WO2021095814A1 - 心理状態改善用組成物、心理状態改善用組成物の製造方法および心理状態改善のためのナスの果実の使用 - Google Patents

心理状態改善用組成物、心理状態改善用組成物の製造方法および心理状態改善のためのナスの果実の使用 Download PDF

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WO2021095814A1
WO2021095814A1 PCT/JP2020/042298 JP2020042298W WO2021095814A1 WO 2021095814 A1 WO2021095814 A1 WO 2021095814A1 JP 2020042298 W JP2020042298 W JP 2020042298W WO 2021095814 A1 WO2021095814 A1 WO 2021095814A1
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Prior art keywords
eggplant
composition
improving
psychological state
blood pressure
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English (en)
French (fr)
Japanese (ja)
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浩蔵 中村
順 西平
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Electronics Development Computer College
WellnasCo ltd
Shinshu University NUC
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Electronics Development Computer College
WellnasCo ltd
Shinshu University NUC
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Priority to JP2021556152A priority Critical patent/JP7713635B2/ja
Priority to CN202080078378.7A priority patent/CN114728034A/zh
Priority to US17/776,939 priority patent/US20220401509A1/en
Publication of WO2021095814A1 publication Critical patent/WO2021095814A1/ja
Anticipated expiration legal-status Critical
Priority to JP2025109903A priority patent/JP2025138789A/ja
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/22Anxiolytics
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23LFOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105Plant extracts, their artificial duplicates or their derivatives
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/81Solanaceae (Potato family), e.g. tobacco, nightshade, tomato, belladonna, capsicum or jimsonweed
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/10Preparation or pretreatment of starting material
    • A61K2236/15Preparation or pretreatment of starting material involving mechanical treatment, e.g. chopping up, cutting or grinding
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30Extraction of the material
    • A61K2236/37Extraction at elevated pressure or temperature, e.g. pressurized solvent extraction [PSE], supercritical carbon dioxide extraction or subcritical water extraction
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/50Methods involving additional extraction steps
    • A61K2236/51Concentration or drying of the extract, e.g. Lyophilisation, freeze-drying or spray-drying

Definitions

  • the present invention relates to a composition for improving psychological state, a method for producing a composition for improving psychological state, and the use of eggplant fruit for improving psychological state.
  • Non-Patent Document 1 cardiovascular disease accounts for about 17 million deaths annually, which is equivalent to about one-third of all deaths worldwide.
  • Hypertension accounts for 9.4 million deaths worldwide each year, with at least 45% due to heart disease and 51% due to stroke. Hypertension also contributes to renal failure, premature death, and disability (Non-Patent Document 1). Therefore, prevention and control of hypertension is a major public health challenge worldwide.
  • lifestyle modifications including dietary changes, exercise, and weight loss, contribute to the primary prevention of hypertension and significantly reduce blood pressure in people with hypertension (non-patent literature). 2-4).
  • Functional foods with antihypertensive action are also expected to prevent and control hypertension (Non-Patent Document 5).
  • “foods for specified health use” approved by the government or "nutritional functional foods” labeled at the responsibility of the food business operator are commercially available.
  • Eggplant Solanum melongena
  • Non-Patent Document 6 Eggplant (Solanum melongena) is a globally popular vegetable that is consumed daily and is an agriculturally and economically important cultivated crop. Since eggplant is low in energy, carbohydrates and protein, and rich in dietary fiber and minerals (Non-Patent Document 6), it is recommended for the purpose of reducing energy intake and body weight (BW) for the prevention of type 2 diabetes. (Non-Patent Document 7-9).
  • Previous clinical trials on the efficacy of eggplant included a study related to the cholesterol-lowering effect of hypercholesterolemia subjects (Non-Patent Document 10) and an evaluation of efficacy in reducing fat mass in overweight women (Non-Patent Document 10). There are two cases in Non-Patent Document 11).
  • Acetylcholine is well known as a neurotransmitter and is present not only in mammals but also in almost all living organisms including those used as food raw materials (Non-Patent Document 12). It has been reported that food materials such as eggplant, bamboo shoots (Phyllostachys bambusoides), and shiitake mushrooms (Lentinus eddoes) contain acetylcholine (Non-Patent Documents 12 and 13).
  • Non-Patent Documents 14 and 15 Recently, we have clarified the antihypertensive effect of eggplant powder rich in acetylcholine in SHR, and suggested that eggplant acetylcholine suppresses sympathetic nerve activity and causes antihypertensive effect.
