JPH08259450A - Enhancer for production of interferon - Google Patents
Enhancer for production of interferonInfo
- Publication number
- JPH08259450A JPH08259450A JP7086478A JP8647895A JPH08259450A JP H08259450 A JPH08259450 A JP H08259450A JP 7086478 A JP7086478 A JP 7086478A JP 8647895 A JP8647895 A JP 8647895A JP H08259450 A JPH08259450 A JP H08259450A
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- enhancer
- interferon
- enterococcus
- ifn
- production
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Abstract
Description
【0001】[0001]
【産業上の利用分野】本発明はエンテロコッカス属に属
する微生物の菌体又はその処理物を有効成分として含有
するインターフェロン産生増強剤に関するものである。FIELD OF THE INVENTION The present invention relates to an interferon production enhancer containing, as an active ingredient, cells of a microorganism belonging to the genus Enterococcus or a treated product thereof.
【0002】[0002]
【従来の技術】インターフェロン(IFN)は、抗ウイ
ルス活性を有する分子量約20,000の蛋白質の総称
である。IFNには大きく分けるとα、β、γの3種の
型が存在し、主にリンパ球等の免疫細胞から産生され
る。生物活性として、抗ウイルス作用、抗腫瘍作用、免
疫応答調節作用等が知られている。BACKGROUND OF THE INVENTION Interferon (IFN) is a general term for proteins having an antiviral activity and a molecular weight of about 20,000. IFN is roughly classified into three types, α, β, and γ, which are mainly produced by immune cells such as lymphocytes. As biological activity, antiviral action, antitumor action, immune response regulating action and the like are known.
【0003】現在、遺伝子組み換え型IFNや、精製I
FNがウイルス感染、ウイルス性肝炎、癌に対する治療
薬等として使用されている。Currently, genetically modified IFN and purified I
FN is used as a therapeutic drug for viral infection, viral hepatitis, cancer and the like.
【0004】IFNの産生を増強する物質又は組成物は
多々知られているが、それらはIFN産生増強活性が十
分とは言えず、又、生体内で用いられる場合、安全性に
問題があるものが多い。従って、IFN産生増強活性が
強く、且つ安全なIFN産生増強剤が求められている。Many substances or compositions that enhance the production of IFN are known, but they do not have sufficient IFN production-enhancing activity, and when used in vivo, there is a problem with safety. There are many. Therefore, a strong IFN production enhancing agent and a safe IFN production enhancing agent are required.
【0005】[0005]
【発明が解決しようとする課題】IFNはヒトの体内で
産生される物質であるが、IFN療法に際して、外部か
らの投与が長期間に及び、大量のIFNが投与される
と、インフルエンザ様症状(頭痛、発熱、関節痛、筋肉
痛、食欲不振、全身倦怠感、悪心・嘔吐等)、自己免疫
性疾患、鬱症状(不眠や焦燥感等)、脱毛、甲状腺機能
異常、ぼけ等多種多様な副作用が生じる。IFN is a substance that is produced in the human body, but during IFN therapy, if it is administered from the outside for a long period of time and a large amount of IFN is administered, influenza-like symptoms ( Various side effects such as headache, fever, arthralgia, myalgia, loss of appetite, general malaise, nausea / vomiting), autoimmune diseases, depressive symptoms (such as insomnia and irritability), hair loss, thyroid dysfunction, and blurring. Occurs.
【0006】そのため、IFNを投与することなく、生
体内でのIFN産生を増強させることによって、ウイル
ス感染の防御や、癌等の改善・治療を図るための研究も
進んでいる。[0006] Therefore, studies have been conducted to prevent viral infection and improve / treat cancer by enhancing IFN production in vivo without administering IFN.
【0007】IFN産生を増強する多くの物質や組成物
が知られているが、それらはウイルスや、病原菌などで
安全性に問題のあるものが多い。本発明は、副作用がな
い安全なIFN産生増強剤を提供しようとするものであ
る。Although many substances and compositions that enhance IFN production are known, many of them are viruses, pathogenic bacteria, etc. and have a safety problem. The present invention is intended to provide a safe IFN production enhancer without side effects.
