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WO2010086972A1 - Agent antistress - Google Patents

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Publication number
WO2010086972A1
WO2010086972A1 PCT/JP2009/051372 JP2009051372W WO2010086972A1 WO 2010086972 A1 WO2010086972 A1 WO 2010086972A1 JP 2009051372 W JP2009051372 W JP 2009051372W WO 2010086972 A1 WO2010086972 A1 WO 2010086972A1
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WIPO (PCT)
Prior art keywords
csf
stress
mcp
ifn
isothiocyanate
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Japanese (ja)
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敦生 関山
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/26—Cyanate or isocyanate esters; Thiocyanate or isothiocyanate esters
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/06—Drugs for disorders of the endocrine system of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH
    • A61P5/08—Drugs for disorders of the endocrine system of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH for decreasing, blocking or antagonising the activity of the anterior pituitary hormones
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Definitions

  • the present invention has an action of suppressing the secretion of ACTH (adrenocorticotropic hormone) after stress loading and / or the action of suppressing increase of inflammatory cytokines after stress loading, and is used as a drug, food, etc.
  • the present invention relates to an agent, and an antagonist and a relieving agent for a mechanism in which a load on a living body causes mental and physical disorders.
  • Non-Patent Documents 1 and 2 Mental and / or physical stress affects host defense including nerves, endocrine and immune systems.
  • blood levels of various inflammatory cytokines eg, IL-18, IL-1 ⁇ , IL-6, TNF- ⁇ , etc.
  • Non-patent Document 4 blood levels of various inflammatory cytokines (eg, IL-18, IL-1 ⁇ , IL-6, TNF- ⁇ , etc.) increase
  • Non-patent Document 4 Further, the present inventor has reported that an increase in inflammatory cytokines caused by stress load is caused by active oxygen molecules (Non-patent Document 5).
  • Non-patent Document 8 In recent studies, it has been reported that IL-18 mRNA is expressed in the adrenal gland in response to adrenocorticotropic hormone (ACTH) and cold stress (Non-patent Document 6). In addition, it has been reported that the adrenal gland and immune cells use different promoters for IL-18 mRNA (Non-patent Document 7). However, induction of mature IL-18 has not been shown in both studies. On the other hand, elevation of IL-18 in plasma has been reported in psychiatric patients (Non-patent Document 8).
  • 6-Methylsulfinylhexyl isothiocyanate is a kind of coconut oil contained in the wasabi (Wasabia Japonica) rhizome. It is detoxifying, improving blood flow, antioxidant (Patent Document 2), cell cycle arrest (Patent) Document 3), glutathione-S-transferase activity-inducing action (Patent Document 4), elastase activity inhibitory action (Patent Document 5) and the like are known.
  • Patent Document 1 suggests in Patent Document 1 that the antioxidants including the isothiocyanate may relieve mental stress by inhibiting the signal transduction of the stress cascade. It remains unknown whether it is more effective.
  • An object of the present invention is to provide a safe and effective anti-stress agent that alleviates in-vivo response due to stress load on a living body.
  • the present invention provides the following. [1] It contains ⁇ -methylsulfinylalkylisothiocyanate (wherein the alkyl group has 4 to 8 carbon atoms) as an active ingredient, and suppresses the secretion of ACTH and / or increase in cytokine or chemokine after stress loading An anti-stress agent or an antagonist or alleviating agent against a physical and mental disorder caused by a biological load.
  • ⁇ -methylsulfinylalkyl isothiocyanate is horseradish, horseradish, cabbage, watercress, brussels sprouts, cauliflower, radish, tangle radish, rapeseed, broccoli, Takana, mustard, turnip, and Chinese cabbage rape.
  • the agent according to [1] above which is obtained from one or more species selected from the family plant family.
  • the agent according to the above [2], wherein the ⁇ -methylsulfinylalkyl isothiocyanate is obtained by physical means of crushing or grinding cruciferous plants, extraction means with a solvent, drying means, or a combination thereof.