  • Non-Patent Document 17 Betanecol, a cholinergic agent, stimulates the parasympathetic nervous system via muscarinic acetylcholine receptors and lowers blood pressure. Therefore, it was presumed that acetylcholine contained in orally administered eggplants enhances parasympathetic nerve activity, suppresses sympathetic nerve activity by antagonism, and lowers blood pressure. Stress and psychological state (PS) are closely related to sympathetic nerve activity (Non-Patent Documents 18 and 19). Psychological factors are also related to blood pressure and may lead to hypertension (Non-Patent Document 20). Therefore, eggplant intake may improve stress and psychological state in addition to blood pressure.
  • PS Stress and psychological state
  • Psychological factors are also related to blood pressure and may lead to hypertension
  • the present inventor studied the antihypertensive effect and vasodilator component contained in fermented Kyobaku (lactic acid fermented product of buckwheat plant), and quaternary alkylammonium mainly composed of multiple choline esters including at least acetylcholine and propionylcholine.
  • An extract composition containing a compound was provided, and it was clarified that a single oral administration of purified acetylcholine, propionylcholine, butyrylcholine, and lactoylcholine to SHR exhibits an antihypertensive effect (Patent Documents 1 and 2). ..
  • freeze-dried powders of edible plants such as eggplant and bamboo shoots and extracts of edible plants with ethanol or hydrous ethanol contain active ingredients having an antihypertensive effect such as acetylcholine for oral ingestion. It was clarified that it can be used as (Patent Document 3).
  • Patent Document 4 a composition containing a vegetable juice such as tomato, carrot, spinach and a sprouted buckwheat juice as an active ingredient
  • Patent Document 5 a water-soluble, sugar-free tomato extract.
  • Guimaraes, PR; Galvao, AMP; Batista, CM; Azevedo, GS; Oliveira, RD; Lamounier, RP; Freire, N .; Barros, AMD; Sakurai, E .; Oliveira, JP; et al. infusion has a modest and transparency effect on hypercholesterolemic subjects.
  • the present inventor can prepare a composition more easily using less raw materials and have a psychological state improving effect more effectively, and if a composition can be obtained, a large amount of it can be used as a health food such as a supplement or a pharmaceutical product at low cost. Focusing on the possibility of production, we searched for new materials that have a psychological state improving effect.
  • an object of the present invention is to provide a new composition having a psychological state improving action.
  • the main invention of the present invention for solving the above-mentioned problems is a composition for improving a psychological state, which contains a water-soluble component of the fruit of eggplant (Solanum melongena) as an active ingredient.
  • FIG. 5 is a flowchart showing subject selection in a placebo-controlled randomized, double-blind, parallel-group comparative study for verifying the effects of continuous ingestion of eggplant powder on improving blood pressure, stress, and psychological state. It is a figure which shows the schedule of a test. It is a figure which shows the blood pressure improving effect by continuous intake of eggplant powder, and shows the amount of change of the diastolic blood pressure at the time of visit of all the subjects (the person with normal hypertension and the person with I degree hypertension). It is a figure which shows the blood pressure improving effect by continuous intake of eggplant powder, and shows the amount of change of diastolic blood pressure at the time of visit of a person with normal high blood pressure.
  • the present invention includes, for example, the following configuration.
  • [Item 1] A composition for improving psychological state, which comprises a fruit-derived component of eggplant (Solanum melongena).
  • [Item 2] The composition for improving a psychological state according to item 1, which contains a water-soluble component of the fruit of eggplant (Solanum melongena) as an active ingredient.
  • [Item 3] The composition for improving a psychological state according to item 1, which comprises a water-soluble component of the fruit of eggplant (Solanum melongena).
  • [Item 4] The composition for improving a psychological state according to any one of items 1 to 3 for oral ingestion at a dose such that the amount of choline ester in the water-soluble component is 0.5 ⁇ g / kg body weight or more and 50 mg / kg body weight or less.
  • [Item 5] The composition for improving a psychological state according to any one of items 1 to 4, wherein the choline ester content is 5 ⁇ g or more and 50 mg or less, and the composition is for oral ingestion.
  • [Item 6] The composition for improving psychological state according to item 4 or 5, wherein the choline ester is any one selected from acetylcholine, butylcholine and propionylcholine.
