WO2003035090A1 - Agents relieving anaphylactic allergic reactions and process for producing the same - Google Patents

Agents relieving anaphylactic allergic reactions and process for producing the same Download PDF

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Publication number
WO2003035090A1
WO2003035090A1 PCT/JP2002/010918 JP0210918W WO03035090A1 WO 2003035090 A1 WO2003035090 A1 WO 2003035090A1 JP 0210918 W JP0210918 W JP 0210918W WO 03035090 A1 WO03035090 A1 WO 03035090A1
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stevia
producing
anaphylactic
extract
filtrate
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PCT/JP2002/010918
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French (fr)
Japanese (ja)
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Tatsuhiko Kon
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Kabushiki Kaisha Thieisutebia
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/28Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00Drugs for disorders of the respiratory system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00Drugs for disorders of the respiratory system
    • A61P11/06Antiasthmatics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • A61P37/08Antiallergic agents

Definitions

  • the present invention relates to a anaphylaxis-type allergic symptom ameliorating substance which is a cause of hay fever, measles measles, bronchial asthma, atopic disease and the like and a method for producing the same.
  • Anaphylaxis generally refers to a systemic allergic reaction triggered by immunological mechanisms.
  • histamine and leukotriene are released from mast cells or basophils throughout the body due to allergic reactions of type I, ie, anaphylaxis, mediated by IgE antibodies. It is thought to cause bronchial asthma.
  • type I ie, anaphylaxis
  • the therapeutic agent, oral medicine, and substance having an antihistamine effect obtained by fermenting the plant tissue of Stevia require a long period of 90 days or more to ferment the plant tissue.
  • An object of the present invention is to obtain a novel substance that improves the symptoms of anaphylactic allergy by shortening the period required for fermentation of stevia extract extracted from plant tissue of stevia, and to obtain the novel substance. Providing new manufacturing methods The purpose is to do so. Disclosure of the invention
  • the anaphylactic allergic symptom improving substance of the present invention is obtained by adding yeast to a stevia extract extracted from a plant tissue of stevia and fermenting the extract.
  • the stevia plant tissue is stevia leaves and stems.
  • the method for producing the anaphylactic allergic symptom improving substance of the present invention comprises the steps of pulverizing and mixing Stevia plant tissue, placing the mixture in purified water, heating, stirring, cooling, and filtering to obtain a filtrate. It is obtained by concentrating under reduced pressure to obtain a stevia extract, fermenting this stevia extract with yeast.
  • the plant tissue of Stevia is a leaf and stem of Stevia.
  • the filtrate under reduced pressure has a sugar content of about 8.
  • the fermentation period is 10 days or more.
  • FIG. 1 is a flow chart showing a production process of the substance of the present invention.
  • the substance for improving the symptoms of anaphylactic allergy of the present invention is As Stevia rebaudiana Bertoni in South America.
  • the upper leaves and stems of Stevia about 15 cm above the ground, are used.
  • the leaves and stems are dried, and both dried leaves and stems are ground to less than 10 microns.
  • crushed stevia leaf and stem are mixed at a ratio of 3:10 to obtain a stevia mixture, and 1 kg of this stevia mixture is placed in 120 liters of purified water and heated from room temperature, often gently. The extraction is continued for several hours while stirring.
  • the mixture is cooled to room temperature, and then filtered with a size of 140 mesh to obtain a filtrate.
  • the filtrate is taken out and further heated and stirred at a temperature of about 80 ° C for about 1 hour.
  • the sugar content is about 8 degrees (concentration under reduced pressure to a solid concentration of about 8w / vtt.
  • the concentrated solution is further filtered to a size of about 0.45 micrometer or less.
  • the obtained filtrate is used as a stevia extract, which is used as a raw material.
  • the fermentation period is 10 days or more, preferably 10 days to 14 days. Filtrate the solution fermented for about 10 S with a size of 0.45 micrometer or less to make it a complete solution.
  • the liquid purified by the above method has an antihistamine action.
  • a pharmacological experiment was conducted on the antihistamine effect of the guinea pig isolated ileum specimen using the substance of the present invention thus obtained.