【0008】[0008]
【課題を解決するための手段】本発明者らはエンテロコ
ッカス属に属する微生物、特にエンテロコッカス・フェ
カリス及びエンテロコッカス・カセリフラブスの菌体標
品が、体内でIFN産生を増強させることを見いだし、
本発明を完成させた。又、本発明剤に使用される菌種
は、健常者の腸内およびサイレージから分離された乳酸
菌の一種であるので、副作用の無い安全な菌種である。The present inventors have found that microorganisms belonging to the genus Enterococcus, particularly Enterococcus faecalis and Enterococcus caseiflaves bacterial cell samples, enhance IFN production in the body,
The present invention has been completed. Further, the bacterial species used in the agent of the present invention is a kind of lactic acid bacterium isolated from the intestines and silage of healthy subjects, and is therefore a safe bacterial species with no side effects.
【0009】エンテロコッカス・フェカリスは、腸内に
存在する常在菌の一種である(Bergey's Manual of Sys
tematic Bacteriology. 2(1986))。本発明においては
この菌種に属する種々の菌株を用いることができるが、
特にIFN産生増強活性が高い点において、NF−10
11菌株を用いることが好ましい。該菌株は工業技術院
微生物工業技術研究所に微工研菌寄第12564号とし
て寄託されている。Enterococcus faecalis is a kind of indigenous bacteria existing in the intestine (Bergey's Manual of Sys
tematic Bacteriology. 2 (1986)). In the present invention, various strains belonging to this strain can be used,
In particular, NF-10 has a high IFN production enhancing activity.
It is preferable to use 11 strains. The strain has been deposited at the Institute of Microbial Science and Technology of the Institute of Industrial Science and Technology as Microorganism Research Institute No. 12564.
【0010】エンテロコッカス・カセリフラブスは、サ
イレージ内に存在する菌の1種である(Bergey's Manua
l of Systematic Bacteriology. 2(1986))。本発明に
おいてはこの菌種に属する種々の菌株を用いることがで
きるが、特にIFN産生増強活性が高い点において、N
F−1004菌株を用いることが好ましい。該菌株は工
業技術院微生物工業技術研究所に微工研菌寄第1437
8号として寄託されている。Enterococcus casei flavus is one of the bacteria present in silage (Bergey's Manua
l of Systematic Bacteriology. 2 (1986)). In the present invention, various strains belonging to this strain can be used, but N is particularly high in that it has a high IFN production enhancing activity.
It is preferred to use the F-1004 strain. The strain was sent to the Institute of Microbial Science and Technology of the Agency of Industrial Science and Technology, Microorganisms Research Institute
Deposited as No. 8.
【0011】以下にエンテロコッカス・フェカリスNF
−1011及びエンテロコッカス・カセリフラブスNF
−1004の分離手段及び同菌株の菌学的及び生理学的
性質を示す。The following is Enterococcus faecalis NF
-1011 and Enterococcus caseiflaves NF
-1004 shows the means of isolation and the mycological and physiological properties of the strain.
【0012】(1)エンテロコッカス・フェカリスNF
−1011の分離手段 健常者の糞便の加熱滅菌水による10倍希釈物を適切な
選択培地(KMN寒天平板及びSF寒天平板)に塗抹
し、好気条件下37℃で、48〜72時間培養し、菌集
落を出現させた。この菌集落を別の同種平板培地に画線
塗布し、同様に培養して菌集落を再び出現させた。同様
の操作を数回繰り返し、単一の菌種だけからなる単一集
落を分離した。この新分離菌株について、菌学的(形態
的、生化学的及び血清学的)性状を調べ、エンテロコッ
カス・フェカリス(Enterococcusfaecalis)に属すると
分類同定した。 (2)エンテロコッカス・カセリフラブスNF−100
4の分離手段 サイレージの加熱滅菌水による10倍希釈物を適切な選
択培地(1.5%寒天含MRS培地)に塗抹し、好気条件下
37℃で、48〜72時間培養し、菌集落を出現させ
た。この菌集落を別の同種平板培地に画線塗布し、同様
に培養して菌集落を再び出現させた。同様の操作を数回
繰り返し、単一の菌種だけからなる単一集落を分離し
た。この新分離菌株について、菌学的(形態的、生化学
的及び血清学的)性状を調べ、エンテロコッカス・カセ
リフラブス(Enterococcuscasseliflavus)に属すると
分類同定した。(1) Enterococcus faecalis NF