  • [Item 7] The composition for improving a psychological state according to any one of items 1 to 6, which is a dry powder.
  • [Item 9] A method for producing a composition for improving psychological state, which comprises a method for producing a composition for improving psychological state, which comprises squeezing an eggplant (Solanum melongena) fruit to obtain a juice.
  • [Item 10] A method for producing a composition for improving a psychological state containing an eggplant-derived component, wherein water is added to the fruit of eggplant (Solanum melongena) and the fruit to which the water is added is squeezed to obtain a squeezed liquid.
  • a method for producing a composition for improving a psychological state including.
  • a composition for improving a psychological state which is produced by the production method according to any one of items 9 to 13.
  • the psychological state improving composition contains a water-soluble component of eggplant fruit as an active ingredient.
  • the composition for improving the psychological state according to another embodiment may consist of a water-soluble component of eggplant fruit.
  • the water-soluble component of the eggplant fruit means a water-soluble component obtained by squeezing the eggplant fruit, but it is contained in the juice obtained by adding water to the eggplant fruit and squeezing it. It also means a water-soluble component.
  • the juice contains a water-insoluble component inevitably, or even if a part of the water-soluble component inevitably remains as a residue during juice extraction, it is contained in the juice.
  • the component corresponds to a water-soluble component.
  • the eggplant used in this embodiment is not particularly limited. Eggplants that are generally eaten are preferable, and varieties such as Tosataka, Shintaro, Ryoma, Senshu Mizunasu, Battennasu, Hiroryo Salad Eggplant (also known as Mio), Higamurasaki, Ocho Eggplant, Chikuyo, and Senryo are used. be able to.
  • examples of the choline ester that can be contained in the composition for improving the psychological state include acetylcholine, butyrylcholine, propionylcholine, and the like, and a composition containing one or more of these may be used. ..
  • the amount of acetylcholine in the water-soluble component is 0.5 ⁇ g / kg body weight to 50 mg / kg body weight, preferably 2 ⁇ g / kg body weight to 20 mg / kg body weight. It is used for oral ingestion at a dose of kg body weight, particularly preferably 5 ⁇ g / kg body weight to 1 mg / kg body weight, more preferably 8 ⁇ g / kg body weight to 100 ⁇ g / kg body weight. By orally ingesting such a dose, a psychological state improving effect can be obtained more effectively.
  • the composition for improving the psychological state is for oral ingestion, and the choline ester content may be 5 ⁇ g or more and 50 mg or less. Further, in the composition for improving the psychological state, the choline ester content is preferably 500 ⁇ g or more and 20 mg or less, and more preferably 1 ⁇ g or more and 10 mg or less. By orally ingesting such a dose, a psychological state improving effect can be obtained more effectively.
  • the composition for improving the psychological state may be, in one embodiment, a dry powder such as a freeze-dried powder or a hot air-dried powder.
  • composition for improving the psychological state of the present embodiment can be used as a food composition such as various functional health foods or a pharmaceutical composition.
  • In the case of food, it may be used in combination with an appropriate food additive. Not limited to such food compositions, it can be blended with green tea, black tea, oolong tea, miscellaneous grain tea, health drinks, sports drinks, etc. as a beverage, or blended with biscuits, bread, candy, chocolate, macaroons, etc. It is also possible to provide it as a food in a form that can be ingested on a daily basis. It is also possible to use it as a so-called supplement as an appropriate dosage form according to the preparation of the following pharmaceutical products.
  • dosage forms When used as a drug, it can be used in various dosage forms according to the usual dispensing method in combination with an appropriate drug additive.
  • dosage forms include solid preparations such as powders, granules, capsules, pills and tablets, and oral administration agents such as liquid preparations such as liquid medicines, suspensions and emulsions.
  • composition for improving the psychological state according to the present embodiment is used as a food, it is used not only as a general food or drink, but also as a food for specified health use or a food with a functional claim that exerts a specific function to promote health. Can be mentioned.
  • supplements including capsules, tablets, powders, granules and the like containing the composition for improving the psychological state according to the present embodiment as an active ingredient, bread, cakes, cookies, macaroons and the like.
  • Bakery foods such as, sauces, soups, dressings, seasonings such as mayonnaise, dairy products such as milk, yogurt, creams, confectionery such as chocolate and candy, or green tea, black tea, dragon tea, wheat tea, miscellaneous grain tea , Fruit juice, vegetable beverages, dairy beverages, soft beverages, carbonated beverages and other various beverages.
