CN1798567A - Antistress agent - Google Patents
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- CN1798567A CN1798567A CN 200480014986 CN200480014986A CN1798567A CN 1798567 A CN1798567 A CN 1798567A CN 200480014986 CN200480014986 CN 200480014986 CN 200480014986 A CN200480014986 A CN 200480014986A CN 1798567 A CN1798567 A CN 1798567A
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Abstract
The present invention provides an anti-stress agent which can effectively prevent or alleviate various symptoms caused by stress and which is safe and easily taken or ingested. The anti-stress agent comprises an aroma component of coffee or teas as an active ingredient.
Description
Technical field
The present invention relates to a kind of coffee or tea of having utilized, as the anti-stress agent of the fragrance ingredient that contains in the oolong tea.The invention still further relates to a kind of coffee or tea of containing, as the medicine or the functional food of fragrance ingredient contained in the oolong tea, these medicines or functional food prevent or alleviate by the mind ﹠ body disease that stress be caused.In addition, the present invention relates to a kind of use coffee or tea, as the cosmetics or the aromatic of the fragrance ingredient that contains in the oolong tea.
Background technology
Twenty four hours running advance and complicated modern society in, people face miscellaneous physicochemical, psychology and social stress.Especially the modern is in the complex personal relationship, psychological factor constituted stress major part.
People have done various about psychological stress and the various studiess on some in dications of that caused thus.For example, report and take care to swash that norepinephrine is accelerated release at many positions of brain, has so just caused the emotion performance, as anxiety and anxiety (non-patent literature 1) by after the brain perception.When stress continuing for a long time, the various organs of human body all are affected, and the possibility of result has caused psychosomatic disorder, depression, gastric ulcer, serious situation such as hypertension.
If current be used to alleviate stress or the drug main benzodiazepine class antianxiety drug and the sleeping pill of prevention or the treatment disease that stress cause.The central GABA nervous system is considered to the site of action of benzodiazepine class antianxiety drug and sleeping pill.The GABA that exists in the GABA nervous system
AReceptor with as the C1 passage at center, also form complex with benzodiazepine receptor and barbital binding site.Report, when benzodiazepine receptor and barbital binding site are upset, GABA
AReceptor strengthens (non-patent literature 2) to the affinity of GABA.
Report that in addition when maincenter GABA nervous system was activated, just having occurred stress mitigation.When rat be exposed to cold limited stress (4 ℃, 2 hours) in the time, gastric ulcer has just appearred.Report that the appearance of this type of gastric ulcer relies on mode with dosage and given GABA (5,10,20,50 μ g) and GABA in the ventricle
AReceptor stimulating agent 5-aminomethyl-3-hydroxyisoxazole (5,10 μ g) suppresses and GABA receptor antagonist bicuculline (40 μ g) alleviates the inhibitory action (non-patent literature 3) of GABA to stress ulcer.In addition, report rat because the inhibition that the hyperkinesia that stress cause and gastric ulcer are subjected to amino oxygen-acetic acid (GABA deaminase inhibitor), this amino oxygen-acetic acid can increase as GABA
AThe 5-aminomethyl-3-hydroxyisoxazole of receptor stimulating agent or the concentration of central GABA (non-patent literature 4).As mentioned above, the central GABA nervous system alleviate stress aspect play an important role.
Although benzodiazepine class anxiolytic drugs is the medicine with relative high security with sleeping pill, but still preferably frequently do not take in daily life they be used for of short duration stress because they have addiction and side effect.In addition, when interrupting using them after administration, can have a rebound, in some cases, so symptom may more be worsened.Therefore, be difficult to think that they are ideal anti-stress agent.
Because modern society's increases of stress loading, and stress be not only to Mental Health but also to the having a strong impact on of live body, therefore developing really effective, safe anti-stress agent needs.Especially from the angle of prevention, the anti-stress agent that exploitation can be used in food and the luxury goods needs.
Report therebetween, increase the α wave frequency, give the sensation of loosening (non-patent literature 5) such as this luxurious fragrance that moves in the product of coffee.Yet active substance wherein is indeterminate.
(non-patent literature 1) Masatoshi Tanaka, Metabolism, vol.26, p122-131,1989
(non-patent literature 2) D.G Nicholls, Amino Acids as Neurotransmitter, in " Proteins, Transmitters and Synapses " .Blackwell ScientificPublication, Oxford, p.155-185,1994
(non-patent literature 3) KP Bhargava, GP Gupta and MB Gupta, " CentralGABA-eragic mechanism in stress-induced gastric ulceration ", BritishJournal of Pharmacology, vol.84, p.619-623,1985
(non-patent literature 4) Psychopharmacology 89:472-476,1986
(non-patent literature 5) Life and Health, August, 2000
Summary of the invention
The object of the invention is to provide a kind of anti-stress agent, and it can effectively prevent or alleviate the various symptoms that stress be brought, and safety, easily take or absorb.Equally, according to coffee of the present invention or tea, make cosmetics or aromatic as the fragrance ingredient that contains in the oolong tea is suitable, because it has volatility and anti-stress activity.
