WO2017022560A1 - Plasmacytoid dendritic cell proliferation promoter - Google Patents
Plasmacytoid dendritic cell proliferation promoter Download PDFInfo
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- WO2017022560A1 WO2017022560A1 PCT/JP2016/071814 JP2016071814W WO2017022560A1 WO 2017022560 A1 WO2017022560 A1 WO 2017022560A1 JP 2016071814 W JP2016071814 W JP 2016071814W WO 2017022560 A1 WO2017022560 A1 WO 2017022560A1
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/74—Bacteria
- A61K35/741—Probiotics
- A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
- A61K35/747—Lactobacilli, e.g. L. acidophilus or L. brevis
Definitions
- the present invention relates to a plasmacytoid dendritic cell increasing agent, a food and beverage for increasing the number of plasmacytoid dendritic cells, an increase in the number of plasmacytoid dendritic cells, comprising lactic acid bacteria belonging to Lactobacillus helveticus as an active ingredient
- the present invention relates to a nutritional composition and a feed for increasing the number of plasmacytoid dendritic cells.
- Immunity is a biological defense mechanism possessed by many animals, and plays a role in eliminating pathogens such as bacteria and viruses that invade from the outside and tumor cells generated in vivo.
- the innate immune system is an innate immune system
- the acquired immune system is an immune system that is acquired in response to the stimulation of a foreign substance.
- foreign substances such as bacteria and viruses enter the body
- macrophages, NK cells, and dendritic cells which are responsible for the innate immune system, work to remove foreign substances.
- dendritic cells transmit information on foreign substances to T cells and B cells, thereby inducing CD8 + T cells that specifically attack the foreign substances and antibody production to activate the acquired immune system.
- the dendritic cell is a cell that is responsible for the innate immune system and that also participates in the acquired immune system, and thus functions as a control tower for the entire immunity.
- dendritic cells There are various types of dendritic cells, which are roughly classified into classical dendritic cells (conventional dendritic cells) and plasmacytoid dendritic cells (pDC).
- Classical dendritic cells play an important role in the induction of the acquired immune system because of their strong antigen-presenting ability.
- Plasmacytoid dendritic cells have a weak antigen-presenting ability, but they regulate not only the immunostimulatory system toward the elimination of foreign substances but also the immune control system that suppresses excessive immune responses, so that the homeostasis of the immune system It is the cell that is the key to keeping it safe.
- Type I and type III interferon are cytokines that induce the production of antiviral factors that are inherently possessed by living bodies in order to prevent the growth of viruses, and have a role in preventing viral infection from spreading to the entire tissue.
- production of type I IFN is strongly stimulated by binding of RNA or DNA derived from virus to TLR7 or TLR9 of cells. Therefore, type I IFN inducers that stimulate TLR7 or TLR9 as antiviral agents have been extensively studied so far.
- the interferon production inducer described in Patent Document 1 contains lactic acid bacteria as an active ingredient.
- plasmacytoid dendritic cells are activated to induce IFN production, and the present invention shows It is essentially different from those that increase the number of plasmacytoid dendritic cells.
- Lactococcus lactis is the only lactic acid bacterium that activates plasmacytoid dendritic cells in the patent document, and its activating effect on lactic acid bacteria belonging to the genus Lactobacillus. It is shown that there is no.
- Lactobacillus helveticus has not been studied at all.
- a characteristic of plasmacytoid dendritic cells in the immune control system is to induce IL-10-producing T cells and regulatory T cells, which greatly contributes to suppression of inflammatory diseases.
- the biological defense function is enhanced with an immunostimulant, there is a concern that inflammation may be caused by the excessive ecological defense function.
- anti-inflammatory agents are used, there has been a concern that the risk of infection will increase due to excessively low biological defense functions.
- plasmacytoid dendritic cells have functions of both immunostimulants and anti-inflammatory agents and are important defense functions against viral infections, but at the same time have a function to act on the immune control system, which is just an immune function. It is a key cell involved in maintaining homeostasis.
- the interferon production inducer described in Patent Document 1 has a certain control effect against virus infection.
- high type I IFN in serum is an exacerbating factor, such as systemic lupus erythematosus. Therefore, when an interferon production inducer such as Patent Document 1 is used, a plasmacytoid tree is more than necessary. It is not preferable because it stimulates dendritic cells to promote production of excess type I IFN. Since a considerable amount of type I IFN is produced from plasmacytoid dendritic cells at the time of virus infection, it is possible to maintain a sufficient number of cells at the time of viral infection rather than to activate plasmacytoid dendritic cells at normal times. Considered important.
- the present invention provides a drug or nutrition having an action of increasing plasmacytoid dendritic cells, which can bring about effects of both prevention of infectious diseases and prevention of inflammatory diseases by increasing plasmacytoid dendritic cells. It is an object to provide a composition, food and drink, and feed.
- the present invention has the following constitutions: (1) A plasmacytoid dendritic cell increasing agent comprising a lactic acid bacterium belonging to Lactobacillus helveticus or a culture thereof as an active ingredient.
- Plasmacytoid administration of a plasmacytoid dendritic cell increasing agent comprising a lactic acid bacterium belonging to Lactobacillus helveticus or its culture as an active ingredient to a subject having a reduced number of plasmacytoid dendritic cells Use method of dendritic cell increasing agent.
- a method of using an immunostimulant comprising administering an immunostimulant comprising a lactic acid bacterium belonging to Lactobacillus helveticus or a culture thereof as an active ingredient to a subject with reduced immunity.
- (11) Use of a lactic acid bacterium belonging to Lactobacillus helveticus or a culture thereof in the production of an immunostimulator.
- (13) A virus infection preventive agent or virus comprising administering a virus infection preventive agent or therapeutic agent comprising a lactic acid bacterium belonging to Lactobacillus helveticus or a culture thereof as an active ingredient to a virus infection preventive subject or a virus infected subject How to use infection treatment.
- a method of using an anti-inflammatory agent comprising administering an anti-inflammatory agent comprising a lactic acid bacterium belonging to Lactobacillus helveticus or a culture thereof as an active ingredient to a subject having inflammation.
- an anti-inflammatory agent comprising a lactic acid bacterium belonging to Lactobacillus helveticus or a culture thereof as an active ingredient to a subject having inflammation.
- Ingestion of Lactobacillus helvetius induces an increase in plasmacytoid dendritic cells in vivo, preventing and improving excessive immune responses in addition to infection prevention and treatment effects against viruses, etc. Can reduce inflammatory effects.
- plasmacytoid dendritic cells can be increased and the above-mentioned action can be achieved.
- FIG. 4 is a graph comparing the number of plasmacytoid dendritic cells in mesenteric lymph nodes after oral administration of Lactobacillus helveticus strain SBT2171 cells to mice.
- FIG. 4 is a graph comparing the numbers of plasmacytoid dendritic cells in mesenteric lymph nodes after oral administration of a bacterial cell culture of Lactobacillus helveticus strain SBT2171 to mice.
- a lactic acid bacterium belonging to Lactobacillus helveticus can be used as a lactic acid bacterium in the present invention.
- Lactobacillus helveticus SBT2171 strain (deposited as FERM BP-5445), SBT-2161 strain (deposited as NITE ABP-01707), SBT2195 strain (deposited as FERM P-11538), SBT2196 strain (FERM P -11676), SBT0064 strain (deposited as FERM P-21079), SBT0402 strain (deposited as FERM P-21559) and the like are preferred, but not limited thereto.
- Lactobacillus helveticus can be cultured according to a conventional method for lactic acid bacteria culture.
- various media such as a milk medium or a medium containing milk components and a semi-synthetic medium not containing the milk medium can be used.
- examples of such a medium include reduced skim milk medium.
- the cells isolated from the obtained culture by means of collection such as centrifugation can be used as they are as the active ingredient of the present invention. Concentrated, dried, freeze-dried cells, etc. can be used, or dead cells can be formed by heat drying. Not only those that are purely isolated as cells, but also cultures, suspensions, other cell-containing materials, and cytoplasm and cell wall fractions obtained by treating cells with enzymes or physical means should be used. it can.
- Examples of the culture form include not only a culture medium using a medium generally used for cultivation of lactic acid bacteria, such as MRS medium (manufactured by DIFCO), which is a synthetic medium, and reduced skim milk medium, but also cheese, fermented milk, milk.
- MRS medium manufactured by DIFCO
- dairy products such as product lactic acid bacteria drink
- a culture supernatant prepared by removing milk protein precipitates and bacterial cell components from the obtained culture using methods such as centrifugation and filtration can also be used. Since it is a supernatant with a low solid content, the range of application to foods and drinks is widened.
- the culture supernatant can be prepared by centrifuging the reduced skim milk culture at 5,000 rpm for 10 minutes.
- the action of increasing plasmacytoid dendritic cells in the present invention refers to an action of increasing the number of plasmacytoid dendritic cells. By increasing the number of plasmacytoid dendritic cells, the functions of the immunostimulant and anti-inflammatory agent possessed by the cells can be exhibited.
- excipients, stabilizers, flavoring agents and the like that are permitted in the formulation are mixed as appropriate and concentrated, freeze-dried, or heat dried to form dead cells. These dried products, concentrates, and pastes are also included.
- excipients, binder, disintegrant, lubricant, flavoring agent, suspending agent, coating agent, and any other optional agent it can also be formulated by mixing drugs.
- the dosage form can be tablets, capsules, granules, powders, powders, syrups, etc., and these are preferably administered orally.
- the plasma cell-like dendritic cell increasing agent of the present invention may be added to any food or drink, and may be added to the raw material during the production process of the food or drink.
- food and drink include dairy products such as cheese, fermented milk, dairy lactic acid bacteria beverages, lactic acid bacteria beverages, butter and margarine, beverages such as dairy beverages, fruit juice beverages and soft drinks, eggs such as jelly, candy, pudding and mayonnaise Processed products, confectionery and breads such as butter cake, and various types of powdered milk, infant foods, nutritional compositions and the like can be mentioned, but are not particularly limited.
- the plasma cell-like dendritic cell-increasing agent of the present invention can be used as an immunostimulant, a viral infection preventive or therapeutic agent, an immune tolerance inducer, or an anti-inflammatory agent containing this as an active ingredient.
- the plasmacytoid dendritic cell increasing agent of this invention can be mix
- the blending ratio of Lactobacillus helveticus to each material is not particularly limited, and is easy to manufacture and preferable What is necessary is just to adjust suitably according to a daily dose.
- the dose is individually determined in consideration of the symptom, age, etc. of the subject of administration, but in general, in the case of an adult, 10 to 200 g / day of the Lactobacillus helveticus culture, or the fungus body itself, is used. What is necessary is just to adjust a compounding quantity so that 0.1-5,000 mg / day can be ingested. A desired effect can be exhibited by ingesting in this way.
- FACS fluorescence activated cell sorting
- Example 1 Production of Lactobacillus helveticus culture
- Raw milk was sterilized by heating (75 ° C, 15 seconds), cooled to 30 ° C, and 0.01% calcium chloride was added.
- 0.7% of commercially available lactic acid bacteria starter (LD starter, Christian Hansen) and 1% of Lactobacillus helveticus strain SBT2171 (FERM BP-5445) are added, and 0.003% of rennet is further added. Solidified.
