JP2003137790A - Medicine including fructooligosaccharide including beta-2, 1 (beta 2 -> beta 1) bond-chain fructose oligomer as active ingredient - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a medicine that can daily and generally be used because it has high safety and prevents and ameliorates widely the deterioration of immune functions. SOLUTION: A fructooligosaccharide including a β-2,1 (β2→β1) bond chain fructose oligomer is used as an active ingredient, to provide an immune function deterioration-preventing and/or ameliorating agent, an immune function retention accelerator, an opportunistic infection-preventing and/or ameliorating agent, a tumor immunology enhancer and a living body control function deterioration- preventing and/or ameliorating agent. The fructooligosaccharide including the β-2,1 (β2→β1) bond chain fructose oligomer is obtained by allowing β- fructofuranosidase to act on sucrose originating from a variety of foods.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to β-2,1 (β) in which fructose (fructose) is bound to sucrose (sucrose).
2 → β1) The present invention relates to a medicament for activating an immune function, which comprises a fructo-oligosaccharide containing a linked-chain fructose oligomer as an active ingredient.

[0002]

2. Description of the Related Art Conventionally, 1-kestose (β-2,1
1 bond, hereinafter also referred to as GF2), nystose (β-
2,1 linked 2 co, hereinafter also referred to as GF3), 1 ^F -fructofuranosyl nystose (β-2,1 linked 3 co, hereinafter G
Β-2,1-linked chain fructose oligomers (also referred to as F4) are sucrose (GF) derived from foods such as sweet potato, sugar beet and sugar cane, which are derived from microorganisms, for example, a specific sugar enzyme derived from Aspergillus niger. It is provided as a fructooligosaccharide industrially produced by using (β-fructofuranosidase). This β-fructofuranosidase shows a hydrolytic enzyme action to 0.5% sucrose (substrate), and decomposes it into glucose and fructose, but as the sucrose concentration increases, a transposable enzyme reaction gradually progresses. To do. For example, this enzyme shows almost a transfer reaction to 50% sucrose, and the content of fructooligosaccharide exceeds 60%. According to this enzymological principle, 75% fructooligosaccharides (55% solid content) can be produced by batch method or immobilized enzyme packed column method.
Content), that is, the fructooligosaccharide content is 5 in the solid component.
A sugar solution of 5% or more is synthesized, and if fractionation and purification are further added, it is possible to produce powdery or granular fructooligosaccharides containing 95% of the solid component. The fructo-oligosaccharide contains about 5% glucose, fructose, sucrose, etc. in addition to the fructose oligomer.

Such fructooligosaccharides are routinely and commonly used as materials for various foods, health supplements and nutritional supplements. On the other hand, regarding the physiological and pharmacological activities of fructooligosaccharide components on the living body, the inhibitory effect on caries induction, the promotion / promotion of secondary intestinal immune system associated with the improvement of intestinal bacterial flora, intestinal regulation or improvement of serum lipid fraction It is well known that it has an effect of improving (hyperlipidemia), but against opportunistic infections and carcinogenesis caused by Candida and drug-resistant Staphylococcus aureus caused by the deterioration of various functions of the immune system. So far, there are no research papers or reports on the fact that fructooligosaccharides activate the immune function of the living body and can protect or prevent them.

[0004] By the way, the immunological monitoring mechanism of the living body is roughly divided into four major immune systems. The four major immune systems and immunocompetent cell groups involved in these immune systems are roughly as follows. [1] Humoral immune system (macrophages → helper T lymphocytes → B lymphocytes (differentiation into antibody-producing plasma cells)
IgG, M, E, A, D antibody production) [2] Cellular immune system (macrophages → helper T lymphocytes → killer T lymphocytes → lymphokines) [3] Non-specific immune system (macrophages → natural killer cells → interferon) α, β, γ) [4] Antibody-dependent target cell killing (ADC
C) system (macrophages → killer cells + IgG antibody).
The immune system of [1] and [2] is an immune system in a narrow sense, and in particular, the immune system of [3] is a purposeful immune system for the living body in order to prevent or prevent emergencies such as infection and carcinogenesis. Activating the activation of the immune system rapidly and efficiently leads to homeostasis of the living body, that is, maintenance of health. In addition, macrophages (macrophagocytic cells) are involved in everything as the primary immunocompetent cells in the four major immune systems, and the activation or activation of these macrophages greatly affects the flow of the immune system, which is the most important factor. It can be said to be an immunocompetent cell.

