201121555 六、發明說明： 【發明所屬之技術領域】 本發明係關於一種敏感肌膚用知覺過敏預防改善劑。 【先前技術】 作為敏感肌膚改善劑，先前已知有神經生長因子（Ngf) ' 產生抑制劑’例如已知有以款冬（Petasites)、知母、白 樺、艾草等作為有效成分之神經生長因子（NGF)產生抑制 劑（專利文獻1)，或包含丁香酚配糖體、異丁香酚配糖體、 覆盆子酮配糖體、杜鵑醇配糖體等之神經生長因子產生抑 制劑（專利文獻2)。 [先前技術文獻] [專利文獻] [專利文獻1]日本專利特開2009-84222號公報 [專利文獻2]曰本專利特開2004-107250號公報 【發明内容】 本發明係提供一種以羅漢柏（777My>〇<^ 仏）或其萃 取物作為有效成分之敏感肌膚用知覺過敏預防改善劑。 另外，本發明係提供—種含有用以預防改善敏感肌膚之 知覺過敏之羅漢柏或其萃取物的組合物。 ' 另外，本發明係提供一種敏感肌膚之知覺過敏預防改善 方法，其特徵在於：將含有羅漢柏或其萃取物之組合物用 於敏感肌膚患者。 另外，本發明係、提供一種含有羅漢柏或其萃取物之組合 物之用it，其係用於製造敏感肌膚用知覺過敏預防改呈 152414.doc 201121555 劑。 進而，本發明係提供一種含有羅漢柏或其萃取物之組合 物之用途，其係用於預防改善敏感肌膚用知覺過敏。 [發明之效果] 根據作為本發明之有效成分之羅漢柏或其萃取物，可於 不使神經生長因子（NGF)之表現量變化之情況下預防及改 善敏感肌膚之知覺過敏症狀。而且，羅漢柏或其萃取物自 古以來廣泛地用於藥用，安全性較高。 【實施方式】 眾所周知於異位性皮膚炎等炎症部位，神經生長因子 (NGF)之產生量增加而引起熱痛覺過敏等，但同時，神經 生長因子(NGF)亦具有冑進分泌'肖皮膚再生才目_之生理活 性物質的作用’因此在儘管未引起特別過度之炎症或免疫 反應但變得容易感知感覺刺激時，有時抑制該神經生長因 子（NGF)之表現之方法並不適宜。 因此，本發明之課題在於提供一種知覺過敏預防改善 劑’其可於不使神經生長因子（NGF)之表現量變化之情況 下有效地預防並改善變得容易感知感覺刺激的敏感肌膚之 知覺過敏症狀。 因此，本發明者們為解決上述課題而廣泛地對植物萃取 物之藥理作用進行了研究，結果發現羅漢柏之萃取物具有 可於不使神經生長因子（NGF)之表現量變化之情況下預防 並改善敏感肌膚之知覺過敏症狀的作用，從而完成本發 明。 I52414.doc 201121555 關於作為本發明之敏感肌膚用知覺過敏預防改善劑之有 效成分的羅漢柏之生理活性，已知有抗微生物作用美白 作用、骨病預防作用、細胞點著抑制作用、抗過敏作用、 免疫抑制作用、抗炎作用等（日本專利特開平2_讓9號、 日本專利特開平5.3457㈣、日本專利特開平㈣㈣ ==本專利特開平9_315991號），但關於其可在不使神經 子（N G F)之表現量變化之情況下預防及改善知f過 敏症狀之作用則完全無人知曉。 中使用之羅漢柏萃取物可使用溶劑萃取羅漢柏之 ^體或部分而獲得。你或： 〇作為，㈣柏之部分，可列舉葉部、小 ’可藉由主要將羅漢柏之葉部、小枝 ==不乾燥而粉碎後’於常溫下或加溫下藉由溶劑 取器等萃取器具進行萃取而獲得。再者， 稀釋r、胃羅漢柏萃取物，係指各種溶劑萃取液或其 液/農&液或乾燥粉末。 溶=取物㈣為以如下方式獲得：使用水、有機 (石油麵、正己烷、環 甲浐、^ T本、本專烴系溶劑， ·二氯 :::仿、四氣化鍋化烴類；二乙越等醚系溶劑； 夂乙δ曰等酯系溶劑；丙酮等酮類；吡啶等鹼性溶劑 醇、丙醇、乙醇、甲醇、聚乙二醇、丙二醇、 疋或多元醇系溶劑等）、含水酒精等，於通常 羅漢柏之全部、部八或其篝 、 下對 彳刀戍以之乾_粉末進行萃取處理。 漢柏2柏進行萃取之較佳具體例可列舉下述方法：將羅 ’、 無粉碎物I〇0 g浸潰於1升乙醇中，於室溫下萃取 I52414.doc 201121555 7曰，然後過濾所獲得之萃取液獲得上清液。 上述萃取物可直接作為本發明之有效成分使用，亦可將 該萃取物濃縮’之後進一步藉由適當之分離方法，例如凝 膠過濾或石夕膠管柱層析法、高效液相層析法等分離出活性 較高之成分而使用。 以上之羅漢柏萃取物可直接使用’或者亦可進行稀釋、 濃縮或冷凍乾燥後，製備成粉末狀或糊狀，適宜地製劑化 而使用。另外，亦可進而視需要使用活性碳等實施除臭、 脫色等純化處理後使用。 尤其是’上述萃取物可藉由溶劑置換等方法除去乙醇而 製成多元醇溶解物使用，可不對敏感肌膚產生刺激地將萃 取成分塗抹於皮膚上，可使該有效成分之效果得到充分發 揮’因而較佳。再者，作為該多元醇，可列舉：乙二醇、 聚乙二醇（平均分子量為1000以下）、丙二醇、二丙二醇、 丁二醇（1，3-丁二醇）等二醇；甘油、雙甘油等3〜4元之醇。 其中’較佳為作為二醇之丙二醇、二丙二醇、L3_ 丁二 醇。於本發明之敏感肌膚用知覺過敏預防改善劑中，多元 醇之含較佳為0.02〜50質量％ ’特佳為2〜20質量。/。。另 外’本發明之敏感肌膚用知覺過敏預防改善劑中的乙醇含 量較佳為未達8質量％，更佳為未達4質量％，進而更佳為 未達1質量。/。’特佳為實質上不含乙醇。 如後述之實施例中所示般，羅漢柏萃取物可於不使神經 生長因子（NGF)之表現量變化之情況下使刺激閾值顯著上 升。因此可較佳地用作敏感肌膚用知覺過敏預防改善劑。 152414.doc 201121555 者本务月中所明敏感肌膚，係指由於神經纖維伸長至 皮内肖質層正下方，而變得容易感知感覺刺激之知覺 過敏狀態，應與引起過度之炎症或免疫反應之過敏狀態及 作為其-種之異位性皮膚炎等疾患肌區別開。具體而言， 係私由於知覺神經過敏，導致即便微小之外部刺激(溫 度濕度、灰塵、過敏原等）亦容易受到影響，使用化妝 品或受到外部刺激時，會感到諸如火辣辣、針紮、瘙疼感 等感覺刺激，但是皮膚性狀相對健康，因而即便施以用於 7制炎症之治療等刺激亦得不到緩和之肌膚。引起過度之 f症或免疫反應之過敏狀態或作為其—種之異位性皮膚炎 等疾患肌係產生在炎症部位神經生長因子(NGF)之表現量 增加’因而痛覺過敏顯著加劇等問題，因而本發明者們認 為藉由如切般投予抗炎劑或神經生長因子（ngf)表現抑 制劑使神經生長因子（NGF)之表現量降低至通常水準，可 向較理想之方向發展。但是，未產生炎症之肌膚原本神經 生長因子（NGF)之表現量並未增加，目而若如先前般投予 神、4生長因子（NGF)表現抑制劑’則有可能導致神經生長 因子（NGF)之表現量減少至通常水準以下，並因神經生長 因子（NGF)不足而產生各種影f n可於不使神經生 長因子（NGF)之表現量變化之情況下預防並改善敏感肌膚 之知覺過敏症狀的本發明之敏感肌膚用知覺過敏預防改善 劑非常理想。 本發明之敏感肌膚用知覺過敏預防改善劑可與 之添加劑-起製劑化成任意形態之組合物。該等製劑中之 152414.doc 201121555 羅漢柏萃取物之含量較佳為以固形物換算為〇 〇〇〇1〜〇」質 量。/。’更佳為0.01〜0.1質量％。再者，所謂固形物換算，係 指根據將測定試樣10 H1L於1〇5〇C下進行6小時乾燥處理後 獲得之固形物量換算所得之值。 本發明之敏感肌膚用知覺過敏預防改善劑中，可視需要 適宜調配.化妝品、準藥品、醫藥品之皮膚外用劑中所調 配之界面活性劑、保濕劑、油劑、增稠劑、顏料、色素、 鹽類、螯合劑、中和劑、紫外線吸收劑、防腐劑、殺菌 劑、純化水、天然水、深層海洋水、乙醇等。另外，作為 劑型，可列舉：軟膏、化妝水（1〇ti〇n)、乳液、霜劑 (cream)、凝膠、敷劑、粉末、氣溶膠、糊劑等。 本發明之敏感肌膚用知覺過敏預防改善劑更佳為並非僅 使用一次’而於皮膚之特定部位使用一定時間以上。