TWI378799B - - Google Patents
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- TWI378799B TWI378799B TW097150734A TW97150734A TWI378799B TW I378799 B TWI378799 B TW I378799B TW 097150734 A TW097150734 A TW 097150734A TW 97150734 A TW97150734 A TW 97150734A TW I378799 B TWI378799 B TW I378799B
- Authority
- TW
- Taiwan
- Prior art keywords
- skin
- extract
- external preparation
- fatty acid
- manufactured
- Prior art date
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- 238000002360 preparation method Methods 0.000 claims description 49
- -1 sucrose fatty acid esters Chemical class 0.000 claims description 49
- 239000000194 fatty acid Substances 0.000 claims description 45
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 40
- 229930195729 fatty acid Natural products 0.000 claims description 40
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- 239000005720 sucrose Substances 0.000 claims description 23
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- 235000013399 edible fruits Nutrition 0.000 claims description 9
- QCDWFXQBSFUVSP-UHFFFAOYSA-N 2-phenoxyethanol Chemical compound OCCOC1=CC=CC=C1 QCDWFXQBSFUVSP-UHFFFAOYSA-N 0.000 claims description 7
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 7
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- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 claims description 6
- FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 claims description 5
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1378799 九、發明說明: 長期保存穩定 【發明所屬之技術領域1 本發明係關於一種對皮膚之刺激性較,』 性優異之美肌及美白效果較高的皮膚外用 【先前技術】 通常,作為化妝品而調配之皮膚外田為 »'用劑中,係使用各種 孔化、分散,其中,
