CN102652019A - Oil or fat composition for prevention or treatment of depression or depressed conditions - Google Patents
Oil or fat composition for prevention or treatment of depression or depressed conditions Download PDFInfo
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- CN102652019A CN102652019A CN2010800394145A CN201080039414A CN102652019A CN 102652019 A CN102652019 A CN 102652019A CN 2010800394145 A CN2010800394145 A CN 2010800394145A CN 201080039414 A CN201080039414 A CN 201080039414A CN 102652019 A CN102652019 A CN 102652019A
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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
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
- A61K31/23—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms
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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
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
- A61K31/23—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms
- A61K31/231—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms having one or two double bonds
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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
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
- A61K31/23—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms
- A61K31/232—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms having three or more double bonds, e.g. etretinate
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- 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
- A61P25/24—Antidepressants
Abstract
Disclosed is an oil or fat composition characterized by containing a medium-chain fatty acid having 8 to 10 carbon atoms and a long-chain fatty acid having 12 to 24 carbon atoms both in the forms of triglycerides, wherein the content ratio of the long-chain fatty acid in the total amount of the medium-chain fatty acid and the long-chain fatty acid is 25 to 90 mass%. The composition is effective for the prevention or treatment of depression or depressed conditions, is highly safe, and causes no adverse side effect when ingested continuously.
Description
Technical field
The present invention relates to be used to prevent or treat the fat or oil composition of depression or depressive state; In detail, relate to the medium-chain fatty acid of triglyceride form and LCFA the fat or oil composition that is used to prevent or treat depression or depressive state as effective ingredient.
Background technology
Depression is a kind of affective disorders (mood disorder), is to be the mental sickness of characteristic with depressive emotion, uneasiness and impatience, ergasia reduction, appetite decline, insomnia etc.According to the statistics of Japanese police agency, baka person number surpassed 30,000 people in continuous 10 years in 2007, and its reason and motivation are depression mostly, therefore are badly in need of seeking its countermeasure.
Clinical proof antidepressant drug is effective to depression.Usually, antidepressant drug might not having immediate effect property, and curative effect also can't show definitely, therefore, must take continuously.But,, when therefore taking continuously, must consider the balance of drug effect and side effect because antidepressant drug has side effect.Therefore, even developing, expectation takes the antidepressant drug that also needn't worry side effect continuously.
Patent documentation 1: No. 2007/070701 pamphlet of International Publication
Summary of the invention
The present invention In view of the foregoing accomplishes, and it is safe that its purpose is to provide, even take the fat or oil composition that is used to prevent or treat depression or depressive state of also not worrying side effect continuously.
The inventor has carried out further investigation repeatedly in order to solve above-mentioned problem, finds to contain through the form with triglyceride the fat or oil composition of a certain proportion of medium-chain fatty acid and LCFA, can solve above-mentioned problem, thereby accomplish the present invention.
Up to now; Known MCT Oil can prevent and postpone to follow age growth by (with reference to patent documentations 1) such as the caused attention of cognitive disorder, concentration power reductions; But it does not effectively report more do not have the medium-chain fatty acid of triglyceride form and LCFA that depression is effectively reported to depression.
The present invention specifically provides following content.
(1) is used to prevent or treat the fat or oil composition of depression or depressive state; It is 8～10 the medium-chain fatty acid and the LCFA of carbon number 12～24 that its form with triglyceride contains carbon number; And; With respect to the total amount of above-mentioned medium-chain fatty acid and above-mentioned LCFA, the ratio of above-mentioned LCFA is 25～90 quality %.
(2) like above-mentioned (1) described fat or oil composition, above-mentioned medium-chain fatty acid is the satisfied fatty acid of carbon number 8 and/or 10, and above-mentioned LCFA is the satisfied fatty acid and/or the unsaturated fatty acid of carbon number 16～24.
(3) be used to prevent or treat above-mentioned (1) or (2) described fat or oil composition of stress induction depression of sex or depressive state.
Fat or oil composition of the present invention has its morbidity of inhibition, improves effect such as symptom depression or depressive state, therefore can be used for prevention or treatment depression or depressive state.And fat or oil composition of the present invention, the medium-chain fatty acid and the LCFA that contain the triglyceride form are as effective ingredient, and be therefore safe, do not worry side effect, so can relievedly take continuously.
Description of drawings
Figure 1 is a forced swim test immobility time measurement results (applied to forced swimming stress (force Shuiyong affiliates su su Suites Ritz load) while giving MLCT, LCT) Fig.
Fig. 2 is the sketch map of the timetable that chronic mild stress (chronic mild stress).
Fig. 3 is mensuration result's's (apply chronic mild stress time give MLCT, LCT) of dead time in the forced swimming test a sketch map.
Fig. 4 is the sketch map that gets into the number of times close arm (apply forced swimming stress then give MLCT simultaneously) in the overhead cross maze test.
Fig. 5 is the sketch map of result of study of the optimal dose of medium-chain fatty acid and LCFA.
Fig. 6 is mensuration result's's (apply chronic mild stress then give MLCT) of dead time in the outstanding tail test a sketch map.
Fig. 7 is the sketch map that gives the result of study of the caused cerebral hippocampal p44/42MAPK of MLCT activation capacity.
The specific embodiment
Following specific embodiments of the invention is elaborated, and the present invention does not receive any qualification of following embodiment, can in the object of the invention scope, suitably change.
The fat or oil composition that is used to prevent or treat depression or depressive state of the present invention; It is characterized in that: containing carbon number with the form of triglyceride is that 8～10 medium-chain fatty acid and carbon number are 12～24 LCFA; With respect to the total amount of above-mentioned medium-chain fatty acid and above-mentioned LCFA, the ratio of above-mentioned LCFA is 25～90 quality %.
Fat or oil composition of the present invention is used for prevention or treatment depression or depressive state.Should explain that depression is meant among the present invention, the depression that the doctor diagnoses out according to the diagnostic criteria of the mental disorder diagnostic & statistical manual (DSM) that for example American Psychiatric Association formulated.And; Depressive state among the present invention is meant, the state that is for example caused by disease symptomses such as the variation of mental pressure, season body interior such as the rhythm and pace of moving things or biorhythm, dysautonomia panic disorder etc., show as enthusiasm reduction, contemplative faculty reduction, concentration power reduction, energy reduction, taediumvitae, powerlessness, feeling of unreality, symptom such as forgetful.And the prevention among the present invention is meant, for example, inhibition, delayed onset etc., treatment is meant, for example, postpones that sb.'s illness took a turn for the worse, alleviates, alleviates, improves, cures symptom etc.
