JP4934304B2 - Antipruritic composition - Google Patents

Description

  The present invention relates to an antipruritic composition, and more particularly, to an antipruritic composition containing Benifuuki extract as an active ingredient.

  Itching is one of the important symptoms in many skin diseases. Itching is a very unpleasant sensation that induces scratching behavior, destroys the skin barrier, promotes percutaneous infiltration of irritants, and exacerbates skin symptoms. Therefore, controlling itching is extremely important in preventing exacerbations of skin symptoms and reducing pain for patients with skin diseases. It is thought that various mediators such as histamine are involved in the development of this itch, and antihistamines are used to suppress itching, but the mechanism of itch generation is complex and not necessarily effective. It was hard to say that

  In addition, a topical steroid preparation is used as an effective therapeutic agent for atopic dermatitis with strong itching. However, steroid agents have problems of side effects such as skin atrophy, purpura, and capillary vasodilation, and their use is not preferred.

  Therefore, development of a highly safe antipruritic composition that effectively suppresses itching associated with skin diseases and the like and does not cause problems such as side effects even after long-term use has been demanded.

On the other hand, it is known that an extract from tea leaves has an antiallergic action. For example, 3- O -methylgalloylepigallocatechin and / or 4- O -methylgalloylepigallocatechin is used as an active ingredient. An antiallergic agent is disclosed (Patent Document 1). In addition, an external medicine for treating allergic dermatitis containing tea leaf extract as an active ingredient has been disclosed (Patent Document 2). However, these documents do not describe that the extract of tea leaves has an antipruritic action.

JP 2000-159670 A JP-A-10-218784

  This invention is made | formed in view of this condition, and makes it a subject to provide the antipruritic composition which suppresses the itch accompanying a skin disease etc. effectively, and does not have problems, such as a side effect.

  As a result of intensive studies on a substance having an effect of suppressing itching, the present inventors have found that an extract extracted from Benifuuki, which is one of tea varieties, has an excellent antipruritic action, and completed the present invention. It came to do.

  That is, the present invention is an antipruritic composition comprising Benifuuki extract as an active ingredient.

  Moreover, this invention is an antipruritic composition which uses the polyphenol fraction of a beef bellows as an active ingredient.

  The antipruritic composition of the present invention can effectively suppress itching associated with skin diseases and the like, and can prevent deterioration of skin symptoms due to scratching behavior. In addition, this product has a high safety because there are few problems such as side effects even if it is used for a long period of time, because it uses benifuuki extract, which is a tea to be drunk, as an active ingredient.

  Benifuuki extract used in the present invention is obtained from Benifuuki tea leaves, one of the tea varieties. Benifuuki tea leaves, which are raw materials, may be any of green tea, green, semi-fermented or fermented, dried or roasted by a conventional manufacturing method.

  The Benifuuki extract of the present invention can be obtained by extracting the above-mentioned Benifuuki tea leaves using an appropriate solvent. Specific examples of the solvent used for the extraction include water, organic solvents such as ethanol, methanol, acetone, 1,3-butylene glycol, and glycerin, or a mixed solution thereof. Preferably, water, water, / Ethanol mixture.

  As a specific method for producing the benifuuki extract used in the present invention, for example, 5 to 100 parts by weight of a solvent is added to 1 part by weight of benifuuki tea leaves and the temperature is about room temperature to about 100 ° C. for 1 to 120 minutes. A method of extracting the degree is mentioned.

  As the Benifuuki extract of the present invention, in addition to the extract obtained by extracting the above-mentioned Benifuuki tea leaves with the above-mentioned solvent, a solvent fraction obtained by further liquid-liquid partitioning of the extract is used. You can also. Examples of the solvent used for this liquid-liquid distribution include ethyl acetate and n-butanol. Alternatively, a fraction obtained by passing the extract through a column filled with an adsorption resin can be used. Examples of the adsorption resin used include activated carbon, Diaion HP-20, Sephadex LH-20, and ODS gel.

  Among the benifuuki extract obtained as described above, a polyphenol fraction containing a large amount of polyphenol components can be preferably used because it has a high antipruritic action. Examples of such a polyphenol fraction include an ethyl acetate fraction obtained by liquid-liquid partitioning of an extract obtained by extracting Benifuuki tea leaves with hot water and further using ethyl acetate. Moreover, the polyphenol fraction which reduced caffeine content can be obtained by wash | cleaning this ethyl acetate fraction with water.

  The above-mentioned Benifuuki extract can be used in the antipruritic composition as it is, or if necessary, purified by a known purification means, concentrated or diluted, and if necessary, spray-dried or freeze-dried, etc. What was pulverized by the above means may be used for the antipruritic composition.

  In the production of the antipruritic composition, for example, it is preferable to add 0.001 to 20%, and more preferably 0.01 to 10%, of the above-mentioned Benifuuki extract to the whole preparation.

