JPH0680575A - Oral immunopotentiating agent - Google Patents
Oral immunopotentiating agentInfo
- Publication number
- JPH0680575A JPH0680575A JP3123178A JP12317891A JPH0680575A JP H0680575 A JPH0680575 A JP H0680575A JP 3123178 A JP3123178 A JP 3123178A JP 12317891 A JP12317891 A JP 12317891A JP H0680575 A JPH0680575 A JP H0680575A
- Authority
- JP
- Japan
- Prior art keywords
- lactic acid
- oral
- cells
- acid bacterium
- product
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Abstract
Description
【０００１】[0001]
【産業上の利用分野】本発明は、免疫賦活剤に関するも
のであり、更に詳細には、極めて安全性の高い、経口投
与用の効果のすぐれた免疫賦活剤に関するものである。
また本発明は、経口ワクチン用佐薬ないしアジュバント
としての利用も可能である。BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an immunostimulant, and more particularly to an immunostimulant which is extremely safe and has an excellent effect for oral administration.
The present invention can also be used as an adjuvant for oral vaccines or an adjuvant.
【０００２】[0002]
【従来の技術】乳酸菌の示す生体免疫賦活作用について
は、抗腫瘍活性を代表として様々なものが知られてい
る。しかし、その多くは乳酸菌菌体あるいは細胞壁など
の菌体画分を腹腔投与など、非経口投与して得られた効
果に基づいたものである。また、経口投与であっても発
酵乳の形で投与された効果を見ているものが多く、乳酸
菌菌体あるいは細胞壁などの菌体画分の持つ固有の免疫
賦活活性を明確に表わしているとは言えない。なぜなら
ば、Ｇ．Ｐｅｒｄｉｇｏｎらが示すように、たとえばラ
クトバチルス属の乳酸菌を用いて製造した発酵乳は、菌
体を含まないその上清画分にも強い免疫賦活活性を有す
ることが知られているからである（Ｉｍｍｕｎｏｌｏｇ
ｙ，Ｖｏｌ．６３，Ｐ１７，１９８８）。したがって乳
酸菌菌体を食品形態にして経口投与（自由摂取）させた
場合、どのような生理効果が得られるかはまだ十分に解
明されていないのが技術の現状である。2. Description of the Related Art Various lactic acid bacteria have been known to have various biological immunity activating actions, typically antitumor activity. However, most of them are based on the effects obtained by parenterally administering lactic acid bacterium cells or cell fractions such as cell walls by intraperitoneal administration. In addition, even if it is orally administered, many observe the effect of being administered in the form of fermented milk, and clearly show the inherent immunostimulatory activity of lactic acid bacterium cells or cell fractions such as cell walls. I can't say. Because G. This is because, as shown by Perdigon et al., For example, fermented milk produced by using lactic acid bacteria of the genus Lactobacillus is known to have strong immunostimulatory activity even in the supernatant fraction containing no cells ( Immunolog
y, Vol. 63, P17, 1988). Therefore, it is the current state of the art that the physiological effects obtained by oral administration (free intake) of lactic acid bacterial cells in the form of food have not been sufficiently clarified.
【０００３】[0003]
【発明が解決しようとする課題】薬剤を投与するに当
り、安全性及び投与の容易性の面から、経口的に投与す
る投与方法がすぐれていることは、当業界において広く
認識されているところであり、経口投与可能な薬剤の開
発が当業界において切望されている。この点は免疫賦活
剤についても例外ではない。It is widely recognized in the art that an oral administration method is superior in terms of safety and ease of administration when administering a drug. There is a long felt need in the art to develop orally administrable drugs. This point is no exception for immunostimulants.
【０００４】しかるに、経口投与により目的物質に対す
る免疫を実施しようとする場合、目的物質の単なる大量
経口投与では生体の免疫寛容機構に妨げられて、全身的
な免疫感作が一般には成立しないとされている。したが
って、乳酸菌を経口投与しても菌体に対する抗体価は全
く上昇しないか、せいぜい一時的な上昇を示す程度であ
り、乳酸菌の経口感作力は、リポ多糖類（ＬＰＳ）を有
するグラム陰性菌などに比べて微弱なものと考えられて
きた。しかしこのことは発酵乳などの食品への使用実績
により、安全性が極めて高いと考えられている乳酸菌を
経口ワクチン等の経口感作性が要求される分野へ応用す
る場合には問題である。However, when attempting to immunize a target substance by oral administration, it is considered that systemic immunization is generally not established by the mere large oral administration of the target substance because of the immune tolerance mechanism of the living body. ing. Therefore, the oral administration of lactic acid bacteria does not increase the antibody titer against the bacterial cells at all, or at most shows a temporary increase, and the oral sensitizing power of lactic acid bacteria is gram-negative bacteria having lipopolysaccharide (LPS). It has been considered to be weaker than the above. However, this is a problem when lactic acid bacteria, which are considered to be extremely safe due to their use in foods such as fermented milk, are applied to fields requiring oral sensitization such as oral vaccines.
