CN1853656A - Fermentation composition having immunomodulating effect - Google Patents

Fermentation composition having immunomodulating effect Download PDF

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Publication number
CN1853656A
CN1853656A CNA2006100587868A CN200610058786A CN1853656A CN 1853656 A CN1853656 A CN 1853656A CN A2006100587868 A CNA2006100587868 A CN A2006100587868A CN 200610058786 A CN200610058786 A CN 200610058786A CN 1853656 A CN1853656 A CN 1853656A
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thallus
fermented
thallus laminariae
thallus eckloniae
fermentation
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野中裕司
泉扶实
出云贵幸
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Suntory Holdings Ltd
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Suntory Ltd
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Abstract

Disclosed is a novel composition having immunomodulating effects including an immunoactivating effect and an anti-allergic effect. The composition comprises a sea tangle alone which has been fermented by a lactic acid bacterium or comprises the sea tangle in combination with a sesame and a soybean both which have been fermented by a lactic acid bacterium. The composition enables the nutrients in the composition to be absorbed in good balance, is highly safe and has excellent immunomodulating effects.

Description

Fermentation composition with immunoregulation effect
Technical field
The present invention relates to contain the Thallus Laminariae (Thallus Eckloniae) behind lactic acid bacteria fermentation and have the compositions of immunoregulation effect, more particularly, relate to compositions with immunity effect effect and/or compositions with anti-allergy action.In addition, the invention still further relates to and contain through the Thallus Laminariae (Thallus Eckloniae) behind the lactic acid bacteria fermentation, through Semen Sesami behind the lactic acid bacteria fermentation and the Semen sojae atricolor behind lactic acid bacteria fermentation and have the compositions of immunoregulation effect.
Background technology
In recent years, relevant with allergy problem displays just sharp.Allergy has various diseases, and well-known, headed by pollinosis, patient's number of atoipc dermatitis, phagopyrism, allergic rhinitis, allergic asthma etc. is especially many, and report is arranged: pollinosis patient's number rises just by leaps and bounds.Facing such present situation, is the center with pharmaceuticals manufacturer, and people have carried out having developed many products to overcome the research that allergy is a purpose.Its representational product has antiallergic action preparation, antihistamine preparation etc., to be known as the release of granulocytic struvite material of mastocyte and receptor etc. be feature but these pharmaceutical preparatioies are to act on allergy mechanism end, the temporary transient symptom that relaxes, but the root that allergy takes place is not influenced.In addition, give anabolic agent etc. sometimes for the patient of symptom especially severe, but the side effect of this type of pharmaceutical preparation becomes problem.Under these circumstances, allergic method is fundamentally treated and is prevented in the fervent hope of people.On the other hand, Japan is just welcoming aging society, increases with the age that to cause hypoimmunity be that the death toll that the person at advanced age of cause infects disease increases.In addition, well-known, in busy modern society and nervous and be full of in the environment of pressure and live, immunity can descend, and people thirst for having corresponding countermeasure.
In order to address the above problem, be badly in need of a kind of safe oral uptake compositions of development, thereby said composition is as coming the enhancing immunity disease of can protecting from infection maybe can prevent or treat allergic means by improving immunoloregulation function, it is obtained by food material manufacturing at one's side, bring into play immunoregulation effect stably for a long time, can support the family in anxiety and the health that is full of people in the pressure environment.
In Japan, the custom, particularly Thallus Laminariae (Thallus Eckloniae) of edible seaweed just arranged since ancient times, be considered to health invigorating and salubrious food, life prolonging food, and be the conventional food material that also contains in the plain vegetarian.Sargassum is rich in mineral, various vitamin, fucoidin dietary fiber such as (fucoidan) such as the easy calcium that lacks of people, sodium, magnesium, phosphorus, ferrum, iodine, and confirms that Sargassum has immunoregulation effect.In addition, about latic acid-fermented food, along with the accumulation of scientific knowledge, the edible wholesome understanding of latic acid-fermented food is more and more higher, and the immunoregulation effect of various lactobacillus and latic acid-fermented food is also understood day by day., no matter be Sargassum or latic acid-fermented food, independent all do not possess sufficient immunoregulation effect.Therefore, the Sargassum lactic acid fermented material that has above-mentioned two key elements simultaneously is considered to a kind of material glamorous that can improve healthy function.But, in Sargassums such as Thallus Laminariae (Thallus Eckloniae), lack fermentation strain implantation, the necessary nutritional labeling of growing.And it is cultivated needs cost many times, labour and expense.Therefore, the research to Sargassum fermented food and physiologically active thereof is not very abundant.
About the Sargassum fermented product, patent documentation 1 discloses a kind of Sargassum fermented food, and this food obtains by following method: promptly provide saccharide as fermentation substrate for making the Sargassum saccharifying, decompose with cellulase etc. and handle seaweeds, unicellularization fermented with lactobacillus and/or yeast then.Record according to above-mentioned document, with this method fermented true Thallus Laminariae (Thallus Eckloniae) and Thallus Laminariae, and be specially in Thallus Laminariae, to add cellulase and inoculate the food that makes after three kinds of strains (a kind of lactobacillus: Lactobacillus brevis NRIFS B5201 strain and two primary yeasts: Debaryomyces hansenii NRIFSY5201 strain and Candida zeylanoides NRIFSY5206 strain) ferment with the Sargassum fermented food of this method manufacturing and have effect that reduces neutral fat in the blood and the effect that reduces liver fat.
In addition, patent documentation 2 discloses that a kind of picked-up is easy, nutrition good, good absorbing, tasty food, and this food is to mix the fermented food that makes with fermented Semen Sesami not by adding in the mixture of Semen sojae atricolor and Thallus Laminariae (Thallus Eckloniae) again after the Rhizopus mushroom ferments.
[patent documentation 1] TOHKEMY 2003-201 communique
No. the 2846547th, [patent documentation 2] Japan special permission
Summary of the invention
The objective of the invention is to: utilize food material at one's side, by giving food material immunoloregulation function at one's side or improve the immunoloregulation function of this material, thereby provide safe and have the compositions of good immunoregulation effect.
The inventor etc. utilize the vegetalitas lactobacillus that the Thallus Laminariae (Thallus Eckloniae) that is considered to usually be difficult to ferment is fermented, and have successfully obtained the lactobacillus fermented product of Thallus Laminariae (Thallus Eckloniae).Then, physiologically active after to this Thallus Laminariae (Thallus Eckloniae) lactobacillus fermented product oral uptake such as the inventor has carried out research repeatedly, found that: compare with picked-up Thallus Laminariae (Thallus Eckloniae) monomer and/or lactobacillus monomer, the immunoregulation effect of this fermented product (effect of immunity effect effect, adjustment immunologic balance) significantly improves.In addition, the inventor etc. can bring into play more efficiently on immunoloregulation function and the food material that be of high nutritive value of this Thallus Laminariae (Thallus Eckloniae) lactobacillus fermented product in exploitation and concentrate on studies, the result is surprised to find: when containing through the Thallus Laminariae (Thallus Eckloniae) behind the lactic acid bacteria fermentation with through the Semen Sesami behind the lactic acid bacteria fermentation and behind the compositions oral uptake of the combination of the Semen sojae atricolor behind the lactic acid bacteria fermentation, demonstrated the immunoregulation effect such as high immunity effect effect, anti-allergy action of beyong contemplation.Also confirmed: compare with independent picked-up lactobacillus, effect when absorbing unfermentable fermentation raw material separately, this immunoregulation effect is more remarkable.And behind the compositions heat sterilization of the present invention, this immunoregulation effect is still kept.
Based on these surprised discoveries of people in addition, finished the present invention.
The present invention is:
1. contain the Thallus Laminariae (Thallus Eckloniae) behind lactic acid bacteria fermentation and have the compositions of immunoregulation effect;
2. in the compositions described in 1, wherein, immunoregulation effect is immunity effect effect and/or anti-allergy action;
3. in the compositions described in 1 or 2, wherein, lactobacillus is the vegetalitas lactobacillus;
4. in 1～3 compositions described in any, as single intake, it contains 5mg or the above Thallus Laminariae (Thallus Eckloniae) behind lactic acid bacteria fermentation of 5mg;
5. contain through the Thallus Laminariae (Thallus Eckloniae) behind the lactic acid bacteria fermentation with through the compositions of Semen Sesami behind the lactic acid bacteria fermentation and the Semen sojae atricolor behind lactic acid bacteria fermentation;
6. in the compositions described in 5, wherein, lactobacillus is the vegetalitas lactobacillus;
7. in the compositions described in 5 or 6, it has immunoregulation effect;
8. in the compositions described in 7, wherein, immunoregulation effect is immunity effect effect and/or anti-allergy action;
9. in 5～9 compositionss described in any, as single intake, what it contained adds up to 1～10000mg, preferred 10～10000mg through the Thallus Laminariae (Thallus Eckloniae) behind the lactic acid bacteria fermentation with through Semen Sesami behind the lactic acid bacteria fermentation and the Semen sojae atricolor behind lactic acid bacteria fermentation;
10. in 1～9 compositions described in any, it is ingesta, food additives, health food or medical composition;
11. in 1～10 compositions described in any, its form is a pill;
12. indicated the Thallus Laminariae (Thallus Eckloniae) that contains behind lactic acid bacteria fermentation as effective ingredient and have the ingesta of immunoregulation effect.
