjigin et al., 1995, Diurnal variation in mRNA encoding serotonin N-acetyltransferase in pineal gland", which is fully incorporated herein by reference. Therefore, if the expression of the AANAT gene can be increased, the physiological function associated with the synthesis of melatonin can be controlled.

The present inventors have found that banana peel extract is effective in controlling the expression of genes such as TPH1, DDC and AANAT. Accordingly, the present invention relates to the use of a banana peel extract to increase the expression of TPH1 gene, DDC gene and / or AANAT gene, comprising a composition comprising a banana peel extract, using a banana peel extract in the preparation of the composition, Comprising administering to a subject in need thereof a composition comprising an effective amount of a banana peel extract capable of increasing the expression of a TPH1 gene, a DDC gene and / or an AANAT gene.

The banana peel extract according to the present invention can be provided by a method comprising the steps of: (a) extracting a banana skin with an extraction solvent to provide a crude extract solution; (b) centrifuging the crude extract solution and filtering the resulting supernatant to obtain a filtrate; (c) concentrating the filtrate in vacuo to obtain a concentrated extract solution; And (d) drying the concentrated extract solution to obtain a dry substance.

In step (a), the extraction solvent is a polar solvent and optionally an acid. The polar solvent may be selected from the group consisting of water, alcohols (e.g., C1-C4 alcohol), and combinations thereof. The acid may be selected from the group consisting of acetic acid, citric acid, hydrochloric acid, and combinations thereof. The extraction solvent may be provided by mixing the acid with a polar solvent in a volume ratio ranging from 0.1: 100 to 5: 100 (acid: polar solvent). For example, the extraction solvent may be provided by mixing citric acid with water in a volume ratio of 0.5: 100 to 1: 100 (citric acid: water). There is no limitation on the amount of the extraction solvent as long as the banana shell can be uniformly dispersed in the extraction solvent. For example, in step (a), the extraction solvent and the banana shell may be used in a volume ratio ranging from about 1: 1 to about 20: 1 (extraction solvent: banana peel). In one embodiment of the invention, the extraction of step (a) was carried out using the extraction solvent and banana shells in a volume ratio of 6: 1 (extraction solvent: banana skin) and the extraction solvent was citric acid in a ratio of 1: 100 : Water). ≪ / RTI >

In step (a), the extraction can be carried out for a suitable time depending on the extraction solvent employed. Citric acid and water are mixed at a volume ratio of 1: 100 (citric acid: water) to provide an extraction solvent. When the volume ratio of the extraction solvent: banana shell is 6: 1, the extraction is generally carried out for at least 0.5 hour, 1.5 hours, more preferably at least 2 hours. Further, before performing step (a), other operations such as heating, cooling, stirring, filtration, and ultrasonic treatment may be selectively performed to further enhance the extraction effect. For example, in one embodiment of the present invention, the stirring step is performed before performing step (a), and then step (a) is carried out at 85 DEG C for 0.5 hour.

In step (c), the temperature for vacuum concentration can be arbitrarily adjusted. For example, the vacuum concentration of step (c) can be carried out at a temperature in the range of from 45 to 70 < 0 > C. In one embodiment of the present invention, the vacuum concentration of step (c) was carried out at 55 占 폚. The banana peel extract employed in accordance with the present invention may be the concentrated extract solution provided by step (c) or the dried material provided by step (d). In step (d), the concentrated extract solution may be dried by a method such as lyophilization or spray drying. In order to achieve as high extraction efficiency as possible, the banana shell may be repeatedly extracted with the same or different extraction solvent prior to step (b), and the thus obtained extracts may be combined and used in step (b) May be provided in the extract solution; Also, the cycle of step (b), step (c), and / or any other optional operation described above may be repeated.

The composition provided according to the present invention may be a pharmaceutical composition or a food composition. The pharmaceutical compositions provided in accordance with the present invention are used in one or more of the treatment of insomnia, the treatment of diseases associated with neurodegenerative disorders, and the prevention of diseases associated with neurodegenerative disorders. Preferably, the pharmaceutical composition is used in the treatment of insomnia. The food composition provided in accordance with the present invention is used for at least one of improving sleep disorder, controlling appetite, controlling sleep, controlling mood, controlling vasoconstriction, controlling hemostatic function, and controlling immune response. Preferably, the food composition is used to ameliorate sleep disorders.

