CN101674841B - Anti-histamine substance and method for production thereof - Google Patents
Anti-histamine substance and method for production thereof Download PDFInfo
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- CN101674841B CN101674841B CN200880011345XA CN200880011345A CN101674841B CN 101674841 B CN101674841 B CN 101674841B CN 200880011345X A CN200880011345X A CN 200880011345XA CN 200880011345 A CN200880011345 A CN 200880011345A CN 101674841 B CN101674841 B CN 101674841B
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Abstract
Disclosed is a method for producing an anti-histamine substance, which comprises the steps of: adding an yeast cell and water to a dried Stevia plant tissue and causing the fermentation of the mixture; extracting a fermented Stevia product produced in the fermentation step with an aqueous ethanol solution; concentrating an extract produced in the extraction step; and fractionating a concentrated solution produced in the concentration step and collecting a 90% ethanol-soluble fraction.
Description
Technical field
The present invention relates to a kind of pollinosis, urticaria, bronchial asthma, spy answer disease etc. allergic symptom improve material and preparation method thereof.
Background technology
So-called allergy refers to that immunoreation occurs for specific antigen superfluously.Allergy roughly is divided into the I type to V-type by its mechanism, and pollinosis and urticaria, bronchial asthma belong to the I type.In addition, the spy answers disease also irritated approximate with the I type.It is generally acknowledged that I type allergy is that the histamine that discharges or leukotriene cause in the whole body migration owing to be combined with mastocyte or basophilic leukocyte by IgE antibody from these cells.
As to the effective external skin Remedies for diseases in association or as to the effective digestive system disease treatment oral medicine such as gastritis, gastric ulcer such as atopic dermatitis, known have with the Fermented Condensed liquid of the Folium Stevlae Rebaudianae stem material as effective ingredient.And then, as the material that has effective antihistamine effects of allergic symptom such as pollinosiss, the known material that the extracting solution fermentation of the plant tissue that makes Folium Stevlae Rebaudianae is arranged and obtain.
And then, the long problem of fermentation needs more than 90 days in view of stevioside plant tissue in above-mentioned technology, for the required time of the fermentation that can shorten Stevia rebaudiana (Bertoni) Hemsl extract, the material of allergic symptom can improve simultaneously, the inventor disclosed the preparation method that a kind of allergic symptom improves material in the past, it is characterized in that, the plant tissue of Folium Stevlae Rebaudianae is pulverized, mix, join in the Purified Water, heating is stirred, cooling, filtration obtains filtrate, this filtrate decompression is concentrated, obtain Stevia rebaudiana (Bertoni) Hemsl extract, add yeast in this Stevia rebaudiana (Bertoni) Hemsl extract to make it fermentation (referring to JP 2005-35888 communique).
As mentioned above, open and sold multiple pollinosis and the special material that improves of answering disease etc., but compare the improvement degree of further raising allergic symptom with present degree, be the common aspiration of most of patients.In the present situation, people seek the allergic symptom more excellent than existing material and improve material, research and develop with great concentration.
Summary of the invention
The object of the invention is to, in order to improve especially I type allergic symptom, provide a kind of material with antihistamine effect more excellent than existing material.
In order to solve above-mentioned problem, carried out repeatedly research, the inventor has successfully made with stevioside plant and has been organized as material raw material, that have the antihistamine effect more excellent than existing material as a result.Preparation method with anti-histamine substance of the present invention of above-mentioned effect is characterised in that, comprises the steps: to add in the stevioside plant tissue of drying the step that yeast and water make it to ferment; Extract the step of the fermentation Folium Stevlae Rebaudianae that is obtained by this fermentation step with ethanol water; The step that will be concentrated by the extracting solution that this extraction step obtains; The concentrated solution fractionated that will be obtained by this concentration step, the step of collecting the solvable fraction of 90% ethanol.
The inventor finds can confirm to have strong antihistamine effect by the material that above-mentioned preparation method obtains.Therefore, this material can be widely used in being particularly suitable for presenting the patient's of I type allergic symptom cosmetic product and external preparation, Oral preparation etc.
