JP2021069289A - Anti-i type allergy agent - Google Patents
Anti-i type allergy agent Download PDFInfo
- Publication number
- JP2021069289A JP2021069289A JP2019196388A JP2019196388A JP2021069289A JP 2021069289 A JP2021069289 A JP 2021069289A JP 2019196388 A JP2019196388 A JP 2019196388A JP 2019196388 A JP2019196388 A JP 2019196388A JP 2021069289 A JP2021069289 A JP 2021069289A
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- Prior art keywords
- lactic acid
- allergic
- lactobacillus
- type
- reducing agent
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Abstract
Description
本発明は、抗Ｉ型アレルギー剤、花粉症軽減剤、アレルゲンによる不快感の軽減剤、及びＩｇＥ低減剤に関する。 The present invention relates to an anti-type I allergic agent, a pollinosis reducing agent, an allergen-induced discomfort reducing agent, and an IgE reducing agent.
近年、日本の多くの人々が、スギ(Cryptomeria japonica)花粉によって引き起こされるアレルギー反応に苦しんでおり、その患者の数は、人口の約３分の１を占め、多くの対策が講じられているが増加している。したがって、花粉症は国民病であり、スギ花粉の季節には、毎日、スギ花粉の飛散予報がマスコミにより発表されている。 In recent years, many people in Japan have suffered from allergic reactions caused by Sugi (Cryptomeria japonica) pollen, and the number of patients accounts for about one-third of the population, and many measures have been taken. It has increased. Therefore, pollinosis is a national disease, and the forecast for the scattering of cedar pollen is announced daily by the media during the cedar pollen season.
くしゃみ、鼻水、鼻づまり及び目のかゆみのようなアレルギー反応は、スギ花粉曝露の最初の段階では現れないが、花粉曝露が反応に必要なしきい値を越えると発症する。したがって、アレルギー反応を最小限にするためには曝露を防ぐことが重要であり、完全にスギ花粉を防ぐことができなくても、多くの人々がスギ花粉の季節中にはマスクを着けている。 Allergic reactions such as sneezing, runny nose, stuffy nose and itchy eyes do not appear in the first stages of cedar pollen exposure, but develop when pollen exposure exceeds the threshold required for the reaction. Therefore, it is important to prevent exposure to minimize allergic reactions, and many people wear masks during the cedar pollen season, even if they cannot completely prevent cedar pollen. ..
抗ヒスタミン剤又はステロイド点鼻薬のような抗アレルギー剤は、花粉曝露後の症状を緩和するために使用されるが、それらの効果は一時的であったり、眠気のような副作用を有している。舌下免疫療法は、日本においてスギ花粉又はダニアレルギーのための治療法として最近承認された。しかしながら、毎日、長期間の摂取が必要であり、口腔そう痒症、口腔浮腫、咽頭刺激感及びくしゃみのような局所的副作用が生じることが知られている。したがって、新しい治療方法の開発が求められている。 Antihistamines or antiallergic agents such as steroid nasal drops are used to relieve symptoms after pollen exposure, but their effects are temporary or have side effects such as drowsiness. Sublingual immunotherapy has recently been approved in Japan as a treatment for cedar pollen or mite allergies. However, it is known that daily ingestion is required for a long period of time, and local side effects such as pruritus, oral edema, pharyngeal irritation and sneezing occur. Therefore, the development of new treatment methods is required.
アレルギー反応の重症度は幅広く、個人のアレルギー反応のタイプ及び重症度に応じて適切な治療が行われるべきである。例えば、軽度の反応を示す人では、アレルギー症状を減少させるだけでなく、ＱＯＬを改善する効果を有する抗アレルギー食品の摂取により、アレルギーをコントロールすることもできる。 The severity of allergic reactions is wide and appropriate treatment should be given according to the type and severity of the individual allergic reaction. For example, in a person with a mild reaction, allergies can be controlled by ingesting antiallergic foods that not only reduce allergic symptoms but also have the effect of improving quality of life.
乳酸菌の一種であるラクトバチルスＯＮＲＩＣｂ０２４０（ＦＥＲＭ ＢＰ−１００６５）株は、抗鳥インフルエンザ抗体産生促進作用（特許文献１）、肺炎予防、風邪予防、生活の質（Ｑｕａｌｉｔｙ ｏｆ Ｌｉｆｅ；ＱＯＬ）の改善作用（特許文献２）を有することが知られている。 Lactobacillus ONRICb0240 (FERM BP-10065) strain, which is a kind of lactic acid bacterium, has an anti-avian antibody production promoting action (Patent Document 1), a pneumonia prevention, a cold prevention, and an improving action of quality of life (QOL) (QOL). It is known to have Patent Document 2).
本発明は、新たな抗Ｉ型アレルギー剤、花粉症軽減剤、アレルゲンによる不快感の軽減剤、及びＩｇＥ低減剤を提供することを目的とする。 An object of the present invention is to provide a new anti-type I allergic agent, a pollinosis reducing agent, an allergen-induced discomfort reducing agent, and an IgE reducing agent.
本発明者らは、上記目的を達成すべく鋭意研究を重ねた結果、アレルギー性鼻炎モデルマウスを用いた試験とヒトの花粉に対するアレルギー反応についての試験により、ラクトバチルスＯＮＲＩＣｂ０２４０（ＦＥＲＭ ＢＰ−１００６５）がＩ型アレルギーに対する抗アレルギー作用を有することを見出した。 As a result of intensive studies to achieve the above object, the present inventors have conducted a test using an allergic rhinitis model mouse and a test on an allergic reaction to human pollen, and found that lactobacillus ONRICb0240 (FERM BP-10065). It was found to have an anti-allergic effect on type I allergy.
本発明は、これら知見に基づき、更に検討を重ねて完成されたものであり、次の抗Ｉ型アレルギー剤、花粉症軽減剤、アレルゲンによる不快感の軽減剤、及びＩｇＥ低減剤を提供するものである。 The present invention has been completed by further studying based on these findings, and provides the following anti-type I allergic agent, pollinosis reducing agent, allergen-induced discomfort reducing agent, and IgE reducing agent. Is.
（１）抗Ｉ型アレルギー剤
項１−１．ラクトバチルス・ペントーサスに属する乳酸菌を含有する、抗Ｉ型アレルギー剤。
項１−２．前記Ｉ型アレルギーが、アトピー性皮膚炎、アレルギー性鼻炎、花粉症、アレルギー性皮膚炎、気管支喘息、蕁麻疹、アレルギー性結膜炎、又はアナフィラキシーショックである、項１−１に記載の抗Ｉ型アレルギー剤。
項１−３．前記ラクトバチルス・ペントーサスに属する乳酸菌が、ラクトバチルスＯＮＲＩＣｂ０２４０（ＦＥＲＭ ＢＰ−１００６５）又はその変異株である、項１−１又は１−２に記載の抗Ｉ型アレルギー剤。
項１−４．飲食品又は医薬品である、項１−１〜１−３のいずれか一項に記載の抗Ｉ型アレルギー剤。
(1) Anti-type I allergic agent Item 1-1. An anti-type I allergic agent containing lactic acid bacteria belonging to Lactobacillus pentosus.
Item 1-2.
Item 1-3.
Item 1-4. The anti-type I allergic agent according to any one of Items 1-1 to 1-3, which is a food or drink or a pharmaceutical product.
（２）花粉症軽減剤
項２−１．ラクトバチルス・ペントーサスに属する乳酸菌を含有する、花粉症軽減剤。
項２−２．前記ラクトバチルス・ペントーサスに属する乳酸菌が、ラクトバチルスＯＮＲＩＣｂ０２４０（ＦＥＲＭ ＢＰ−１００６５）又はその変異株である、項２−１に記載の花粉症軽減剤。
項２−３．飲食品又は医薬品である、項２−１又は２−２に記載の花粉症軽減剤。
(2) Pollinosis reducing agent Item 2-1. A pollinosis reducing agent containing lactic acid bacteria belonging to Lactobacillus pentosus.
Item 2-2.
Item 2-3.
（３）アレルゲンによる不快感の軽減剤
項３−１．ラクトバチルス・ペントーサスに属する乳酸菌を含有する、アレルゲンによる不快感の軽減剤。
項３−２．前記アレルゲンが花粉である、項３−１に記載のアレルゲンによる不快感の軽減剤。
項３−３．前記ラクトバチルス・ペントーサスに属する乳酸菌が、ラクトバチルスＯＮＲＩＣｂ０２４０（ＦＥＲＭ ＢＰ−１００６５）又はその変異株である、項３−１又は３−２に記載のアレルゲンによる不快感の軽減剤。
項３−４．飲食品又は医薬品である、項３−１〜３−３のいずれか一項に記載のアレルゲンによる不快感の軽減剤。
(3) Allergen-induced discomfort reducing agent Item 3-1. An allergen-induced discomfort reducing agent containing lactic acid bacteria belonging to Lactobacillus pentosus.
Item 3-2.
Item 3-3.
Item 3-4. The agent for reducing discomfort caused by an allergen according to any one of Items 3-1 to 3, which is a food or drink or a pharmaceutical product.
（４）ＩｇＥ低減剤
項４−１．ラクトバチルス・ペントーサスに属する乳酸菌を含有する、ＩｇＥ低減剤。
項４−２．前記ラクトバチルス・ペントーサスに属する乳酸菌が、ラクトバチルスＯＮＲＩＣｂ０２４０（ＦＥＲＭ ＢＰ−１００６５）又はその変異株である、項４−１に記載のＩｇＥ低減剤。
項４−３．飲食品又は医薬品である、項４−１又は４−２に記載のＩｇＥ低減剤。
(4) IgE reducing agent Item 4-1. An IgE reducing agent containing lactic acid bacteria belonging to Lactobacillus pentosus.