  • the liquid obtained by the above method was used as a test liquid (referred to as Stevia test liquid), and this test liquid was freeze-dried.
  • the obtained solid (referred to as Stevia solid) was dissolved in a Lock-Ringer solution and used.
  • Nutrient solution using lock Ringer solution (mM) (Lock- Ringer solution (mM)), composition N a C 1 1 5 4, KC 1 5. 6, C a C l 2 2. 2, Mg C l 2 2.1, Na HCO 35.9, Glucose 2.8 (pH 7.4).
  • the drugs used were Stevia test solution, histamine ( ⁇ ko) (histamine (Wako)), and diphenhydramine ( ⁇ ko) (diphenhydramine (Wako)). Stevia solids were dissolved in Lock-Ringer solution and applied directly to Magnus tubes. The results obtained were judged to be significantly different by a Dunnett's multiple comparison test with a risk factor of 5%. -As a result, the effect of stevia on the histamine contractile response was observed.
  • the substance of the present invention was made into a cream form (referred to as stevia cream) and an extract form (referred to as stevia extract), and a skin sticking test was performed as a skin safety test of the stevia cream and the stevia extract.
  • the present invention has clarified for the first time that a liquid produced by fermenting a stevia extract with a yeast bacterium has an antihistamine action. This effect was reversible observed from stevia solid 1 0- 5 g / ral or more concentrations. It was concluded that the antihistamine action of Stevia solid was a histamine H i (histamine H i) receptor blocking action. This mechanism of action is thought to be due to the fact that stevia solids bind to the histamine Hi receptor and suppress the histamine expression effect. It was shown that the liquid (Stevia test solution) produced by fermenting the stevia extract with yeast bacteria contained a compound showing an antihistamine action. If the substance of the present invention is anaphylactic allergy It has been shown to be effective in reducing symptoms for diseases such as hay fever, measles, bronchial asthma or atopy.
  • a substance capable of improving the symptoms of anaphylactic allergy could be obtained in a relatively short period of time by fermenting stevia extract with yeast.

Abstract

It is intended to obtain novel agents for relieving anaphylactic allergic reactions and a novel process for producing the novel agents. Novel agents obtained by adding a yeast to a stevia plant extract obtained by extracting stevia plant tissues. Namely, stevia plant tissues are ground, mixed, added to purified water and heated. Then it is stirred, cooled and filtered. Then the filtrate thus obtained is concentrated under reduced pressure to give a stevia extract. Subsequently, a yeast is added to this stevia extract followed by fermentation.

Description

明 細 書 シー型アレルギー症状改善物質およびその製造方法  Description Sea type allergy symptom ameliorating substance and method for producing the same
技術分野 Technical field
本発明は、 花粉症、 羲麻疹、 気管支喘息、 アトピー症等の病因とされるァナフ イラキシー型アレルギー症状改善物質及ぴその製造方法に関する。  The present invention relates to a anaphylaxis-type allergic symptom ameliorating substance which is a cause of hay fever, measles measles, bronchial asthma, atopic disease and the like and a method for producing the same.
アナフィラキシーとは、 一般に免疫学的機序によって惹起される全身性のァレ ルギー反応をさす。 近年、 アレルギー疾患の中で I g E抗体を介する I型すなわ ちアナフィラキシー型のアレルギー反応により、 肥満細胞あるいは好塩基球から ヒスタミンやロイコ トリェンが全身に遊離されるため、 花粉症、 蓴麻疹、 気管支 喘息などを発症すると考えられている。 背景技術  Anaphylaxis generally refers to a systemic allergic reaction triggered by immunological mechanisms. In recent years, in allergic diseases, histamine and leukotriene are released from mast cells or basophils throughout the body due to allergic reactions of type I, ie, anaphylaxis, mediated by IgE antibodies. It is thought to cause bronchial asthma. Background art
アトピー症皮膚炎等に有効とされる外用皮膚病治療剤として、 あるいは胃炎、 胃カイョゥ等に有効とされる消化器系疾患治療用内服薬として、 ステビア茎部の 発酵濃縮液を有効成分とするものが知られている (特公平 6— 9 2 3 1 4号、 特 公平 7 _ 1 3 0 2 1号)。  As an active ingredient for external dermatitis, which is effective for atopic dermatitis, etc., or as an internal medicine for treating gastrointestinal diseases, which is effective for gastritis, stomach disease, etc. Are known (Japanese Patent Publication No. Hei 6—9 2 3 14 No. 7, Japanese Patent Publication No. 7 _ 1 3 0 2 1).