And the material that is obtained by above-mentioned preparation method does not produce the abnormal smells from the patient that makes the people unhappy fully.With respect to this, when being had by the anti-histamine substance that obtains of preparation method of record in the above-mentioned patent documentation 1 with allowing the problem of the unhappy abnormal smells from the patient of people.There are not the problems referred to above in the material that is obtained by the present invention, when therefore cooperating in external preparation, particularly cosmetic product, has than the wieldy obvious advantage of existing material.Therefore, the present invention comprises cosmetic product and the medicine (using agent in the external preparation) that contains the material that is obtained by above-mentioned preparation method in its scope.
The specific embodiment
Below, explain embodiments of the present invention with accompanying drawing.
At first, explain the preparation method of anti-histamine substance of the present invention according to the flow chart of Fig. 1.
Step 1 is with the step as the plant tissue drying and crushing of the Folium Stevlae Rebaudianae of raw material.Stevioside plant as one of raw material of the present invention is the perennial plant that originates in the Compositae of South America Paraguay, and formal name used at school is Folium Stevlae Rebaudianae (Stevia Rebaudiana Bertoni).When Japan cultivates, usually through February to May, with seed, young plant or the Seedling field planting of transplanting, begin cultivation.Generally gather in the crops about ripe October to early November fully at stevioside plant.
Anti-histamine substance of the present invention is so that the plant tissue of this Folium Stevlae Rebaudianae dry Folium Stevlae Rebaudianae powder fully dry, that its fine pulverizing is made is used as raw material.So-called powder is so long as be ground into the size of each sheet general for to get final product below the 1cm.In addition, the leaf section and the stem that preferably select stevioside plant use.
In the drying of the leaf section of stevioside plant and stem preferred as far as possible take a breath indoor, carry out at normal temperatures, preferably sharply do not heat etc.
Step 2 is the steps that make the dry Folium Stevlae Rebaudianae powder fermentation that obtains in the step 1.As mentioned above, one of feature of the preparation method of anti-histamine substance of the present invention is, makes the direct fermentation of dry Folium Stevlae Rebaudianae powder.With respect to this, in the disclosed preparation method of above-mentioned JP 2005-35888 communique, according at first from dry Folium Stevlae Rebaudianae powder, extracting extract, again the order of this extraction extract fermentation being carried out.But, show according to inventor's result of study subsequently, make the method for dry Folium Stevlae Rebaudianae powder direct fermentation can prepare the strong material of antihistamine effect.
The fermentation of dry Folium Stevlae Rebaudianae powder can followingly be carried out: add entry and yeast in dry Folium Stevlae Rebaudianae powder, with its stirring, place.Add the amount of entry so long as the required amount of fermenting gets final product, the amount of the degree that integral body is moistening is fully to measure.As yeast, preferably use yeast (Saccharomyces) to belong to.
The fermentation of dry Folium Stevlae Rebaudianae powder preferred " fully " is carried out.If lick and taste the Folium Stevlae Rebaudianae powder that do not have fermentation then pleasantly sweet, but unconfirmed to sweet taste through the Folium Stevlae Rebaudianae powder of complete fermentation.Therefore, preferably ferment until complete imperceptible sweet taste.In order to make it fully to ferment, in the situation of room temperature, need to place the time in general 2～3 weeks.
The kind of yeast uses yeast (Saccharomyces) to belong to.In the step of fermentation, at first, make in the dry Folium Stevlae Rebaudianae powder and contain moisture, then, add above-mentioned yeast, make it continue fermentation while keep the skin wet at normal temperatures during 2～3 weeks.Judge that whether the fermentation of Folium Stevlae Rebaudianae powder is carried out " fully ", for example can carry out as follows: the Folium Stevlae Rebaudianae powder is kept in the mouth, the moment of imperceptible its sweet taste is regarded as " fully " fermentation ends.
Ethanol extraction can followingly carry out: prepare about 30% ethanol water, to wherein adding fermentation Folium Stevlae Rebaudianae powder, Yi Bian Yi Bian leniently stirring makes it to infiltrate a few hours～a few days at normal temperatures.With its filtration of large young pathbreaker about 140 orders, with gained filtrate as extracting solution.In the preparation method of the present invention, with said extracted liquid further concentrating under reduced pressure, thus concentrated extracting solution under the temperature about 60 ℃.
For the ease of preserving carrying, also can the solvable fraction lyophilization of 90% ethanol (step 5) of separation will be graded.Thus, finished the preparation process of the anti-histamine substance of the preferred embodiment for the present invention.
