JPH0614794A - Immunostimulant composition composed of soybean protein-derived peptide - Google Patents
Immunostimulant composition composed of soybean protein-derived peptideInfo
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- JPH0614794A JPH0614794A JP5066201A JP6620193A JPH0614794A JP H0614794 A JPH0614794 A JP H0614794A JP 5066201 A JP5066201 A JP 5066201A JP 6620193 A JP6620193 A JP 6620193A JP H0614794 A JPH0614794 A JP H0614794A
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- arg
- gln
- pro
- cys
- peptide
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Abstract
Description
【0001】[0001]
【産業上の利用分野】本発明は、大豆蛋白質起源の生理
活性ペプチドを有効成分とする医薬組成物に関するもの
である。TECHNICAL FIELD The present invention relates to a pharmaceutical composition containing a physiologically active peptide derived from soybean protein as an active ingredient.
【0002】[0002]
【従来の技術】食品蛋白質起源のペプチドには多様な生
理活性を有するものがあることが知られており、食品起
源で生体に対する安全性が期待できることから種々の研
究がなされている。このうちの一つとして貪食作用(フ
ァゴサイトシス)が知られている。生体内に細菌等の外
的異物が侵入してきた場合、マクロファージや好中球に
よる異物の貪食作用は生体防御の初発反応として重要で
ある。このファゴサイトシスを活性化するペプチドとし
ては、生体内で免疫グロブリンから派生するタフトシン
( Tuftsin:Thr-Lys-Pro-Arg )およびリギン( Rigi
n:Gly-Gln-Pro-Arg )が知られている。本発明者は先
に、これらに類似の構造を持つ大豆グリシニンA1aサブ
ユニットに含まれているペプチド:Gln-Arg-Pro-Arg が
マクロファージの貪食能を高めることについてその合成
ペプチドを用いて証明し、新規なペプチドとして報告し
た(特開平1-249800号公報)。2. Description of the Related Art It is known that some peptides derived from food proteins have various physiological activities, and various studies have been conducted because they are expected to be safe for living organisms due to food origin. Phagocytosis (phagocytosis) is known as one of them. When external foreign substances such as bacteria enter the living body, phagocytosis of the foreign substances by macrophages and neutrophils is important as the initial reaction of biological defense. Peptides that activate this phagocytosis include immunoglobulin-derived tuftsin (Thft-Lys-Pro-Arg) and rigin (Rigi).
n: Gly-Gln-Pro-Arg) is known. The present inventor has previously demonstrated using a synthetic peptide that a peptide contained in a soybean glycinin A 1a subunit having a structure similar to these: Gln-Arg-Pro-Arg enhances phagocytic ability of macrophages. And reported it as a novel peptide (Japanese Patent Laid-Open No. 1-249800).
【0003】しかして、食品蛋白質起源の生理活性ペプ
チドは、内因性生理活性ペプチドと比較して意外な構造
−活性相関を示す物質が多いことおよび複数の機能を有
するペプチドが多いことから、ペプチドの構造からその
有する機能については予測できないとされている。[0003] However, physiologically active peptides derived from food proteins have many substances which show a surprising structure-activity relationship as compared with endogenous physiologically active peptides, and many peptides having multiple functions. It is said that its function cannot be predicted from its structure.
【0004】[0004]
【発明が解決しようとする課題】本発明者らは食品蛋白
質起源のペプチドについて更に研究を進めた結果、マク
ロファージの貪食能を高める作用を有する他に更に優れ
た生理活性を有するペプチドを見いだして本発明を完成
した。したがって、本発明は該ペプチドの新規な医薬用
途を提供せんとするものである。DISCLOSURE OF INVENTION Problems to be Solved by the Invention As a result of further research on peptides derived from food proteins, the present inventors have found peptides having further excellent physiological activity in addition to the action of enhancing phagocytic ability of macrophages. Completed the invention. Therefore, the present invention is intended to provide a novel pharmaceutical use of the peptide.