  Furthermore, the antipruritic composition of the present invention has an excellent antipruritic action even if only the above-mentioned Benifuuki extract is blended as an active ingredient, but if necessary, other medicinal ingredients can be blended. Examples of this medicinal component include antihistamines, antiallergic agents, immunosuppressive agents, anti-inflammatory agents, local anesthetics, refreshing agents, moisturizing agents and the like.

  Furthermore, the antipruritic composition of the present invention contains other known optional components as necessary, for example, hydrocarbons, ester oils, ether oils, higher fatty acids, higher alcohols, sphingosine derivatives, synthetic ceramide analogs and the like. Oil agent, polyhydric alcohol, film forming agent, moisturizer, antioxidant, surfactant, antibacterial agent, antiseptic agent, powder, clay mineral, inorganic salt, pigment, solvent, UV inhibitor, pH adjuster, viscosity adjuster An agent, a fragrance | flavor, etc. can be mix | blended.

  The dosage form of the antipruritic composition is arbitrary, ampoules, capsules, powders, granules, pills, tablets, solids, liquids, gels, bubbles, emulsions, creams, ointments , Sheet-like, mousse-like, powder-dispersed, multilayered, aerosol-like pharmaceuticals, quasi-drugs, cosmetics or foods and drinks. In particular, it is preferable to apply to external preparation compositions such as pharmaceuticals, quasi-drugs, and cosmetic compositions applied to the outer skin.

  EXAMPLES Next, although an Example is given and this invention is demonstrated in more detail, this invention is not restrict | limited at all by these Examples.

Example 1
(Manufacturing method of Benifuuki extract)
4 kg of Benifuuki tea leaves were extracted with 40 L of hot water for 30 minutes to obtain an extract. The extract was concentrated and dried, dissolved by adding water, and extracted by shaking with ethyl acetate. The ethyl acetate layer was concentrated to about half volume under reduced pressure, and then washed with water. The washed ethyl acetate layer was concentrated under reduced pressure while adding water, the solvent was distilled off, and the residue was freeze-dried to obtain about 200 g of benifuki extract.

(Component analysis of Benifuuki extract)
When the tannin content in the Benifuuki extract obtained in Example 1 was measured by the iron tartrate spectrophotometric method described in the “Japanese Food Standard Component Table Analysis Manual”, the tannin content was 91.0%. In addition, the content of 3- O -methylgalloylepigallocatechin and caffeine was quantified by reverse phase HPLC using an ODS column (mobile phase: acetonitrile / water / phosphoric acid mixture (50: 330: 0.3)). As a result, the content of 3- O -methylgalloylepigallocatechin was 10.1% and the caffeine content was 3.4%.

Example 2
(Manufacturing method of Benifuuki extract)
5 kg of Benifuuki tea leaves were extracted with 50 L of acetone / water (1: 1) mixture at room temperature for 1 day to obtain an extract. The extract is concentrated under reduced pressure to distill off the solvent, then adsorbed onto a column packed with the adsorbent Sephadex LH-20, and water is first passed as the eluent, followed by monitoring by thin layer chromatography (TLC). While gradually increasing the methanol concentration, the polyphenol component was eluted. The obtained polyphenol fraction was concentrated under reduced pressure, the solvent was distilled off, and the residue was freeze-dried to obtain about 250 g of benifuki extract.

Example 3
(Manufacturing method of Benifuuki extract)
10 kg of Benifuuki tea leaves were extracted with 100 L of hot water for 30 minutes, and the resulting extract was washed with chloroform to remove unnecessary substances. The washed aqueous solution is adsorbed on a column packed with the adsorbent Diaion HP-20, and water is first passed as an eluent, and then the methanol concentration is gradually increased while monitoring with TLC, so that the polyphenol component is removed. Elute. The obtained polyphenol fraction was concentrated under reduced pressure, the solvent was distilled off, and then spray-dried to obtain about 500 g of a bean-fuki extract.