為使 敏感肌膚之刺激閾值上升，較佳為將以固形物換算含有 0.000 1〜〇. 1質量％之羅漢柏萃取物之組合物，以每次〇」 mg/cm2〜5 mg/cm2之量、1曰1〜5次地對皮膚使用3曰以上， 更佳為1週以上。更佳為以每次1 mg/cm2〜3 mg/cm2之量、 1曰1〜3次地對皮膚使用1週以上，更佳為1 〇日以上。 [實施例] 藉由以下之實施例、試驗例更詳細地說明本發明。 參考例1 (羅漢柏萃取物之製法） 將羅漢柏之乾燥枝葉（約1 kg)細細切碎，浸潰於乙醇（10 升）中，於室溫下一面不時地攪拌一面萃取7曰，過濾所獲 152414.doc 201121555 得之萃取液，將渡液於5°c下靜置3日後，再次過滤獲得上 清液:於其中添加9倍量之50%<1，3_丁二醇溶液，然後過 滤。濃縮其遽液，於其中進而添加以丁二醇及純化水， 再-次過濾而獲得製品(約100 L)。所獲得的羅漢柏萃取物 之1，3-丁二醇之含量為54 75%，含水量為45%，羅漢柏固 形物成分之含量為025 %。 試驗例1 使用試驗皮膚LSE_High(東洋紡公司製造）作為人皮膚 重組模型，進行培養。於培養基中，以成為2 mg/cm2之量 之方式添加參考例！的羅漢柏萃取物之丨％(v/v)丨，3-丁二 醇：乙醇=1:1之溶液或對照溶劑（1，3_丁二醇：乙醇=1 ”， 培養72小時後，用小鑷子剝除試驗皮膚表皮部分，回收 RNA(rib〇nuCleic acid，核糖核酸），藉由 RT pCR (reverse transcripti〇n-p〇iymerase chain reacU〇n，反轉錄聚合酶鏈 反應）檢查神經生長因子（NGF)及G3PDH(glycer〇1_3_ phosphate dehydrogenase ’ 3-磷酸甘油脫氫酶）之表現。 其結果示於圖1。如由圖丨亦可明確般，即便應用羅漢柏 萃取物’神經生長因子（NGF)之表現程度（NGF/G3PDH)亦 未產生變化。 试驗例2連續塗抹羅漢柏萃取物對於電流感覺刺激閾值 之效果 為選出敏感肌膚之被試驗者，以如下方法實施1%乳酸 水溶液刺痛試驗。使不為異位性皮膚炎等過敏性皮膚炎等 之疾患肌的被試驗者洗臉後’適應i 〇分鐘，將浸有1 %乳 152414.doc 201121555 酸水溶液1.2 mL的20 cm2之不織布用於臉頰部，使被試驗 者報告剛使用後、以及使用後之每丨分鐘直至1〇分鐘後為 止關於所感知之感覺刺激的評分（0=無刺激，〇 5 =稍感覺 到刺激，1=較弱，1.5=明確感覺到刺激，2〇 =較強，25 = 非常強，3 =無法忍受），得到合計1〇次之累積評分，並以 同樣之方式使用蒸餾水進行試驗，將兩頰之評分與蒸餾水 之情形相比為5以上之被試驗者作為本發明中之敏感肌 膚。 對12名該敏感肌膚之被試驗者，將參考例1之羅漢柏萃 取物之4%水溶液以一頰部位2 mg/cm2之量之方式1日3次地 塗抹，塗抹2週（對另一頰部位塗抹蒸餾水作為對照）。為檢 查連續使用前後末梢神經之知覺過敏程度，使用感覺神經 測量儀（neurometer·)測定電流感覺閾值，結果如圖2所示， 判明塗抹羅漢柏萃取物水溶液之側的電流感覺閾值上升， 知覺過敏狀態得到改善。 再者，根據以上之結果可認為，藉由使用該藥劑，由與 神經生長因子（NGF)產生抑制劑不同之因子抑制住伸長之 神經進入至表皮，因而知覺過敏之狀態得到改善。 再者，利用感覺神經測量儀測定電流感覺閾值之方法如 下所述。 <<電流感覺閾值之測定方法>> 將直徑約1 cm之電極貼於臉頰部，使用Neur〇tr〇n公司製 造之感覺神經測量儀，將流通25〇 Hz之交流電流時被試驗 者可感覺到其刺激的最低水準之電流量作為電流感覺閾值 152414.doc 201121555 (CPT : Current Perception Threshold)。 試驗例3連續塗抹羅漢柏萃取物引起的乳酸刺痛評分之 變4匕 對試驗例3之被§式驗者，同樣地將參考例丨之羅漢柏萃取 物之4%水溶液以一頰2 mg/cm2之量1日3次地連續使用2 週，與試驗例2同樣地在連續使用前後進行1%乳酸水溶液 刺痛試驗。其結果，被試驗者於剛使用後、以及使用後每 1分知直至10分知後為止關於所感知之感覺刺激合計丨〇次 報告之評分（0=無刺激，0.5 =稍感覺到刺激，1=較弱，15 = 明確感覺到刺激’ 2.0=較強，2.5 =非常強，3 =無法忍受）之 累積評分的12人之平均值如圖3所示般，塗抹羅漢柏萃取 物水溶液之側之臉頰於連續使用前後刺痛評分減少，判明 知覺過敏得到改善。而且，未觀察到皮膚肌理變得粗縫等 因皮膚之再生延遲而引起的不良影響。 【圖式簡單說明】 圖1係顯示羅漢柏萃取物對於人皮膚重組模型中之神經 生長因子（NGF)表現之效果的圖。 圖2係顯示連續塗抹羅漢柏萃取物前後之敏感肌膚之電 流感覺閾值（CPT)的圖。 圖3係顯示連續塗抹羅漢柏萃取物前後之敏感肌膚之刺 痛評分的圖。 1524I4.doc201121555 VI. Description of the Invention: [Technical Field of the Invention] The present invention relates to a sensory allergy prevention and improvement agent for sensitive skin. [Prior Art] As a sensitive skin improving agent, a nerve growth factor (Ngf) production inhibitor is known, for example, a nerve growth factor having an active ingredient such as Petasites, Anemarrhena, Betula platyphylla, and wormwood is known. (NGF) production inhibitor (Patent Document 1), or a nerve growth factor production inhibitor comprising an eugenol glycoside, an isoeugenol glycoside, a raspberry ketone glycoside, a rhododendron glycoside, etc. (Patent Literature 2). [Prior Art Document] [Patent Document 1] Japanese Patent Laid-Open Publication No. 2009-84222 [Patent Document 2] Japanese Patent Laid-Open Publication No. 2004-107250 (Invention) The present invention provides a Luo Hanbai (777My>〇<^ 仏) or an extract thereof as an active ingredient for a sensory allergy prevention and improvement agent. Further, the present invention provides a composition containing Rohan cypress or an extract thereof for preventing