さらに、 花粉症等のアレルギー症状に有効とされる抗ヒスタミン作用を有する 物質として、 ステビアの植物組織の抽出液を発酵させたものが知られている (特 開平 1 0— 3 3 0 2 7 9号)。  Furthermore, as a substance having an antihistamine action that is effective for allergic symptoms such as hay fever, a substance obtained by fermenting an extract of a plant tissue of Stevia is known (Japanese Patent Laid-Open Publication No. Hei 10-330-279). issue).
上記ステビアの植物組織を発酵させて得た治療剤、 内服薬剤、 抗ヒスタミン作 用を有する物質は、 それぞれその植物組織の発酵に 9 0日以上の長期の期間が必 要である。  The therapeutic agent, oral medicine, and substance having an antihistamine effect obtained by fermenting the plant tissue of Stevia require a long period of 90 days or more to ferment the plant tissue.
本発明は、 ステビアの植物組織から抽出したステビアエキスの発酵に要する期 間を短縮して、 新規なアナフィラキシー型アレルギーの症状を改善させる物質を 得ることを目的とするとともに、 該新規な物質を得る新規な製造方法を提供する ことを目的とするものである。 発明の開示 An object of the present invention is to obtain a novel substance that improves the symptoms of anaphylactic allergy by shortening the period required for fermentation of stevia extract extracted from plant tissue of stevia, and to obtain the novel substance. Providing new manufacturing methods The purpose is to do so. Disclosure of the invention
そのために本発明アナフィラキシー型アレルギー症状改善物質は、 ステビアの 植物組織から抽出したステビアエキスにイース ト菌を加えて発酵させてなるもの である。  Therefore, the anaphylactic allergic symptom improving substance of the present invention is obtained by adding yeast to a stevia extract extracted from a plant tissue of stevia and fermenting the extract.
そして、 上記ステビアの植物組織がステビアの葉と茎である。  The stevia plant tissue is stevia leaves and stems.
また、 本発明アナフィラキシー型アレルギー症状改善物質の製造方法は、 ステ ビアの植物組織を粉砕、 混合し、 これを精製水に入れて加熱、 攪拌、 冷却、 ろ過 してろ液を得、 このろ液を減圧濃縮してステビアエキスを得て、 このステビアェ キスにィースト菌を加えて発酵させてなるものである。  Further, the method for producing the anaphylactic allergic symptom improving substance of the present invention comprises the steps of pulverizing and mixing Stevia plant tissue, placing the mixture in purified water, heating, stirring, cooling, and filtering to obtain a filtrate. It is obtained by concentrating under reduced pressure to obtain a stevia extract, fermenting this stevia extract with yeast.
上記製造方法において、 ステビアの植物組織がステビアの葉と茎である。 また、 上記ろ液の減圧濃度は糖度 8程度である。  In the above production method, the plant tissue of Stevia is a leaf and stem of Stevia. The filtrate under reduced pressure has a sugar content of about 8.
さらに、 上記発酵期間が 1 0日以上である。 図面の簡単な説明  Further, the fermentation period is 10 days or more. BRIEF DESCRIPTION OF THE FIGURES
第 1図 本発明物質の製造工程を示すフローチャート。  FIG. 1 is a flow chart showing a production process of the substance of the present invention.
第 2図 モルモッ ト摘出回腸標本においてヒスタミン (10—6M) により誘発 される収縮反応に及ぼすステビアの影響を示す図。 それぞれの値は 5例の平均値 土標準誤差を示す。 ステビアエキスは低い濃度から 1 0— 3 g/rnlまでの範囲で適 用した。 Shows the effect of stevia on contractile response induced by histamine (10- 6 M) in FIG. 2 guinea pig isolated ileum specimen. Each value represents the average value of 5 cases. Stevia extract was applied in a range of from a low concentration to 1 0- 3 g / rnl.