Fat or oil composition of the present invention is characterised in that, containing carbon number with the form of triglyceride is that 8～10 medium-chain fatty acid and carbon number are 12～24 LCFA.As containing form, can enumerate: only contain with above-mentioned medium-chain fatty acid as the triglyceride (hereinafter to be referred as MCT) of structural fatty acid with only with above-mentioned LCFA as both forms of triglyceride (hereinafter to be referred as LCT) of structural fatty acid, contain with above-mentioned medium-chain fatty acid and above-mentioned LCFA as the form of the sour triglyceride (hereinafter to be referred as MLCT) of structural fatty, contain MCT and LCT and MLCT form, contain the form of MCT and MLCT and contain LCT and the form of MLCT.Should explain; Among the present invention; To contain medium-chain fatty acid and LCFA and be referred to as middle chain fatty acid triglycerides (hereinafter to be referred as MLCT), and distinguish and in the triglyceride of 1 molecule, mix the MLCT that contains medium-chain fatty acid and LCFA as the material of whole triglyceride.Meaning of the present invention is to have found first; Do not demonstrate prevention or therapeutic effect to depression or depressive state though only contain the fat or oil composition of LCT, the fat or oil composition that contains MLCT (wherein the proportion of LCT is high) has demonstrated prevention or therapeutic effect to depression or depressive state.
Medium-chain fatty acid among the present invention is the fatty acid of carbon number 8～10.From easy acquisition, cheap viewpoint, preferred carbon number is that the promptly sad or carbon number of 8 satisfied fatty acid is that 10 satisfied fatty acid is a capric acid.In addition; LCFA is that carbon number is 12～24 fatty acid; For example can enumerate chain saturated fatty acids such as dodecylic acid, tetradecanoic acid, hexadecanoic acid, octadecanoid acid, arachic acid, behenic acid, lignoceric acid, myristoleic acid, pentadecylenic acid, palmitoleic acid, oleic acid, linoleic acid, linolenic acid, gamma-Linolenic acid, arachidonic acid, eicosapentaenoic acid long-chain unsaturated fatty acids such as (icosapentaenoic acid).In the fat or oil composition of the present invention; Preferably; Medium-chain fatty acid is that carbon number is 8 and/or 10 satisfied fatty acid, and above-mentioned LCFA is that carbon number is 16～24 satisfied fatty acid and/or unsaturated fatty acid, more preferably; Medium-chain fatty acid is that carbon number is 8 and/or 10 satisfied fatty acid, and above-mentioned LCFA is that carbon number is 16～24 satisfied fatty acid and/or unsaturated fatty acid.
Fat or oil composition of the present invention contains above-mentioned medium-chain fatty acid and above-mentioned LCFA with the form of triglyceride; This triglyceride can be with same acid glycerol three esters of fatty acid of the same race as structural fatty acid, also can be with the nitration mixture triglyceride of fatty acid not of the same race as structural fatty acid.When using the nitration mixture triglyceride, the position that combines with the glycerol of each fatty acid is not special to be limited.
The manufacturing approach of triglyceride is not special to be limited, and can use known method.For example; With carbon number is that 8 medium-chain fatty acid and carbon number are 10 the medium-chain fatty acid MCT as structural fatty acid, can be that 8 medium-chain fatty acid and carbon number are that 10 medium-chain fatty acid and glycerol carry out esterification and gets through the carbon number from Oleum Cocois or palm-kernel oil.The method of esterification is not special to be limited; For example can be set forth in the method for not using catalyst and solvent to make it to react under the pressurized conditions, chemical ester-interchange method that synthetic catalysts such as use Feldalat NM make it to react and the enzyme ester-interchange method that uses lipase to make it to react as catalyst.For example, can with the raw oil material intensive drying, behind the catalyst to raw oil material interpolation 0.1～1 quality %, under reduced pressure, stir 0.5～1 hour down, make it that chemical ester exchange reaction takes place thus according to common method at 80～120 ℃.After ester exchange reaction is accomplished, water flushing catalyst, decolouring, the deodorization carrying out then being carried out in the general edible oil refining step are handled and are got final product.For example, can stir 0.5～48 hour down at 40～80 ℃, make it that enzyme ester exchange reaction take place through after raw oil material is added the lipase powder or immobilized-lipase of 0.02～10 quality %.Ester exchange reaction is removed lipase powder or immobilized-lipase through operations such as filtrations after accomplishing, and decolouring, the deodorization carrying out then being carried out in the general edible oil refining step are handled and got final product.Should explain that ester exchange reaction can be the location specific ester exchange reaction, also can be at random ester exchange reaction also can, not special the qualification.
Should explain, LCT can from the oil expression raw material through squeeze and the refining soybean oil that obtains, rapeseed oil, Semen Maydis oil, Testa oryzae oil, Oleum sesami, Oleum Gossypii semen, Oleum Helianthi, safflower oil, Semen Lini oil, perilla oil, Fructus Canarii albi wet goods obtain.And, also can obtain through the ester exchange reaction more than 2 kinds of above-mentioned LCT.MLCT can obtain through three kinds of methods, that is: the ester exchange reaction of above-mentioned medium-chain fatty acid and above-mentioned LCFA and the esterification of glycerol, above-mentioned MCT and above-mentioned LCT and above-mentioned MCT and above-mentioned LCT's mixes.
In the fat or oil composition of the present invention; Total amount with respect to above-mentioned medium-chain fatty acid and above-mentioned LCFA; The necessary ratio of above-mentioned LCFA is 25～90 quality %, is preferably 27～90 quality %, more preferably 29～90 quality %; Further be preferably 80～90 quality %, most preferably be 85～88 quality %.If the ratio of LCFA in above-mentioned scope, then can suppress the morbidity of depression or depressive state (hereinafter to be referred as depressive state etc.), improve its symptom etc.Should explain; As confirming that LCFA accounts for the method for ratio of the total amount of medium-chain fatty acid that the form with triglyceride contains and LCFA; For example can enumerate the medium-chain fatty acid that constitutes triglyceride and LCFA carried out methyl-esterified after, the method for analyzing through gas chromatography again.