hypersensitivity of sensitive skin. Further, the present invention provides a method for improving hypersensitivity prevention of sensitive skin, which comprises using a composition containing Rohan cypress or an extract thereof for a patient with sensitive skin. Further, the present invention provides a composition comprising a composition of Rohan cypress or an extract thereof for use in the manufacture of sensitive skin for the detection of hypersensitivity 152414.doc 201121555. Further, the present invention provides a use of a composition comprising Rohan Cypress or an extract thereof for preventing hypersensitivity of sensitive skin. [Effects of the Invention] According to the arborvitae or the extract thereof, which is an active ingredient of the present invention, it is possible to prevent and improve the hypersensitivity symptoms of sensitive skin without changing the expression amount of nerve growth factor (NGF). Moreover, Rohan cypress or its extract has been widely used for medicinal purposes since ancient times and is highly safe. [Embodiment] It is known that in the inflammatory site such as atopic dermatitis, the amount of nerve growth factor (NGF) is increased to cause thermal hyperalgesia, but at the same time, nerve growth factor (NGF) also has hyperactive secretion. The action of the physiologically active substance is therefore not suitable for inhibiting the expression of the nerve growth factor (NGF) sometimes, although it does not cause a particularly excessive inflammation or immune response, but it becomes easy to perceive the sensory stimulation. Therefore, an object of the present invention is to provide a hyperalgesia preventive agent which can effectively prevent and improve the hypersensitivity of sensitive skin which is easy to perceive sensory stimuli without changing the amount of expression of nerve growth factor (NGF). symptom. Therefore, the present inventors have extensively studied the pharmacological action of plant extracts in order to solve the above problems, and as a result, it has been found that the extract of Rohan has an effect of preventing the change in the amount of nerve growth factor (NGF). The present invention has been accomplished by improving the effects of hypersensitivity symptoms of sensitive skin. I52414.doc 201121555 It is known that the physiological activity of arborvitae, which is an active ingredient of a hypersensitivity prophylactic agent for sensitive skin of the present invention, is an antibacterial effect, a whitening effect, a bone disease prevention effect, a cell point inhibition effect, and an anti-allergic action. , immunosuppressive effects, anti-inflammatory effects, etc. (Japanese Patent Laid-Open No. 2 _ No. 9, Japanese Patent Lai-Ping 5.3457 (four), Japanese Patent Special Kaiping (four) (four) == this patent special Kaiping 9_315991), but regarding it can not make nerves The role of prevention and improvement of allergic symptoms in the case of changes in the performance of the child (NGF) is completely unknown. The extract of Luohanbai used in the method can be obtained by extracting the body or part of Luohanbai using a solvent. You or: 〇 as, (4) the part of the cypress, which can be