In order to develop a kind of effective and safe anti-stress agent, the inventor has studied various chemical compound through repetition test.As a result, they are surprised to find that the fragrance ingredient in the coffee ﹠ tea has the anti-stress activity.
More particularly, the potentiation that the inventor uses the GABA to the Xenopus oocyte of expressing the GABA receptor to reply is index, has carried out the screening of anti-stress active substance.As a result, the inventor finds that the fragrance ingredient in the coffee ﹠ tea has the activity of replying of enhancing GABA to the GABA receptor.And then, the inventor uses when giving mice GABA receptor activation medicine pentobarbital, and the activity that prolongs sleep time is an index, has carried out pharmaceutical research in the body, they find that the fragrance ingredient of coffee or tea obviously prolongs by the inductive sleep time of pentobarbital.As mentioned above because the central GABA nervous system alleviate stress aspect play an important role, the fragrance ingredient in coffee or the tea by activate the central GABA receptor have alleviate stress effect.
In addition, because people habitually drink coffee and tea for a long time, the anti-stress agent that therefore contains the fragrance ingredient in coffee or the tea does not have safety issue.
That is to say, the present invention relates to:
(1) contain fragrance ingredient in coffee or the tea as the anti-stress agent of active component,
(2) according to the anti-stress agent of above-mentioned (1), fragrance ingredient wherein is one or more components that are selected from following substances: 2-methyl-3-butene-2-alcohol, 3-methyl-2-butene-1-alcohol, 1-amylene-3-alcohol, (B)-the 2-hexen-1-ol, 1-octene-3-alcohol, high sand (sotolone), 2, the 4-dimethyl styrene, benzothiazole, 2,3, the 5-pseudocuminol, cis-jasmone, methyl jasmonate, JSM-LAC (Z)-7-Decen-5-olide and linalool oxide
(3) according to the anti-stress agent of above-mentioned (1), tea wherein is oolong tea,
(4) according to the anti-stress agent of above-mentioned (1), fragrance ingredient wherein is to be selected from 1-octene-3-alcohol, one or more compositions of cis-jasmone and methyl jasmonate,
(5) according to above-mentioned (1) any one anti-stress agent in (4), wherein the amount of the fragrance ingredient of each dosage or each picked-up is 5-50mg,
(6) according to above-mentioned (1) any one anti-stress agent in (5), it is a medicine,
(7) according to above-mentioned (1) any one anti-stress agent in (5), it is a functional food,
(8) according to above-mentioned (1) any one anti-stress agent in (5), it is cosmetics,
(9) according to above-mentioned (1) any one anti-stress agent in (5), its aromatic,
(10) according to above-mentioned (1) any one anti-stress agent in (9), its GABA receptor stimulating agent,
(11) a kind of prevent or alleviate stress method, comprise give fragrance ingredient that mammal contains in coffee or tea and
(12) fragrance ingredient that contains in coffee or the tea preparation be used for preventing or alleviate stress the purposes of medicine.
Anti-stress agent of the present invention especially activates the central GABA nervous system by activating the GABA receptor, and can effectively prevent or alleviate stress.Therefore, can suppress or prevent stress caused various symptoms for anti-stress agent of the present invention.
And because anti-stress agent of the present invention comprises coffee ﹠ tea, as active component, it is good and do not have the advantage of particular restriction when using that this anti-stress agent has a safety as the fragrance ingredient in the oolong tea.
In addition, because anti-stress agent of the present invention has comprised the fragrance ingredient in luxury goods such as the coffee ﹠ tea, this anti-stress agent is easily taken or is taken in.Particularly, when anti-stress agent of the present invention is made functional food, during as healthy beverage, this anti-stress agent can be used by every day stress so that prevent and/or alleviate.In addition, coffee or tea as the fragrance ingredient in the oolong tea, can be used as cosmetics or aromatic, because it has volatility, and not only have happy fragrance but also the anti-stress activity is arranged.
Description of drawings
Fig. 1 is the active figure of external GABA receptor activation that shows the various fragrance ingredients in coffee or the tea.
Fig. 2 is the figure that shows the active dose dependent of GABA receptor activation of 1-octene-3-alcohol.
Fig. 3 shows that when to mice oral administration 1-octene-3-when pure, pentobarbital is to the figure of the influence of sleep time.1-OCOL (20) shows the group that gives 20mg/kg 1-octene-3-alcohol, and 1-OCOL (100) shows the group that gives 100mg/kg 1-octene-3-alcohol, and CONT shows matched group.
Fig. 4 is the active figure of external GABA receptor activation that shows various fragrance ingredients in the oolong tea.Among the figure, cis-jasmone, methyl jasmonate, JSM-LAC (Z)-7-Decen-5-olide and linalool oxide are used cis-JSM respectively, Me-JSM, JSM-LAC and LINL-OX representative.
Fig. 5 is the figure that shows the active dose dependent of GABA receptor activation of cis-jasmone and methyl jasmonate.