Constitute the method for ratio of medium-chain fatty acid and the LCFA of triglyceride as adjustment; After the LCT of the triglyceride that for example can enumerate the MCT of the triglyceride that manufacturing is made up of medium-chain fatty acid and constitute by LCFA, carry out method of mixing according to the ratio of expectation; Prepare in advance after the medium-chain fatty acid and LCFA of desired proportion, glycerol is carried out esterification method with them; Prepare the LCT of the triglyceride that constitutes by LCFA of MCT and desired proportion of the triglyceride that constitutes by medium-chain fatty acid of desired proportion in advance, their are mixed making their that the method etc. of ester exchange reaction take place.
In the scope of not damaging effect of the present invention, for further improving storage stability and the property handled, fat or oil composition of the present invention can add known emulsifying agent, antioxidant, pigment, spice etc.Specifically can enumerate polyglyceryl fatty acid ester, sucrose fatty acid ester, sorbitan fatty ester, polysorbate, vitamin E, ascorbic acid aliphatic ester, lignan, coenzyme Q10, ferulic acid ester, diglyceride, polysiloxanes, tocopherol, lecithin, phytosterol, phytosterol ester etc.
Fat or oil composition of the present invention to suffer from depression or be depressive state to comprise the people effective interior animal.Especially the effect that the depressive state that stress cause etc. is had prevention or treatment.The triglyceride that is contained in the fat or oil composition of the present invention and be widespread in nature as the medium-chain fatty acid and the LCFA of its structural fatty acid in edible natural thing, also contain, so its safety is very high.Therefore, fat or oil composition of the present invention for example is suitable as medicine (contain animal use), food, feedstuff etc.
When fat or oil composition of the present invention is used as medicine, the administering mode preferred oral.This is owing to the mucosa of triglyceride major part via intestinal (small intestinal) absorbed in the body.As being suitable for oral preparation, for example can enumerate capsule, tablet, pill, powder, granula subtilis, granule, liquid agent, syrup etc.Preferably comprise the preparation of formation as the composite medicine form of permissible additive on the medium-chain fatty acid of the triglyceride of effective ingredient and LCFA and the pharmacology and in the pharmacy.As on the pharmacology with pharmacy on permissible additive; For example can enumerate the excipient, disintegrating agent, binding agent, coating materials, pigment, diluent of glucose, lactose, crystalline cellulose, starch etc. etc., can use commonly used and material that can not react with oils and fats of the present invention in pharmaceutical field usually.
Fat or oil composition safety of the present invention is very high; And can not have side effect as the medicine of existing prevention or treatment depression, therefore, can be through using with existing drug regimen; Reduce this existing amount of drug, reducing should existing side effects of pharmaceutical drugs.When using, can be included in the same composite medicine, also can be included in respectively in the different composite medicines as combination drug with the other drug combination.
The dosage of fat or oil composition of the present invention can suitably be selected according to each conditions such as patient's symptom, prevention or treatment, age, body weight, medication, administration times.For example, in that when be purpose, effective dose is generally 230～1230mg/kg/ day with treatment people (adult 60kg), this dose once or divide several to take to get final product.
Can be processed in the soft capsule through fat or oil composition of the present invention is filled, take as the nutrition supplementary food.In addition, fat or oil composition of the present invention directly absorbs after can maintaining the original state or be processed into powdered oil, aqueous emulsified fat etc., and it is edible indirectly through processing perhaps can further to use it for normal food.
As the normal food that can use fat or oil composition of the present invention,, do not have special qualification so long as use greasy processed food to get final product; For example can enumerate bread snack categories such as bread, cake, cooky are done, cookies, cake, chocolate, soft sweet, whipped cream, ice cream, beverage classes such as fruit drink, energy drink, sports drink, soup class; Seasonings such as sauce, mayonnaise, margarine processed food; Cooking is with oil, frying oil, various instant food; Supping is swallowed food etc.
[embodiment]
Below, through embodiment the present invention is described in more details, but the present invention does not receive any qualification of these embodiment.
< make the manufacturing approach of example 1>test food 1
Add the MLCT (trade name: ヘ Le シ one リ セ Star タ of 7 mass parts; Day, clear オ イ リ オ グ Le one プ (strain) made; Total amount with respect to medium-chain fatty acid and LCFA; The ratio of LCFA: 87%, fatty acid contain form: MLCT+MCT+LCT) as the lubricant component in the feedstuff, obtain containing the test food 1 of 7 quality %MLCT thus.Feedstuff is formed as shown in table 1.
< make the manufacturing approach of example 2>test food 2
The LCT (trade name: day clear キ ヤ ノ one ラ oil, day clear オ イ リ オ グ Le one プ (strain) system) that adds 7 mass parts as the lubricant component in the feedstuff, obtains containing the test food 2 of 7 quality %LCT thus.The composition of feedstuff is as shown in table 1.
< make the manufacturing approach of example 3>test food 3
Add the MCT (trade name: ODO of 1 mass parts respectively; Day clear オ イ リ オ グ Le one プ (strain) system) (trade name: day clear キ ヤ ノ one ラ is oily with the LCT of 6 mass parts; Day clear オ イ リ オ グ Le one プ (strain) system), contained the test food 3 of LCT of MCT and the 6 quality % of 1 quality % thus respectively as the lubricant component in the feedstuff.The composition of feedstuff is as shown in table 1.Should explain that with respect to the medium-chain fatty acid in this test food 3 and the total amount of LCFA, the ratio of LCFA is 86%.
< make the manufacturing approach of example 4>test food 4
Add the MCT (trade name: ODO of 5 mass parts respectively; Day clear オ イ リ オ グ Le one プ (strain) system) (trade name: day clear キ ヤ ノ one ラ is oily with the LCT of 2 mass parts; Day clear オ イ リ オ グ Le one プ (strain) system), contained the test food 4 of LCT of MCT and the 2 quality % of 5 quality % thus respectively as the lubricant component in the feedstuff.The composition of feedstuff is as shown in table 1.Should explain that with respect to the medium-chain fatty acid in this test food 4 and the total amount of LCFA, the ratio of LCFA is 29%.