＜test example 〉
The step 1 shown in Figure 1 to process～5 materials of the present invention that obtain, use isolated ileum segments in guinea pigs specimen is carried out the pharmacology test about antihistamine effect.Test following carrying out: from Cavia porcellus, extract ileum, measure the isometric property contraction of being brought out by histamine according to the Magnus method.
With histamine 10
-6M (histamine10
-6When M) being used for the isolated ileum segments in guinea pigs specimen, can bring out contraction.Therefore, in the front and back of using the material of the present invention that is obtained by above-mentioned method for making, use histamine 10
-6M, the difference of observing contractile response is investigated material of the present invention thus on the impact of contractile response.Shrink by tension transducer (BG-10, Kulite Semiconductor, U.S.A) and carry out record with direct current amplifier (AM20 processed of Unipulse Co., Ltd.).Histamine uses the product of Wako Pure Chemical Industries, Ltd.'s system.
In order to use material of the present invention, make substance dissolves of the present invention in as the Luo of nutritional solution-Lin liquid (Locke-Ringer liquid), make test solution.Make 3 kinds of different test solutions of concentration of material of the present invention, the concentration of regulating respectively material of the present invention makes it be respectively 10
-5G/ml, 10
-4G/ml, 10
-3G/ml.Test solution directly uses in the Magnus pipe.
Luo-Lin liquid consist of NaCl=154, KCl=5.6, CaCl
2=2.2, MgCl
2=2.1, NaHCO
3=5.9, Glucose=2.8 (pH=7.4).Nutritional solution passes into 95%O
2And 5%CO
2Mist.
Experiment is carried out under room temperature (23～24 ℃).
Experimental result is shown in Fig. 2 A～Fig. 2 C.Fig. 2 A is material concentration 10 of the present invention
-5The experimental result of the test solution of g/ml.At the 6th hour 22 minutes with 10
-6The histamine of mole is used for the isolated ileum segments in guinea pigs specimen, measures contractile response, with it in contrast.After the contraction of specimen finishes, at the 6th hour 30 minutes with material concentration 10 of the present invention
-5The test solution of g/ml is used for specimen, so at the 6th hour 33 minutes again with histamine 10
-6Mole is used for specimen.The recording curve figure that is obtained by the AM20 processed of Unipulse Co., Ltd. in the said determination is shown in Fig. 2 A.
The transverse axis express time of the curve chart of Fig. 2 A, 1 lattice represent 2 minutes.The longitudinal axis represents voltage, with the amplitude of the contraction of ileum specimen roughly proportional (Fig. 2 B, Fig. 2 C is same).The amplitude of the contraction when using histamine take the first time was as 100 o'clock, and the amplitude of the contraction when using histamine for the second time can be read as 89.7 on curve chart.The amplitude of shrinking when for the second time using histamine diminishes, and the antihistamine effect of being commonly considered as test solution causes.
Fig. 2 B is material concentration 10 of the present invention
-4The experimental result of the test solution of g/ml similarly is the recording curve figure that is obtained by the AM20 processed of Unipulse Co., Ltd..Be used for the isolated ileum segments in guinea pigs specimen at the 4th hour 47 minutes histamine with the 10-6 mole, measure contractile response, with it in contrast.After the contraction of specimen finishes, at the 4th hour 55 minutes with material concentration 10 of the present invention
-4The test solution of g/ml is used for specimen, so at the 4th hour 58 minutes again with histamine 10
-6Mole is used for specimen.
The material concentration of the present invention of test solution is 10
-4During g/ml, the shrinkage amplitude (magnitude of voltage of direct current amplifier) when using histamine take the first time was as 100 o'clock, and the shrinkage amplitude when using histamine for the second time can be read as 60 on curve chart.Therefore, be 10 with material concentration of the present invention as can be known
-5The situation of g/ml is compared and has been brought into play stronger antihistamine effect.
Fig. 2 C is expression material concentration 10 of the present invention
-3The recording curve figure of the experimental result of the test solution of g/ml.At the 6th hour 40 minutes with 10
-6The histamine of mole is used for the isolated ileum segments in guinea pigs specimen, measures contractile response, with it in contrast.After the contraction of specimen finishes, at the 6th hour 50 minutes with material concentration 10 of the present invention
-3The test solution of g/ml is used for specimen, so at the 6th hour 52 minutes again with histamine 10
-6Mole is used for specimen.