  • Cytokines are IL-1 ⁇ , IL-1ra, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL -11, IL-12, IL-13, IL-15, IL-17, IL-18, Eotaxin, FGF basic, G-CSF, GM-CSF, IFN- ⁇ , IFN- ⁇ , IP-10, MCP- 1, MIP-1 ⁇ , MIP-1 ⁇ , PDGF-BB, RANTES, TNF- ⁇ , VEGF, CSF-2, TGF- ⁇ , neurotrophin 5, MCP-3, ⁇ -2-microglobulin, angiotensin II, CSF- 3, CXC chemokine lig
  • [14] including a step of administering an effective amount of ⁇ -methylsulfinylalkylisothiocyanate (wherein the alkyl group has 4 to 8 carbon atoms) to a subject in need thereof, whereby the adrenal gland after stress loading
  • ⁇ -methylsulfinylalkylisothiocyanate wherein the alkyl group has 4 to 8 carbon atoms
  • ⁇ -methylsulfinylalkyl isothiocyanate is horseradish, horseradish, cabbage, watercress, brussels sprouts, cauliflower, radish, leach radish, rapeseed, broccoli, Takana, mustard, turnip, and Chinese cabbage rape.
  • the ⁇ -methylsulfinylalkylisothiocyanate is obtained by physical means of crushing or grading cruciferous plants, extraction means with a solvent, drying means, or a combination thereof.
  • Cytokines are IL-1 ⁇ , IL-1ra, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL -11, IL-12, IL-13, IL-15, IL-17, IL-18, Eotaxin, FGF basic, G-CSF, GM-CSF, IFN- ⁇ , IFN- ⁇ , IP-10, MCP- 1, MIP-1 ⁇ , MIP-1 ⁇ , PDGF-BB, RANTES, TNF- ⁇ , VEGF, CSF-2, TGF- ⁇ , neurotrophin 5, MCP-3, ⁇ -2-microglobulin, angiotensin II, CSF- 3, CXC chemokine ligand 1, CXC chemokine ligand 5, HGF, IL-1 ⁇ , IL-2ra, IL-16, CTACK, GRO- ⁇ , ICAM-1, IFN- ⁇ 2, LIF, MCP-3, M-CSF, The method according to
  • cytokine is IL-18.
  • [21] comprising administering an effective amount of ⁇ -methylsulfinylalkyl isothiocyanate (wherein the alkyl group has 4 to 8 carbon atoms) to a subject in need thereof, thereby IL-1 ⁇ , IL-1ra, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-11, IL- 12, IL-13, IL-15, IL-17, IL-18, Eotaxin, FGF basic, G-CSF, GM-CSF, IFN- ⁇ , IFN- ⁇ , IP-10, MCP-1, MIP-1 ⁇ , MIP-1 ⁇ , PDGF-BB, RANTES, TNF- ⁇ , VEGF, CSF-2, TGF- ⁇ , neurotrophin 5, MCP-3, ⁇ -2-microglobulin, angiotensin II, CSF-3
  • Antagonistic or mitigating methods [22] The method according to any one of [14] to [21] above, wherein the ⁇ -methylsulfinylalkyl isothiocyanate is 6-methylsulfinylhexyl isothiocyanate.
  • the anti-stress agent of the present invention contains ⁇ -methylsulfinylalkylisothiocyanate as an active ingredient, and by ingesting this as a food or a medicine, secretion of ACTH and glucocorticoid after stress loading on the living body and / or There is an effect of suppressing an increase in cytokine or chemokine after stress loading and reducing an excessive reaction of a living body.
  • the anti-stress agent of the present invention also acts as an antagonist or alleviating agent against a physical load causing mental and physical disorders. Since an excessive reaction of a living body is associated with various diseases, the present invention can be applied to prevention or treatment of diseases caused by stress.
  • FIG. 1 It is a figure which shows the avoidance and suppression effect with respect to collapse of the healthy pattern of the cytokine and chemokine by night shift stress of 6-MSITC or placebo administration.
  • a healthy pattern is maintained in the 6-MSITC administration group. It is the figure which showed collapse of the healthy pattern of cytokine and chemokine by the exercise stress in humans. It is a figure which shows the effect with respect to the decay
  • a healthy pattern is maintained in the 6-MSITC administration group. It is the figure which showed collapse of the healthy pattern of cytokine and chemokine by the mental workload stress in humans.