  • the dose varies depending on the ratio of each ingredient, and the age, weight, sex, symptom, administration method, etc. of the patient, etc. It depends on various factors. It can also be increased or decreased as appropriate depending on the degree of symptom improvement.
  • the number of administrations can be divided into 1 to several times a day.
  • the intake amount when the composition for improving the psychological state according to the present embodiment is used as a food can be selected according to the case of oral administration of the above-mentioned drug.
  • the dose and frequency of administration are not particularly limited, so the purpose of maintaining health, as well as taste and palatability are taken into consideration unless particularly serious symptoms occur. Then, the intake amount may be selected without limitation.
  • composition for improving psychological state is used not only for the composition for improving psychological state, but also for a subject with hypertension and a subject who is healthy (not hypertensive) but has high blood pressure. Can be done.
  • additives can be added to the psychological state improving composition according to the present embodiment, if necessary.
  • Various additives can be used and are not particularly limited, and for example, sugars such as lactose hydrate, sucrose, glucose, reduced malt sugar, mannitol and sorbitol, corn starch, potato starch, and portions.
  • Starches such as alferated starch, dextrin, and purulan and their derivatives, celluloses such as crystalline cellulose and microcrystalline cellulose, derivatives such as carboxymethyl cellulose, macrogol, and one or a mixture of two or more kinds of magnesium aluminometasilicate.
  • dextrin is more preferred.
  • One type of additive may be used alone, or two or more types may be used in combination. These additives are preferably contained in an amount of 1 to 1000 parts by mass, more preferably 10 to 300 parts by mass, based on 100 parts by mass of the composition of the present invention.
  • the choline ester which is the active ingredient of the composition for improving the psychological state according to the present embodiment, is not limited to the above-mentioned eggplant, and any of those derived from animals, those derived from plants, and those derived from microorganisms are used. be able to. In particular, it is preferable to use an organism derived from an organism that humans have eaten, and it is preferable to use an edible plant. That is, the composition for improving the psychological state according to the present embodiment is not limited to the fruit derived from eggplant, and may contain a water-soluble component of a food made from an agricultural product containing a high amount of choline ester as an active ingredient.
  • the edible plant other than eggplant is not particularly limited as long as it contains choline ester.
  • Edible plants include, for example, cucumber, tomato, paprika, pepper, asparagus, yam, cabbage, lettuce, carrot, apple, sweet pepper, Japanese pear, grape, radish sprouts, broccoli, alfalfa, bean sprouts, buckwheat. , Takenoko, etc.
  • it is preferably an agricultural product containing a high choline ester, and from the viewpoint of the content of acetylcholine, bamboo shoots and Bambusoideae bamboo shoots are preferable, and bamboo shoots are preferably tips.
  • the psychological state improving composition according to the present embodiment is obtained in one embodiment by the following manufacturing method.
  • the method for producing the composition for improving the psychological state according to the present embodiment is to squeeze the eggplant fruit to obtain a juice, or to add water to the eggplant fruit, and to squeeze the water-added fruit. Including soup. Even when it is produced from a raw material other than eggplant fruit, a composition for improving psychological state can be obtained by the same method.
  • the water to be added to the eggplant fruit is not particularly limited, and water in a temperature range of 5 ° C. or higher and 40 ° C. or lower may be added. It is preferable to add water at room temperature.
  • the amount of water added is preferably 50 parts by mass or more and 200 parts by mass or less, more preferably 75 parts by mass or more and 150 parts by mass or less, and particularly preferably 100 parts by mass with respect to 100 parts by mass of the raw eggplant fruit. If the amount of water is small, the extraction of the water-soluble component as an active ingredient may be insufficient, and if the amount of water is large, the processing volume becomes large, and it may not be easy to process into a dry powder, for example.
  • the eggplant fruit is preferably crushed before or after the addition of water, and is particularly preferable to be crushed before the addition of water from the viewpoint of ease of crushing. Crushing the eggplant fruit facilitates the extraction of water-soluble components.
  • the crushing can be performed in various forms such as strip cutting, dice-shaped blocks, and paste-like forms, but it is preferable to crush the paste-like crushing in order to facilitate squeezing.
  • a juicer, a mixer, a mill, a crusher or the like can be used for example.