By Fig. 2 C as can be known, the material concentration of the present invention of test solution is 10
-3During g/ml, when using histamine for the second time, specimen does not show contractile response fully.This is the wonderful result that the inventor does not expect fully.In view of the above results, can think that the antihistamine effect of material of the present invention is very strong, far surpass present known level.
Fig. 3 is the curve chart that the experimental result of Fig. 2 A～C is concluded, and transverse axis represents the logarithm of the material concentration of the present invention in the test solution, and the longitudinal axis represents to use the ratio of contractile response measured value and contrast behind the test solution.Can be readily seen that thus contractile response is die-offed along with the material concentration of the present invention in the test solution increases.
More than, provided anti-histamine substance of the present invention preparation method detailed step and show the experimental result of the effect of the anti-histamine substance that preparation method thus prepares.Shown that by experimental result anti-histamine substance of the present invention has wonderful antihistamine effect.Therefore, anti-histamine substance of the present invention can be widely used in cosmetic product and medicine, particularly, can expect to be applied to be fit to pollinosis and special cosmetic product and the medicine of answering the patient of the I type allergy such as disease or presenting the patient of similar symptom.And anti-histamine substance of the present invention has the advantage that does not produce undesirable abnormal smells from the patient fully, it easily can be used for the cosmetic product to abnormal smells from the patient problem sensitivity.Therefore, anti-histamine substance of the present invention has been given very large expectation as at the composition that is used for presenting pollinosis and the spy answers the patient's of the symptoms such as disease cosmetics to cooperate.
Anti-histamine substance of the present invention can be widely used in the Hair grooming cosmetics in cosmetic product, the articles for use of haircuting, the hair care articles for use, nourish the scalp articles for use, the chromotrichia articles for use, hair shampoo article, hair conditioner (hair rinse), the skin cosmetic astringent, skin lotion, frost (cream), emulsion, shine black frost, sunscreen cream, articles for washing, shaving cream, depilatory cream, facial cleaning cream (facial rinse), facial film (pack), oil for cosmetic purpose, bath gel (body rinse), massage article, the decoration foundation cream (foundation) that applies some make up, the cosmetic cream base, XIANGFEN, lipstick, eye cosmetics (eyemakeup), the cheek cosmetic product, body cosmetic (body makeup), GULONG water perfume, bathe and use cosmetic product, the fingernail cosmetic product, talcum powder (body powder) etc., in addition, in medicine, can be widely used in the powder granula subtilis, granule, tablet, capsule, pill, bacillum, pencil, the content liquor, liquid for external use, extractum, plaster, suppository, aerosol, aerosol, the medicine adsorbent, the ophthalmic agent, injection, adhesive plaster etc.
Description of drawings
[Fig. 1] is the flow chart of flow process of the preparation method of expression anti-histamine substance of the present invention.
[Fig. 2 A] is the figure of one of experimental result of the expression antihistamine effect of investigating material of the present invention.
[Fig. 2 B] is the figure of one of experimental result of the expression antihistamine effect of investigating material of the present invention.
[Fig. 2 C] is the figure of one of experimental result of the expression antihistamine effect of investigating material of the present invention.
[Fig. 3] is the figure of one of experimental result of the expression antihistamine effect of investigating material of the present invention.
Claims (6)
1. the preparation method of an anti-histamine substance is characterized in that, comprises the steps:
Place by adding yeast and water in the stevioside plant tissue of drying, make described dry stevioside plant organize the step of direct fermentation;
Make the fermentation Folium Stevlae Rebaudianae that is obtained by described fermentation step infiltrate the step of in 30% ethanol water, extracting;
The step that will be concentrated by the extracting solution that described extraction step obtains;
The concentrated solution fractionated that will be obtained by described concentration step, the step of collecting the solvable fraction of 90% ethanol.
2. preparation method as claimed in claim 1 is characterized in that, in described fermentation step, makes stevioside plant organize fully fermentation.
3. anti-histamine substance, to collect by the solvable fraction of 90% ethanol that will concentrate the concentrated solution that following extracting solution obtains to obtain, described extracting solution is to make the fermentation Folium Stevlae Rebaudianae infiltrate to extract in 30% ethanol water to obtain, described fermentation Folium Stevlae Rebaudianae is to place by adding yeast and water in the stevioside plant tissue of drying, makes described dry stevioside plant organize direct fermentation to obtain.