【0005】[0005]
【課題を解決するための手段】本発明は、次式I: His-Cys-Gln-Arg-Pro-Arg (I) (式中、His はヒスチジン、Cys はシステイン、Gln は
グルタミン、Arg はアルギニンおよびPro はプロリンを
表す。)で表されるペプチドまたはその薬学上許容され
る塩を有効成分とする免疫系賦活組成物に関するもので
ある。本発明者らは、大豆タンパク質の酵素分解によっ
て得られた上記式Iで示されるペプチドが好中球の集
積、活性酸素の産生および腫瘍壊死因子の産生を高める
とともに、腹水ガンに対する抑制作用を有することを見
いだした。The present invention provides the following formula I: His-Cys-Gln-Arg-Pro-Arg (I) (wherein His is histidine, Cys is cysteine, Gln is glutamine, and Arg is arginine. And Pro represent proline) or a pharmaceutically acceptable salt thereof as an active ingredient. The present inventors have found that the peptide represented by the above formula I obtained by enzymatic decomposition of soybean protein enhances neutrophil accumulation, active oxygen production and tumor necrosis factor production, and has an inhibitory action on ascites cancer. I found a thing.
【0006】本発明の有効成分であるペプチド:His-Cy
s-Gln-Arg-Pro-Arg (以下、HCQRPRと略記す
る。)は、従来知られているペプチド化学合成法によっ
て合成することができる。この他、大豆蛋白質などの上
記式Iのアミノ酸配列を含む蛋白質より酵素加水分解に
よって得ることもできると考えられるが、その方法につ
いては知られていなかった。本発明者らは酵素加水分解
法による新規な製法を見いだした。それ故、本発明は上
記ペプチドの新規な製造方法をも提供するものである。
本発明の酵素加水分解法は、大豆蛋白質をトリプシンで
消化し、得られた消化物をオクタデシルシリル(OD
S)カラムおよびフェニルカラムによる高速液体クロマ
トグラフィー(HPLC)によって分画することを特徴
とする。Peptide which is the active ingredient of the present invention: His-Cy
s-Gln-Arg-Pro-Arg (hereinafter abbreviated as HCQRPR) can be synthesized by a conventionally known peptide chemical synthesis method. In addition, it is considered that the protein can be obtained by enzymatic hydrolysis from a protein containing the amino acid sequence of the above formula I, such as soybean protein, but its method has not been known. The present inventors have found a new production method by the enzymatic hydrolysis method. Therefore, the present invention also provides a novel method for producing the above peptide.
According to the enzymatic hydrolysis method of the present invention, soybean protein is digested with trypsin, and the resulting digest is octadecylsilyl (OD).
S) column and phenyl column for high performance liquid chromatography (HPLC).
【0007】[0007]
【製造例】次に本発明の製造例を示すが、本発明はこれ
らの例に限定されるものではない。PRODUCTION EXAMPLES Next, production examples of the present invention will be shown, but the present invention is not limited to these examples.
