JP2007197331A - Composition for ameliorating allergic physical constitution - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a composition for ameliorating allergic constitution naturally ingestible in daily life. <P>SOLUTION: The composition for ameliorating the allergic constitution comprises a galactooligosaccharide as a main ingredient. Furthermore, a food and drink uses the composition. Since the galactooligosaccharide is already widely used in heath-oriented foods such as a specific food for health and is a material in which the safety is sufficiently established, the galactooligosaccharide is naturally ingestible over a long period in the daily life. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to an allergic constitution improving composition that is effective in preventing or treating allergic diseases. Specifically, the present invention relates to an allergic constitution improving composition containing galactooligosaccharide as a main component. Furthermore, it is related with the food and drink using it.

In recent years, the number of patients suffering from various allergic diseases such as hay fever and atopic dermatitis has increased remarkably and has become a national problem. The mechanism of allergic diseases is complex, and there are many unexplained parts, but it is gradually becoming clear that there is a cause for disturbance of the immune regulatory system. Helper T cells play an important role in immune regulation, but there are two types of helper T cells, Th1 cells and Th2 cells, which control cellular and humoral immunity through the production of cytokines. . Th1 cells and Th2 cells suppress each other's activation by the cytokines they produce and maintain a balance (Th1 / Th2 balance). However, if Th2 cells are strongly induced for some reason, they develop allergies.
IL-4 and IL-13 produced by Th2 cells stimulate B cells to produce IgE. When IgE binds to an allergen, binds to a high affinity IgEFc receptor, and crosslinks on mast cells, chemical mediators such as histamine are released. Eosinophils that have infiltrated tissues from the blood are also activated by cytokines made by Th2 cells and secrete various mediators. These mediators are thought to cause increased mucus distribution, smooth muscle contraction, and induce allergic symptoms.
In general, the immune system in the fetal and neonatal period is biased toward Th2 cells, and the Th1 / Th2 balance is established with the growth after birth. For normal development of this balance, stimulation from bacterial infections and intestinal flora is considered essential. The hypothesis that the recent increase in the prevalence of allergic diseases in developed countries, including Japan, may be due to a decrease in infectious diseases due to improvements in the hygienic environment and a delay in the formation of normal intestinal flora. Advocated (hygiene hypothesis).

  Measures against allergic diseases include administration of drugs such as antihistamines and steroids, desensitization therapy that gradually weakens the reaction after long-term administration of a small amount of allergen, diet therapy to avoid contact with allergen , Masks, etc., but these have problems such as side effects, the need for long-term treatment, and decreased QOL, so as a simpler method, food that can improve symptoms by ingestion The development of food ingredients is also actively promoted.

  As foods for improving allergic symptoms, foods containing β-glucan and foods containing specific lactic acid bacteria have been developed. In addition, some oligosaccharides such as isomaltoligosaccharide, raffinose, and melibiose have been studied (Patent Documents 1, 2, and 3, Non-Patent Documents 1 and 2). However, there are no reports on galactooligosaccharides that differ in constituent sugar and binding mode from these, and in which the degradation mode in vivo and the sugar produced by degradation are also different. I don't know.

Patent Document 4 describes the use of an external drug as an immunomodulator of an oligosaccharide having a galactose residue. This is based on the action of the oligosaccharide to inhibit the activation and proliferation of lymphocytes via the receptor by the elastin peptide, but this method always involves a sufficient amount of the oligosaccharide around the lymphocytes. However, the administration method is limited because it must be present, and the excessive immune reaction is not fundamentally prevented or ameliorated merely by alleviating the inflammatory reaction. In addition, this patent document only describes parenteral use as an external medicine, and does not mention the use by oral intake shown in the present invention.
JP2001-288093 JP2003-40779 JP2005-281298 Special table 2000-516591 Abstracts of the 59th Annual Meeting of the Japanese Society of Nutrition and Food Science p113 British Journal of Nutrition (2002), 88, 421-426

  An object of the present invention is to provide an allergic constitution improving composition that can be taken naturally in daily life.

  In order to solve these problems, the present inventors have intensively searched for substances that suppress the production of IgE, which plays a central role in the development of allergies, and as a result, have found that galactooligosaccharides have a function of suppressing IgE production.

