Longan Flower Extract to Increase Melatonin in the Body

Abstract

The present invention provides a use of a longan flower extract for increasing the melatonin content in the body, wherein the longan flower extract has the effect of increasing the melatonin content in an individual, and can effectively and directly improve the individual's sleep disturbance and insomnia problems, and improve sleep quality, and all of these can take effect within a short number of days of taking.

Description

Technical Field

[0001] The present invention relates to the technical field of longan flower extracts, and specifically to a use of a longan flower extract to increase melatonin in the body, and more particularly to a use of a longan flower extract to increase melatonin in the body to improve insomnia, sleep disturbance, or sleep quality. Background Art

[0002] Longan (Dimocarpus longans Lour.) is an evergreen tree plant of the genus Euphoria in the family Sapindaceae. Taiwan Province of China is one of the major regions for the production and research of longan in the world, and longan is one of the top five fruit trees in Taiwan Province of China. According to statistics, the planting area of ​​longan in Taiwan Province of China in 2020 was 10,612 hectares, and the output was 64,543 metric tons. The production season of longan flowers is from March to April every year, and the flowering period is about one month, and there are three batches of flowering periods a year. Longan flowers can be divided into male flowers and female flowers. After the longan flowers bloom, they will be pollinated by wind and bees. After pollination, the female flowers are ready to bear fruit and have the characteristic of not falling off easily. The male flowers will fall naturally about 3-5 days after flowering. They can also be slightly knocked to promote falling and collection to assist pollination, and it does not affect fruiting. The male flowers that are not capable of bearing fruit have become a by-product of the longan planting process. Because longan flowers have a special longan aroma with a slightly sweet and astringent taste, they are often consumed in the form of scented tea or tea bags. They are rich in polyphenols and have good antioxidant, anti-inflammatory, uric acid-lowering and other biological activities, and are worth developing.

[0003] Melatonin is a hormone secreted by the pineal gland in the brain that has the function of regulating the biological clock. During the day, the secretion of melatonin is inhibited by light, so the human body can stay awake. At night, the secretion of melatonin increases, allowing the human body to enter a state of sleep. Long-term night shifts, rotating shifts, jet lag during travel, mental stress, or a lifestyle of using electronic products will lead to insufficient melatonin secretion at night, which will reduce the quality of sleep and even cause sleep problems such as insomnia, as well as daytime fatigue, day and night reversal, and decreased immunity, which will have a serious impact on daily life.

[0004] At present, the drugs commonly used in clinical treatment of sleep disturbances include sedative hypnotics (e.g., benzodiazepines and barbiturates) and antidepressants (e.g., clomipramine and imipramine). However, the use of the above drugs is very addictive and may cause side effects such as drowsiness, nausea, headache, vomiting, gastrointestinal discomfort, memory impairment, rebound insomnia, mental confusion, movement disorders, respiratory depression, and / or sleepwalking. Currently, melatonin extracted from bovine pineal glands or chemically synthesized is also sold on the market, but the above products are still strictly controlled drugs or even banned drugs in many countries due to the prevalence of mad cow disease and uncertainty about safe dosage. Therefore, it is necessary and urgent to continue to develop drugs or methods that can effectively treat insomnia, improve sleep disturbances and / or regulate sleep, and are not easy to cause addiction and side effects. Summary of the invention

[0005] Therefore, one object of the present invention is to provide a use of a longan flower extract for preparing a composition for increasing the melatonin content in the body; wherein the longan flower extract is obtained by extracting a longan flower with a solvent, and the solvent is water, alcohol, an alcohol-water mixture, or a combination thereof.

[0006] In one embodiment of the present invention, the longan flower extract is used to improve insomnia, sleep disturbance, or sleep quality of the individual.

[0007] In another embodiment of the present invention, the composition comprises at least 0.2 wt % of longan flower extract.

[0008] In another embodiment of the present invention, the longan flower is further hydrolyzed with a composite cellulase before being extracted with the solvent.

[0009] In another embodiment of the present invention, the composition is a pharmaceutical composition or a food composition.

[0010] In another embodiment of the present invention, the composition further comprises a pharmaceutically acceptable carrier or an edible material.

[0011] In another embodiment of the present invention, the composition has a powder, a granule, a solution, a gel, or a paste form.