【0008】製造例1:His-Cys-Gln-Arg-Pro-Arg の化
学合成 2gのBoc-Arg(Tos)- 樹脂(0.3meq/g,バイオサーチ
社製)をSAM2(バイオサーチ社製)ペプチド合成装
置の反応容器にセットし、デブロック液(45%トリフル
オロ酢酸、 2.5%アニソール、2%エタンジチオール、
50.5%ジクロロメタン)中で25分間攪拌してBoc 基を除
去した。この樹脂をジクロロメタン、10%ジイソプロピ
ルエチルアミンを含むジクロロメタンおよびジクロロメ
タンにて順次洗浄した後、10mlの 0.4M Boc-Proのジメ
チルフォルムアミド溶液と10mlのジイソプロピルカルボ
ジイミドの塩化メチレン溶液を加え室温で2時間攪拌し
てBoc-Proとカップルさせ、Boc-Pro-Arg(Tos)−樹脂を
得た。以下同様にBoc-Arg(Tos)、Boc-Gln 、Boc-Cys(MB
zl) およびBoc-His(Tos)を順次カップルさせ、Boc-His
(Tos)-Cys(Bzl)-Gln-Arg(Tos)-Pro-Arg(Tos) 樹脂を得
た。なお、Boc-Gln のカップリングに際してはBoc-Gln
のジメチルフォルムアミド液に 0.6M1−ヒドロキシベ
ンゾトリアゾールを添加してニトリルの形成を防いだ。Production Example 1: Chemical synthesis of His-Cys-Gln-Arg-Pro-Arg 2 g of Boc-Arg (Tos) -resin (0.3 meq / g, manufactured by Biosearch) was used as SAM2 (manufactured by Biosearch). Set in the reaction vessel of the peptide synthesizer, and use the deblocking solution (45% trifluoroacetic acid, 2.5% anisole, 2% ethanedithiol,
The Boc group was removed by stirring in 50.5% dichloromethane) for 25 minutes. The resin was washed successively with dichloromethane, dichloromethane containing 10% diisopropylethylamine and dichloromethane, then 10 ml of 0.4M Boc-Pro in dimethylformamide solution and 10 ml of diisopropylcarbodiimide in methylene chloride solution were added and stirred at room temperature for 2 hours. And coupled with Boc-Pro to give Boc-Pro-Arg (Tos) -resin. Similarly, Boc-Arg (Tos), Boc-Gln, Boc-Cys (MB
zl) and Boc-His (Tos) are sequentially coupled, and Boc-His
A (Tos) -Cys (Bzl) -Gln-Arg (Tos) -Pro-Arg (Tos) resin was obtained. Note that when coupling Boc-Gln, Boc-Gln
0.6M 1-Hydroxybenzotriazole was added to the dimethylformamide solution to prevent the formation of nitrile.
【0009】上記樹脂を10%のアニソールを含む液体フ
ッ化水素約20ml中で0℃1時間攪拌してペプチドの脱保
護を行った。フッ化水素を減圧除去した後、エーテルに
て樹脂を洗浄し、15%酢酸にてペプチドを抽出し、凍結
乾燥して粗 His-Cys-Gln-Arg-Pro-Argを得た。さらに
0.1%トリフルオロ酢酸の存在下、ODSカラム(Cosmo
sil 5C18・AR,ナカライテスク製)による高速液
体クロマトグラフィーにより 200mgの純品を得た。な
お、上記においてHis はヒスチジン、Cys はシステイ
ン、Gln はグルタミン、Arg はアルギニン、Pro はプロ
リンの各アミノ酸残基を示し、Boc はt−ブトキシカル
ボニル基、Toc はトシル基を示す。The resin was deprotected by stirring in about 20 ml of liquid hydrogen fluoride containing 10% anisole for 1 hour at 0 ° C. After removing hydrogen fluoride under reduced pressure, the resin was washed with ether, the peptide was extracted with 15% acetic acid, and freeze-dried to obtain crude His-Cys-Gln-Arg-Pro-Arg. further
In the presence of 0.1% trifluoroacetic acid, an ODS column (Cosmo
200 mg of pure product was obtained by high performance liquid chromatography using sil 5C 18 AR, manufactured by Nacalai Tesque. In the above, His is histidine, Cys is cysteine, Gln is glutamine, Arg is arginine, Pro is each amino acid residue of proline, Boc is t-butoxycarbonyl group, and Toc is tosyl group.
【0010】製造例2:酵素消化によるHis-Cys-Gln-Ar
g-Pro-Arg (HCQRPR)の調製 以下に調製法の概要を図式で示す。Production Example 2: His-Cys-Gln-Ar by enzymatic digestion
Preparation of g-Pro-Arg (HCQRPR) The outline of the preparation method is shown schematically below.