Item 4-2. Item 4. The IgE reducing agent according to Item 4-1. The lactic acid bacterium belonging to Lactobacillus pentosus is Lactobacillus ONRICb0240 (FERM BP-10065) or a mutant strain thereof.
Item 4-3.
ラクトバチルス・ペントーサスに属する乳酸菌は優れたＩ型アレルギーに対する抗アレルギー作用を有するので、抗Ｉ型アレルギー剤、花粉症軽減剤、及びアレルゲンによる不快感の軽減剤の有効成分として有用である。また、より詳細には、ラクトバチルス・ペントーサスに属する乳酸菌は優れたＩｇＥ低減作用を有するので、ＩｇＥ低減剤の有効成分として有用である。そのため、本発明によれば、ラクトバチルス・ペントーサスに属する乳酸菌を有効成分とする、抗Ｉ型アレルギー剤、花粉症軽減剤、アレルゲンによる不快感の軽減剤、及びＩｇＥ低減剤を提供することができる。 Lactic acid bacteria belonging to Lactobacillus pentosus have an excellent anti-allergic action against type I allergy, and are therefore useful as active ingredients of anti-type I allergic agents, pollinosis reducing agents, and allergen-induced discomfort reducing agents. More specifically, lactic acid bacteria belonging to Lactobacillus pentosas have an excellent IgE reducing action, and are therefore useful as an active ingredient of an IgE reducing agent. Therefore, according to the present invention, it is possible to provide an anti-type I allergic agent, a pollinosis reducing agent, an allergen-induced discomfort reducing agent, and an IgE reducing agent containing lactic acid bacteria belonging to Lactobacillus pentosus as an active ingredient. ..
以下、本発明の実施の形態について説明する。 Hereinafter, embodiments of the present invention will be described.
本発明の抗Ｉ型アレルギー剤、花粉症軽減剤、アレルゲンによる不快感の軽減剤、及びＩｇＥ低減剤は、ラクトバチルス・ペントーサスに属する乳酸菌を有効成分として含有することを特徴とする。 The anti-type I allergic agent, pollinosis reducing agent, allergen-induced discomfort reducing agent, and IgE reducing agent of the present invention are characterized by containing lactic acid bacteria belonging to Lactobacillus pentosas as an active ingredient.
本発明におけるＩ型アレルギーとしては、特に制限されないが、アトピー性皮膚炎、アレルギー性鼻炎、花粉症、アレルギー性皮膚炎、気管支喘息、蕁麻疹、アレルギー性結膜炎、アナフィラキシーショックなどが挙げられる。 The type I allergy in the present invention is not particularly limited, and examples thereof include atopic dermatitis, allergic rhinitis, pollinosis, allergic dermatitis, bronchial asthma, urticaria, allergic conjunctivitis, and anaphylactic shock.
本発明におけるアレルゲンとしては、特に制限されないが、ハウスダスト、ほこり、花粉、ダニ、カビ、細菌及び動物のフケなどが挙げられ、特に花粉である。花粉の種類としては、特に制限されないが、スギ、ヒノキ、ハンノキ、シラカンバ、サワラ、ブタクサ、ヨモギ、カナムグラ、イネ科植物などの花粉が挙げられ、特にスギ花粉である。 The allergen in the present invention is not particularly limited, and examples thereof include house dust, dust, pollen, mites, molds, bacteria, and animal dandruff, and are particularly pollen. The type of pollen is not particularly limited, and examples thereof include pollen of Sugi, Hinoki, Alder, Shirakamba, Sawara, Ragweed, Mugwort, Humulus japonicus, and Rice plant, and are particularly Sugi pollen.
本発明のアレルゲンによる不快感の軽減剤における不快感としては、例えば、目、鼻のアレルギー反応及びＱＯＬ低下を総括した不快感であり、具体的には、鼻水、くしゃみ、鼻づまり、鼻のかゆみ、目のかゆみ、流涙などの症状やアレルゲン曝露によるＱＯＬ低下を含む総括的な不快感が挙げられる。 The discomfort in the allergen-induced discomfort reducing agent of the present invention is, for example, discomfort that summarizes allergic reactions in the eyes and nose and a decrease in QOL. Specifically, it is a runny nose, sneezing, stuffy nose, and itchy nose. , Itching of the eyes, lacrimation and general discomfort including QOL reduction due to allergen exposure.
本発明において使用されるラクトバチルス・ペントーサス(Lactobacillus pentosus)としては、例えば、ラクトバチルス・ペントーサスＳ−ＰＴ８４、ラクトバチルスＯＮＲＩＣｂ０２４０株などが挙げられ、好ましくはラクトバチルスＯＮＲＩＣｂ０２４０株である。ラクトバチルス・ペントーサスに属する乳酸菌は、１種又は２種以上を任意に組み合わせて使用することができる。 Examples of the Lactobacillus pentosus used in the present invention include Lactobacillus pentosus S-PT84, Lactobacillus ONRICb0240 strain, and the like, and Lactobacillus ONRICb0240 strain is preferable. Lactic acid bacteria belonging to Lactobacillus pentosus can be used alone or in any combination of two or more.
ラクトバチルスＯＮＲＩＣｂ０２４０（以下、Ｂ２４０と表記することもある）株は、天然物から単離された乳酸菌であり、平成１５年８月６日に、日本国茨城県つくば市東１丁目１番地１ 中央第６に住所を有する独立行政法人 産業技術総合研究所 特許生物寄託センター（ＩＰＯＤ）に寄託番号ＦＥＲＭ Ｐ−１９４７０として寄託され、現在、国際寄託に移管されており、その国際寄託番号はＦＥＲＭ ＢＰ−１００６５である。なお、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は、２０１２年４月に独立行政法人製品評価技術基盤機構（ＮＩＴＥ）特許微生物寄託センターと統合され、現在、独立行政法人製品評価技術基盤機構バイオテクノロジーセンター特許生物寄託センター（ＮＩＴＥ−ＩＰＯＤ）（〒２９２−０８１８ 日本国千葉県木更津市かずさ鎌足２−５−８ １２０号室）にてその微生物寄託業務は承継されている。ラクトバチルスＯＮＲＩＣｂ０２４０株の菌学的性質については、既知である。なお、本発明で使用されるラクトバチルスＯＮＲＩＣｂ０２４０株は、国際寄託の時点では、ラクトバチルス・プランタラム(Lactobacillus plantarum)に属すると分類されていたが、その後の分類基準の変更(Francois Bringle et al., International Journal of Systematic and Evolutionary Microbiology, Vol. 55, 2005, p.1629-1634)に伴い、本株は、ラクトバチルス・ペントーサス(Lactobacillus pentosus)に分類されることになった。 The Lactobacillus ONRICb0240 (hereinafter sometimes referred to as B240) strain is a lactic acid bacterium isolated from a natural product, and on August 6, 2003, 1-1-1, Higashi, Tsukuba-shi, Ibaraki, Japan, Chuo-dai. It was deposited as deposit number FERM P-19470 at the National Institute of Advanced Industrial Science and Technology Patent Organism Depositary (IPOD), which has an address in 6, and is currently being transferred to international deposit, and the international deposit number is FERM BP-10065. Is. The Patent Organism Depositary of the National Institute of Advanced Industrial Science and Technology was integrated with the Patented Microbial Depositary of the National Institute of Technology and Evaluation (NITE) in April 2012, and is currently the National Institute of Technology and Evaluation. The microbial deposit business has been taken over at the Biotechnology Center Patent Organism Depositary Center (NITE-IPOD) (Room 2-5-8 Kazusakamatari, Kisarazu City, Chiba Prefecture, Japan 292-0818). The mycological properties of the Lactobacillus ONRICb0240 strain are known. The Lactobacillus ONRICb0240 strain used in the present invention was classified as belonging to Lactobacillus plantarum at the time of international deposit, but the classification criteria were changed thereafter (Francois Bringle et al. , International Journal of Systematic and Evolutionary Microbiology, Vol. 55, 2005, p.1629-1634), this strain has been classified as Lactobacillus pentosus.
ラクトバチルスＯＮＲＩＣｂ０２４０株の変異株としては、ラクトバチルスＯＮＲＩＣｂ０２４０株から得られた任意の株であって、ラクトバチルスＯＮＲＩＣｂ０２４０株と同様に抗アレルギー作用を有するものである限り特に制限されない。このような変異株は、例えば、自然突然変異、化学的若しくは物理的変異原による誘発変異によって人工的に突然変異の頻度を高める方法、又は遺伝子組換え技術により得ることができる。変異原の例としては、例えば、エチルメタンスルホネート、亜硝酸、Ｎ−メチル−Ｎ’−ニトロ−Ｎ−ニトロソグアニジン、ＵＶ照射、重イオンビーム照射、Ｘ線照射、ガンマ線照射などが挙げられる。 The mutant strain of the Lactobacillus ONRICb0240 strain is not particularly limited as long as it is any strain obtained from the Lactobacillus ONRICb0240 strain and has an antiallergic effect like the Lactobacillus ONRICb0240 strain. Such mutants can be obtained, for example, by means of artificially increasing the frequency of mutations by spontaneous mutations, induced mutations by chemical or physical mutagens, or by genetic recombination techniques. Examples of mutagens include ethylmethane sulfonate, nitrite, N-methyl-N'-nitro-N-nitrosoguanidine, UV irradiation, heavy ion beam irradiation, X-ray irradiation, gamma ray irradiation and the like.