Depending on the intended purpose, the pharmaceutical composition of the present invention may be provided in any suitable form without any particular limitation. For example, the pharmaceutical compositions may be administered to subjects in need thereof by oral or parenteral (such as transdermal) routes, but are not limited thereto. Depending on the form and purpose, suitable carriers may be selected and used to provide pharmaceutical compositions, wherein the carrier is selected from the group consisting of excipients, diluents, adjuvants, stabilizers, absorption inhibitors, disintegrating agents, agents, emulsifiers, antioxidants, adhesives, binders, tackifiers, dispersants, suspending agents, lubricants, hygroscopic agents and the like.

As dosage forms suitable for oral administration, the pharmaceutical compositions according to the present invention may comprise any pharmaceutically acceptable carrier which does not adversely affect the desired effect of the active ingredient (i. E., The banana peel extract). Examples of suitable carriers include, but are not limited to, water, saline, dextrose, glycerol, ethanol or an analogue thereof, cellulose, starch, sugar bentonite and combinations thereof. The pharmaceutical composition may be provided in any suitable form for oral administration such as in the form of tablets (e.g., dragees), pills, capsules, granules, pulvis, fluidextract, solutions, syrups, suspensions, .

As a formulation suitable for transdermal administration, the pharmaceutical composition may be a patch, an emulsion, a cream, a gel (e.g., hydrogel), a paste (e.g., dispersion paste, ointment), a spray or a solution for external use It does not.

Depending on the needs, age, weight and health of the patient, the pharmaceutical compositions provided in accordance with the present invention may be administered at varying frequency, such as once a day, several times a day, or once every several days. The proportion of the amount of the banana bark extract in the pharmaceutical composition provided can be adjusted according to the actual application requirements. The pharmaceutical composition may also be used to further enhance the effect of the pharmaceutical composition, or to enhance the effectiveness of the formulation provided herein, as long as the other active ingredient does not adversely affect the desired effect of the active ingredient (i. E., The banana peel extract) (S) (e.g., hypnotic drugs, antidepressants, and melatonin), or may include one or more other active ingredient (s), to further enhance the application flexibility and adaptability Can be used in combination.

Alternatively, the pharmaceutical composition or food composition provided in accordance with the present invention may further comprise a suitable amount of an additive such as a flavoring, toner or coloring agent to improve the palatability and visual perception of the pharmaceutical composition or food composition Preservatives, preservatives, antimicrobials or antifungal agents to improve the stability and shelf-life of the pharmaceutical composition or food composition.

The food composition provided according to the present invention may be a health food, a nutritional supplement, a functional food, a nutritional supplement or a special nutritional food and may be a dairy product, a meat product, a bread ingredient, pasta, cookie, troch, capsule, fruit juice, Tea, sport drinks, nutritional drinks, and the like, but the present invention is not limited thereto. Preferably, the food composition provided in accordance with the present invention is a health food.

Depending on the age, weight and health condition, the health food, health supplement, functional food, nutritional supplement and nutritional food provided by the present invention may be ingested at various frequencies, for example, once a day, Several times a day or once a few days. The amount of the banana peel extract in the health food, the health supplement, the functional food, the nutritional supplement and the special nutrition food provided according to the present invention can be adjusted, and preferably the daily dose should be taken according to the specific population Should be administered in an amount of.

Recommendations for use with a recommended daily dosage, use standard and use conditions, or other food products or medicaments for a particular population (e.g., insomnia patients, depressed patients and pregnant women) , Nutritional supplements, functional foods, nutritional supplements and / or special nutritional foods. Therefore, the user can safely and safely take health food, health functional food, functional food, nutritional supplement and / or special nutrition food without instruction of doctor, pharmacist or related officer. In the food composition provided in accordance with the present invention, the type and related uses of the banana peel extract are all consistent with the above description.

The present invention also provides a method for increasing the expression of a TPH1 gene, a DDC gene and / or an AANAT gene, comprising administering a composition to a subject in need thereof, wherein said composition comprises an effective amount of banana bark extract do. The application type, application route, application type, frequency of application and application in the relevant application fields of composition are all consistent with the above description.

Hereinafter, the present invention will be described in more detail with reference to specific examples. However, the following examples are intended to illustrate the present invention, but the scope of the present invention is not limited thereto. The scope of the invention will be indicated in the appended claims.