Fig. 6 shows that when mice sucks cis-jasmone and methyl jasmonate pentobarbital is to the figure that influences of sleep time, and * represents with respect to contrast p＜0.05.
Implement optimal mode of the present invention
The invention provides a kind of anti-stress agent that contains the fragrance ingredient of coffee ﹠ tea.The example of used tea comprises unfermentable tea among the present invention, for example, a kind of tea that steamed such as Sencha (Japanese most popular green tea), Hojicha (tea of baking), Gyokuro (the purified green tea that is grown in shady place), kabusecha (is grown in the green tea of shady place, period ratio Gyokuro is short) and Tencha (except not stirring drying, the green tea that other preparation methoies are the same with Gyokuro) or the tea such as the Ureshinocha (green tea that Japanese Saga is produced) that cross with the pan roast, Aoyagicha (the bluish tea that Japanese Miyazaki is produced) or various Chinese tea; The tea of half fermentation is as Bao Zhon tea (wen shan area, Taiwan produces), TIEGUANYIN tea and oolong tea; The tea such as the black tea of fermentation, Awabancha (inferior tea that Japanese Tokushima is produced), Goishicha (inferior tea that Japanese Tosa is produced) and Folium camelliae assamicae; And Genmaicha (inferior tea that has mixed the rice of baking and explosion), herb tea, Rhizoma Curcumae Longae tea, the Fructus Hordei Vulgaris tea of baking, the Semen Coicis tea of baking, Ilex paraguarensis etc.In above-mentioned all tea, oolong tea is preferred, because it contains employed a large amount of effective fragrance ingredient among the present invention.
Contained fragrance ingredient can be to adopt those that known method such as column chromatography purify from coffee ﹠ tea in the anti-stress agent of the present invention, maybe can be unpurified concentrate.As for described fragrance ingredient, the purified product that can use commercial sources to obtain.In addition, also can use the fragrance ingredient of chemosynthesis.Contained a large amount of fragrance ingredients are can admixture involved in the coffee ﹠ tea, perhaps can be that single fragrance ingredient is comprised in the anti-stress agent of the present invention.
Fragrance ingredient in the coffee ﹠ tea has no particular limits, and can be a kind of known composition.Specifically, the example of preferred fragrance ingredient comprises 2-methyl-3-butene-2-alcohol, 3-methyl-2-butene-1-alcohol, 1-amylene-3-alcohol, (E)-the 2-hexen-1-ol, 1-octene-3-alcohol, high sand, 2, the 4-dimethyl styrene, benzothiazole, 2,3,5-pseudocuminol, cis-jasmone, methyl jasmonate, JSM-LAC (Z)-7-Decen-5-olide and linalool oxide etc.Known in coffee and black tea, all contain these compositions as fragrance ingredient (Food Rev.Int., 1989,5,317-414).In these fragrance ingredients, preferred 1-octene-3-alcohol, cis-jasmone and methyl jasmonate.These fragrance ingredients can be the products that commercial sources obtains, synthetic product or extract product, and synthetic method and extracting method can be known methods.
In tea, known oolong tea contains a large amount of above-mentioned fragrance ingredients.For example, the content of JSM-LAC (Z)-7-Decen-5-olide has only 0.33ppm in the dragon well green tea (Chinese green tea), and among the oolong tea Huang jing gui 26.43ppm is arranged.Equally, do not detect methyl jasmonate in the dragon well green tea of one of green tea, but the Huangjing gui of one of oolong tea contains 3.33ppm (Keiichiro Muramatsu, Function of Tea, Gakkaishuppan Center, 2002).It is reported that JSM-LAC (Z)-7-Decen-5-olide produces in the sweat of oolong tea, and the fermentation by oolong tea increased by 50 times of JSM-LAC (Z)-7-Decen-5-olide (J.Agric.Food Chem.2001,49,5391-5396).Yet with regard to the black tea that further ferments, Darjeeling Tea only has the JSM-LAC (Z)-7-Decen-5-olide of 0.74ppm.In addition, as the analog of methyl jasmonate, the content of methyl table jasmonate in the black tea 1ppm (Michiko kawakami, Study Note of Tea Perfume, Koseikan, 2000) that at most only has an appointment.Should be interpreted as, in the present invention, methyl jasmonate comprises methyl table jasmonate.
When the fragrance ingredient of the coffee ﹠ tea in being included in anti-stress agent of the present invention was free acid or alkali, the form that described fragrance ingredient can pharmaceutically acceptable salt was involved.The example of pharmaceutically acceptable salt comprises the salt with pharmaceutically acceptable acid (as organic acid or mineral acid), perhaps with the salt of pharmaceutically acceptable alkali (as inorganic base or organic base).Example comprises and mineral acid more specifically, example hydrochloric acid, sulphuric acid, phosphoric acid and hydrobromic salt; With organic acid, as oxalic acid, maleic acid, fumaric acid, malic acid, tartaric acid, citric acid and benzoic salt; Salt with inorganic base such as alkali metal (as sodium, potassium) and alkaline-earth metal (as magnesium, calcium); With with organic base, as organic amine (as triethylamine), the salt of basic amino acid (as arginine).