- the curd thus obtained was cut and stirred until the pH was 6.2 to 6.1, and the whey was discharged to obtain curd grains. Then, the curd grains were packed and pressed, further salted, and aged at 10 ° C.
- Test Example 2 Oral administration test of Lactobacillus helveticus culture to mice Test Method An oral administration test was performed using the culture of Lactobacillus helveticus SBT2171 obtained in Example 1. The test method was performed according to Test Example 1. The ratio of plasmacytoid dendritic cells to the total number of cells in the mesenteric lymph nodes after dissection was measured, and the results are shown in FIG. 2. 2. Test results From FIG. 2, the trait in the mesenteric lymph node in the group (LH2171 group) ingesting the diet to which the culture of Lactobacillus helveticus SBT2171 was added was greater than in the group ingesting the diet not added (control group). It was found that the proportion of cell-like dendritic cells was significantly higher. That is, it was shown that the number of plasmacytoid dendritic cells increased by ingesting the Lactobacillus helveticus culture.
- Example 2 Manufacture of a plasmacytoid dendritic cell increasing agent (granule) 5 in an edible synthetic medium (with 0.5% yeast extract and 0.1% trypticase peptone), Lactobacillus helveticus strain SBT2171 After inoculating a weight% and culturing at 38 ° C. for 15 hours, the cells were collected by centrifugation. The collected cells were lyophilized to obtain a freeze-dried powder of the cells. 1 g of this lyophilized powder was mixed with 5 g of lactose and formed into granules to obtain the plasmacytoid dendritic cell increasing agent of the present invention.
- Example 3 Production of plasmacytoid dendritic cell increasing agent (granule) Synthetic medium edible with Lactobacillus helveticus JCM-1120 strain (0.5% yeast extract, 0.1% trypticase peptone added) 5% by weight was inoculated and cultured at 38 ° C. for 15 hours, and the cells were collected by centrifugation. The collected cells were lyophilized to obtain a freeze-dried powder of the cells. 1 g of this lyophilized powder was mixed with 5 g of lactose and formed into granules to obtain the plasmacytoid dendritic cell increasing agent of the present invention.
- Example 4 Manufacture of a plasmacytoid dendritic cell increasing agent (powder)
- the Lactobacillus helveticus SBT2171 obtained in Example 2 above in accordance with the provisions of the 13th revised Japanese Pharmacopoeia Description of Drugs General Rules "Powder” Lactose (JP) 400 g and potato starch (JP) 600 g were added to 10 g of the lyophilized powder of the strain and mixed uniformly to produce the plasmacytoid dendritic cell increasing agent of the present invention.
- Example 5 Manufacture of a plasmacytoid dendritic cell increasing agent (powder)
- the Lactobacillus helveticus JCM obtained in Example 3 above in accordance with the provisions of the 13th revised Japanese Pharmacopoeia explanation general formulation "powder" Lactose (JP) 400 g and potato starch (JP) 600 g were added to 10 g of lyophilized powder of the -1120 strain and mixed uniformly to produce the plasmacytoid dendritic cell increasing agent of the present invention.
- Example 6 Production of nutritional health food for increasing plasma-like dendritic cells in the form of sticks 40 g of vitamin C or an equal mixture of vitamin C and citric acid, 100 g of granulated sugar, 60 g of an equal mixture of corn starch and lactose 40 g of lyophilized powder of Lactobacillus helveticus SBT2171 strain obtained in Example 2 was added and mixed. The mixture was packed in a bag to produce 150 bags of the stick-like nutritional health food of the present invention.
- Example 7 Production of feed for increasing plasmacytoid dendritic cells Soybean meal 12 kg, skim milk powder 14 kg, soybean oil 4 kg, corn oil 2 kg, palm oil 23.2 kg, corn starch 14 kg, wheat flour 9 kg, bran 2 kg, vitamin mixture 5 kg, 2.8 kg of cellulose and 2 kg of a mineral mixture were blended, sterilized at 120 ° C. for 4 minutes, and 10 kg of Lactobacillus helveticus SBT2171 strain obtained in Example 2 was blended to produce a feed.
- Lactobacillus helveticus SBT2171 The name and address of the depository institution where the biological material was deposited National Institute of Advanced Industrial Science and Technology Patent Biological Deposit Center Date 1-3-1 Higashi 1-chome, Tsukuba City, Ibaraki, Japan Date of deposit of biological material in Heisei June 22, 6 (June 22, 1994) (original deposit date) March 6, 1996 (March 6, 1996) (Date of transfer to deposit under the Budapest Treaty by original deposit) The deposit number assigned by the depository in Hai for the deposit FERM BP-5445
Abstract
The present invention addresses the problem of providing a pharmaceutical, food/beverage, and feed having a plasmacytoid dendritic cell proliferation-promoting effect by promoting the proliferation of plasmacytoid dendritic cells, thereby imparting the dual effect of preventing infection and preventing inflammatory disease. The use of lactic acid bacteria belonging to Lactobacillus helveticus or a culture thereof as an active ingredient made it possible to provide a pharmaceutical, food/beverage, and feed for promoting the proliferation of plasmacytoid dendritic cells within the body.
Description
本発明は、ラクトバチルス・ヘルベティカス（Lactobacillus helveticus）に属する乳酸菌を有効成分とする、形質細胞様樹状細胞増加剤、形質細胞様樹状細胞数増加用飲食品、形質細胞様樹状細胞数増加用栄養組成物および形質細胞様樹状細胞数増加用飼料に関する。
The present invention relates to a plasmacytoid dendritic cell increasing agent, a food and beverage for increasing the number of plasmacytoid dendritic cells, an increase in the number of plasmacytoid dendritic cells, comprising lactic acid bacteria belonging to Lactobacillus helveticus as an active ingredient The present invention relates to a nutritional composition and a feed for increasing the number of plasmacytoid dendritic cells.
免疫は、多くの動物に備わった生体防御機構であり、外部より侵入する細菌やウイルスなどの病原体や生体内で生じた腫瘍細胞を排除する役割を担う。免疫系には、自然免疫系と獲得免疫系の２つのシステムが存在し、生体防御機能を担っている。自然免疫系は，先天的に備わった免疫系であり、獲得免疫系は，後天的に外来異物の刺激に応じて形成される免疫系である。細菌やウイルスなどの異物が体内に進入すると、まず自然免疫系を担うマクロファージ、ＮＫ細胞、樹状細胞が異物の除去に向けて働く。引き続いて樹状細胞は、異物の情報をＴ細胞やＢ細胞に伝達することで、異物を特異的に攻撃するＣＤ８＋Ｔ細胞や抗体産生を誘導して獲得免疫系を活性化させる。
Immunity is a biological defense mechanism possessed by many animals, and plays a role in eliminating pathogens such as bacteria and viruses that invade from the outside and tumor cells generated in vivo. There are two systems in the immune system, the innate immunity system and the acquired immunity system, which are responsible for biological defense functions. The innate immune system is an innate immune system, and the acquired immune system is an immune system that is acquired in response to the stimulation of a foreign substance. When foreign substances such as bacteria and viruses enter the body, first, macrophages, NK cells, and dendritic cells, which are responsible for the innate immune system, work to remove foreign substances. Subsequently, dendritic cells transmit information on foreign substances to T cells and B cells, thereby inducing CD8 + T cells that specifically attack the foreign substances and antibody production to activate the acquired immune system.
このように樹状細胞は、自身が自然免疫系を担当する細胞であり、かつ獲得免疫系にも関与する細胞であることから、免疫全体の司令塔として機能している。樹状細胞には様々な種類が存在するが、大きく分けて古典的樹状細胞（conventional dendritic cell:ｃＤＣ）と形質細胞様樹状細胞（plasmacytoid dendritic cell:ｐＤＣ）に分類される。古典的樹状細胞は強い抗原提示能を有することから、獲得免疫系の誘導に重要な役割を果たす。一方、形質細胞様樹状細胞は抗原提示能は弱いものの、異物の排除に向かう免疫賦活系だけではなく、過剰な免疫応答を抑制する免疫制御系をも調節することから、免疫系の恒常性を保つための要となっている細胞である。
Thus, the dendritic cell is a cell that is responsible for the innate immune system and that also participates in the acquired immune system, and thus functions as a control tower for the entire immunity. There are various types of dendritic cells, which are roughly classified into classical dendritic cells (conventional dendritic cells) and plasmacytoid dendritic cells (pDC). Classical dendritic cells play an important role in the induction of the acquired immune system because of their strong antigen-presenting ability. Plasmacytoid dendritic cells, on the other hand, have a weak antigen-presenting ability, but they regulate not only the immunostimulatory system toward the elimination of foreign substances but also the immune control system that suppresses excessive immune responses, so that the homeostasis of the immune system It is the cell that is the key to keeping it safe.
異物排除における形質細胞様樹状細胞の特徴として、ウイルス感染時に大量のＩ型およびIII型インターフェロン（ＩＦＮ）を産生することがあげられる。Ｉ型およびIII型ＩＦＮは、ウイルスの増殖を阻止するために生体が本来保有している抗ウイルス因子の産生を誘導するサイトカインであり、ウイルス感染が組織全体へ拡大するのを防ぐ役割がある。この反応では、ウイルス由来のＲＮＡまたはＤＮＡが細胞のＴＬＲ７またはＴＬＲ９と結合することでＩ型ＩＦＮの産生が強く刺激される。したがって、これまでにも抗ウイルス剤としてＴＬＲ７またはＴＬＲ９を刺激するようなＩ型ＩＦＮ誘導剤が広く研究されてきた。特許文献１に記載されるインターフェロン産生誘導剤は乳酸菌を有効成分とするものであるが、当該特許文献では形質細胞様樹状細胞を活性化してＩＦＮ産生を誘導するものであり、本発明が示す形質細胞様樹状細胞数を増加させるものとは本質的に異なるものである。また、当該特許文献で形質細胞様樹状細胞を活性化させる乳酸菌として示されているのはラクトコッカス・ラクティス（Lactococcus lactis）のみであり、ラクトバチルス（Lactobacillus）属の乳酸菌にはその活性化作用は無いことが示されている。また、ラクトバチルス・ヘルベティカス（Lactobacillus helveticus）については一切検討されてこなかった。
A characteristic of plasmacytoid dendritic cells in excluding foreign bodies is that they produce a large amount of type I and type III interferon (IFN) during viral infection. Type I and type III IFNs are cytokines that induce the production of antiviral factors that are inherently possessed by living bodies in order to prevent the growth of viruses, and have a role in preventing viral infection from spreading to the entire tissue. In this reaction, production of type I IFN is strongly stimulated by binding of RNA or DNA derived from virus to TLR7 or TLR9 of cells. Therefore, type I IFN inducers that stimulate TLR7 or TLR9 as antiviral agents have been extensively studied so far. The interferon production inducer described in Patent Document 1 contains lactic acid bacteria as an active ingredient. However, in this patent document, plasmacytoid dendritic cells are activated to induce IFN production, and the present invention shows It is essentially different from those that increase the number of plasmacytoid dendritic cells. In addition, Lactococcus lactis is the only lactic acid bacterium that activates plasmacytoid dendritic cells in the patent document, and its activating effect on lactic acid bacteria belonging to the genus Lactobacillus. It is shown that there is no. Moreover, Lactobacillus helveticus has not been studied at all.