  • the water used in the method for producing the composition for improving the psychological state according to the present embodiment is mineral water, distilled water, deionized water, ion-exchanged water, electrolyzed water, tap water, well water, industrial water used for food, etc.
  • Water generally used for food processing can be used.
  • the pH is not particularly limited, but in order to keep acetylcholine stable, pH 9.0 or less and pH 3.0 or more are preferable, pH 8.0 or less and pH 4.0 or more, and more preferably pH 6.5 or less and pH 4.5 or more. Yes, you can use water whose pH has been adjusted using a pH adjuster such as citric acid or ascorbic acid.
  • ethanol may be added to reduce bacterial contamination during squeezing work. Increasing the ethanol concentration helps reduce microbial contamination, but the solubility of the water extract deteriorates and the extraction efficiency of water-soluble components decreases. Therefore, the ethanol concentration is preferably 9.9% or less, preferably 6% or less. , More preferably 4% or less.
  • the eggplant fruit may be heated.
  • the acetylcholine degrading enzyme can be inactivated, and acetylcholine can be efficiently extracted.
  • the eggplant fruit tissue is softened, the cell wall is destroyed, and the extraction of water-soluble components of the eggplant fruit and the crushing of the eggplant fruit can be facilitated.
  • the mode of heating is not particularly limited, and for example, heating can be performed for 2 to 60 minutes in a temperature range of 30 ° C. or higher and 120 ° C. or lower.
  • the heating temperature is preferably 80 ° C. or higher and 100 ° C. or lower.
  • Examples of the method for heating eggplant fruits include a method of heating in a microwave oven, a hot plate or a pot, a method of immersing in boiling water, and a method of applying steam.
  • the method of immersing in boiling water and the method of applying steam to the eggplant are preferable.
  • the eggplant fruit may be heated before, after the addition of water, during heating with water, before crushing, after crushing, or during crushing, but the heated eggplant is crushed and crushed. It is preferable to heat the eggplant quickly to inactivate the acetylcholine degrading enzyme.
  • the method of squeezing the crushed eggplant fruit is not particularly limited as long as it can be divided into a squeezed liquid and a residue.
  • the soup stock can be squeezed with a juice squeezing machine such as wine using a soup stock bag, or with a fruit juice squeezer.
  • a centrifuge or screw press may be used.
  • the obtained juice can be dried into a lumpy or powdery dried product.
  • the drying method is not particularly limited, but it is preferable that the moisture contained in the dried product can be dried to 0% by mass or more and 10% by mass or less.
  • it can be dried by heat drying such as hot air drying, drum drying, freeze drying, spray drying and the like.
  • the dried product can be made into a dry powder by crushing.
  • the crushing method is not particularly limited, but it is preferable that the crushing method can be crushed to about 5 to 100 mesh. For example, it can be pulverized using a mill.
  • the composition produced by the method for producing the composition for improving the psychological state according to the present embodiment tends to contain a small amount of dietary fiber and a large amount of sugar.
  • the ratio of dietary fiber to sugar in the composition of the present invention is, for example, 1: 2 to 1: 100, preferably 1: 5 to 1:40, and particularly preferably 1:10 to 1. : 20.
  • the composition for improving the psychological state containing eggplant-derived choline ester has the blood pressure and psychological state of a person with normal high blood pressure and a person with high I degree hypertension who are feeling stress by continuously ingesting the composition. Significant improvement. This is demonstrated, for example, in placebo-controlled randomized, double-blind, parallel-group controlled trials as described in Examples below.
  • the composition for improving the psychological state according to the present embodiment is continuously ingested, and for a person with normal high blood pressure, the blood pressure at the time of visit (diastole / diastole after loading), Home blood pressure (wake-up systole / diastole / bedtime diastole) is significantly improved, and for those with degree I hypertension, on-site blood pressure (constriction / diastole) is significantly improved.
  • blood pressure at the time of visit (systole / diastole) and home blood pressure (systole / diastole at wake up) are significantly improved.
  • composition for improving the psychological state according to the present embodiment is continuously ingested, and no side effects or problematic adverse events are observed during the ingestion period of 12 weeks.
  • the psychological state improving composition and the method for producing the psychological state improving composition according to the present embodiment can provide a new composition having a psychological state improving action.
  • the effect of improving the psychological state can also be obtained by eating the eggplant fruit itself.
  • a psychological state improving effect or other effects for example, an effect of improving blood pressure can be obtained.