第 3図 モルモッ ト摘出回腸標本においてヒスタミン (10— 6M) により誘発 される収縮反応に及ぼすステビア 1 0— 5 M、 1 0— 4 M、 1 0— 3 g/mlの影響を 示す図。 発明を実施するための最良の形態 Shows the effect of Figure 3 guinea pig isolated histamine in the ileum specimen (10- 6 M) stevia 1 0 5 on the the contractile response elicited by M, 1 0- 4 M, 1 0- 3 g / ml. BEST MODE FOR CARRYING OUT THE INVENTION
本発明のアナフィラキシー型アレルギーの症状を改善させる物質は、 その原料 を南米のステビァ · レノ ウディ了ナ -ベノレトニ (Stevia rebaudiana Bertoni) とする。 The substance for improving the symptoms of anaphylactic allergy of the present invention is As Stevia rebaudiana Bertoni in South America.
先ず、 ステビアの地上部、 地面からおよそ 1 5 cm程から上部の葉と茎を用い、 これを乾燥させて乾燥させた葉部、 茎部を双方とも 1 0ミクロンメートル以下に 粉砕する。  First, the upper leaves and stems of Stevia, about 15 cm above the ground, are used. The leaves and stems are dried, and both dried leaves and stems are ground to less than 10 microns.
粉砕したステビアの葉部と茎部を 3 : 1 0の割合で混合し、 ステビア混合物を 得て、 このステビア混合物 1 O kgを精製水 1 2 0リツトルに入れ、 常温より加熱 して、 しばしば穏やかに撹拌しながら数時間抽出を続ける。  The crushed stevia leaf and stem are mixed at a ratio of 3:10 to obtain a stevia mixture, and 1 kg of this stevia mixture is placed in 120 liters of purified water and heated from room temperature, often gently. The extraction is continued for several hours while stirring.
その後常温まで冷却し、 その後 1 4 0メッシュの大きさでろ過を行ないろ液を 得る。  Thereafter, the mixture is cooled to room temperature, and then filtered with a size of 140 mesh to obtain a filtrate.
このろ液を取り出し、 これをさらに 8 0 °Cほどの温度で 1時間ほど加熱撹拌を 行なう。  The filtrate is taken out and further heated and stirred at a temperature of about 80 ° C for about 1 hour.
上記ろ液を加熱撹拌後、 糖度 8度ほど (固形物濃度およそ 8w/vtt まで減圧濃 縮を行なう。  After heating and stirring the above filtrate, the sugar content is about 8 degrees (concentration under reduced pressure to a solid concentration of about 8w / vtt.
濃縮された溶液をさらにほぼ 0 . 4 5マイクロメートル以下の大きさにてろ過 する。 得られたろ液をステビアエキスとし、 これを原料とする。  The concentrated solution is further filtered to a size of about 0.45 micrometer or less. The obtained filtrate is used as a stevia extract, which is used as a raw material.
上記工程で得たステビアエキス 1リットルにっき、 およそ 2 . 0 gの乾燥ィー ス ト菌を加え、 常温にて穏やかに撹拌し、 他の微生物の侵入を認めない条件下に て、 発酵を行なう。 乾燥イース ト菌はサッカロマイセス (Saccharomyces) 類を 用いる。  To 1 liter of the stevia extract obtained in the above process, add about 2.0 g of dried yeast, stir gently at room temperature, and perform fermentation under conditions that prevent the invasion of other microorganisms. . Saccharomyces are used as the dry yeast.
この発酵期間は 1 0日間以上とするが、 望ましくは 1 0日〜 1 4日間とする。 1 0 S程発酵させた液を 0 . 4 5マイクロメーター以下の大きさにてろ過を行な レ、、 完全に溶液状態とする。 以上の方法で精製された液体が抗ヒスタミン作用を 有する。  The fermentation period is 10 days or more, preferably 10 days to 14 days. Filtrate the solution fermented for about 10 S with a size of 0.45 micrometer or less to make it a complete solution. The liquid purified by the above method has an antihistamine action.
