JP7398192B2 - Antistress composition - Google Patents

Description

The present invention relates to antistress compositions. More specifically, the present invention relates to anti-stress compositions containing absinthin.

In today's society, people are exposed to various types of stress, and stress-induced diseases such as psychosomatic disorders, neuroses, and depression are on the rise. In particular, the number of people suffering from stress-induced depression is increasing year by year among people in their prime working age. Against this background, the Industrial Safety and Health Act has been revised in Japan, making it mandatory for some companies to conduct stress checks within their workplaces.

Relaxing entertainment such as traveling and hot springs can be considered as a means of preventing or relieving stress, but considering that enjoying leisure time requires time and money, it is better to utilize food and drink. It is considered to be cheap and easy. GABA (γ-aminobutyric acid) is a typical example of active ingredients in foods and drinks that alleviate such stress. Currently, there are foods and drinks on the market that contain theanine and the like as active ingredients in addition to GABA, and their stress-relieving effects are being promoted. However, it is difficult to actually experience the effects, and it is not known that it is effective against more mental stress such as that caused by interpersonal relationships.

Regarding food and drink, luxury goods such as tea and coffee are often ingested when people are under mental stress, and these luxury goods are characterized by having a sensually bitter taste. Regarding the relationship between stress and bitter taste, it has been reported that people who have undergone mental stress have a decreased sensitivity to bitter taste (Non-Patent Document 1), and mice that have been subjected to mental stress drink more bitter solutions. The result of ingestion has been reported (Non-Patent Document 2).

In addition to food and drink, benzodiazepine anti-anxiety drugs and sleeping pills are sometimes used to reduce stress. However, since such medicines are accompanied by side effects such as dizziness and decreased concentration, it is not preferable to use them frequently for temporary stress. In addition, symptoms may actually worsen if the drug is discontinued after taking it.

Thus, in order to quickly reduce the number of stress diseases that have been on the rise over the years, there is a strong desire to develop anti-stress compositions that are highly effective, provide a good experience, and are also safe. ing.

Nakagawa M. et al., Chemical senses (1996) p.195-200 Scinska A. et al., Neurosci. Lett. (2009), Vol.461, p.285-288

An object of the present invention is to provide an antistress composition that is highly effective and excellent in terms of safety.

The present inventors conducted extensive studies to solve the above problems and found that absinthin has a stress-reducing effect. Based on this knowledge, the present inventors have completed the present invention.

That is, the present invention relates to the following, but is not limited thereto.
(1) An anti-stress composition containing absinthin.
(2) The composition according to (1), wherein absinthin is derived from Artemisia extract.
(3) The composition according to (1) or (2), wherein the stress is mental stress.
(4) The composition according to any one of (1) to (3), which is used for preventing and/or treating diseases caused by stress.
(5) The composition according to (4), wherein the stress-induced disease is depression, anxiety, or insomnia.
(6) The composition according to any one of (1) to (5), which is a food composition.
(7) The composition according to any one of (1) to (6), which is labeled with a function exhibited by anti-stress.
(8) Functions are displayed as ``preventing stress'', ``reducing stress'', ``alleviating stress'', ``improving depressive symptoms'', ``reducing mental fatigue'', and ``enhancing neurological function''. ”, “relieves anxiety”, “calms the mind”, “relaxes”, “suppresses shortness of breath and palpitations”, “relieves insomnia” and “reduces headache”. , (7).
(9) Use of absinthin to prevent, reduce or alleviate stress.
(10) A method for preventing, reducing or alleviating stress using absinthin.

The anti-stress composition containing absinthin according to the present invention can effectively prevent and alleviate stress. As a result, the anti-stress composition of the present invention can effectively prevent and treat diseases caused by stress, and can be used as a composition for preventing and/or treating the diseases.

Furthermore, absinthin used in the present invention is one of the components contained in the extract from Artemisia annua. Since the mugwort extract is a material that can be used as a food ingredient, the absinthin contained therein is also edible and considered to be highly safe. From this point of view, the anti-stress composition of the present invention is considered to be highly safe, and its side effects are considered to be extremely low compared to conventional pharmaceuticals containing non-natural compounds.

FIG. 1 is a diagram showing the results of a human test to verify the anti-stress effect. The vertical axis of the graph indicates the peripheral vascular resistance value, and the horizontal axis of the graph is the time axis, which indicates the adaptation period, stress period (TSST), and recovery period, respectively.

One aspect of the present invention is an anti-stress composition containing absintin.