本発明の抗Ｉ型アレルギー剤、花粉症軽減剤、アレルゲンによる不快感の軽減剤、及びＩｇＥ低減剤（以下、抗Ｉ型アレルギー剤等と表記することもある）に含有されるラクトバチルス・ペントーサスに属する乳酸菌は、生菌の状態であってもよく、死菌の状態であってもよく、菌体処理物であってもよく、また、これらが混合された状態であってもよい。ここで、生菌とは、生きた状態の乳酸菌であり、乳酸菌の培養液、当該培養液の懸濁物、粗精製物、精製物や、また、これらの生きた乳酸菌を凍結乾燥やスプレードライ等により乾燥させた菌体粉末なども含まれ、生きた状態である限り制限されない。また、死菌とは、生きた状態の乳酸菌を加熱処理、放射線処理等の物理的処理又は化学的処理に供して殺菌された状態の乳酸菌であり、殺菌された状態の乳酸菌が凍結乾燥やスプレードライ等により乾燥された菌体粉末なども含まれ、死菌である限り制限されない。また、菌体処理物とは、乳酸菌をホモジナイズ処理、酵素処理、超音波処理等で破壊した菌体破砕物であり、当該菌体破砕物を凍結乾燥やスプレードライ等により乾燥させた菌体破砕物の粉末も含まれる。本発明に含有されているラクトバチルス・ペントーサスに属する乳酸菌は、好ましくは生菌、死菌、菌体処理物又はこれらの混合物の状態であり、より好ましくは死菌又は生菌と死菌の混合物の状態であり、更に好ましくは死菌の状態ある。 Lactobacillus pentosus contained in the anti-type I allergic agent, pollinosis reducing agent, allergen-induced discomfort reducing agent, and IgE reducing agent (hereinafter, may be referred to as anti-type I allergic agent, etc.) of the present invention. The lactic acid bacterium belonging to the above may be in a viable state, a dead bacterium state, a cell-treated product, or a mixed state thereof. Here, the live bacterium is a living lactic acid bacterium, and the culture solution of the lactic acid bacterium, the suspension of the culture solution, the crude purified product, the purified product, and these live lactic acid bacteria are freeze-dried or spray-dried. It also contains bacterial cell powder dried by the like, and is not limited as long as it is alive. The dead bacterium is a lactic acid bacterium in a state in which a living lactic acid bacterium is subjected to physical treatment such as heat treatment or radiation treatment or a chemical treatment to be sterilized, and the sterilized lactic acid bacterium is freeze-dried or sprayed. It also includes bacterial cell powder dried by drying or the like, and is not limited as long as it is a dead bacterium. The cell-treated product is a cell-crushed product obtained by destroying lactic acid bacteria by homogenization treatment, enzyme treatment, ultrasonic treatment, etc., and the cell-crushed product is dried by freeze-drying, spray-drying, or the like. The powder of the thing is also included. The lactic acid bacterium belonging to Lactobacillus pentosus contained in the present invention is preferably in the state of a live bacterium, a dead bacterium, a treated cell product, or a mixture thereof, and more preferably a dead bacterium or a mixture of a live bacterium and a dead bacterium. It is in the state of, more preferably in the state of dead bacteria.
本発明の抗Ｉ型アレルギー剤等に使用されるラクトバチルス・ペントーサスに属する乳酸菌は、当該乳酸菌株の生育に適した培地で培養することによって増殖させることができる。培養方法は制限されないが、例えば、ＭＲＳ培地、ＬＢＳ培地、Ｒｏｇｏｓａ培地等の培地中で３０℃で１６時間程度培養することによって増殖させることができる。また、菌体は、培養後に、例えば、培養物（培養液）を遠心分離（例えば、３，０００ｒｐｍ、４℃、１０分間）して集菌することができる。また、本発明で使用されるラクトバチルス・ペントーサスに属する乳酸菌は、乳、野菜類、果物類、豆乳等などの素材等の存在下で培養（発酵）してもよい。前述同様、菌体は、培養後に遠心分離を行うことにより集菌することができる。本発明においては、このようにして得られる培養物（発酵物）や集菌された菌体、当該培養物又は菌体の懸濁物や濃縮物、また、このようにして得られた培養物、菌体、懸濁物、濃縮物を凍結乾燥やスプレードライ等により乾燥させて粉末化したものなども用いることもできる。これらの調製は、当業界で公知の方法に従って行うことができる。また、培養（発酵）がより効率よく行われる点から、発酵前の乳、野菜類、果物類、豆乳などの素材は、液状など一定以上の流動性を有することが好ましい。 The lactic acid bacterium belonging to Lactobacillus pentosus used in the anti-type I allergic agent of the present invention can be grown by culturing in a medium suitable for the growth of the lactic acid bacterium strain. The culturing method is not limited, but the culturing can be carried out by culturing in a medium such as MRS medium, LBS medium, Rogosa medium at 30 ° C. for about 16 hours. In addition, after culturing, the cells can be collected by, for example, centrifuging the culture (culture solution) (for example, 3,000 rpm, 4 ° C., 10 minutes). Further, the lactic acid bacterium belonging to Lactobacillus pentosus used in the present invention may be cultured (fermented) in the presence of materials such as milk, vegetables, fruits, soymilk and the like. As described above, the cells can be collected by centrifuging after culturing. In the present invention, the culture (fermented product) thus obtained, the collected bacterial cells, the suspension or concentrate of the culture or bacterial cells, and the culture thus obtained. , Bacteria, suspensions, concentrates, dried by freeze-drying, spray-drying, etc. and pulverized can also be used. These preparations can be performed according to methods known in the art. Further, from the viewpoint of more efficient culture (fermentation), it is preferable that the material such as milk, vegetables, fruits and soymilk before fermentation has a certain level of fluidity such as liquid.
本発明の抗Ｉ型アレルギー剤等は、前述するように、ラクトバチルス・ペントーサスに属する乳酸菌を有効成分として含有すればよい。したがって、例えば、前記培養物をそのまま、あるいは均質化等の処理を施して、抗Ｉ型アレルギー剤等として使用してもよいし、前記調製したものを抗Ｉ型アレルギー剤等として使用してもよい。 As described above, the anti-type I allergic agent of the present invention may contain lactic acid bacteria belonging to Lactobacillus pentosas as an active ingredient. Therefore, for example, the culture may be used as it is or after being subjected to a treatment such as homogenization and used as an anti-type I allergic agent or the like, or the prepared product may be used as an anti-type I allergic agent or the like. Good.
本発明の抗Ｉ型アレルギー剤等に、生きた状態のラクトバチルス・ペントーサスに属する乳酸菌が含有されている場合、生きた状態を一層良好に維持させる点から、必要に応じて更に、ラクトバチルス・ペントーサスに属する乳酸菌の生育に適した栄養成分を抗Ｉ型アレルギー剤等に含有させることが望ましい。当該栄養成分としては、例えば、グルコース、澱粉、蔗糖、乳糖、デキストリン、ソルビトール、フラクトース等の炭素源；酵母エキス、ペプトン等の窒素源；ビタミン類；ミネラル類；微量金属元素；その他の栄養成分等の各成分を挙げることができる。ビタミン類としては、具体的には、ビタミンＢ、ビタミンＤ、ビタミンＣ、ビタミンＥ、ビタミンＫ等を例示できる。微量金属元素としては、具体的には、亜鉛、セレン等を例示できる。その他の栄養成分としては、具体的には、乳果オリゴ糖、大豆オリゴ糖、ラクチュロース、ラクチトール、フラクトオリゴ糖、ガラクトオリゴ糖等の各種オリゴ糖を例示できる。 When the anti-type I allergic agent of the present invention contains lactic acid bacteria belonging to Lactobacillus pentosus in a living state, Lactobacillus can be further maintained in a living state as necessary. It is desirable that an anti-type I allergic agent or the like contains a nutritional component suitable for the growth of lactic acid bacteria belonging to Pentosas. Examples of the nutritional components include carbon sources such as glucose, starch, sucrose, lactose, dextrin, sorbitol and fructose; nitrogen sources such as yeast extract and peptone; vitamins; minerals; trace metal elements; other nutritional components and the like. Each component of is mentioned. Specific examples of vitamins include vitamin B, vitamin D, vitamin C, vitamin E, and vitamin K. Specific examples of the trace metal element include zinc and selenium. Specific examples of other nutritional components include various oligosaccharides such as milk fruit oligosaccharide, soybean oligosaccharide, lactitol, lactitol, fructooligosaccharide, and galactooligosaccharide.
