JP2005035888A - Substance for ameliorating anaphylactic type allergic symptom and method for producing the same - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a new substance for ameliorating anaphylactic type allergic symptoms and to provide a new method for obtaining the new substance. <P>SOLUTION: A yeast fungus is added to ferment a stevia extract obtained by extraction from a plant tissue of the stevia. In the method, the plant tissue of the stevia is pulverized and mixed and the resultant mixture is introduced into purified water, heated, stirred, cooled and filtered to afford a filtrate. The resultant filtrate is then vacuum concentrated to provide the stevia extract. The yeast fungus is added to ferment the stevia extract. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

[0001]
BACKGROUND OF THE INVENTION
The present invention relates to an anaphylactic-type allergic symptom-improving substance which is considered to be an etiology such as hay fever, urticaria, bronchial asthma and atopy, and a method for producing the same.
[0002]
Anaphylaxis refers to a systemic allergic reaction that is generally caused by an immunological mechanism. Recently, histamine and leukotrienes are released from mast cells or basophils throughout the body due to allergic reactions of type I, ie, anaphylaxis, through IgE antibodies among allergic diseases, causing hay fever, urticaria and bronchial asthma It is considered to be.
[0003]
[Prior art]
As a therapeutic agent for external dermatitis effective for atopic dermatitis, etc., or as an internal medicine for treatment of digestive system diseases effective for gastritis, stomach moss, etc. Are known (Japanese Patent Publication No. 6-92314, Japanese Patent Publication No. 7-13021).
Further, as a substance having an antihistaminic action that is effective for allergic symptoms such as pollinosis, fermented stevia plant tissue extract is known (Japanese Patent Laid-Open No. 10-330279).
[0004]
[Problems to be solved by the invention]
The therapeutic agent obtained by fermenting the above Stevia plant tissue, the internal medicine, and the substance having an antihistamine action each require a long period of 90 days or longer for fermentation of the plant tissue.
An object of the present invention is to obtain a novel substance that improves the symptoms of anaphylaxis-type allergy by shortening the time required for fermentation of stevia extract extracted from a plant tissue of stevia, and to obtain the novel substance An object of the present invention is to provide a simple manufacturing method.
[0005]
[Means for Solving the Problems]
Therefore, the anaphylaxis type allergic symptom-improving substance of the present invention is obtained by adding yeast to fermented stevia extract extracted from stevia plant tissue and fermenting it.
The Stevia plant tissues are Stevia leaves and stems.
[0006]
In addition, the method for producing an anaphylaxis type allergy symptom-improving material of the present invention is obtained by pulverizing and mixing stevia plant tissue, putting it in purified water, heating, stirring, cooling and filtering to obtain a filtrate, and reducing the filtrate under reduced pressure. A stevia extract is obtained by concentration, and yeast is added to this stevia extract and fermented.
[0007]
In the above production method, Stevia plant tissues are Stevia leaves and stems.
The reduced pressure concentration of the filtrate is about 8 in sugar content.
Furthermore, the said fermentation period is 10 days or more.
[0008]
DETAILED DESCRIPTION OF THE INVENTION
The substance for improving the symptom of anaphylaxis type allergy of the present invention is made from Stevia rebaudiana Bertoni of South America.
[0009]
First, the upper leaves and stems from the ground part of Stevia and about 15 cm from the ground are used, and the dried leaves and stems are both pulverized to 10 microns or less.
The crushed stevia leaves and stems were mixed at a ratio of 3:10 to obtain a stevia mixture, 10 kg of this stevia mixture was put into 120 liters of purified water, heated from room temperature, and often with gentle stirring. Continue time extraction.
Thereafter, it is cooled to room temperature, and then filtered at 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 filtrate is heated and stirred, and then concentrated under reduced pressure to a sugar content of about 8 degrees (solid matter concentration: about 8 w / v%).
The concentrated solution is further filtered to a size of approximately 0.45 micrometers or less. The obtained filtrate is used as a stevia extract.
[0010]
About 1 liter of stevia extract obtained in the above step, about 2.0 g of dry yeast is added, and the mixture is gently stirred at room temperature, and fermentation is carried out under conditions where no other microorganisms are invaded. Saccharomyces are used as the dry yeast.
The fermentation period is 10 days or longer, preferably 10 to 14 days.
The liquid fermented for about 10 days is filtered at a size of 0.45 micrometers or less to make it completely in solution. The liquid purified by the above method has an antihistaminic action.
[0011]
Using the substance of the present invention thus obtained, a pharmacological experiment was conducted on the antihistamine action in the guinea pig isolated ileal specimen. In the experiment, the liquid obtained by the above production method was used as a test liquid (referred to as Stevia test liquid), this test liquid was freeze-dried, and the obtained solid (referred to as Stevia solid) was used as a Rock Ringer liquid (Lock- (Ringer solution).
In the experiment, 20 male guinea pigs (Hartley strain, 300 to 350 g) were used.