[0005] Mushroom extracts, streptococcus preparations, etc. have been conventionally provided as drugs that activate the immunological function by activating the immunological monitoring mechanism.

[0006]

However, the conventionally provided pharmaceuticals for activating the immune function are used for immunotherapy of cancer and have side effects and are widely used for the prevention and improvement of the reduction of immune function on a daily basis. It cannot be used for. On the other hand, with the advent of an aging society, the number of elderly people with impaired immune function will increase, and it is expected that various diseases caused by the impaired immune function will become a serious medical problem.
In addition, the decrease in the immune system of young people has become a problem today, and the emergence of medicines that are highly safe, such as materials used as foods for specified health uses, and that can prevent / improve immune system deterioration extensively. Was long-awaited.

The present invention has been made based on the above circumstances, and an object of the present invention is to provide a medicine which is excellent in safety, can be used on a daily basis, and can widely prevent / ameliorate a decrease in immune function.

[0008]

In order to solve the above-mentioned problems, the present inventors have found that indigenous bacterium-derived or plant-derived saccharides, especially in the non-specific immune system, are among human immunological surveillance mechanisms. It has a remarkable activating effect, and as a result, an anti-infectious disease enhancing effect (Watanabe T, Yokokura T. et al.
et al. J. Infect. Chemother.
4:76, 1998) and antitumor enhancing effect (Watana).
be T, Watanaba K .; et al. Cancel
r Detect. Present. 24: 173, 2
000, Hayashi I.M. Watanabe T. e
t al. Jpn. J. Clin. Immun. 24:
11, 2001) and the like, and focused on an enzymatically non-degradable (hardly degradable) fructooligosaccharide having a β-2,1 linkage and having a complicated stereomolecular structure. . Then, as a model, mice with weakened immune function prepared by continuous administration of dexamethasone, which is one of the adrenocortical hormones, were used as a model, and as with fructooligosaccharides, enzymatically non-degradable (hardly degradable) isomaltooligosaccharides were used as controls. Conducted animal experiments to restore / improve immune function and search for new materials with excellent safety, and diligently examined activation of non-specific immune system, especially activation stimulating action for macrophages and sustained activation action The present invention has been repeated.

The present invention relates to a preventive and / or ameliorating agent for lowering immune function, which comprises a fructooligosaccharide containing a β-2,1 (β2 → β1) linked fructose oligomer as an active ingredient. By using fructooligo as an active ingredient, the preventive and / or ameliorative agent for lowering immune function of the present invention has a activating effect on the immune function, in particular, a remarkable activating effect on a non-specific immune system, and reduces the immune function. It can prevent and improve the deterioration of immune function caused by various causes such as prevention and various diseases and trauma.

The present invention also provides β-2,1 (β2 → β
1) An agent for promoting sustained immune function, which comprises a fructo-oligosaccharide containing a linked-chain fructose oligomer as an active ingredient. The immune function duration-promoting agent of the present invention can activate the immune function, particularly, the continuous activation of the immune function by using fructooligo as an active ingredient.

The present invention also provides β-2,1 (β2 → β
1) A prophylactic and / or ameliorating agent for opportunistic infections containing fructooligosaccharides containing a linked-chain fructose oligomer as an active ingredient. The opportunistic infection preventive and / or ameliorating agent of the present invention, by using fructooligosaccharide as an active ingredient, the immune function is activated, and bacteria such as Staphylococcus epidermidis and mycobacteria, Candida, Aspergillus, etc. It is possible to prevent and improve opportunistic infections caused by viruses such as fungi, cytomegalovirus and herpes zoster virus.

The present invention also provides β-2,1 (β2 → β
1) A tumor immunity enhancer comprising a fructo-oligosaccharide containing a linked-chain fructose oligomer as an active ingredient.
The tumor immunity enhancer of the present invention activates immune function by using fructooligosaccharide as an active ingredient, and induces various cytokines such as tumor necrosis factor (TNF) and interleukin to immunize against tumor such as cancer. Can be strengthened.