[table 1]
< Test Example 1>is to the research (1) of the preventive effect of depressive state
To mice apply force swimming stress the time, make its edible feedstuff that contains MLCT, study the preventive effect of fat or oil composition of the present invention to depression or depressive state.
[forced swimming stress test]
Method (Eur.J.Pharmacol., 47,379-391 (1978)) according to people such as Porsolt R.D. exploitation is carried out forced swimming test (FST:Forced Swim Test).This test is by a kind of test of often using in the animal model experiment of depression.In this test, force to make animal such as mice in the space that can not escape, to be swum, make it be in motionless state again.That is, for from this environment, escaping the mice of the swimming of risking one's life,, progress into motionless state during beginning because of the pressure that can't run away is absorbed in helplessness.This motionless state can be regarded a kind of desperate state of abandoning the escape behavior as, and is similar with the mankind's depression.And, in fact, there is report to point out, most antidepressant drugs can shorten the time (hereinafter to be referred as the dead time) of the motionless state that causes because of forced swimming.Dead time when this means forced swimming is the index of the degree of depressive state.Dead time when therefore, this test is forced swimming is as the index of estimating preventive effect.
It is male mice (Japanese SLC, body weight 28～30g) that the ddY in 6 ages in week is adopted in this test.Mice is put into rearging cage, is to carry out in the cycle raising in the receptacle of light and shade conversion in 22 ± 4 ℃ of room temperatures, relative humidity 55 ± 15%, with 12 hours.Let its free drinkable water and feedstuff.Test is divided into two groups to be carried out, that is, and and edible " test food 1 picked-up group (embodiment 1) " and edible " the test food 2 picked-up groups (comparative example 1) " that contain the feedstuff of LCT that contain the feedstuff of MLCT.With the equal mode of average weight of every group of mice before the experiment beginning, divide into groups.Should explain that every group has 11 mices in the test, apply stress in let mice eat feedstuff.
Applying forced swimming according to following method stress.That is, to the polyethylene beaker (poly beaker) of 5L (internal diameter: 27cm, highly: inject 27cm) 18cm high (total amount of water: water 4L) (24～26 ℃), let mice swim every day therein 1 time, each 6 minutes, carried out continuously 14 days.Then, the 1st day of on-test, the 7th day and the 14th day of on-test of on-test, be determined at the time that is regarded as dead time (second) in 4 minutes remaining in the above-mentioned 6 minutes pressure swimming time with stopwatch.Should explain that mice is judged as the dead time at the floating and immobilized state of the water surface.Then, obtain the meansigma methods of each dead time, calculate the meansigma methods of dead time of the 1st day of on-test relative value (%) as 100 o'clock.
Should explain, measure the result and represent with the above-mentioned relative value ± standard error of each group.Significant difference between each group is passed through student ' st-check and is measured (significance level: 5%).
The result is as shown in Figure 1.The relative value of dead time is high more in this test, representes that its depressive state is strong more.The relative value of the dead time of the picked-up group (embodiment 1) of the edible test food 1 that contains the MLCT feedstuff compares with the picked-up group (comparative example 1) of the test food that contains the LCT feedstuff 2, and the significance reduction is arranged.
< Test Example 2>is to the research (2) of the preventive effect of depressive state
Through apply chronic mild stress the time make the edible feedstuff that contains MLCT of mice, study the preventive effect of fat or oil composition of the present invention to depression or depressive state.Should explain that the dead time in this test during with forced swimming is as the index of estimating preventive effect.
[chronic mild stress test]
It is male mice (Japanese SLC, body weight 28～30g) that the ddY in 6 ages in week is adopted in this test.Mice is put into rearging cage, is to carry out in the cycle raising in the receptacle of light and shade conversion in 22 ± 4 ℃ of room temperatures, relative humidity 55 ± 15%, with 12 hours.Make its free drinkable water and feedstuff.Test is divided into four groups and carries out, that is, apply stress the time make " apply stress test food 1 picked-up group (embodiment 2) " of the edible feedstuff that contains MLCT of mice; Apply stress the time make " apply stress test food 2 picked-up groups (comparative example 2) " of the edible feedstuff that contains LCT of mice; Do not apply " do not apply stress test food 1 picked-up group (reference example 1) " that stress make the edible feedstuff that contains MLCT of mice; And do not apply " do not apply stress test food 2 picked-up groups (reference example 2) " that stress make the edible feedstuff that contains LCT of mice.Mode so that the average weight of every group of mice before on-test is equal is divided into groups.Should explain that 5 every group make an experiment, apply stress in make mice eat feedstuff.
Stress according to applying chronic mild by following method.At first, at 15 minutes the forced swimming of carrying out in the 1st day of on-test.In the forced swimming, (internal diameter: 27cm, highly: injecting 18cm 27cm), high (total amount of water: water 4L) (24～26 ℃) lets mice forced swimming 15 minutes therein to the polyethylene beaker of 5L.Afterwards, in common cage, raise and let its rest in 1 day.Then, raised 2 days at (inclination angle: 20 °) in the cage that tilts, and in common cage, raises afterwards to let its rest in 1 day.Next, in the cage that dirt is arranged of the water-soaked of 200mL, raised 1 day, in common cage, raise afterwards and let its rest on the 1st.At last, be to raise mice 1 day in the rotation cage of 180rpm at rotating speed, in common cage, raise afterwards and let its rest in 1 day.Stress carry out 3 test units (3 week) altogether as 1 test unit with what use that these 3 kinds of cages apply 1 week by a definite date.Schedule is as shown in Figure 2.