Anti-stress agent of the present invention relate to a kind of have loosely or tranquil stress and can keep the active material of anti-stress of the stable state of live body, or a kind of compositions that comprises this material.In other words, anti-stress agent of the present invention relate to a kind of cause defence stress or adapt to stress the material of biologically, or comprise the compositions of described material.Here, stress typically refer to, when cause stress stimulation (stresser) when being applied to live body, the strain that produces in spirit or the health.The example of stresser comprises physical stimulation, and as cold, weather changes, radiation and noise; Chemical stimulation such as medicine, vitamin deficiency and anoxia; Biostimulation such as bacterial infection; Come from disease or disorderly body-stimulating as pain and fever; By direct stimulation such as the anxiety, anxiety and the fear that cause of inter personal contact in society and the family.
Therefore, anti-stress agent of the present invention is used for prevention and stress or promotes that from recovering be effectively, thereby can prevent, promotion or treat by stress caused medical symptom.
Example that stress caused medical symptom comprises: (a) circulatory diseases such as arteriosclerosis, ischemic heart disease (angina pectoris, myocardial infarction), essential hypertension, cardiac neurosis and arrhythmia, (b) respiratory disorder such as bronchial asthma, accelerated breathing syndrome and nerve cough, (c) digestive disease such as peptic ulcer, ulcerative colitis, irritable bowel syndrome, anorexia nervosa, nervous vomiting, abdominal distention, and aerophagia, (d) incretion metabolism disease such as obesity, diabetes, spirituality polyposis and Basedow's disease, (e) nervous system disease such as migraine, muscle contraction headache and autonomic imbalance (f) urinary disorders such as enuresis nocturna, sexual impotence and nervous bladder and (g) skeleton and muscle disease such as rheumatoid arthritis, general myalgia and spinal column stimulation.
In addition, example that stress caused medical symptom also comprises (h) dermatosis such as neurodermatitis, alopecia areata, hyperhidrosis and eczema, (i) hals,Nasen und Ohrenheilkunde disease such as Meniere syndrome, foreign body sensation in the throat, dysacousis, the ear noise, motion disease and aphasia stutter, (j) ophthalmic diseases such as primary glaucoma, the eyestrain, blepharospasm and eye hysteria, (k) gynecological and obstetrics' disease such as dysmenorrhea, amenorrhea, menoxenia, dysfunctional uterine bleeding, menopause disorder, hyposexuality and infertility, (l) pediatric disease such as vertical obstacle, recurrent umbilicus angor, spirituality fever and fright at night, (m) preceding and postoperative situation such as intestinal adhesion of operation, dumping syndrome, polysurgery behind the plastic operation and neurosis, (n) oral disease such as spontaneous glossodynia, the stomatitis of some types, halitosis, salivation is unusual, and the masseter function suppresses (masseter check) and artificial tooth neurosis, (o) neurosis and (p) depression.
Anti-stress agent of the present invention can be used as medicine or functional food.When anti-stress agent of the present invention was used as medicine, as long as advantageously carry out oral or gastrointestinal tract external administration, this medicine can be any dosage form.The example of the dosage form of medicine of the present invention comprises injection, infusion solution, powder, granule, tablet, capsule, casing agent, lozenge, solution for oral administration, suspension, Emulsion, syrup, the solution of external, hot compress agent, nasal drop, ear drop, eye drop, inhalant, ointment, washing liquid and suppository.Equally, in the present invention, the medicine of the present invention of above-mentioned dosage form can use separately or according to symptom with they drug combinations.
In medicine of the present invention, in main component, can add known pharmaceutical field additive such as excipient, binding agent, disintegrating agent, lubricant, correctives and stabilizing agent commonly used according to purpose.
More particularly, when medicine of the present invention is solid preparation such as capsule, tablet when powder and granule, can contain additive in the preparation, for example excipient such as lactose, glucose, sucrose, and mannitol; Disintegrating agent such as starch and sodium alginate; Lubricant such as magnesium stearate and Pulvis Talci; Binding agent such as polyvinyl alcohol, hydroxypropyl cellulose and gelatin; Show activating agent such as fatty acid ester; Plasticizer such as glycerol.On the other hand, when medicine of the present invention is liquid preparation, can contain additive in the preparation, for example sugared as sucrose, sorbitol, fructose; Glycol such as Polyethylene Glycol and propylene glycol; Oily as Oleum Sesami, olive oil and Oleum Glycines; Antiseptic such as p-Hydroxybenzoate.In addition, under the situation of liquid preparation, medicine of the present invention can be the preparation that is such form, so that dissolved in use as the fragrance ingredient of active component.
The medicine of the invention described above can utilize the known or conventional method of pharmaceutical field itself easily to prepare.
The route of administration of medicine of the present invention is not subjected to particular determination, and can be oral administration or gastrointestinal tract external administration.Especially, consider that from the angle that is easy to take in medicine of the present invention that can be oral is preferred.