また、本発明の抗Ｉ型アレルギー剤等には、更に必要に応じて任意の成分を含有させることができ、当該任意の成分として、例えば、可食性又は薬学的に許容される担体や添加物等を含有させることができる。可食性又は薬学的に許容される担体や添加物としては、水性媒体、賦形剤、結合剤、崩壊剤、滑沢剤、増粘剤、界面活性剤、浸透圧調節剤、付湿剤、ｐＨ調整剤、甘味料、香料、色素等が例示される。これらは当業者により公知であり、適宜選択して使用される。具体的には、これらの一例として、水、生理食塩水、果汁等の水性媒体；乳糖、白糖、塩化ナトリウム、ブドウ糖、尿素、デンプン、炭酸カルシウム、カオリン、結晶セルロース、ケイ酸、リン酸カリウム、コーンスターチ、デキストリン等の賦形剤；水、エタノール、プロパノール、単シロップ、ブドウ糖液、デンプン液、ゼラチン溶液、カルボキシメチルセルロース、ヒドロキシプロピルセルロース、メチルセルロース、ポリビニルピロリドン等の結合剤；カルボキシメチルセルロースナトリウム、カルボキシメチルセルロースカルシウム、低置換度ヒドロキシプロピルセルロース、乾燥デンプン、アルギン酸ナトリウム、カンテン末、ラミナラン末、炭酸水素ナトリウム、炭酸カルシウム等の崩壊剤；精製タルク、ステアリン酸塩、ホウ酸末、ポリエチレングリコール等の滑沢剤；ゼラチン、アラビアガム、デキストリン、メチルチセルロース、ポリビニルピロリドン、ポリビニルアルコール、ヒドロキシプロピルセルロース、キサンタンガム、ペクチン、トラガントガム、カゼイン、アルギン酸等の増粘剤；リオキシエチレンソルビタン脂肪酸エステル類、ラウリル硫酸ナトリウム、ステアリン酸モノグリセリド等の界面活性剤；ステビア、サッカリン、アセスルファムＫ、アスパラテーム、スクラロース等の甘味料等が挙げられる。 Further, the anti-type I allergic agent of the present invention may further contain an arbitrary component as required, and the optional component includes, for example, an edible or pharmaceutically acceptable carrier or additive. Etc. can be contained. Edible or pharmaceutically acceptable carriers and additives include aqueous media, excipients, binders, disintegrants, lubricants, thickeners, surfactants, osmoregulators, wetting agents, etc. Examples include pH adjusters, sweeteners, flavors, pigments and the like. These are known to those skilled in the art and are appropriately selected and used. Specifically, as an example of these, aqueous media such as water, physiological saline, fruit juice; lactose, sucrose, sodium chloride, glucose, urea, starch, calcium carbonate, kaolin, crystalline cellulose, silicic acid, potassium phosphate, etc. Excipients such as corn starch and dextrin; binders such as water, ethanol, propanol, simple syrup, glucose solution, starch solution, gelatin solution, carboxymethyl cellulose, hydroxypropyl cellulose, methyl cellulose, polyvinylpyrrolidone; sodium carboxymethyl cellulose, calcium carboxymethyl cellulose , Low-substituted hydroxypropyl cellulose, dried starch, sodium alginate, canten powder, laminaran powder, sodium hydrogen carbonate, calcium carbonate and other disintegrants; purified talc, stearate, borate powder, polyethylene glycol and other lubricants; Thickeners such as gelatin, arabic gum, dextrin, methyl thycellulose, polyvinylpyrrolidone, polyvinyl alcohol, hydroxypropyl cellulose, xanthan gum, pectin, tragant gum, casein, alginic acid; lyoxyethylene sorbitan fatty acid esters, sodium lauryl sulfate, stearic acid Surfactants such as monoglyceride; sweeteners such as stevia, saccharin, assesulfam K, aspartame, sclarose and the like can be mentioned.
必要に応じて使用される成分は当業者であれは適宜選択可能であり、また、当該成分の配合量は、目的とする形態や嗜好等に適合するよう、本発明の効果を妨げない範囲で、適宜調整すればよい。 The ingredients used as necessary can be appropriately selected by those skilled in the art, and the blending amount of the ingredients is within a range that does not interfere with the effects of the present invention so as to suit the desired form, taste, etc. , Should be adjusted as appropriate.
本発明の抗Ｉ型アレルギー剤等の形態は特に制限されないが、例えば、散剤、顆粒剤、錠剤、丸剤、トローチ等の固形形態；ゼリー、ムース、ヨーグルト、プディング、クリームのような半固形形態、液剤、懸濁剤、乳剤、シロップ剤等の液状形態が挙げられる。また、これらの形態は、マイクロカプセル、ソフトカプセル、ハードカプセル等に充填されて、カプセル剤の形態とすることもできる。また、本発明の抗Ｉ型アレルギー剤等は、発泡製剤の形態とすることもできる。これらの形態の製造方法は、当業界で公知の方法に従って行うことができる。 The form of the anti-type I allergic agent of the present invention is not particularly limited, but is, for example, a solid form such as powder, granule, tablet, pill, troche; a semi-solid form such as jelly, mousse, yogurt, pudding, cream. , Liquids, suspensions, emulsions, syrups and the like in liquid form. Further, these forms can be filled in microcapsules, soft capsules, hard capsules and the like to form capsules. Further, the anti-type I allergic agent and the like of the present invention can also be in the form of a foaming preparation. The manufacturing method of these forms can be carried out according to a method known in the art.
本発明の抗Ｉ型アレルギー剤等におけるラクトバチルス・ペントーサスに属する乳酸菌の含有量は、１日当たりの投与量、投与形態、投与回数、使用目的等に応じて適宜設定される。本発明の効果が奏されることを限度として制限されないが、例えば、本発明の抗Ｉ型アレルギー剤等におけるラクトバチルス・ペントーサスに属する乳酸菌の含有量は、ラクトバチルス・ペントーサスに属する乳酸菌が総菌数（すなわち、生菌、死菌、菌体処理物の合計数）として１０４ｃｅｌｌｓ／ｍｇ以上、好ましくは１０５〜１０１２ｃｅｌｌｓ／ｍｇ、より好ましくは１０６〜１０１１ｃｅｌｌｓ／ｍｇである。 The content of lactic acid bacteria belonging to Lactobacillus pentosus in the anti-type I allergic agent of the present invention is appropriately set according to the daily dose, administration form, number of administrations, purpose of use and the like. The content of the lactic acid bacterium belonging to Lactobacillus pentosas in the anti-type I allergic agent of the present invention is not limited to the extent that the effect of the present invention is exhibited. The number (that is, the total number of live bacteria, dead bacteria, and processed bacterial cells) is 10 4 cells / mg or more, preferably 10 5 to 10 12 cells / mg, and more preferably 10 6 to 10 11 cells / mg. ..
また、本発明の抗Ｉ型アレルギー剤等におけるラクトバチルス・ペントーサスに属する乳酸菌の含有量は、本発明の効果が奏されることを限度として制限されないが、例えば、当該剤あたり、ラクトバチルス・ペントーサスに属する乳酸菌が総菌数して１０４ｃｅｌｌｓ以上、好ましくは１０６〜１０１２ｃｅｌｌｓ、より好ましくは１０７〜１０１２ｃｅｌｌｓ、更に好ましくは１０８〜１０１２ｃｅｌｌｓ、効率良く所望の効果が得られる点から特に好ましくは総菌数として１０８〜１０１１ｃｅｌｌｓ、一層好ましくは総菌数として１０９〜１０１０ｃｅｌｌｓである。 Further, the content of lactic acid bacteria belonging to Lactobacillus pentosus in the anti-type I allergic agent of the present invention is not limited as long as the effect of the present invention is exhibited. The total number of lactic acid bacteria belonging to is 10 4 cells or more, preferably 10 6 to 10 12 cells, more preferably 10 7 to 10 12 cells, further preferably 10 8 to 10 12 cells, and the desired effect can be obtained efficiently. From this point of view, the total number of bacteria is particularly preferably 10 8 to 10 11 cells, and more preferably 10 9 to 10 10 cells.
また、本発明の抗Ｉ型アレルギー剤等の投与量は、年齢、性別、症状等によって適宜調整されるが、成人１日当たりの投与量として、ラクトバチルス・ペントーサスに属する乳酸菌が総菌数として１０４ｃｅｌｌｓ以上、好ましくは１０６〜１０１２ｃｅｌｌｓ、より好ましくは１０７〜１０１２ｃｅｌｌｓ、更に好ましくは１０８〜１０１２ｃｅｌｌｓ、効率良く所望の効果が得られる点から特に好ましくは１０８〜１０１１ｃｅｌｌｓ、一層好ましくは１０９〜１０１０ｃｅｌｌｓが例示される。これは、１日に１回又は数回に分けて投与することができる。投与方法は、本発明の効果を奏する限り制限されないが、経口投与が好ましい。 The dose of the anti-type I allergic agent of the present invention is appropriately adjusted according to age, sex, symptoms, etc., but the total number of lactic acid bacteria belonging to Lactobacillus pentosus is 10 as the daily dose for adults. 4 cells or more, preferably 10 6 to 10 12 cells, more preferably 10 7 to 10 12 cells, further preferably 10 8 to 10 12 cells, particularly preferably 10 8 to 10 from the viewpoint of efficiently obtaining the desired effect. 11 cells, more preferably 10 9 to 10 10 cells, are exemplified. It can be administered once or in several divided doses per day. The administration method is not limited as long as the effects of the present invention are obtained, but oral administration is preferable.
なお、ラクトバチルス・ペントーサスに属する乳酸菌の総菌数は、公知の細菌数測定法や細菌数測定装置を使用して測定すればよい。例えば、公知の細菌数測定装置として顕微鏡、フローサイトメーター、また迅速検査装置バイオプローラ（登録商標）（パナソニックエコシステムズ社製）などが使用できる。後述する実施例においては、凍結乾燥原末を製造した段階でフローサイトメーターを使用して総菌数を測定した。 The total number of lactic acid bacteria belonging to Lactobacillus pentosus may be measured by using a known bacterial number measuring method or a bacterial number measuring device. For example, as a known bacterial count measuring device, a microscope, a flow cytometer, a rapid test device Bioprowler (registered trademark) (manufactured by Panasonic Ecology Systems Co., Ltd.) and the like can be used. In the examples described later, the total number of bacteria was measured using a flow cytometer at the stage of producing the freeze-dried raw powder.
また、本発明における適用対象は、Ｉ型アレルギー症状を緩和することを目的とする動物であれば制限されない。例えば、当該動物としてヒトなどの哺乳動物が挙げられるが、このほか、哺乳動物以外のペットや家畜をはじめとする多様な動物が挙げられる。本発明は、適用対象の年齢や性別を問わない。 Further, the application target in the present invention is not limited as long as it is an animal whose purpose is to alleviate type I allergic symptoms. For example, mammals such as humans can be mentioned as the animals, and various animals such as pets and livestock other than mammals can be mentioned. The present invention is not limited to the age and gender of the subject.