一方、免疫制御系における形質細胞様樹状細胞の特徴は、ＩＬ－１０産生型Ｔ細胞や制御性Ｔ細胞を誘導することであり、炎症性疾患の抑制に大きく寄与している。一般的に免疫賦活剤で生体防御機能を高めると、生態防御機能が行き過ぎたことによる炎症の惹起が懸念される。逆に抗炎症剤などを使用すると、行き過ぎた生体防御機能の低下による感染リスクの上昇が懸念されてきた。しかし、形質細胞様樹状細胞は、免疫賦活剤と抗炎症剤の機能を併せ持ち、ウイルス感染からの重要な防御機能でありながら、同時に免疫制御系に働きかける機能を有しており、まさしく免疫機能の恒常性維持に関わる要の細胞である。したがって、生体内で形質細胞様樹状細胞の数が低下すると、ウイルス感染リスクが高まるばかりでなく炎症性疾患のリスクも高まることから、生体内での形質細胞様樹状細胞の数を増やすような薬剤または食品成分が期待されてきた。
On the other hand, a characteristic of plasmacytoid dendritic cells in the immune control system is to induce IL-10-producing T cells and regulatory T cells, which greatly contributes to suppression of inflammatory diseases. In general, when the biological defense function is enhanced with an immunostimulant, there is a concern that inflammation may be caused by the excessive ecological defense function. On the other hand, when anti-inflammatory agents are used, there has been a concern that the risk of infection will increase due to excessively low biological defense functions. However, plasmacytoid dendritic cells have functions of both immunostimulants and anti-inflammatory agents and are important defense functions against viral infections, but at the same time have a function to act on the immune control system, which is just an immune function. It is a key cell involved in maintaining homeostasis. Therefore, reducing the number of plasmacytoid dendritic cells in vivo increases not only the risk of viral infection but also the risk of inflammatory diseases, so increase the number of plasmacytoid dendritic cells in vivo. New drugs or food ingredients have been expected.
特許文献１に記載されるインターフェロン産生誘導剤は、ウイルス感染に対して一定の防除効果を有する。しかし、全身性エリスマトーデスのように血清中のＩ型ＩＦＮ高値が憎悪因子となる疾病も存在することから、特許文献１のようなインターフェロン産生誘導剤を用いると、必要以上に形質細胞様樹状細胞を刺激して過剰なＩ型ＩＦＮの産生を促してしまい好ましくない。ウイルス感染時には形質細胞様樹状細胞から相当量のＩ型ＩＦＮが産生されることから、平時には形質細胞様樹状細胞を活性化させるよりも、ウイルス感染時に対応できるだけの細胞数を保つことが重要と考えられる。そこで、本発明は、形質細胞様樹状細胞を増加させることで、感染症の予防と炎症疾患の予防の両者の効果をもたらすことができる形質細胞様樹状細胞増加作用を有するする医薬品や栄養組成物、飲食品および飼料を提供することを課題とする。
The interferon production inducer described in Patent Document 1 has a certain control effect against virus infection. However, there is a disease in which high type I IFN in serum is an exacerbating factor, such as systemic lupus erythematosus. Therefore, when an interferon production inducer such as Patent Document 1 is used, a plasmacytoid tree is more than necessary. It is not preferable because it stimulates dendritic cells to promote production of excess type I IFN. Since a considerable amount of type I IFN is produced from plasmacytoid dendritic cells at the time of virus infection, it is possible to maintain a sufficient number of cells at the time of viral infection rather than to activate plasmacytoid dendritic cells at normal times. Considered important. Therefore, the present invention provides a drug or nutrition having an action of increasing plasmacytoid dendritic cells, which can bring about effects of both prevention of infectious diseases and prevention of inflammatory diseases by increasing plasmacytoid dendritic cells. It is an object to provide a composition, food and drink, and feed.
本発明者らは、生体内で形質細胞様樹状細胞数を増加させる因子を鋭意探索した結果、乳酸菌のラクトバチルス・ヘルベティカス（Lactobacillus helvetivcus）に形質細胞様樹状細胞数を増加させる作用を見出し、本発明を完成させるに至った。
即ち本発明は以下の構成を有する
（１）ラクトバチルス・ヘルベティカス（Lactobacillus helveticus）に属する乳酸菌又はその培養物を有効成分とする形質細胞様樹状細胞増加剤。
（２）前記ラクトバチルス・ヘルベティカス（Lactobacillus helveticus）に属する乳酸菌がラクトバチルス・ヘルベティカス（Lactobacillus helveticus）SBT2171株（FERM BP-5445）であることを特徴とする、（１）に記載の形質細胞様樹状細胞増加剤。
（３）（１）又は（２）に記載の剤を有効成分として含む免疫賦活剤。
（４）（１）又は（２）に記載の剤を有効成分として含むウイルス感染予防または治療剤。
（５）（１）又は（２）に記載の剤を有効成分として含む免疫寛容誘導剤。
（６）（１）又は（２）に記載の剤を有効成分として含む抗炎症剤。
（７）（１）～（６）のいずれかに記載の剤を添加した形質細胞様樹状細胞増加用栄養組成物、形質細胞様樹状細胞増加用飲食品又は形質細胞様樹状細胞増加用飼料。
（８）ラクトバチルス・ヘルベティカス（Lactobacillus helveticus）に属する乳酸菌又はその培養物を有効成分とする形質細胞様樹状細胞増加剤を、形質細胞様樹状細胞数の減少した対象に投与する形質細胞様樹状細胞増加剤の使用方法。
（９）形質細胞様樹状細胞増加剤の製造における、ラクトバチルス・ヘルベティカス（Lactobacillus helveticus）に属する乳酸菌又はその培養物の使用。
（１０）ラクトバチルス・ヘルベティカス（Lactobacillus helveticus）に属する乳酸菌又はその培養物を有効成分とする免疫賦活剤を、免疫の低下した対象に投与する免疫賦活剤の使用方法。
（１１）免疫賦活剤の製造におけるラクトバチルス・ヘルベティカス（Lactobacillus helveticus）に属する乳酸菌又はその培養物の使用。
（１３）ラクトバチルス・ヘルベティカス（Lactobacillus helveticus）に属する乳酸菌又はその培養物を有効成分とするウイルス感染予防剤または治療剤を、ウイルス感染予防対象またはウイルス感染した対象に投与するウイルス感染予防剤またはウイルス感染治療剤の使用方法。
（１２）ウイルス感染予防剤またはウイルス感染治療剤の製造におけるラクトバチルス・ヘルベティカス（Lactobacillus helveticus）に属する乳酸菌又はその培養物の使用。
（１４）ラクトバチルス・ヘルベティカス（Lactobacillus helveticus）に属する乳酸菌又はその培養物を有効成分とする免疫寛容誘導剤を、過剰な免疫応答対象に投与する免疫寛容誘導剤の使用方法。
（１５）免疫寛容誘導剤の製造におけるラクトバチルス・ヘルベティカス（Lactobacillus helveticus）に属する乳酸菌又はその培養物の使用。
（１６）ラクトバチルス・ヘルベティカス（Lactobacillus helveticus）に属する乳酸菌又はその培養物を有効成分とする抗炎症剤を、炎症を有する対象に投与する抗炎症剤の使用方法。
（１７）抗炎症剤の製造におけるラクトバチルス・ヘルベティカス（Lactobacillus helveticus）に属する乳酸菌又はその培養物の使用。 As a result of diligent search for factors that increase the number of plasmacytoid dendritic cells in vivo, the present inventors have found that Lactobacillus helvetivcus has an effect of increasing the number of plasmacytoid dendritic cells. The present invention has been completed.
That is, the present invention has the following constitutions: (1) A plasmacytoid dendritic cell increasing agent comprising a lactic acid bacterium belonging to Lactobacillus helveticus or a culture thereof as an active ingredient.
(2) The plasmacytoid tree according to (1), wherein the lactic acid bacterium belonging to Lactobacillus helveticus is Lactobacillus helveticus SBT2171 strain (FERM BP-5445) Dendritic cell increasing agent.
(3) An immunostimulant comprising the agent according to (1) or (2) as an active ingredient.
(4) A preventive or therapeutic agent for viral infection comprising the agent according to (1) or (2) as an active ingredient.
(5) An immune tolerance inducer comprising the agent according to (1) or (2) as an active ingredient.
(6) An anti-inflammatory agent comprising the agent according to (1) or (2) as an active ingredient.
(7) Nutritional composition for increasing plasmacytoid dendritic cells, food or drink for increasing plasmacytoid dendritic cells, or increasing plasmacytoid dendritic cells to which the agent according to any one of (1) to (6) is added Feed.
(8) Plasmacytoid administration of a plasmacytoid dendritic cell increasing agent comprising a lactic acid bacterium belonging to Lactobacillus helveticus or its culture as an active ingredient to a subject having a reduced number of plasmacytoid dendritic cells Use method of dendritic cell increasing agent.
(9) Use of a lactic acid bacterium belonging to Lactobacillus helveticus or a culture thereof in the production of a plasmacytoid dendritic cell increasing agent.
(10) A method of using an immunostimulant comprising administering an immunostimulant comprising a lactic acid bacterium belonging to Lactobacillus helveticus or a culture thereof as an active ingredient to a subject with reduced immunity.
(11) Use of a lactic acid bacterium belonging to Lactobacillus helveticus or a culture thereof in the production of an immunostimulator.
(13) A virus infection preventive agent or virus comprising administering a virus infection preventive agent or therapeutic agent comprising a lactic acid bacterium belonging to Lactobacillus helveticus or a culture thereof as an active ingredient to a virus infection preventive subject or a virus infected subject How to use infection treatment.
(12) Use of a lactic acid bacterium belonging to Lactobacillus helveticus or a culture thereof in the production of a viral infection preventive or a viral infection therapeutic agent.
(14) A method for using an immune tolerance inducer, wherein an immune tolerance inducer comprising a lactic acid bacterium belonging to Lactobacillus helveticus or a culture thereof as an active ingredient is administered to an excessive immune response subject.
(15) Use of a lactic acid bacterium belonging to Lactobacillus helveticus or a culture thereof in the production of an immune tolerance inducer.
(16) A method of using an anti-inflammatory agent comprising administering an anti-inflammatory agent comprising a lactic acid bacterium belonging to Lactobacillus helveticus or a culture thereof as an active ingredient to a subject having inflammation.
(17) Use of a lactic acid bacterium belonging to Lactobacillus helveticus or a culture thereof in the production of an anti-inflammatory agent.