【０００５】[0005]
【課題を解決するための手段】本発明は、上記した課題
を解決して、経口投与することのできる安全でしかも効
果の高い免疫賦活剤を開発する目的でなされたものであ
る。The present invention has been made for the purpose of solving the above-mentioned problems and developing a safe and highly effective immunostimulant which can be orally administered.
【０００６】そこで上記したように従来より経口投与し
ても免疫感作が成立しない、つまり免疫賦活剤としては
使用できないとされていた乳酸菌について、敢えて本発
明者らは着目した。そして鋭意研究の結果、全く予期せ
ざることに、というより全くそれとは正反対に、本発明
者らは、乳酸菌の培養液もしくは培養液の遠心濃縮物あ
るいは乾燥物を食餌に添加することにより、経口投与時
の免疫寛容現象を回避し、効果的に腸管隣接リンパ組織
を活性化して、経口感作を成立させることを見いだし、
本発明を完成するに至った。Therefore, as described above, the present inventors dared to pay attention to the lactic acid bacterium which has not been conventionally immunized even if it is orally administered, that is, cannot be used as an immunostimulant. And, as a result of earnest research, unexpectedly, rather than the opposite, the present inventors orally, by adding a culture solution of lactic acid bacteria or a centrifugal concentrate or dried product of the culture solution to the diet, It was found that the immune tolerance phenomenon at the time of administration is avoided and the intestinal adjacent lymphoid tissue is effectively activated to establish oral sensitization.
The present invention has been completed.
【０００７】すなわち本発明は、乳酸菌菌体及び／又は
菌体含有物を有効成分とする経口免疫賦活剤に関するも
のである。That is, the present invention relates to an oral immunostimulant containing a lactic acid bacterium and / or a substance containing the bacterium as an active ingredient.
【０００８】本発明においては、乳酸菌であればすべて
の菌の菌体が使用でき、その非限定的例としては次のも
のが挙げられる：ラクトバチルス属（Ｌａｃｔｏｂａｃ
ｉｌｌｕｓ ａｃｉｄｏｐｈｉｌｕｓ ＩＦＯ３９５
３、Ｌ．ｃａｓｅｉ ＡＴＣＣ７４６９、Ｌ．ｆｅｒｍ
ｅｎｔｕｍ ＡＴＣＣ９３３８等）；ビフィドバクテリ
ウム属（Ｂｉｆｉｄｏｂａｃｔｅｒｉｕｍ ｌｏｎｇｕ
ｍ ＡＴＣＣ１５７０８等）；ペディオコッカス属（Ｐ
ｅｄｉｏｃｏｃｃｕｓ ｃｅｒｅｖｉｓｉａｅＡＴＣＣ
８０４２等）；ストレプトコッカス属（Ｓｔｒｅｐｔｏ
ｃｏｃｃｕｓｌａｃｔｉｓ ＩＦＯ１２５４６等）；ロ
イコノストック属（Ｌｅｕｃｏｎｏｓｔｏｃ ｍｅｓｅ
ｎｔｅｒｏｉｄｅｓ ＩＦＯ３４２６等）等に属する各
種微生物。In the present invention, any lactic acid bacterium may be used, and non-limiting examples thereof include the following: Lactobacillus (Lactobac)
illus acidophilus IFO395
3, L.S. casei ATCC 7469, L. ferm
entum ATCC9338); Bifidobacterium longu (Bifidobacterium longu)
m ATCC15708 etc.); Pediococcus genus (P
ediococcus cerevisiae ATCC
8042); Streptococcus (Strepto)
coccus lactis IFO12546 etc.); Leuconostoc genus (Leuconostoc mese)
various microorganisms belonging to such as N. teroides IFO3426).