The dosage of medicine of the present invention is because of route of administration, the serious situation of dosage form and symptom, and therefore patient's age or body weight and change cannot treat different things as the same.Specifically, be such for the amount of the every dosage of adult, the total amount that is included in the fragrance ingredient of the present invention in a kind of solid preparation such as the capsule is about 5 to 500mg, preferred about 5 to 50mg.
When anti-stress agent of the present invention was used as functional food, its form can be identical with the form of said medicine preparation.Alternatively, food can be processed to as natural liquid food, the nourishing food of half digestion, forms such as composition nourishing food and beverage.In addition, functional food of the present invention can be made diffluent preparation, in use said preparation is joined in alcoholic beverage or the mineral water.More particularly, the example of the form of functional food of the present invention comprises confectionery such as cookies, cooky, cake, confection, chocolate, chewing gum and japanese confectionery; Bread, noodles, rice and bean curd, or their converted products; Fermented food is as refining rice wine and the alcoholic beverage with property of medicine; Flavoring agent such as Mirin (the Japanese sweet rice wine of culinary art usefulness), vinegar, soy sauce, miso (bean sauce of fermentation) and flavouring agent; Livestock food product such as yoghourt, Petaso, bacon, sausage and mayonnaise; The alec of finished marine product as boiling, fried alec and Hampen (alec cake); Beverage such as fruit beverage, soft drink, isoosmotic beverage, alcoholic beverage, tea, coffee and cocoa.When fragrance ingredient of the present invention is used in the beverage by being added on, content be preferably in every 1L beverage 0.0005 to 1.0wt% and each intake be about 5 to 500mg, preferred about 5 to 50mg.
Selectively, functional food of the present invention can be offered the patient with the form of the functional food of the preparation of original place by the following method: write out a prescription based on doctor's food, under the supervision of nutritionist, in the meals of preparation hospital, add anti-stress agent of the present invention in food arbitrarily.Anti-stress agent of the present invention can be a liquid, or solid such as powder and granule.
Functional food of the present invention can contain field of food complementary element commonly used.The example of complementary element comprises lactose, sucrose, liquid sugar, Mel, magnesium stearate, propoxyl group cellulose, various vitamin, trace element, citric acid, malic acid, spice and inorganic salt.
When expection take place stress, or just experiencing stress the time, for example, physical work in mental work and the motor process, can be taken functional food of the present invention.Alternately, for prevent or alleviate stress, can take this functional food regularly.
The amount of the picked-up of functional food of the present invention is taken in the people's of described food age in response to sharp situation, and therefore sex etc. and changing cannot treat different things as the same.Specifically, be such for the each amount of taking in of adult, make that the total amount of fragrance ingredient of the present invention is about 5 to 500mg, preferred about 5 to 50mg.
Medicine of the present invention or functional food can with other anti-stress agent, nutrient such as vitamin, hormones preparation etc., trace element or iron compound coupling.For example, when functional food of the present invention is healthy beverage, if desired, by with other physiologically active ingredient, mineral, hormone, nutritional labeling, mixing such as spice can be given the character of luxurious beverage in the beverage of the present invention better.
Stress comprise depressed trend to people's effect.Before reaching pathological state, this trend is found out in the normal daily life of being everlasting.Therefore, providing a kind of method that alleviates this trend has been a significant challenge that needs to be resolved hurrily.Recently, particularly, the aromatic therapy alleviates the method for depressed trend and causes concern as a kind of.Have volatility and have the fragrance ingredient of the present invention of dulcet fragrance, can be used as cosmetics or aromatic.
Fragrance ingredient in coffee of the present invention or the tea can be used as cosmetics or aromatic, comprises, for example, body care product such as perfume, esu de toilette, Cologne, anti-perspirant, deodorizer, shampoo, the hair irrigation, hair conditioner, agent for treatment of hair, the hair dressing agent, soap, Clean Living soap, basic skin nursing products etc.; Laundry product such as laundry detergent, household cleaners, domestic fabric softener, laundry bleach etc.; Household products such as dishwashing detergent, detergent for toilet, household bleach, aromatic, floor polisher etc.; Oral care product such as toothpaste, collutory, cleaning agent for mouth cavity, oral cleansing lotion etc.; And various products such as paste etc.
Employed selectable cosmetic composition of cosmetic field such as oil ﹠ fat, wetting agent, natural dye, surfactant, antioxidant, antiseptic etc. all can be used in the cosmetics that contain the fragrance ingredient in the coffee ﹠ tea of the present invention, and described cosmetics can be by the known method preparation in this area own.The Physiological Psychology situation of using cosmetics of the present invention people to be experienced in daily life generation from them, as drowsiness, fatigue frees in the asthenia etc., refresh oneself, and the effect of the vigor that refreshes.Although according to dosage form and use the purpose of these cosmetics to decide the amount of fragrance ingredient contained in the cosmetics, this amount is generally 0.005 to 10% by the gross weight of cosmetics.