即ち本発明は以下の構成を有する
（１）ラクトバチルス・ヘルベティカス（Lactobacillus helveticus）に属する乳酸菌又はその培養物を有効成分とする形質細胞様樹状細胞増加剤。
（２）前記ラクトバチルス・ヘルベティカス（Lactobacillus helveticus）に属する乳酸菌がラクトバチルス・ヘルベティカス（Lactobacillus helveticus）SBT2171株（FERM BP-5445）であることを特徴とする、（１）に記載の形質細胞様樹状細胞増加剤。
（３）（１）又は（２）に記載の剤を有効成分として含む免疫賦活剤。
（４）（１）又は（２）に記載の剤を有効成分として含むウイルス感染予防または治療剤。
（５）（１）又は（２）に記載の剤を有効成分として含む免疫寛容誘導剤。
（６）（１）又は（２）に記載の剤を有効成分として含む抗炎症剤。
（７）（１）～（６）のいずれかに記載の剤を添加した形質細胞様樹状細胞増加用栄養組成物、形質細胞様樹状細胞増加用飲食品又は形質細胞様樹状細胞増加用飼料。
（８）ラクトバチルス・ヘルベティカス（Lactobacillus helveticus）に属する乳酸菌又はその培養物を有効成分とする形質細胞様樹状細胞増加剤を、形質細胞様樹状細胞数の減少した対象に投与する形質細胞様樹状細胞増加剤の使用方法。
（９）形質細胞様樹状細胞増加剤の製造における、ラクトバチルス・ヘルベティカス（Lactobacillus helveticus）に属する乳酸菌又はその培養物の使用。
（１０）ラクトバチルス・ヘルベティカス（Lactobacillus helveticus）に属する乳酸菌又はその培養物を有効成分とする免疫賦活剤を、免疫の低下した対象に投与する免疫賦活剤の使用方法。
（１１）免疫賦活剤の製造におけるラクトバチルス・ヘルベティカス（Lactobacillus helveticus）に属する乳酸菌又はその培養物の使用。
（１３）ラクトバチルス・ヘルベティカス（Lactobacillus helveticus）に属する乳酸菌又はその培養物を有効成分とするウイルス感染予防剤または治療剤を、ウイルス感染予防対象またはウイルス感染した対象に投与するウイルス感染予防剤またはウイルス感染治療剤の使用方法。
（１２）ウイルス感染予防剤またはウイルス感染治療剤の製造におけるラクトバチルス・ヘルベティカス（Lactobacillus helveticus）に属する乳酸菌又はその培養物の使用。
（１４）ラクトバチルス・ヘルベティカス（Lactobacillus helveticus）に属する乳酸菌又はその培養物を有効成分とする免疫寛容誘導剤を、過剰な免疫応答対象に投与する免疫寛容誘導剤の使用方法。
（１５）免疫寛容誘導剤の製造におけるラクトバチルス・ヘルベティカス（Lactobacillus helveticus）に属する乳酸菌又はその培養物の使用。
（１６）ラクトバチルス・ヘルベティカス（Lactobacillus helveticus）に属する乳酸菌又はその培養物を有効成分とする抗炎症剤を、炎症を有する対象に投与する抗炎症剤の使用方法。
（１７）抗炎症剤の製造におけるラクトバチルス・ヘルベティカス（Lactobacillus helveticus）に属する乳酸菌又はその培養物の使用。 As a result of diligent search for factors that increase the number of plasmacytoid dendritic cells in vivo, the present inventors have found that Lactobacillus helvetivcus has an effect of increasing the number of plasmacytoid dendritic cells. The present invention has been completed.
That is, the present invention has the following constitutions: (1) A plasmacytoid dendritic cell increasing agent comprising a lactic acid bacterium belonging to Lactobacillus helveticus or a culture thereof as an active ingredient.
(2) The plasmacytoid tree according to (1), wherein the lactic acid bacterium belonging to Lactobacillus helveticus is Lactobacillus helveticus SBT2171 strain (FERM BP-5445) Dendritic cell increasing agent.
(3) An immunostimulant comprising the agent according to (1) or (2) as an active ingredient.
(4) A preventive or therapeutic agent for viral infection comprising the agent according to (1) or (2) as an active ingredient.
(5) An immune tolerance inducer comprising the agent according to (1) or (2) as an active ingredient.
(6) An anti-inflammatory agent comprising the agent according to (1) or (2) as an active ingredient.
(7) Nutritional composition for increasing plasmacytoid dendritic cells, food or drink for increasing plasmacytoid dendritic cells, or increasing plasmacytoid dendritic cells to which the agent according to any one of (1) to (6) is added Feed.
(8) Plasmacytoid administration of a plasmacytoid dendritic cell increasing agent comprising a lactic acid bacterium belonging to Lactobacillus helveticus or its culture as an active ingredient to a subject having a reduced number of plasmacytoid dendritic cells Use method of dendritic cell increasing agent.
(9) Use of a lactic acid bacterium belonging to Lactobacillus helveticus or a culture thereof in the production of a plasmacytoid dendritic cell increasing agent.
(10) A method of using an immunostimulant comprising administering an immunostimulant comprising a lactic acid bacterium belonging to Lactobacillus helveticus or a culture thereof as an active ingredient to a subject with reduced immunity.
(11) Use of a lactic acid bacterium belonging to Lactobacillus helveticus or a culture thereof in the production of an immunostimulator.
(13) A virus infection preventive agent or virus comprising administering a virus infection preventive agent or therapeutic agent comprising a lactic acid bacterium belonging to Lactobacillus helveticus or a culture thereof as an active ingredient to a virus infection preventive subject or a virus infected subject How to use infection treatment.
(12) Use of a lactic acid bacterium belonging to Lactobacillus helveticus or a culture thereof in the production of a viral infection preventive or a viral infection therapeutic agent.
(14) A method for using an immune tolerance inducer, wherein an immune tolerance inducer comprising a lactic acid bacterium belonging to Lactobacillus helveticus or a culture thereof as an active ingredient is administered to an excessive immune response subject.
(15) Use of a lactic acid bacterium belonging to Lactobacillus helveticus or a culture thereof in the production of an immune tolerance inducer.
(16) A method of using an anti-inflammatory agent comprising administering an anti-inflammatory agent comprising a lactic acid bacterium belonging to Lactobacillus helveticus or a culture thereof as an active ingredient to a subject having inflammation.
(17) Use of a lactic acid bacterium belonging to Lactobacillus helveticus or a culture thereof in the production of an anti-inflammatory agent.
ラクトバチルス・ヘルベティカス（Lactobacillus helvetius）を摂取する事で、生体内で形質細胞様樹状細胞の増加が誘導され、ウイルスなどに対する感染予防・治療効果のほかに、過剰な免疫応答の予防・改善、炎症作用を鎮めることができる。また、該乳酸菌を含有するチーズまたは乳酸菌飲料などの培養物を摂取することで、形質細胞様樹状細胞を増加させ、前記作用を奏することも可能となる
Ingestion of Lactobacillus helvetius induces an increase in plasmacytoid dendritic cells in vivo, preventing and improving excessive immune responses in addition to infection prevention and treatment effects against viruses, etc. Can reduce inflammatory effects. In addition, by ingesting a culture such as cheese or a lactic acid bacteria beverage containing the lactic acid bacteria, plasmacytoid dendritic cells can be increased and the above-mentioned action can be achieved.
本発明における乳酸菌としては、ラクトバチルス・ヘルベティカス（Lactobacillus helveticus）に属する乳酸菌を用いることができる。特に、ラクトバチルス・ヘルベティカス（Lactobacillus helveticus）SBT2171株（FERM BP-5445として寄託）、SBT-2161株(NITE ABP-01707として寄託)、SBT2195株（FERM P-11538として寄託）、SBT2196株（FERM P-11676として寄託）、SBT0064株（FERM P-21079として寄託）、SBT0402株（FERM P-21559として寄託）等が好ましいが、これらに限定されるものではない。
ラクトバチルス・ヘルベティカスは、乳酸菌培養の常法に従って培養することができる。培養培地には、乳培地又は乳成分を含む培地、これを含まない半合成培地など種々の培地を用いることができる。このような培地としては、還元脱脂乳培地などを例示することができる。
得られた培養物から遠心分離などの集菌手段によって分離された菌体をそのまま本発明の有効成分として用いることができる。濃縮、乾燥、凍結乾燥などした菌体を用いることもできるし、加熱乾燥などにより死菌体にしてもよい。
菌体として純粋に分離されたものだけでなく、培養物、懸濁物、その他の菌体含有物や、菌体を酵素や物理的手段を用いて処理した細胞質や細胞壁画分も用いることができる。
培養物などの形態としては、合成培地であるＭＲＳ培地（ＤＩＦＣＯ社製）、還元脱脂乳培地など一般的に乳酸菌の培養に用いられる培地を用いた培養物だけでなく、チーズ、発酵乳、乳製品乳酸菌飲料などの乳製品などを例示することができるが特に限定されるものではない。
さらに、得られた培養物から遠心分離、濾過操作などの方法を用いて、乳タンパク質沈殿や菌体成分を除去することによって調製した培養上清なども用いることができる。固形分が少ない上清であるため、飲食品などへの適用範囲が広くなる。例えば、還元脱脂乳培養物を５，０００ｒｐｍ、１０分間遠心分離することにより培養上清を調製することができる。
本発明における形質細胞様樹状細胞増加作用とは、形質細胞様樹状細胞の数を増加する作用をいう。形質細胞様樹状細胞数を増加させることで当該細胞が有する免疫賦活剤と抗炎症剤の機能を発揮させることができる。 As a lactic acid bacterium in the present invention, a lactic acid bacterium belonging to Lactobacillus helveticus can be used. In particular, Lactobacillus helveticus SBT2171 strain (deposited as FERM BP-5445), SBT-2161 strain (deposited as NITE ABP-01707), SBT2195 strain (deposited as FERM P-11538), SBT2196 strain (FERM P -11676), SBT0064 strain (deposited as FERM P-21079), SBT0402 strain (deposited as FERM P-21559) and the like are preferred, but not limited thereto.
Lactobacillus helveticus can be cultured according to a conventional method for lactic acid bacteria culture. As the culture medium, various media such as a milk medium or a medium containing milk components and a semi-synthetic medium not containing the milk medium can be used. Examples of such a medium include reduced skim milk medium.
The cells isolated from the obtained culture by means of collection such as centrifugation can be used as they are as the active ingredient of the present invention. Concentrated, dried, freeze-dried cells, etc. can be used, or dead cells can be formed by heat drying.
Not only those that are purely isolated as cells, but also cultures, suspensions, other cell-containing materials, and cytoplasm and cell wall fractions obtained by treating cells with enzymes or physical means should be used. it can.
Examples of the culture form include not only a culture medium using a medium generally used for cultivation of lactic acid bacteria, such as MRS medium (manufactured by DIFCO), which is a synthetic medium, and reduced skim milk medium, but also cheese, fermented milk, milk. Although dairy products, such as product lactic acid bacteria drink, can be illustrated, it is not specifically limited.
Furthermore, a culture supernatant prepared by removing milk protein precipitates and bacterial cell components from the obtained culture using methods such as centrifugation and filtration can also be used. Since it is a supernatant with a low solid content, the range of application to foods and drinks is widened. For example, the culture supernatant can be prepared by centrifuging the reduced skim milk culture at 5,000 rpm for 10 minutes.
The action of increasing plasmacytoid dendritic cells in the present invention refers to an action of increasing the number of plasmacytoid dendritic cells. By increasing the number of plasmacytoid dendritic cells, the functions of the immunostimulant and anti-inflammatory agent possessed by the cells can be exhibited.