【0011】 [0011]
【0012】単離工程:大豆タンパク質消化物からのHi
s-Cys-Gln-Arg-Pro-Arg (HCQRPR)の単離 分離大豆タンパク質2gを32ml水に溶解しpH7.0 に調整
後、3000rpm 30分の遠心により不溶物を除去した。30分
間煮沸の後、16mgのトリプシンを添加し、37℃、5時間
の消化を行った。さらに10分間煮沸の後、10,000rpm.,
10分の遠心上清をトリプシン消化物とした。上記消化物
に1%となるよう2−メルカプトエタノールを添加し、
その50mg蛋白質相当量を 0.1%トリフルオロ酢酸で平衡
化したODS−カラム(Cosmosil5C18、20×250mm 、
ナカライテスク製)にロードし、 0.1%トリフルオロ酢
酸を含むアセトニトリルの直線的濃度勾配(1%/10ml
/min )により展開した。HCQRPRは16〜17%アセ
トニトリルで溶出した画分に含まれているが、他のペプ
チドも共存するので、さらにフェニルカラム(Cosmosil
5Ph、 4.6× 250mm、ナカライテスク製)、次いでシ
アノプロピルカラム(Cosmosil 5CN、4.6× 250m
m、ナカライテスク製)により精製し、HCQRPRを
得た。なお両カラムは 0.1%トリフルオロ酢酸を含むア
セトニトリルの直線的濃度勾配(1%/1ml/min )に
よって展開した。Isolation process: Hi from soybean protein digest
Isolation of s-Cys-Gln-Arg-Pro-Arg (HCQRPR) 2 g of the isolated soybean protein was dissolved in 32 ml of water to adjust the pH to 7.0, and the insoluble matter was removed by centrifugation at 3000 rpm for 30 minutes. After boiling for 30 minutes, 16 mg of trypsin was added, and digestion was carried out at 37 ° C for 5 hours. After boiling for another 10 minutes, 10,000 rpm.,
The 10-minute centrifugation supernatant was used as a trypsin digest. 2-mercaptoethanol was added to the above digest to give 1%,
An ODS-column (Cosmosil 5C 18 , 20 × 250 mm, equilibrated with 50 mg protein equivalent amount thereof by 0.1% trifluoroacetic acid,
Loaded on Nacalai Tesque), and linear gradient of acetonitrile containing 0.1% trifluoroacetic acid (1% / 10ml)
/ Min). HCQRPR is contained in the fraction eluted with 16 to 17% acetonitrile, but since other peptides also coexist, HCQRPR is added to the phenyl column (Cosmosil
5Ph, 4.6 × 250mm, manufactured by Nacalai Tesque, then cyanopropyl column (Cosmosil 5CN, 4.6 × 250m)
m, manufactured by Nacalai Tesque, Inc.) to obtain HCQRPR. Both columns were developed by a linear concentration gradient (1% / 1 ml / min) of acetonitrile containing 0.1% trifluoroacetic acid.
【0013】HCQRPRはフェニルカラムおよびシア
ノプロピルカラムからそれぞれ13%および 4.7%のアセ
トニトリルによって溶出された。分離大豆蛋白質からの
HCQRPRの収率は0.06%であった。大豆蛋白質トリ
プシン消化物のODS−カラムによる分画の吸光度のチ
ャートを図1に、ODS−カラム画分のフェニルカラム
による分画のチャートを図2に、そしてフェニルカラム
画分のシアノプロピルカラムによる分画のチャートを図
3に示す。各チャート中にAで示した画分にHCQRP
Rは回収される。HCQRPR was eluted from the phenyl and cyanopropyl columns with 13% and 4.7% acetonitrile, respectively. The yield of HCQRPR from the isolated soybean protein was 0.06%. The absorbance chart of the fraction of the soybean protein trypsin digested by the ODS-column is shown in FIG. 1, the chart of the fractionation of the ODS-column fraction by the phenyl column is shown in FIG. 2, and the fraction of the phenyl column fraction by the cyanopropyl column is shown. An image chart is shown in FIG. HCQRP is added to the fraction indicated by A in each chart.