  • 6 is a graph showing the effect of administration of 6-MSITC or placebo on disruption of healthy patterns of cytokines and chemokines due to mental workload stress in humans.
  • a healthy pattern is maintained in the 6-MSITC administration group.
  • the recovery effect is remarkable in the 6-MSITC administration group.
  • FIG. 6 is a graph showing the effect of 6-MSITC or placebo administration on recovery by rest after disruption of the normal pattern of cytokines and chemokines due to mental workload stress in humans. The recovery effect is remarkable in the 6-MSITC administration group.
  • the present invention provides an anti-stress agent, an antagonist or mitigation agent (hereinafter referred to as “the agent of the present invention”) against a physical and psychological disorder caused by biological stress.
  • stress means various responses of the living body due to the extraordinary chemical, physical, mental, verbal or exertional stress on the mental and physical body (stress load). . Further, “stress” also means various responses of the living body due to the application of a constant load from inside the living body (stress load).
  • Mental stress due to physical stress, anger, anxiety, fear, tension, restraint, and labor stress due to labor and work can be exemplified, but in the present invention, physical stress, chemical stress, labor stress, and mental stress are preferable.
  • the mental stress restraint stress is more preferable, and long-term restraint stress is particularly preferable.
  • the long time cannot be generally described due to living organisms or individual differences, but in the case of animals, 6 hours or more are exemplified.
  • stress due to ultraviolet irradiation is preferable
  • chemical stress stress due to exposure to harmful chemical substances is preferable.
  • stress loading activates the hypothalamic-pituitary-adrenal (HPA) axis to induce the secretion of ACTH (adrenocorticotropic hormone), induces glucocorticoids, while induces cytokines and chemokines such as IL-18 To do.
  • ACTH hypothalamic-pituitary-adrenal
  • cytokines and chemokines such as IL-18
  • increases in vivo cytokines represented by IL18 cause further secretion of ACTH and glucocorticoid. Therefore, in the present invention, “stress” specifically refers to the secretion of ACTH and / or the increase of cytokines and chemokines in vivo (preferably an increase in blood concentration). It is also meant to include the disease caused by it.
  • anti-stress specifically refers to suppression of ACTH secretion after stress loading and / or suppression of in vivo cytokine increase (preferably an increase in blood concentration), and the excess of the living body associated therewith. It also includes the reduction of response as well as the prevention or treatment of diseases resulting therefrom.
  • cytokine and chemokine are IL-1 ⁇ , IL-1ra, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL. -10, IL-11, IL-12, IL-13, IL-15, IL-17, IL-18, Eotaxin, FGF basic, G-CSF, GM-CSF, IFN- ⁇ , IFN- ⁇ , IP- 10, MCP-1, MIP-1 ⁇ , MIP-1 ⁇ , PDGF-BB, RANTES, TNF- ⁇ , VEGF, CSF-2, TGF- ⁇ , Neurotrophin 5, MCP-3, ⁇ -2-microglobulin, Angiotensin II, CSF-3, CXC chemokine ligand 1, CXC chemokine ligand 5, HGF, IL-1 ⁇ , IL-2ra, IL-16, CTACK, GRO- ⁇ , ICAM-1, IFN- ⁇ 2, LIF, MCP-3,
  • ⁇ -methylsulfinylalkyl isothiocyanate may be a chemically synthesized substance or a natural product as an extract obtained from a cruciferous plant.
  • Specific examples of these substances include 5-methylsulfinylpentyl isothiocyanate, 6-methylsulfinyl hexyl isothiocyanate, 7-methylsulfinyl heptyl isothiocyanate, and 8-methylsulfinyl octyl isothiocyanate.
  • 6-methylsulfinylhexyl isothiocyanate is preferable.