The specific embodiment
The lactic acid bacteria fermentation Thallus Laminariae (Thallus Eckloniae)
Thallus Laminariae (Thallus Eckloniae) described in the present invention refers to the general name of Brown algae Laminariaceae Larminaria (Laminaria spp.) and sibling species thereof, for example comprise: true Thallus Laminariae (Thallus Eckloniae) (L.japonica), sharp buttocks Thallus Laminariae (Thallus Eckloniae) (L.japonica var.ochotensis), narrow leaf Thallus Laminariae (Thallus Eckloniae) (L.angustata), Changhai band (L.angustata var.longissima), wrinkle Thallus Laminariae (Thallus Eckloniae) (L.religiosa), twoly split Thallus Laminariae (Thallus Eckloniae) (Arthrothamnus bifidus), circle Qie Shi Thallus Laminariae (Thallus Eckloniae) (Kjellmaniella gyrata), Scytosiphon lomentarius (Lyngh.)J. Ag. (Kjellmaniella crassifolia), but be not limited to these.
As the Thallus Laminariae (Thallus Eckloniae) raw material of the Thallus Laminariae (Thallus Eckloniae) (lactic acid bacteria fermentation Thallus Laminariae (Thallus Eckloniae)) of the present invention behind lactic acid bacteria fermentation, employing be dry product after the former algae of above-mentioned Thallus Laminariae (Thallus Eckloniae) or its have been removed foreign bodies such as sand.From the angle of easy fermentation, the Thallus Laminariae (Thallus Eckloniae) after preferred use cut-out or the powdered also can be used the Thallus Laminariae (Thallus Eckloniae) with seasonings such as salt, sugar, aminoacid, organic acid, nucleic acid.Above-mentioned Thallus Laminariae (Thallus Eckloniae) is generally on sale on market, for example: trade name " Thallus Laminariae (Thallus Eckloniae) powder " (Japanese Kiyatsu Aquatic Product Chemical Co., Ltd.), trade name " Thallus Laminariae (Thallus Eckloniae) powder " (the Japanese limited Zong of commercial firm ten thousand Aquatic products) etc.
Do not have particular restriction to being used for the lactobacillus of fermented Thallus Laminariae (Thallus Eckloniae) raw material,, can use the lactobacillus or the cryopreserved lactobacillus that prepare according to the usual way lyophilization so long as the lactobacillus of Thallus Laminariae (Thallus Eckloniae) fermentation get final product.As lactobacillus, can enumerate as Lactobacillus (Lactobacillus), Lactococcus (Lactococcus), Streptococcus (Streptcoccus), Bifidobacterium (Bifidobacterium), Leuconostoc (Leuconostoc) etc., therefrom select one or both or two or more lactobacilluss, can use simultaneously or use one by one.Wherein, the lactobacillus (vegetalitas lactobacillus) that utilizes plant component existence that preferable separate obtains, because this lactobacillus also can ferment in the vegetable raw material that nutrition such as Thallus Laminariae (Thallus Eckloniae) are not enriched, and acidproof, alkaline-resisting, also can survival and reproduction in the presence of high concentration Sal thereby be easy in food, utilize, and this lactobacillus has patience etc. in the intestinal tract useful to the people.As above-mentioned vegetalitas lactobacillus, can enumerate: Lactobacillus plantarum (Lactobacillus plantarum), Lactobacillus pentosus (Lactobacilluspentosus), Lactobacillus brevis (Lactobacillus brevis), Lactobacillus fermenti (Lactobacillus fermentum), pediococcus halophilus (Tetragenococcushalophilus), Pediococcus pentosaceus (Pediococcus pentosaceus) etc.In addition, the applicant isolates the various plants lactobacillus (with reference to TOHKEMY 2005-333919 communique) with immunoregulation effect from Folium Perillae salts Fructus Solani melongenae down.In the present invention, also can preferably use these lactobacilluss.
In addition, lactobacillus of the present invention can use the lactobacillus of any fermented type in homotype lactate fermentation and the heterolactic fermentation, can also utilize the acetic acid, carbon dioxide, the ethanol that in heterolactic fermentation, produce to wait and give fragrance, but when carbon dioxide produced in a large number, the operability of the manufacturing process of use fermentation tank etc. is variation sometimes.On the other hand, the homotype lactate fermentation is because generate a large amount of lactic acid, so during the fermentation because of the putrid danger of influence from the putrefaction bacteria of Thallus Laminariae (Thallus Eckloniae) etc. is little, be fit to use in the present invention.
Lactic acid bacteria fermentation Thallus Laminariae (Thallus Eckloniae) of the present invention adds water usually in the Thallus Laminariae (Thallus Eckloniae) raw material, inoculate above-mentioned lactobacillus and ferment, and heating or irradiation then (preferred heating) sterilizes to fermented product.Fermented product after the above-mentioned sterilization is filtered or centrifugalize (the preferred filtration), remove the mushroom that major part has been died, thereby can obtain the lactic acid bacteria fermentation Thallus Laminariae (Thallus Eckloniae).
In the time of will fermenting, preferably carry out sterilization treatment in advance.As long as set suitable sterilization treatment temperature and time, for example, remained on 90 ℃ of following sterilization treatment 10 minutes.In addition, during the Thallus Laminariae (Thallus Eckloniae) fermentation, the polysaccharide of Thallus Laminariae (Thallus Eckloniae) can make fermentation broth viscosity obviously increase sometimes, therefore adds enzymes such as alginic acid lyases, can improve operability.
Carry out fermentation process by in above-mentioned sterilization treatment thing, adding the bottle opener (starter) that comprises lactobacillus.At this moment, promote additive, preferably add the nitrogenous source etc. of the saccharide, soybean protein and so on of glucose and so on as fermentation.According to the character of employed lactobacillus, set suitable fermentation process temperature and time and get final product.By measuring the pH value of fermentation product, can judge attenuation degree, the fermentation of lactic acid bacteria fermentation Thallus Laminariae (Thallus Eckloniae) of the present invention is till preferably proceeding to pH value and becoming below 5.0 or 5.0.
The lactic acid bacteria fermentation Thallus Laminariae (Thallus Eckloniae) that obtains as stated above can be to use with liquid original state, but from operability and conservatory angle, preferably passes through spray drying or lyophilization with its powdered.
Lactic acid bacteria fermentation Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae) (Thallus Laminariae (Thallus Eckloniae) behind lactic acid bacteria fermentation, Semen Sesami and Semen sojae atricolor)
The invention is characterized in: by in above-mentioned lactic acid bacteria fermentation Thallus Laminariae (Thallus Eckloniae), cooperating again through Semen Sesami behind the lactic acid bacteria fermentation and the Semen sojae atricolor behind lactic acid bacteria fermentation, thus the enhance immunity regulating action.
Semen Sesami described in the present invention refers to the seed of the plant of Sesamun indicum, for example comprises: Semen sesami Albae, Semen Sesami Nigrum, Rhizoma Polygonati fiber crops, dark brown Semen Sesami etc., but be not limited to these.In addition, these Semen Sesamis can use separately, also can multiple mixing use.Semen Sesami raw material as the Semen Sesami (lactic acid bacteria fermentation Semen Sesami) behind lactic acid bacteria fermentation of the present invention, its form is unrestricted, can be granular, ground product, pastel any forms such as (paste), but, preferably use the ground product or the pastel of Semen Sesami from the angle of easy fermentation.Sell the pastel of many Semen Sesamis on the market, for example trade name " black sesame paste " (Japanese Zhu Ben's Oil Corporation) etc.In addition, when being purpose, can using the defat Semen Sesami as raw material, but consider, preferably use the unskimmed Semen Sesami that contains oil content from nutritive value and function that Semen Sesami had to obtain the few lactic acid bacteria fermentation Semen Sesami of fat content.
Semen sojae atricolor described in the present invention refers to the seed of the plant of Glycine max, and it comprises multiple different kind according to the difference in trophophase, the place of production.Do not have particular restriction in the present invention, can use any kind.Soybean material as the Semen sojae atricolor (lactic acid bacteria fermentation Semen sojae atricolor) behind lactic acid bacteria fermentation of the present invention, can use solid shape Semen sojae atricolor, Semen sojae atricolor powder, soybean cake (soybeanoil cake), defatted soybean, ripe Semen Glycines powder and their hydrolyzate etc. any, there is not particular restriction, but, preferably use the Semen sojae atricolor after the powdered from the angle of easy fermentation.Above-mentioned Semen sojae atricolor powder is on sale on market, for example: trade name " ripe Semen sojae atricolor powder " (Japanese Kei Kobayashi Co., Ltd.), trade name " プ ロ ラ イ Off J " (Japan's reason is ground agricultural production Chemical Co., Ltd) etc.In addition, when being purpose, can use defatted soybean to obtain the few lactic acid bacteria fermentation Semen sojae atricolor of fat content.