Separation means of 1011 A 10-fold dilution of feces of a healthy person with heat-sterilized water is smeared on an appropriate selective medium (KMN agar plate and SF agar plate), and cultured at 37 ° C under aerobic conditions for 48 to 72 hours. , A bacterial colony appeared. The bacterial colonies were streaked on another homogeneous plate medium and cultured in the same manner to reappear the bacterial colonies. The same operation was repeated several times to separate a single colony consisting of a single bacterial species. The new isolate was examined for mycological (morphological, biochemical and serological) properties and classified and identified as belonging to Enterococcus faecalis. (2) Enterococcus caseiflaves NF-100
4. Separation means 4 A 10-fold dilution of silage with heat-sterilized water is smeared on an appropriate selective medium (1.5% agar-containing MRS medium), and cultured at 37 ° C under aerobic conditions for 48 to 72 hours to reveal bacterial colonies. Let The bacterial colonies were streaked on another homogeneous plate medium and cultured in the same manner to reappear the bacterial colonies. The same operation was repeated several times to separate a single colony consisting of a single bacterial species. The new isolate was examined for mycological (morphological, biochemical and serological) properties and classified and identified as belonging to Enterococcus casseliflavus.
【0013】 (3)菌学的及び生理学的性質 ──────────────────────────── 性状 NF-1011 NF-1004 ──────────────────────────── グラム染色性 + + 菌形態 球形 球形 カタラーゼ − − 溶血性 α α 血清群 D D 増殖性 10℃ + + 45℃ + + 50℃ + + 熱耐性 60℃ 30分 + + 胆汁エスクリン添加培地での生育 + + pH9.6培地での生育 + + 6.5%食塩添加培地での生育 + + メチレンブルー染色性 + + ゼラチン液化 − − 0.01%TTC添加培地での生育 + + テルライト添加培地での生育 + + 酸生成の有無 グリセロール + + L−アラビノース − + D−リボース + + D−キシロース − + D−グルコース + + D−ガラクトース + + D−フラクトース + + D−マンノース + + マルトース + + マンニトール + + シュクロース + + L−ソルボース − − D−ソルビトール + − L−ラムノース + + ラクトース + + アミグダリン + + エスクリン + + セロビオース + + メリビオース − + イヌリン − + メレジトース + − ──────────────────────────── +;陽性、−;陰性 TTC;2,3,5−トリフェニルテトラゾリウムクロリド(3) Mycological and Physiological Properties ──────────────────────────── Property NF-1011 NF-1004 ── ────────────────────────── Gram stain + + Bacterial morphology Spherical sphere Catalase − − Hemolytic αα Serogroup D D Proliferation 10 ° C + + 45 ° C + + 50 ° C + + Thermotolerance 60 ° C 30 minutes + + Growth on medium supplemented with bile esculin + + Growth on medium pH 9.6 + + + Methylene blue staining + 6.5% Sex ++ Gelatin liquefaction --- Growth in 0.01% TTC-supplemented medium ++ Growth in tellurite-supplemented medium ++ Presence / absence of acid production Glycerol + + L-arabinose- + D-ribose + + D-xylose- + D -Glucose + + D-galactose + + D-fract Source + + D-mannose + + Maltose + + Mannitol + + Sucrose + + L-sorbose − − D-sorbitol + − L-rhamnose + + Lactose + + amygdalin + + + esculin + + cellobiose in + + − + Merezitose + − ──────────────────────────── +; Positive, −; Negative TTC; 2,3,5-Triphenyl Tetrazolium chloride
【0014】本発明に使用するエンテロコッカス・フェ
カリス及びエンテロコッカス・カセリフラブスを培養し
て得られる菌体は死菌体又は生菌体、或いは菌体を磨
砕、水抽出などの処理をしたものを用いることができ
る。これらを製剤するにはデンプン、乳糖、大豆蛋白等
の担体、賦形剤、結合剤、崩壊剤、滑沢剤、安定剤、矯
味矯具剤等の添加物を用いて周知の方法で錠剤や顆粒剤
に製剤される。The cells obtained by culturing Enterococcus faecalis and Enterococcus casei flavus used in the present invention are dead cells or viable cells, or cells that have been subjected to treatment such as grinding and water extraction are used. You can To formulate these, tablets and tablets are prepared by a known method using additives such as carriers such as starch, lactose and soybean protein, excipients, binders, disintegrating agents, lubricants, stabilizers, and corrigents. It is formulated into granules.