[0012] The longan flower extract of the present invention has the effect of increasing the melatonin content in an individual, and can effectively and directly improve the individual's sleep disturbance, insomnia problems, and improve sleep quality, and all of these can take effect within a short number of days of taking; therefore, the longan flower extract of the present invention can be used to prepare a composition for helping sleep and / or improving sleep quality, wherein the composition is a medicine, a food, or a skin care product, and can be administered to an individual by oral administration, skin application, etc.

[0013] BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 The efficacy results of longan flower extract in increasing individual melatonin levels.

[0014] Figure 2 The efficacy results of longan flower extract in improving sleep disturbance in individuals.

[0015] Figure 3 The results show that longan flower extract can improve sleep quality in individuals. DETAILED DESCRIPTION

[0016] The following will further illustrate the implementation mode of the present invention with the help of drawings. The following examples are only used to illustrate the present invention and are not used to limit the scope of the present invention. Anyone skilled in the art can make some changes and modifications without departing from the spirit and scope of the present invention. Therefore, the protection scope of the present invention shall be determined by the scope of the attached patent application.

[0017] The numerical values ​​used herein are approximate values, and all experimental data are expressed within a range of 20%, preferably within a range of 10%, and most preferably within a range of 5%.

[0018] Statistical analysis was performed using Excel software. Data were expressed as mean ± standard deviation (SD), and differences between individuals were analyzed using student's t-test.

[0019] Unless otherwise specified herein, the terms "a", "an", "the" and similar terms used in this specification (especially in the scope of the patent application described below) should be understood to include both singular and plural forms; the so-called "treatment" should not be interpreted as treating an individual until complete recovery, but should include maintaining the disease progression or symptoms of an individual at a substantially static level, increasing the recovery rate of an individual, improving the severity of a specific condition, or improving the quality of life of a patient; the so-called "regulation" refers to positive regulation (including induction, stimulation, and enhancement) or negative regulation (including inhibition and attenuation) to move the individual toward the normal state of the physiological function; the so-called "subject" refers to a human or non-human mammal.

[0020] The "longan flower" mentioned herein refers to the flower of the longan plant; and the "longan flower extract" mentioned herein refers to the product obtained by extracting the longan flower with a solvent for a specific time and temperature.

[0021] The "sleep disturbance" mentioned in this article includes but is not limited to difficulty falling asleep, shallow sleep, insufficient sleep depth, easy awakening, inability to maintain long sleep, and quality of life affected by sleep.

[0022] The longan flower extract used in the present invention can be provided by an operation comprising the following steps: (a) extracting the longan flower with an extraction solvent to provide a crude extract; (b) centrifuging the crude extract and filtering the supernatant to provide a filtrate; (c) concentrating the filtrate under reduced pressure to obtain a concentrated extract; and (d) drying the concentrated extract to obtain a dried product.

[0023] In addition, other operations such as heating, cooling, stirring, ultrasonication, etc. may be performed before or during step (a) as needed to improve the extraction effect. For example, in one embodiment of the present invention, stirring is performed before step (a).

[0024] In addition, in step (c), the temperature during the reduced pressure concentration can be adjusted as needed. For example, the reduced pressure concentration of step (c) can be performed at 45-70°C; in a specific embodiment of the present invention, the reduced pressure concentration of step (c) is performed at 55±5°C. The longan flower extract used in the present invention can be the concentrated extract provided in step (c) or the dried product provided in step (d), wherein step (d) can be performed by freeze drying, spray drying, etc. In order to achieve the maximum extraction efficiency as much as possible, as needed, before performing step (b), the longan flower can be repeatedly extracted with the same or different extraction solvents, and the extracts obtained from the multiple extractions can be combined to provide a crude extract for performing step (b); the cycle of step (b), step (c), and other operations as needed can also be repeated.

[0025] The composition provided according to the present invention may be a pharmaceutical composition or a food composition. The pharmaceutical composition provided according to the present invention may be used for at least one of the following: increasing the content of melatonin, improving or treating insomnia, improving sleep disturbance, or improving sleep quality; preferably, for increasing the content of melatonin. The food composition provided according to the present invention is used for at least one of the following: increasing the content of melatonin, improving or treating insomnia, improving sleep disturbance, or improving sleep quality; preferably, for increasing the content of melatonin.

[0026] The pharmaceutical composition provided according to the present invention may be a medicine, a nutritional supplement, a health food, or any combination thereof, and may further comprise a pharmaceutically acceptable excipient, carrier, adjuvant, and / or food additive.

[0027] The pharmaceutical composition provided according to the present invention may be in any suitable form without particular limitation, and may be in a suitable dosage form corresponding to the intended use. For example, but not limited thereto, the pharmaceutical composition may be administered orally or parenterally (e.g., transdermally) to a subject in need.