The present invention relates to contain the compositions (being also referred to as in this manual, " lactic acid bacteria fermentation Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae) ", " fermented Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae) ") of lactic acid bacteria fermentation Thallus Laminariae (Thallus Eckloniae) and lactic acid bacteria fermentation Semen Sesami and lactic acid bacteria fermentation Semen sojae atricolor.Said composition can make by earlier Thallus Laminariae (Thallus Eckloniae), Semen Sesami and soybean material being carried out the lactic acid bacteria fermentation remix respectively, also can inoculate lactobacillus by first mixed material Thallus Laminariae (Thallus Eckloniae), Semen Sesami and Semen sojae atricolor and prepare.
When fermentation back remix prepares separately, promptly when mixing lactic acid bacteria fermented Thallus Laminariae (Thallus Eckloniae), lactic acid bacteria fermentation Semen Sesami and lactic acid bacteria fermentation Semen sojae atricolor,, can preferably use lactic acid bacteria fermentation Thallus Laminariae (Thallus Eckloniae) by preparations such as above-mentioned manufacture methods as the lactic acid bacteria fermentation Thallus Laminariae (Thallus Eckloniae).As the lactic acid bacteria fermentation Semen Sesami, can use with the lactic acid bacteria fermentation Semen Sesami of the same preparation of above-mentioned lactic acid bacteria fermentation Thallus Laminariae (Thallus Eckloniae), TOHKEMY 2004-173692 communique in the lactic acid bacteria fermentation Semen Sesami put down in writing etc.As the lactic acid bacteria fermentation Semen sojae atricolor, can use with the lactic acid bacteria fermentation Semen sojae atricolor of the same preparation of above-mentioned lactic acid bacteria fermentation Thallus Laminariae (Thallus Eckloniae), TOHKEMY 2003-335695 communique in the lactic acid bacteria fermentation Semen sojae atricolor put down in writing etc.
With following method is example, can illustrate after raw material Thallus Laminariae (Thallus Eckloniae), Semen Sesami and Semen sojae atricolor mix to inoculate the method that lactobacillus prepares, but be not limited thereto.
At first, preparation is as Thallus Laminariae (Thallus Eckloniae), Semen sojae atricolor, the Semen Sesami of fermentation raw material.According to circumstances these raw materials are processed into powder or pasty state.Perhaps, also can buy commercially available powder or pastes uses as fermentation raw material.Then,, add water, carry out sterilization treatment raw material Thallus Laminariae (Thallus Eckloniae) (for example, the Thallus Laminariae (Thallus Eckloniae) powder), Semen sojae atricolor (for example, Semen sojae atricolor powder), Semen Sesami (for example sesame paste) mixed in accordance with regulations.Set suitable sterilization treatment temperature and time and get final product, for example, 90 ℃ of following sterilization treatment 10 minutes.Then, in the sterilization treatment thing that obtains, add lactobacillus (for example, adding comprises the bottle opener of lactobacillus etc.), carry out fermentation process.When carrying out fermentation process, promote additive, preferably add the nitrogenous source etc. of the saccharide, soybean protein and so on of glucose and so on as fermentation.According to the character of employed lactobacillus, set suitable fermentation process temperature and time and get final product.By measuring the pH value of fermentation product, can judge attenuation degree.The fermentation of compositions of the present invention is till preferably proceeding to pH value and becoming below 5.0 or 5.0.In addition, in sterilization treatment operation and/or fermentation process operation, when the viscosity of raw material mixing and water adding thing or sterilization treatment thing is very high,, can reduces the viscosity of mixture and improve operability by adding enzyme such as alginic acid lyases.
After the fermentation ends, carry out pasteurization, cooling is filtered in case of necessity.The temperature of pasteurization is as long as set aptly.The liquid fermentation composition that obtains as stated above can directly use, but considers from operability and keeping quality, preferably aforesaid liquid shape fermentation composition is carried out spray drying, makes body of powder.This powder is the superfine powder body of dark brown, and it has the fragrance of raw material and the tart flavour of lactobacillus.
In addition, the same when the selection of employed lactobacillus can be with the lactic acid bacteria fermentation Thallus Laminariae (Thallus Eckloniae) in any manufacture method, preferably use the vegetalitas lactobacillus.The inventor etc. find by having adopted from the Folium Perillae pilot study of isolating lactobacillus that salts down the Fructus Solani melongenae: Lactobacillus pentosus (Lactobacillus pentosus) and Lactobacillus plantarum (Lactobacillus plantarum) can be well to any fermentations the in Thallus Laminariae (Thallus Eckloniae), Semen sojae atricolor and the Semen Sesami.Therefore, even in the vegetalitas lactobacillus, also can preferably use these lactobacilluss (Lactobacillus pentosus (Lactobacilluspentosus) and Lactobacillus plantarum (Lactobacillus plantarum)).Formerly mixing Thallus Laminariae (Thallus Eckloniae), Semen Sesami and Semen sojae atricolor inoculates in the manufacture method of lactobacillus, as lactobacillus, can use above-mentioned Lactobacillus pentosus (Lactobacillus pentosus) and Lactobacillus plantarum (Lactobacillusplantarum) and so on can be to any lactobacillus that ferments in Thallus Laminariae (Thallus Eckloniae), Semen Sesami and the Semen sojae atricolor, perhaps, use the multiple lactobacillus that can ferment to each raw material simultaneously.
Immunoregulation effect
Compositions of the present invention is that lactic acid bacteria fermentation Thallus Laminariae (Thallus Eckloniae) or lactic acid bacteria fermentation Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae) are characterised in that: have immunoregulation effect.
Thereby immunity is meant by resisting countless pathogen, various harmful substance and waits the function of protecting body prevention various diseases; the function that promptly keeps organism stability; when immunologic function is crossed Sheng or destroyed, can cause allergic disease, autoimmune disease etc.Immunoregulation effect described in the present invention refers to, the effect (immunity effect effect) that activate immunity is replied when causing partial immunity function destruction or immunologic hypofunction because of age increase, anxiety and pressure, fatigue, do not have enough sleep etc., or, when immunologic function is crossed the effect (immunosuppressive action) that flower suppresses immunne response.The present composition seeks to reach the optimum state of immunologic balance by bringing into play above-mentioned immunity effect effect and immunosuppressive action aptly.
In the immune system in vivo, there is the antigenic lymphocyte T cell of identification, can be divided into Th1 cell and Th2 cell according to the cytokine that is produced.The balance of this Th1 and Th2 (Th1/Th2 balance) exerts an influence to the intravital immunne response of biology, for example, as everyone knows in allergy, when Th1 preponderates, cause delayed anaphylaxis (as organ transplantation time take place IV allergic reaction types such as rejection), when Th2 preponderates, produce antigenic specificity IgE antibody, cause immediate hypersensitivity disease (as I allergic reaction types such as asthma, allergic rhinitis, pollinosis, atoipc dermatitis).Because the Th1 cell produces IFN-γ, the Th2 cell produces IL-4, so can (IFN-γ/IL-4) is as the index of immunologic balance with the ratio of above-mentioned IL-4 and IFN-γ.
Compositions of the present invention (lactic acid bacteria fermentation Thallus Laminariae (Thallus Eckloniae) and lactic acid bacteria fermentation Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae)) is characterised in that its Th1/Th2 balance with organism is guided the dominant state of Th1 into.As mentioned above, known in I allergic reaction types such as asthma, pollinosis, atoipc dermatitis, Th2 preponderates.And report is arranged: in HIV infects also is that Th2 preponderates.Also known: as when Th1 preponderates, to promote the activity of macrophage, NK cell, cytotoxic T cell (CTL), improve anti-cancer ability.Therefore, directly absorb compositions of the present invention or, Th1 is preponderated, singly can treat and prevent the I allergic reaction type, can also improve resistivity, thereby prevent and treat HIV, cancer, bacterial infection etc. with forms such as food, pharmaceuticals picked-ups.
The feature of the present composition is that also it improves intestinal immune power.So-called intestinal immune refers to the system of defense that is present in the intestinal mucosa face, and the pathogenic factor that this system of defense will be invaded intestinal is got rid of or got rid of with ingesta etc. from nose, throat etc.Known distribution is in the effect of the peyer's patches performance command centre of small intestinal mucosa, and it is the foreign body of representative that the antibody (IgA) that peyer's patches produces is attacked with pathogen, virus etc.
As mentioned above, compositions of the present invention (lactic acid bacteria fermentation Thallus Laminariae (Thallus Eckloniae) or lactic acid bacteria fermentation Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae)) can be used as the compositions that immunomodulating is used, immunity effect is used, immunosuppressant is used or antiallergic action is used, and is very useful.
Ingesta pharmaceuticals etc.