【0015】使用量は、症状、年齢等により異なるが、
有効成分として1日0.002〜0.1g/kg体重を通常成人に対
して1日1回又は数回に分けて投与することができる。The amount used depends on symptoms, age, etc.,
As an active ingredient, 0.002 to 0.1 g / kg body weight per day can be usually administered to an adult once a day or in several divided doses.
【0016】以下にIFN力価測定の実験方法を示す。The experimental method for measuring IFN titer is shown below.
【0017】(1)マウス脾細胞の調製 C3H/He N系のマウス(雌性6〜12週齢)の脾臓を無菌
的に取り出し、5%FCS−RPMI 1640培地(以下培養液)の
入った培養皿に移し、はさみで細片にした後、ナイロン
メッシュを通して遠心管へ移す。この細胞懸濁液を遠心
分離(1,200rpm)し、沈殿した細胞を赤血球除去用トリ
ス緩衝液に懸濁、再び遠心分離を行い、沈殿した細胞を
培養液に懸濁する。この細胞懸濁液の、脾細胞数が5×
106個/ml〜1×107個/mlになるように調整する。(1) Preparation of mouse spleen cells The spleen of a C3H / He N strain mouse (female 6 to 12 weeks old) was aseptically removed and cultured in 5% FCS-RPMI 1640 medium (hereinafter referred to as culture medium). Transfer to a dish, cut into small pieces with scissors, and transfer to a centrifuge tube through a nylon mesh. The cell suspension is centrifuged (1,200 rpm), the precipitated cells are suspended in Tris buffer for red blood cell removal, and the cells are centrifuged again to suspend the precipitated cells in the culture medium. The number of splenocytes in this cell suspension is 5 ×
Adjust so as to be 10 6 pieces / ml to 1 × 10 7 pieces / ml.
【0018】(2)IFN液の調製 プレートウエル内の脾細胞からのIFN産生を増強す
る場合 96ウエル平底プレートを用いてマウス脾細胞懸濁液
(100μl/ウエル)に供試標品を終濃度10μg/
mlとなるように添加し、CO2インキュベーター内で2
0時間培養する。対照として、LPS(リポ多糖)又
は、PHA−P(赤血球凝集素であり、IFN産生を増
強する)を同量添加する。培養後得られた遠心上清をI
FN液とする。(2) Preparation of IFN solution When enhancing IFN production from splenocytes in plate wells: A 96-well flat-bottom plate was used to make a final concentration of the test sample in a mouse splenocyte suspension (100 μl / well). 10 μg /
Add so that the amount becomes ml, and add 2 in a CO 2 incubator.
Incubate for 0 hour. As a control, LPS (lipopolysaccharide) or PHA-P (hemagglutinin, which enhances IFN production) is added in the same amount. The centrifugal supernatant obtained after the culturing was
Use FN liquid.
【0019】生体内でIFN産生を増強する場合 2群のC3H/He N系のマウス(雌性8週齢)の各々にシク
ロホスファミド(200mg/kg体重)を腹腔内に投与し、一
方の群には翌日から3日間連続して供試する菌体標品を
経口、又は腹腔内に投与する。他方の対照群マウスには
生理的食塩水を同様に投与する。次に実験方法(1)の
方法でマウス脾細胞懸濁液を調製し、これにIFNイン
デューサーとしてのLPS又はPHA−Pを添加して、
同(2)と同様にしてCO2インキュベーター内で2
0時間培養する。培養後得られた遠心上清をIFN液と
する。In the case of enhancing IFN production in vivo, cyclophosphamide (200 mg / kg body weight) was intraperitoneally administered to each of two groups of C3H / He N mice (female 8 weeks old), and one of The cell preparation to be tested is orally or intraperitoneally administered to the group for 3 consecutive days from the next day. The other control mouse is similarly administered with physiological saline. Next, a mouse splenocyte suspension was prepared by the method of Experimental method (1), and LPS or PHA-P as an IFN inducer was added thereto,
2 in the CO 2 incubator as in (2)
Incubate for 0 hour. The centrifugal supernatant obtained after the culture is used as an IFN solution.