R is recovered.
【0014】[0014]
【試験例】以下、本発明のペプチドの各作用について説
明する。 試験例1:好中球の集積作用 7週令の雄 ddYマウスの腹腔内に3mgのペプチドを投与
し1日後の腹腔内細胞を採取し、ディフクイック(ミド
リ十字製)にて染色後、好中球の割合を顕微鏡により算
定した。結果を表1に示す。TEST EXAMPLE Each action of the peptide of the present invention will be described below. Test Example 1: Accumulation of Neutrophils 7-week-old male ddY mice were intraperitoneally administered with 3 mg of the peptide, and one day later, the intraperitoneal cells were collected and stained with Diffquick (Midori Cross). The percentage of neutrophils was calculated by microscopy. The results are shown in Table 1.
【0015】 [0015]
【0016】試験例2:ファゴサイトシスの測定 7週令のddY 雄マウスに3mgのペプチドを腹腔内投与し
3日後に腹腔内細胞を回収し、それにオイルレッドを含
むパラフィンエマルジョンを1/10量加えて反応を開始
し、5分後、氷冷した生理食塩水を加え、反応を止め
る。遠心後、ペレットにパラジオキサンを加え、細胞に
取り込まれた色素を抽出する。その色素量を 524nmと 6
00nmの吸光度から測定し、その差より、ファゴサイトシ
ス量を評価した。なお、 600nmの吸光度は濁度の補正で
ある。Test Example 2: Measurement of phagocytosis 3 weeks of ddY male mice were intraperitoneally administered with 3 mg of the peptide, and 3 days after the intraperitoneal cells were collected, a paraffin emulsion containing oil red was added in an amount of 1/10. In addition, the reaction is started, and after 5 minutes, ice-cooled physiological saline is added to stop the reaction. After centrifugation, paradioxane is added to the pellet to extract the dye taken up by the cells. The dye amount is 524 nm and 6
The amount of phagocytosis was evaluated based on the difference measured from the absorbance at 00 nm. The absorbance at 600 nm is a correction for turbidity.
【0017】 [0017]
【0018】試験例3:活性酸素産生能の測定 活性酸素産生および測定の仕組みを図式1および2に示
す。活性酸素は、図式1に示すように、食細胞内でHM
P経路から供給されるNADPHにより酸素が還元さ
れ、作られる。そして、活性酸素は試験管中で、チトク
ロムCを定量的に還元するので、その還元量を吸光度計
で吸光度(OD)を測り、活性酸素産生量を決定した。Test Example 3: Measurement of active oxygen production capacity Mechanisms of active oxygen production and measurement are shown in Schemes 1 and 2. As shown in Scheme 1, active oxygen is absorbed by HM in phagocytes.
Oxygen is reduced and produced by NADPH supplied from the P pathway. Since active oxygen quantitatively reduces cytochrome C in a test tube, the amount of reduction was measured by measuring the absorbance (OD) with an absorptiometer to determine the amount of active oxygen production.
【0019】[0019]
【表1】 [Table 1]
【0020】[0020]
【表2】 [Table 2]
【0021】図式2に示すように、細胞に異物であるザ
イモサン(酵母の細胞壁)をオプソニン化したものと、
チトクロムCを加えて反応を開始し、15分後氷水中に入
れ、反応を止める。遠心後、上清の 550nmと 468nmの吸
光度を測定し、その差から活性酸素産生量を計算した。
計算式は以下のようになる。 [O2 -]=A/ε・2×10-3・500/400 [μmol /2×106 ・15min ] ε=0.0245より =102・A[nmol/2×106 ・15min ] なお、A:吸光度 結果を表3に示す。As shown in Scheme 2, cells are obtained by opsonizing zymosan (yeast cell wall) which is a foreign substance,
Start the reaction by adding cytochrome C, and after 15 minutes, put it in ice water to stop the reaction. After centrifugation, the absorbance of the supernatant was measured at 550 nm and 468 nm, and the amount of active oxygen production was calculated from the difference.