The present invention also provides β-2,1 (β2 → β
1) It relates to a preventive and / or ameliorating agent for reduced bioregulatory function, which comprises a fructooligosaccharide containing a linked-chain fructose oligomer as an active ingredient. The preventive and / or ameliorative agent for reduced bioregulatory function of the present invention activates immune function by using fructooligo as an active ingredient, and, for example, of various bioregulatory functions caused by decrease in immune function with aging. Can prevent and improve the decline.

Further, fructooligosaccharides containing β-2,1 (β2 → β1) linked chain fructose oligomers, which are the active ingredients of the various pharmaceuticals of the present invention, act on β-fructofuranosidase on sucrose derived from various foods. You can get it.

[0015]

BEST MODE FOR CARRYING OUT THE INVENTION A fructooligosaccharide containing a β-2,1 (β2 → β1) linked chain fructose oligomer, which is an active ingredient of various medicines of the present invention, is 1-kestose, nystose, 1 ^F- fructofuranosyl. Β- which is a fructosyl transferase that contains nystose, etc., and sucrose derived from various foods such as sweet potato, sugar beet and sugar cane
It can be obtained by an experimental production method or an industrial production method by allowing fructofuranosidase to act. β-fructofuranosidase has a transfer reaction activity, and has the above-mentioned β-2,
As long as it produces a 1 (β2 → β1) linked chain fructose oligomer, those derived from various sources can be used. For example, Aspergillus niger (Asp
ergillus niger, Aureobasidium pullulans
β-fructofuranosidase derived from A. lurans), particularly Aspergillus niger (A
β-fructofuranosidase derived from spergillus niger) is preferred. The β-2,1 (β2 → β1) linked chain fructose oligomer contained in the fructooligosaccharide according to the present invention is not limited to the above-mentioned GF2, GF3 and GF4 in which 1 to 3 molecules of fructose are bound to sucrose, Those containing 4 or more molecules of fructose may be included, and these various β-2,
The content ratio of the 1 (β2 → β1) linked chain fructose oligomer is not particularly limited.

Commercially available products of such fructooligosaccharides are easily available. For example, GF2 contains about 35%, GF3 contains about 50%, and GF4 contains about 10%. In addition to these, sucrose contains about 3% and glucose. A powdered oligosaccharide (trade name: May-oligo P) manufactured by Meiji Seika Co., Ltd. containing about 2% fructose can be used.

The effective amount of fructooligosaccharide in the medicine for activating the immune function of the present invention is 200 to 500 mg per 1 kg of body weight (in terms of solid content) / day 2 to 4 times for healthy persons, considering age. It is preferable to administer daily, divided into two groups, and if you are not feeling well, if you have accumulated fatigue, or if you are an unhealthy person or patient whose immune system functions have been impaired, The dose can be increased appropriately according to the type, etc.
It is preferable to administer about 5 times the dose. In addition, when fructooligosaccharide is contained in various other food materials as a functional food, it is preferable to add an amount based on the dose to healthy subjects, but the type, form, and shape of the food used. It can be increased or decreased depending on the situation.

The fructooligosaccharide is generally orally administered in liquid or powder form, but the present invention is not limited to this. That is, the dosage form of fructooligosaccharide can be appropriately selected, and a suppository, an ointment, a pharmaceutically acceptable excipient, a binder, a disintegrating agent, and various other auxiliaries are used.
It can also be processed into a dosage form such as a poultice. Further, as long as the action and effect of fructooligosaccharide are not lost, other plant-derived active ingredients or drugs can be mixed and provided as a medical preparation. For example, infusion solution for parenteral nutrition (central and peripheral parenteral nutrition) in which fructooligosaccharide is mixed with nutrients, vitamins or minerals, subcutaneous / intradermal / intramuscular injections with other drugs, and Providing poultices and ointments containing plant-derived active ingredients with antibacterial and bactericidal action and antibiotics for the prevention and amelioration of opportunistic infections to atopic dermatitis, purulent dermatitis or severely damaged skin wounds. be able to.