ラクトバチルス・ヘルベティカスは、乳酸菌培養の常法に従って培養することができる。培養培地には、乳培地又は乳成分を含む培地、これを含まない半合成培地など種々の培地を用いることができる。このような培地としては、還元脱脂乳培地などを例示することができる。
得られた培養物から遠心分離などの集菌手段によって分離された菌体をそのまま本発明の有効成分として用いることができる。濃縮、乾燥、凍結乾燥などした菌体を用いることもできるし、加熱乾燥などにより死菌体にしてもよい。
菌体として純粋に分離されたものだけでなく、培養物、懸濁物、その他の菌体含有物や、菌体を酵素や物理的手段を用いて処理した細胞質や細胞壁画分も用いることができる。
培養物などの形態としては、合成培地であるＭＲＳ培地（ＤＩＦＣＯ社製）、還元脱脂乳培地など一般的に乳酸菌の培養に用いられる培地を用いた培養物だけでなく、チーズ、発酵乳、乳製品乳酸菌飲料などの乳製品などを例示することができるが特に限定されるものではない。
さらに、得られた培養物から遠心分離、濾過操作などの方法を用いて、乳タンパク質沈殿や菌体成分を除去することによって調製した培養上清なども用いることができる。固形分が少ない上清であるため、飲食品などへの適用範囲が広くなる。例えば、還元脱脂乳培養物を５，０００ｒｐｍ、１０分間遠心分離することにより培養上清を調製することができる。
本発明における形質細胞様樹状細胞増加作用とは、形質細胞様樹状細胞の数を増加する作用をいう。形質細胞様樹状細胞数を増加させることで当該細胞が有する免疫賦活剤と抗炎症剤の機能を発揮させることができる。 As a lactic acid bacterium in the present invention, a lactic acid bacterium belonging to Lactobacillus helveticus can be used. In particular, Lactobacillus helveticus SBT2171 strain (deposited as FERM BP-5445), SBT-2161 strain (deposited as NITE ABP-01707), SBT2195 strain (deposited as FERM P-11538), SBT2196 strain (FERM P -11676), SBT0064 strain (deposited as FERM P-21079), SBT0402 strain (deposited as FERM P-21559) and the like are preferred, but not limited thereto.
Lactobacillus helveticus can be cultured according to a conventional method for lactic acid bacteria culture. As the culture medium, various media such as a milk medium or a medium containing milk components and a semi-synthetic medium not containing the milk medium can be used. Examples of such a medium include reduced skim milk medium.
The cells isolated from the obtained culture by means of collection such as centrifugation can be used as they are as the active ingredient of the present invention. Concentrated, dried, freeze-dried cells, etc. can be used, or dead cells can be formed by heat drying.
Not only those that are purely isolated as cells, but also cultures, suspensions, other cell-containing materials, and cytoplasm and cell wall fractions obtained by treating cells with enzymes or physical means should be used. it can.
Examples of the culture form include not only a culture medium using a medium generally used for cultivation of lactic acid bacteria, such as MRS medium (manufactured by DIFCO), which is a synthetic medium, and reduced skim milk medium, but also cheese, fermented milk, milk. Although dairy products, such as product lactic acid bacteria drink, can be illustrated, it is not specifically limited.
Furthermore, a culture supernatant prepared by removing milk protein precipitates and bacterial cell components from the obtained culture using methods such as centrifugation and filtration can also be used. Since it is a supernatant with a low solid content, the range of application to foods and drinks is widened. For example, the culture supernatant can be prepared by centrifuging the reduced skim milk culture at 5,000 rpm for 10 minutes.
The action of increasing plasmacytoid dendritic cells in the present invention refers to an action of increasing the number of plasmacytoid dendritic cells. By increasing the number of plasmacytoid dendritic cells, the functions of the immunostimulant and anti-inflammatory agent possessed by the cells can be exhibited.
製剤化に際しては製剤上許可されている賦型剤、安定剤、矯味剤などを適宜混合して濃縮、凍結乾燥するほか、加熱乾燥して死菌体にしてもよい。これらの乾燥物、濃縮物、ペースト状物も含有される。また、ラクトバチルス・ヘルベティカスの形質細胞様樹状細胞増加作用を妨げない範囲で、賦型剤、結合剤、崩壊剤、滑沢剤、矯味矯臭剤、懸濁剤、コーティング剤、その他の任意の薬剤を混合して製剤化することもできる。剤形としては、錠剤、カプセル剤、顆粒剤、散剤、粉剤、シロップ剤などが可能であり、これらを経口的に投与することが望ましい。
For formulation, excipients, stabilizers, flavoring agents and the like that are permitted in the formulation are mixed as appropriate and concentrated, freeze-dried, or heat dried to form dead cells. These dried products, concentrates, and pastes are also included. In addition, as long as the plasmacytoid dendritic cell increasing action of Lactobacillus helveticus is not hindered, it is an excipient, binder, disintegrant, lubricant, flavoring agent, suspending agent, coating agent, and any other optional agent. It can also be formulated by mixing drugs. The dosage form can be tablets, capsules, granules, powders, powders, syrups, etc., and these are preferably administered orally.
本発明の形質細胞様樹状細胞増加剤はどのような飲食品に配合しても良く、飲食品の製造工程中に原料に添加しても良い。飲食品の例としては、チーズ、発酵乳、乳製品乳酸菌飲料、乳酸菌飲料、バター、マーガリンなどの乳製品、乳飲料、果汁飲料、清涼飲料などの飲料、ゼリー、キャンディー、プリン、マヨネーズなどの卵加工品、バターケーキなどの菓子・パン類、さらには、各種粉乳の他、乳幼児食品、栄養組成物などを挙げることができるが特に限定されるものではない。
The plasma cell-like dendritic cell increasing agent of the present invention may be added to any food or drink, and may be added to the raw material during the production process of the food or drink. Examples of food and drink include dairy products such as cheese, fermented milk, dairy lactic acid bacteria beverages, lactic acid bacteria beverages, butter and margarine, beverages such as dairy beverages, fruit juice beverages and soft drinks, eggs such as jelly, candy, pudding and mayonnaise Processed products, confectionery and breads such as butter cake, and various types of powdered milk, infant foods, nutritional compositions and the like can be mentioned, but are not particularly limited.
本発明の形質細胞様樹状細胞増加剤は、これを有効成分とする免疫賦活剤、ウイルス感染予防または治療剤、免疫寛容誘導剤、または抗炎症剤として利用することができる。
さらに、本発明の形質細胞様樹状細胞増加剤を飼料に配合することができる。前記飲食品と同様にどのような飼料に配合しても良く、飼料の製造工程中に原料に添加しても良い。 The plasma cell-like dendritic cell-increasing agent of the present invention can be used as an immunostimulant, a viral infection preventive or therapeutic agent, an immune tolerance inducer, or an anti-inflammatory agent containing this as an active ingredient.
Furthermore, the plasmacytoid dendritic cell increasing agent of this invention can be mix | blended with feed. Like the said food-drinks, you may mix | blend with what kind of feed, and may add to a raw material during the manufacturing process of a feed.
さらに、本発明の形質細胞様樹状細胞増加剤を飼料に配合することができる。前記飲食品と同様にどのような飼料に配合しても良く、飼料の製造工程中に原料に添加しても良い。 The plasma cell-like dendritic cell-increasing agent of the present invention can be used as an immunostimulant, a viral infection preventive or therapeutic agent, an immune tolerance inducer, or an anti-inflammatory agent containing this as an active ingredient.
Furthermore, the plasmacytoid dendritic cell increasing agent of this invention can be mix | blended with feed. Like the said food-drinks, you may mix | blend with what kind of feed, and may add to a raw material during the manufacturing process of a feed.
ラクトバチルス・ヘルベティカスの菌体又は培養物を医薬品、飲食品、栄養組成物、飼料などに配合する場合、ラクトバチルス・ヘルベティカスの各素材への配合割合は特に限定されず、製造の容易性や好ましい一日投与量に合わせて適宜調節すればよい。
投与量は、投与対象者の症状、年齢などを考慮してそれぞれ個別に決定されるが、通常、成人の場合、ラクトバチルス・ヘルベティカスの培養物を１０～２００ｇ／日、あるいはその菌体自体を０．１～５，０００ｍｇ／日摂取できるように配合量を調整すればよい。このようにして摂取することにより所望の効果を発揮することができる。 When blending Lactobacillus helveticus cells or cultures into pharmaceuticals, foods and drinks, nutritional compositions, feeds, etc., the blending ratio of Lactobacillus helveticus to each material is not particularly limited, and is easy to manufacture and preferable What is necessary is just to adjust suitably according to a daily dose.
The dose is individually determined in consideration of the symptom, age, etc. of the subject of administration, but in general, in the case of an adult, 10 to 200 g / day of the Lactobacillus helveticus culture, or the fungus body itself, is used. What is necessary is just to adjust a compounding quantity so that 0.1-5,000 mg / day can be ingested. A desired effect can be exhibited by ingesting in this way.
投与量は、投与対象者の症状、年齢などを考慮してそれぞれ個別に決定されるが、通常、成人の場合、ラクトバチルス・ヘルベティカスの培養物を１０～２００ｇ／日、あるいはその菌体自体を０．１～５，０００ｍｇ／日摂取できるように配合量を調整すればよい。このようにして摂取することにより所望の効果を発揮することができる。 When blending Lactobacillus helveticus cells or cultures into pharmaceuticals, foods and drinks, nutritional compositions, feeds, etc., the blending ratio of Lactobacillus helveticus to each material is not particularly limited, and is easy to manufacture and preferable What is necessary is just to adjust suitably according to a daily dose.
The dose is individually determined in consideration of the symptom, age, etc. of the subject of administration, but in general, in the case of an adult, 10 to 200 g / day of the Lactobacillus helveticus culture, or the fungus body itself, is used. What is necessary is just to adjust a compounding quantity so that 0.1-5,000 mg / day can be ingested. A desired effect can be exhibited by ingesting in this way.
以下に、実施例及び試験例を示し、本発明についてより詳細に説明するが、これらは単に例示するのみであり、本発明はこれらによって何ら限定されるものではない。
Hereinafter, the present invention will be described in more detail with reference to examples and test examples. However, these are merely illustrative, and the present invention is not limited to these examples.
［試験例１］マウスへのLactobacillus helveticus生菌体の経口投与試験
１．試験方法
２０匹のＢａｌｂ／ｃマウス（７週齢、雄）を対照群（ｃｏｎｔｒｏｌ群）とＬＨ２１７１群の２群（ｎ＝１０）に分け、対照群には標準食（ＡＩＮ９３Ｇ）を、ＬＨ２１７１群には標準食（ＡＩＮ９３Ｇ）にラクトバチルス・ヘルベティカス（Lactobacillus helveticus）SBT2171株の凍結乾燥粉末を１％添加した食餌を自由に摂取させた。摂取開始から５週間後に解剖し、腸間膜リンパ節を摘出し細胞懸濁液を調製した。細胞を蛍光活性化細胞ソーティング（ＦＡＣＳ）解析するために、ＡＰＣ標識抗マウスＣＤ１１ｃ抗体、ＰＥ標識抗マウスＰＤＣＡ－１抗体、ＦＩＴＣ標識抗マウスＭＨＣ抗体、ＰＢ標識抗マウスＢ２２０抗体で細胞表面を染色した。ＦＡＣＳで検出されたＰＤＣＡ－１＋，ＣＤ１１ｃｉｎｔ，Ｂ２２０＋，ＭＨＣ＋である細胞群を形質細胞様樹状細胞としてカウントし、全細胞数に対する割合を測定し図１に示した。 [Test Example 1] Oral administration test of live Lactobacillus helveticus cells to mice Test Method Twenty Balb / c mice (7 weeks old, male) were divided into two groups (n = 10) of control group (control group) and LH2171 group, standard food (AIN93G) as control group and LH2171 group Was freely fed with a standard diet (AIN93G) supplemented with 1% lyophilized powder of Lactobacillus helveticus SBT2171 strain. Dissection was performed 5 weeks after the start of ingestion, the mesenteric lymph nodes were removed, and a cell suspension was prepared. For fluorescence activated cell sorting (FACS) analysis of cells, the cell surface was stained with APC-labeled anti-mouse CD11c antibody, PE-labeled anti-mouse PDCA-1 antibody, FITC-labeled anti-mouse MHC antibody, and PB-labeled anti-mouse B220 antibody. . A cell group of PDCA-1 +, CD11cint, B220 +, and MHC + detected by FACS was counted as a plasmacytoid dendritic cell, and the ratio to the total cell number was measured and shown in FIG.