1. Absinthin Absinthin contained in the anti-stress composition of the present invention has an IUPAC name (1R, 2R, 5S, 8S, 9S, 12S, 13R, 14S, 15S, 16R, 17S, 20S, 21S, 24S). -12,17-dihydroxy-3,8,12,17,21,25-hexamethyl-6,23-dioxaheptacyclo[13.9.2.01,16.02,14.04,13.05,9.020,24]hexacosa-3,25-diene-7 ,22-dione, and its CAS registration number is 13624-21-0. Absinthin is a dimer of guaiane sesquiterpene, and its structure is classified as a sesquiterpene lactone.

Abcinthin has a unique taste, and is particularly characterized by a strong bitter taste. Since absinthin is a substance with a strong bitter taste, by ingesting the anti-stress composition of the present invention, one can feel the bitter taste and can fully experience the effect of alleviating stress.

Absintin may be obtained from natural products or may be obtained by chemical synthesis. Absinthin is a naturally occurring organic compound found in Artemisia absinthium (scientific name: Artemisia absinthium). Artemisia absinthium (scientific name: Artemisia absinthium) is a perennial plant or subshrub of the Asteraceae family, Artemisia absinthium. In the present invention, absinthin is not particularly limited, but can be obtained by isolating and purifying it from the whole plant of Artemisia or from Artemisia extract by a method known per se. Absinthin in the present invention is preferably derived from Artemisia extract. Since absinthin is contained in the Artemisia extract, it is also possible to use the Artemisia extract itself as an active ingredient in the present invention.

The mugwort extract can be extracted from a part or the whole (whole plant) of the mugwort, and is preferably extracted from the whole (whole plant) of the mugwort. The method for preparing the mugwort extract is not particularly limited, but for example, the whole dried mugwort plant is extracted with water at 30 to 120°C, a solvent acceptable for food production (an organic solvent such as ethanol), or a mixture thereof. You can get it by doing this. Examples of the mixture of water and organic solvent include 40 to 60% ethanol. Further, the temperature and time for the extraction process are not particularly limited, and for example, the extraction can be performed at room temperature for 3 to 12 hours.

The absinthin and mugwort extracts used in the present invention are commercially available, and are preferably those whose quality is guaranteed to be suitable for human consumption (for example, those certified as food additives). .

2. Anti-stress As used herein, "anti-stress" refers to an effect that includes any one or more of preventing, reducing, and alleviating stress, and a composition having such an effect is referred to as an "anti-stress composition." Specifically, prevention of stress refers to the action of reducing the degree (degree) of stress that will be received from now on compared to the degree that would normally be received.

Furthermore, as used herein, "stress" refers to strain that occurs in the mind and body when a stress-causing stimulus (also referred to as a stressor) is applied to a living body. Such stimuli include physical stimuli such as cold, noise, radiation, and weather changes; chemical stimuli such as drugs, metals, and oxygen deprivation; biological stimuli such as bacterial infections and inflammation; and diseases such as pain and fever. These include physical stimulation caused by the disorder; mental stimulation such as tension, anxiety, and fear arising from interpersonal relationships in society and at home. The anti-stress composition of the present invention is suitable for, but not limited to, stress caused by mental stimulation (so-called mental stress), and among mental stress, mental stress caused by human relationships. It is particularly suitable for Examples of mental stress caused by human relationships include, but are not limited to, mental stress caused by interpersonal interviews, public speeches, and the like.

Evaluation of the anti-stress effect is not particularly limited, and can be performed using methods known to those skilled in the art. For example, there is a method of measuring the concentration of cortisol in blood or saliva and comparing it before and after stress is applied. In this case, if the increase in cortisol concentration after stress is suppressed, it can be determined that the drug has an anti-stress effect. Furthermore, the anti-stress effect can also be evaluated, for example, by measuring electrocardiograms to examine sympathetic or parasympathetic nerve activity, or by using a stress checklist provided by the Ministry of Health, Labor and Welfare.