The ileum was removed from the guinea pig and the isometric contraction induced by histamine was measured by the Magnus method. Shrinkage was recorded with a DC amplifier (AM 20, Unipulse) via a tension transducer (BG-10, Kulite Semiconductor, USA). Stevia solids (10 ⁻⁶ , 10 ⁻⁵ , 10 ⁻⁴ , 10 ⁻³ g / ml) were applied in advance to the guinea pig excised ileum, and the contraction reaction by histamine 10 ⁻⁶ M (histamine 10 ⁻⁶ M) was examined. An antihistamine, diphein hydramine, was compared as a control drug. The nutrient solution used was Rock Ringer solution (mM) (Lock-Ringer solution (mM)), and the composition was NaCl 154, KCl 5.6, CaCl ₂ 2.2, MgCl ₂ 2.1, NaHCO ₃ 5.9, Glucose. It was 2.8 (pH 7.4). The nutrient solution was aerated with a mixed gas of 95% O ₂ and 5% CO ₂ . The experiment was performed at room temperature (23-24 ° C.). The drugs used were Stevia test solution, histamine (Wako), diphenhydramine (Wako), diphenhydramine (Wako). Stevia solids were dissolved in Rock Ringer solution (Lock-Ringer solution) and applied directly to the Magnus tube. The obtained results were significantly different from Dunnett's multiple comparison test with a risk rate of 5%.
[0012]
As a result, we observed the effect of stevia on the histamine contraction response.
Shrinkage histamine ^{10 -6} M (Histamine10 -6 M) and applied to isolated guinea pig ileum specimen is induced. Histamine was applied twice to confirm that it was in a steady state and used as a control. FIG. 1 examines the effects of stevia solids on the histamine contraction response of five cases. The contraction response of histamine did not affect the contraction response of stevia solids 10 ⁻⁶ g / ml. Stevia solids 10 ⁻⁵ , 10 ⁻⁴ and 10 ⁻³ g / ml reduced the contraction response due to histamine to 93%, 78% and 55% of the control, respectively (FIGS. 1 and 2). Stevia solids 10 ⁻³ g / ml showed significant inhibition. These reactions with stevia solids were reversible because they recovered by washing the stevia solids.
[0013]
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 patch test was conducted as a skin safety test for the stevia cream and stevia extract.
This test was conducted by Dr. Masahiko Toyoda at the Department of Dermatology, Toyama Medical and Pharmaceutical University School of Medicine, Dr. Masaaki Morohashi, 2630 Sugitani, Toyama, Toyama Prefecture.
This test was conducted on 18 healthy persons (12 males, 6 females, ages 21 to 43 years, average age 32.5 years). In this method, stevia cream and stevia extract were both applied to the inside or back of the upper arm using a fin chamber with as is, and the application test was evaluated 48 hours and 72 hours later. Evaluation was made according to the ICDRG standard evaluation method.
As a result, in all 18 patients who underwent a test for stevia cream and stevia extract, neither substance showed a positive reaction (temporary irritation, contact dermatitis) at 48 hours or 72 hours after application.
[0014]
【The invention's effect】
The present invention revealed for the first time that the liquid produced by fermenting stevia extract with yeast has antihistaminic activity. This effect was observed and reversible at concentrations of stevia solids of 10 ⁻⁵ g / ml or higher. Antihistaminic action of Stevia solids was concluded that blocking the action of histamine _{H 1 (histamineH} 1) receptor. This mechanism of action is considered that Stevia solids bind to the histamine H ₁ receptor and suppress the expression of histamine. It was shown that the liquid (stevia test liquid) produced by fermenting stevia extract with yeast bacteria contains a compound exhibiting antihistamine action. It was shown that the substance of the present invention is effective in reducing symptoms for diseases such as hay fever, urticaria, bronchial asthma or atopy, which are anaphylactic allergies.
Furthermore, in the method of the present invention, a substance capable of improving the symptoms of anaphylaxis-type allergy could be obtained in a relatively short period of time by adding yeast and fermenting to stevia extract.
[Brief description of the drawings]
FIG. 1 is a flowchart showing a production process of a substance of the present invention.
FIG. 2 shows the effect of stevia on the contractile response induced by histamine (10 ⁻⁶ M) in guinea pig isolated ileal specimens. Each value represents an average value ± standard error of 5 cases. Stevia extract was applied in the range from low concentration to 10 ⁻³ g / ml.
FIG. 3 is a graph showing the effect of stevia 10 ⁻⁵ M, 10 ⁻⁴ M, 10 ⁻³ g / ml on the contractile response induced by histamine (10 ⁻⁶ M) in guinea pig isolated ileal specimens.

Claims (6)

An anaphylactic allergy symptom-improving substance produced by adding yeast to fermented stevia extract extracted from stevia plant tissue. The anaphylactic-type allergic symptom-improving substance according to claim 1, wherein the stevia plant tissue is stevia leaves and stems. Stevia plant tissue is pulverized, mixed, put into purified water, heated, stirred, cooled, filtered to obtain a filtrate, and the filtrate is concentrated under reduced pressure to obtain stevia extract. A method for producing an anaphylactic allergy symptom-improving substance. The method for producing an anaphylaxis-type allergic symptom-improving substance according to claim 3, wherein the plant tissue of stevia is stevia leaves and stems. The method for producing an anaphylactic allergy 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. The method for producing an anaphylactic allergy 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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