[0028] In a preferred embodiment of the present invention, the composition of the present invention is formulated in a pharmaceutically acceptable vehicle and prepared into a dosage form suitable for oral administration, and the pharmaceutical composition is preferably in a dosage form selected from the following group: solution, suspension, powder, tablet, pill, syrup, lozenge, troche, chewing gum, capsule, and the like.

[0029] According to the present invention, the pharmaceutically acceptable carrier may include one or more agents selected from the following: solvent, buffer, emulsifier, suspending agent, decomposer, disintegrating agent, dispersing agent, binding agent, excipient, stabilizing agent, chelating agent, diluent, gelling agent, preservative, wetting agent, lubricant, absorption delaying agent, liposome and the like. The selection and amount of these agents fall within the professional accomplishment and routine technical scope of those skilled in the art.

[0030] According to the present invention, the pharmaceutically acceptable carrier comprises a solvent selected from the group consisting of: water, normal saline, phosphate buffered saline (PBS), an aqueous solution containing alcohol, and combinations thereof.

[0031] Taking the dosage form suitable for transdermal administration as an example, the pharmaceutical composition provided by the present invention can be in the form of a patch, lotion, cream, gel (e.g., hydrogel), paste (e.g., dispersion paste, ointment), spray, or solution (e.g., suspension) for direct external use, but is not limited thereto.

[0032] The pharmaceutical composition provided according to the present invention can be administered at different dosing frequencies such as once a day, multiple times a day, or once every few days, depending on the needs, age, weight, and health status of the individual being administered. In the pharmaceutical composition provided according to the present invention, the content ratio of the longan flower extract in the composition can be adjusted according to the actual application needs. In addition, the pharmaceutical composition can contain one or more other active ingredients (for example, sleeping pills, antidepressants, and melatonin, etc.) as needed, or be used in combination with drugs containing the one or more other active ingredients to further enhance the efficacy of the pharmaceutical composition or increase the flexibility and degree of formulation of the preparation, as long as the other active ingredients do not have an adverse effect on the benefits of the active ingredient of the present invention (i.e., the longan flower extract).

[0033] Optionally, the pharmaceutical composition or food composition provided by the present invention may contain an appropriate amount of additives, for example, flavoring agents, colorants, etc. that can improve the taste and visual experience of the pharmaceutical composition or food composition when taken, as well as buffers, preservatives, preservatives, antibacterial agents, antifungal agents, etc. that can improve the stability and storage properties of the pharmaceutical composition or food composition.

[0034] The food composition provided by the present invention can be a food product, and is prepared with edible materials to include but not limited to: beverages, fermented foods, bakery products, health foods, nutritional supplements, and dietary supplements.

[0035] According to the present invention, the edible material is selected from the group consisting of water, fluid milk products, milk, concentrated milk; fermented milk, such as yogurt, sour milk, frozen yogurt, lactic acid bacteria-fermented beverages; milk powder; ice cream; cream cheeses; dry cheeses; soybean milk; fermented soybean milk; vegetable-fruit juices; juices; sports drinks; confectionery; jellies; candies; infant formulas; health foods; animal feeds; Chinese herbal medicines; and dietary supplements.

[0036] According to the present invention, the food product can be used as a food additive, which is added during the raw material preparation or during the food production process by conventional methods, and is formulated with any edible material into a food product for human and non-human animals to consume.

[0037] The beverages, fermented foods, baked products, health foods, nutritional supplements, and dietary supplements provided by the present invention can be consumed once a day, multiple times a day, or once every few days, depending on the age, weight, and health status of the individual. The content of the longan flower extract in the beverages, fermented foods, baked products, health foods, nutritional supplements, and dietary supplements provided by the present invention can also be adjusted to meet the needs of a specific group, for example, to the amount that should be taken daily.

[0038] For beverages, fermented foods, baked products, health foods, nutritional supplements, and / or dietary supplements provided according to the present invention, the recommended dosage, usage standards and conditions for specific groups (e.g., insomniacs, depression patients, pregnant women, etc.), or recommended items for taking with other foods or medicines, etc. can be marked on their outer packaging, so that users can take them without the guidance of doctors, pharmacists or related deacons without safety concerns. In the food composition provided by the present invention, the state of the longan flower extract and related applications are as described above.

[0039] The present invention is further illustrated by the following examples. These examples are provided for illustration only and are not intended to limit the scope of protection of the present invention. The scope of protection of the present invention is shown in the attached patent claims.