【0020】(3)CPE(細胞変性効果)阻止法によ
るIFNの力価測定 96ウエル平底プレートに、あらかじめ5×105個/m
lに調製したL929細胞を添加し、CO2インキュベータ
ー内で6時間培養して、プレートに細胞を付着させる。
これに(2)で調製したIFN液を添加して、CO2イ
ンキュベーター内で16時間培養した後上清を捨て、Ve
sicular Stomatitis Virus(VSV)を2,500PFU/ウエ
ル添加し、さらに48時間培養する。培養終了後上清を
捨て、VSVによって変性剥離した細胞を除去した後、
付着したまま残った細胞をクリスタルバイオレットで染
色し、620nmでの吸光度を測定する。(3) Measurement of IFN titer by CPE (cytopathic effect) inhibition method In a 96-well flat bottom plate, 5 × 10 5 cells / m 2 were prepared in advance.
L 929 cells prepared in 1 are added and cultured in a CO 2 incubator for 6 hours to attach the cells to the plate.
The IFN solution prepared in (2) was added to this, the mixture was incubated in a CO 2 incubator for 16 hours, and the supernatant was discarded.
Add 2,500 PFU / well of sicular Stomatitis Virus (VSV) and incubate for another 48 hours. After culturing, the supernatant is discarded, and the cells denatured and detached by VSV are removed.
The cells that remain attached are stained with crystal violet and the absorbance at 620 nm is measured.
【0021】[0021]
【実施例】以下実施例を示すが、本発明はこれらの実施
例の記載によって何ら制限されるものではない。EXAMPLES Examples will be shown below, but the present invention is not limited to the description of these Examples.
【0022】実施例1.(エンテロコッカスの培養) エンテロコッカス・フェカリス(Enterococcus faecali
s)NF−1011及びエンテロコッカス・カセリフラ
ブス(Enterococcus casseliflavus)NF−1004
を、代表的培地として以下に示す組成のロゴサ液体培地
に接種し(菌数:106個/ml)、37℃で10〜1
6時間培養し、生菌数約109個/mlの培養液を得
た。得られた培養液を12,000rpmで20分間遠心
分離して集菌し、これを蒸留水で2回洗浄して菌体を得
た。この菌体を、用いた液体培地量の100分の1量の
蒸留水で懸濁し、110℃で10分間加熱して死菌体懸
濁液を得た。次に、熱風乾燥法あるいは凍結乾燥法など
適当な方法で乾燥処理し、死菌体菌末(菌体標品)を得
た。Example 1. (Cultivation of Enterococcus faecalis)
s) NF-1011 and Enterococcus casseliflavus NF-1004
Was inoculated into a Rogosa liquid medium having a composition shown below as a typical medium (the number of bacteria: 10 6 cells / ml), and 10-1 at 37 ° C
After culturing for 6 hours, a culture solution containing about 10 9 viable cells / ml was obtained. The obtained culture solution was centrifuged at 12,000 rpm for 20 minutes to collect the cells, and the cells were washed twice with distilled water to obtain cells. The cells were suspended in distilled water in an amount 1/100 of the amount of the liquid medium used, and heated at 110 ° C. for 10 minutes to obtain a suspension of dead cells. Next, it was dried by an appropriate method such as a hot air drying method or a freeze drying method to obtain dead bacterial cell powder (fungal cell preparation).