The compositions that the present invention relates to can be used as ingesta, pharmaceuticals wait and use, said composition is by giving the food material immunoloregulation function that is of high nutritive value at one's side or improving the compositions that its immunoloregulation function makes, it is safe, and is therefore preferred as ingesta that can daily picked-up.During as ingesta, be suitable as health food with immunoregulation effect.Health food described here is included in container, the description etc. and has indicated the ingesta (for example, the functional foods such as specific food for health care under specific food for health care, the certain condition) with immunologic function regulating action, immunity effect effect and/or anti-allergy action.For marker location (description that container or its have etc.), container form (bottle, jar, vinyon bottle, plastic bottle, wrapper etc.) and marker method (printing, mint-mark, seal etc.) without any restriction.In addition, as the form that food uses, also comprise the form that compositions of the present invention is used as food additive.
When using as ingesta, compositions of the present invention can directly use, also can with make the product that meets consumer taste after various compositions such as known host, adjuvant, sweet taste flavoring agent, tart flavour flavoring agent, vitamin mix, for example, compositions of the present invention can provide with forms such as tablet, capsule, pill, powder agent, granule, sugar-coat agent (candy), drop (drop), lozenge (troch), chewing gum, juice powder, health-care nutrient liquor, flavouring agent, processed food, Dessert or snack categories.In addition, lactic acid bacteria fermentation Thallus Laminariae (Thallus Eckloniae) of the present invention or lactic acid bacteria fermentation Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae) have light taste, and therefore can chew the form of tasting ingesta becomes one of preferred configuration.Specifically, for example pill, the such form of cookies.The oil content of pill is adjusted to below 1% or 1% usually.This is to adhere between pill oxidative degradation, pill etc. because of oozing out of the oil content that produces in preserving causes in order to prevent.In lactic acid bacteria fermentation Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae) of the present invention, if use defatted soybean, defat Semen Sesami, then the oil content of pill can be adjusted to below 1% or 1%, but considers the nutritive value of material (particularly Semen Sesami), uses fat-free material not necessarily suitable.When not using fat-free material, compositions contains the oil content about 4～15%, and oozing out of above-mentioned oil content may be taken place.The inventor etc. have studied the manufacture method that can prevent the pill that this oil content oozes out, and found that: with the good looking appearance be purpose and in the plain ball polishing process usually implemented (polishing on plain ball surface), oil content obviously oozes out; Do not carry out above-mentioned plain ball polishing process, and plain ball is carried out coating, can prevent oozing out of oil content with Lac or sugar.
Ingesta of the present invention is that purpose also can be used on one's body the animal beyond the people with the adjusting (immunity effect, antiallergic action etc.) of immunologic function.As the animal of using object, can enumerate: outside the laboratory animals such as poultries such as livestocks such as pets such as Canis familiaris L., cat, pig, cattle, chicken, mice, Cavia porcellus, can also be aquatic animal etc.As the form of ingesta, can use its original shape, also can add in the feedstuff (pet food) that animal or fish and shellfish use and supply with, or supply with to replenish the such form of material (supplement).
When the pharmaceuticals, can enumerate as immunomodulators such as immunity effect preparation, antiallergic action preparations.In addition, compositions of the present invention can be used normally used known adjuvant in the pharmaceutical preparations technology fields such as excipient, binding agent, disintegrating agent, lubricant, drug flavoring, cosolvent, suspending agent, coating materials in principal agent, make preparation.Dosage form can be pill, tablet, capsule, granule, powder, syrup, seat agent, injection etc., but is not limited to these.Do not have particular restriction to during giving, give continuously more than can 1 week～10 day, preferably give continuously steadily in the long term.
The content of compositions of the present invention (lactic acid bacteria fermentation Thallus Laminariae (Thallus Eckloniae) or lactic acid bacteria fermentation Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae)) in ingesta of the present invention or pharmaceuticals does not have particular restriction, is generally 0.1～100 weight %, preferred 1～90 weight %, more preferably 1～50 weight %.
By compositions of the present invention food that form or that contain compositions of the present invention or pharmaceuticals, the content of lactic acid bacteria fermentation Thallus Laminariae (Thallus Eckloniae) or lactic acid bacteria fermentation Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae) converts with dry weight and is generally 1～10000mg in its administered dose, preferred 10～10000mg, but the present composition is safe, so in fact its content do not exist the upper limit.
Compositions of the present invention is by the food material manufacturing, and is therefore safe, can short-term or daily chronically picked-up or suitably continue picked-up behind the natural law at interval.Therefore, during as ingesta or health food picked-up,, can prevent the immunologic hypofunction that a variety of causes causes by long-term adjusting immunologic function.And, by regulating the balance of immunologic function, can also prevent from organism is produced the excessively hyperfunction of dysgenic immunologic function.
In addition, compositions of the present invention as pharmaceuticals throw with after, can relax or cure the various symptoms that cause because of immunologic hypofunction or immunologic hyperfunction with the effectiveness of gentleness.
And then compositions of the present invention can also be utilized Thallus Laminariae (Thallus Eckloniae), Semen sojae atricolor and good nutritive value and function that Semen Sesami had efficiently.
Description of drawings
The measurement result of the macrophage IL-12 generation of the mice after [Fig. 1] Fig. 1 represents with the S-PT84 strain, fermented Thallus Laminariae (Thallus Eckloniae), fermented Thallus Laminariae (Thallus Eckloniae), fermented Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae) are not handled.
[Fig. 2] Fig. 2 represents to absorb fermented Thallus Laminariae (Thallus Eckloniae) not, fermented Thallus Laminariae (Thallus Eckloniae), the macrophage IL-12 generation of the mice behind fermented Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae), the fermented Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae) not.
[Fig. 3] Fig. 3 represents to absorb S-PT84, the splenocyte NK activity of the mice behind fermented Thallus Laminariae (Thallus Eckloniae), the fermented Thallus Laminariae (Thallus Eckloniae) not.
[Fig. 4] Fig. 4 represents to absorb S-PT84, not splenocyte IFN-γ, the IL-4 generation of the mice behind fermented Thallus Laminariae (Thallus Eckloniae), the fermented Thallus Laminariae (Thallus Eckloniae).
[Fig. 5] Fig. 5 represents to absorb S-PT84, the splenocyte Th1/Th2 balance of the mice behind fermented Thallus Laminariae (Thallus Eckloniae), the fermented Thallus Laminariae (Thallus Eckloniae) not.
[Fig. 6] Fig. 6 represents the active measurement result of splenocyte NK of the mice behind difference oral uptake S-PT84, the fermentation composition.
[Fig. 7] Fig. 7 represents the measurement result of the splenocyte IL-4 production of the mice behind difference oral uptake S-PT84, the fermentation composition.
[Fig. 8] Fig. 8 represents the measurement result of the splenocyte IFN-γ production of the mice behind difference oral uptake S-PT84, the fermentation composition.
[Fig. 9] Fig. 9 is illustrated in the active measurement result of splenocyte NK that stress descend the mice behind oral uptake S-PT84, the fermentation composition respectively.
[Figure 10] Figure 10 is illustrated in the measurement result of the splenocyte IL-4 production that stress descend the mice behind oral uptake S-PT84, the fermentation composition respectively.
[Figure 11] Figure 11 is illustrated in the measurement result of the splenocyte IFN-γ production that stress descend the mice behind oral uptake S-PT84, the fermentation composition respectively.
[Figure 12] Figure 12 represents oral uptake S-PT84 respectively, fermentation composition, the S-PT84+ measurement result of total IgE concentration of the OVA sensitized mice behind fermentation composition, the fermentation composition not.
[Figure 13] Figure 13 represents the not measurement result of the splenocyte IL-4 production of the OVA sensitized mice behind fermentation composition, the fermentation composition of oral uptake S-PT84+ respectively.
[Figure 14] Figure 14 represents the not measurement result of the splenocyte IFN-γ production of the OVA sensitized mice behind fermentation composition, the fermentation composition of oral uptake S-PT84+ respectively.
[Figure 15] Figure 15 represents the measurement result of total IgA amount in the intestinal chamber of the mice behind respectively oral uptake S-PT84, the fermentation composition.
[Figure 16] Figure 16 represents the measurement result of the peyer's patches cell IL-4 production of the mice behind difference oral uptake S-PT84, the fermentation composition.
[Figure 17] Figure 17 represents the measurement result of the peyer's patches cell IFN-γ production of the mice behind difference oral uptake S-PT84, the fermentation composition.
[Figure 18] Figure 18 represents the not measurement result of the Salcoma180 tumor size of the mice behind fermented Thallus Laminariae (Thallus Eckloniae) or the fermented Thallus Laminariae (Thallus Eckloniae) of oral uptake respectively.
[Figure 19] Figure 19 represents to absorb the active measurement result of NK of the people behind the fermentation grain.
[Figure 20] Figure 20 represents to absorb the NK activity change amount of the people behind the fermentation grain.
[Figure 21] Figure 21 represents to absorb the variable quantity of the Th1/Th2 ratio of the people behind the fermentation grain.
Embodiment
Below, by enumerating embodiment, explain compositions of the present invention.But, the invention is not restricted to embodiment.