[0040] Example 1 Preparation method of longan flower extract of the present invention

[0041] In one embodiment of the present invention, the dried longan flower and an extraction solvent of water, alcohol, or an alcohol-water mixture are uniformly mixed in a volume ratio of (1-5):(5-20), and then extracted at 50-100° C. for 30-60 minutes to obtain a crude extract, wherein the extraction solvent is preferably water or alcohol and more preferably ethanol. After the crude extract is cooled to room temperature, it is centrifuged at 1,000 g for 10 minutes and the supernatant is collected. The supernatant is then filtered through a 400 mesh filter to obtain a filtrate. The filtrate is then concentrated under reduced pressure at 45-70° C. to obtain a concentrated liquid formulation of the longan flower extract of the present invention, which is then spray-dried to obtain a dry formulation of the longan flower extract of the present invention.

[0042] In a preferred embodiment of the present invention, an enzyme hydrolysis step can be selectively performed before the extraction step. Specifically, after the dried longan flowers are added to the extraction solvent, 0.05-0.2% (w / w) of the composite fiber enzyme is additionally added for 30-60 minutes, and then the extraction is performed at 50-100°C for 30-60 minutes; wherein the composite fiber enzyme can be (Sigma, containing β-dextranase, xylanase, cellulase, hemicellulase), or (Sigma, activity ≥700 units / g, containing cellulase); wherein the enzymatic hydrolysis step can increase the yield and content of active ingredients of the longan flower extract of the present invention.

[0043] In the following examples, the longan flower extract used was mixed with water as an extraction solvent at a volume ratio of 1:(10-20), extracted at 75-85° C. for 30-60 minutes to obtain a crude extract, cooled to room temperature, centrifuged at 1,000 g for 10 minutes and the supernatant was collected, filtered through a 400 mesh filter, and the filtrate was concentrated under reduced pressure at 55-60° C. and then spray-dried to obtain the longan flower extract of the present invention.

[0044] Example 2 The longan flower extract of the present invention increases the melatonin content of an individual

[0045] Melatonin is known to be an important hormone for regulating the biological clock of an individual. It can help sleep and regulate metabolism. Therefore, in one embodiment of the present invention, in order to verify the efficacy of the longan flower extract of the present invention in promoting the production of melatonin in an individual, the longan flower extract of the present invention obtained by the aforementioned preparation method is firstly used to recruit 5 subjects aged 25-40 who are determined to have sleep disorders after being evaluated by the Athens Insomnia Scale and the Pittsburgh Sleep Quality Scale described later. Three days before the start of the experiment, these subjects are asked to stop taking drugs and related health foods that affect sleep. Then, 0.4 g of the dry dosage form is brewed with 150-200 mL of warm water. The longan flower extract of the present invention (converted mass percentage concentration is 0.2wt%-0.267wt%) was administered to the subjects once 1 hour before going to bed for a total of 28 days; on the 0th day, 3rd day, and 28th day of the experiment, the saliva of each subject was sampled at the same time in the evening to detect the melatonin content in the saliva, wherein the subjects had to stop eating for 30 minutes before sampling, and gargled to clear the food residue in the mouth, swallowed all the saliva remaining in the mouth before sampling, and collected about 1 mL of saliva under the tongue with a plastic dropper, and placed in a test tube and stored at -20°C, and the collected samples were Melatonin Direct Saliva ELISA Assay Kit was used for analysis.

[0046] The longan flower extract of the present invention has the following effects on increasing the melatonin content of an individual: Figure 1As shown in the figure, compared with before taking the longan flower extract of the present invention (i.e., day 0), on the third day after taking the longan flower extract, the melatonin content in the subject's saliva at night can be significantly increased by 2.2 times, and on the 28th day after taking the longan flower extract, the melatonin content is significantly increased by 9.15 times. This result shows that the longan flower extract of the present invention can effectively increase the melatonin content in the individual to achieve the effect of helping sleep and regulating metabolism, and can take effect in a short time; wherein, the longan flower extract of the present invention may be by regulating the expression of genes related to melatonin in the individual, such as: human tryptophan hydroxylase isoform (TPH) gene, arylalkylamine N-acetyltransferase (AANAT) gene, acetylserotonin methyltransferase (ASMT) gene, dopa decarboxylase (DDC) gene, thereby increasing the melatonin content in the individual and having a role in regulating the nervous system.