Further, a function for preventing or improving the function of the immune function monitoring mechanism or the metabolic regulation function of the present invention is mixed with existing appropriate foods to enhance or promote these functions. It is also possible to provide a sex food. For example,
By incorporating fructo-oligosaccharides into various food materials in consideration of the percentage of total sugars, ingestion causes disturbance of eating habits (unbalanced diet, irregularity) and extreme Considering that immune functions are uniformly reduced due to lack of exercise, etc., functional foods or general foods that can be expected to have the effect of preventing / improving the functional deterioration of the immunological monitoring mechanism from early childhood and the effect of promoting continuous functioning. The biological homeostasis of elderly and elderly people, who are liable to deteriorate immune function
It is also easy to provide functional foods for maintaining health.

[0020]

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

Reference Example (Production of Immune System-Depleted Mice by Dexamethasone Treatment) A modified method (J. Jpn) by the present inventors using dexamethasone (decadron, manufactured by Banyu Pharmaceutical Co., Ltd.), which is one of the adrenocortical hormones treated by dexamethasone. . Assoc.I
nfect. Dis. 70: 574, 1996). That is, 5-week-old ICR female mice (average body weight: 21 g) were intraperitoneally injected with dexamethasone (hereinafter,
DM) Dissolved phosphate buffer (1.5m / ml)
containing 0.2 g of DM) (14.28 mg / kg)
/ Day) was administered (total concentration: 57.12 mg / kg) for a total of 4 times on days 0, 3, 4, and 7 to prepare mice with weakened immune system. In the following description, DM
Mice with weakened immune system due to treatment are referred to as DM-treated mice.

Example 1 (Examination of effect of fructooligosaccharide on body weight change of DM-treated mice) DM-treated mice prepared in the above-mentioned reference example (3 mice in each group)
On the other hand, fructooligosaccharide (Mei-oligo P, manufactured by Meiji Seika Co., Ltd., also in each of the following examples, also referred to as FO)
Was adjusted to 250 mg / ml with physiological saline, and then 0.2 ml (50 mg / mouse: 2380 m)
g / kg) DM treatment 3rd (4th day) and 4th (7
Immediately after each day, the mice were intraperitoneally administered twice in total (hereinafter, those treated with DM in each example and administered with fructooligosaccharide are referred to as DM + FO administration group). As an experimental group to which other oligosaccharides were administered, isomalt oligosaccharides containing α-1,6-linked glucose oligomer in the abdominal cavity of DM-treated mice (Iso-oligo, manufactured by Mie Kasei Co., Ltd. (Also referred to as IO) was adjusted in the same manner as above, and the same amount was administered by the same administration method as fructooligosaccharide (hereinafter, treated with DM in each Example,
Those administered with isomaltooligosaccharide are referred to as DM + IO administration group). As a control group, DM-treated mice were not administered with any oligosaccharide (in each of the following Examples,
A group treated with DM alone) and a group not treated with DM and each oligosaccharide (referred to as a non-administration normal control group in each Example below) were prepared, and immediately before the start of the experiment and after the first administration of the oligosaccharide (the experiment). The body weight of the mice in each group was measured 5 days after the start) and immediately after the second oligosaccharide administration (7 days after the start of the experiment).

As a result, as shown in Table 1, the body weight in the non-administered normal control group, which had an average body weight of 20.9 ± 0.4 g immediately before the start of the experiment, increased with the passage of breeding days,
On the 7th day after the start of the experiment, the amount reached 25 ± 0.8 g. On the other hand, the body weight in the DM-only administration group was almost the same as the average body weight on the fifth day after the start of the experiment even on the seventh day after the start of the experiment (mean body weight 21.6 ± 0.6).
g). On the other hand, although the increase in the average body weight in the DM + FO administration group and the DM + IO administration group was inferior to that in the non-administration normal control group, the average weight on the 7th day after the start of the experiment was larger than that in the DM single administration group. . It was suggested that this may be a result of recovery and improvement of the metabolism of the mouse, which was decreased by DM treatment, by the administration of each oligosaccharide.