The calculation formula is as follows. [O 2 − ] = A / ε · 2 × 10 −3 · 500/400 [μmol / 2 × 10 6 · 15 min] From ε = 0.0245 = 102 · A [nmol / 2 × 10 6 · 15 min] In addition, A : Absorbance results are shown in Table 3.
【0022】 [0022]
【0023】試験例4:腫瘍壊死因子(TNF)レベル
の上昇作用の測定 7週令の雄C3H/Hcマウスにペプチドを静脈内また
は経口投与し、3時間後に 0.3mgのピシバニール(OK
−432)を静脈内投与した。さらに2時間後に採血
し、血清中のTNFレベルをラジオイムノアッセイによ
り測定した。結果を表4に示す。本発明のペプチドは静
脈内投与において特に効果を示す。Test Example 4 Measurement of Elevating Effect of Tumor Necrosis Factor (TNF) Level 7-week-old male C3H / Hc mice were intravenously or orally administered with the peptide, and 3 hours later, 0.3 mg of picibanil (OK) was administered.
-432) was administered intravenously. After 2 hours, blood was collected and TNF level in serum was measured by radioimmunoassay. The results are shown in Table 4. The peptides of the present invention are particularly effective in intravenous administration.
【0024】 [0024]
【0025】試験例5:腹水ガンに対する抑制作用 ペプチド3mgと1×105 個のL−1210細胞を6週令の雄
のDBA/2マウスの腹腔内に投与し、マウスが腹水ガ
ンで死亡するまでの日数を測定した。1群は5または6
匹とした。生存日数を表5に示し、生存率を図4に示
す。Test Example 5: Inhibitory activity against ascites cancer Cancer 3 mg of peptide and 1 × 10 5 L-1210 cells were intraperitoneally administered to 6-week-old male DBA / 2 mice, and the mice died of ascites cancer. The number of days until was measured. 5 or 6 for 1 group
I made it The survival days are shown in Table 5, and the survival rate is shown in FIG.
【0026】 コントロール(生理食塩水)との差異はあまり大きくな
いが、腹水ガン抑制作用を持つとされているタフトシン
と同程度の作用を示す。[0026] Although the difference from the control (physiological saline) is not so large, it shows the same level of action as tuftsin, which is said to have an ascites cancer suppressing action.
【0027】試験例6:免疫増強作用 10匹1群のマウスに生理食塩水に溶解したペプチドを腹
腔内投与し、1時間後にキャンディダ・アルビカンス
( Candida albicans )菌を対照群の10日後の致死率が
90〜100 %になるような菌数を静脈内に接種し、10日後
の生存数で免疫増強作用を判定した。結果を表6に示
す。Test Example 6: Immunity-enhancing action A group of 10 mice was intraperitoneally administered with a peptide dissolved in physiological saline, and 1 hour later, Candida albicans was killed 10 days after the control group. Rate is
The number of bacteria was 90 to 100%, which was intravenously inoculated, and the immunopotentiating effect was determined by the number of surviving 10 days later. The results are shown in Table 6.
【0028】 [0028]
【0029】試験例7:免疫回復作用 10匹1群のマウスに生理食塩水に溶解したペプチドを第
1日、第3日、第5日に腹腔内投与する。さらに免疫抑
制剤シクロホスファミド25mg/Kgを第2日、第4日、第
6日に経口投与する。シクロホスファミドの最後の投与
の1時間後にキャンディダ・アルビカンス( Candida a
lbicans )菌を対照群の10日後の致死率が90〜100 %に
なるような菌数を静脈内に接種し、10日後の生存数で免
疫回復作用を判定した。結果を表7に示す。Test Example 7: Immune-restoring action A group of 10 mice was intraperitoneally administered with a peptide dissolved in physiological saline on the 1st, 3rd and 5th days. Furthermore, the immunosuppressant cyclophosphamide 25 mg / Kg is orally administered on the 2nd, 4th and 6th days. One hour after the last dose of cyclophosphamide, Candida albicans
Lbicans) was inoculated intravenously with a number of bacteria so that the lethality rate after 10 days was 90 to 100% in the control group, and the immune recovery effect was determined by the survival number after 10 days. The results are shown in Table 7.