In addition, aromatic of the present invention can be contained in known container that is used for aromatic itself and can use.The form of aromatic comprises spray and solid (granule), and this aromatic can create and smells pleasant space.Although the concentration of place that foundation is used or essential fragrance decides the amount of the fragrance ingredient that uses in the aromatic, this amount is generally 0.005 to 10% by the gross weight of aromatic.
Embodiment
The following examples are further set forth the present invention, but do not limit scope of the present invention.
In the activation activity of external fragrance ingredient (9 kinds) to the GABA receptor
As experiment material, use the oocyte of Xenopus.A kind of GABA receptor mrna that comes from rat is injected oocyte nuclei be used for receptor at the surface expression GABA of ovum.Oocyte is at ringer's solution (115mM NaCl, 1mM KCl, the 1.8mM CaCl of the Rana nigromaculata of routine
2, 5mM Tris, pH 7.2) the middle cultivation.Utilize resulting oocyte, measure the inhibition current potential of the inhibition current potential of GABA (10 μ M) and GABA (10 μ M) and the mixed solution of the sample of mentioning below.Clamp amplifier (CEZ-1100 service voltage; NIHONKODEN CORPORATION makes), measure the generation that suppresses current potential by the voltage clamp method.
As sample, the concentration the when fragrance ingredient that contains in following 9 kinds of coffees or the tea uses is 2 μ 1/ml.Employed sample is as described below: 2-methyl-3-butene-2-alcohol (representing with 2-M3BOL in Fig. 1), 3-methyl-2-butene-1-alcohol (is represented with 3-M2BOL in Fig. 1,1-amylene-3-alcohol (in Fig. 1, representing) with 1-POL, (E)-2-hexen-1-ol (in Fig. 1, representing) with HXOL, 1-octene-3-alcohol (in Fig. 1, representing) with 1-OCOL, high sand (in Fig. 1, representing) with STOL, 2,4-dimethyl styrene (with 2,4-DMS represents in Fig. 1), benzothiazole (in Fig. 1, representing) and 2 with BZT, 3,5-pseudocuminol (with 2,3,5-TEP represents in Fig. 1).Employed above-mentioned sample is the obtainable product of commercial sources in the experiment.In other words, employed high sand is by Ogawa ﹠amp; Co., Ltd. makes, and other chemical compound is by Tokyo Kasei Co., and Ltd. makes.
The result shows in Fig. 1.With sample to the enhanced activity of the inhibition current potential that brings out by GABA as index.Result's inhibition current potential (being set at 100%) that produces when only adding GABA (0.25 μ M) suppresses the percentage ratio increase of unit and represents when GABA and sample coupling.As conspicuous from Fig. 1, find that all assess sample have all strengthened GABA to the replying of GABA receptor, and particularly 1-octene-3-alcohol has the activity that strong enhancing is replied.
In embodiment 1, use hexanol as positive control.The hexanol of known composition as phytocide has the GABA of activation receptor active (Biosci.Biotechnol.Biochem., 63,743-748,1999) and alleviate stress activity (1998-1999 Scientific Research Subsidy, Fundamental Research (C) (2) Research Outcome Report, Research ThemeNo.10670070).
Research to the dose dependent of 1-octene-3-alcohol
Now study and in embodiment 1, be proved dose dependent with strong active 1-octene-3-alcohol.Those of experimental technique and embodiment 1 are identical.The concentration of GABA is 5 μ M, and the concentration of 1-octene-3-alcohol is 0.3-1mM.The result shows in Fig. 2.As conspicuous from Fig. 2,1-octene-3-alcohol demonstrates 400% GABA replying the GABA receptor at the most.Result displayed is used and is suppressed current potential (being set at 100%) when only adding GABA (5 μ M) among Fig. 2, and the relative value of the inhibition current potential when GABA and 1-octene-coupling of 3-alcohol represents.
1-octene-3-alcohol is to the enhanced activity of the inductive sleep of pentobarbital
As laboratory animal, ddy male mice (8 week age) is bought from Shimizu Laboratory SuppliesCo., and Ltd. is used for experiment after raising a week.Per five mices are raised in the polyisoamylene cage (Clea Japan.Inc. manufacturing) of receptacle, raising condition enactment is 23 ± 2 ℃ of room temperatures, humidity is 55 ± 5%, and ventilation frequency is 12-15/ hour (all fresh air circulations), lighting hours 12 hours/day (from 7a.m. to 7p.m.).Mice feeds solid feed CE-2 (Clea Japan Inc.) and allows water inlet arbitrarily.
Be dissolved in the olive oil 1-octene-3-alcohol according to 20 or the dosage of 100mg/Kg to the mice oral administration.8 mices are arranged in every group.After 30 minutes, be dissolved in pentobarbital in the normal saline, measure sleep time according to the dosage intraperitoneal administration of 50mg/kg.Be defined as time period the length of one's sleep from the forfeiture righting reflex to its recovery.
The result shows in Fig. 3.The experimental result that shows among Fig. 3 is represented with mean+/-standard error, uses the Student-t check in significant difference detects.As conspicuous from Fig. 3, in the mode of dose dependent, 1-octene-3-alcohol has prolonged the persistent period of the inductive sleep of pentobarbital.