Then, in order to estimate preventive effect, mice is carried out forced swimming test the 24th day of on-test.Should explain that forced swimming test carries out according to method same as described above.Promptly; To the polyethylene beaker of 5L (internal diameter: 27cm, highly: injecting 18cm 27cm), high (total amount of water: water 4L) (24～26 ℃) lets mice forced swimming 6 minutes therein; Be determined at the time that is regarded as dead time (second) in remaining 4 minutes with stopwatch, obtain meansigma methods.As 100, calculate the relative value (%) of " apply stress test food 1 picked-up group (embodiment 2) " of the edible feedstuff that contains MLCT with the meansigma methods of dead time of " do not apply stress test food 1 picked-up group (reference example 1) " of the edible feedstuff that contains MLCT; As 100, calculate the relative value (%) of " apply stress test food 2 picked-up groups (comparative example 2) " of the edible feedstuff that contains LCT with the meansigma methods of dead time of " do not apply stress test food 2 picked-up groups (reference example 2) " of the edible feedstuff that contains LCT.
Should explain, measure the result and represent with the above-mentioned relative value ± standard error of each group.Significant difference between each group is passed through student ' s t-check and is measured (significance level: 5%).
The result is as shown in Figure 3.The relative value of dead time is high more in this test, representes that its depressive state is strong more.The 24th day of on-test, the relative value of the dead time of the test food 1 picked-up group (embodiment 2) of the edible feedstuff that contains MLCT compares with the edible feeding experiment food 2 picked-up groups (comparative example 2) that contain LCT, and the significance reduction is arranged.This result shows that edible MLCT not only produces effect to the depressive state that chronic stress caused that is caused by above-mentioned successive forced swimming test, also the depressive state that chronic stress caused that is caused by other tests is produced effect.
< Test Example 3>is to the research (3) of the preventive effect of depressive state
Through apply forced swimming stress the time, make the edible feedstuff that contains MLCT of mice, study the preventive effect of fat or oil composition of the present invention to depression or depressive state.Should explain; Dead time when this research is not adopted forced swimming is as evaluation index; But get into mice in the overhead cross maze test close arm number of times as the index of estimating preventive effect, thereby whether the shortening of confirming the caused dead time of fat or oil composition of the present invention in above-mentioned research (1) and (2) is caused by the increase of activity.
[forced swimming test]
It is male mice (Japanese SLC, body weight 28～30g) that the ddY in 6 ages in week is adopted in this test.Mice is put into rearging cage, is to carry out in the cycle raising in the receptacle of light and shade conversion in 22 ± 4 ℃ of room temperatures, relative humidity 55 ± 15%, with 12 hours.Let its free drinkable water and feedstuff.Test is divided into 3 groups, that is, and and edible " the test food 1 picked-up group (embodiment 3) " that contains the feedstuff of MLCT; Edible " the test food 2 picked-up groups (comparative example 3) " that contain the feedstuff of LCT; " common food picked-up group (reference example 3) " of edible commercially available feedstuff (trade name: ラ ボ MR ス ト Star Network, Japanese agriculture industry (strain) system).Mode so that the average weight of respectively organizing mice before on-test equates is divided into groups.Should explain that " test food 1 picked-up group (embodiment 3) " and " test food 2 picked-up groups (comparative example 3) " has 15 mices, " common food picked-up group (reference example 3) " this group has 25 mices, apply stress in let mice eat feedstuff.
Same as described above, according to carrying out forced swimming test by the method for exploitations such as Porsolt R.D..That is, to the polyethylene beaker of 5L (internal diameter: 27cm, highly: inject 27cm) 18cm high (total amount of water: water 4L) (24～26 ℃), let mice swim every day therein 1 time, each 6 minutes, carried out continuously 14 days.
[overhead cross maze test]
Then, the 15th day of on-test mice is carried out overhead cross maze test.Overhead cross maze test carries out according to the method (J.Nutr., 123 (11), 1923-1931 (1993)) of exploitations such as Reeves P.G.This test be in the screening method of antianxiety drugs a kind of test method of often using.It is uneasy that mice can be felt in bright environment, therefore can avoid bright road.But simultaneously mice can produce and want the ambivalence explored.Therefore, explore the strong mice of desire, it explores action can increase, and is holding arm and closing the number of times of walking up and down between the arm and can increase as dark road as bright road.This research is with the index that to get into this number of times that closes arm be activity, and number of times is many more, just thinks that its activity is high more.
Should explain that overhead cross maze test is undertaken by following method.Adopt the overhead cross labyrinth experiment device of brachium 66cm, wide 6cm, high 62cm; Mice is placed on head that lost central part (opening the arm and the portion of reporting to the leadship after accomplishing a task that closes arm) makes mice towards the direction of closing arm; The number of times that arm is closed in its entering is measured in the action of observation mice 5 minutes, tries to achieve meansigma methods.
Should explain, measure the result and represent with the mean+/-standard error of the above-mentioned entering number of times of each group.Significant difference between group adopts the one factor analysis of variance method, examines and determine as significance level with 5%.
The result is as shown in Figure 4.There is not the situation of the activity increase that is caused by MLCT in there was no significant difference between the activity of the test food 1 picked-up group (embodiment 3) of the edible feedstuff that contains MLCT and the activity of common food picked-up group (reference example 3).Therefore can know that the shortening of the dead time that MLCT causes is not that the increase by activity causes.
< Test Example 4>is to the research (4) of the preventive effect of depressive state
Through apply forced swimming stress the time, let mice is edible to contain the medium-chain fatty acid of different use levels and the feedstuff of LCFA, studying has the medium-chain fatty acid of preventive effect and the optimal dose of LCFA to depression or depressive state.In addition, through letting the edible feedstuff that contains MLCT that has cooperated the feedstuff that contains MLCT of MCT and LCT and cooperated MLCT, MCT and LCT of mice, study the picked-up form that depression or depressive state is had the triglyceride of preventive effect.Should explain that the dead time of this test during with forced swimming is as the index of estimating preventive effect.
[forced swimming test]
It is male mice (Japanese SLC, body weight 28～30g) that the ddY in 6 ages in week is adopted in this test.Mice is put into rearging cage, is to carry out in the cycle raising in the receptacle of light and shade conversion in 22 ± 4 ℃ of room temperatures, relative humidity 55 ± 15%, with 12 hours.Let its free drinkable water and feedstuff.Test is divided into 4 groups, that is, and and edible " the test food 1 picked-up group (embodiment 4) " that contain the MLCT feedstuff that has cooperated MLCT, MCT and LCT; Edible " the test food 2 picked-up groups (comparative example 4) " that contain the LCT feedstuff; Edible " the test food 3 picked-up groups (embodiment 5) " that contain the MLCT feedstuff that cooperated MCT (5 quality %) and LCT (2 quality %); Edible " the test food 4 picked-up groups (embodiment 6) " that contain the MLCT feedstuff that cooperated MCT (1 quality %) and LCT (6 quality %).Mode so that the average weight of every group of mice before on-test is equal is divided into groups.Should explain that 5 every group make an experiment, to mice apply stress the time let mice eat feedstuff.