本発明の抗Ｉ型アレルギー剤等は飲食品に応用できる。すなわち、本発明の抗Ｉ型アレルギー剤等は、そのまま飲食品として使用できる。また、飲食品への添加剤として使用できる。このような本発明の抗Ｉ型アレルギー剤等を含有する飲食品によれば、本発明の抗Ｉ型アレルギー剤等に起因する効果、すなわち、ラクトバチルス・ペントーサスに属する乳酸菌に起因する前記効果が得られる。また、本発明の抗Ｉ型アレルギー剤等は、そのまま医薬品として使用できる。また、本発明の抗Ｉ型アレルギー剤等は医薬品への添加剤として使用できる。このような本発明の抗Ｉ型アレルギー剤等を含有する医薬品によれば、本発明の抗Ｉ型アレルギー剤等に起因する効果、すなわち、ラクトバチルス・ペントーサスに属する乳酸菌に起因する前記効果が得られる。 The anti-type I allergic agent of the present invention can be applied to foods and drinks. That is, the anti-type I allergic agent of the present invention can be used as it is as a food or drink. It can also be used as an additive to foods and drinks. According to such foods and drinks containing the anti-type I allergic agent of the present invention, the effect caused by the anti-type I allergic agent of the present invention, that is, the effect caused by the lactic acid bacterium belonging to Lactobacillus pentosas is obtained. can get. In addition, the anti-type I allergic agent of the present invention can be used as it is as a pharmaceutical product. In addition, the anti-type I allergic agent of the present invention can be used as an additive to pharmaceutical products. According to the drug containing the anti-type I allergic agent of the present invention, the effect caused by the anti-type I allergic agent of the present invention, that is, the effect caused by the lactic acid bacterium belonging to Lactobacillus pentosus can be obtained. Be done.
本発明の抗Ｉ型アレルギー剤等がこのように飲食品又は医薬品に応用される場合、当該飲食品又は医薬品の種類は限定されず、ラクトバチルス・ペントーサスに属する乳酸菌を一成分として飲食品や医薬品に配合すればよく、また、必要に応じて任意の成分、例えば、可食性又は薬学的に許容される担体や添加物等を更に含有させることができる。可食性又は薬学的に許容される担体や添加物等としては、水性媒体、賦形剤、結合剤、崩壊剤、滑沢剤、増粘剤、界面活性剤、浸透圧調節剤、付湿剤、ｐＨ調整剤、甘味料、香料、色素等の前述のものが例示されるがこれらに限定されない。なお、これらの成分は当業者であれは適宜選択可能であり、また、当該成分の配合量は、目的とする形態や嗜好等に適合するよう、本発明の効果を妨げない範囲で、適宜調整すればよい。 When the anti-type I allergic agent of the present invention is applied to foods and drinks or pharmaceuticals in this way, the types of the foods and drinks or pharmaceuticals are not limited, and the foods and drinks and pharmaceuticals contain lactic acid bacteria belonging to Lactobacillus pentosas as one component. And, if necessary, any component such as an edible or pharmaceutically acceptable carrier or additive can be further contained. Examples of edible or pharmaceutically acceptable carriers and additives include aqueous media, excipients, binders, disintegrants, lubricants, thickeners, surfactants, osmoregulators, and wetting agents. , PH adjusters, sweeteners, flavors, pigments and the like, but are not limited thereto. It should be noted that these components can be appropriately selected by those skilled in the art, and the blending amount of the components is appropriately adjusted within a range that does not interfere with the effects of the present invention so as to suit the desired form, taste, etc. do it.
また、このように本発明の抗Ｉ型アレルギー剤等が飲食品又は医薬品に応用される場合の飲食品又は医薬品も本発明の効果を奏する限り制限されない。例えば、飲食品として、制限されないが、菓子類（ガム、キャンディー、クッキー、グミ、せんべい、ビスケット、ゼリー、ムース、クリームキャラメル、ラムネ菓子、可食性シート、可食性フィルム、トローチ等）、口中清涼剤（ガム、飴、グミ、可食性フィルム、トローチ等）、飲料（炭酸飲料、清涼飲料、乳飲料、アルコール飲料、果汁飲料、茶類、栄養飲料等）、粉末飲料（粉末ジュース、粉末スープ等）、乳製品（チーズ、ヨーグルト等）、パン、麺類、シリアル等が挙げられる。また、飲食品として、例えば、特定保健用食品、栄養補助食品、サプリメント、機能性表示食品、病者用食品等を挙げることができる。また、医薬品についても限定されないが、前述するような固形形態、半固形形態、液状形態の製剤、カプセル剤、発泡製剤等が挙げられる。これらの製造方法は、当業界で公知の方法に従って行うことができる。 Further, the food or drink or the drug when the anti-type I allergic agent or the like of the present invention is applied to the food or drink or the drug is not limited as long as the effect of the present invention is exhibited. For example, as food and drink, confectionery (gum, candy, cookie, gummy, senbei, biscuits, jelly, mousse, cream caramel, ramune confectionery, edible sheet, edible film, troche, etc.), mouth softener, etc. (Gum, candy, gummy, edible film, troche, etc.), beverages (carbonated beverages, soft drinks, dairy beverages, alcoholic beverages, fruit juice beverages, teas, nutritional beverages, etc.), powdered beverages (powdered juice, powdered soup, etc.) , Dairy products (cheese, yogurt, etc.), bread, noodles, cereals, etc. In addition, examples of foods and drinks include foods for specified health use, dietary supplements, supplements, foods with functional claims, foods for the sick, and the like. Further, the pharmaceutical product is also not limited, and examples thereof include the above-mentioned solid form, semi-solid form, liquid form, capsule, effervescent preparation and the like. These manufacturing methods can be carried out according to methods known in the art.
本発明の抗Ｉ型アレルギー剤等を含有する飲食品又は医薬品におけるラクトバチルス・ペントーサスに属する乳酸菌の含有量は、１日当たりの投与量、投与形態、投与回数、使用目的等に応じて適宜設定される。本発明の効果が奏されることを限度として制限されないが、例えば、当該飲食品又は医薬品あたり、ラクトバチルス・ペントーサスに属する乳酸菌が総菌数として１０４ｃｅｌｌｓ／ｍｇ以上、好ましくは１０５〜１０１２ｃｅｌｌｓ／ｍｇ、より好ましくは１０６〜１０１１ｃｅｌｌｓ／ｍｇである。 The content of lactic acid bacteria belonging to Lactobacillus pentosus in foods and drinks or pharmaceuticals containing the anti-type I allergic agent of the present invention is appropriately set according to the daily dose, administration form, number of administrations, purpose of use and the like. To. Although the effect of the present invention can be attained not limited as limits, e.g., food or beverage or per pharmaceuticals, lactic acid bacteria belonging to Lactobacillus pentosus is 10 4 cells / mg or more as the total number of bacteria, preferably 10 5 to 10 It is 12 cells / mg, more preferably 10 6 to 11 cells / mg.
また、当該飲食品又は医薬品におけるラクトバチルス・ペントーサスに属する乳酸菌の含有量は、本発明の効果が奏されることを限度として制限されないが、例えば、飲食品又は医薬品あたり、ラクトバチルス・ペントーサスに属する乳酸菌が総菌数して１０４ｃｅｌｌｓ以上、好ましくは１０６〜１０１２ｃｅｌｌｓ、より好ましくは１０７〜１０１２ｃｅｌｌｓ、更に好ましくは１０８〜１０１２ｃｅｌｌｓ、効率良く所望の効果が得られる点から特に好ましくは総菌数として１０８〜１０１１ｃｅｌｌｓ、一層好ましくは総菌数として１０９〜１０１０ｃｅｌｌｓである。 Further, the content of lactic acid bacteria belonging to Lactobacillus pentosas in the food or drink or pharmaceutical product is not limited as long as the effect of the present invention is exhibited, but for example, the food or drink or pharmaceutical product belongs to Lactobacillus pentosas. The total number of lactic acid bacteria is 10 4 cells or more, preferably 10 6 to 10 12 cells, more preferably 10 7 to 10 12 cells, still more preferably 10 8 to 10 12 cells, and the desired effect can be efficiently obtained. Therefore, the total number of bacteria is particularly preferably 10 8 to 10 11 cells, and more preferably the total number of bacteria is 10 9 to 10 10 cells.
また、当該飲食品又は医薬品の投与量は、年齢、性別、症状等によって適宜調整されるが、成人１日当たりの投与量として、ラクトバチルス・ペントーサスに属する乳酸菌が総菌数として１０４ｃｅｌｌｓ以上、好ましくは１０６〜１０１２ｃｅｌｌｓ、より好ましくは１０７〜１０１２ｃｅｌｌｓ、更に好ましくは１０８〜１０１２ｃｅｌｌｓ、効率良く所望の効果が得られる点から特に好ましくは１０８〜１０１１ｃｅｌｌｓ、一層好ましくは１０９〜１０１０ｃｅｌｌｓが例示される。これは、１日に１回又は数回に分けて投与することができる。 The dose of food or beverage or pharmaceutical the age, sex, is appropriately adjusted according to the symptoms and the like, as the dose for adult per day, lactic acid bacteria belonging to Lactobacillus pentosus is 10 4 cells or as the total number of bacteria, It is preferably 10 6 to 10 12 cells, more preferably 10 7 to 10 12 cells, further preferably 10 8 to 10 12 cells, and particularly preferably 10 8 to 10 11 cells from the viewpoint of efficiently obtaining the desired effect. Preferably, 10 9 to 10 10 cells are exemplified. It can be administered once or in several divided doses per day.