cited as the leaf part, the small 'can be smashed by the main part of the arborvitae leaflet, the twigs == not dry, and the solvent is taken at room temperature or under heating It is obtained by extraction with an extraction device. Further, the diluted r, stomach arborvitae extract refers to various solvent extracts or their liquid/agricultural & liquid or dry powder. Solution = (4) is obtained by using water, organic (oil surface, n-hexane, cyclomethazine, ^ T, this special hydrocarbon solvent, · dichloro::: imitation, four gasification pot hydrocarbons Ether solvent such as diethyl ether; ester solvent such as 曰B δ ;; ketone such as acetone; alkaline solvent alcohol such as pyridine, propanol, ethanol, methanol, polyethylene glycol, propylene glycol, hydrazine or polyol Solvents, etc., aqueous alcohol, etc., are usually extracted from the dried shovel of the shovel. A preferred embodiment of the extraction of Hanbo 2 cypress can be exemplified by immersing Luo's, pulverized material I 〇 0 g in 1 liter of ethanol, and extracting I52414.doc 201121555 7 室温 at room temperature, followed by filtration. The obtained extract obtained the supernatant. The above extract may be directly used as an active ingredient of the present invention, or the extract may be concentrated, and then further separated by a suitable separation method such as gel filtration or Shihe gum column chromatography, high performance liquid chromatography, etc. It is used by separating the component with higher activity. The above-mentioned Luohanbai extract may be used as it is, or may be diluted, concentrated or freeze-dried, prepared into a powder or a paste, and suitably formulated for use. In addition, it may be used after purification treatment such as deodorization or decolorization using activated carbon or the like as needed. In particular, the above-mentioned extract can be used to remove alcohol by solvent replacement or the like to form a polyol lysate, and the extract component can be applied to the skin without irritating the sensitive skin, so that the effect of the active ingredient can be fully utilized. Therefore, it is preferred. Further, examples of the polyhydric alcohol include glycols such as ethylene glycol and polyethylene glycol (having an average molecular weight of 1,000 or less), propylene glycol, dipropylene glycol, and butylene glycol (1,3-butylene glycol); glycerin, Alcohol of 3 to 4 yuan such as diglycerin. Among them, propylene glycol, dipropylene glycol and L3_butanediol are preferred as the diol. In the sensory allergy prevention and improvement agent for sensitive skin of the present invention, the content of the polyol is preferably 0.02 to 50% by mass, particularly preferably 2 to 20% by mass. /. . Further, the ethanol content in the hypersensitivity preventing agent for sensitive skin of the present invention is preferably less than 8% by mass, more preferably less than 4% by mass, and even more preferably less than 1% by mass. /. 