Test example 1
Itching suppression test for 1-fluoro-2,4-dinitrobenzene (DNFB) repeated application-induced pruritus model:
(1) Preparation of sensitizing solution DNFB was dissolved in acetone to a concentration of 0.15 w / v% to obtain a sensitizing solution.
(2) Preparation of test substance The test sample substance was prepared by dissolving the peanut extract obtained in Example 1 with a 50% ethanol solution to a concentration of 1, 3, 10 w / v%. The test substance was prepared at the time of use.
(3) Test method 0.1 mL of DNFB solution prepared in (1) was applied to a shaved abdomen of male BALB / c mice for sensitization. Furthermore, 0.05 mL of DNFB solution was applied to the shaved back of the neck on days 4, 7, 11, 14, 18, 21, 25 and 28 from the first sensitization day. The test substance was applied to the back of the neck from the 14th day to the 27th day of sensitization by 0.1 mL daily. When applying the DNFB solution and the test substance on the same day, the test substance was applied one hour before the DNFB solution application. The number of scratches on the back of the neck by the hind limbs of the mice 60 minutes after application of the DNFB solution on the 28th day was measured. For the measurement of the number of scratches, MicroAct (manufactured by Neuroscience) was used. In addition to the above-mentioned test substance application groups, as a sensitization control, a group in which a DNFB solution is applied and no test substance is applied, and as a non-sensitization control, acetone is applied instead of the DNFB solution and the test substance is applied. The number of scratches was measured in the same manner for the groups not coated with. About each experimental group, the body weight was measured every seven days from the first sensitization day. The result of the number of scratches is shown in FIG. 1, and the result of weight change is shown in FIG. Furthermore, the skin state of the mouse | mouth of each experimental group of the sensitization control, the non-sensitization control, and a 10% Benifuuki extract was observed with the microscope. These are shown in FIGS.

  From the results shown in FIG. 1, it was shown that the number of scratches was significantly decreased in the 10% benifu extract extract group compared to the sensitization control group, and the effect was dose-dependent. Further, from FIG. 2, no change in body weight due to the application of Benifuuki extract was observed. Therefore, Benifuuki extract was found to have an antipruritic action and there was no change in body weight. 3 to 6, skin erosion / ulcer and epidermal thickening were observed in the sensitization control group, but these conditions were cured in the 10% Benifuuki extract application group. It became clear that it has the effect | action which suppresses the scarring formation by suppression of thickening and scratching. Furthermore, although existing antiallergic agents and steroidal agents do not inhibit the scratching behavior of this model (Reference: Allergology, 16 (1): 80-86, 2003), Benifukuki Extract has an antipruritic effect on this model. This suggested that it had a new mechanism of action.

Test example 2
Pruritus inhibition test for ovalbumin (OVA) sensitized pruritus model:
(1) Preparation of test substance The test sample substance was prepared by dissolving the peanut extract obtained in Example 1 with a 50% ethanol solution to a concentration of 1, 3, 10 w / v%. The test substance was prepared at the time of use.
(2) Test method An equal amount of mixed antigen solution of 0.5 mg / mL OVA and 20 mg / mL aluminum hydroxide was intraperitoneally administered to male BALB / c mice. The same antigen solution was intraperitoneally administered on the 7th, 14th and 21st days after the first sensitization. The test substance was applied every day from the 14th day to the 28th day of sensitization on the back shaved by 0.1 mL. On day 28, 0.05 mL of a 1 mg / mL OVA solution was subcutaneously injected into the back of the neck. The number of scratches to the back of the neck by the hind limbs of the mice for 60 minutes after the antigen challenge was measured. For the measurement of the number of scratches, MicroAct (manufactured by Neuroscience) was used. On the antigen challenge day, the test substance was applied 1-2 hours before the antigen challenge. Further, in addition to the above-mentioned test substance application groups, the group that administers the antigen solution and does not apply the test substance, the sensitization control, the group that does not administer the antigen solution and does not apply the test substance, non-sensitization control, The group to which 3% diphenhydramine hydrochloride was applied was used as a positive control, and the number of scratches was measured in the same manner. About each experimental group, the body weight was measured every seven days from the first sensitization day. The result of the number of scratches is shown in FIG. 7, and the result of weight change is shown in FIG.

  From FIG. 7, it was shown that the number of scratches in the mouse can be suppressed by applying 1 to 10% of the extract. Moreover, from FIG. 8, since the weight change of the mouse | mouth by application | coating of Benifuuki extract was not recognized, it was guessed that there is no harmful influence on Benifuuki extract.

Example 4
A cream (W / O type) having the following composition was produced by a conventional method.
Isostearyl glyceryl ether 2.0%
Squalane 7.0%
Isopropyl myristate 8.0%
Octyldodecyl myristate 4.0%
Dextrin palmitate 0.8%
Benifuuki Extract 6.0%
Magnesium sulfate 0.5%
Dipotassium glycyrrhizinate 0.1%
Tocopherol acetate 0.05%
Glycerin 12.0%
P-Hydroxybenzoate 0.5%
Phenoxyethanol 0.2%
Purified water balance <br/> Total 100.0%

Example 5
A cream (O / W type) having the following composition was produced by a conventional method.
Sorbitan monostearate 2.0%
Polyoxyethylene hydrogenated castor oil (40E.O.) 0.5%
Cetanol 1.0%
Stearyl alcohol 1.0%
Stearic acid 2.8%
Myristic acid 0.2%
Liquid paraffin 20.0%
Carboxyvinyl polymer 0.05%
Methyl polysiloxane 0.5%
Glycerin 8.0%
Benifuuki Extract 1.0%
Ethanol 1.0%
Dipotassium glycyrrhizinate 0.1%
Tocopherol acetate 0.05%
P-Hydroxybenzoate 0.4%
Phenoxyethanol 0.1%
Fragrance 0.1%
Purified water balance <br/> Total 100.0%