後述する実施例で示すように、ラクトバチルス・ペントーサスに属する乳酸菌は優れたＩ型アレルギーに対する抗アレルギー作用を有するので、抗Ｉ型アレルギー剤、花粉症軽減剤、及びアレルゲンによる不快感の軽減剤の有効成分として使用することができる。また、より詳細には、ラクトバチルス・ペントーサスに属する乳酸菌は優れたＩｇＥ低減作用を有するので、ＩｇＥ低減剤の有効成分として使用することができる。そのため、本発明によれば、ラクトバチルス・ペントーサスに属する乳酸菌を有効成分とする、抗Ｉ型アレルギー剤、花粉症軽減剤、アレルゲンによる不快感の軽減剤、及びＩｇＥ低減剤を提供することができる。また、本発明の抗Ｉ型アレルギー剤等は、食品として使用し得るラクトバチルス・ペントーサスに属する乳酸菌を有効成分とするものであり、副作用が無いか又は極めて少ない。さらに、本発明の抗Ｉ型アレルギー剤等は、軽度のアレルギー反応を示す人のＱＯＬ低下を軽減する目的でも使用することができる。 As shown in Examples described later, lactic acid bacteria belonging to Lactobacillus pentosus have an excellent anti-allergic effect on type I allergies, and therefore, of anti-type I allergic agents, pollinosis reducing agents, and allergen-induced discomfort reducing agents. It can be used as an active ingredient. More specifically, since lactic acid bacteria belonging to Lactobacillus pentosas have an excellent IgE reducing action, they can be used as an active ingredient of an IgE reducing agent. Therefore, according to the present invention, it is possible to provide an anti-type I allergic agent, a pollinosis reducing agent, an allergen-induced discomfort reducing agent, and an IgE reducing agent containing lactic acid bacteria belonging to Lactobacillus pentosus as an active ingredient. .. In addition, the anti-type I allergic agent of the present invention contains lactic acid bacteria belonging to Lactobacillus pentosas that can be used as food as an active ingredient, and has no or extremely few side effects. Furthermore, the anti-type I allergic agent of the present invention can also be used for the purpose of reducing the decrease in QOL of a person who exhibits a mild allergic reaction.
前述するように、ラクトバチルス・ペントーサスに属する乳酸菌は、優れたＩ型アレルギーに対する抗アレルギー作用、また、より詳細には、優れたＩｇＥ低減作用を有している。このことから、本発明は更に、ラクトバチルス・ペントーサスに属する乳酸菌を用いてＩ型アレルギー症状を緩和する方法、花粉症を軽減する方法、アレルゲンによる不快感を軽減する方法、及びＩｇＥを低減する方法（以下、Ｉ型アレルギー症状を緩和等する方法と表記することもある）を提供する。本発明のＩ型アレルギー症状を緩和等する方法は、Ｉ型アレルギー症状の緩和等を求める動物にラクトバチルス・ペントーサスに属する乳酸菌を投与することにより実施できる。すなわち、本発明のＩ型アレルギー症状を緩和等する方法は、Ｉ型アレルギー症状の緩和等が要求される動物に、前記抗Ｉ型アレルギー剤等、又は前記抗Ｉ型アレルギー剤等を含有する飲食品又は医薬品を摂取させる工程を含む。本発明の方法におけるラクトバチルス・ペントーサスに属する乳酸菌、前記抗Ｉ型アレルギー剤等、前記抗Ｉ型アレルギー剤等を含有する飲食品又は医薬品の投与量、投与回数、投与方法、投与部位等は前述に従う。 As described above, the lactic acid bacterium belonging to Lactobacillus pentosus has an excellent anti-allergic action against type I allergy, and more specifically, an excellent IgE reducing action. From this, the present invention further describes a method of alleviating type I allergic symptoms using a lactic acid bacterium belonging to Lactobacillus pentosus, a method of reducing pollinosis, a method of reducing discomfort caused by an allergen, and a method of reducing IgE. (Hereinafter, it may be referred to as a method for alleviating type I allergic symptoms). The method for alleviating type I allergic symptoms of the present invention can be carried out by administering a lactic acid bacterium belonging to Lactobacillus pentosus to an animal seeking alleviation of type I allergic symptoms. That is, the method for alleviating type I allergic symptoms of the present invention is to eat and drink containing the anti-type I allergic agent or the like or the anti-type I allergic agent or the like in an animal that is required to alleviate the type I allergic symptoms or the like. Includes the step of ingesting a product or drug. The dose, frequency of administration, administration method, administration site, etc. of foods and drinks or pharmaceuticals containing the lactic acid bacteria belonging to Lactobacillus pentosus, the anti-type I allergic agent, etc. in the method of the present invention are described above. Follow.
以下、実施例を挙げて本発明を説明するが、本発明はこれらの実施例に限定されるものではない。 Hereinafter, the present invention will be described with reference to examples, but the present invention is not limited to these examples.
試験例１
＜試験方法＞
・試験動物：７週齢雄性マウスＢＡＬＢ／ｃＣｒＳｌｃ（日本エスエルシー株式会社）
Test Example 1
<Test method>
-Test animal: 7-week-old male mouse BALB / cCrSlc (Nippon SLC Co., Ltd.)
・試験群：
（１）コントロール群（ＣＲＦ−１粉末食）（ｎ＝８）
（２）ＰｒｅＢ２４０群（０．２５％ｂ０２４０含有ＣＲＦ−１粉末食）（ｎ＝８）
（３）ＰｏｓｔＢ２４０群（０．２５％ｂ０２４０含有ＣＲＦ−１粉末食）（ｎ＝８）
（４）非感作群（ＣＲＦ−１粉末食）（ｎ＝３）
０．２５％ｂ０２４０含有ＣＲＦ−１粉末食は、ＣＲＦ−１粉末１ｋｇに、乳酸菌ラクトバチルスＯＮＲＩＣｂ０２４０原末２．５ｇを混合して調製した。なお、０．２５％ｂ０２４０は１０ｍｇに相当する。
・ Test group:
(1) Control group (CRF-1 powder diet) (n = 8)
(2) PreB240 group (CRF-1 powder diet containing 0.25% b0240) (n = 8)
(3) PostB240 group (CRF-1 powder diet containing 0.25% b0240) (n = 8)
(4) Non-sensitized group (CRF-1 powder diet) (n = 3)
A CRF-1 powder diet containing 0.25% b0240 was prepared by mixing 1 kg of CRF-1 powder with 2.5 g of raw powder of lactic acid bacterium Lactobacillus ONRICb0240. In addition, 0.25% b0240 corresponds to 10 mg.
・評価項目：鼻掻き回数、血清ＩｇＥ（総ＩｇＥ）
鼻掻き回数については、観察用ケージ内に入れたマウスに５０ｍｇ／ｍＬ ＯＶＡ溶液を点鼻投与し、その直後からマウスの行動をビデオカメラで撮影した。鼻掻き回数は、マウスが前肢で鼻部を引っ掻いた行動のみを鼻掻き行動として計数した。なお、撮影画像がどの群であるかが分からないよう盲検化し、鼻掻き回数データ固定後に開錠した。
血清ＩｇＥ（総ＩｇＥ）については、Mouse OptEIA ELISA Set Mouse IgEを用い、キットの説明書に従い実施した。
-Evaluation items: number of nose scratches, serum IgE (total IgE)
Regarding the number of nasal scratches, 50 mg / mL OVA solution was nasally administered to the mice placed in the observation cage, and immediately after that, the behavior of the mice was photographed with a video camera. As for the number of nose scratches, only the behavior of the mouse scratching the nose with the forelimbs was counted as the nose scratching behavior. The group was blinded so that it was not possible to know which group the photographed image belonged to, and the lock was unlocked after fixing the data on the number of scratches on the nose.
Serum IgE (total IgE) was performed using Mouse OptEIA ELISA Set Mouse IgE according to the instructions of the kit.
・試験スケジュール：図１に示すスケジュールにてＯＶＡによる感作及びラクトバチルスＯＮＲＩＣｂ０２４０の投与を行った。
初回感作は，マウスに腹腔投与用感作液（ＯＶＡ０．５ｍｇ＋水酸化アルミニウムゲル５ｍｇ＋百日咳毒素１．５μｇ／ｍＬ溶液）０．２ｍＬを腹腔内投与した。感作２回目は皮下投与用感作液（ＯＶＡ０．５ｍｇ／ｍＬ溶液）０．１ｍＬを背部皮下投与した。症状惹起は、惹起日午前中に、局所感作として１日１回の頻度で惹起用抗原投与液（ＯＶＡ５０ｍｇ／ｍＬ溶液）を、無麻酔下で保定したマウス両側鼻腔に２μＬずつ、合計４μＬを点鼻投与し、鼻アレルギー症状を惹起させた。非感作群では生理食塩水を感作群と同様の方法で投与した。ラクトバチルスＯＮＲＩＣｂ０２４０の投与は、初回感作以前から０．２５％ｂ０２４０含有ＣＲＦ−１粉末食を給餌する群（ＰｒｅＢ２４０群）と感作２回目翌日から給餌する群（ＰｏｓｔＢ２４０）を設定した。対照群は、ＣＲＦ−１粉末食を給餌した。
-Test schedule: Sensitization by OVA and administration of Lactobacillus ONRICb0240 were performed according to the schedule shown in FIG.
For the first sensitization, 0.2 mL of a sensitization solution for intraperitoneal administration (OVA 0.5 mg +
＜試験結果＞
試験期間中の体重推移の結果を図２に、鼻掻き回数の結果を図３に、血清ＩｇＥ濃度の結果を図４に示す。
<Test result>
The results of body weight transition during the test period are shown in FIG. 2, the results of the number of nose scratches are shown in FIG. 3, and the results of serum IgE concentration are shown in FIG.