  • ⁇ -methylsulfinylalkyl isothiocyanate is a group of cruciferous plants such as Japanese horseradish, horseradish, cabbage, watercress, Brussels sprouts, cauliflower, radish, radish, rapeseed, broccoli, Takana, mustard, turnip, Chinese cabbage, etc. Those obtained from one or more selected from the above are preferred. Among these, Japanese wasabi (Wasabia ⁇ Japonica) having a high content of 6-methylsulfinylhexyl isothiocyanate is more preferable, and either Japanese wasabi leaves or Japanese wasabi rhizome may be used. Particularly preferred.
  • the plant body is subjected to extraction pretreatment by physical means such as grinding or grated water, methanol, ethanol, acetone, acetone, ethyl acetate, diethyl ether, Extraction with an organic solvent such as dichloromethane or dichloroethane, or extraction with a distillation method such as steam distillation or molecular distillation is preferred, but it is not particularly limited to these methods.
  • the specific extraction method of this wasabi with an organic solvent is as follows. After the rhizome of this wasabi is grated, it is extracted with an ethyl acetate solvent, and this extract is dehydrated with anhydrous sodium sulfate and then concentrated with an evaporator. ⁇ -methylsulfinylalkylisothiocyanate is obtained.
  • This method is particularly suitable for the extraction of 6-methylsulfinylhexyl isothiocyanate.
  • Commercially available 6-methylsulfinylhexyl isothiocyanate may be used, and examples thereof include Wasabi sulfinyl (registered trademark) (6-MSITC (registered trademark)) manufactured by Kinshi Co., Ltd.
  • the above-mentioned extract is extracted and concentrated, and then purified by an arbitrary method such as a liquid-liquid distribution method, chromatography, molecular distillation, or rectification.
  • drying means such as hot air drying and freeze drying may be combined.
  • flavonoids such as apigenin, luteolin and kaempferol, glycosides or multimers thereof, and phenylpropanoids such as ferulic acid and sinapinic acid as active ingredients of the antistress agent of the present invention Or their glycosides or multimers, other isothiocyanates, or other polyphenols.
  • flavonoids such as apigenin, luteolin and kaempferol, glycosides or multimers thereof, and phenylpropanoids such as ferulic acid and sinapinic acid
  • glycosides or multimers, other isothiocyanates, or other polyphenols may be used alone or in combination of two or more.
  • isothiocyanates include allyl isothiocyanate, secondary butyl isothiocyanate, 3-butenyl isothiocyanate, 4-pentenyl isothiocyanate, 5-hexenyl isothiocyanate, 5-methylthiopentyl isothiocyanate, Examples include 6-methylthiohexyl isothiocyanate, 7-methylthioheptyl isothiocyanate, and 8-methylthiooctyl isothiocyanate.
  • Active ingredients other than ⁇ -methylsulfinylalkylisothiocyanate may be synthesized by various chemical synthesis methods in addition to extraction from plants by the above-described method. Those skilled in the art can synthesize these active ingredients by methods well known in the art.
  • the agent of the present invention is useful as a medicine, food, and the like, and examples of its administration include mammals (eg, humans, mice, rats, hamsters, rabbits, cats, dogs, cows, sheep, monkeys, etc.). It is done.
  • mammals eg, humans, mice, rats, hamsters, rabbits, cats, dogs, cows, sheep, monkeys, etc.
  • the intake of the agent of the present invention may be appropriately adjusted according to the body weight or size of the animal.
  • the agent of the present invention When the agent of the present invention is a medicine, it generally contains an active ingredient and a carrier.
  • the carrier is not particularly limited as long as it is a pharmaceutically acceptable carrier, and examples thereof include a substance for formulation described below (eg, excipient, solvent, etc.).
  • the administration form of the medicament of the present invention is not particularly limited, but can be performed through general administration routes such as oral administration, rectal administration, injection, administration by infusion.
  • Oral dosage forms include granules, fine granules, powders, coated tablets, tablets, suppositories, powders, (micro) capsules, chewables, syrups, juices, liquids, suspensions, emulsions, etc.
  • general dosage forms of pharmaceutical preparations such as direct intravenous injection, infusion administration, and preparations that prolong the release of active substances can be adopted as injections.
  • These drugs can be formulated by conventional methods.