4. a cosmetic product contains the anti-histamine substance that is prepared by claim 1 or 2 described preparation methoies, or anti-histamine substance claimed in claim 3.
5. an antihistamine medicine contains the anti-histamine substance that is prepared by claim 1 or 2 described preparation methoies, or anti-histamine substance claimed in claim 3.
6. the method for an effective component extracting from plant is characterized in that, comprises the steps:
Place by adding mushroom and water in the described plant tissue of drying, make described dried plant organize the step of direct fermentation;
The step that the fermenting plant tissue infiltration that obtained by described fermentation step is extracted in 30% ethanol water;
The step that will be concentrated by the extracting solution that described extraction step obtains;
The step of the concentrated solution fractionated that will be obtained by described concentration step,
Described plant is Folium Stevlae Rebaudianae, and described mushroom is yeast.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2007099944 | 2007-04-06 | ||
| JP099944/2007 | 2007-04-06 | ||
| PCT/JP2008/054847 WO2008126638A1 (en) | 2007-04-06 | 2008-03-17 | Anti-histamine substance and method for production thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101674841A CN101674841A (en) | 2010-03-17 |
| CN101674841B true CN101674841B (en) | 2013-03-20 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN200880011345XA Active CN101674841B (en) | 2007-04-06 | 2008-03-17 | Anti-histamine substance and method for production thereof |
Country Status (4)
| Country | Link |
|---|---|
| JP (1) | JP4375758B2 (en) |
| KR (1) | KR101394524B1 (en) |
| CN (1) | CN101674841B (en) |
| WO (1) | WO2008126638A1 (en) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP5031001B2 (en) * | 2009-07-02 | 2012-09-19 | 学校法人 関西大学 | Method for producing nanosphere, nanosphere, external composition for skin containing the same, and cosmetic |
| JP5017386B2 (en) * | 2009-12-03 | 2012-09-05 | 株式会社シャローム | Method for producing melanin synthesis promoting substance, melanin synthesis promoting substance, external preparation for skin, method for producing tyrosinase active substance, tyrosinase active substance, and pharmaceutical |
| CN102987334B (en) * | 2011-09-09 | 2014-07-09 | 浙江海洋学院 | Method for controlling content of histamine in fermented aquatic products |
| WO2014080666A1 (en) * | 2012-11-26 | 2014-05-30 | 株式会社シャローム | Diterpene compound, skin-whitening agent, and method for producing diterpene compound |
| JP6013180B2 (en) * | 2012-12-28 | 2016-10-25 | 株式会社シャローム | Whitening agent |
| JP6590658B2 (en) * | 2015-11-24 | 2019-10-16 | 株式会社シャローム | Novel labdane-type diterpene compounds and degranulation inhibitors |
| WO2018230733A1 (en) | 2017-06-16 | 2018-12-20 | マルホ株式会社 | External preparation for skin |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1317540A (en) * | 2000-04-07 | 2001-10-17 | 山名俊彦 | Powdered stevia rebaudiana and enriched liquid and mfg. process thereof |
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| JPH10330279A (en) * | 1997-03-31 | 1998-12-15 | Naohiko Sato | Substance having antihistamic activity |
| JP2005035888A (en) * | 2001-10-25 | 2005-02-10 | Ta Stevia Co Ltd | Substance for ameliorating anaphylactic type allergic symptom and method for producing the same |
| JP2004075602A (en) * | 2002-08-19 | 2004-03-11 | Ta Stevia Co Ltd | External therapeutic preparation for skin and cosmetic containing the same |
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| CN1317540A (en) * | 2000-04-07 | 2001-10-17 | 山名俊彦 | Powdered stevia rebaudiana and enriched liquid and mfg. process thereof |
Non-Patent Citations (1)
| Title |
|---|
| 金辰彦.甜叶菊发酵提取物的抗组胺作用.《国外医学中医中药分册》.2003,第25卷(第4期),234-235. * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101674841A (en) | 2010-03-17 |
| KR101394524B1 (en) | 2014-05-13 |
| WO2008126638A1 (en) | 2008-10-23 |
| JPWO2008126638A1 (en) | 2010-07-22 |
| JP4375758B2 (en) | 2009-12-02 |
| KR20090130021A (en) | 2009-12-17 |
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