Further studies on the immunoregulation of galactooligosaccharides revealed that galactooligosaccharides reduce the production of cytokine IL-4. IL-4 is a cytokine produced by Th2 cells, and promotes the induction of naive T cells into Th2 cells themselves and stimulates B cells to promote the production of IgE. The galacto-oligosaccharide is also found to reduce the production of IgG ₁ that is controlled on the Th2 side is one of the subtypes of IgG.

  From these examination results, we obtain important knowledge that galactooligosaccharide has a function to suppress the production of allergy and improve allergic constitution by improving the Th1 / Th2 balance biased to Th2 to suppress IgE production. To complete the invention.

  That is, the present invention relates to an allergic constitution improving composition characterized by containing galactooligosaccharide as a main component, and food and drink using the same.

The galactooligosaccharide used in the present invention is an oligosaccharide having a structure in which a plurality of galactoses are bonded to glucose, and is represented by the following general formula.
Gal- (Gal) n-Glc (n = 1-3, β-1,4 bond)

  Such galactooligosaccharides can be produced by allowing β-galactosidase to act on lactose, and are actually industrially produced and marketed. However, the production method of the galactooligosaccharide of the present invention is not limited, and a product produced by a method other than the enzymatic method can be used.

  The galactooligosaccharide used in the present invention is not necessarily a highly purified product, and a mixture with other saccharides can also be used. For example, cup oligos (Nisshin Sugar Co., Ltd.) are galacto-oligosaccharides that account for about 70% of the total (of which most are trisaccharides, including a small amount of tetrasaccharides and pentasaccharides), as well as lactose Although it is a composition in which a disaccharide and a few monosaccharides are mixed, it can be used without any problem as the allergic constitution improving composition of the present invention.

  The allergic constitution improving composition containing the galactooligosaccharide of the present invention as a main component is not limited in its form, and can be used in a form that meets the needs of the user, such as a lump, powder, or liquid. Specific examples of foods and drinks using the same include sweeteners, soft drinks, lactic acid bacteria drinks, yogurt, bread, and various supplements.

  The amount of galactooligosaccharide used in the present invention is influenced by age, constitution, symptom, body weight, administration method, etc., but usually 0.1 to 20 g per day is desirable for adults.

  Galactooligosaccharides have an intestinal regulating action, a lipid metabolism improving action, and a mineral absorption action, and are widely used for foods intended for health, including foods for specified health use. In addition, as an effect on the immune system, an intestinal immunity activation effect has been found by the present inventors (Japanese Patent Application 2005-119136). Furthermore, since galactooligosaccharide is also a component contained in human breast milk, its safety is well established.

  EXAMPLES Next, the present invention will be specifically described with reference to examples, but the present invention is not limited to the examples.

Allergy suppression effect by galactooligosaccharide Allergic state was induced by administering ovalbumin intraperitoneally into mice. By quantifying IgE antibodies in serum and spleen cell culture, IgG ₁ antibody, various cytokines, was assessed allergy effect of improving gave galactooligosaccharides mixed into the feed.

(Experimental materials and methods)
1. Breeding of experimental animals As experimental animals, 6-week-old female BALB / c mice (Tokyo Experimental Animal Co., Ltd.) were purchased and used. As the galactooligosaccharide, cup oligo P (Nisshin Sugar Co., Ltd., galactooligosaccharide content 70%) was used. The mice were divided into two groups (6 mice per group): a control feed group and a galactooligosaccharide intake group (feed group containing cup oligo P5.0%). Each group shown in Table 1 was fed and fed. Feed and drinking water were ad libitum.

  2. Induction of allergic condition Three weeks after the start of the breeding, 200 μl of a mixed solution of ovalbumin (OVA) and Imject Alum (PIERCE) (OVA solution: Imject Alum = 3: 1). OVA content in 200 μl of the mixed solution 20 μg) was intraperitoneally administered to mice to induce allergic conditions.