  • Various pharmacologically acceptable substances for preparation can be blended as necessary in the preparation.
  • the substance for the preparation can be appropriately selected depending on the dosage form of the preparation.
  • the excipient, the diluent, the additive, the disintegrant, the binder, the coating agent, the lubricant, the lubricant, the lubricant, and the flavoring agent. Sweeteners, solubilizers, solvents and the like.
  • the pharmaceutical substance examples include magnesium carbonate, titanium dioxide, lactose, mannitol and other sugars, talc, milk protein, gelatin, starch, cellulose and derivatives thereof, animal and vegetable oils, polyethylene glycol, and solvents, Examples include sterilized water and mono- or polyhydric alcohols such as glycerol.
  • the dose of the active ingredient in the medicament of the present invention varies depending on the symptoms, age, and administration method of the patient to be administered, but the daily dose of the active ingredient for an adult (with a body weight of 60 kg) is usually 10 pg. About 5 g, preferably about 100 ng to 10 mg, more preferably about 0.5 mg to 3 mg.
  • the daily dose of 6-methylsulfinylhexyl isothiocyanate is usually about 10 pg to 5 g, preferably about 100 ng to 10 mg, more preferably 0.5 mg to About 3 mg.
  • the above-mentioned amount is administered in 1 to 3 divided doses per day.
  • the dose of the active ingredient in the case of parenteral administration (intake), such as infusion administration, injection administration (intravenous administration), etc. is 10 to 20 minutes within the preferable dose (intake amount) range for oral administration.
  • About 1 can be administered.
  • the above-mentioned amount is administered in 1 to 3 divided doses per day.
  • the medicament of the present invention may be combined (contained) with other drugs.
  • drugs include other anti-stress agents, vitamins, hormones, nutrients, peptic ulcers, steroids,
  • tumor agents include antiviral agents, antibacterial agents, antidepressants, antipsychotics, and tranquilizers. These can use together (contain) 1 type, or 2 or more types.
  • the agent of the present invention suppresses the secretion of ACTH and / or the increase of inflammatory cytokines after stress loading. Increases in inflammatory cytokines after stress loading are closely associated with various diseases by causing excessive responses in the body. Therefore, the agent of the present invention is also useful for preventing or treating diseases caused by stress. Diseases caused by stress include diseases that develop, worsen, or recur due to the involvement of cytokines such as IL-18.
  • Examples of these diseases include depression, PTSD, anxiety, obsessive-compulsive disorder, schizophrenia, psychosomatic disease, appendicitis, peptic ulcer, gastric ulcer, duodenal ulcer, peritonitis, pancreatitis, ulcerative, pseudomembranous, acute And ischemic colitis, diverticulitis, epiglottitis, achalasia, cholangitis, cholecystitis, hepatitis, Crohn's disease, enteritis, Whipple disease, (bronchial) asthma, allergy, anaphylactic shock, immune complex disease, organ ischemia Reperfusion injury, organ necrosis, hay fever, sepsis, sepsis, endotoxin shock, cachexia, hyperthermia, eosinophilic granulomas, granulomatosis, sarcoidosis, septic abortion, epididymis, vagina Inflammation, prostatitis, urethritis, bronchi
  • the agent of the present invention may be contained in food.
  • any form may be used as long as it is a general meal form containing the active ingredient of the present invention.
  • drinks such as soft drinks and powdered drinks can be prepared by adding an appropriate flavor. Specifically, for example, it can be mixed with juice, milk, confectionery, jelly, yogurt, rice cake, etc. to eat and drink. It is also possible to provide such foods as health functional foods or dietary supplements.
  • This health functional food includes food for specified health use and food with nutritional function.
  • the food for specific health is a food that can indicate that a specific health purpose can be expected, for example, prevention or reduction of stress.
  • nutritional functional foods are foods that can display the function of nutritional components when the amount of nutritional components included in the daily intake standard amount conforms to the standards for the upper and lower limits established by the national government. It is. Dietary supplements include so-called nutritional supplements or health supplements.