3. Antistress Composition The antistress composition of the present invention contains absinthin as an active ingredient. The content of absinthin in the anti-stress composition of the present invention is not particularly limited, as long as the desired effect of the present invention can be obtained, taking into account its dosage form, administration method, etc. . For example, the content of absintin in the antistress composition of the present invention is 4×10 ⁻⁷ % by weight or more, preferably 1×10 ⁻⁶ % by weight or more, more preferably 4×10 ⁻⁶ % by weight or more. , 100% by weight or less, preferably 1×10 ⁻⁴ % by weight or less, more preferably 4×10 ⁻⁵ % by weight or less, typically 4×10 ⁻⁷ to 100% by weight, preferably 1× The amount is 10 ^-6 to 1×10 ^-4 % by weight, more preferably 4×10 ^-6 to 4×10 ^-5 % by weight. As used herein, "wt %" means weight % weight/weight (w/w) unless otherwise specified. The content of absinthin in the present invention can be measured according to a method known to those skilled in the art, for example, by using LC/MS, HPLC, etc. under appropriate conditions.

Further, in the anti-stress composition of the present invention, a mugwort extract can also be used as a material containing absinthin. When the anti-stress composition of the present invention contains a mugwort extract, the content can be set based on the content of absinthin described above. That is, the amount of absinthin contained in the wormwood extract is measured in advance, and the amount of the wormwood extract is calculated so that the absinthin content in the anti-stress composition of the present invention falls within the above range, The content of Artemisia extract in the composition can be set. Incidentally, the weight of the wormwood extract can be defined by the weight of the powdered wormwood extract.

The anti-stress composition of the present invention can contain, in addition to absinthin and Artemisia extract, any additives or any components used in ordinary compositions, depending on its form. Examples of these additives and/or ingredients include vitamins such as vitamin E and vitamin C, minerals, nutritional ingredients, physiologically active ingredients such as fragrances, as well as excipients and binders used in formulation. , emulsifiers, tonicity agents, buffers, solubilizers, preservatives, stabilizers, antioxidants, colorants, coagulants, coating agents, etc., but are not limited to these. It's not something you can do.

The anti-stress composition of the present invention is not particularly limited, but can be provided as a food composition, a pharmaceutical composition, etc., for example. Here, in this specification, the food composition is a concept that also includes beverages (beverage compositions). The antistress composition of the present invention is preferably a food composition.

When the anti-stress composition of the present invention is a food composition, its form is not particularly limited, but it may be in the form of a health food such as a tablet (including a coated tablet), a capsule, a powder, a granule, or a drink. It can be done. It can also be in the form of soft drinks, tea drinks, dairy products such as yogurt and lactic acid bacteria drinks, seasonings, processed foods, desserts, confectionery (eg, gum, candy, jelly), and the like.

Furthermore, when the anti-stress composition of the present invention is a pharmaceutical composition, the route of administration is not particularly limited, but oral administration is preferred. Forms of pharmaceutical compositions suitable for oral administration include solid preparations such as tablets (including coated tablets), granules, powders, powders, or capsules, oral solutions, suspensions, emulsions, syrups, etc. It also includes liquid preparations such as drinks.

The anti-stress composition of the present invention can be taken as it is or with water or the like. Furthermore, although not particularly limited, the anti-stress composition of the present invention can be used in food compositions, pharmaceutical compositions, etc. after being prepared in a form that can be easily blended (e.g., powder form or granule form). It can also be used as a raw material.

4. Applications The anti-stress composition of the present invention is useful for any one or more of preventing, alleviating, and alleviating stress as described above. As a result, the anti-stress composition of the present invention can also be used as a composition for preventing and/or treating diseases and symptoms caused by stress. Note that "treatment" in this specification may also include concepts such as improvement, recovery, alleviation, and alleviation.

Diseases caused by stress include, but are not particularly limited to, respiratory diseases such as bronchial asthma and hyperarousal syndrome; cardiovascular diseases such as essential hypertension and coronary artery disease (angina pectoris, myocardial infarction); Gastrointestinal diseases such as gastric/duodenal ulcer, irritable bowel syndrome, ulcerative colitis, and psychogenic vomiting; endocrine/metabolic diseases such as simple obesity and diabetes; muscle contraction headaches, spastic torticollis, and writer's cramp. Neuromuscular diseases such as; dermatological diseases such as chronic urticaria, atopic dermatitis, and alopecia areata; orthopedic diseases such as rheumatoid arthritis and low back pain; urinary and muscular diseases such as nocturnal enuresis and psychogenic impotence. Examples include reproductive system diseases; ophthalmological diseases such as asthenopia and essential blepharospasm; otorhinolaryngological diseases such as Meniere's disease; and dental and oral surgery diseases such as temporomandibular joint disease. Other examples include depression (reactive depression, neurotic depression, etc.), anxiety, insomnia, mental fatigue, autonomic imbalance, menopausal disorder, and nervous vomiting. In the present invention, the diseases caused by stress are preferably depression, anxiety, and insomnia, although they are not particularly limited.