Test example 1 lactic acid bacteria fermentation test (1)
Studied the probability of utilizing the lactic acid bacteria fermentation Thallus Laminariae (Thallus Eckloniae).What Thallus Laminariae (Thallus Eckloniae) was adopted is Powdered Thallus Laminariae (Thallus Eckloniae) (production of Japanese Kiyatsu Aquatic Product Chemical Co., Ltd., trade name " Thallus Laminariae (Thallus Eckloniae) powder ").In Powdered Thallus Laminariae (Thallus Eckloniae), add distilled water and be mixed into Thallus Laminariae (Thallus Eckloniae): the mixed liquor of water=5: 95 (weight ratio), this mixed liquor was sterilized 1 minute down at 110 ℃, (a kind of as bottle opener (starter) among the A～F) (with reference to TOHKEMY 2005-333919 communique) plants bacterium with 0.5% to use eight kinds of lactobacilluss shown in the table 1 then.The mixture that obtains is 37 ℃ of bottom fermentations 48 hours, measures pH value before the fermentation and the pH value after the fermentation, and measured the bacterium number after lactobacillus A～D fermentation.In addition, the lactobacillus A (S-PT84) in the table is deposited at Independent Administrative Leged Industrial Technology Complex Inst's special permission biology as FERM ABP-10028 and deposits the center.
[table 1]
The bacterial strain name Plant name Extracellular polysaccharide (EPS)
A DS84C(S-PT84) Lactobacillus.pentosus +
B DS84N Lactobacillus.pentosus -
C DW69C Lactobacillus.pentosus +
D DW69N Lactobacillus.pentosus -
E DB22C Lactobacillus.plantarum +
F DB22N Lactobacillus.plantarum -
G DS2C Lactobacillus.plantarum +
H DS2N Lactobacillus.plantarum -
Bacterium number after the fermentation and the fermentation before pH value and the fermentation after pH value the results are shown in Table 2.Utilize any in eight kinds of lactobacilluss, can find that all lactic acid bacteria number increases and/or the decline of pH value, show that lactobacillus can fermented Thallus Laminariae (Thallus Eckloniae).
[table 2]
A B C D E F G H
10 7cuf/g 2 3 6 3 - - - -
10 5cuf/g 235 116 ＞300 ＞300 - - - -
Initial pH 5.83
Final pH 4.78 4.59 4.33 4.52 4.55 5.38 4.80 5.01
Experimental example 2 lactic acid bacteria fermentations tests (2)
Studied and utilized the lactobacillus that uses in the test example 1 to come the probability of fermented Semen Sesami and Semen sojae atricolor.What Semen Sesami adopted is the pasty state Semen Sesami (trade name " pure sesame paste is black ") that Zhu Ben's Oil Corporation produces, and what Semen sojae atricolor was adopted is the Powdered Semen sojae atricolor (trade name " ripe Semen sojae atricolor powder ") that Kei Kobayashi Co., Ltd. produces.Add distilled water and be mixed and made into Semen Sesami: water=25: 75 (weight ratio), Semen sojae atricolor: water=15: 85 (weight ratio), same with test example 1, sterilize, fermentation process, measure pH value before the fermentation and the pH value after the fermentation, measure the bacterium number after the fermentation.In addition, when the bacterium after measuring fermentation is counted, Semen Sesami: measured the bacterium number behind eight kinds of lactic acid bacteria fermentations, and Semen sojae atricolor: measured the bacterium number after lactobacillus A～D fermentation.
Bacterium number after the fermentation and the fermentation before pH value and the fermentation after pH value the results are shown in Table 3.Use any in eight kinds of lactobacilluss, can find that all lactic acid bacteria number increases and/or the decline of pH value, show that lactobacillus can fermented Semen Sesami and Semen sojae atricolor.
[table 3]
A B C D E F G H
Semen Sesami
10 7cuf/g 30 73 28 40 33 15 5 5
Initial pH 6.13
Final pH 4.58 4.50 4.67 4.68 4.77 4.74 5.22 5.16
Semen sojae atricolor 10 7cuf/g 73 56 92 106 - - - -
Initial pH 6.08
Final pH 4.36 4.33 4.51 4.54 4.53 4.54 4.28 4.24
The preparation of the lactobacillus fermented product of embodiment 1 Thallus Laminariae (Thallus Eckloniae)
What Thallus Laminariae (Thallus Eckloniae) was adopted is the Powdered Thallus Laminariae (Thallus Eckloniae) (trade name " Thallus Laminariae (Thallus Eckloniae) powder ") (hereinafter referred to as " not fermented Thallus Laminariae (Thallus Eckloniae) ") that Kiyatsu Aquatic Product Chemical Co., Ltd. produces.In fermented Thallus Laminariae (Thallus Eckloniae), add the aquesterilisa that has disperseed alginic acid lyases (production of Nagasechemtex company), 90 ℃ of following heat sterilizations 20 minutes.As bottle opener (starter), employing be that lactobacillus (Lactobacillus.Pentosus S-PT84 strain) was cultivated 20 hours down and the production usefulness bottle opener (bulk starter) that obtains at the nutritional condition of 2% glucose, 1% yeast extract (Mitsubishi chemistry food Co., Ltd.), 1% soybean protein (Japanese Fuji Oil Co., Ltd. produces).This bottle opener is added in the Thallus Laminariae (Thallus Eckloniae) mixed liquor that has carried out sterilization treatment, be about under 37 ℃, carried out about 14 hours fermentation in temperature.After the fermentation ends, with fermentation liquid 90 ℃ of following pasteurizations 10 minutes, cooling, filter with 20 order drainage screens, (Japanese Buchi Co., Ltd. makes with spray dryer for the filtrate that obtains, Minispray Dryer B-290 type) carries out drying, obtain the lactic acid bacteria fermentation compositions (below be referred to as " fermented Thallus Laminariae (Thallus Eckloniae) ") of Thallus Laminariae (Thallus Eckloniae).
The preparation of the lactobacillus fermented product of embodiment 2 Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae) mixture (Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae))
What Semen Sesami adopted is " pure sesame paste is black " that Zhu Ben's Oil Corporation produces, what Semen sojae atricolor was adopted is " the ripe Semen sojae atricolor powder " of Kei Kobayashi Co., Ltd., and what Thallus Laminariae (Thallus Eckloniae) was adopted is " the Thallus Laminariae (Thallus Eckloniae) powder " that Kiyatsu Aquatic Product Chemical Co., Ltd. through alginic acid lyases (production of Nagasechemtex company) is handled similarly to Example 1 produces.Semen Sesami, Semen sojae atricolor and Thallus Laminariae (Thallus Eckloniae) are mixed into Semen Sesami: Semen sojae atricolor: Thallus Laminariae (Thallus Eckloniae): the mixture (hereinafter referred to as " not fermented Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae) " or " not fermentation composition ") that is 1: 3: 1 (weight ratio), promote additive as fermentation, in this mixture, add muscovado (with the weight ratio of Semen Sesami be 1/3), soybean protein (with the weight ratio of Semen Sesami be 1/15).After this Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae) mixture ferments similarly to Example 1, with fermented product 90 ℃ of following pasteurizations 10 minutes, cooling, filter with 20 order drainage screens, (Japanese Buchi Co., Ltd. makes with spray dryer for the filtrate that obtains, Minispray Dryer B-290 type) carries out drying, make the lactic acid bacteria fermentation compositions (hereinafter referred to as " fermented Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae) " or " fermentation composition ") of Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae) mixture.
3 pairs of macrophages of embodiment produce the facilitation (In vitro test) of IL-12
Give PBS (Phosphate-Buffer Salines) with every 5mL, aseptic recovery intraperitoneal cell for the intraperitoneal of C57BL/6 mice (7 ages in week, male, 10, clear water experiment material).The cell that reclaims is washed (the RPMI1640 culture medium (Japan day water Pharmaceutical Co., Ltd) that contains 10%FBS (hyclone)) with cell culture with culture medium, remove erythrocyte with haemolysis buffer haemolysis.That is, in the cell that reclaims, add 1mL haemolysis buffer (155mM NH 4Cl, 10mMKHCO 3, 0.1mM EDTA), at room temperature, left standstill 2～3 minutes, add 9mL cell culture culture medium.After the stirring, centrifugalize (20 ℃, 1500rpm, 3 minutes), precipitate is with cell culture with the culture medium washing once.Calculate plate instrumentation cell number with hemocyte, with culture medium concentration is modulated into 1 * 10 with cell culture 6Cells/mL goes into (tissue culturing plate) in 48 well culture plates with every hole 500 μ L kinds.It after 3 hours, is removed non-adherent cell by removing culture medium in 5%CO2,37 ℃ of following cultivations, add the cell culture culture medium once more.