  3. Dissection, blood collection, spleen cell culture Two weeks after OVA administration, the mice were dissected under ether anesthesia, and blood was collected from the posterior vena cava. The obtained blood was centrifuged to prepare serum. Spleen cells were prepared by physical treatment, the number of cells was adjusted to 1E7 cell / ml, and then cultured in a 48-well culture plate by adding 480 μl / well. 10 μl of 5 mg / ml OVA solution was added to all wells. RPMI1640 medium was used as the medium. The culture solution was collected at 3 days and 7 days of culture.

4. Antibodies and cytokines quantification IgE antibody, IgG ₁ antibodies, quantitation of various cytokines was performed by ELISA using commercially available kits.

  5. Statistical analysis The experimental data were expressed as mean ± standard deviation. Statistical analysis of the results was performed by the Student's-t method, and a significant difference was determined when p ≦ 0.05.

(result)
IgE level As shown in FIG. 1, the total IgE level in serum was significantly lower in the galactooligosaccharide intake group than in the control feed group (p = 0.024). The results of analyzing the spleen cell culture medium for 7 days also showed a significant decrease (p = 0.05, FIG. 2). As shown in FIG. 3, the amount of IgE specific to OVA contained in serum tended to be lower in the galactooligosaccharide intake group, although no significant difference was obtained.

IgG ₁ amount As shown in Fig. 4-6, when comparing the amount of IgG ₁ controlled by Th2 in one of the IgG subtypes, the total IgG ₁ in serum and spleen cell cultures is not very clear Although there was no significant difference, IgG ₁ specific for OVA contained in the spleen cell culture was significantly decreased in the galactooligosaccharide-ingested group (p = 0.007).

  Cytokine levels As shown in Fig. 7-9, various cytokines contained in the 3-day culture of spleen cells were analyzed, and there was no clear difference between the groups for IFN-γ and IL-12 on the Th1 side. However, Th2 side IL-4 significantly decreased in the galactooligosaccharide intake group (p = 0.03).

  From the above results, it was revealed that galactooligosaccharide has an effect of improving the allergic constitution by improving the Th1 / Th2 balance inclined to the Th2 side and reducing the IgE antibody production.

  100 g of cup oligo P (Nisshin Sugar Co., Ltd., galactooligosaccharide content 70%) and 0.35 g of a high-sweetness sweetener aspartame were mixed well to produce 100 g of a table-type sweetener having the same sweetness as sugar.

It is the graph which showed the influence which the galactooligosaccharide added to the feed has on the serum total IgE of the mouse | mouth which intraperitoneally administered OVA. It is the graph which showed the influence which the galactooligosaccharide added to the feed has on the spleen cell culture solution total IgE of the mouse | mouth which intraperitoneally administered OVA. It is the graph which showed the influence which the galactooligosaccharide added to the feed has on serum OVA specific IgE of the mouse | mouth which intraperitoneally administered OVA. The value of one mouse in the control group was defined as 1000 U / ml, and the values of other mice were converted based on this value. Galactooligosaccharides was added to the feed is a graph showing the effect of OVA in serum total IgG ₁ mice were intraperitoneally administered. Galactooligosaccharides was added to the feed is a graph showing the effect of OVA spleen cell culture total IgG ₁ mice were intraperitoneally administered. Galactooligosaccharides was added to the feed is a graph showing the effect of OVA spleen cell culture OVA-specific IgG ₁ mice were intraperitoneally administered. The value of one mouse in the control group was defined as 1000 U / ml, and the values of other mice were converted based on this value. It is the graph which showed the influence which the galactooligosaccharide added to the feed has on the spleen cell culture medium IFN-γ of the mouse which intraperitoneally administered OVA. It is the graph which showed the influence which the galactooligosaccharide added to the feed has on the spleen cell culture solution IL-12 of the mouse | mouth which intraperitoneally administered OVA. It is the graph which showed the influence which the galactooligosaccharide added to the feed has on the spleen cell culture solution IL-4 of the mouse | mouth which intraperitoneally administered OVA.

Claims (2)

An allergic constitution improving composition comprising a galactooligosaccharide represented by the following general formula as a main component.
Gal- (Gal) n-Glc (n = 1-3, β-1,4 bond) A food or drink containing the allergic constitution improving composition according to claim 1.

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