[0024]

[Table 1]

Example 2 (Study on increase-improving effect and increase-sustaining effect of fructooligosaccharide on DM-treated mouse intraperitoneal exudate cell group) DM-treated mouse prepared in the above-mentioned reference example (3 mice in each group)
On the other hand, the concentration of fructooligosaccharide and isomaltooligosaccharide was adjusted to 500 mg / ml with physiological saline, and 0.2 ml of each was (100 mg / mouse: 476
0 mg / kg) DM-treated mouse (mouse after 4 doses of DM) was intraperitoneally administered, and 5 ml of Eagle's MEM culture medium containing 10% fetal bovine serum was administered 2, 5 and 7 days after administration.
(4 units / ml of heparin added) was injected into the abdominal cavity of the mouse with a syringe, and the abdomen was thoroughly rubbed and loosened, and the culture solution in the abdominal cavity was collected with the same syringe, and 1 ml of the culture solution was added to a plastic microplate (6 wells: 30 mm in diameter). ).
After incubating the plastic microplate at 37 ° C for 3 hours, the culture solution was gently removed by suction, washed twice with phosphate buffer solution, fixed with methanol, stained with Giemsa, and the total number of peritoneal exudate cells on the well ( Hereinafter, the total cell number) was calculated under a microscope. Further, the same experiment was conducted for the non-administration normal control group and the DM single administration group.

As a result, as shown in Table 2, the statistically significant difference between the total number of cells in the non-administered normal control group and those in the DM-administered group on days 2, 5 and 7 after administration of each oligosaccharide. When the difference (assay method: Student t-test method, the same applies to each of the following examples) was examined, a significant decrease (90%) in the total number of cells was observed by DM treatment in any number of experimental days ( Danger rate: 0.1% or less, P
∠ 0.001). On the other hand, in the experimental group in which DM-treated mice were administered fructooligosaccharide or isomaltooligosaccharide, a marked increase in the total cell number was observed on the second day after the administration of each oligosaccharide (vs. normal group of non-administration control, risk ratio: 0. 1% or less, P ∠ 0.001), and higher than that of the non-administered normal control group (about 3 to 4 times), and the amplification effect on the total cell number is 7 days after oligosaccharide administration. The persistence was also seen in. In addition, between both oligosaccharide administration groups,
It was confirmed that the action of fructooligosaccharide to promote the perfusion of the immunocompetent cell group into the abdominal cavity was significantly stronger than that of isomaltooligosaccharide 5 to 7 days after the administration of each oligosaccharide. From the above results, fructooligosaccharides having a complicated three-dimensional molecular structure have a strong activating effect on the nonspecific immune system during the immunological surveillance like the isomaltooligosaccharides, and the effect is sustained. It became clear.

[0027]

[Table 2]

Example 3 (Classification of Peritoneal Exudate Cell Groups in DM-treated Mice by Administration of Fructooligosaccharide and Their Ratio) Experiments relating to the classification and ratio of intraperitoneal exudate cells with the number of days after administration of fructooligosaccharide were carried out. The plastic microplate experimental material obtained in 2 was used and examined under a microscope. As a result, as shown in Table 3, the ratio of mouse macrophages (hereinafter referred to as MP) to lymphocytes (hereinafter referred to as LP) in the non-administered normal control group from day 2 to day 7 after administration of each oligosaccharide. The ratios were 45% to 48% and 46% to 50%, respectively, which were almost the same, but the MP of the DM alone administration group was only 31 to 33%, and the MP of the non-administration normal control group was also reduced by about 15%. (Danger rate: 1% or less, P∠0.
01), and conversely, LP was increased by 59 to 62%, which was about 13% of that of the non-treated normal control group. The ratio of MP on the second day after the administration of fructooligosaccharide increased to about 68% (vs. DM.
Single administration control group: risk rate 1% or less, P ∠ 0.01),
Moreover, the value was higher than that of the non-administration normal control group-derived MP (about 45%), and the effect was sustained even after 7 days from the administration of fructooligosaccharide (about 72%). On the other hand, the MP rate on the 5th to 7th day after the administration of DM-treated mice to which isomaltooligosaccharide was administered was lower than those of the fructooligosaccharide-administered experimental group. It has been shown that not only the increase promoting effect on macrophages but also the sustaining effect of the promoting effect. From the above, it was confirmed that fructooligosaccharide strongly mobilizes macrophages, which are the cells responsible for initial immunity in the immunological surveillance mechanism, to mobilize them, and has an effect of preventing and improving immune function decline.