  • the food for specified health use is a food with a label indicating that it is used for applications such as prevention or reduction of stress, and further a document (so-called notation) describing that it is used for such applications. Foods that include the above as a package are also included.
  • the agent of the present invention can be used as a concentrated liquid food or a food supplement.
  • the food supplement in the present invention refers to those taken for the purpose of supplementing nutrition in addition to those taken as food, and also includes nutritional supplements and supplements.
  • the active ingredient is 6-methylsulfinylhexyl isothiocyanate
  • the daily dose of 6-methylsulfinylhexyl isothiocyanate is usually about 10 pg to 5 g, preferably about 100 ng to 10 mg, more preferably 0.5 mg to About 3 mg.
  • the intake When taking as food, the intake varies depending on the symptom, age, weight, dosage form, method of intake, etc. of the subject of intake, but the daily dose is from 1 pg / kg body weight to 800 mg / kg body weight as an active ingredient.
  • the active ingredient is 6-methylsulfinyl hexyl isothiocyanate
  • 6-methylsulfinyl hexyl isothiocyanate 15 ng / kg body weight to 1.5 mg / kg body weight, more preferably 10 ng / kg body weight per adult day About 50 ng / kg body weight is preferred.
  • the amount per day can be taken at once or divided into several times.
  • the intake period is not particularly limited.
  • the food of the present invention suppresses the secretion of ACTH and / or the increase of inflammatory cytokines after stress loading. Increases in inflammatory cytokines after stress loading are closely associated with various diseases by causing excessive responses in the body. Therefore, the food of the present invention is also useful for preventing or ameliorating a disease caused by stress. Examples of the disease caused by stress include those described above.
  • the agent containing ⁇ -methylsulfinylalkylisothiocyanate as an active ingredient includes a description that can be used or should be used for prevention or reduction of stress, etc. Commercial packages are also included.
  • Example 1 Male C57 / B6 mice (10 weeks old; purchased from Seac Yoshitomi) were bred with free drinking of 0.5 ng% by weight of 6-MSITC (registered trademark) (manufactured by Kinshi Co., Ltd.). At 1 and 2 weeks after the start of 6-MSITC® administration, the mice were fixed in a restraint (27 mm diameter round plastic tube) and restraint stress was applied for up to 6 hours. Immediately after release from restraint stress, blood was collected from the heart, and the serum was separated by centrifugation at 2500 rpm for 10 minutes at 4 ° C., and the ACTH and IL-18 concentrations in the serum were measured. ACTH concentration was measured by SRL for measurement by RIA method, and IL-18 concentration was measured by ELISA using Quantikine TM immunoassay kit (R & D Systems).
  • 6-MSITC® The inhibitory action of these 6-MSITC® was more strongly observed in the 2-week administration group (FIG. 4) than in the 1-week administration group (FIG. 2). Furthermore, mice that received 6-MSITC (registered trademark) were less quarreled during breeding and were mild during stress. (Discussion) It was revealed that 6-MSITC (registered trademark) has an effect of suppressing acute stress response. 6-MSITC® has been shown not only to prevent exacerbations of inflammation due to stress, but also to reduce the load on the hypothalamic-pituitary adrenal system related to obesity and diabetes.
  • test meal or placebo start date was defined as day 0. (Subject management during study period) ⁇ Record of daily life log (sleeping time, alcohol, medicine) during the whole test period ⁇ Record of meal (morning, noon, evening) during test meal (or placebo) intake period ⁇ Steps by pedometer (registered trademark) Record (inspection) 1) Evaluation of personality and subjective symptoms TEG (Tokyo University egogram) (-1 week only) CMI, SDS, MAS (0, 4, 6 weeks) Every blood collection: GHQ, subjective research (Occupational Health Research Institute) Those who were subject to Kraepelin performed the Kraepelin test at the time when they should end the night shift at 0 points.
  • VAS Visual Analogue Scale
  • Every blood sampling Fatigue questionnaire: -1, 0, 4, 6 weeks 3) Physical examination Blood pressure, pulse, body weight, height, body fat percentage, steps ( Commercial pedometer (registered trademark) use) Blood pressure and pulse are around -1, 0, 4, 6 weeks. Otherwise, after working at -1, 0, 4, 6 weeks.