Same as described above, according to carrying out forced swimming test by the method (Eur.J.Pharmacol., 47,379-391 (1978)) of exploitations such as Porsolt R.D..That is, to the polyethylene beaker of 5L (internal diameter: 27cm, highly: inject 27cm) 18cm high (total amount of water: water 4L) (24～26 ℃), let mice swim every day therein 1 time, each 6 minutes, carried out continuously 20 days.In the 1st day and the 20th day on-test of on-test, be determined at above-mentioned 6 minutes forced swimming is regarded as dead time (second) in remaining 4 minutes in the time time with stopwatch, obtain meansigma methods.Then, obtain the meansigma methods of each dead time, as 100, calculate relative value (%) with the meansigma methods of dead time of the 1st day of on-test.
Should explain, measure the result and represent with the above-mentioned relative value ± standard error of each group.Significant difference between group adopts the one factor analysis of variance method, is that significance level is examined and determine with 5%.
The result is as shown in Figure 5.Edible test food 1 picked-up group (embodiment 4) and the relative value of the dead time that eats the test food that the contains the MLCT feedstuff 4 picked-up groups (embodiment 6) that cooperated MCT (1 quality %) and LCT (6 quality %) who has cooperated the feedstuff that contains MLCT of MLCT, MCT and LCT; Compare with the edible test food 2 picked-up groups (comparative example 4) that contain the LCT feedstuff, have significance to reduce.Eat the relative value of the dead time of the test food that the contains the MLCT feedstuff 3 picked-up groups (embodiment 5) that cooperated MCT (5 quality %) and LCT (2 quality %); Compare with the edible test food 2 picked-up groups (comparative example 4) that contain the LCT feedstuff; Though there was no significant difference has the tendency of reduction.This is because the difference of meansigma methods is big between each group, if increase some sample numbers more a little, just can have significant difference.
In addition; Although the dead time of the edible test food 2 picked-up groups (comparative example 4) that contain the LCT feedstuff is elongated; But the edible test food that the contains the MLCT feedstuff 3 picked-up groups (embodiment 5) that cooperated MCT (5 quality %) and LCT (2 quality %); Compare with the test food that the contains the MLCT feedstuff 4 picked-up groups (embodiment 6) that cooperated MCT (1 quality %) and LCT (6 quality %), contain the tendency that there is the dead time shortening in the more test food of LCT 4 picked-up groups (embodiment 6).The LCFA that this results suggest constitutes triglyceride has optimal dose (Fig. 5).
And; The edible test food that the contains the MLCT feedstuff 1 picked-up group (embodiment 4) that has cooperated MLCT, MCT and LCT, cooperated between the test food that the contains the MLCT feedstuff 4 picked-up groups (embodiment 6) of MCT (1 quality %) and LCT (6 quality %) with eating; Its dead time does not have significant difference; Therefore can know that the picked-up form of triglyceride is to the not influence (Fig. 5) of preventive effect of depressive state.
< Test Example 5>is to the research (1) of the therapeutic effect of depressive state
Through apply chronic mild stress after, let the edible feedstuff that contains MLCT of mice, study the therapeutic effect of fat or oil composition of the present invention to depression or depressive state.
[chronic mild stress stress test]
It is male mice (Japanese SLC, body weight 28～30g) that the ddY in 6 ages in week is adopted in test.Mice is put into rearging cage, is to carry out in the cycle raising in the receptacle of light and shade conversion in 22 ± 4 ℃ of room temperatures, relative humidity 55 ± 15%, with 12 hours.Let its free drinkable water and feedstuff.Carrying out in initial 24 days of chronic mild stress test, letting the edible commercially available feedstuff of mice (trade name: ラ ボ MR ス ト Star Network, Japanese agricultural production industry (strain) system) as common food.After above-mentioned test is accomplished, let mice eat test food 16 days.Test is divided into four groups, that is, applying and stress eat " the test food 1 picked-up group (embodiment 7) " that contains the MLCT feedstuff by the relief mice; Applying and to eat " the test food 2 picked-up groups (comparative example 5) " that contain the LCT feedstuff by the relief mice; Apply stress the relief mice " common food picked-up group (reference example 4) " of edible commercially available feedstuff; Do not apply and to let mice eat " common food picked-up group (reference example 5) " of commercially available feedstuff.Divide into groups with the equal mode of the average weight of respectively organizing mice before the experiment beginning.Should explain that 5 every group make an experiment.
Applying chronic mild according to following method stress.At first, in on-test the 1st day lets mice carry out 15 minutes forced swimming.In the forced swimming, (internal diameter: 27cm, highly: injecting 18cm 27cm), high (total amount of water: water 4L) (24～26 ℃) lets mice forced swimming 15 minutes therein to the polyethylene beaker of 5L.Afterwards, in common cage, raise mice and let its rest in 1 day.Then, raised 2 days at (inclination angle: 20 °) in the cage that tilts, and in common cage, raises afterwards to let its rest in 1 day.Then, in the cage that dirt is arranged of the water-soaked of 200mL, raised 1 day, in common cage, raise afterwards and let its rest on the 1st.At last, be to raise mice 1 day in the rotation cage of 180rpm at rotating speed, in common cage, raise afterwards and let its rest on the 1st.Stress carry out 3 test units (3 week) altogether as 1 test unit with what use that these 3 kinds of cages apply 1 week by a definite date.