'Specially good is essentially free of ethanol. As shown in the examples described later, the Luohanbai extract can significantly increase the stimulation threshold without changing the amount of expression of nerve growth factor (NGF). Therefore, it can be preferably used as a sensory allergy prevention and improvement agent for sensitive skin. 152414.doc 201121555 The sensitive skin described in the current month of the month refers to the hypersensitivity state of the sensory stimuli due to the elongation of the nerve fibers to the underside of the intradermal cortex, which should cause excessive inflammation or immune response. The allergic state is distinguished from the diseased muscles such as atopic dermatitis. Specifically, because of the sensory nervousness, even small external stimuli (temperature, humidity, dust, allergens, etc.) are easily affected. When using cosmetics or being stimulated externally, you may feel hot, pinched, and painful. Feelings such as sensation, but the skin is relatively healthy, so even if it is applied to the 7-inflammation treatment, the skin will not be alleviated. An allergic condition causing excessive f disease or an immune reaction, or a disease such as atopic dermatitis, which causes an increase in the expression of nerve growth factor (NGF) at the site of inflammation, and thus the hyperalgesia is remarkably aggravated. The present inventors believe that the expression level of nerve growth factor (NGF) can be reduced to a normal level by administering an anti-inflammatory agent or a nerve growth factor (ngf) expression inhibitor as it is, and it can progress in a more desirable direction. However, the amount of expression of the original nerve growth factor (NGF) in the skin that did not produce inflammation did not increase, and it was possible to cause nerve growth factor (NGF) if it was administered to God, 4 growth factor (NGF) performance inhibitors as before. ) The amount of performance is reduced to below the normal level, and various shadows due to insufficient nerve growth factor (NGF) can prevent and improve the hypersensitivity symptoms of sensitive skin without changing the expression of nerve growth factor (NGF). The sensory allergy prevention and improvement agent for sensitive skin of the present invention is very desirable. The sensory allergy prevention improving agent for sensitive skin of the present invention can be formulated into a composition in any form with the additive. In the preparations, the content of the 152414.doc 201121555 Rohan cypress extract is preferably converted to 〇 〇〇〇 1 〇 〇 quality in solid matter. /. More preferably, it is 0.01 to 0.1% by mass. In addition, the solid matter conversion means a value obtained by converting the amount of the solid matter obtained after the measurement sample 10 H1L is dried at 1〇5〇C for 6 hours. In the sensory allergy prevention and improvement agent for sensitive skin of the present invention, a surfactant, a moisturizer, an oil agent, a thickener, a pigment, and a pigment which are formulated in a skin external preparation for cosmetics, a quasi-drug, and a pharmaceutical product can be appropriately formulated. , salts, chelating agents, neutralizers, UV absorbers, preservatives, fungicides, purified water, natural water, deep ocean water, ethanol, etc. Further, examples of the dosage form include an ointment, a lotion, a lotion, a cream, a gel, a dressing, a powder, an aerosol, a