響’為了確保化妝品在通常保存之溫 界面活性劑以實現不溶成分之增溶、 &性劑在水或油中之 ’多受到溫度之影 度區域中之長期穩定 性,必須設法將活性劑之調配量設定得較多,因而無法忽 視其對皮膚之刺激性》 又,於通常作為化妝品而調配之皮膚外用劑中為了防 止由微生物所引起之腐敗、變質而普遍使用對羥基苯甲酸 類或苯氧基乙醇等防腐劑,但其對皮膚自身之刺激性等則 長久以來被視為問題。 尤其在近期,皮膚承受各種外在、内在壓力,例如乾燥 或紫外線、以及引起過敏症狀之花粉'因社會生活而受到 的心理影響等’皮膚即使受到微小刺激亦會變得敏感之情 況較多’因而業界正謀求更關注刺激性之皮膚外用劑。 杜鵑醇(rhododendrol)及其衍生物已知係可預防、改善 斑點、雀斑等皮膚之色素沈積的成分(參照專利文獻 137274.doc « 、 ' · · -U) ’但關於將杜鵑醇及其街生物用於防腐防徵之情況則 v 尚不為所知。 又,杜糾及其Μ物在水巾之轉性㈣,調配有杜 鵑醇及其衍生物之製劑、尤其是幾乎不具有黏性之化妝水 2中,為了提高製劑之穩定性而使用比通常更多之用作增 溶劑之聚氧乙烤加成型非離子界面活性劑,進而必須設法 . 組合調配低級醇,而成為增加對皮膚之刺激性的一個原 因。 ’、 [專利文獻1]日本專利第3340928號說明書 [專利文獻2]曰本專利第334〇935號說明書 [專利文獻3]曰本專利第34554〇6號說明書 【發明内容】 本發明提供-種皮膚外用劑,其特徵在於含有:⑷選自 下述通式(1)所表示之杜鵑醇及其衍生物中之丨種或2種以 上、(b)選自蔑糖脂肪酸醋及聚甘油脂肪酸醋令之】種或2種 • 以上、以及(c)多元醇。 [化1]
(式中,R為氫原子、碳數2〜2〇之醯基、或者單醣類或二醣 類之醣殘基)。 【實施方式】 本案發明提供一 種皮膚外用劑,其將杜鵑醇及其衍生物 137274.doc * 6 - 1378799 穩定地調配於皮膚外用劑中,並且減少被認為是皮膚刺激 之原因的界面活性劑或防腐劑之添加量,從而刺激性較 /J、〇 本發明者等人繁於上述狀況而進行積極研究,結果發 現.藉由將杜鵑醇及/或其衍生物,與蔗糖脂肪酸酯及/或 聚甘油脂肪酸g旨及多元醇組合使用,可獲得製劑之穩定性 優異、皮膚刺激性較低、且防腐防黴效果優異之皮膚外用 劑。 藉由本發明’可提供一種能夠穩定地調配杜鵑醇及其衍 生物之皮膚外用劑。本發明巾,可抑制存在皮膚刺激問題 之聚氧乙稀加成型非離子界面活性劑之使用因此可減小 皮膚刺激。進而’因杜鵑醇及其衍生物自身之防腐防黴效 果優異’故亦可抑制先前之對羥基苯曱酸酯或苯氧基乙醇 等防腐劑的使用,故而亦可減小由該等防腐劑所引起之皮 膚刺激,從而提供於安全性方面亦優異之皮膚外用劑。 以下,對本發明之構成進行詳細說明。 本發明之皮膚外用劑中,調配下述通式(1)所表示之杜 鵑醇或其衍生物作為(a)成分。 [化2]
(式中,R為氫原子、碳數2〜2〇之醢基、或者單醣類或二醣 類之醣殘基)。 137274.doc [Si 1378799 上述通式(1)中,r為氫原子之杜鵑醇[4_(對羥基苯基 丁醇]為眾所周知之化合物,並且已知在槭樹(Acer nik0ence Maxim.)等中含有該化合物。杜鵑醇可藉由先前 眾所周知之方法來合成,亦可使用市售品。又,亦可使用 由槭樹之萃取物純化而成者。 本發明所使用之杜鵑醇及杜鵑醇衍生物中存在光學異構 體,可單獨使用(+)體、㈠體,亦可使用(+)體與㈠體之混 合物(表示為(±),日本專利特開平3_251548號公報)。 本發明所使用之以通式(1)表示之杜鵑醇衍生物中,尺為 碳數2〜20之醯基的醯基化杜鵑醇只要為通常所使用者則並 無特別限定。醯基化杜鵑醇可藉由利用先前眾所周知之方 法將杜鵑醇加以醯基化而容易地獲得。