このようにして得た本発明物質によってモルモッ ト摘出回腸標本における、 抗 ヒスタミン作用に関し薬理学的実験を行った。 実験では、 上記製法にて得られた 液体を試験液 (ステビア試験液という) とし、 この試験液を凍結乾燥処理し、 得 られた固形物 (ステビア固形物という) を、 ロックリ ンガー液 (Lock-Ringer液) に溶解して用いた。 A pharmacological experiment was conducted on the antihistamine effect of the guinea pig isolated ileum specimen using the substance of the present invention thus obtained. In the experiment, the liquid obtained by the above method was used as a test liquid (referred to as Stevia test liquid), and this test liquid was freeze-dried. The obtained solid (referred to as Stevia solid) was dissolved in a Lock-Ringer solution and used.
実験には雄性モルモット (Hartley系、 3 0 0〜3 5 0 g) 2 0匹を用いた。 モルモットより回腸を摘出しマグヌス法によりヒスタミンによって誘発される等 尺性収縮を測定した。 収縮は張力トランスジューサー (BG- 10,Kulite Semicon ductor、 U.S. A) を介し直流増幅器 (AM 20、 Unipulse) にて記録した。 ステビア 固形物 (1 0— 6 、 1 0— 5、 1 0— 4、 1 0— 3g/ml) をあらかじめモルモッ ト摘 出回腸に適用し、 ヒスタミン 1 0— 6 M (histamine 1 0—6 M) による収縮反 応を検討した。 抗ヒスタミン薬であるジフェインヒドラミンを対照薬として比較 検討した。 栄養液はロックリンガー液 (mM) (Lock- Ringer液 (mM)) を用い、 組成は N a C 1 1 5 4、 KC 1 5. 6、 C a C l 2 2. 2、 Mg C l 2 2. 1、 N a H C O 3 5. 9、 Glucose 2. 8 (pH 7.4) であった。 栄養液 は 9 5 %02と 5 %C 02の混合ガスを通気した。 実験は室温 (2 3〜24°C) で行なった。 使用した薬物は、 ステビア試験液、 ヒスタミン (ヮコ) (histamin e (Wako) )、 ジフェインヒ ドラミン (ヮコ) (diphenhydramine (Wako) ) であつ た。 ステビア固形物はロックリンガー液 (Lock-Ringer液) に溶解させマグヌス 管に直接適用した。 得られた成績はダネット (Dunnett' s) のマルチプル コン パリソン テスト (multiple comparison test) により危険率 5 %をもって有意 差ありとした。 - その結果、 ヒスタミンの収縮反応の及ぼすステビアの影響を観た。 Twenty male guinea pigs (Hartley strain, 300 to 350 g) were used in the experiment. The ileum was removed from guinea pigs, and isometric contraction induced by histamine was measured by the Magnus method. Contractions were recorded with a DC amplifier (AM 20, Unipulse) via a tension transducer (BG-10, Kulite Semiconductor, USA). Stevia solid (1 0- 6, 1 0- 5 , 1 0- 4, 1 0- 3 g / ml) was applied to pre-guinea pig hysterectomy out ileum, histamine 1 0- 6 M (histamine 1 0- 6 M) was studied. A comparative study was conducted using dipheninhydramine, an antihistamine, as a control. Nutrient solution using lock Ringer solution (mM) (Lock- Ringer solution (mM)), composition N a C 1 1 5 4, KC 1 5. 6, C a C l 2 2. 2, Mg C l 2 2.1, Na HCO 35.9, Glucose 2.8 (pH 7.4). Nutrient solution was aerated with 95% 0 2 and 5% mixed gas of C 0 2. The experiments were performed at room temperature (23-24 ° C). The drugs used were Stevia test solution, histamine (ヮ ko) (histamine (Wako)), and diphenhydramine (ヮ ko) (diphenhydramine (Wako)). Stevia solids were dissolved in Lock-Ringer solution and applied directly to Magnus tubes. The results obtained were judged to be significantly different by a Dunnett's multiple comparison test with a risk factor of 5%. -As a result, the effect of stevia on the histamine contractile response was observed.