  • Eggplants to be eaten can be effective even if they are eaten raw or heated, and even processed foods such as pickles can be effective.
  • Blood pressure is classified according to the Hypertension Treatment Guideline 2014 (edited by the Japanese Society of Hypertension Hypertension Treatment Guideline Development Committee, April 2014, published by the Japanese Society of Hypertension, ISBN: 978-4-89775-322-5) and defined as follows. Will be done. Normal high blood pressure 130 mmHg ⁇ systolic blood pressure ⁇ 139 mmHg and / or 85 mmHg ⁇ diastolic blood pressure ⁇ 89 mmHg, I degree hypertension 140 mmHg ⁇ systolic blood pressure ⁇ 159 mmHg and / or 90 mmHg ⁇ diastolic blood pressure ⁇ 99 mmHg
  • Subjects who met the eligibility criteria were randomly divided into an eggplant (capsule containing eggplant powder) group and a placebo (capsule containing dextrin) group according to the stratification of gender, age, systolic blood pressure and diastolic blood pressure at the first visit. It was assigned.
  • the attributes of the subjects in each group are shown in Table 1.
  • the test meals were allocated by a third-party data center (Ebetsu City, Hokkaido, Media Education Center, Hokkaido Institute of Information Technology) by blocking using a computer. Collaborators are blinded to the allocation information during the study. The key open was done after the data analysis was completed.
  • Eggplant powder was prepared from eggplant juice containing excipients for dry powdering.
  • the test food was defined by the daily intake of eggplant-derived choline ester (acetylcholine).
  • the amount of acetylcholine to be ingested was 2.3 mg per day (equivalent to 22 g of fresh eggplant used in this test).
  • Eggplant from Kochi prefecture was used as the raw material eggplant.
  • Raw eggplants were washed and shredded immediately after harvest and heated to prevent spoilage.
  • Eggplant juice was obtained by squeezing to remove solids. After adding dextrin to the juice, it was freeze-dried. 1.92 mg of eggplant-derived choline ester (acetylcholine) was contained in 1 g of eggplant powder, and the yield was 4.08%.
  • Eggplant powder was packed in capsules with a volume of 300 mg. Placebo capsules were filled with dextrin only.
  • Capsules for the eggplant group and the placebo group are prepared according to a strict quality control protocol and have the same appearance.
  • the nutritional composition of each group of capsules was analyzed at the Japan Food Research Laboratories. See Table 2 for analysis results.
  • Acetylcholine was analyzed using LC-MS / MS at Shinshu University. In this study, subjects ingested 1200 mg of eggplant powder (300 mg capsules containing 25% dextrin-containing eggplant powder x 4 times) per day. This is equivalent to eating about 22g of fresh eggplant a day.
  • the primary endpoint is blood pressure at the time of visit, which consists of systolic blood pressure and diastolic blood pressure.
  • Secondary evaluation items are home blood pressure (at the time of waking up and at bedtime), stress evaluation using the visual analog scale (VAS: Visual Analogue Scale), and "mood evaluation scale (POMS (Profile of Mood States) -2) Japanese version”. It is a psychological state evaluation using the complete version of "for adults”.
  • Acetylcholine and EN contained in the sample were subjected to LC-MS / MS analysis under the following conditions. Separation was performed by isocratic mobile phase (33% methanol containing 0.010% formic acid) on a YMC-Triart PFP column (4.6 mm ⁇ 250 mm, 5 ⁇ m, manufactured by YMC Co., Ltd., Kyoto). Acetylcholine and EN were detected by the following MRM transitions using positive multiplex reaction monitoring (MRM). 146.15> 87.10 (Acetylcholine) 187.30> 128.15 (EN)
  • MRM positive multiplex reaction monitoring
  • GABA ⁇ -aminobutyric acid
  • CA chlorogenic acid
  • the subject measured home blood pressure using an automatic sphygmomanometer HEM-7080IC using the upper arm of a non-dominant arm.
  • the subjects measured their blood pressure daily one week before 2 to 6 visits, within 1 hour after waking up (morning blood pressure), and before going to bed (nighttime blood pressure). The measurement was performed three times in a row, and the median value of the measured value was obtained every day. The mean blood pressure 3 days before each evaluation point was evaluated.