【0030】 [0030]
【0031】[0031]
【発明の効果】上記の各結果からわかるように、本発明
のペプチドはタフトシンおよびQRPRと比較して貪食
能、腫瘍壊死因子レベルの上昇作用に優れており、免疫
系賦活作用を有することから種々の疾病の医薬組成物と
して使用できる。また、本発明の酵素加水分解法によれ
ば、得られたペプチドは食品蛋白質を起源とするため安
全性が充分に期待できる。本発明のペプチドは使用に当
たり、それ自体でまたは製薬上使用される担体および助
剤と共に適当な剤形に調製して経口または静脈内投与す
ることができる。EFFECTS OF THE INVENTION As can be seen from the above results, the peptides of the present invention are superior to tuftsin and QRPR in phagocytic activity and tumor necrosis factor level-elevating action, and have various immune system activating actions. It can be used as a pharmaceutical composition for the above diseases. Further, according to the enzymatic hydrolysis method of the present invention, the obtained peptide is derived from a food protein, so that safety can be expected sufficiently. In use, the peptide of the present invention can be orally or intravenously prepared by itself or in a suitable dosage form together with pharmaceutically used carriers and auxiliaries.
【図1】大豆蛋白質トリプシン消化物のODS−カラム
による分画の吸光度のチャート。FIG. 1 is an ODS-column fraction absorbance chart of a soy protein trypsin digest.
【図2】ODS−カラム画分のフェニルカラムによる分
画の吸光度のチャート。FIG. 2 is a chart of the absorbance of ODS-column fractions obtained by phenyl column fractionation.
【図3】フェニルカラム画分のシアノプロピルカラムに
よる分画の吸光度のチャート。FIG. 3 is a chart of the absorbance of a phenyl column fraction obtained by a cyanopropyl column fraction.
【図4】腹水ガンに対する抑制作用(生存率)を示すグ
ラフである。FIG. 4 is a graph showing an inhibitory effect (survival rate) on ascites cancer.
Claims (4)
グルタミン、Arg はアルギニンおよびPro はプロリンを
表す。)で表されるペプチドまたはその塩を有効成分と
する免疫系賦活組成物。1. The following formula I: His-Cys-Gln-Arg-Pro-Arg (I) (wherein His is histidine, Cys is cysteine, Gln is glutamine, Arg is arginine and Pro is proline). An immune system activating composition comprising a peptide represented by: or a salt thereof as an active ingredient.
性酸素の産生能および腫瘍壊死因子の産生能を高める作
用である請求項1記載の医薬組成物。2. The pharmaceutical composition according to claim 1, wherein the immune system activating action is an action of enhancing neutrophil accumulation ability, active oxygen production ability and tumor necrosis factor production ability.
項1記載の医薬組成物。3. The pharmaceutical composition according to claim 1, wherein the immune system activating action is a carcinostatic action.
れた消化物をオクタデシルシリル(ODS)カラムおよ
びフェニルカラムによる高速液体クロマトグラフィーに
よって分画することを特徴とする次式I: His-Cys-Gln-Arg-Pro-Arg (I) (式中、His はヒスチジン、Cys はシステイン、Gln は
グルタミン、Arg はアルギニンおよびPro はプロリンを
表す。)で表されるペプチドの製造方法。4. A soybean protein is digested with trypsin, and the resulting digest is fractionated by high performance liquid chromatography using an octadecylsilyl (ODS) column and a phenyl column. The following formula I: His-Cys- A method for producing a peptide represented by Gln-Arg-Pro-Arg (I) (wherein, His is histidine, Cys is cysteine, Gln is glutamine, Arg is arginine, and Pro is proline).