此處,作為該醯 基,可列舉乙醯基、丙醯基、丁醯基、戊醯基、己醯基、 癸醯基等,就穩定性、易合成性之方面而言,較好的是直 鏈飽和醯基。另外,作為本發明中使用.之醯基化杜鵑醇, 可列舉己酿杜鵑醇、乙醯杜鵑醇等之(+)體、㈠體、(幻 體。 本發明所使用之以通式(1)表示之杜鵑醇衍生物中,尺為 醣殘基之杜鵑醇糖苷中的醣殘基係還原性之單醣類或二醣 類’具體可列舉:葡萄糖、半乳糖、木糖、甘露糖、义乙 醯基葡萄糖胺等單醣類’麥芽糖、纖維雙糖、龍膽雙糖等 二醣類。本發明之糖苦中存在具有α鍵結及β鍵結之異構 體,該等可單獨使用,亦可使用該等之混合物。 本發明之杜鵑醇糖苷可使用以熊果苷之合成方法而為眾 137274.doc 1378799 所周知的方法(USP第3201385號)而獲得。例如,可於甲苯 等有機溶劑中將三氟㈣或相氯等作為觸媒而使杜鹃醇 /、乙醯化糖缩合,然後於鹼之存在下使乙醯基脫離,藉此 以白色粉末結晶之形態而容易地獲得本發明之杜鵑醇糖 苷。又,亦可藉由將覆盆子酮葡萄糖苷還原而獲得。進 而,亦可自天然物分離而獲得。又,本發明之糖苷中存在 光學異構體,可單獨使用(+)體、(_)體,亦可使用該等光 學異構體之混合物(±)。 作為本發明中所使用之具體糖苷,可列舉:杜鹃醇_D-葡萄糖苷(α及β體)、杜鵑醇·ε>-半乳糖苷(〇1及!3體)、杜鵑 醇-D-木糖苷(α及β體)、杜鵑醇_D_麥芽糖苷仏及^體)等之 (+)體、㈠體、(±)體。 (a)成分之杜鵑醇及其衍生物中,就防腐防黴效果、皮膚 刺激性等觀點而言,尤其好的是杜鵑醇。 關於本發明中所使用之(a)成分的含量,於通式(1)中R為 氫原子之杜鵑醇之情形時,以皮膚外用劑之總量為基準, 較好的是0· 1〜3質量%,更好的是0.2〜3質量%,尤其好的是 0.5〜3質量。。又,於r為碳數2〜20之酿基的醯基化杜鵑醇 之情形時,以皮膚外用劑之總量為基準,較好的是〇· 1~5 質量%,更好的是0.5〜5質量%,尤其好的是1〜5質量%。 又’於R為醣殘基之杜鵑醇糖苷之情形時,以皮膚外用劑 之總量為基準,較好的是0.1〜5質量%,更好的是〇.5〜5質 量%,尤其好的是1~5質量%。 若含量在該等範圍内,則可有效地發揮防腐、防黴效 137274.doc 1378799 果,並且可獲得在皮膚外用劑之配方中的廣泛自由度。 本發明之皮膚外用劑中’與上述(a)成分一併組合調配作 為(b)成分之選自蔗糖脂肪酸酯及聚甘油脂肪酸酯中之非離 子界面活性劑、以及作為(c)成分之多元醇。 作為蔗糖脂肪酸酯,可列舉蔗糖單脂肪酸酯、蔵糖二脂 肪酸酯、蔗糖三脂肪酸酯等,於本發明中,較好的是使用 具有如下酯分布之混合蔗糖脂肪酸酯:以蔗糖脂肪酸酯之 總量為基準,蔗糖單脂肪酸酯為60〜90質量❹/。,簾糖二脂 肪酸醋為5〜40質量%。簾糖脂肪酸酯申之脂肪酸為碳數 12~18之飽和或不飽和脂肪酸,可較砝地例示月桂酸、肉 豆蔻酸、棕櫚酸、硬脂酸、油酸等❶作為調配比率較高之 蔗糖單脂肪酸酯,較好地可列舉蔗糖單月桂酸酯、嚴糖單 硬脂酸S旨。 本發明中所使用之聚甘油脂肪酸酯中之甘油的平均聚合 度較好的是2〜16。作為酯化度,可列舉單酯、二醋、三 酯。於本發明中,可較好地使用甘油之平均聚合度為 2〜1 0、且為單醋者。 本發明中所使用之聚甘油脂肪酸酯中之脂肪酸,較好的 是碳數為10〜18之脂肪酸。尤其好地可例示月桂酸、肉豆 蔻酸、椋櫊酸、硬脂酸、異硬脂酸、油酸、亞麻油酸或山 茶酸等。 本發明中所使用之聚甘油脂肪酸醋在市面上銷售有多 種,作為尤其好的聚甘油脂肪酸酯可例示:十甘油單月 桂酸醋、十甘油單油酸醋、十甘油單硬脂酸醋等。 I37274.doc 1Λ -1U - [S] 1378799 本發明中所使用之上述特定非離子界面活性劑(b)較好 的是 HLB值(hydrophilic-lipophilic balance value,親水親 油平衡值)為10以上,尤其好的是11〜18。