Take by weighing the not fermented Thallus Laminariae (Thallus Eckloniae), fermented Thallus Laminariae (Thallus Eckloniae) and the fermented Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae) that obtain in a certain amount of embodiment 1 and 2, in mortar, pulverize, be suspended in cell culture with (not fermented Thallus Laminariae (Thallus Eckloniae) suspension, fermented Thallus Laminariae (Thallus Eckloniae) suspension, fermented Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae) suspension) in the culture medium, as sample.These samples are respectively 1 μ g/mL with ultimate density and 10 μ g/mL add on the above-mentioned cell plates, cultivated 18 hours down 5%CO2,37 ℃.As a comparison, S-PT84 (dry dead bacterium) being suspended in cell culture with the suspension of making in the culture medium, is that 1.5ng/mL and 15ng/mL add with the ultimate density, in 5%CO2,37 ℃ cultivation 18 hours down.In addition, the ultimate density of S-PT84 strain be with 1 μ g/mL and 10 μ g/mL fermented Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae) suspensions in the suitable concentration of amount of S-PT84 strain.Amount (the interleukin 12 of the cytokine that contains in the culture supernatant; IL-12) measure with ELISA test kit (OptEIA, BD Pharmingen company).In addition, with the culture fluid that do not add any material (Cont) in contrast, measure in the same way.
The result of the test of IL-12 concentration in the culture supernatant (meansigma methods of N=2) is seen Fig. 1.Found that: the high concentration of fermented Thallus Laminariae (Thallus Eckloniae), fermented Thallus Laminariae (Thallus Eckloniae), fermented Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae) interpolation does not make IL-12 concentration rising in the culture fluid.Also prompting: when adding the fermented Thallus Laminariae (Thallus Eckloniae) ratio and adding not fermented Thallus Laminariae (Thallus Eckloniae), IL-12 concentration increases, and adds fermented Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae) when adding fermented Thallus Laminariae (Thallus Eckloniae), and IL-12 concentration increases.Above result shows that the immunity effect effect of fermented Thallus Laminariae (Thallus Eckloniae) is than fermented Thallus Laminariae (Thallus Eckloniae) is not strong, and the immunity effect effect of fermented Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae) is stronger than fermented Thallus Laminariae (Thallus Eckloniae).
4 pairs of macrophages of embodiment produce the facilitation (Ex vivo test) of IL-12
C57BL/6 mice (7 ages in week, male, 15) is divided into roughly the same 5 groups of average weight, 3 every group.Constituting of group: no disposal group (Control), fermented Thallus Laminariae (Thallus Eckloniae) does not organize that (10mg/ mice), fermented Thallus Laminariae (Thallus Eckloniae) are organized (10mg/ mice), fermented Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae) is not organized (10mg/ mice), fermented Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae) is organized (10mg/ mice).Except that Control, the amount intraperitoneal of respectively organizing respectively with every of 0.5mL gives suspension, and above-mentioned suspension is: the not fermented Thallus Laminariae (Thallus Eckloniae) that obtains in embodiment 1 and 2, fermented Thallus Laminariae (Thallus Eckloniae), not add the concentration that PBS makes in fermented Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae) and the fermented Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae) be the suspension of 20mg/mL.After giving 18 hours, intraperitoneal gives the PBS of 5mL, aseptic recovery intraperitoneal cell.The cell that reclaims washs with culture medium with cell culture, according to the method for embodiment 3, removes erythrocyte with the haemolysis buffer.Calculate plate instrumentation cell number with hemocyte, with culture medium concentration is modulated into 2 * 10 with cell culture 6Cells/mL goes in 48 well culture plates (tissue culturing plate) with every hole 500 μ L kinds.It after 5%CO2,37 ℃ cultivate 3 hours down, is removed non-adherent cell, add LPS (Lipopolysaccharide) and make ultimate density become 100ng/mL, cultivated 24 hours down 5%CO2,37 ℃.The IL-12 amount that contains in the culture supernatant is measured with ELISA test kit (OptEIA, BDPharmingen company).
The measurement result of IL-12 concentration in the culture supernatant (meansigma methodss of N=2～3) is seen Fig. 2.This result shows, organize and do not find the increase of IL-12 concentration during fermented Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae) organize at fermented Thallus Laminariae (Thallus Eckloniae) not, and fermented Thallus Laminariae (Thallus Eckloniae) organize and fermented Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae) organize in the generation of IL-12 increase greatly, especially the generation of IL-12 significantly rises in fermented Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae) is organized.Above result shows, not fermented Thallus Laminariae (Thallus Eckloniae), fermented Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae) does not strengthen LPS stimulates the huge effect of having a liking for cell activation cause, and fermented Thallus Laminariae (Thallus Eckloniae), fermented Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae) have above-mentioned effect, and this effect of fermented Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae) is stronger than fermented Thallus Laminariae (Thallus Eckloniae).
Embodiment 3 and 4 result show that compositions of the present invention has the good immunoregulation effect that does not detect in advance from its fermentation raw material.
Embodiment 5 Thallus Laminariae (Thallus Eckloniae) fermented products are to the influence of the balance (Th1/Th2 ratio) of NK activity and Th1 cell and Th2 cell
12 C57BL/6 mices (6 week age, male) are divided into roughly the same 4 groups of average weight, 3 every group.Constituting of group: no interpolation group (Control), S-PT84 organize, fermented Thallus Laminariae (Thallus Eckloniae) is not organized and fermented Thallus Laminariae (Thallus Eckloniae) is organized.Except that no interpolation group, in respectively organizing, give S-PT84 (dry dead bacterium) (S-PT84 organizes), give not fermented Thallus Laminariae (Thallus Eckloniae) (fermented Thallus Laminariae (Thallus Eckloniae) is not organized) and the fermented Thallus Laminariae (Thallus Eckloniae) (fermented Thallus Laminariae (Thallus Eckloniae) is organized) of embodiment 1 with every 0.75mg/kg with every 500mg/kg, force day after day oral administration with.In addition, the amount of the amount of S-PT84 S-PT84 quite and in the fermented Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae) during S-PT84 organizes.Throwing and beginning the 7th day, aseptic taking-up spleen, cell culture with culture medium in (RPMI 1640 culture medium that contain 10% hyclone, 0.2% antibiotic-antifungal preparation mixed solution (production of Nacalai Tesque company)) by on cell filter (70 μ m, BD Falcon company produce) gently compressing obtain cell.Behind the pipetting cell dispersion, centrifugalize (1500rpm, 3 minutes, 4 ℃).According to the method for embodiment 3, after haemolysis is removed erythrocyte, the preparation splenocyte.The NK of this splenocyte is active to measure (so-called PINK method by the PINK method, be fluorochrome 3 promptly with hydrophobic film, 3 '-dioctadecyloxacarbocyanine perchlorate (Dio) labels targets cell Yac-1, reuse film impermeability nucleic acid embedded type fluorochrome propidium iodide (PI) carries out double staining to the nuclear of dead cell, the Yac-1 that is not hurt is the Dio simple stain, the Yac-1 that comes to harm is a double staining, detect by flow cytometer, thereby calculate the cytotoxic activity of mouse boosting cell).In addition, cultivated 24 hours under the stimulation of concanavalin A (2.5 μ g/mL), IFN-γ that produces in the culture supernatant and the amount of IL-4 are measured by the ELISA method of having used OptEIA (BD Pharmingen company).
NK is active to the results are shown in Figure 3.In Fig. 3, NK activity (%) expression (is mouse lymphoma cell, is used as the sensitive cells of NK cells in mice on the standard mouse spleen lymphocyte Yac-1.The result shows mouse spleen lymphocyte: Yac-1=20: 1 and 10: 1 data.) cytotoxicity.Fig. 3 shows, compares with matched group, and the NK activity increases successively with the order that S-PT84 organizes, fermented Thallus Laminariae (Thallus Eckloniae) is not organized, the Thallus Laminariae (Thallus Eckloniae) fermented product is organized.
(result of IFN-γ/IL-4) sees Fig. 4,5 respectively for IFN-γ concentration and IL-4 concentration, balance index Th1/Th2.Fig. 4,5 shows, compares with matched group, and IFN-γ concentration does not change in S-PT84 organizes, and increases in fermented Thallus Laminariae (Thallus Eckloniae) is not organized, and significantly increases in fermented Thallus Laminariae (Thallus Eckloniae) is organized.On the other hand, compare with matched group, IL-4 concentration all has a little increase in any one group is organized, rest on 40～70% but increase.Do not change during Th1/Th2 organizes at S-PT84, fermented Thallus Laminariae (Thallus Eckloniae) is not organized, only Th1 preponderates in fermented Thallus Laminariae (Thallus Eckloniae) is organized.Above result shows that fermented Thallus Laminariae (Thallus Eckloniae) has the effect of the immunologic function when strengthening steady statue, also has the effect that the Th1/Th2 balance is regulated to Th1.
The result of this embodiment shows that fermented Thallus Laminariae (Thallus Eckloniae) has the immunity effect effect, also has very strong with the effect of Th1/Th2 balance to the dominant status adjustment of Th1.