  • the anti-stress agent of the present invention suppresses the secretion of ACTH and glucocorticoid after stress loading on the living body and / or the increase in cytokine or chemokine after stress loading by ingesting as a food or a pharmaceutical, Reduce.
  • the anti-stress agent of the present invention also acts as an antagonist or alleviating agent against a physical load causing mental and physical disorders. Since an excessive reaction of a living body is associated with various diseases, the present invention can be applied to prevention or treatment of diseases caused by stress.

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  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

L'invention porte sur un agent antistress sûr et efficace soulageant les réponses in vivo provoquées par une contrainte de stress. Un agent antistress ou un antagoniste ou un agent de soulagement contre des troubles physiques et mentaux provoqués par des contraintes in vivo, est caractérisé en ce qu'il contient un isothiocyanate de ?-méthylsulfinylalkyle (où le groupe alkyle a de 4 à 8 atomes de carbone) en tant qu'ingrédient actif et inhibant la sécrétion de ACTH et/ou une augmentation d'une cytokine ou d'une chimiokine après une contrainte de stress. Comme l'isothiocyanate de ?-méthylsulfinylalkyle, l'isothiocyanate de 6-méthylsulfinylhéxyle peut être en particulier utilisé de façon appropriée.
PCT/JP2009/051372 2009-01-28 2009-01-28 Agent antistress Ceased WO2010086972A1 (fr)

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JP2010184892A (ja) * 2009-02-12 2010-08-26 Kinjirushi Kk 男性ホルモン様作用を呈する医薬品、医薬部外品、化粧品、飲食品および動物用飼料
CN102697045A (zh) * 2012-06-09 2012-10-03 东莞市照燕生物科技有限公司 一种促进红细胞生长的保健品
WO2018124258A1 (fr) * 2016-12-28 2018-07-05 株式会社 Ｐａｌ Agent thérapeutique pour le syndrome de fatigue chronique
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EP3932485A4 (fr) * 2019-02-27 2022-11-23 Otsuka Pharmaceutical Co., Ltd. Composition contenant un extrait végétal et/ou un produit transformé d'origine végétale
US12048683B2 (en) 2017-08-30 2024-07-30 Otsuka Pharmaceutical Co., Ltd. Kaempferol analog-containing composition

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Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2010184892A (ja) * 2009-02-12 2010-08-26 Kinjirushi Kk 男性ホルモン様作用を呈する医薬品、医薬部外品、化粧品、飲食品および動物用飼料
CN102697045A (zh) * 2012-06-09 2012-10-03 东莞市照燕生物科技有限公司 一种促进红细胞生长的保健品
US20180289660A1 (en) * 2015-10-08 2018-10-11 Productive Aging Laboratory, Co., Ltd. Inhibitor of muscle damage or muscle fatigue
US10471038B2 (en) * 2015-10-08 2019-11-12 Productive Aging Laboratory, Co., Ltd. Inhibitor of muscle damage or muscle fatigue
WO2018124258A1 (fr) * 2016-12-28 2018-07-05 株式会社 Ｐａｌ Agent thérapeutique pour le syndrome de fatigue chronique
JPWO2018124258A1 (ja) * 2016-12-28 2019-10-31 株式会社Ｐａｌ 慢性疲労症候群の治療剤
US10925304B2 (en) 2016-12-28 2021-02-23 Productive Aging Laboratory, Co., Ltd. Method for treating chronic fatigue syndrome, idiopathic chronic fatigue, and fibromyalgia
JP7274725B2 (ja) 2016-12-28 2023-05-17 株式会社Pal 慢性疲労症候群の治療剤
US12048683B2 (en) 2017-08-30 2024-07-30 Otsuka Pharmaceutical Co., Ltd. Kaempferol analog-containing composition
EP3932485A4 (fr) * 2019-02-27 2022-11-23 Otsuka Pharmaceutical Co., Ltd. Composition contenant un extrait végétal et/ou un produit transformé d'origine végétale

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