若HLB在該範圍 内,則容易將(c)成分調配至乳化製劑中,且在(a)成分於 製劑中之穩定性方面可獲得尤其良好的結果。 再者,混合使用2種以上之非離子界面活性劑時,若其 混合HLB值在上述範圍内,則一部分非離子界面活性劑之 HLB值亦可為1〇以下。此處,混合HLB值係藉由將各非離 子界面活性劑之HLB值乘以各自之比例,並將所獲得之值 進行合計而算出。 各非離子界面活性劑之HLB值可依據J. T. Davies and B. Κ· Rideal,Interfacial Phenomea,Academic Press,New York 1963, pp. 371-383 來計算。 作為本發明中所使用之多元醇(c),可例示甘油、二甘 油、1,3-丁二醇、聚乙二醇、二丙二醇、丙二醇、己二 知、異戊二醇、赤藻糖醇、木糖醇、麥芽糖醇、海藻糖 醇、山梨糖醇等。其中’尤其好的是甘油、丨,3_丁二醇、 —丙二醇。 於本發明中,(b)成分與(c)成分一併發揮對(&)成分增溶 之作用,在將皮膚外用劑製成乳化物時,其兼具乳化劑之 作用’而與製劑之穩定性有關。 以皮膚外用劑之總量為基準,本發明之(b)成分即特定 之非離子界面活性劑的含量較好的是〇〇1〜5質量。/。,更好 的是0’05〜3質量%。於該等含量範圍β,作為界面活性劑 137274.doc I S1 1378799 之基本功能即增溶、乳化、分散作用良好,同時皮膚外用 劑之使用性亦優異。又,亦不易產生由界面活性劑所引起 之刺激感。 又,以皮膚外用劑之總量為基準,(C)成分即多元醇之含 量較好的是0.1〜30質量%,更好的是〗·〇〜20質量%。於該等 含量範圍内’作為界面活性劑之基本功能即增溶、乳化、 分散作用良奸’同時皮膚外用劑之使用性亦優異。 本發明所使用之杜鵑醇或其衍生物,其自身具有優異之 抗菌作用,即使於不調配為防止製劑之一次及二次污染而 調配之對羥基苯甲酸酯及/或苯氧基乙醇之情形時,亦可 防止由微生物所引起的製劑之腐敗、變質。因此,本發明 之皮膚外用劑中較好的是實質上不含對羥基苯曱酸酯及/ 或苯氧基乙醇。 本發明之皮膚外用劑中,可進而含有中文名為「火棘」 之物質。「火棘」係薔薇科火棘屬(R〇saceae pyracantha)之
一種,其果實之中藥名為「赤陽子」,已知其具有健脾、 治療消化不良等藥效。X,其具有路胺酸酶活性抑制效果 及黑色素生成抑制效果,已提出有調配有其萃取物之美白 用化妝料(曰本專利特開平5、5587〇號公報)。 該「火棘」之果實即中藥名為「赤陽子」之有效成分 (以下簡稱為「火棘萃取物」),係藉由水、甲醇、乙醇或 丙醇等低級醇或者其等之混合液而萃取出。其萃取液亦可 直接調配於皮膚外用劑中,較好的是利用冷;東乾燥法或喷 霧乾燥法等將其製成粉末後再進行使用。又亦可利用 137274.doc •12· 1378799 • 液-液分佈、吸附層析等方法將萃取液純化,而調配出液 . 狀者或粉末化者。 以此種方式獲得之火棘萃取物,就其特性而言,亦可作 為抑制由高溫或光所引起之製劑褐變的還原劑而進行 配。 = - 以皮膚外用劑之總量為基準,本發明之皮膚外用劑中之 (d)成分即上述火棘萃取物之含量,以萃取物之固形物換 鲁 算,較好的是0.001〜5質量%,更好的是0.005〜2質量%。若 在該等範圍内’則可更有效地抑制製劑之褐變。 又,當本發明之皮膚外用劑含有聚氧乙烯加成型非離子 界面活性劑時,根據其調配平衡,而存在會妨礙(b)成分之 功能、且對杜鵑醇或其衍生物之穩定調配有較大影響的情 況,故而以(b)成分之含量為基準,將其含量設為5〇質量% 以下,較好的是設為20質量%以下,尤其好的是實質上不 含有該聚氧乙烯加成型非離子界面活性劑。 • 進而,本發明之皮膚外用劑中,除上述必需成分以外, 可於無損本發明效果之範圍内視需要而適當調配通常藥 . 品、準藥品、化妝品等中所調配之其他成分,例如油劑、 界面活丨生劑、增黏劑、金屬離子螯合劑、pH值調節劑、 水、醇類、化學試劑、紫外線吸收劑、紫外線散射劑、色 素、香料等。 又’可製成軟膏類、化妝水類、乳液類、霜類、面膜類 等任意劑型。 [實施例] 137274.doc 1378799 其次’藉由實施例對本發明加以更詳細說明’但本發明 不限定於該實施例。再者,調配量均為質量0/〇。 於實施例中,製劑之穩定性係藉由對渾濁及沈澱之外觀 坪價、加速條件下之變色評價以及日光暴露下之變色評價 而進行。又,皮膚刺激性係藉由一組女性官能檢查員之皮 膚刺激性評價而進行,防腐防黴性係藉由使用標準菌之評 價而進行。以下,對各評價之具體試驗方法加以說明。 •穩定性評價(1) 將評價樣品於45 °C下保存個2月後,依據以下基準目測 评價其外觀(有無渾濁、沈澱)。 (評價基準) x :有大量洸澱或渾濁 △:有沈澱或渾濁 〇:有少許沈澱或渾濁 ◎:無沈澱、渾濁 •穩定性評價(2) 將怦價樣品於601下保存!個月後,依據以下基準目測 比較評價其變色程度。 (評價基準) X :嚴重 變色 △ :有變 色 〇 :稍許 變色 ◎ :無變 色 • 穩定性評價(3) 137274.doc 1378799 將評價樣品曝露於日光下保存1週後,依據以下美準目 測比較評價其變色程度》 (評價基準) X : 嚴重變色 Δ : 有變色 〇: 稍許變色 ® : 無變色 •皮膚刺激性評價 由20名自認為肌膚敏感之一組女性官能檢查員(2〇多歲 至50多歲)進行評價。讓女性官能檢查員連續3天早晚2次 使用被檢樣品,最後一天依據以下基準來評價關於皮膚刺 激性之使用感。1次對一種評價樣品進行評價,休息2天後 以同樣之方式進行下一評價樣品之評價。 (評價基準) 得分3 :感覺到刺激 得分2 :稍許感覺到刺激 得分1 :幾乎感覺不到刺激 得分0 ··完全感覺不到刺激 對照以上4等級之基準進行評價。以出現例數作為結果 並將其示於表4中。由此可確認,本發明之皮膚外用劑在 刺激性較低之方面亦優異。 •防腐防黴性評價 使用被指定為標準菌之真菌[黴菌(Aspergi丨lus niger ATCC 16404’ 黑麵黴 ATCC 16404)、酵母(Candida albicans 137274.doc -15- 1378799 ATCC 10231,白色念珠菌 ATcc 1023 1)]及細菌(Escherichia coli ATCC 8739,大腸桿菌ATCC 8739)株,以相對於每1 g 。平4貝樣。口達到1X10菌落形成單位(c〇l〇ny f〇rrning unit,以 下稱為cfu)之方式接種黴菌之胞子或48小時前培養之酵 母,或以相對於每1 g評價樣品達到lxl〇6 efu之方式接種24 小時前培養之細菌,並放置於室溫下。接種後第1天起至 28天為止經曰測量評價樣品中之存活微生物數,依據以下 基準以3個等級進行評價。再者,將黴菌、酵母、細菌各 自之評價中最低之評價作為關於防腐防黴性之综合評價。 (評價基準) —------ 〇:接種之黴菌28天減少至未滿lxl02cfu/g。 接種之酵母28天減少至未滿ixi〇2 cfu/g。 接種之細菌14天減少至未滿lxl〇2 cfu/g。 ---------- △:接種之黴菌28天減少至1Χ1〇2〜ixl04 efu/g。 接種之酵母28天減少至1χ1〇2〜ixl04 cfu/g。 接種之細菌14天減少至ΙχΙΟ2〜ixi〇5 efu/g。 X:接種之黴菌28天未減少至1χ1〇4 Cfu/g以下 接種之酵母28天未減少至lxl〇4 Cfu/g以下 接種之細菌14天未減少至lxl〇5 Cfu/g以下 實施例1〜24,比較例1〜6(化妝水) 進行上述 依照表1〜3所示之配方利用常法製備化妝水 各種評價試驗。其結果亦一併表示。 -16- 137274.doc [S] 1378799 【I Ϊ I37274.doc 一一 〇一 •一 •一 Γ0 ΙΌ Γ0 ΙΌ ΙΌ ΙΌ 〇〇〇〇 ¥#葚 <3 ◎〇〇 〇◎〇〇 ΙΌ ΙΌ ΙΌ 〇◎〇Ο