[0029]

[Table 3]

Example 4 (Study on effect of enhancing recovery of phagocytic function of DM-treated mouse peritoneal macrophages of fructooligosaccharide) Intraperitoneal exudates derived from non-administered normal control group, DM alone administration group, DM + FO administration group and DM + IO administration group were administered. 2, 5, or 7 days after the administration of each oligosaccharide, the oligosaccharides were collected according to Example 2 and transferred to a plastic microplate at 37 ° C.
Cultured for 3 hours. After culturing, Candida albicans (C
and 15 CA per 1 peritoneal exudate cell of clinical isolates of C. andida albicans)
It was prepared with an Eagle MEM growth medium so that the number of cells (MOI = 15) was reached, added to a plastic microplate, and further incubated at 37 ° C. for 2 hours. Thereafter, the plastic microplate was washed, fixed, and stained according to the method of Example 2, and then, under a microscope, the phagocytosis rate of CA bacteria per 300 MPs and the CA phagocytosed per MP MPs.
The number of bacteria was calculated. As a result, as shown in Table 4, C of MPs from non-administered normal control group mice on days 2 to 7
Although the A bacterium phagocytosis rate was 47 to 49% on average, the CA bacterium phagocytosis rate of MP in the DM alone administration group was significantly reduced to 4 to 6% on average. On the other hand, the phagocytosis rate of MP from the DM + FO administration group on the 2nd to 7th days was significantly increased (vs. DM alone administration group: risk rate of 0.1% or less, P∠0.00.
1) and higher than those of the non-treated normal control group (average 62 to 69%). In addition, the CA + bacterial phagocytosis rate of MP on the 7th day after administration in the DM + FO administration group was DM
A significant difference was observed as compared with that of the + IO administration group (risk rate of 5% or less, P∠0.05). As described above, fructooligosaccharide was shown to be superior to that of MP in the DM + IO-administered group in terms of the effect of MP on sustained phagocytosis by CA bacteria.

[0031]

[Table 4]

On the other hand, as shown in Table 5, when the number of CA bacteria phagocytosed per 1 culture MP was calculated, the average number of phagocytic bacteria of non-administered normal control group-derived MPs on days 2 to 7 was 4 However, the phagocytic function against CA bacteria in the DM alone administration group was remarkably reduced, and the number of CA bacteria per 1 MP was only 0.6 to 0.9 CO / MP. there were. When fructooligosaccharides were administered to such DM-treated mice, the number of CA bacteria phagocytosed per MP1 was significantly increased 2 to 7 days after the administration, and more markedly than in the MPs derived from the non-administration normal control group. And (average 1
3.1 to 14.5 co / MP), the enhancement of the phagocytic function of MP reached 2.8 to 3.2 times. On the other hand, D
Also in the M + IO administration group, the number of CA bacteria phagocytosed by the cultured MP showed a high value during the experimental period (9.7 to 10.7 co /).
MP), but C phagocytosed by MP on days 5-7
The number of bacteria A was significantly lower than those of MPs derived from the DM + FO administration group (risk rate of 5% or less, P∠0.0.
5). From this, fructooligosaccharides have the same preventive and ameliorating effect on opportunistic infections via the activated immune system as isomaltooligosaccharides, and at the same time the isolating effect on the sustained effect of the phagocytic bactericidal function of activated macrophages. It was found to be significantly superior to that of maltooligosaccharides. These facts are also clear from FIG. 1, which shows a state in which peritoneal macrophages derived from DM-treated mice administered with fructooligosaccharides actively phagocytose CA bacteria.

[0033]

[Table 5]

Example 5 (Study on safety test of fructooligosaccharide) ICR female and male mice (5 weeks old) were prepared for each group of 5 mice,
Oral administration of fructooligosaccharide and isomaltooligosaccharide preparations (2-fold serial dilution) was used to record the number of deaths in mice over 7 days, and the 50% lethal dose of these preparations was determined according to the Behrens-Kurber method. As a result, the 50% lethal dose was 5950 mg / kg or more for both males and females.