【0023】ロゴサ液体培地の組成を示す。 トリプチケース 10g 酵母エキス 5g トリプトース 3g リン酸一カリウム 3g リン酸二カリウム 3g クエン酸三アンモニウム 2g ツイーン80(界面活性剤) 1g グルコース 20g システイン塩酸塩 0.2g 塩類溶液(1のとおり) 5ml 蒸留水 1000ml (pH7.0に調整、121℃で15分間加熱滅菌) (1)塩類溶液:MgSO4・7H2O 11.5
g FeSO4・7H2O 0.68g MnSO4・2H2O 2.4g 蒸留水 100mlThe composition of Rogosa liquid medium is shown below. Trypticase 10 g Yeast extract 5 g Tryptose 3 g Monopotassium phosphate 3 g Dipotassium phosphate 3 g Triammonium citrate 2 g Tween 80 (surfactant) 1 g Glucose 20 g Cysteine hydrochloride 0.2 g Salt solution (as in 1) 5 ml Distilled water 1000 ml (adjusted to pH 7.0, heat sterilized at 121 ° C. for 15 minutes) (1) Salt solution: MgSO 4 .7H 2 O 11.5
g FeSO 4 · 7H 2 O 0.68g MnSO 4 · 2H 2 O 2.4g distilled water 100ml
【0024】実施例2.プレートウエル内での脾細胞か
らのIFN産生の増強 実験方法(1)に従って調製したマウス脾細胞を用い
て、同(2)に示した方法でIFN液を調製した。供
試標品として、実施例1で調製したNF−1004菌体
標品及びNF−1011菌体標品を用いた。Embodiment 2 FIG. Enhancement of IFN Production from Splenocytes in Plate Well Using mouse splenocytes prepared according to the experimental method (1), an IFN solution was prepared by the method shown in (2). As test specimens, the NF-1004 bacterial cell preparation and the NF-1011 bacterial cell preparation prepared in Example 1 were used.
【0025】実験方法(3)に従って、IFNの力価を
測定し、供試標品の持つ脾細胞からのIFN産生増強活
性とした。結果は表1に示したように、供試標品は、対
照としてのLPS又はPHA−Pと同等又はそれ以上の
強い増強活性を示した。According to the experimental method (3), the titer of IFN was measured and used as the activity of enhancing IFN production from splenocytes of the test sample. As the results are shown in Table 1, the test sample showed a strong enhancing activity equivalent to or higher than that of LPS or PHA-P as a control.
【0026】[0026]
【表1】 ─────────────────────────── IFNの力価(IU/ml) ─────────────────────────── 菌体標品 NF−1011 216 NF−1004 176 LPS 163 PHA−P 21.6 ─────────────────────────── [Table 1] ─────────────────────────── IFN titer (IU / ml) ─────────── ───────────────── Bacterial preparation NF-1011 216 NF-1004 176 LPS 163 PHA-P 21.6 ───────────── ──────────────
【0027】実施例3.生体内でのIFN産生の増強 (1)菌体標品の投与及び脾細胞の調製 C3H/He N系のマウス(雌性8週齢)にシクロホスファミ
ド(200mg/kg体重)を腹腔内に投与し、次の日から3日
間連続で、実施例1で調製したNF−1011菌体標品
を経口投与の場合で2.4mg/g体重、腹腔内投与の場合で
4.0μg/g体重になるように各々投与した。最終投与の2
日後に実験方法(1)に従って、マウス脾細胞を調製し
た。Embodiment 3 FIG. Enhancement of IFN production in vivo (1) Administration of bacterial cell preparation and preparation of splenocytes Cyclophosphamide (200 mg / kg body weight) was intraperitoneally administered to C3H / He N strain mice (female 8 weeks old) After administration, the NF-1011 bacterial cell preparation prepared in Example 1 was administered for 3 consecutive days from the next day. The oral preparation was 2.4 mg / g body weight, and the intraperitoneal administration was 3 days.
Each dose was adjusted to 4.0 μg / g body weight. 2 of the final administration
After a day, mouse splenocytes were prepared according to the experimental method (1).
【0028】(2)IFN液の調製 得られたマウス脾細胞を用いて、実験方法(2)に準
じて、IFN液を調製した。すなわち、供試菌体標品を
投与したマウスの脾細胞懸濁液に、LPSを1μg/ml、
又は、PHA−Pを10μg/mlになるように添加し、実験
方法(2)と同様にして、CO2インキュベーター内
で20時間培養した。培養後得られた遠心上清をIFN
液とした。(2) Preparation of IFN Solution Using the obtained mouse splenocytes, an IFN solution was prepared according to the experimental method (2). That is, 1 μg / ml of LPS was added to a splenocyte suspension of a mouse to which the test bacterial cell preparation was administered,
Alternatively, PHA-P was added to 10 μg / ml and cultured in a CO 2 incubator for 20 hours in the same manner as in the experimental method (2). The centrifugal supernatant obtained after culturing is IFN
It was a liquid.