[outstanding tail test]
Then, be evaluating efficacy, apply chronic mild stress after, begin in edible test food the 0th day, the 9th day and the 16th day, mice hang tail tests.Outstanding tail test is the same with above-mentioned forced swimming test, is a kind of method of often being used in the animal model experiment of depression, hangs upside down through the tail of fixing mice and with it, apply unavoidable stress, cause motionless state.Dead time when therefore, this research is outstanding tail hanging is as the index of estimating the MLCT effect.Should explain that outstanding tail test is undertaken by following method.At first, use laboratory table, use wrench that metal hold-down bars is fixed on height parallel to the ground place as 35cm.Then, make dividing plate, make mice can't see the state that the other side hangs upside down each other, hang the clip of mousetail (under the mountain skill development) tail of mice is fixed, make its hanging 6 minutes with being fixed on being used on the hold-down bars with paper.Be determined at the time that is regarded as dead time (second) in these 6 minutes with stopwatch, promptly mice keeps the quiescent time of suspended state, obtains meansigma methods.
Should explain, measure the result and represent with each mean+/-standard error of organizing the above-mentioned dead time.Significant difference between group adopts the one factor analysis of variance method, is that significance level is examined and determine with 5%.
The result is as shown in Figure 6.At the 9th day that ingests, applying between stress the back edible test food 1 picked-up group (embodiment 7) that contain the MLCT feedstuff and the common food picked-up group (reference example 5) did not have significant difference, has the tendency of approaching no stress state.This results suggest, edible MLCT can alleviate or improve depressive state of having fallen ill etc.
More than the prevention of depressive state or the result of the test of therapeutic effect are shown fat or oil composition of the present invention demonstrates excellent ground antidepressant effect in animal experiment, therefore to the prevention of depression or depressive state or treat useful.
< Test Example 6>is to the research of the cerebral hippocampal p44/42MAPK activation capacity of MLCT
In recent years, there is report to point out that the BDNF of the serum of untreated patients with depression (BDNF) is than lack (Huang T.L.et al., J.Psychiatr.Res., 42 (7), the 521-525 (2008)) of healthy subjects.In addition, the phosphorylation level of the p44/42 MAPK (MAPK) in depressive symptom and the mice Hippocampus is negative correlation (Behavioural Brain Research, 175,233-240 (2006)).MAPK is had activity as signal pipeline in the main cell of BDNF (intracellular signaling pathway) after the phosphorylation.The phosphorylation level of its prompting MAPK is an antidepressant index.Therefore, give the phosphorylation level of cerebral hippocampal p44/42MAPK in the mice of MLCT through mensuration, confirm that MLCT has antidepressant effect.
< making example 5>test is with the manufacturing approach of emulsion 1
Under 65 ℃ heated condition, after emulsifiers dissolve is in normal saline, mix with ultrasound wave, obtain test with emulsion 1.
< making example 6>test is with the manufacturing approach of emulsion 2
Under 65 ℃ heated condition, after emulsifiers dissolve is in normal saline, mix with ultrasound wave; Cooperate therein 1.2 quality % MLCT (trade name: ヘ Le シ one リ セ Star タ, day clear オ イ リ オ グ Le one プ (strain) system is with respect to the total amount of medium-chain fatty acid and LCFA; The ratio of LCFA: 87%; Fatty acid contain form: MLCT+MCT+LCT), further use ultrasonic emulsification, obtain test with emulsion 2.
< making example 7>test is with the manufacturing approach of emulsion 3
Under 65 ℃ heated condition, after emulsifiers dissolve is in normal saline, mix with ultrasound wave; Cooperate therein 6 quality % MLCT (trade name: ヘ Le シ one リ セ Star タ, day clear オ イ リ オ グ Le one プ (strain) system is with respect to the total amount of medium-chain fatty acid and LCFA; The ratio of LCFA: 87%; Fatty acid contain form: MLCT+MCT+LCT), further use ultrasonic emulsification, obtain test with emulsion 3.
< making example 8>test is with the manufacturing approach of emulsion 4
Under 65 ℃ heated condition, after emulsifiers dissolve is in normal saline, mix with ultrasound wave; LCT (the trade name: day clear キ ヤ ノ one ラ oil that cooperates 1.2 quality % therein; Day, clear オ イ リ オ グ Le one プ (strain) made), further use ultrasonic emulsification, obtain test with emulsion 4.
< making example 9>test is with the manufacturing approach of emulsion 5
Under 65 ℃ heated condition, after emulsifiers dissolve is in normal saline, mix with ultrasound wave; LCT (the trade name: day clear キ ヤ ノ one ラ oil that cooperates 6 quality % therein; Day, clear オ イ リ オ グ Le one プ (strain) made), further use ultrasonic emulsification, obtain test with emulsion 5.
It is male mice (Japanese SLC, body weight 31～33g) that the ddY in 7 ages in week is adopted in this test.Mode so that the average weight of every group of mice is equal is divided into groups.Should explain that 3 every group make an experiment.Give the oral test of making through said method of mice with emulsion 1～5, broken end is handled and is taken out cerebral hippocampal after 3 hours.Measure the phosphorylation level of the p44/42MAPK of cerebral hippocampal through Western blotting (western blotting method).The ホ ラ イ ズ Block ロ Star ト that trace appearance (blotting device) adopts the ATTO manufactured measures under electric current 2mA/cm2, voltage 100V, 60 minutes condition of electrophoresis time.In the RIPA of 19 times of amounts buffer, cerebral hippocampal is carried out homogenize with homogenizer.With 16.1k * g homogenate is carried out 10 minutes centrifugalize, get supernatant.Use above-mentioned supernatant, in 10% PAAG, carry out electrophoresis (SDS-PAGE).After being transferred on the nitrocellulose filter, in confining liquid (TBS that contains 5% skim milk), soaking and changeed film (translocation is write メ Application Block ラ Application) 1 hour.Afterwards, under 4 ℃, hatch diel with anti-rabbit p44/42MAPK antibody (Cell Signaling society system) or phospho-p44/42MAPK antibody (manufacturing of Cell Signaling society).Then, wash film 3 times with the TBS (TBS-T) that contains 0.1%Tween20, the goat anti-rabbit igg antibody of reuse alkali phosphatase enzyme mark was hatched 1 hour, after the TBS-T washing, in BCIP-NBT solution (Dig3 buffer), made its colour developing, detected p44/42MAPK albumen.Should explain; The protein content of each sample solution is measured through having used dihomocinchonine acid (bicinchoninic acid) test kit (BCA); At the 2 mercapto ethanol of the electrophoresis that contains 4 times of concentration of adding 1/3 amount in the proteinic extracting solution of 5 μ g with sample buffer and 1/10 amount; After 95 ℃ heating was handled in 5 minutes down, carry out electrophoresis.