[0035]

The drug containing fructooligosaccharide as an active ingredient of the present invention contains a β-2,1-linked chain fructose oligomer having an extremely complex and specific stereomolecular structure, and is quantitatively and qualitatively reduced. Since it is excellent in the cell proliferation / migration promotion action of the immunocompetent cell group and the enhancement and sustaining action of these various cell functions, it exerts an excellent effect on immunosuppressive diseases and immunodeficiency disorders in which various immune functions are weakened. Further, the β-2,1-linked chain fructose oligomer has an immunostimulatory action such as a hyperactivity effect on macrophages, which are the first cells for activation of immunological surveillance, and therefore the pharmaceutical composition of the present invention is aged. It is possible to prevent / improve various functions of the four major immune systems, which tend to decrease with changes. Furthermore, since fructooligosaccharides are excellent in safety and can be taken on a daily basis, the medicament of the present invention is extremely useful because it can prevent a decrease or weakening of the immune system, which is important for maintaining homeostasis of the living body. .

[Brief description of drawings]

FIG. 1 Candida albicans (Ca) of peritoneal macrophages derived from immunodeficient mice treated with dexamethasone (DM)
3 shows an image of phagocytosis of N. albicans). 1: Derived from normal mouse (non-administered normal control group) 2: Derived from DM-treated mouse (DM alone administration group) 3: Derived from DM-treated mouse + isomaltooligosaccharide (DM +)
IO administration group) 4: DM-treated mouse + fructo-oligosaccharide-derived (DM + F)
O administration group)

─────────────────────────────────────────────────── ─── Continuation of front page (51) Int.Cl. ⁷ Identification code FI theme code (reference) A61P 43/00 105 A61P 43/00 105 C07H 3/06 C07H 3/06 (72) Inventor Makoto Watanabe Mie Prefecture 227 Takamatsu, Kawagoe-cho, Mie-gun (72) Inventor Yasuyuki Watanabe 15-1 Hiramachi, Yokkaichi-shi, Mie (72) Inventor Takahisa Tokunaga 5-3-1 Chiyoda, Sakado-shi, Saitama F-term (reference) 4C057 BB01 BB04 4C086 AA01 AA02 EA01 MA01 MA04 MA52 NA14 ZB09 ZB26 ZB35

Claims (11)

[Claims] 1. A preventive and / or ameliorating agent for lowering immune function, which comprises a fructooligosaccharide containing a β-2,1 (β2 → β1) linked fructose oligomer as an active ingredient. 2. A fructooligosaccharide containing a β-2,1 (β2 → β1) linked chain fructose oligomer is obtained by reacting sucrose derived from various foods with β-fructofuranosidase. The agent for preventing and / or ameliorating the deterioration of immune function according to [4]. 3. An immune function sustained-promoting agent comprising a fructooligosaccharide containing a β-2,1 (β2 → β1) linked chain fructose oligomer as an active ingredient. 4. A fructooligosaccharide containing a β-2,1 (β2 → β1) linked chain fructose oligomer is obtained by reacting sucrose derived from various foods with β-fructofuranosidase. An agent for promoting sustained immune function according to item 4. 5. A prophylactic and / or ameliorator for opportunistic infections, which comprises a fructooligosaccharide containing a β-2,1 (β2 → β1) linked fructose oligomer as an active ingredient. 6. The opportunistic infection preventive and / or ameliorating agent according to claim 5, wherein the opportunistic infection is caused by Candida albicans. 7. A fructooligosaccharide containing a β-2,1 (β2 → β1) linked chain fructose oligomer is obtained by reacting sucrose derived from various foods with β-fructofuranosidase. Alternatively, the opportunistic infection preventive and / or ameliorating agent according to claim 6. 8. A tumor immunity enhancer comprising a fructooligosaccharide containing a β-2,1 (β2 → β1) linked chain fructose oligomer as an active ingredient. 9. A fructooligosaccharide containing a β-2,1 (β2 → β1) linked chain fructose oligomer is obtained by reacting sucrose derived from various foods with β-fructofuranosidase. The tumor immunity enhancer according to 1. 10. A preventive and / or ameliorating agent for bioregulatory function decline, which comprises a fructooligosaccharide containing a β-2,1 (β2 → β1) linked fructose oligomer as an active ingredient. 11. A fructooligosaccharide containing a β-2,1 (β2 → β1) linked chain fructose oligomer is obtained by reacting sucrose derived from various foods with β-fructofuranosidase. The preventive and / or ameliorating agent for deterioration of biological regulation function according to the item 1.