paste, and the like. The sensory allergy prevention and improvement agent for sensitive skin of the present invention is preferably used in a specific part of the skin for a certain period of time or more, not only once. In order to increase the stimulation threshold of the sensitive skin, it is preferred to contain a composition of 0.0001 to 0.1% by mass of the Luohanbai extract in terms of solid content, in an amount of mgmg/cm2 to 5 mg/cm2 per dose. The skin is used for 3 曰 or more, preferably 1 week or longer, from 1 to 1 to 5 times. More preferably, it is applied to the skin for 1 week or more, more preferably 1 day or more, in an amount of 1 mg/cm 2 to 3 mg/cm 2 per 1 to 1 3 times. [Examples] The present invention will be described in more detail by way of the following examples and test examples. Reference Example 1 (Manufacturing method of Luohanbai extract) The dried leaves (about 1 kg) of Luohanbai were finely chopped, immersed in ethanol (10 liters), and extracted while stirring at room temperature for 7 不. The filtrate obtained by 152414.doc 201121555 was filtered, and the ferment was allowed to stand at 5 ° C for 3 days, and then filtered again to obtain a supernatant: 50% of the amount was added thereto <1,3_丁二The alcohol solution was then filtered. The mash was concentrated, and further, butanediol and purified water were added thereto, followed by filtration to obtain a product (about 100 L). The obtained arbutin extract had a 1,3-butanediol content of 54 75%, a water content of 45%, and a Rohan cypress solid content of 05%. Test Example 1 The test skin LSE_High (manufactured by Toyobo Co., Ltd.) was used as a human skin remodeling model and cultured. Add a reference example in the medium to the amount of 2 mg/cm2!罗% (v/v) 丨, 3-butanediol: ethanol = 1:1 solution or control solvent (1,3-butanediol: ethanol = 1), after 72 hours of culture, The test skin epidermis was stripped with a small forceps, RNA (rib〇nuCleic acid, ribonucleic acid) was recovered, and nerve growth factor was examined by RT pCR (reverse transcripti〇np〇iymerase chain reacU〇n, reverse transcriptase polymerase chain reaction). The performance of NGF) and G3PDH (glycerol 1_3_phosphate dehydrogenase '3-phosphoglycerol dehydrogenase). The results are shown in Fig. 1. As can be seen from the figure, even if the application of Rohan cypress extract 'nerve growth factor (NGF) The degree of performance (NGF/G3PDH) did not change. Test Example 2 The effect of continuous application of Luohanbai extract on the current sensory stimulation threshold was selected from the subjects who tested sensitive skin, and the 1% lactic acid aqueous solution was stinged as follows. In the test, the subject who is not suffering from allergic dermatitis such as atopic dermatitis washes his face and 'fits for 〇 minutes, and is immersed in 1 cm of milk 152414.doc 201121555 acid aqueous solution 1.2 mL of 20 cm2 non-woven fabric For cheeks To allow the subject to report the score of the perceived sensory stimulus just after use and every minute after use until 1 minute (0 = no stimulation, 〇 5 = slightly felt stimuli, 1 = weaker, 1.5= Clearly feel the stimulus, 2〇=strong, 25=very strong, 3=unbearable), get the