１．試験方法
２０匹のＢａｌｂ／ｃマウス（７週齢、雄）を対照群（ｃｏｎｔｒｏｌ群）とＬＨ２１７１群の２群（ｎ＝１０）に分け、対照群には標準食（ＡＩＮ９３Ｇ）を、ＬＨ２１７１群には標準食（ＡＩＮ９３Ｇ）にラクトバチルス・ヘルベティカス（Lactobacillus helveticus）SBT2171株の凍結乾燥粉末を１％添加した食餌を自由に摂取させた。摂取開始から５週間後に解剖し、腸間膜リンパ節を摘出し細胞懸濁液を調製した。細胞を蛍光活性化細胞ソーティング（ＦＡＣＳ）解析するために、ＡＰＣ標識抗マウスＣＤ１１ｃ抗体、ＰＥ標識抗マウスＰＤＣＡ－１抗体、ＦＩＴＣ標識抗マウスＭＨＣ抗体、ＰＢ標識抗マウスＢ２２０抗体で細胞表面を染色した。ＦＡＣＳで検出されたＰＤＣＡ－１＋，ＣＤ１１ｃｉｎｔ，Ｂ２２０＋，ＭＨＣ＋である細胞群を形質細胞様樹状細胞としてカウントし、全細胞数に対する割合を測定し図１に示した。 [Test Example 1] Oral administration test of live Lactobacillus helveticus cells to mice Test Method Twenty Balb / c mice (7 weeks old, male) were divided into two groups (n = 10) of control group (control group) and LH2171 group, standard food (AIN93G) as control group and LH2171 group Was freely fed with a standard diet (AIN93G) supplemented with 1% lyophilized powder of Lactobacillus helveticus SBT2171 strain. Dissection was performed 5 weeks after the start of ingestion, the mesenteric lymph nodes were removed, and a cell suspension was prepared. For fluorescence activated cell sorting (FACS) analysis of cells, the cell surface was stained with APC-labeled anti-mouse CD11c antibody, PE-labeled anti-mouse PDCA-1 antibody, FITC-labeled anti-mouse MHC antibody, and PB-labeled anti-mouse B220 antibody. . A cell group of PDCA-1 +, CD11cint, B220 +, and MHC + detected by FACS was counted as a plasmacytoid dendritic cell, and the ratio to the total cell number was measured and shown in FIG.
２．試験結果
図１より、ラクトバチルス・ヘルベティカスを添加した食餌を摂取した群（ＬＨ２１７１群）の方が、添加しない食餌を摂取した群（ｃｏｎｔｒｏｌ群）よりも腸間膜リンパ節における形質細胞様樹状細胞の割合が有意に高いことが分かった。すなわち、ラクトバチルス・ヘルベティカス菌体の摂取によって、形質細胞様樹状細胞数が増加することが示された。 2. Test results From FIG. 1, the plasmacytoid dendritic group in the mesenteric lymph node in the group (LH2171 group) ingesting the diet added with Lactobacillus helveticus than in the group (control group) ingesting the diet not added It was found that the percentage of cells was significantly higher. That is, it was shown that the number of plasmacytoid dendritic cells increased by ingestion of Lactobacillus helveticus cells.
図１より、ラクトバチルス・ヘルベティカスを添加した食餌を摂取した群（ＬＨ２１７１群）の方が、添加しない食餌を摂取した群（ｃｏｎｔｒｏｌ群）よりも腸間膜リンパ節における形質細胞様樹状細胞の割合が有意に高いことが分かった。すなわち、ラクトバチルス・ヘルベティカス菌体の摂取によって、形質細胞様樹状細胞数が増加することが示された。 2. Test results From FIG. 1, the plasmacytoid dendritic group in the mesenteric lymph node in the group (LH2171 group) ingesting the diet added with Lactobacillus helveticus than in the group (control group) ingesting the diet not added It was found that the percentage of cells was significantly higher. That is, it was shown that the number of plasmacytoid dendritic cells increased by ingestion of Lactobacillus helveticus cells.
[実施例１]ラクトバチルス・ヘルベティカスの培養物の製造
原料乳を加熱殺菌（７５℃、１５秒間）した後、３０℃まで冷却し、０．０１％塩化カルシウムを添加した。さらに、市販乳酸菌スターター（ＬＤスターター、クリスチャン・ハンセン社）０．７％及びラクトバチルス・ヘルベティカスSBT2171株（FERM BP-5445）１％を添加し、さらにレンネット０．００３％を添加して、乳を凝固させた。このようにして得られた凝乳をカッティングし、ｐＨが６．２～６．１となるまで撹拌してホエーを排出して、カード粒を得た。そして、このカード粒を型詰めして圧搾し、さらに加塩して、１０℃で熟成させ、ゴーダチーズタイプの硬質ナチュラルチーズを調製した。この硬質ナチュラルチーズ（６ヶ月熟成）をミンチ器（ＧＭ‐ＤＸ、日本キャリア社製）を用いてミンチし、凍結乾燥を行った。その後、コーヒーミルにより微細化し、ラクトバチルス・ヘルベティカスの培養物であるチーズ粉を得た。 [Example 1] Production of Lactobacillus helveticus culture Raw milk was sterilized by heating (75 ° C, 15 seconds), cooled to 30 ° C, and 0.01% calcium chloride was added. Furthermore, 0.7% of commercially available lactic acid bacteria starter (LD starter, Christian Hansen) and 1% of Lactobacillus helveticus strain SBT2171 (FERM BP-5445) are added, and 0.003% of rennet is further added. Solidified. The curd thus obtained was cut and stirred until the pH was 6.2 to 6.1, and the whey was discharged to obtain curd grains. Then, the curd grains were packed and pressed, further salted, and aged at 10 ° C. to prepare Gouda cheese type hard natural cheese. This hard natural cheese (aged for 6 months) was minced using a mincer (GM-DX, manufactured by Nippon Carrier Co., Ltd.) and freeze-dried. Then, it refined | miniaturized with the coffee mill and the cheese powder which is a culture of Lactobacillus helveticus was obtained.
原料乳を加熱殺菌（７５℃、１５秒間）した後、３０℃まで冷却し、０．０１％塩化カルシウムを添加した。さらに、市販乳酸菌スターター（ＬＤスターター、クリスチャン・ハンセン社）０．７％及びラクトバチルス・ヘルベティカスSBT2171株（FERM BP-5445）１％を添加し、さらにレンネット０．００３％を添加して、乳を凝固させた。このようにして得られた凝乳をカッティングし、ｐＨが６．２～６．１となるまで撹拌してホエーを排出して、カード粒を得た。そして、このカード粒を型詰めして圧搾し、さらに加塩して、１０℃で熟成させ、ゴーダチーズタイプの硬質ナチュラルチーズを調製した。この硬質ナチュラルチーズ（６ヶ月熟成）をミンチ器（ＧＭ‐ＤＸ、日本キャリア社製）を用いてミンチし、凍結乾燥を行った。その後、コーヒーミルにより微細化し、ラクトバチルス・ヘルベティカスの培養物であるチーズ粉を得た。 [Example 1] Production of Lactobacillus helveticus culture Raw milk was sterilized by heating (75 ° C, 15 seconds), cooled to 30 ° C, and 0.01% calcium chloride was added. Furthermore, 0.7% of commercially available lactic acid bacteria starter (LD starter, Christian Hansen) and 1% of Lactobacillus helveticus strain SBT2171 (FERM BP-5445) are added, and 0.003% of rennet is further added. Solidified. The curd thus obtained was cut and stirred until the pH was 6.2 to 6.1, and the whey was discharged to obtain curd grains. Then, the curd grains were packed and pressed, further salted, and aged at 10 ° C. to prepare Gouda cheese type hard natural cheese. This hard natural cheese (aged for 6 months) was minced using a mincer (GM-DX, manufactured by Nippon Carrier Co., Ltd.) and freeze-dried. Then, it refined | miniaturized with the coffee mill and the cheese powder which is a culture of Lactobacillus helveticus was obtained.
［試験例２］マウスへのラクトバチルス・ヘルベティカス培養物の経口投与試験
１．試験方法
実施例１で得られたラクトバチルス・ヘルベティカスSBT2171の培養物を用いて経口投与試験を行った。試験方法は試験例１に準じて行った。解剖後の腸間膜リンパ節における形質細胞様樹状細胞の全細胞数に対する割合を測定し、その結果を図２に示した。
２．試験結果
図２より、ラクトバチルス・ヘルベティカスSBT2171の培養物を添加した食餌を摂取した群（ＬＨ２１７１群）の方が、添加しない食餌を摂取した群（ｃｏｎｔｒｏｌ群）よりも腸間膜リンパ節における形質細胞様樹状細胞の割合が有意に高いことが分かった。すなわち、ラクトバチルス・ヘルベティカス培養物の摂取によって、形質細胞様樹状細胞数が増加することが示された。 [Test Example 2] Oral administration test of Lactobacillus helveticus culture to mice Test Method An oral administration test was performed using the culture of Lactobacillus helveticus SBT2171 obtained in Example 1. The test method was performed according to Test Example 1. The ratio of plasmacytoid dendritic cells to the total number of cells in the mesenteric lymph nodes after dissection was measured, and the results are shown in FIG.
2. 2. Test results From FIG. 2, the trait in the mesenteric lymph node in the group (LH2171 group) ingesting the diet to which the culture of Lactobacillus helveticus SBT2171 was added was greater than in the group ingesting the diet not added (control group). It was found that the proportion of cell-like dendritic cells was significantly higher. That is, it was shown that the number of plasmacytoid dendritic cells increased by ingesting the Lactobacillus helveticus culture.
１．試験方法
実施例１で得られたラクトバチルス・ヘルベティカスSBT2171の培養物を用いて経口投与試験を行った。試験方法は試験例１に準じて行った。解剖後の腸間膜リンパ節における形質細胞様樹状細胞の全細胞数に対する割合を測定し、その結果を図２に示した。
２．試験結果
図２より、ラクトバチルス・ヘルベティカスSBT2171の培養物を添加した食餌を摂取した群（ＬＨ２１７１群）の方が、添加しない食餌を摂取した群（ｃｏｎｔｒｏｌ群）よりも腸間膜リンパ節における形質細胞様樹状細胞の割合が有意に高いことが分かった。すなわち、ラクトバチルス・ヘルベティカス培養物の摂取によって、形質細胞様樹状細胞数が増加することが示された。 [Test Example 2] Oral administration test of Lactobacillus helveticus culture to mice Test Method An oral administration test was performed using the culture of Lactobacillus helveticus SBT2171 obtained in Example 1. The test method was performed according to Test Example 1. The ratio of plasmacytoid dendritic cells to the total number of cells in the mesenteric lymph nodes after dissection was measured, and the results are shown in FIG.