【０００９】本発明に係る経口免疫賦活剤は、これらの
乳酸菌菌体の１種又は２種以上を有効成分として含有す
るものであるが、乳酸菌としては単離精製した乳酸菌の
ほか、乳酸菌菌体含有物も使用することができる。The oral immunostimulant according to the present invention contains one or more of these lactic acid bacterium cells as an active ingredient. The lactic acid bacterium includes isolated and purified lactic acid bacterium and lactic acid bacterium cells. Inclusions can also be used.
【００１０】乳酸菌菌体含有物とは、乳酸菌菌体を含有
するものすべてを包含するものであって、例えば次のも
のが非限定的に例示される：乳酸菌培養物；それを濾過
ないし遠心分離等固液分離手段によって分離した固体残
渣；こ（れら）の濃縮物；こ（れら）の希釈物；こ（れ
ら）の乾燥物。The lactic acid bacterium cell-containing material includes all those containing lactic acid bacterium cells, and examples thereof include, but are not limited to, the following: lactic acid bacterium culture; filtration or centrifugation thereof. Solid residue separated by iso-solid separation means; concentrate of these; dilution of these; dried product of these.
【００１１】本発明の経口免疫賦活剤は乳酸菌菌体を
１．０×１０５個／ｇ以上，好ましくは１．０×１０８
〜１．０×１０１２個／ｇ含んでいるものであり、これ
を単独あるいは他の食餌成分と混合し、経口投与する。
ただし、乳酸菌は生菌および死菌のいずれでもよいし、
菌体は、破砕したり細胞壁を酵素や機械的手段によって
溶解ないし除去したりして使用してもよい。The oral immunostimulant of the present invention contains lactic acid bacterium cells in an amount of 1.0 × 10 5 cells / g or more, preferably 1.0 × 10 8
˜1.0 × 10 12 cells / g, which is orally administered alone or in combination with other dietary ingredients.
However, the lactic acid bacterium may be either live or dead,
The cells may be crushed or the cell wall may be dissolved or removed by an enzyme or mechanical means before use.
【００１２】このように本発明に係る経口免疫賦活剤
は、食用に供される乳酸菌を有効成分として使用するの
で安全性については全く問題がなく、また、経口投与剤
であるので、乳酸菌菌体単独でもあるいは通常の食餌成
分と混合してまたは経口投与剤の製剤に通常用いられる
各種補助剤と混合して製剤すれば良い。投与量も格別の
限定はないけれども、１日当り乳酸菌菌体を１．０×１
０３個以上となるように投与すれば良い。As described above, since the oral immunostimulant according to the present invention uses lactic acid bacteria to be used for food as an active ingredient, there is no problem in safety, and since it is an orally administered drug, the lactic acid bacteria cells It may be prepared alone or in admixture with usual dietary ingredients, or in admixture with various auxiliary agents usually used in the preparation of orally administered drugs. Although the dose is not particularly limited, 1.0 × 1 lactic acid bacteria per day
0 three may be administered in such a way that more.
【００１３】以下、本発明の実施例について述べる。Examples of the present invention will be described below.
【００１４】[0014]
【実施例１】ビフィドバクテリウム・ロンガム（Ｂｉｆ
ｉｄｏｂａｃｔｅｒｉｕｍ ｌｏｎｇｕｍ ＡＴＣＣ１
５７０８）を２．０×１０１１個／ｇ含有する菌体粉末
を３％含有する乳清蛋白質（ＷＰＩ）固型飼料を作製
し、菌体粉末を全く含まないＷＰＩ固型飼料を対照とし
てマウス（ＢＡＬＢ／ｃ、６Ｗ、雌）を飼育した（一群
５匹、ＷＰＩ固型飼料の組成はＡＩＮ−７６に準拠）。
飼育開始後、２週間ごとに尾静脈より採血し、Ｂ．ｌｏ
ｎｇｕｍの細胞質に対する抗体量（ＩｇＧ）をＥＬＩＳ
Ａ法で測定した。Example 1 Bifidobacterium longum (Bif
idobacterium longum ATCC1
5708) to produce a whey protein (WPI) solid feed containing 3% of bacterial cell powder containing 2.0 × 10 11 cells / g, and using a WPI solid feed containing no bacterial cell powder as a control (BALB / c, 6W, female) were bred (5 animals per group, composition of WPI solid feed was based on AIN-76).