ヒスタミン 1 0— 6 M (Histamine 1 0— 6 M) をモノレモッ ト摘出回腸標本に適 用すると収縮が誘発される。 ヒスタミン (Histamine) は 2回適用して定常状態 になったことを確認してコントロールとした。 図 1は 5例のヒスタミン (histam ine) 収縮反応に及ぼすステビア固形物の影響を検討したものである。 ヒスタミ ン (Histamine) の収縮反応はステビア固形物 1 0— 6 g/mlはその収縮反応に対し て影響を及ぼさなかった。 ステビア固形物 1 0—5、 1 0— 4、 1 0— 3g/mlでは ヒスタミン (histamine) による収縮反応をそれぞれコントロールの 9 3 %、 7 8 %、 5 5 %に減少させた (図 1, 2 )。 ステビア固形物 1 0 - 3 g/mlは有意な抑 制を示した。 これらステビア固形物による反応はステビア固形物を洗浄すること により回復したことから可逆性であった。 Shrinkage to apply histamine 1 0- 6 M (Histamine 1 0- 6 M) in Monoremo' bets isolated ileum specimen is induced. Histamine was applied twice to confirm that it was in a steady state and was used as a control. Figure 1 shows the effect of stevia solids on the histamine contractile response in five cases. Contractile responses of Hisutami emissions (Histamine) Stevia solid 1 0- 6 g / ml had no effect with respect to the contractile response. Stevia solid 1 0- 5, 1 0- 4, 1 0- 3 g / 9 3% of each control contractile responses by ml in histamine (histamine), 7 8% and 55% (Figs. 1 and 2). Stevia solid 1 0 - 3 g / ml showed a significant suppression. The reaction with these stevia solids was reversible because they were recovered by washing the stevia solids.
上記本発明物質をクリーム状 (ステビアクリームと云う) とエキス状 (ステビ ァエキスと云う) にして、 このステビアク リーム及びステビアエキスの皮膚安全 試験として、 皮膚貼付試験をした。  The substance of the present invention was made into a cream form (referred to as stevia cream) and an extract form (referred to as stevia extract), and a skin sticking test was performed as a skin safety test of the stevia cream and the stevia extract.
この試験は、 富山県富山巿杉谷 2 6 3 0番地の富山医科薬科大学医学部皮膚科 学教室 (医学博士、 諸橋正昭教授) にて豊田雅彦講師が試験責任者となって行わ れた。  This test was conducted by Lecturer Masahiko Toyoda at the Toyama Medical and Pharmaceutical University School of Medicine Department of Dermatology at 2630, Toyama, Suyama, Toyama Prefecture (Doctor of Medicine, Professor Masaaki Morohashi).
この試験は、 健常人 1 8名 (男性 1 2名、 女性 6名、 年齢 2 1〜4 3歳、 平均 年齢 3 2 . 5歳) を対象に行われた。 その方法は、 ステビアクリーム及びステビ ァエキスを両者とも as isにてフィンチャンバ一を用いて上腕内側あるいは背部 に貼付し、 4 8時間後および 7 2時間後に貼付試験の評価を行った。 評価判定は I C D R G基準の評価法にのっとって行った。 The study was conducted on 18 healthy individuals (12 males, 6 females, ages 21 to 43, average age 32.5). In this method, both the stevia cream and the stevia extract were applied to the inner side of the upper arm or the back of the upper arm using a fin chamber as is, and the adhesion test was evaluated 48 hours and 72 hours later. Evaluation was performed according to the ICDRG standard evaluation method.