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP5066201A JP2660379B2 (en) | 1992-03-04 | 1993-03-02 | Immune system activating composition comprising peptide derived from soy protein |
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP4-82659 | 1992-03-04 | ||
JP8265992 | 1992-03-04 | ||
JP5066201A JP2660379B2 (en) | 1992-03-04 | 1993-03-02 | Immune system activating composition comprising peptide derived from soy protein |
Publications (2)
Publication Number | Publication Date |
---|---|
JPH0614794A true JPH0614794A (en) | 1994-01-25 |
JP2660379B2 JP2660379B2 (en) | 1997-10-08 |
Family
ID=26407370
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP5066201A Expired - Lifetime JP2660379B2 (en) | 1992-03-04 | 1993-03-02 | Immune system activating composition comprising peptide derived from soy protein |
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JP (1) | JP2660379B2 (en) |
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH08231589A (en) * | 1995-03-01 | 1996-09-10 | Suetsuna Yoko | New peptide and immunopotentiator |
US5726549A (en) * | 1995-02-10 | 1998-03-10 | Nippondenso Co., Ltd. | Sensor-less control apparatus for permanent magnet synchronous motor |
US5903129A (en) * | 1995-02-10 | 1999-05-11 | Denso Corporation | Method and apparatus for sensor-less control of permanent magnet synchronous motor |
US7285279B2 (en) | 1999-07-09 | 2007-10-23 | Sun Farm Corporation | Method of treating malignancies and viral infections and improving immune function with a dietary supplement |
EP2121002A1 (en) * | 2006-12-22 | 2009-11-25 | Fontera Co-Operative Group Limited | Methods of immune or haematological enhancement, inhibiting tumour formation or growth, and treating or preventing cancer |
US7928232B2 (en) | 2005-05-20 | 2011-04-19 | Daiichi Sankyo Company, Limited | Method for producing asymmetric tetrasubstituted carbon atom-containing compound |
-
1993
- 1993-03-02 JP JP5066201A patent/JP2660379B2/en not_active Expired - Lifetime
Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5726549A (en) * | 1995-02-10 | 1998-03-10 | Nippondenso Co., Ltd. | Sensor-less control apparatus for permanent magnet synchronous motor |
US5903129A (en) * | 1995-02-10 | 1999-05-11 | Denso Corporation | Method and apparatus for sensor-less control of permanent magnet synchronous motor |
JPH08231589A (en) * | 1995-03-01 | 1996-09-10 | Suetsuna Yoko | New peptide and immunopotentiator |
US7285279B2 (en) | 1999-07-09 | 2007-10-23 | Sun Farm Corporation | Method of treating malignancies and viral infections and improving immune function with a dietary supplement |
US7928232B2 (en) | 2005-05-20 | 2011-04-19 | Daiichi Sankyo Company, Limited | Method for producing asymmetric tetrasubstituted carbon atom-containing compound |
US8378119B2 (en) | 2005-05-20 | 2013-02-19 | Daiichi Sankyo Company, Limited | Method for producing asymmetric tetrasubstituted carbon atom-containing compound |
EP2121002A1 (en) * | 2006-12-22 | 2009-11-25 | Fontera Co-Operative Group Limited | Methods of immune or haematological enhancement, inhibiting tumour formation or growth, and treating or preventing cancer |
EP2121002A4 (en) * | 2006-12-22 | 2011-10-05 | Fonterra Co Operative Group | Methods of immune or haematological enhancement, inhibiting tumour formation or growth, and treating or preventing cancer |
Also Published As
Publication number | Publication date |
---|---|
JP2660379B2 (en) | 1997-10-08 |
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