After starting breeding, blood was collected from the tail vein every two weeks, and B. lo
ELISA for the amount of antibody (IgG) to the cytoplasm of ngum
It was measured by Method A.
【００１５】その結果を図１に示した。本発明によれ
ば、図１に示すように、投与６週目以降、菌体粉末を含
む固型飼料を摂取させた群では対照群に比べ抗体価の著
しい上昇が継続した。The results are shown in FIG. According to the present invention, as shown in FIG. 1, after the 6th week of administration, the antibody titer in the group fed with the solid feed containing the bacterial cell powder continued to increase remarkably as compared with the control group.
【００１６】[0016]
【実施例２】実施例１で用いた２種類の固型飼料を用い
て、マウス（ＢＡＬＢ／ｃ、６Ｗ、雌）１６匹を２群に
分け飼育した。４週間後にパイエル板をマウスの小腸か
ら無菌的に取り出し、スライドガラスで穏やかにティー
スしてｓｉｎｇｌｅ ｃｅｌｌとした。各群ごとに集め
たパイエル板細胞を９６穴平底プレートを用い、Ｂ．ｌ
ｏｎｇｕｍの細胞質の存在下（０〜２０μｇ／ｗｅｌ
ｌ）、５％牛胎児血清を含むＲＰＭＩ１６４０培地（Ｇ
ｉｂｃｏ社製）で、５％ＣＯ２／Ａｉｒ条件下、３７℃
４８時間それぞれ培養した（５×１０５個／ｗｅｌ
ｌ）。次に１．０μＣｉ３Ｈ−ＴｄＲを添加し、２０時
間後、３Ｈ−ＴｄＲの細胞への取り込みをシンチレーシ
ョンカウンターで測定した。結果は各群ごとにコントロ
ール（細胞質０μｇ／ｗｅｌｌ）のカウント数を１とし
たときの各ｗｅｌｌのカウント数（刺激係数：ＳＩ）で
表わした。Example 2 Sixteen mice (BALB / c, 6W, female) were divided into two groups and bred using the two types of solid diets used in Example 1. Four weeks later, the Peyer's patches were aseptically removed from the small intestine of the mouse and gently teethed with a slide glass to give single cells. The Peyer's patch cells collected for each group were used for B. l
In the presence of ongum cytoplasm (0-20 μg / wel
l) RPMI1640 medium containing 5% fetal bovine serum (G
(manufactured by ibco) at 37 ° C. under 5% CO 2 / Air conditions.
Cultured for 48 hours each (5 × 10 5 cells / well
l). Next, 1.0 μCi 3 H-TdR was added, and 20 hours later, uptake of 3 H-TdR into cells was measured with a scintillation counter. The result was represented by the count number (stimulation coefficient: SI) of each well when the count number of the control (cytoplasm 0 μg / well) was set to 1 for each group.
【００１７】その結果を図２に示した。本発明によれ
ば、図２に示すように菌体粉末を含む固型飼料を摂取さ
せた群では、対照群に比べ、Ｂ．ｌｏｎｇｕｍの細胞質
存在下で約３倍以上の細胞増殖が見られ、菌体粉末が腸
管隣接リンパ組織を感作することが確認された。The results are shown in FIG. According to the present invention, as shown in FIG. 2, in the group fed with the solid feed containing the bacterial cell powder, B. About 3 times or more cell proliferation was observed in the presence of longum cytoplasm, and it was confirmed that the bacterial cell powder sensitized the intestinal adjacent lymphoid tissue.
【００１８】[0018]
【実施例３】ラクトバチルス・アシドフィラス（Ｌａｃ
ｔｏｂａｃｉｌｌｕｓ ａｃｉｄｏｐｈｉｌｕｓ ＡＴ
ＣＣ１１５０６）を３．０×１０１１個／ｇ含有する菌
体濃縮物を３％含有するＭＦ固型飼料を作製し、マウス
（ＢＡＬＢ／ｃ、６Ｗ、雌）を飼育した（対照は通常の
ＭＦ固型飼料（オリエンタル酵母社製）、１群５匹）。
飼育開始後２週間ごとに尾静脈より採血し、Ｌ．ａｃｉ
ｄｏｐｈｉｌｕｓの細胞壁に対する抗体量（ＩｇＧ）を
ＥＬＩＳＡ法で測定した。Example 3 Lactobacillus acidophilus (Lac
tobacillus acidophilus AT
CC11506) was prepared as an MF solid feed containing 3% of cell concentrate containing 3.0 × 10 11 cells / g, and mice (BALB / c, 6W, female) were bred (control was normal MF). Solid feed (manufactured by Oriental Yeast Co., Ltd., 1 group 5).