  • WBC fast and white blood cells
  • RBC red blood cells
  • Hb hemoglobin
  • Hct hematocrit
  • Plt platelet count
  • Liver function (aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase ( ⁇ -GTP), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) levels for biological tests Renal function (blood urea nitrogen (BUN), creatinine (CRE), and uric acid (UA) levels), lipid profile (total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density Lipoprotein cholesterol (HDL-C), and triglyceride (TG) levels), glycemic profile (fasting plasma glucose (FPG) and hemoglobin (Hb) Alc levels).
  • AST blood urea nitrogen
  • CRE creatinine
  • U lactate dehydrogenase
  • TC total cholesterol
  • LDL-C low density lipoprotein cholesterol
  • HDL-C high density Lipoprotein cholesterol
  • TG triglyceride
  • FPG fast
  • the first urine was collected and the sample was used for qualitative evaluation of pH, sugar, protein, occult blood, urobilinogen, and ketones.
  • Body composition BW, body fat percentage (BFR), and BMI was evaluated using a body composition analyzer DC-320 (Tanita, Tokyo, Japan).
  • VAS questionnaire was used for the stress evaluation of the subjects. Subjects are instructed to answer each question about their current state of mind and body with an "X" somewhere on the 100 mm line that represents the worst (leftmost, 0 mm) to best (rightmost, 100 mm). It was. The result of the questionnaire is evaluated by the distance from the start point of the left line to "X", and it is evaluated that the stress is improved as the score number increases.
  • the POMS-2 questionnaire was used for the purpose of evaluating the effect of eggplant on the psychological state. Subjects were instructed to complete a questionnaire before ingesting the test food. Anger-hostility, confusion-embarrassment, depression-depression, fatigue-lethargy, tension-anxiety were defined as negative psychological states, while vitality-vitality and friendship were defined as positive psychological states.
  • TMD Schizoaffective Disorder Index
  • FFQg Food Intake Frequency Survey
  • the subgroup analysis was as follows: systolic blood pressure 130-139 mmHg or diastolic blood pressure 85-89 mmHg (normally high blood pressure) and systolic blood pressure 140-159 mmHg or diastolic blood pressure 90-99 mmHg (I-degree hypertensive).
  • the analysis was divided into. SPSS v25 (manufactured by IBM Japan Ltd., Tokyo) was used for all statistical analyzes. The same method was used for exploratory data analysis using measured values. All results are expressed as sample mean ⁇ standard error. A statistically significant difference was found when the p-value was 0.05 or less.
  • FIG. 3 shows diastolic blood pressure of all subjects
  • FIG. 4 shows diastolic blood pressure of normal high blood pressure subjects
  • FIG. 5 shows systolic blood pressure of all subjects
  • FIG. 6 shows systolic blood pressure of I-degree hypertensive subjects
  • FIG. 7 shows I. Shows diastolic blood pressure in people with high blood pressure. Values are displayed as mean ⁇ standard error. Statistical significance by Student's t-test: * p ⁇ 0.05 and *** p ⁇ 0.001 vs placebo group.
  • FIG. 8 shows systolic blood pressure and diastolic blood pressure when all subjects wake up
  • FIG. 9 shows systolic blood pressure and diastolic blood pressure when waking up of all subjects
  • FIG. 10 shows diastolic blood pressure at bedtime of normal high blood pressure subjects. Is shown. Values are displayed as mean ⁇ standard error. Statistical significance by Student's t-test: * p ⁇ 0.05 and *** p ⁇ 0.01 vs placebo group.
  • Improvements were also seen with eggplant intake in the secondary endpoints of home systolic blood pressure and diastolic blood pressure. Improvements were seen in systolic blood pressure and diastolic blood pressure at wake-up in all subjects and normal high blood pressure subjects, and diastolic blood pressure at bedtime in normal high blood pressure subjects, supporting the effect of improving blood pressure at the time of visit by eggplant intake. became.
  • Control of early morning blood pressure is important for the prevention of heart failure [White, WB Clinical assessment of early morning blood pressure in patients with hypertension. Prev. Cardiol. 2007, 10, 210-214.], [Wang, JG; Kario , K .; Chen, CH; Park, JB; Hoshide, S .; Huo, Y .; Lee, HY; Li, Y .; Mogi, M .; Munakata, M .; et al. Management of morning hypertension: A consensus statement of an Asian expert panel. J. Clin. Hypertens. 2018, 20, 39-44.].