Then, behind the shade with the resulting protein band of scanner (ES-2200, EPSON society system) scanning colour developing; With image analysis software (Image J, Wayne Rasband, NIH (NIH) exploitation; Http:// rsb.info.nih.gov/ij/) handles, obtain numerical value.Then, obtain the phosphorylation/unphosphorylated numerical value of test respectively, obtain the meansigma methods of test again with the phosphorylation/non-phosphorylating numerical value of the administration group of emulsion 1 with each administration group of emulsion 1～5.Then, with above-mentioned test with the meansigma methods of the phosphorylation/non-phosphorylating numerical value of the administration group of emulsion 1 as 100, calculate the relative value (%) of above-mentioned test with the phosphorylation/non-phosphorylating numerical value of each administration group of emulsion 1～5, obtain the meansigma methods of administration group.With these relative value's meansigma methods phosphorylation level, compare as the p44/42MAPK of each administration group.
[statistical disposition]
Measuring the result representes with the above-mentioned relative value ± standard error of each group.Significant difference between group adopts the one factor analysis of variance method, is that significance level is examined and determine with 5%.
The result is as shown in Figure 7.The phosphorylation level of the p42MAPK (ERK2) relevant with neurocyte proliferation among the p44/42MAPK rises because of the emulsion that contains MLCT is concentration dependent ground.In contrast, there is not such tendency in the emulsion that contains LCT.
Claims (3)
1. fat or oil composition that is used to prevent or treat depression or depressive state, its form with triglyceride contains: carbon number is that 8～10 medium-chain fatty acid and carbon number are 12～24 LCFA,
With respect to the total amount of said medium-chain fatty acid and said LCFA, the ratio of said LCFA is 25～90 quality %.
2. fat or oil composition as claimed in claim 1, wherein, said medium-chain fatty acid is the satisfied fatty acid of carbon number 8 and/or 10, and said LCFA is the satisfied fatty acid and/or the unsaturated fatty acid of carbon number 16～24.
3. according to claim 1 or claim 2 fat or oil composition, it is used for prevention or treatment stress induction depression of sex or depressive state.
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| PCT/JP2010/071271 WO2011080982A1 (en) | 2009-12-28 | 2010-11-29 | Oil or fat composition for prevention or treatment of depression or depressed conditions |
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| CN105638927A (en) * | 2014-11-13 | 2016-06-08 | 丰益(上海)生物技术研发中心有限公司 | Grease composition and preparation method thereof |
| CN106771113A (en) * | 2017-02-27 | 2017-05-31 | 苏州市广济医院 | Application and kit of the triglycerides as mark in Diagnosis of Depression or curative effect evaluation kit is prepared |
| CN107136514A (en) * | 2017-05-23 | 2017-09-08 | 深圳泰乐德营养与健康有限公司 | One kind is by vitamin D, K and vitamin B12The nutrient composition of composition |
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| JP6935994B2 (en) * | 2016-08-19 | 2021-09-15 | 株式会社明治 | Composition for promoting ketone body production |
| JP2020083852A (en) * | 2018-11-30 | 2020-06-04 | 株式会社明治 | Stress disease preventive composition |
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| CN1338929A (en) * | 1999-01-27 | 2002-03-06 | 拉克斯戴尔有限公司 | Highly purified ethyl EPA and other EPA derivatives for psychiatric and neurological disorders |
| JP2008188010A (en) * | 2007-01-09 | 2008-08-21 | Ishikawa Pref Gov | Oil and fat-glucide powdery material and method for producing the same |
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| JP2003048831A (en) * | 2001-08-02 | 2003-02-21 | Suntory Ltd | Composition having preventing and ameliorating action on symptom or disease caused by decrease in brain function |
| JP5967855B2 (en) * | 2005-06-30 | 2016-08-10 | サントリーホールディングス株式会社 | Composition having an activity of reducing daytime activity and / or depressive symptoms |
| JPWO2008081989A1 (en) * | 2006-12-28 | 2010-04-30 | サントリーホールディングス株式会社 | Nerve regeneration agent |
| WO2009038110A1 (en) * | 2007-09-19 | 2009-03-26 | Nagoya Industrial Science Research Institute | Agent having neurotrophic factor-like activity |
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| CN1338929A (en) * | 1999-01-27 | 2002-03-06 | 拉克斯戴尔有限公司 | Highly purified ethyl EPA and other EPA derivatives for psychiatric and neurological disorders |
| CN1739496A (en) * | 1999-01-27 | 2006-03-01 | 拉克斯戴尔有限公司 | Highly purified ethyl EPA and other EPA derivatives for psychiatric and neurological disorders |
| JP2008188010A (en) * | 2007-01-09 | 2008-08-21 | Ishikawa Pref Gov | Oil and fat-glucide powdery material and method for producing the same |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN105638927A (en) * | 2014-11-13 | 2016-06-08 | 丰益(上海)生物技术研发中心有限公司 | Grease composition and preparation method thereof |
| CN105638927B (en) * | 2014-11-13 | 2020-11-10 | 丰益(上海)生物技术研发中心有限公司 | Oil and fat composition and method for producing oil and fat composition |
| CN106771113A (en) * | 2017-02-27 | 2017-05-31 | 苏州市广济医院 | Application and kit of the triglycerides as mark in Diagnosis of Depression or curative effect evaluation kit is prepared |
| CN106771113B (en) * | 2017-02-27 | 2019-04-02 | 苏州市广济医院 | Triglycerides is preparing application and kit in Diagnosis of Depression or curative effect evaluation kit as marker |
| CN107136514A (en) * | 2017-05-23 | 2017-09-08 | 深圳泰乐德营养与健康有限公司 | One kind is by vitamin D, K and vitamin B12The nutrient composition of composition |
| CN107136514B (en) * | 2017-05-23 | 2021-02-26 | 深圳奥萨制药有限公司 | A health food containing vitamin D, K and vitamin B12Composed nutrient composition |
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