Embodiment 4
Fragrance ingredient in external luxury goods (oolong tea) is to the activation activity of GABA receptor
As experiment material, use the oocyte of Xenopus.A kind of GABA receptor mrna that comes from rat is injected oocyte nuclei be used for receptor at the surface expression GABA of ovum.Oocyte is at ringer's solution (115mM NaCl, 1mM KCl, the 1.8mM CaCl of the Rana nigromaculata of routine
2, 5mM Tris, pH 7.2) the middle cultivation.Clamp amplifier (CEZ-1100 service voltage; Nihon Koden corporation makes), measure the generation of the caused inhibition current potential of GABA (0.25 μ m) by the voltage clamp method.
As sample, the concentration when 4 kinds of fragrance ingredients in the following oolong tea use is 0.5mM.Employed sample is as follows: cis-jasmone, methyl jasmonate, JSM-LAC (Z)-7-Decen-5-olide and linalool oxide.
The sample that uses in the described experiment is by Ogawa ﹠amp; Co., Ltd. makes.
The result shows in Fig. 4.With sample to the enhanced activity of the inhibition current potential that brings out by GABA as index.Result's inhibition current potential (being set at 100%) that produces when only adding GABA (0.25 μ M), the percentage ratio increase of the inhibition current potential when GABA and sample coupling is represented.As conspicuous from Fig. 4, the sample of finding all evaluations has all strengthened GABA to have the replying of GABA receptor, particularly cis-jasmone and methyl jasmonate and strengthens the activity of replying.
In embodiment 4, use hexanol as positive control.The hexanol of known composition as phytocide has the activity (Biosci.Biotechnol.Biochem that activates the GABA receptor, 63,743-748,1999) active and alleviate stress (1998-1999 Scientific Research Subsidy, Fundamental Research (C) (2) Research Outcome Report, Research ThemeNo.10670070).
Embodiment 5
Research to the dose dependent of cis-jasmone and methyl jasmonate
Now study and in embodiment 4, be proved dose dependent with strong active cis-jasmone and methyl jasmonate.Those of experimental technique and embodiment 4 are identical.The concentration of GABA is 5 μ M, and the concentration of cis-jasmone and methyl jasmonate is 0.2-1mM.The result shows in Fig. 5.As conspicuous from Fig. 5, cis-jasmone and methyl jasmonate demonstrate 200% and 300% GABA replying the GABA receptor at the most respectively.The result displayed inhibition current potential (being set at 100%) that produces when only adding GABA (5 μ M) among Fig. 5, the inhibition current potential relative value when GABA and cis-jasmone and methyl jasmonate coupling represents.
Embodiment 6
Cis-jasmone and methyl jasmonate are to the enhanced activity of the inductive sleep of pentobarbital
As laboratory animal, ddy male mice (8 week age) is bought from Shimizu Laboratory SuppliesCo., and Ltd. is used for experiment after raising a week.Per five mices are raised in the polyisoamylene cage (Clea Japan.Inc. manufacturing) of receptacle, raising condition enactment is 23 ± 2 ℃ of room temperatures, humidity is 55 ± 5%, and ventilation frequency is 12-15/ hour (all fresh air circulations), lighting hours 12 hours/day (from 7a.m. to 7p.m.).Mice feeds solid feed CB-2 (Clea Japan Inc.) and allows water inlet arbitrarily.
Mice is sucked in the box that exposes to the open air be diluted to 0.1% cis-jasmone and methyl jasmonate, finish up to experiment.5 mices are arranged in every group.Air-breathing beginning is after 30 minutes, is dissolved in pentobarbital in the normal saline according to the dosage intraperitoneal administration of 50mg/kg, and measures sleep time.Be defined as time period the length of one's sleep from the forfeiture righting reflex to its recovery.
The result shows in Fig. 6.Experimental result among Fig. 6 is represented with mean+/-standard error, uses the Student-t check in significant difference detects.As conspicuous from Fig. 6, cis-jasmone and methyl jasmonate significant prolongation the persistent period of the inductive sleep of pentobarbital.
Example of formulations
Example of formulations 1
Capsule
A. fill a prescription (every 500mg)
1-octene-3-alcohol: 5mg
Lactose: 493mg
Magnesium stearate: 2mg
B. method
According to above-mentioned prescription, the pure and mild lactose of 1-octene-3-is mixed compacting and grinding.In this material, mix magnesium stearate according to formula ratio.Every 500mg mixture packed into contain the capsule of 5mg1-octene-3-alcohol in making every in No. 2 capsules.
Example of formulations 2
Healthy beverage
A. fill a prescription
1-octene-3-alcohol: 5g
DL-sodium tartrate: 0.1g
Succinic acid: 9mg
Liquid sugar: 800g
Citric acid: 12g
Vitamin C: 10g
Spice: 12ml
Potassium chloride: 1g
Magnesium sulfate: 0.5g
B. method
According to above-mentioned prescription, mentioned component is dissolved in the 8L distilled water, it is 10L to total amount wherein that distilled water is added.The solution of gained is crossed the germ tight filter of 0.22 μ m, the above-mentioned solution of every 100ml is encased in the healthy beverage that contains 5mg 1-octene-3-alcohol in making every dose in the brown bottle under the sterile working.