【0029】(3)IFNの力価測定 実験方法(3)に準じた。結果を表2に示した。NF−
1011菌体標品を経口投与、又は、腹腔内投与するこ
とによって、IFN産生が著しく増強された。(3) Measurement of IFN titer This was based on the experimental method (3). The results are shown in Table 2. NF-
IFN production was markedly enhanced by oral administration or intraperitoneal administration of 1011 bacterial cell preparation.
【0030】[0030]
【表2】 ────────────────────────────── IFNの力価(IU/ml) LPS PHA−P ────────────────────────────── 生理的食塩水 253.0± 58.4 65.1±52.7 (対照) ────────────────────────────── NF-1011菌体標品 419.9± 98.7* 153.4±79.9* 経口投与 ────────────────────────────── NF-1011菌体標品 281.5±143.2 251.3±91.7* 腹腔内投与 ────────────────────────────── *:p<0.05(対照値に対して有意差あり)[Table 2] ────────────────────────────── IFN titer (IU / ml) LPS PHA-P ─── ─────────────────────────── Physiological saline 253.0 ± 58.4 65.1 ± 52.7 (control) ────────── ──────────────────── NF-1011 cell preparation 419.9 ± 98.7 * 153.4 ± 79.9 * Oral administration ────────────── ───────────────── NF-1011 microbial preparation 281.5 ± 143.2 251.3 ± 91.7 * Intraperitoneal administration ──────────────── ────────────── * : p <0.05 (significantly different from the control value)
【0031】[0031]
【発明の効果】エンテロコッカス属に属する菌体を用い
ることによって、副作用のない安全なIFN産生増強剤
を提供できる。又、これらの微生物は、経口でも効果が
得られるため、経口剤としても利用できる。INDUSTRIAL APPLICABILITY By using cells belonging to the genus Enterococcus, a safe IFN production enhancer without side effects can be provided. Further, since these microorganisms can be orally effective, they can be used as an oral preparation.
───────────────────────────────────────────────────── フロントページの続き (51)Int.Cl.6 識別記号 庁内整理番号 FI 技術表示箇所 C12R 1:01) (72)発明者 山本 哲郎 三重県阿山郡阿山町大字円徳院1406番地69 号─────────────────────────────────────────────────── ─── Continuation of front page (51) Int.Cl. 6 Identification number Internal reference number FI technical display location C12R 1:01) (72) Inventor Tetsuro Yamamoto 1406 Entoku-in, Ayama-cho, Ayama-cho, Mie Prefecture 69 issue
Claims (3)
又はその処理物を有効成分として含有するインターフェ
ロン産生増強剤1. An interferon production enhancer containing, as an active ingredient, cells of a microorganism belonging to the genus Enterococcus or a processed product thereof.
テロコッカス・フェカリス又はエンテロコッカス・カセ
リフラブスである請求項1記載のインターフェロン産生
増強剤2. The interferon production enhancer according to claim 1, wherein the microorganism belonging to the genus Enterococcus is Enterococcus faecalis or Enterococcus caseiflaves.
テロコッカス・フェカリスNF−1011又はエンテロ
コッカス・カセリフラブスNF−1004である請求項
1記載のインターフェロン産生増強剤3. The interferon production enhancer according to claim 1, wherein the microorganism belonging to the genus Enterococcus is Enterococcus faecalis NF-1011 or Enterococcus caseiflaves NF-1004.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP7086478A JPH08259450A (en) | 1995-03-17 | 1995-03-17 | Enhancer for production of interferon |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP7086478A JPH08259450A (en) | 1995-03-17 | 1995-03-17 | Enhancer for production of interferon |
Publications (1)
Publication Number | Publication Date |
---|---|
JPH08259450A true JPH08259450A (en) | 1996-10-08 |
Family
ID=13888089
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP7086478A Pending JPH08259450A (en) | 1995-03-17 | 1995-03-17 | Enhancer for production of interferon |
Country Status (1)
Country | Link |
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JP (1) | JPH08259450A (en) |
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