[0047] Example 3 The longan flower extract of the present invention improves insomnia and sleep quality of an individual

[0048] In one embodiment of the present invention, in order to verify the efficacy of the longan flower extract of the present invention in directly improving insomnia and sleep quality of an individual, the longan flower extract of the present invention obtained by the aforementioned preparation method was first administered to subjects in accordance with the method described in Example 2, and then the Athens Insomnia Scale and the Pittsburgh Sleep Quality Scale were evaluated on the 0th, 3rd, and 28th days of the experiment, respectively.

[0049] The Athens Insomnia Scale was developed in 2000 by a group of researchers from Athens, Greece, to assess insomnia patients with sleep disorders. After the subjects have completed the questionnaire, all scores are added up, with a total score of 24. A score of 4-5 indicates potential insomnia; a score >6 (inclusive) indicates sleep disturbances caused by insomnia.

[0050] The Pittsburgh sleep quality index (PSQI) was established in 1989 by Buysse et al. from the University of Pittsburgh in the United States to assess the sleep quality of patients with sleep disorders, mental disorders and the general public. Its content includes seven indicators, including sleep quality, sleep hysteresis period, total sleep time, habitual sleep efficiency, sleep disturbance (such as insomnia), use of sleeping pills and daytime dysfunction. In addition, it also includes assessment factors such as whether sleep interruption is caused by physiological factors such as coughing and heat. After the subjects have completed the questionnaire, all scores are added up. If the score is ≥5 points, it can be determined that the subject has a sleep quality disorder. The higher the score, the worse the sleep quality.

[0051] The longan flower extract of the present invention improves the sleep disturbance of an individual. Figure 2 As shown, the statistics were performed in a self-control manner, and the statistical formula was: relative value of sleep disturbance (%) = [score after using the longan flower extract of the present invention / score before using the longan flower extract of the present invention] * 100%; compared with before taking the longan flower extract of the present invention (i.e., day 0), on the 3rd day after taking the longan flower extract of the present invention, the sleep disturbance of the subjects was significantly reduced by 47%, and on the 28th day after taking the longan flower extract, the sleep disturbance was significantly reduced by 69%. This result shows that the longan flower extract of the present invention can effectively improve the insomnia problem of an individual and can take effect in a short time.

[0052] The longan flower extract of the present invention improves the sleep quality of an individual. Figure 3 As shown, the statistics were performed in a self-control manner, and the statistical formula was: relative percentage of sleep quality (%) = 1-[score after using the longan flower extract of the present invention / score before using the longan flower extract of the present invention]*100%; compared with before taking the longan flower extract of the present invention (i.e., day 0), on the 3rd day after taking the longan flower extract of the present invention, the sleep quality of the subjects was significantly improved by 55.2%, and on the 28th day after taking the longan flower extract, the sleep quality was significantly improved by 60.6%. This result shows that the longan flower extract of the present invention can effectively improve the sleep quality of an individual and can take effect in a short time.

[0053] In summary, the longan flower extract of the present invention has the effect of increasing the melatonin content in an individual, and can effectively and directly improve the individual's sleep disturbance, insomnia problems, and improve sleep quality, and all of these can take effect within a short number of days of taking; therefore, the longan flower extract of the present invention can be used to prepare a composition for helping sleep and / or improving sleep quality, wherein the composition is a medicine, a food, or a skin care product, and can be administered to an individual by oral administration, skin application, etc.

[0054]

Explanation of symbols

[0055] none.

[0056]

Biological material storage

[0057] none.

Claims

1. A use of a longan flower extract for preparing a composition for increasing the content of melatonin in the body, characterized in that: in, The longan flower extract is obtained by extracting a longan flower with a solvent at 75-85° C. for 30-60 minutes, and the solvent is water, alcohol, an alcohol-water mixture, or a combination thereof, and the volume ratio of the longan flower to the solvent is 1:(10-20).

2. The use according to claim 1, characterized in that The longan flower extract improves insomnia, sleep disturbance, or sleep quality of an individual.

3. The use according to claim 1, characterized in that The composition contains at least 0.2 wt % of the longan flower extract.

4. The use according to claim 1, characterized in that The longan flower is further hydrolyzed with a composite cellulase before being extracted with the solvent.

5. The use according to claim 1, characterized in that: The composition is a pharmaceutical composition or a food composition.

6. The use according to claim 1, characterized in that: The composition further comprises a pharmaceutically acceptable carrier or an edible material.

7. The use according to claim 1, characterized in that The composition has a powdery, granular, solution, gel, or paste form.

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