Example 6
The lotions shown below were produced by a conventional method.
Polyoxyethylene hydrogenated castor oil (60 EO) 0.2%
1,3-butylene glycol 1.0%
Glycerol 3.0%
Polyethylene glycol 1000 2.0%
L-serine 0.5%
Succinic acid 0.02%
Edetate disodium 0.05%
Benifuuki extract 0.03%
P-Hydroxybenzoate 0.2%
Tocopherol acetate 0.03%
Ethanol 3.0%
Purified water balance <br/> Total 100.0%

Example 7
The following emulsions were produced by conventional methods.
Cetyl alcohol 1.0%
Petrolatum 2.0%
Squalane 6.5%
Dimethylpolysiloxane 2.0%
Ethanol 3.0%
1,3-butylene glycol 4.0%
Glycerol 3.0%
Synthetic ceramide analog 0.5%
Self-emulsifying glyceryl monostearate 3.0%
Carboxyvinyl polymer 0.25%
Potassium hydroxide 0.06%
Benifuuki extract 0.3%
P-Hydroxybenzoate 0.3%
Phenoxyethanol 0.05%
Fragrance 0.1%
Purified water balance <br/> Total 100.0%

Example 8
The following powders were produced by a conventional method.
Zinc flower 3.0%
Magnesium stearate 3.0%
Benifuuki Extract 3.0%
Fragrance 0.1%
Talc balance <br/> Total 100.0%

Example 9
The following body shampoo was produced by a conventional method.
Lauric acid 2.5%
Myristic acid 7.5%
Palmitic acid 2.5%
Oleic acid 2.5%
Potassium hydroxide 3.6%
Ethylene glycol distearate 2.0%
Lauryl hydroxysulfobetaine 2.0%
Palm oil fatty acid diethanolamide 2.5%
Propylene glycol 2.0%
Hydroxyethane diphosphonic acid 0.05%
Benifuuki Extract 5.0%
P-Hydroxybenzoate 0.3%
Fragrance 1.0%
Purified water balance <br/> Total 100.0%

Example 10
The following liquid bath was prepared by a conventional method.
Glycerol monostearate 3.0%
Sorbitan monopalmitate 3.0%
POE (15) cetyl ether 3.0%
Jojoba oil 1.0%
Rice bran oil 5.0%
Isopropyl myristate 5.0%
Liquid paraffin 20.0%
Tallow fatty acid potassium 1.0%
Benifuuki Extract 1.0%
Isoprene glycol 5.0%
P-Hydroxybenzoate 0.3%
Phenoxyethanol 0.1%
Fragrance 1.5%
Purified water balance <br/> Total 100.0%

Example 11
The powder bathing agent shown below was produced by a conventional method.
Sodium bicarbonate 3.0%
Magnesium sulfate 1.0%
Silicic anhydride 0.3%
Sodium L-glutamate 0.3%
Glycerin 0.1%
Benifuuki Extract 10.0%
Fragrance 1.0%
Dye 0.1%
Sodium sulfate balance 100.0% total

  As described above, the antipruritic composition of the present invention has an excellent antipruritic action, is highly safe with few problems such as side effects, and further has an action of suppressing thickening of the epidermis and formation of scratch marks. It is what you have.

  Therefore, the preparation for pruritus using the antipruritic composition of the present invention is useful as a therapeutic agent for skin diseases accompanied by itching.

It is a figure which shows the antipruritic action by the Benifuuki extract in Test Example 1. It is a figure which shows the weight change of the mouse | mouth in the test example 1. FIG. 2 is a photomicrograph of the skin of a non-sensitized control group mouse in Test Example 1. 2 is a photomicrograph showing skin erosion / ulcer in sensitized control group mice in Test Example 1. 2 is a photomicrograph showing epidermis thickening of sensitized control group mice in Test Example 1. 2 is a photomicrograph of the skin of a mouse coated with 10% benifuki extract in Test Example 1. FIG. It is a figure which shows the antipruritic effect of the Benifuuki extract in Test Example 2. It is a figure which shows the weight change of the mouse | mouth in the test example 2. FIG.

Claims (3)

An antipruritic composition comprising, as an active ingredient, a solvent fraction obtained by liquid-liquid partition using Benifuuki extract with ethyl acetate . The antipruritic composition according to claim 1, wherein the solvent fraction obtained by liquid-liquid partition using Benifuuki extract with ethyl acetate is a polyphenol fraction of Benifuuki extract. The antipruritic composition according to claim 1 or 2, wherein the dosage form is an external preparation for skin.

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