Example of formulations 3
Capsule
A. fill a prescription (every capsules)
Methyl jasmonate: 5mg
Lactose: 493mg
Magnesium stearate: 2mg
500mg
B. method
According to above-mentioned prescription, methyl jasmonate and lactose are mixed compacting and grinding.In this material, mix magnesium stearate according to formula ratio.Every 500mg mixture packed into make the capsule that contains the 5mg methyl jasmonate in every capsules in No. 2 capsules.
Example of formulations 4
The preparation of healthy beverage
A. fill a prescription
Cis-jasmone: 5g
DL-sodium tartrate: 0.1g
Succinic acid: 9mg
Liquid sugar: 800g
Citric acid: 12g
Vitamin C: 10g
Spice: 12ml
Potassium chloride: 1g
Magnesium sulfate: 0.5g
B. method
According to above-mentioned prescription, mentioned component is dissolved in the 8L distilled water, it is 10L to total amount wherein that distilled water is added.The solution of gained is crossed the germ tight filter of 0.22 μ m, the above-mentioned solution of every 100ml is encased in the healthy beverage that contains 5mg cis-jasmone in making every dose in the brown bottle under the sterile working.
Industrial applicability
Antistress agent of the present invention can suppress or prevent various with stress symptom, and be suitable for and make medicine, Functional food, cosmetics or aromatic.
Claims (12)
1, a kind of anti-stress agent, it comprises the fragrance ingredient of coffee or tea as active component.
2, according to the anti-stress agent of claim 1, fragrance ingredient wherein is one or more components that are selected from following substances: 2-methyl-3-butene-2-alcohol, 3-methyl-2-butene-1-alcohol, 1-amylene-3-alcohol, (E)-the 2-hexen-1-ol, 1-octene-3-alcohol, high sand, 2, the 4-dimethyl styrene, benzothiazole, 2,3, the 5-pseudocuminol, cis-jasmone, methyl jasmonate, JSM-LAC (Z)-7-Decen-5-olide and linalool oxide.
3, according to the anti-stress agent of claim 1, tea wherein is oolong tea.
4, according to the anti-stress agent of claim 1, fragrance ingredient wherein is to be selected from 1-octene-3-alcohol, one or more compositions of cis-jasmone and methyl jasmonate.
5, the anti-stress agent any according to claim 1 to 4, wherein each dosage or the amount of at every turn absorbing fragrance ingredient are 5-50mg.
6, the anti-stress agent any according to claim 1 to 5, it is pharmaceutical preparation.
7, the anti-stress agent any according to claim 1 to 5, it is a functional food.
8, the anti-stress agent any according to claim 1 to 5, it is cosmetics.
9, the anti-stress agent any according to claim 1 to 5, it is an aromatic.
10, the anti-stress agent any according to claim 1 to 9, it is the GABA receptor activators.
11, a kind of prevent or alleviate stress method, it comprises and gives mammal a kind of fragrance ingredient that is included in coffee or the tea.
12, be included in coffee or the tea fragrance ingredient preparation prevention or alleviate stress medicine in purposes.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2003155597 | 2003-05-30 | ||
| JP155597/2003 | 2003-05-30 | ||
| JP308041/2003 | 2003-08-29 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1798567A true CN1798567A (en) | 2006-07-05 |
Family
ID=36819159
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200480014986 Pending CN1798567A (en) | 2003-05-30 | 2004-05-28 | Antistress agent |
Country Status (1)
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| CN (1) | CN1798567A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102660383A (en) * | 2012-06-02 | 2012-09-12 | 哈尔滨工业大学 | Separation process of essential oil in toad maggots |
| CN103140223A (en) * | 2010-05-19 | 2013-06-05 | 布罗迪健康科学有限公司 | Use of jasmonates for treating heart failure and related cardiac disorders |
| CN104585750A (en) * | 2014-12-25 | 2015-05-06 | 李德远 | Food with resistance to nitrogen tetroxide stress and preparation method of food |
-
2004
- 2004-05-28 CN CN 200480014986 patent/CN1798567A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103140223A (en) * | 2010-05-19 | 2013-06-05 | 布罗迪健康科学有限公司 | Use of jasmonates for treating heart failure and related cardiac disorders |
| CN102660383A (en) * | 2012-06-02 | 2012-09-12 | 哈尔滨工业大学 | Separation process of essential oil in toad maggots |
| CN104585750A (en) * | 2014-12-25 | 2015-05-06 | 李德远 | Food with resistance to nitrogen tetroxide stress and preparation method of food |
| CN104585750B (en) * | 2014-12-25 | 2016-06-01 | 李德远 | A kind of anti-nitrogen tetroxide stress food and preparation method |
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