Embodiment 6 fermented Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae)s are to the influence of the balance (Th1/Th2 ratio) of NK activity and Th1 cell and Th2 cell
18 C57BL/6 mices (6 week age, male) are divided into roughly the same 3 groups of average weight, 6 every group.Constituting of group: the fermented Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae) absorption group (fermentation composition) that obtains among no interpolation group (Control), S-PT84 absorption group (S-PT84) and the embodiment 2.Allow each absorption group absorb respectively to have added S-PT84 (dry dead bacterium) and make its solid feed that accounts for 0.0075 weight %, added fermented Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae) and make its solid feed that accounts for 5 weight %, freely ingest a week.In addition, the amount of S-PT84 is equivalent to the amount of S-PT84 in the fermented Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae) in the S-PT84 absorption group.Picked-up beginning the 8th day, take out spleen, prepare splenocyte according to the method identical with embodiment 5.According to the method identical, measure the NK activity (PINK method) of the splenocyte that obtains and concanavalin A (2.5 μ g/mL, 24 hours) post-stimulatory IL-4 and IFN-γ concentration with embodiment 5.
NK is active to the results are shown in Figure 6.In Fig. 6, NK activity (%) expression (is mouse lymphoma cell, is used as the sensitive cells of NK cells in mice on the standard the Yac-1 of mouse spleen lymphocyte.The result shows mouse spleen lymphocyte: Yac-1=80: 1 data.) cytotoxicity.Fig. 6 shows, compares with no interpolation group, and NK is active in S-PT84 absorption group improves, and the active raising of NK is more remarkable in fermented Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae) absorption group.Therefore point out the present composition to have the immunity effect effect.
IL-4 concentration, IFN-γ concentration result are seen Fig. 7,8 respectively.Fig. 7 shows that IL-4 concentration does not change because of absorbing S-PT84 and absorbing fermented Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae).On the other hand, as shown in Figure 8, compare with no interpolation group, IFN-γ concentration rises in S-PT84 absorption group, significantly rises in fermented Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae) absorption group.
That is, this embodiment show the present composition with the Th1/Th2 balance to the dominant status adjustment of Th1.
Embodiment 7 fermented Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae)s to stress due to immunocompromised and the influence of the balance of Th1 cell and Th2 cell (Th1/Th2 than)
24 C57BL/6 mices (6 week age, male) are divided into roughly the same 4 groups of average weight, 6 every group.Constituting of group: no disposal group (Control), stress group (Stress), stress+S-PT84 absorption group (S-PT84) and stress+the fermented Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae) absorption group (fermentation composition) that obtains among the embodiment 2.Allow the picked-up of each absorption group add S-PT84 (dry dead bacterium) and make its solid feed that accounts for 0.0075 weight %, added fermented Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae) and make its solid feed that accounts for 5 weight %, freely ingest a week.In addition, the amount of S-PT84 is equivalent to the amount of S-PT84 in the fermented Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae) in the S-PT84 absorption group.Picked-up beginning the 8th day, after 18 the mice water loggings (submerge) once with stress group, put into the 50mL polyethylene tube that the top has airport, fettered 24 hours.No disposal group is carried out 24 hours exhausted water and is gone on a hunger strike.Then, according to method similarly to Example 5, take out spleen, the preparation splenocyte is measured NK activity (PINK method).Concanavalin A (2.5 μ g/mL, 24 hours) post-stimulatory IL-4 and IFN-γ concentration have also been measured.
NK is active to the results are shown in Figure 9.In Fig. 9, NK activity (%) expression is to the cytotoxicity of the Yac-1 of mouse spleen lymphocyte.Fig. 9 shows, compares with no disposal group, and the NK activity descends in stress group (Stress).In S-PT84 absorption group, by stress due to active decline of NK obtained inhibition, in fermented Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae) absorption group, the NK activity maintains the level of no disposal group.IL-4 concentration and IFN-γ concentration result are seen Figure 10,11.Figure 10,11 shows, stress make all significantly decline (Stress) of IL-4 and IFN-γ concentration.The decline of suppression ratio IL-4 concentration of IFN-γ concentration is more remarkable in this group, thinks that therefore Th2 preponderates in the Th1/Th2 balance.Stress under IL-4 concentration do not change because of picked-up S-PT84 and picked-up fermented Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae).But then, compare with stress group, IFN-γ concentration rises in S-PT84 absorption group, significantly rises in fermented Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae) absorption group.
Above result shows, the immunologic function of the lactobacillus fermented product of Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae) (fermented Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae)) in the time of can not only strengthening steady statue, can also suppress by stress due to immunocompromised.Also find: be not when picked-up lactobacillus separately but in fermented Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae), this effect is remarkable.
The anti-allergy action of embodiment 8 fermented Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae)s
BALB/C mice (7 age, male in week) is divided into 6 groups.Constituting of group: i) no disposal group (Normal) (3), ii) matched group (Control) (9), iii) S-PT84 (dry dead bacterium 0.0075% mixes bait) absorption group (12), the iv) not fermented Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae) that obtains of embodiment 2 (5% mixes bait) absorption group (not fermentation composition) (9), v) fermented Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae) (5% mixes bait) the absorption group (10) of S-PT84 (0.0075% mix bait)+not, the vi) fermented Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae) that obtains of embodiment 2 (5% mixes bait) absorption group (fermentation composition) (8).In addition, at S-PT84 group and S-PT84+ not in the fermented Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae) absorption group, added in the feedstuff with fermented Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae) in the S-PT84 of the suitable bacterium number of bacterium number that contains.Allow no disposal group, matched group AIN-93M (the Japanese Oriental Bio-service Co., Ltd. produce) normal diet of freely ingesting respectively, the special feedstuff that allows all the other groups freely ingest and to have mixed above-mentioned special component among the AIN-93M and made.Picked-up beginning one week back and after two weeks, mix 20 μ g ovalbumin (OVA) and 2mg gel aluminum hydroxides, give in all the other outer mouse peritoneals of five groups of no disposal group throwing and.After picked-up 4 weeks of beginning, carry out the heart blood sampling, preparation serum feedstuff is measured total IgE concentration in the serum.Also separate, cultivate splenocyte this moment, under concanavalin A (2.5 μ g/mL) stimulates, cultivated 24 hours, IFN-γ that produces in the mensuration culture supernatant and the amount of IL-4.Measure total IgE, IFN-γ, IL-4 by the ELISA method of having used OptEIA (production of BDPharmingen company).In addition, the total intake of feedstuff of each group all is about 3.0g.
The result of the test of total IgE concentration is seen Figure 12.Figure 12 shows to have only fermented Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae) absorption group to suppress the rising of IgE significantly.
Each is organized splenocyte and sees Figure 13 through the post-stimulatory IL-4 generation of concanavalin A.Compare with no disposal group, throw the generation reduction (matched group) that makes IL-4 with OVA.Not in the fermented Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae) absorption group, the generation of IL-4 is lower at S-PT84+.But, compare with matched group, in fermented Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae) absorption group, the generation of IL-4 rises.
Each is organized splenocyte and sees Figure 14 through the post-stimulatory IFN-γ of concanavalin A generation.Compare with no disposal group, throw the generation reduction (matched group) that makes IFN-γ with OVA.But, with matched group relatively, not in fermented Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae) absorption group, the fermented Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae) absorption group, the generation of IFN-γ rises at S-PT84+.This effect is especially remarkable in fermented Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae) absorption group.
The result of this embodiment shows that fermented Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae) of the present invention has anti-allergy action.In addition, absorb not fermented Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae), fermented Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae)+lactobacillus does not have anti-allergy action.Therefore show: in order to bring into play anti-allergy action, it is very important that Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae) is carried out lactic acid bacteria fermentation.
The IgA secretion potentiation that embodiment 9 is caused by fermented Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae) oral uptake
C57BL/6 mice (7 week age, male) is divided into roughly the same 3 groups of average weight.Constituting of group: fermented Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae) (5% mixes bait) the absorption group (fermentation composition) (9) that matched group (Control) (7), S-PT84 (dry dead bacterium 0.0075% mixes bait) absorption group (9) and embodiment 2 obtain.In addition, the S-PT84 of the bacterium number that the bacterium number that contains in use of S-PT84 group and the fermented Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae) is suitable.Allow the matched group AIN-93M normal diet of freely ingesting respectively, the special feedstuff that allows all the other groups freely ingest and to have mixed above-mentioned special component in the AIN-93M normal diet and made.After picked-up 1 week of beginning, take out small intestinal, after with PBS inside being cleaned, add the PBS that 4 times of amounts contain 0.05%Tween20, with POLYTRON homogenizer homogeneity.After the centrifugalize, reclaim supernatant, obtain the small bowel extract.(Purified IgA Antibody is anti-as one with ELISA method mensuration for the amount of IgA in the small bowel extract, Biotin Conjugate IgAAntibody is as two anti-(producing by Southern Biotech company), with Avidin-Horseradish peroxidase Conjugate colour developing).
The amount of IgA is seen Figure 15.Figure 15 shows, compares with matched group, and in fermented Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae) absorption group, the amount of IgA significantly rises in the small bowel extract.This effect ratio of fermented Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae) of the present invention is stronger when absorbing S-PT84 separately.