図２から試験期間中に平均体重が減少した群は無かった。図３からラクトバチルスＯＮＲＩＣｂ０２４０摂取によりアレルギー性鼻炎モデルマウスの鼻掻き回数が減少していた。図４からＰｒｅＢ２４０群について血清ＩｇＥは減少傾向を認めた。 From FIG. 2, no group lost average body weight during the test period. From FIG. 3, ingestion of Lactobacillus ONRICb0240 reduced the number of nasal scratches in allergic rhinitis model mice. From FIG. 4, serum IgE tended to decrease in the PreB240 group.
試験例２
＜試験方法＞
・被験者
被験者は、ＮＰＯ日本健康増進支援機構によって２０〜６５歳の間の健康なボランティアから募集された。全てのボランティアは、スギ花粉によると思われるアレルギー症状を経験していた。書面によるインフォームドコンセントを与えたボランティアは、次の選択基準に従い試験責任医師によって試験に適切であると判断され、被験者として登録された。１）同意時に２０〜６５歳であること；２）試験に参加するために書面による同意を提供したこと；３）スギ花粉飛散時期以外にアレルギー性鼻炎の症状を示さず、投薬が必要でなかったこと；４）スギ花粉特異的ＩｇＥ値が≧０．７ＵＡ／ｍＬであること；及び５）事前診断後に試験責任医師によって試験に適切であると判断されたこと。
Test Example 2
<Test method>
-Subjects Subjects were recruited from healthy volunteers between the ages of 20 and 65 by the NPO Japan Health Promotion Support Organization. All volunteers experienced allergic symptoms, probably due to Japanese cedar pollen. Volunteers who gave written informed consent were enrolled as subjects as judged by the investigator to be appropriate for the study according to the following selection criteria: 1) Being 20-65 years old at the time of consent; 2) Providing written consent to participate in the study; 3) No symptoms of allergic rhinitis other than the time of cedar pollen dispersal, no medication required 4) The cedar pollen-specific IgE value was ≥0.7 UA / mL; and 5) it was judged by the investigator to be suitable for the study after the pre-diagnosis.
除外基準は以下のとおりであった。１）妊娠中又は妊娠している可能性のある女性、及び試験中に妊娠を計画している女性；２）授乳中の女性；３）重度の呼吸器疾患、心臓病、肝臓病、腎臓病、糖尿病、自己免疫性疾患又はこれらの疾患の既往歴を有する被験者；４）急性鼻炎、副鼻腔炎又は肥厚性鼻炎を有する被験者；５）気管支喘息を有する被験者；６）試験の結果に影響し得る治療（舌下の免疫療法など）を受けている被験者；７）抗ヒスタミン剤、抗ロイコトリエン薬、鼻内噴霧ステロイド、経口ステロイド又は免疫療法を受けている被験者；８）牛乳アレルギーを有する被験者；９）乳酸菌が豊富な食品（キムチ、ピクルス、飲料、ヨーグルト、特定保健用食品、機能性表示食品、又はサプリメント）又はプロバイオティクス含有医薬品を定期的に摂取した被験者；１０）抗アレルギー食品を定期的に消費した被験者；１１）事前診断の１２週間以内に４００ｍＬの血液又は４週間以内に２００ｍＬの血液を提供した被験者；及び１２）主任試験責任医師及び主任研究者によって試験に不適切であると考えられた被験者。 The exclusion criteria were as follows. 1) Women who are pregnant or may be pregnant, and women who are planning to become pregnant during the study; 2) Women who are breastfeeding; 3) Severe respiratory disease, heart disease, liver disease, kidney disease , Diabetes, autoimmune disorders or subjects with a history of these disorders; 4) subjects with acute rhinitis, sinusitis or hypertrophic rhinitis; 5) subjects with bronchial asthma; 6) influencing test results Subjects receiving treatment to obtain (sublingual immunotherapy, etc.); 7) Subjects receiving antihistamines, anti-leukotrienes, intranasal spray steroids, oral steroids or immunotherapy; 8) Subjects with milk allergy; 9) Subjects who regularly took lactic acid bacteria-rich foods (kimchi, pickles, beverages, yogurt, foods for specified health uses, foods with functional claims, or supplements) or probiotics-containing drugs; 10) Regular antiallergic foods Subjects who consumed; 11) Subjects who provided 400 mL of blood or 200 mL of blood within 4 weeks of prior diagnosis; and 12) Principal investigator and principal investigator considered inappropriate for study Subject.
・試験デザイン
試験は、無作為化二重盲検プラセボ対照試験としてデザインされ、２０１８年９月と１２月の間にＮＰＯ日本健康増進支援機構（和歌山、日本）によって実施された。スギ花粉曝露を含む事前検診を受けた５０人のボランティアからインフォームドコンセントを得た。スギ花粉曝露については、ボランティアは曝露施設に入り、３時間、スギ花粉８，０００個／ｍ３に曝露され、その間、３０分ごとに症状を記録した。被験者は、選択基準と除外基準の両方に基づき選ばれ、年齢及び男女比により調整された層別無作為化によって２群に分けられた。１）プラセボ錠剤摂取群（プラセボ群）、２）２０億個のＢ２４０含有錠剤摂取群（Ｂ２４０群）。被験者は、８週間連続して毎日朝食前に１粒の錠剤を摂取し、試験期間中毎日、錠剤の摂取と健康状態を自己評価した。４週目及び８週目において、スギ花粉曝露が、事前検診と同じ方法で行なわれた（図５）。
-Study Design The study was designed as a randomized, double-blind, placebo-controlled study and was conducted by the NPO Japan Health Promotion Organization (Wakayama, Japan) between September and December 2018. Informed consent was obtained from 50 volunteers who had undergone pre-examination, including exposure to Japanese cedar pollen. For cedar pollen exposure, volunteers entered the exposure facility and were exposed to 8,000 cedar pollen / m3 for 3 hours, during which symptoms were recorded every 30 minutes. Subjects were selected based on both selection and exclusion criteria and were divided into two groups by stratified randomization adjusted for age and gender ratio. 1) Placebo tablet intake group (placebo group), 2) 2 billion B240-containing tablet intake group (B240 group). Subjects took one tablet daily before breakfast for eight consecutive weeks and self-assessed tablet intake and health status daily during the study period. At the 4th and 8th weeks, cedar pollen exposure was performed in the same manner as the pre-examination (Fig. 5).
・試験食品
加熱殺菌されたＢ２４０を含有する錠剤は次のように調製した。Ｂ２４０細胞を培養し、繰り返し洗浄し、殺菌、凍結乾燥を行い、２０億個のＢ２４０細胞を含有する乳糖錠剤を作製した。Ｂ２４０を含まない乳糖錠剤はプラセボとして使用した。２つの錠剤は、大きさ、味及び外観において判別不能だった。
-Test food Tablets containing heat-sterilized B240 were prepared as follows. B240 cells were cultured, washed repeatedly, sterilized, and freeze-dried to prepare lactose tablets containing 2 billion B240 cells. B240-free lactose tablets were used as placebo. The two tablets were indistinguishable in size, taste and appearance.
・測定
評価項目は、みずっぱな、くしゃみ、鼻づまり、鼻のかゆみ、目のかゆみ、なみだめ、鼻水を拭くために使用されたティッシュペーパーの枚数及び総括的な顔スケールを含むアレルギー症状であり、環境曝露施設での３時間のスギ花粉への曝露によって引き起こされ、ＪＲＱＬＱ Ｎｏ．１に基づいたアンケートを参考にして評価された。被験者は、曝露施設に入る前に、症状の重症度、鼻を拭くために使用されたティッシュペーパーの枚数、及び総括的状態を自ら記録した。スギ花粉への曝露中に、アレルギー症状とＱＯＬを評価するために一般的に使用されるＪＲＱＬＱ Ｎｏ．１(1)を参考にして作成されたアンケートを使用して、３０分毎に症状を記録した。ＪＲＱＬＱ Ｎｏ．１は、一般にアレルギー症状、ＱＯＬ、ＱＯＬとアレルギー症状を組み合わせた総括的な顔スコアに関する質問からなる(2)。アンケートは、５段階評価で７つのパラメーター（みずっぱな、くしゃみ、鼻づまり、鼻のかゆみ、目のかゆみ、なみだめ、及び総括的な顔スケール）を含んでいる。鼻水を拭くために使用されたティッシュペーパーの枚数は、パラメーターに追加した（図６）。
(1) Okubo K, Kurono Y, Ichimura K, Enomoto T, Okamoto Y, Kawauchi H et al, Japanese guidelines for allergic rhinitis 2017. Allergol Int2017; 66: 205-19.
(2) Okuda M, Ohkubo K, Goto M, Okamoto Y, Konno A, Baba K, et al. Japanese allergic rhinitis QOL questionnaire. Jpn J Allergology 2003; 52(suppl 1): 21-56.
-Measurement endpoints are allergic symptoms including freshness, sneezing, stuffy nose, nasal itching, itchy eyes, soothing, the number of tissue papers used to wipe the runny nose and a comprehensive face scale. Caused by 3 hours of exposure to sneeze pollen at an environmental exposure facility, JRQLQ No. It was evaluated with reference to the questionnaire based on 1. Subjects themselves recorded the severity of symptoms, the number of tissue papers used to wipe the nose, and overall condition prior to entering the exposure facility. JRQLQ No., commonly used to evaluate allergic symptoms and quality of life during exposure to Japanese cedar pollen. 1 Symptomatology was recorded every 30 minutes using the questionnaire created with reference to (1). JRQLQ No. 1 generally consists of allergic symptoms, quality of life, and questions regarding a comprehensive facial score that combines QOL and allergic symptoms (2) . The questionnaire includes 7 parameters (sneezing, sneezing, stuffy nose, nasal itching, itchy eyes, epiphora, and general facial scale) on a 5-point scale. The number of tissue papers used to wipe the runny nose was added to the parameter (Figure 6).