  • M3 muscarinic acetylcholine receptor M3 mAChR
  • M3 mAChR M3 muscarinic acetylcholine receptor
  • Impaired autonomic nervous regulation is thought to contribute to the increase in SHR blood pressure. It has been reported that the amount of catecholamines in the blood of SHR is higher than that of normotensive Wistar-Kyoto (WKY) rats, which is due to the abnormal increase in sympathetic nerve activity of SHR [Tsunoda, M .; Takezawa, K .; Ina. , Y .; Nagashima, K .; Ohomori, K .; Kobayashi, S .; Imai, K. New approach for measurement of sympathetic nervous abnormality in conscious, spontaneously hypertensive rats.
  • eggplant intake improved only in diastolic blood pressure in subjects with normal hypertension, but improved in both systolic and diastolic blood pressure in subjects with grade I hypertension.
  • the difference in blood pressure between the eggplant group and the placebo group was 5.6 mmHg for diastolic blood pressure of normal hypertensive subjects, 7.6 mmHg for systolic blood pressure of I-degree hypertensive subjects, and 7.3 mmHg for diastolic blood pressure.
  • the tendency of the psychological state to improve from the 0th week to the 4th week suggests the effect of adapting the subject to the test.
  • the psychological state deteriorated. Although there was no effect on the entire test, this may be due to the earthquake that occurred 15 days before the 8th week of the test (September 6).
  • Non-Patent Document 16 the main compound that caused the antihypertensive effect of eggplant in SHR is not GABA and CA but eggplant-derived choline ester (acetylcholine) (Non-Patent Document 16).
  • the composition according to the present embodiment can provide a new composition having an excellent antihypertensive effect and a psychological state improving effect that can be easily and inexpensively produced from the fruit of eggplant (Solanum melongena). ..
  • it when orally administered, it has a remarkable antihypertensive effect as compared with the conventional composition having an antihypertensive effect containing choline ester as an active ingredient, and using this, a food with a functional claim or a therapeutic drug for hypertension etc. can be obtained.
  • the eggplant fruit that is the raw material of the composition according to the present embodiment is widely edible, and the composition of the present invention can be composed only of eggplant-derived components, is highly safe, and continues for a long period of time. Ingestion is possible.
  • the composition of the present invention includes a water extract of eggplant fruit, a concentrated extract obtained by concentrating the extract, a dry powder (freeze-dried powder, hot air-dried powder, spray-dried powder, etc.), a suspension of the dry powder, and the like. , Can be used for foods and drinks and pharmaceuticals in various forms.

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PCT/JP2020/042298 2019-11-15 2020-11-12 心理状態改善用組成物、心理状態改善用組成物の製造方法および心理状態改善のためのナスの果実の使用 Ceased WO2021095814A1 (ja)

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CN202080078378.7A CN114728034A (zh) 2019-11-15 2020-11-12 用于改善心理状态的组合物及其制造方法及茄子果实在改善心理状态中的用途
US17/776,939 US20220401509A1 (en) 2019-11-15 2020-11-12 Composition For Improving Mental State, Production Method For Composition For Improving Mental State, And Use Of Fruit Of Eggplant For Improving Mental State
JP2025109903A JP2025138789A (ja) 2019-11-15 2025-06-30 心理状態改善用組成物、心理状態改善用組成物の製造方法および心理状態改善のためのナスの果実の使用

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WO2018070545A1 (ja) * 2016-10-14 2018-04-19 国立大学法人信州大学 経口摂取用コリンエステル含有組成物

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JP3017926B2 (ja) * 1995-06-16 2000-03-13 株式会社ヤクルト本社 保存可能な野菜搾汁液の製造法
CN1169557C (zh) * 2002-04-14 2004-10-06 郑子新 治疗痛风病的中药及其制备方法

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Publication number Priority date Publication date Assignee Title
WO2018070545A1 (ja) * 2016-10-14 2018-04-19 国立大学法人信州大学 経口摂取用コリンエステル含有組成物

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* Cited by examiner, † Cited by third party
Title
HORIE HIDEKI, ANDO AKIRA, SAITO TAKEO: "The Contents of γ-Amino Butyric Acid in Eggplant and its Accumulation with Heat Treatment", NIPPON SHOKUHIN KAGAKU KOGAKU KAISHI, vol. 60, no. 11, 1 January 2013 (2013-01-01), pages 661 - 664, XP055823708 *

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