Blood was collected from the tail vein every two weeks after the start of breeding, and L. aci
The amount of antibody (IgG) to the cell wall of dophilus was measured by the ELISA method.
【００１９】その結果、図３に示すように投与４週目以
降、菌体濃縮物を含むＭＦ固型飼料を摂取させた群で
は、対照群に比べ、抗体価の著しい上昇が継続した。As a result, as shown in FIG. 3, after the 4th week from the administration, in the group fed with the MF solid feed containing the cell concentrate, the antibody titer continued to increase remarkably as compared with the control group.
【００２０】[0020]
【実施例４】実施例３で用いた２種類の固型飼料を用い
て、マウス（ＢＡＬＢ／ｃ、６Ｗ、雌）１６匹を２群に
分けを飼育した。３週間後にパイエル板をマウス小腸か
ら無菌的に取り出し、以後実施例２と同様の方法で、パ
イエル板細胞をＬ．ａｃｉｄｏｐｈｉｌｕｓの細胞壁の
存在下（０〜２０μｇ／ｗｅｌｌ）培養し、細胞増殖の
程度を２群間で比較した。その結果、図４に示すよう
に、菌体濃縮物を含む固型飼料を摂取させた群では対照
群に比べ、約２倍以上の細胞増殖が見られ、菌体濃縮物
が腸管隣接リンパ組織を感作することが確認された。Example 4 Using the two types of solid feed used in Example 3, 16 mice (BALB / c, 6W, female) were divided into two groups and bred. After 3 weeks, the Peyer's patches were aseptically removed from the mouse small intestine, and the Peyer's patch cells were treated with L. cerevisiae in the same manner as in Example 2. The cells were cultured in the presence of the cell wall of acidophilus (0 to 20 μg / well), and the degree of cell proliferation was compared between the two groups. As a result, as shown in FIG. 4, in the group fed with the solid feed containing the microbial cell concentrate, about 2 times or more of the cell proliferation was observed as compared with the control group, and the microbial cell concentrate showed the lymphatic tissue adjacent to the intestinal tract. It was confirmed to sensitize.
【００２１】[0021]
【発明の効果】本発明によって、きわめて安全性が高く
しかも効果のすぐれた免疫賦活剤が経口投与可能な剤型
で提供される。INDUSTRIAL APPLICABILITY The present invention provides an immunostimulant having extremely high safety and excellent effect in a dosage form which can be orally administered.
【００２２】本発明の経口免疫賦活剤は、腸管隣接リン
パ組織を刺激することにより、生体の免疫寛容機構を回
避して経口免疫を誘導することができる。したがって、
免疫原性の弱い物質の担体として経口ワクチンなどの薬
剤へ応用可能であるし、ヒトのみでなく各種の動物にも
広く適用することができる。The oral immunostimulant of the present invention can induce oral immunity by evading the immune tolerance mechanism of the living body by stimulating the lymphatic tissue adjacent to the intestinal tract. Therefore,
It can be applied to a drug such as an oral vaccine as a carrier of a substance having a weak immunogenicity, and can be widely applied to various animals as well as humans.
【図１】Ｂ．ｌｏｎｇｕｍ菌体経口投与による抗Ｂ．ｌ
ｏｎｇｕｍ抗体産生の誘導を示した図である。FIG. 1B. anti-B. l
It is the figure which showed induction | guidance | derivation of ongum antibody production.
【図２】Ｂ．ｌｏｎｇｕｍ菌体経口投与による細胞増殖
の促進を示した図である。FIG. 2B. FIG. 3 is a diagram showing promotion of cell growth by oral administration of longum bacterial cells.
【図３】Ｌ．ａｃｉｄｏｐｈｉｌｕｓ菌体経口投与によ
る抗Ｌ．ａｃｉｄｏｐｈｉｌｕｓ抗体産生の誘導を示し
た図である。FIG. 3 L. anti-L. It is the figure which showed induction of the acidophilus antibody production.