cumulative score of 1〇 total, and test it in distilled water in the same way, scoring the cheeks with distilled water In the case of a subject having a sensitivity of 5 or more, it is a sensitive skin of the present invention. For 12 subjects of the sensitive skin, a 4% aqueous solution of the Luohanbai extract of Reference Example 1 is used as a cheek portion of 2 mg/ The amount of cm2 was applied three times a day for 2 weeks (distilled water was applied to the other cheek as a control). To examine the degree of hypersensitivity of the peripheral nerves before and after continuous use, the sensory nerve was measured using a sensory neurometer (neurometer). The threshold value was as shown in Fig. 2. It was found that the current sensory threshold on the side of the aqueous solution of the arhatin extract was increased, and the hypersensitivity state was improved. Further, based on the above results, it can be considered that Using this agent, a factor different from the inhibitor of nerve growth factor (NGF) production inhibits the elongation of the nerve into the epidermis, and thus the state of hypersensitivity is improved. Further, the method of measuring the current sensory threshold using a sensory neurometer is as follows <<Measurement method of current sensing threshold>> An electrode having a diameter of about 1 cm is attached to the cheek portion, and a sensory neurometer manufactured by Neurottr〇n Co., Ltd. is used to circulate an AC of 25 Hz. At the current, the tester can feel the minimum level of current of the stimulus as the current sense threshold 152414.doc 201121555 (CPT: Current Perception Threshold). Test Example 3 Continuous application of the lactic acid stinging score change caused by the extract of Rohan cypress. 4 匕 For the § tester of Test Example 3, the reference example of the 4% aqueous solution of Luohanbai extract was used as a cheek 2 mg. The amount of /cm2 was continuously used for 3 weeks three times a day, and in the same manner as in Test Example 2, a 1% lactic acid aqueous solution tingling test was performed before and after continuous use. As a result, the subject's scores for the perceived sensory stimuli total after the use and after each use until after 10 minutes of use (0 = no stimulation, 0.5 = slight stimulation, 1 = weaker, 15 = the average of 12 people who clearly felt the stimulus '2.0 = stronger, 2.5 = very strong, 3 = unbearable), and the cumulative score of 12 people, as shown in Figure 3, was applied to the aqueous solution of Luohanbai extract. The cheeks on the side of the cheeks were reduced before and after continuous use, and the hypersensitivity was improved. Further, no adverse effects due to delayed skin regeneration such as rough skin texture were observed. BRIEF DESCRIPTION OF THE DRAWINGS Fig. 1 is a graph showing the effect of Luohanbai extract on the expression of nerve growth factor (NGF) in a human skin remodeling model. Fig. 2 is a graph showing the current perception threshold (CPT) of sensitive skin before and after continuous application of the Rohana extract. Fig. 3 is a graph showing the stinging score of sensitive skin before and after continuous application of the extract of Rohan. 1524I4.doc