(1) Okubo K, Kurono Y, Ichimura K, Enomoto T, Okamoto Y, Kawauchi H et al, Japanese guidelines for allergic rhinitis 2017. Allergol Int2017; 66: 205-19.
(2) Okuda M, Ohkubo K, Goto M, Okamoto Y, Konno A, Baba K, et al. Japanese allergic rhinitis QOL questionnaire. Jpn J Allergology 2003; 52 (suppl 1): 21-56.
・統計分析
全てのデータは平均又は最小二乗平均±ＳＥＭ又はＳＤとして表し、有意水準が５％の両側検定を統計分析に使用した。
-Statistical analysis All data were expressed as mean or least squares mean ± SEM or SD, and a two-sided test with a significance level of 5% was used for statistical analysis.
曝露３時間の増分スコアは、３時間の間の症状の重症度を示すために、０、４及び８週で、曲線下面積（ＡＵＣ）として合計した。群間で有意差を示したスコアについては、曝露３時間の変化を参考のために示した。 Incremental scores for 3 hours of exposure were summed as area under the curve (AUC) at 0, 4 and 8 weeks to indicate the severity of symptoms during the 3 hours. For the scores that showed a significant difference between the groups, the change at 3 hours of exposure was shown for reference.
データは、０週値（基準値）を共変量とし、各症状を従属変数とし、群、週及び週ごとの群を独立変数として、混合モデルを用いた分散分析による経時測定データ解析を実施した。各週での２群間の統計的な相違は単純主効果テストを実施した。総括的な顔スケールと各症状スコアの間の単純相関は、ピアソンの相関係数を使用して分析し、各症状が総括的な顔スケールにどの程度影響したかを調査するために逐次重回帰分析を行った。変数は、総括的な顔スケール以外の７つの症状を選択した。８週の３時間曝露後の各症状のスコアから、０週のスコアを引いたデルタ値は、対応のないｔ検定（ｖｓプラセボ）を使用して群間で比較した。両側１０％未満を傾向差ありと設定した。統計分析はＳＡＳバージョン９．４(SAS Institute Japan Ltd.)統計ソフトウェアを使用して行った。
The data was analyzed over time by analysis of variance using a mixed model, with the 0-week value (reference value) as the covariate, each symptom as the dependent variable, and the group, weekly, and weekly groups as the independent variables. .. Statistical differences between the two groups during each week were tested by a simple main effect test. The simple correlation between the overall face scale and each symptom score is analyzed using Pearson's correlation coefficient and sequential multiple regression to investigate how each symptom affected the overall face scale. Analysis was carried out. For the variables, seven symptoms other than the general face scale were selected. The delta value, which was obtained by subtracting the score at
＜試験結果＞
・被験者
図７は試験のフローを示す。書面によるインフォームドコンセントは、５２人の応募者のうちの５０人から得られ、３４人のボランティアが適格基準に基づき選ばれ、試験に登録された。全ての被験者が８週間の試験を完了したので、最大の解析対象集団（ＦＡＳ）は３４人のボランティアを含んだ。曝露前にアレルギー症状及び風邪の症状を示した４人のボランティア（４週で５人のボランティア）を除外した。したがって、３０人のボランティア（４週で２９人のボランティア）が、per-protocol set（ＰＰＳ）として有効性の分析に含まれた。試験食品の摂取率は、＞８５．７％であり、２つの群の性別又は年齢の間に有意差はなかった（表１）。
<Test result>
-Subject Figure 7 shows the flow of the test. Written informed consent was obtained from 50 of the 52 applicants, and 34 volunteers were selected based on eligibility criteria and enrolled in the study. The largest population to be analyzed (FAS) included 34 volunteers, as all subjects completed the 8-week study. Four volunteers (5 volunteers in 4 weeks) who showed allergic and cold symptoms before exposure were excluded. Therefore, 30 volunteers (29 volunteers in 4 weeks) were included in the efficacy analysis as a per-protocol set (PPS). The intake rate of the test food was> 85.7%, and there was no significant difference between the gender or age of the two groups (Table 1).
・スギ花粉曝露時の症状スコアのＡＵＣ
ＦＡＳ及びＰＰＳを使用してＢ２４０群とプラセボ群の間の各症状の３時間の合計スコアを比較した。顔スケールスコアは、ＰＰＳとＦＡＳのいずれにおいても、８週において、Ｂ２４０摂取群はプラセボ群より有意に低かった（表２）。０週及び８週における、曝露３時間にわたる顔スケールスコアの変化を図８に示す。
・ AUC of symptom score when exposed to Japanese cedar pollen
FAS and PPS were used to compare the 3-hour total scores of each symptom between the B240 and placebo groups. Face scale scores were significantly lower in the B240 intake group than in the placebo group at 8 weeks in both PPS and FAS (Table 2). The changes in the face scale score over 3 hours of exposure at 0 and 8 weeks are shown in FIG.
各週での２群間の統計的な相違は単純主効果テストを実施した。
算術平均±SEM (0 w), 最小二乗平均±SEM (4 w, 8 w) *P < 0.05 (vs.プラセボ)
Arithmetic mean ± SEM (0 w), least squares mean ± SEM (4 w, 8 w) * P <0.05 (vs. placebo)
・顔スケールと各症状に関する曝露３時間の総スコアのＡＵＣの相関
単純相関分析は、３時間の合計の顔スケールスコアが全ての症状と有意に、正の相関関係があることを示した（表３）。さらに、相関係数は鼻づまりで特に高く、水っぱな、鼻のかゆみ、鼻紙枚数に関するものも高かった。
Correlation of AUC between face scale and total score for 3 hours of exposure for each symptom Simple correlation analysis showed that the total face scale score for 3 hours was significantly positively correlated with all symptoms (Table). 3). In addition, the correlation coefficient was particularly high for stuffy nose, and was also high for watery, itchy nose, and the number of nasal sheets.
・安全性
副作用：分析対象は、３４人の適格とされたボランティアであった。皮膚のかゆみ及び眼瞼膨張（ｎ＝１）、細菌性結膜炎（ｎ＝１）並びに腎盂炎（ｎ＝１）が副作用として定義されたが、重篤では無いと判断された。３人全てのボランティアがＢ２４０摂取群であった。しかしながら、全ての副作用が試験食品摂取前に生じたか又は一時的であったので、試験責任医師は有害事象と試験食品摂取の間に関係はないと判断した。
-Safety side effects: The subjects of analysis were 34 qualified volunteers. Itching of the skin and swelling of the eyelids (n = 1), bacterial conjunctivitis (n = 1) and pyelonephritis (n = 1) were defined as side effects, but were judged to be non-serious. All three volunteers were in the B240 intake group. However, because all side effects occurred or were temporary before ingestion of the study food, the investigator determined that there was no relationship between the adverse event and ingestion of the study food.
・３時間曝露後の各症状のスコアの比較
８週の３時間曝露後の各症状のスコアから０週のスコアを引いたデルタ（Δ）値は、プラセボ群とＢ２４０群で比較された（表４）。顔スケール、鼻づまり及び鼻水を拭くために使用されたティッシュペーパーの枚数は、プラセボ群と比べて改善する傾向にあった。
-Comparison of scores for each symptom after 3 hours of exposure The delta (Δ) value, which is the score of each symptom after 3 hours of exposure for 8 weeks minus the score for 0 weeks, was compared between the placebo group and the B240 group (Table). 4). The number of tissue papers used to wipe the face scale, stuffy nose and runny nose tended to improve compared to the placebo group.
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2003300887A (en) * | 2002-04-05 | 2003-10-21 | Tanglewood Co Ltd | Mixture having antiallergic effect and food product containing the same |
| WO2005019438A1 (en) * | 2003-08-21 | 2005-03-03 | Otsuka Pharmaceutical Co., Ltd. | Lactic acid bacteria having mucosal immunopotentiation effect |
| JP2006321786A (en) * | 2005-04-21 | 2006-11-30 | Hokuren Federation Of Agricult Coop:The | Allergy-inhibiting composition, allergy-inhibiting food, and allergy inhibitor |
| WO2008023665A1 (en) * | 2006-08-21 | 2008-02-28 | Sapporo Breweries Limited | Bacterial strain having anti-allergic activity and immunostimulating activity, and beverage, food, anti-allergic agent and immunostimulating agent comprising the bacterial strain |
| JP2011004620A (en) * | 2009-06-23 | 2011-01-13 | Tokai Igaku Kensa Kenkyusho:Kk | Genus lactobacillus strain and food and medicine containing the strain |
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Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2003300887A (en) * | 2002-04-05 | 2003-10-21 | Tanglewood Co Ltd | Mixture having antiallergic effect and food product containing the same |
| WO2005019438A1 (en) * | 2003-08-21 | 2005-03-03 | Otsuka Pharmaceutical Co., Ltd. | Lactic acid bacteria having mucosal immunopotentiation effect |
| JP2006321786A (en) * | 2005-04-21 | 2006-11-30 | Hokuren Federation Of Agricult Coop:The | Allergy-inhibiting composition, allergy-inhibiting food, and allergy inhibitor |
| WO2008023665A1 (en) * | 2006-08-21 | 2008-02-28 | Sapporo Breweries Limited | Bacterial strain having anti-allergic activity and immunostimulating activity, and beverage, food, anti-allergic agent and immunostimulating agent comprising the bacterial strain |
| JP2011004620A (en) * | 2009-06-23 | 2011-01-13 | Tokai Igaku Kensa Kenkyusho:Kk | Genus lactobacillus strain and food and medicine containing the strain |
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| JP7372112B2 (en) | 2023-10-31 |
| JP2023174869A (en) | 2023-12-08 |
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