Embodiment 10 oral uptake fermented Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae)s produce the facilitation of cytokine to the intestinal immune competent cell
C57BL/6 mice (7 week age, male) is divided into roughly the same 3 groups of average weight.Constituting of group: (9: fermentation composition) of fermented Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae) (5% mixes bait) the absorption groups that matched group (7), S-PT84 absorption group (dry dead bacterium 0.0075% mixes bait) (9) and embodiment 2 obtain.Allow the matched group AIN-93M normal diet of freely ingesting respectively, the special feedstuff that allows all the other groups freely ingest and to have mixed above-mentioned special component in the AIN-93M normal diet and made.After one week, take out peyer's patches, cell culture with culture medium in (the RPMI1640 culture medium that contains 10% hyclone, 0.2% antibiotic-antifungal preparation mixed solution (production of Nacalai Tesque company)) by at cell filter (70 μ m, BD Falcon company produce) thus on gently compressing obtain cell, preparation peyer's patches cell sample.In having added the RPMI culture medium of 10%FBS, use concanavalin A 2.5 μ g/mL to 5 * 10 6Individual cytosis 24 hours, the amount of IL-4 that produces in the supernatant and IFN-γ is measured by the ELISA method of having used OptEIA (BD Pharmingen company).The result of the test of IL-4 generation is seen Figure 16, and the result of the test of IFN-γ generation is seen Figure 17.
Figure 16 and Figure 17 show, compare with matched group, significantly rise from the IFN-γ of the peyer's patches cell that absorbs fermented Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae) mice and the generation of IL-4.And on the other hand, in lactobacillus absorption group (S-PT84), do not find above-mentioned effect.
The result of embodiment 9 and embodiment 10 shows, is not to absorb lactobacillus separately but have only just to have intestinal immune to compose the effect of living when oral uptake fermented Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae).The above-mentioned effect of fermentation composition of the present invention is to obtain from the prediction on of fermentation raw material.
The antitumor action of embodiment 11 Thallus Laminariae (Thallus Eckloniae) fermented products
Ddy mice (Japanese SLC (strain)) is divided into 3 groups (10 every group), forces per os to give water (0.6mL), 50mg/kg not fermented Thallus Laminariae (Thallus Eckloniae) (500mg/kg), fermented Thallus Laminariae (Thallus Eckloniae) (500mg/kg) day after day.Force oral administration and beginning second day, in the mice chest with every 1 * 10 6Cells subcutaneous vaccination Sarcoma180 sarcoma cell, the carcinogenic mice of preparation Sarcoma180.The carcinogenic mice of Sarcoma180 is continued oral administration and 18 days.Duration of test is measured the tumor footpath, tries to achieve tumor size (Figure 18) according to (I) formula.Its result is, not fermented Thallus Laminariae (Thallus Eckloniae) organize the tumor size organized with fermented Thallus Laminariae (Thallus Eckloniae) respectively with the matched group that gives water relatively, tumor diminishes, in fermented Thallus Laminariae (Thallus Eckloniae) was organized, the tumor size of tumor inoculation after 11 days, 15 days and 19 days significantly diminished.Hence one can see that, and fermented Thallus Laminariae (Thallus Eckloniae) has better antitumor action.
(I) tumor size (mm 2)=maximum diameter (mm) * path * 3.14
Embodiment 12
Adopt the lactic acid bacteria fermentation compositions (fermented Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae)) of Semen Sesami, Semen sojae atricolor and the Thallus Laminariae (Thallus Eckloniae) of preparation among the embodiment 2, press the prescription shown in the table 4, make pill (to call the fermentation grain in the following text) (1 the weight: 350mg) that contains fermented Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae).Be specially, in fermented Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae) admixed excipients, be used for the raw materials such as sweeting agent of seasoning, after mediating in kneader, pill is made in molding in pellet processing machine.After the appropriateness drying, particle surface is carried out coating with Lac.In addition, fermented Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae) is not implemented in the plain ball surface finish operation of carrying out usually in the pill manufacturing.Also made the pill (shape is identical with the fermentation grain) that does not contain fermented Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae) simultaneously, as placebo.Each prescription sees Table 4.
[table 4]
Form table (w/w%)
The fermentation grain Placebo
Fermented Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae) 45.0 0
Excipient (starch etc.) 18.5 63.5
Sweeting agent (Mel, anhydrous crystal maltose, oligomeric xylose) 36.5 36.5
Meter 100 100
Take to 40 healthy volunteers of intra-company above-mentioned pill, 30 of every days (fermented Semen Sesami Semen sojae atricolor Thallus Laminariae (Thallus Eckloniae) is 4.7g/ days), immunoregulation effect is studied.The picked-up test adopts cross matching to carry out.That is, the experimenter is divided into NK activity, age, sex is benchmark and do not have two groups of difference statistically, as the picked-up sample, allow each group picked-up fermentation grain or the identical placebo of shape, absorbed for 4 weeks (I during the picked-up), the eluting phase was made as for 6 weeks.Then, change the picked-up sample of each group, 1 month placebo of reuptake or fermentation grain (II during the picked-up).Taking a blood sample in front and back during absorbing, with Ficoll-Hypaque density (Nycomed Pharma company) preparation leukocyte, measures the NK activity.About the NK activity, with leukocyte: K562=20: 1, measuring with K562 with the PINK method is the cytotoxic activity of target cell.In addition, leukocyte was cultivated 22 hours in the presence of PHA (phytohemagglutinin), measured the generation of IFN-γ, IL-4 in the culture supernatant, had analyzed the Th1/Th2 balance.
The active result of the test of NK is seen Figure 19.Picked-up fermentation grain makes that the NK activity of I, II significantly improves during the picked-up.Obtain among Figure 19 NK activity change amount (poor before and after the picked-up: Δ NK activity), calculate its meansigma methods of I, II during the picked-up.The results are shown in Figure 20.Compare with placebo absorption group, the NK activity change amount of fermentation grain absorption group is remarkable.
Then, measuring PHA stimulates IFN-γ that the back leukocyte produces and the amount of IL-4, obtains during the picked-up Th1/Th2 among I, the II than the variable quantity of (generation of generation/IL-4 of IFN-γ) (poor before and after the picked-up: Δ Th1/Th2), calculate its meansigma methods.The results are shown in Figure 21.With placebo absorption group relatively, the variable quantity of Th1/Th2 ratio is remarkable in the fermentation grain absorption group, has pointed out by picked-up fermentation grain Th1 is preponderated.
The invention is not restricted to the respective embodiments described above, can in the claim scope, carry out all distortion, and be also included within the technical scope of the present invention by making up the embodiment that disclosed various technological means form in the different embodiments aptly.

Claims (9)

1. compositions, it contains the Thallus Laminariae (Thallus Eckloniae) behind lactic acid bacteria fermentation and has immunoregulation effect.
2. compositions according to claim 1, wherein, immunoregulation effect is immunity effect effect and/or anti-allergy action.
3. compositions according to claim 1 and 2, wherein, lactobacillus is the vegetalitas lactobacillus.
4. compositions, it contains through the Thallus Laminariae (Thallus Eckloniae) behind the lactic acid bacteria fermentation, through Semen Sesami behind the lactic acid bacteria fermentation and the Semen sojae atricolor behind lactic acid bacteria fermentation.
5. compositions according to claim 4, wherein, lactobacillus is the vegetalitas lactobacillus.
6. according to claim 4 or 5 described compositionss, it has immunoregulation effect.
7. compositions according to claim 6, wherein, immunoregulation effect is immunity effect effect and/or anti-allergy action.
8. according to any described compositions of claim 1～7, it is ingesta, food additives, health food or medical composition.
9. according to any described compositions of claim 1～8, its form is a pill.
CNA2006100587868A 2005-03-04 2006-03-03 Fermentation composition having immunomodulating effect Pending CN1853656A (en)

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101677608B (en) * 2007-05-31 2013-02-27 可果美株式会社 Fermented food/beverage and method for production thereof
CN103932273A (en) * 2014-05-09 2014-07-23 福建农林大学 Kelp active lactobacillus buccal tablet and preparation method thereof
CN106520450A (en) * 2016-12-22 2017-03-22 阜阳市殿兴农业科技有限公司 Iodine-rich strawberry fruit wine and preparing method thereof
CN107312673A (en) * 2017-07-05 2017-11-03 界首市鲜天下家庭农场 A kind of preparation method of selenium rich strawberry wine

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101677608B (en) * 2007-05-31 2013-02-27 可果美株式会社 Fermented food/beverage and method for production thereof
CN103932273A (en) * 2014-05-09 2014-07-23 福建农林大学 Kelp active lactobacillus buccal tablet and preparation method thereof
CN103932273B (en) * 2014-05-09 2016-06-08 福建农林大学 One main laminaria Lactobacillus buccal tablet and preparation method thereof
CN106520450A (en) * 2016-12-22 2017-03-22 阜阳市殿兴农业科技有限公司 Iodine-rich strawberry fruit wine and preparing method thereof
CN107312673A (en) * 2017-07-05 2017-11-03 界首市鲜天下家庭农场 A kind of preparation method of selenium rich strawberry wine

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