[Example]

The sources of materials used in the following examples are as follows:

1. Banana: Taiwan.

2. Human neuroblastoma cells (SH-SY5Y): purchased from ATCC, product number CRL-2266.

3. DMEM medium: purchased from Gibco, product number 12100-038.

4. Fetal Bovine Serum (FBS): purchased from Gibco, product number 10438-062.

5. Penicillin / streptomycin: purchased from Gibco, product numbers 15140-122.

6. RNA Extraction Kit: purchased from Geneaid.

7. SuperScript® III reverse transcriptase: purchased from Invitrogen.

8. KAPA SYBR FAST qPCR kit: purchased from KAPA Biosystems.

9. Step One Plus system: purchased from ABI.

10. Melatonin direct Saliva ELISA, 96T: purchased from IBL, part number RE54041.

11. Ficoll-Paque Plus: purchased from GE Healthcare.

Example  1: Manufacture of banana peel extract

Work was carried out on the banana skin to include the following steps in order to separate the bark from the bark and to provide the banana, bark extract:

1. Mix the banana shell and extraction solvent (volume ratio of extraction solvent: banana shell = 6: 1, extraction solvent: citric acid and water in a volume ratio of 1: 100 (citric acid: water) Time extraction to obtain a crude extract solution;

2. The crude extract solution from step 1 was centrifuged at 5000 rpm for 10 minutes, and the supernatant was filtered with a 400-mesh filter to obtain a filtrate;

3. Concentrate the filtrate from step 2 under vacuum at 55 +/- 5 DEG C to provide a concentrated extract solution; And

4. The concentrated extract solution of step 3 is lyophilized to provide a dry substance (i. E. The banana peel extract used in the Examples below).

Example  2: Cell experiment

Human neuroblastoma cells were seeded in 6-well plates (2 x 10 ⁵ cells / well) and incubated for 24 hours. The cells were then divided into control and extract groups (3 times for each group) and incubated for 6 hours in each of the following media:

1. Control group: DMEM medium containing 10% fetal bovine serum and 1% penicillin / streptomycin; And

2. Extract group: The same 15.625 占 퐂 / ml banana bark extract obtained in Example 1 was added to the same medium as the control group.

The cells of the above groups were then harvested and RNA was extracted with an RNA extraction kit. The RNA was transcribed into cDNA by reverse transcriptase. Thereafter, the cDNA was subjected to quantitative PCR (qPCR) using a Step One Plus system and a KAPA SYBR FAST qPCR kit to quantitate the expression level of the melatonin (including TPH1, DDC and AANAT) Respectively. Next, each gene expression level in each group was calculated based on the results of the control group (i. E., The expression level of the control was multiplied by 1). The results are shown in Fig.

As shown in Fig. 1, the expression levels of TPH1, DDC and AANAT gene were much higher in the cells of the extract group than in the control group, and the expression level of the AANAT gene in the cells of the extract was 3.33 times that of the control group. These results indicate that the banana bark extract according to the present invention is effective for increasing the expression of TPH1, DDC and AANAT genes, and thus can be used for the improvement of melatonin expression and the secretion of melatonin, thereby achieving the treatment of insomnia and the improvement of sleeping disorder it means.

Example  3: Human Experiment

(3-1) Collection of samples

There were three groups (one for each group) of recruiting volunteers (excluding those taking hypnotics, those taking hypoglycemic agents, or pregnant women), and the following three groups: "People with severe sleep disorders (Group I) , "Persons with potential sleep disorders (hereinafter referred to as" group II "), and persons without sleep disorders (hereinafter referred to as" group III "). Next, the subject's sleep state was evaluated. Before drinking the beverage containing the banana peel extract according to the present invention, each subject was invited to fill in the sleep questionnaire (i.e., the 0 day sleep questionnaire, the questionnaire listed in Table 1 below), and the saliva and blood of each subject (I.e., saliva and blood on day 0), and subsequent experiments were performed. The subject then drank a drink of the 200 mg banana bark extract obtained in Example 1 (i.e., 7 drinks each day) for 7 days each night (after dinner). Then, each subject was asked to write a sleep questionnaire (the 7th sleep questionnaire, the same as the sleep questionnaire on the 0th day), and the saliva and blood of each subject were collected (ie, saliva and blood on the 7th day).