2. 2. Test results From FIG. 2, the trait in the mesenteric lymph node in the group (LH2171 group) ingesting the diet to which the culture of Lactobacillus helveticus SBT2171 was added was greater than in the group ingesting the diet not added (control group). It was found that the proportion of cell-like dendritic cells was significantly higher. That is, it was shown that the number of plasmacytoid dendritic cells increased by ingesting the Lactobacillus helveticus culture.
[実施例２] 形質細胞様樹状細胞増加剤（顆粒）の製造
ラクトバチルス・ヘルベティカスSBT2171株を食用可能な合成培地（０．５％酵母エキス、０．１％トリプチケースペプトン添加）に５重量％接種し、３８℃で１５時間培養後、遠心分離で菌体を回収した。回収した菌体を凍結乾燥し、前記菌体の凍結乾燥粉末を得た。この凍結乾燥粉末１ｇを乳糖５ｇと混合し、顆粒状に成形して本発明の形質細胞様樹状細胞増加剤を得た。 [Example 2] Manufacture of a plasmacytoid dendritic cell increasing agent (granule) 5 in an edible synthetic medium (with 0.5% yeast extract and 0.1% trypticase peptone), Lactobacillus helveticus strain SBT2171 After inoculating a weight% and culturing at 38 ° C. for 15 hours, the cells were collected by centrifugation. The collected cells were lyophilized to obtain a freeze-dried powder of the cells. 1 g of this lyophilized powder was mixed with 5 g of lactose and formed into granules to obtain the plasmacytoid dendritic cell increasing agent of the present invention.
ラクトバチルス・ヘルベティカスSBT2171株を食用可能な合成培地（０．５％酵母エキス、０．１％トリプチケースペプトン添加）に５重量％接種し、３８℃で１５時間培養後、遠心分離で菌体を回収した。回収した菌体を凍結乾燥し、前記菌体の凍結乾燥粉末を得た。この凍結乾燥粉末１ｇを乳糖５ｇと混合し、顆粒状に成形して本発明の形質細胞様樹状細胞増加剤を得た。 [Example 2] Manufacture of a plasmacytoid dendritic cell increasing agent (granule) 5 in an edible synthetic medium (with 0.5% yeast extract and 0.1% trypticase peptone), Lactobacillus helveticus strain SBT2171 After inoculating a weight% and culturing at 38 ° C. for 15 hours, the cells were collected by centrifugation. The collected cells were lyophilized to obtain a freeze-dried powder of the cells. 1 g of this lyophilized powder was mixed with 5 g of lactose and formed into granules to obtain the plasmacytoid dendritic cell increasing agent of the present invention.
[実施例３] 形質細胞様樹状細胞増加剤（顆粒）の製造
ラクトバチルス・ヘルベティカスJCM-1120株を食用可能な合成培地（０．５％酵母エキス、０．１％トリプチケースペプトン添加）に５重量％接種し、３８℃で１５時間培養後、遠心分離で菌体を回収した。回収した菌体を凍結乾燥し、前記菌体の凍結乾燥粉末を得た。この凍結乾燥粉末１ｇを乳糖５ｇと混合し、顆粒状に成形して本発明の形質細胞様樹状細胞増加剤を得た。 [Example 3] Production of plasmacytoid dendritic cell increasing agent (granule) Synthetic medium edible with Lactobacillus helveticus JCM-1120 strain (0.5% yeast extract, 0.1% trypticase peptone added) 5% by weight was inoculated and cultured at 38 ° C. for 15 hours, and the cells were collected by centrifugation. The collected cells were lyophilized to obtain a freeze-dried powder of the cells. 1 g of this lyophilized powder was mixed with 5 g of lactose and formed into granules to obtain the plasmacytoid dendritic cell increasing agent of the present invention.
ラクトバチルス・ヘルベティカスJCM-1120株を食用可能な合成培地（０．５％酵母エキス、０．１％トリプチケースペプトン添加）に５重量％接種し、３８℃で１５時間培養後、遠心分離で菌体を回収した。回収した菌体を凍結乾燥し、前記菌体の凍結乾燥粉末を得た。この凍結乾燥粉末１ｇを乳糖５ｇと混合し、顆粒状に成形して本発明の形質細胞様樹状細胞増加剤を得た。 [Example 3] Production of plasmacytoid dendritic cell increasing agent (granule) Synthetic medium edible with Lactobacillus helveticus JCM-1120 strain (0.5% yeast extract, 0.1% trypticase peptone added) 5% by weight was inoculated and cultured at 38 ° C. for 15 hours, and the cells were collected by centrifugation. The collected cells were lyophilized to obtain a freeze-dried powder of the cells. 1 g of this lyophilized powder was mixed with 5 g of lactose and formed into granules to obtain the plasmacytoid dendritic cell increasing agent of the present invention.
［実施例４］形質細胞様樹状細胞増加剤（散剤）の製造
第１３改正日本薬局方解説書製剤総則「散剤」の規定に準拠し、上記実施例２で得られたラクトバチルス・ヘルベティカスSBT2171株の凍結乾燥粉末１０ｇに乳糖（日局）４００ｇ、バレイショデンプン（日局）６００ｇを加えて均一に混合し、本発明の形質細胞様樹状細胞増加剤を製造した。 [Example 4] Manufacture of a plasmacytoid dendritic cell increasing agent (powder) The Lactobacillus helveticus SBT2171 obtained in Example 2 above in accordance with the provisions of the 13th revised Japanese Pharmacopoeia Description of Drugs General Rules "Powder" Lactose (JP) 400 g and potato starch (JP) 600 g were added to 10 g of the lyophilized powder of the strain and mixed uniformly to produce the plasmacytoid dendritic cell increasing agent of the present invention.
第１３改正日本薬局方解説書製剤総則「散剤」の規定に準拠し、上記実施例２で得られたラクトバチルス・ヘルベティカスSBT2171株の凍結乾燥粉末１０ｇに乳糖（日局）４００ｇ、バレイショデンプン（日局）６００ｇを加えて均一に混合し、本発明の形質細胞様樹状細胞増加剤を製造した。 [Example 4] Manufacture of a plasmacytoid dendritic cell increasing agent (powder) The Lactobacillus helveticus SBT2171 obtained in Example 2 above in accordance with the provisions of the 13th revised Japanese Pharmacopoeia Description of Drugs General Rules "Powder" Lactose (JP) 400 g and potato starch (JP) 600 g were added to 10 g of the lyophilized powder of the strain and mixed uniformly to produce the plasmacytoid dendritic cell increasing agent of the present invention.
［実施例５］形質細胞様樹状細胞増加剤（散剤）の製造
第１３改正日本薬局方解説書製剤総則「散剤」の規定に準拠し、上記実施例３で得られたラクトバチルス・ヘルベティカスJCM-1120株の凍結乾燥粉末1０ｇに乳糖（日局）４００ｇ、バレイショデンプン（日局）６００ｇを加えて均一に混合し、本発明の形質細胞様樹状細胞増加剤を製造した。 [Example 5] Manufacture of a plasmacytoid dendritic cell increasing agent (powder) The Lactobacillus helveticus JCM obtained in Example 3 above in accordance with the provisions of the 13th revised Japanese Pharmacopoeia explanation general formulation "powder" Lactose (JP) 400 g and potato starch (JP) 600 g were added to 10 g of lyophilized powder of the -1120 strain and mixed uniformly to produce the plasmacytoid dendritic cell increasing agent of the present invention.
第１３改正日本薬局方解説書製剤総則「散剤」の規定に準拠し、上記実施例３で得られたラクトバチルス・ヘルベティカスJCM-1120株の凍結乾燥粉末1０ｇに乳糖（日局）４００ｇ、バレイショデンプン（日局）６００ｇを加えて均一に混合し、本発明の形質細胞様樹状細胞増加剤を製造した。 [Example 5] Manufacture of a plasmacytoid dendritic cell increasing agent (powder) The Lactobacillus helveticus JCM obtained in Example 3 above in accordance with the provisions of the 13th revised Japanese Pharmacopoeia explanation general formulation "powder" Lactose (JP) 400 g and potato starch (JP) 600 g were added to 10 g of lyophilized powder of the -1120 strain and mixed uniformly to produce the plasmacytoid dendritic cell increasing agent of the present invention.
［実施例６］スティック状の形質細胞様樹状細胞増加用栄養健康食品の製造
ビタミンＣ４０ｇまたはビタミンＣとクエン酸の等量混合物４０ｇ、グラニュー糖１００ｇ、コーンスターチと乳糖の等量混合物６０ｇに、上記実施例２で得られたラクトバチルス・ヘルベティカスSBT2171株の凍結乾燥粉末４０ｇを加えて混合した。混合物を袋に詰め、本発明のスティック状栄養健康食品を１５０袋製造した。 [Example 6] Production of nutritional health food for increasing plasma-like dendritic cells in the form of sticks 40 g of vitamin C or an equal mixture of vitamin C and citric acid, 100 g of granulated sugar, 60 g of an equal mixture of corn starch and lactose 40 g of lyophilized powder of Lactobacillus helveticus SBT2171 strain obtained in Example 2 was added and mixed. The mixture was packed in a bag to produce 150 bags of the stick-like nutritional health food of the present invention.
ビタミンＣ４０ｇまたはビタミンＣとクエン酸の等量混合物４０ｇ、グラニュー糖１００ｇ、コーンスターチと乳糖の等量混合物６０ｇに、上記実施例２で得られたラクトバチルス・ヘルベティカスSBT2171株の凍結乾燥粉末４０ｇを加えて混合した。混合物を袋に詰め、本発明のスティック状栄養健康食品を１５０袋製造した。 [Example 6] Production of nutritional health food for increasing plasma-like dendritic cells in the form of sticks 40 g of vitamin C or an equal mixture of vitamin C and citric acid, 100 g of granulated sugar, 60 g of an equal mixture of corn starch and lactose 40 g of lyophilized powder of Lactobacillus helveticus SBT2171 strain obtained in Example 2 was added and mixed. The mixture was packed in a bag to produce 150 bags of the stick-like nutritional health food of the present invention.
［実施例７］形質細胞様樹状細胞増加用飼料の製造
大豆粕１２ｋｇ、脱脂粉乳１４ｋｇ、大豆油４ｋｇ、コーン油２ｋｇ、パーム油２３．２ｋｇ、トウモロコシ澱粉１４ｋｇ、小麦粉９ｋｇ、ふすま２ｋｇ、ビタミン混合物５ｋｇ、セルロース２．８ｋｇ、ミネラル混合物２ｋｇを配合し、１２０℃、４分間殺菌して、実施例２で得られたラクトバチルス・ヘルベティカスSBT2171株１０ｋｇを配合して、飼料を製造した。 [Example 7] Production of feed for increasing plasmacytoid dendritic cells Soybean meal 12 kg, skim milk powder 14 kg, soybean oil 4 kg, corn oil 2 kg, palm oil 23.2 kg, corn starch 14 kg, wheat flour 9 kg, bran 2 kg, vitamin mixture 5 kg, 2.8 kg of cellulose and 2 kg of a mineral mixture were blended, sterilized at 120 ° C. for 4 minutes, and 10 kg of Lactobacillus helveticus SBT2171 strain obtained in Example 2 was blended to produce a feed.