結果は、 ステビアクリーム及びステビアエキスの貼付試験を施行した 1 8名全 例において、 貼付後 4 8時間後及び 7 2時間後ともいずれの物質も陽性反応 (一 時刺激、 接触皮膚炎) を示さなかった。 産業上の利用の可能性  As a result, in all of the 18 subjects who performed the application test of stevia cream and stevia extract, all the substances showed a positive reaction (temporary irritation, contact dermatitis) at 48 hours and 72 hours after application. Did not. Industrial applicability
本発明は、ステビア抽出エキスをィースト菌にて発酵させて生成された液体が、 抗ヒスタミン作用を有することを初めて明らかにした。 この作用はステビア固形 物 1 0— 5 g/ral以上の濃度より観察され可逆的であった。 ステビア固形物の抗 ヒスタミン作用はヒスタミン H i (histamineH i )受容体の遮断作用と結論した。 この作用機序はステビア固形物がヒスタミンの H i受容体に結合し、 ヒスタミン の発現作用を抑制すると考えられる。 ステビア抽出エキスをイース ト菌にて発酵 させて生成された液体 (ステビア試験液) の中に抗ヒスタミン作用を示す化合物 が含まれていることが示された。 本発明物質がアナフィラキシー型アレルギーで ある、 花粉症、 奪麻疹、 気管支喘息あるいはアトピーなどの疾患に対する症状の 軽減に有効であることが示された。 The present invention has clarified for the first time that a liquid produced by fermenting a stevia extract with a yeast bacterium has an antihistamine action. This effect was reversible observed from stevia solid 1 0- 5 g / ral or more concentrations. It was concluded that the antihistamine action of Stevia solid was a histamine H i (histamine H i) receptor blocking action. This mechanism of action is thought to be due to the fact that stevia solids bind to the histamine Hi receptor and suppress the histamine expression effect. It was shown that the liquid (Stevia test solution) produced by fermenting the stevia extract with yeast bacteria contained a compound showing an antihistamine action. If the substance of the present invention is anaphylactic allergy It has been shown to be effective in reducing symptoms for diseases such as hay fever, measles, bronchial asthma or atopy.
さらに本発明方法では、 ステビアエキスにィースト菌を加えて発酵させること により、 比較的短期間でアナフィラキシー型アレルギーの症状を改善させる物質 を得ることができた。  Furthermore, in the method of the present invention, a substance capable of improving the symptoms of anaphylactic allergy could be obtained in a relatively short period of time by fermenting stevia extract with yeast.

Claims

請 求 の 範 囲 The scope of the claims
1 . ステビアの植物組織から抽出したステビアエキスにィースト菌を加えて発酵 させ生成されるアナフィラキシー型ァレルギ一症状改善物質。 1. An anaphylactic allergic symptom ameliorating substance produced by the addition of yeast and fermentation to stevia extract extracted from plant tissues of stevia.
2 . 上記ステビアの植物組織がステビアの葉と茎である上記請求項 1に記載のァ ナフイラキシー型アレルギー症状改善物質。  2. The anaphylactic allergy symptom improving substance according to claim 1, wherein the stevia plant tissue is stevia leaves and stems.
3 . ステビアの植物組織を粉碎、 混合し精製水に入れて加熱、 攪袢、 冷却、 ろ過 してろ液を得、 このろ液を減圧濃縮してステビアエキスを得て、 このステビアェ キスにィースト菌を加えて発酵させてなるアナフィラキシー型アレルギー症状改 善物質の製造方法。  3. Stevia plant tissue is ground, mixed, put in purified water, heated, stirred, cooled, and filtered to obtain a filtrate, and the filtrate is concentrated under reduced pressure to obtain a stevia extract. A method for producing an anaphylactic type allergic symptom ameliorating substance, which is fermented by adding to a mixture.
4 . ステビアの植物組織がステビアの葉と茎である上記請求項 3に記载のァナフ ィラキシー型ァレルギ一症状改善物質の製造方法。  4. The method for producing a anaphylaxis type allergic symptom improving substance according to claim 3, wherein the plant tissue of Stevia is stevia leaves and stems.
5 . 上記減圧濃縮して得られたろ液の濃度が糖度 8程度である上記請求項 3又は 4に記載のアナフィラキシー型アレルギー症状改善物質の製造方法。  5. The method for producing an anaphylactic allergic symptom improving substance according to claim 3 or 4, wherein the filtrate obtained by concentration under reduced pressure has a sugar content of about 8.
6 . 上記発酵期間が 1 0日以上である上記請求項 3〜5の何れかに記載のァナフ ィラキシー型ァレルギ一症状改善物質の製造方法。 6. The method for producing a anaphylaxis type allergic symptom improving substance according to any one of claims 3 to 5, wherein the fermentation period is 10 days or more.
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