The antistress composition of the present invention can be applied to either therapeutic (medical) or non-therapeutic (non-medical) applications. Specifically, regardless of whether it is classified as a drug, quasi-drug, cosmetic, food or drink, etc., it cannot be used as a composition that explicitly or implicitly claims to prevent, reduce, or alleviate stress. Can be mentioned. Furthermore, the anti-stress composition of the present invention can prevent not only stress-induced diseases but also stress-induced performance deterioration. Examples of such performance include, but are not limited to, desk work, physical labor, presentations, calculations, and the like.

In another aspect, the invention relates to compositions labeled with anti-stress function. This type of labeling is also called functional labeling, and the content of the labeling is not particularly limited, but includes, for example, "prevents stress," "reduces stress," "alleviates stress," and "improves depressive symptoms." , "Reduce mental fatigue", "Improve nervous function", "Eliminate anxiety", "Calm your mind", "Relax", "Reduce shortness of breath and palpitations", "Eliminate insomnia" and "Headache" Examples include "reducing the amount of stress" or other functional expressions that can be considered the same as these. In the present invention, the label may be attached to the composition itself, or to the container or package of the composition.

The anti-stress composition of the present invention can be ingested by an appropriate method depending on its form. The method of ingestion is not particularly limited as long as the active ingredient according to the present invention can be transferred into the circulating blood. For example, it may be in the form of an orally available preparation as described above, or a parenteral preparation such as an injection, an external preparation, a suppository, or a transdermal absorption agent, but is not limited thereto. Note that in this specification, "ingestion" is used to include all aspects such as ingestion, dosing, and drinking.

The amount of the anti-stress composition of the present invention to be applied is determined appropriately depending on its form, administration method, purpose of use, and the age, weight, and symptoms of the patient or animal to which it is administered, and is not constant. The effective human intake of the anti-stress composition of the present invention is also not constant and is not particularly limited. The effective human intake of the antistress composition of the present invention is, for example, 0.001 mg or more, preferably 0.004 mg or more per day for a human weighing 50 kg, as absinthin weight. Further, the administration may be carried out once or in divided doses within a day within a desired dosage range. The administration period is also arbitrary. In addition, in this specification, the effective human intake amount refers to the intake amount that shows an effective effect in humans.

The anti-stress composition of the present invention is preferably applied to humans, but also to livestock animals such as cows, horses, and goats, pet animals such as dogs, cats, and rabbits, or mice, rats, guinea pigs, monkeys, etc. may be experimental animals. When administering to animals other than humans, the daily usage amount of the anti-stress composition of the present invention depends on the content of the active ingredient in the composition, the condition of the subject, body weight, sex, age, etc. Depends on conditions.

5. Use of absintin to prevent, reduce or alleviate stress One aspect of the present invention is the use of absintin to prevent, reduce or alleviate stress.

The use of absintin of the present invention also includes use for the prevention and/or treatment of stress-induced diseases from the viewpoint of preventing, reducing, or alleviating stress (anti-stress). Diseases caused by stress are as described above, but are not particularly limited. The use of the present invention may also be in humans or non-human animals, and may be therapeutic or non-therapeutic. Here, "non-therapeutic" is a concept that does not include medical treatment, that is, treatment of the human body through treatment.

6. Methods of preventing, reducing or alleviating stress One aspect of the present invention is a method of preventing, reducing or alleviating stress using absinthin.

The method of the present invention also includes a method for preventing and/or treating diseases caused by stress from the viewpoint of preventing, reducing, or alleviating stress (anti-stress). Diseases caused by stress are as described above, but are not particularly limited.

Another aspect of the present invention is a method for preventing, reducing, or alleviating stress, which comprises administering an effective amount of absintin to a subject in need of preventing, reducing, or alleviating stress. These methods also include methods for preventing and/or treating diseases caused by stress. Diseases caused by stress are as described above, but are not particularly limited.

In the above method, the subject requiring prevention, reduction or relaxation of stress is the same as the subject to which the anti-stress composition of the present invention is applied. In addition, as used herein, the term "effective amount" refers to the amount by which stress is prevented, reduced, or alleviated when the anti-stress composition of the present invention is administered to the above subject, compared to a subject to which it is not administered. It is. The specific effective amount is not fixed and is determined at the appropriate time depending on the dosage form, administration method, purpose of use, age, weight, symptoms of the subject, etc.