大豆粕１２ｋｇ、脱脂粉乳１４ｋｇ、大豆油４ｋｇ、コーン油２ｋｇ、パーム油２３．２ｋｇ、トウモロコシ澱粉１４ｋｇ、小麦粉９ｋｇ、ふすま２ｋｇ、ビタミン混合物５ｋｇ、セルロース２．８ｋｇ、ミネラル混合物２ｋｇを配合し、１２０℃、４分間殺菌して、実施例２で得られたラクトバチルス・ヘルベティカスSBT2171株１０ｋｇを配合して、飼料を製造した。 [Example 7] Production of feed for increasing plasmacytoid dendritic cells Soybean meal 12 kg, skim milk powder 14 kg, soybean oil 4 kg, corn oil 2 kg, palm oil 23.2 kg, corn starch 14 kg, wheat flour 9 kg, bran 2 kg, vitamin mixture 5 kg, 2.8 kg of cellulose and 2 kg of a mineral mixture were blended, sterilized at 120 ° C. for 4 minutes, and 10 kg of Lactobacillus helveticus SBT2171 strain obtained in Example 2 was blended to produce a feed.
ラクトバチルス・ヘルベティカスの菌体、該乳酸菌を含有するチーズまたは乳酸菌飲料を摂取する事で、形質細胞様樹状細胞数を増加させ、ウイルスなどに対する感染予防効果とともに、過剰な免疫応答を予防、改善することができ、免疫疾患に有効な医薬品となる。
By ingesting Lactobacillus helveticus cells, cheese containing lactic acid bacteria or lactic acid bacteria beverages, the number of plasmacytoid dendritic cells is increased, preventing and improving excessive immune responses as well as preventing infection against viruses. Can be an effective medicine for immune diseases.
[寄託生物材料への言及]
（１）ラクトバチルス・ヘルベティカス（Lactobacillus helveticus）SBT2171
イ 当該生物材料を寄託した寄託機関の名称及び住所
独立行政法人 産業技術総合研究所 特許生物寄託センター
日本国茨城県つくば市東１丁目１番3号
ロ イの寄託機関に生物材料を寄託した日付
平成６年６月２２日（１９９４年６月２２日）（原寄託日）
平成８年３月６日（１９９６年３月６日）（原寄託によりブタペスト条約に基づく寄託への移管日）
ハ イの寄託機関が寄託について付した受託番号
FERM BP-5445 [Reference to deposited biological materials]
(1) Lactobacillus helveticus SBT2171
The name and address of the depository institution where the biological material was deposited National Institute of Advanced Industrial Science and Technology Patent Biological Deposit Center Date 1-3-1 Higashi 1-chome, Tsukuba City, Ibaraki, Japan Date of deposit of biological material in Heisei June 22, 6 (June 22, 1994) (original deposit date)
March 6, 1996 (March 6, 1996) (Date of transfer to deposit under the Budapest Treaty by original deposit)
The deposit number assigned by the depository in Hai for the deposit
FERM BP-5445
（１）ラクトバチルス・ヘルベティカス（Lactobacillus helveticus）SBT2171
イ 当該生物材料を寄託した寄託機関の名称及び住所
独立行政法人 産業技術総合研究所 特許生物寄託センター
日本国茨城県つくば市東１丁目１番3号
ロ イの寄託機関に生物材料を寄託した日付
平成６年６月２２日（１９９４年６月２２日）（原寄託日）
平成８年３月６日（１９９６年３月６日）（原寄託によりブタペスト条約に基づく寄託への移管日）
ハ イの寄託機関が寄託について付した受託番号
FERM BP-5445 [Reference to deposited biological materials]
(1) Lactobacillus helveticus SBT2171
The name and address of the depository institution where the biological material was deposited National Institute of Advanced Industrial Science and Technology Patent Biological Deposit Center Date 1-3-1 Higashi 1-chome, Tsukuba City, Ibaraki, Japan Date of deposit of biological material in Heisei June 22, 6 (June 22, 1994) (original deposit date)
March 6, 1996 (March 6, 1996) (Date of transfer to deposit under the Budapest Treaty by original deposit)
The deposit number assigned by the depository in Hai for the deposit
FERM BP-5445
Claims (17)
- ラクトバチルス・ヘルベティカス（Lactobacillus helveticus）に属する乳酸菌又はその培養物を有効成分とする形質細胞様樹状細胞増加剤。 A plasmacytoid dendritic cell increasing agent comprising a lactic acid bacterium belonging to Lactobacillus helveticus or a culture thereof as an active ingredient.
- 前記ラクトバチルス・ヘルベティカス（Lactobacillus helveticus）に属する乳酸菌がラクトバチルス・ヘルベティカス（Lactobacillus helveticus）SBT2171（FERM BP-5445）であることを特徴とする、請求項１に記載の形質細胞様樹状細胞増加剤。 The plasma cell-like dendritic cell increasing agent according to claim 1, wherein the lactic acid bacterium belonging to Lactobacillus helveticus is Lactobacillus helveticus SBT2171 (FERM BP-5445). .
- 請求項１又は２に記載の剤を有効成分として含む免疫賦活剤。 The immunostimulant which contains the agent of Claim 1 or 2 as an active ingredient.
- 請求項１又は２に記載の剤を有効成分として含むウイルス感染予防又は治療剤。 A virus infection preventive or therapeutic agent comprising the agent according to claim 1 or 2 as an active ingredient.
- 請求項１又は２に記載の剤を有効成分として含む免疫寛容誘導剤。 An immune tolerance inducer comprising the agent according to claim 1 or 2 as an active ingredient.
- 請求項１又は２に記載の剤を有効成分として含む抗炎症剤。 An anti-inflammatory agent comprising the agent according to claim 1 or 2 as an active ingredient.
- 請求項１～６のいずれかに記載の剤を添加した形質細胞様樹状細胞増加用栄養組成物、形質細胞様樹状細胞増加用飲食品又は形質細胞様樹状細胞増加用飼料。 A nutritional composition for increasing plasmacytoid dendritic cells, a food or drink for increasing plasmacytoid dendritic cells, or a feed for increasing plasmacytoid dendritic cells, to which the agent according to any one of claims 1 to 6 is added.
- ラクトバチルス・ヘルベティカス（Lactobacillus helveticus）に属する乳酸菌又はその培養物を有効成分とする形質細胞様樹状細胞増加剤を、形質細胞様樹状細胞数の減少した対象に投与する形質細胞様樹状細胞増加剤の使用方法。 A plasmacytoid dendritic cell to which a plasmacytoid dendritic cell increasing agent comprising a lactic acid bacterium belonging to Lactobacillus helveticus or its culture as an active ingredient is administered to a subject having a reduced number of plasmacytoid dendritic cells How to use the increasing agent.
- 形質細胞様樹状細胞増加剤の製造における、ラクトバチルス・ヘルベティカス（Lactobacillus helveticus）に属する乳酸菌又はその培養物の使用。 Use of a lactic acid bacterium belonging to Lactobacillus helveticus or a culture thereof in the production of a plasmacytoid dendritic cell increasing agent.
- ラクトバチルス・ヘルベティカス（Lactobacillus helveticus）に属する乳酸菌又はその培養物を有効成分とする免疫賦活剤を、免疫の低下した対象に投与する免疫賦活剤の使用方法。 The use method of the immunostimulant which administers the immunostimulant which uses the lactic acid bacteria which belong to Lactobacillus helvetticus (Lactobacillus helhelticus) or its culture as an active ingredient to the subject who reduced immunity.
- 免疫賦活剤の製造におけるラクトバチルス・ヘルベティカス（Lactobacillus helveticus）に属する乳酸菌又はその培養物の使用。 Use of a lactic acid bacterium belonging to Lactobacillus helveticus or a culture thereof in the production of an immunostimulant.
- ラクトバチルス・ヘルベティカス（Lactobacillus helveticus）に属する乳酸菌又はその培養物を有効成分とするウイルス感染予防剤または治療剤を、ウイルス感染予防対象またはウイルス感染した対象に投与するウイルス感染予防剤またはウイルス感染治療剤の使用方法。 Viral infection preventive agent or therapeutic agent for administering a viral infection preventive agent or therapeutic agent comprising a lactic acid bacterium belonging to Lactobacillus helveticus or its culture as an active ingredient to a viral infection preventive subject or a virally infected subject How to use.
- ウイルス感染予防剤またはウイルス感染治療剤の製造におけるラクトバチルス・ヘルベティカス（Lactobacillus helveticus）に属する乳酸菌又はその培養物の使用。 Use of a lactic acid bacterium belonging to Lactobacillus helveticus or a culture thereof in the manufacture of a viral infection preventive agent or a viral infection therapeutic agent.
- ラクトバチルス・ヘルベティカス（Lactobacillus helveticus）に属する乳酸菌又はその培養物を有効成分とする免疫寛容誘導剤を、過剰な免疫応答対象に投与する免疫寛容誘導剤の使用方法。 A method for using an immune tolerance inducer, wherein an immune tolerance inducer comprising a lactic acid bacterium belonging to Lactobacillus helveticus or a culture thereof as an active ingredient is administered to an excessive immune response subject.
- 免疫寛容誘導剤の製造におけるラクトバチルス・ヘルベティカス（Lactobacillus helveticus）に属する乳酸菌又はその培養物の使用。 Use of a lactic acid bacterium belonging to Lactobacillus helveticus or a culture thereof in the production of an immune tolerance inducer.
- ラクトバチルス・ヘルベティカス（Lactobacillus helveticus）に属する乳酸菌又はその培養物を有効成分とする抗炎症剤を、炎症を有する対象に投与する抗炎症剤の使用方法。 A method of using an anti-inflammatory agent comprising administering an anti-inflammatory agent comprising a lactic acid bacterium belonging to Lactobacillus helveticus or a culture thereof as an active ingredient to a subject having inflammation.
- 抗炎症剤の製造におけるラクトバチルス・ヘルベティカス（Lactobacillus helveticus）に属する乳酸菌又はその培養物の使用。 Use of a lactic acid bacterium belonging to Lactobacillus helveticus or a culture thereof in the manufacture of an anti-inflammatory agent.
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| JP2020080785A (en) * | 2018-11-29 | 2020-06-04 | 雪印メグミルク株式会社 | Periodontal disease preventive composition |
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| JP2019210242A (en) * | 2018-06-04 | 2019-12-12 | 雪印メグミルク株式会社 | Srcap expression-inhibiting compositions containing lactic acid bacteria of the genus lactobacillus as an effective ingredient |
| JP7224114B2 (en) | 2018-06-04 | 2023-02-17 | 雪印メグミルク株式会社 | Composition for suppressing SRCAP expression containing lactic acid bacteria of the genus Lactobacillus as an active ingredient |
| JP2020080785A (en) * | 2018-11-29 | 2020-06-04 | 雪印メグミルク株式会社 | Periodontal disease preventive composition |
| JP7160652B2 (en) | 2018-11-29 | 2022-10-25 | 雪印メグミルク株式会社 | Periodontal disease preventive composition |
| JP7410250B2 (en) | 2018-11-29 | 2024-01-09 | 雪印メグミルク株式会社 | Composition for preventing periodontal disease |
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