【図４】Ｌ．ａｃｉｄｏｐｈｉｌｕｓ菌体経口投与によ
る細胞増殖の促進を示した図である。FIG. It is a figure showing promotion of cell growth by oral administration of acidophilus bacterium.
─────────────────────────────────────────────────────
─────────────────────────────────────────────────── ───
【手続補正書】[Procedure amendment]
【提出日】平成４年３月２４日[Submission date] March 24, 1992
【手続補正１】[Procedure Amendment 1]
【補正対象書類名】明細書[Document name to be amended] Statement
【補正対象項目名】０００６[Correction target item name] 0006
【補正方法】変更[Correction method] Change
【補正内容】[Correction content]
【０００６】そこで上記したように従来より経口投与し
ても免疫感作が継続して成立しないとされていた乳酸菌
について、敢えて本発明者らは着目した。そして鋭意研
究の結果、全く予期せざることに、というより全くそれ
とは正反対に、本発明者らは、乳酸菌の培養液もしくは
培養液の遠心濃縮物あるいは乾燥物を食餌に添加するこ
とにより、経口投与時の免疫寛容現象を回避し、効果的
に腸管隣接リンパ組織を活性化して、経口感作を成立さ
せることを見いだし、本発明を完成するに至った。[0006] Therefore, as described above, the present inventors dared to pay attention to the lactic acid bacterium, which has been conventionally considered to fail to establish immunization even after oral administration. And, as a result of earnest research, unexpectedly, rather than the opposite, the present inventors orally, by adding a culture solution of lactic acid bacteria or a centrifugal concentrate or dried product of the culture solution to the diet, It was found that the immune tolerance phenomenon at the time of administration is avoided, the intestinal tract adjacent lymphoid tissue is effectively activated, and oral sensitization is established, and the present invention has been completed.
───────────────────────────────────────────────────── フロントページの続き (51)Int.Cl.5 識別記号 庁内整理番号 ＦＩ 技術表示箇所 Ｃ１２Ｒ 1:225） 7804−4Ｂ (Ｃ１２Ｎ 1/20 Ｃ１２Ｒ 1:46） 7804−4Ｂ (Ｃ１２Ｎ 1/20 Ｃ１２Ｒ 1:01） 7804−4Ｂ (72)発明者 桑田 有 東京都東村山市栄町１の21の３ 明治乳業 株式会社中央研究所内 (72)発明者 山本 良郎 東京都東村山市栄町１の21の３ 明治乳業 株式会社中央研究所内─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. 5 Identification code Internal reference number FI Technical display location C12R 1: 225) 7804-4B (C12N 1/20 C12R 1:46) 7804-4B (C12N 1 / 20 C12R 1:01) 7804-4B (72) Inventor Yu Kuwata 1-21 3 Sakaemachi, Higashimurayama, Tokyo Meiji Dairy Co., Ltd. Central Research Laboratory (72) Inventor Ryo Yamamoto 21-3, 1 Sakaemachi, Higashimurayama, Tokyo Meiji Dairy Co., Ltd. Central Research Institute
Claims (4)
成分として含有することを特徴とする経口免疫賦活剤。1. An oral immunostimulant comprising a lactic acid bacterium and / or a substance containing a bacterium as an active ingredient.
上、好ましくは１．０×１０８〜１．０×１０１２個／
ｇ含有することを特徴とする請求項１の経口免疫賦活
剤。2. Lactobacillus cells are 1.0 × 10 5 cells / g or more, preferably 1.0 × 10 8 to 1.0 × 10 12 cells / g.
The oral immunostimulant according to claim 1, which contains g.
得た培養物、その固体残渣、こ（れら）の濃縮物、こ
（れら）の希釈物、及び／又は、こ（れら）の乾燥物で
あることを特徴とする請求項１又は請求項２の経口免疫
賦活剤。3. The lactic acid bacterium-containing material is a culture obtained by culturing lactic acid bacterium, a solid residue thereof, a concentrate of these, a dilution of these, and / or The oral immunostimulant according to claim 1 or 2, which is a dried product of these).