In the method of the present invention, absintin may be administered as it is or as a composition containing absintin so as to achieve the above-mentioned effective amount.

According to the method of the present invention, stress can be prevented, reduced, or alleviated without causing side effects.

EXAMPLES Hereinafter, the present invention will be explained in more detail with reference to Examples, but the scope of the present invention is not limited thereby. Those skilled in the art can make various changes and modifications to the method of the present invention, and these are also included within the scope of the present invention. Note that unless otherwise specified, "%" means "% by weight (w/w)".

Test example 1. Human test to verify anti-stress effects (1) Test foods The following four types of test foods were used. The volume of each test food was 100 mL. Each test food was difficult to distinguish from its appearance, including color tone, and could not be distinguished from each other by scent. However, foods containing high doses of absinthin had a bitter taste.
・Placebo food: absinthin-free food (water)
・Foods containing high doses of absinthin: 0.04 mg/100 mL of water
・Foods containing low doses of absinthin: 0.004 mg/100 mL of water
・Food containing theanine: 200 mg/100 mL of water

Absinthin-containing foods were prepared by adding Artemisia extract containing 9.2% absinthin to water at the above concentration. The mugwort extract used was thujone-free. Absinthin was quantified using an LCMS-8050 ultrafast triple quadrupole LC/MS/MS (SHIMADZU). Theanine was purchased from Taiyo Kagaku Co., Ltd.

(2) Subjects The subjects were 100 university students aged 20 years or older who were naive, healthy, and freely volunteered for this type of research, and who were deemed suitable for research participation by the research director, etc., and a control (Wednesday) group of 25 The participants were randomly divided into 26 patients in the absinthin high-dose group, 24 in the absinthin low-dose group, and 25 in the theanine group. Participants received informed consent regarding the content of this study and agreed to participate in this study in writing. Subjects were asked to refrain from eating, drinking, smoking, and exercising for 2 hours before the experiment.

(3) Experimental Procedures After the subjects entered the laboratory, their height and weight were measured, and they drank the test food. After that, there was a 10-minute adaptation period, and the TSST (Trier Social Stress Test) was administered as a mental stress test. Thereafter, there was a 30-minute recovery period, and during the experiment, peripheral vascular resistance was continuously measured non-invasively as a stress marker. Peripheral vascular resistance was measured using a continuous blood pressure monitor: Finapres NOVA (Finapres Medical Systems).

(4) Results Compared to the placebo group, the high-dose absintin group, low-dose absintin group, and theanine group all suppressed the acute stress response caused by TSST loading. From the task period (stress period) to the recovery period, the high-dose absintin group was shown to recover the stress state more than the low-dose absintin group and theanine. It was also shown that the placebo group recovered from the stress state from the task period (stress period) to the recovery period compared to the absinthin low-dose group and the theanine group. These results suggested that absinthin (high and low doses) and theanine have the effect of suppressing stress responses. Furthermore, it was suggested that high doses of absinthin were more effective in promoting recovery from stress load than theanine. On the other hand, recovery from stress appears to be more accelerated in the placebo group than in the other groups, but this is due to significantly higher reactivity (stress state) when stress is applied; It had not yet recovered to its original value.

The present invention provides an anti-stress composition containing absinthin as an active ingredient. INDUSTRIAL APPLICABILITY The present invention has high industrial applicability because it provides a new means for preventing, reducing, or alleviating stress.

Claims (8)

An anti-stress composition containing a mugwort extract and 4x10 ^-7 % by weight or more of absinthin derived from the mugwort extract. The composition according to claim 1, wherein the stress is mental stress. The composition according to claim 1 or 2, which is used for preventing and/or treating diseases caused by stress. The composition according to claim 3, wherein the stress-induced disease is depression, anxiety, or insomnia. The composition according to any one of claims 1 to 4, which is a food composition. The composition according to any one of claims 1 to 5, which is labeled with an indication of the function exerted by anti-stress. The functions displayed are ``Prevent stress'', ``Reduce stress'', ``Relieve stress'', ``Improve depressive symptoms'', ``Reduce mental fatigue'', ``Improve nervous function'', `` The claimed invention is selected from the group consisting of ``relieves anxiety'', ``calms the mind'', ``relaxes'', ``suppresses shortness of breath and palpitations'', ``relieves insomnia'', and ``reduces headaches''. 6. The composition according to 6. The composition according to any one of claims 1 to 7, wherein the content of absinthin is 4 x 10 ^-6 % by weight or more.

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