[Table 1]

(3-2) Sleep disorder score ( Sleep disturbance score )

On the 0th and 7th day from 3-1, the sleep questionnaires were analyzed and the sleep disorder scores of the subjects in each group were calculated. The baseline of sleep disturbance was set at 8 (ie, if the subject's score is greater than 8, the subject has a sleeping disorder). The results are shown in Fig.

As shown in FIG. 2, the scores for sleep disorders on Day 7 of "Group I" and "Group II" were significantly reduced compared to Day 0, while scores for Sleep Disorder of "Group III" did not change significantly. These results indicate that the banana peel extract of the present invention can effectively reduce sleep disorders of "persons with severe sleep disorders" and "people with potential sleep disorders" and does not adversely affect "people without sleep disorders" .

(3-3) Content of melatonin

The saliva on day 0 and day 7 of each group provided by 3-1 was tested using a Melatonin direct Saliva ELISA, 96T to determine the content of melatonin in the saliva (affecting both melatonin expression and secretion). Then, the relative content of melatonin on day 7 was calculated based on the result on day 0 (i.e., the content of melatonin on day 0 was set at 1 time). The results are shown in Fig.

As shown in FIG. 3, the content of melatonin in saliva of "Group I", "Group II" and "Group III" was significantly increased on day 7 compared with day 0. These results indicate that banana peel extract can effectively enhance the expression of melatonin and promote melatonin secretion, thereby improving insomnia and improving sleeping disorder.

(3-4) Expression level of melatonin-related gene

Blood on days 0 and 7 of each group provided by 3-1 was isolated with Ficoll-Paque Plus to obtain peripheral blood mononuclear cells (PBMCs). Then, the expression level of the melatonin-related genes (including TPH1 and AANAT) was determined in PBMC of each group using the assay method of Example 2, and the amount of gene expression on the 7th day was determined on the basis of 0 day The expression level was set to 1-fold). The results are shown in Fig.

As shown in Fig. 4, the levels of TPH1 and AANAT gene expression were significantly increased in PBMC of group "I" and "group II " at day 7 compared with day 0. These results suggest that banana peel extract may be effective in increasing the expression of melatonin and promoting melatonin secretion as it is effective in increasing the expression of TPH1 and AANAT genes in "persons with significant sleep disturbances" and "persons with potential sleep disorders" Whereby the insomnia treatment and the sleeping disorder improvement effect can be achieved.

As shown in the above experiment, the banana peel extract is effective in increasing the expression of TPH1, DDC and AANAT genes, and thus can be used to increase the expression of melatonin and promote melatonin secretion, and can be used for the treatment of insomnia, Can be used for at least one of treatment of related diseases, prevention of diseases related to neuro-metabolic disorders, control of appetite, control of sleep, control of mood, control of vasoconstriction, control of hemostatic function and control of immune response, Can be used.

Claims (10)

(DOPA dicarboxylase) gene expression and / or increased expression of TPH1 (tryptophan hydroxylase 1) gene, including an effective amount of banana bark extract, and / or AANAT (aralkylamine N-acetyl Transferase) gene expression. The composition of claim 1, used to increase expression of melatonin and / or promote secretion of melatonin. 3. The composition according to claim 1 or 2, wherein the composition is a pharmaceutical composition or a food composition. 4. The composition according to claim 3, which is a pharmaceutical composition and is used for at least one of treatment of insomnia, treatment of neurodegenerative disorders-related diseases, and prevention of diseases related to neuro-metabolic disorders. 5. The composition of claim 4, wherein the pharmaceutical composition is used in the treatment of insomnia. 5. The composition of claim 4, wherein the pharmaceutical composition is provided in a form suitable for oral or transdermal administration. The composition according to claim 3, which is a food composition and is used for at least one of the improvement of sleep disorder, appetite regulation, sleep control, mood regulation, vasoconstriction regulation, hemostatic function regulation and immune response regulation. 8. The composition of claim 7, wherein the food composition is used for improving sleep disorders. The composition according to claim 7, wherein the food composition is a health food, a health supplement, a functional food, a nutritional supplement or a special nutrition food. 8. The composition of claim 7, wherein the food composition is provided as a dairy product, a meat product, a bread ingredient, pasta, cookies, troches, capsules, fruit juices, tea, sports drinks or nutritional drinks.

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