ｂａｃｉｌｌｕｓ）、ビフィドバクテリウム（Ｂｉｆｉ
ｄｏｂａｃｔｅｒｉｕｍ）、ペディオコッカス（Ｐｅｄ
ｉｏｃｏｃｃｕｓ）、ストレプトコッカス（Ｓｔｒｅｐ
ｔｃｏｃｃｕｓ）、ロイコノストック（Ｌｅｕｃｏｎｏ
ｓｔｏｃ）の各属に属する１種又は２種以上であること
を特徴とする請求項１〜請求項３のいずれか１項に記載
の経口免疫賦活剤。4. The lactic acid bacterium is Lactobacillus (Lacto).
bacillus), Bifidobacterium (Bifi
dobacterium), Pediococcus (Ped)
iococcus), Streptococcus (Strep)
tcoccus), Leuconostoc (Leucono)
The oral immunostimulant according to any one of claims 1 to 3, which is one kind or two or more kinds belonging to each genus of stoc).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3123178A JPH0680575A (en) | 1991-03-05 | 1991-03-05 | Oral immunopotentiating agent |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3123178A JPH0680575A (en) | 1991-03-05 | 1991-03-05 | Oral immunopotentiating agent |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH0680575A true JPH0680575A (en) | 1994-03-22 |
Family
ID=14854121
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP3123178A Pending JPH0680575A (en) | 1991-03-05 | 1991-03-05 | Oral immunopotentiating agent |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0680575A (en) |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH10139674A (en) * | 1996-11-11 | 1998-05-26 | Yakult Honsha Co Ltd | Production promoter of interleukin 12 |
| JPH1192389A (en) * | 1997-09-17 | 1999-04-06 | Nichinichi Seiyaku Kk | Immunostimulator |
| JP2001323001A (en) * | 2000-05-16 | 2001-11-20 | Asahi Denka Kogyo Kk | beta-GLUCAN HAVING ACTIVITY FOR ENHANCING IMMUNITY AND FORMED INTO THE LOW MOLECULAR ONE |
| JP2003533489A (en) * | 2000-05-19 | 2003-11-11 | ニューモバイオティックス・プロプライエタリー・リミテッド | Compositions and methods for the treatment of mucosal infections |
| WO2010119936A1 (en) | 2009-04-17 | 2010-10-21 | 株式会社アネロファーマ・サイエンス | Lactic acid bacterium mutated into obligatory anaerobe, method for constructing same, and expression vector functioning in obligatory anaerobic lactic acid bacterium |
| JP2011041258A (en) * | 2009-06-16 | 2011-02-24 | Intel Corp | Mobile device, apparatus and method having computer readable storage medium |
| US8334371B2 (en) | 2007-07-04 | 2012-12-18 | Kikkoman Corporation | Lactic acid bacteria-derived double-stranded RNA |
-
1991
- 1991-03-05 JP JP3123178A patent/JPH0680575A/en active Pending
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH10139674A (en) * | 1996-11-11 | 1998-05-26 | Yakult Honsha Co Ltd | Production promoter of interleukin 12 |
| JPH1192389A (en) * | 1997-09-17 | 1999-04-06 | Nichinichi Seiyaku Kk | Immunostimulator |
| JP2001323001A (en) * | 2000-05-16 | 2001-11-20 | Asahi Denka Kogyo Kk | beta-GLUCAN HAVING ACTIVITY FOR ENHANCING IMMUNITY AND FORMED INTO THE LOW MOLECULAR ONE |
| JP2003533489A (en) * | 2000-05-19 | 2003-11-11 | ニューモバイオティックス・プロプライエタリー・リミテッド | Compositions and methods for the treatment of mucosal infections |
| JP2012153706A (en) * | 2000-05-19 | 2012-08-16 | Hunter Immunology Ltd | Composition and method for treating mucosal infectious disease |
| US8334371B2 (en) | 2007-07-04 | 2012-12-18 | Kikkoman Corporation | Lactic acid bacteria-derived double-stranded RNA |
| WO2010119936A1 (en) | 2009-04-17 | 2010-10-21 | 株式会社アネロファーマ・サイエンス | Lactic acid bacterium mutated into obligatory anaerobe, method for constructing same, and expression vector functioning in obligatory anaerobic lactic acid bacterium |
| US8338162B2 (en) | 2009-04-17 | 2012-12-25 | Anaeropharma Science, Inc. | Obligately anaerobic mutant lactic acid bacterium and preparation method therefor, and expression vector functioning in obligately anaerobic lactic acid bacterium |
| JP2011041258A (en) * | 2009-06-16 | 2011-02-24 | Intel Corp | Mobile device, apparatus and method having computer readable storage medium |
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