10Ό IL •一 •一 Γ0 Γ0 ΙΌ ΙΌ ΓΟ Ο © Ο χ 〇◎〇〇 Γ0 ΙΌ 〇◎〇〇 ζε ΓΟ ◎〇〇〇 ΙΌ ΙΌ ΙΌ ◎〇〇<3 •一 Γ0 ΓΟ ΙΌ 〇〇〇〇
•I ΙΌ ◎〇〇〇 珈窭诹涵-9敏瑶龙 敏瑞龙滷0 敏瑞T令 (ε 祐)塯湓铨-·®·-'10鉍 (一雄)溫窗锭-邀海 敏-rh_- ss^ • 17· (IFl^^^-^B^y?^(SI' a09)s (呎厚z ,ps寸,粳晚 (Γ卜 l = 3H * ?F 鉍 i?々、^-^Y)A--byosuns(n:o (•-HalH *^蕻1?々/釙-^51-1 u-3s3alox>ilN<^l) (9l = 81H - iF鉍阳^05。伞卧-沏 M)s69l-lJss3JBSnsoloAy (1¾) 1378799
實施例 ..g 1 1 Ο Ο Ο 剩餘量 〇◎〇〇 cn ΓΊ .,S 1 1 VO 2寸 剩餘量 〇◎〇〇 (Ν CN νη 1 攀 00 1 1 m »n cn o 剩餘量 〇◎〇〇 m « 1 1 | » cn 1 1 m un cn 剩餘量 〇◎〇〇 • 1 1 ' S 1 1 m m <N oo 剩餘量 〇◎ ◎〇 〇\ . 1 1 ,.^ 1 1 c〇 (N CN 剩餘量 〇◎ ◎〇 00 • 1 1 ^―( 1 . g 1 1 r〇 to (N | 0.005 I 剩餘量 〇◎〇〇 卜 。,, m i i 1 ( m ^ (N c5 剩餘量 ◎〇〇〇 m • 1 1 〇 I 1 〇 1 1 m (N d> 剩餘量: ◎〇〇〇 »n ^ ,, 0.05 :0.05 1 1 m in (N 1 剩餘量: ◎ X <]〇 寸 ^ ,, 0.05 0.05 1 1 ro ^ CN o 0.1 0.1 剩餘量 〇◎ ◎〇 m »—η ^ , _ 0.05 0.05 1 1 m <N 剩餘量 ◎ ◎ ◎〇 (Ν ^ ,. T—4 c; ' o 1 1 m m cs 剩餘量 ◎ ◎〇〇 讳1 截 w 敏® S 9 鮏龙鮏 链鐳铿 边<〇龙 π p 二'捃找 lJ S·^ N««X 5避避 怒运运 松 Αίατ ιίσι ax; a^ a^ 鹊溲淚 寒 Φ1 i〇 /*—s d ω 0/ Έ Q邀 ω, S畤 璲鮏 滅墩 ^蘇 ^ -β 装费 t0 ό ¢5^ ^ —”1 i 火棘萃取物 &- 键 B·鮏 i-4 »0 地辦¥ 澈®ί (Ν '―· ^ C: ^ 5 ^ ^ Ξ Η- i〇 ^ ^ ,:、s 食 l 照<β3 <i〇涠 137274.doc -18· 1378799 [表3]
比較例 1 2 3 4 5 6 杜鵑醇 1.5 1.5 1.5 1.5 1.5 - 乙醱杜鵑醇 • - - - - - 杜鹃醇-D-葡萄糖苷 - - - - - 蔗糖脂肪酸酯(註1) - - - - 0.05 0.05 聚甘油脂肪酸酯(註2) - - - - - - 聚甘油脂肪酸酯(註3) - - - - 0.05 0.05 聚氧乙烯硬化蓖麻油(60ΕΌ.) 0.1 1 - 0.5 - - 聚氧乙烯山梨糖醇酐單月桂酸醋(20E.O.) - 0.5 0.5 1,3-丁二醇 3 3 3 3 - 3 二丙二醇 5 5 5 5 - 5 甘油 2 2 2 2 - 2 火棘萃取物 0.1 0.1 0.1 0.1 0.1 0.1 對羥基苯甲酸甲酯 . • - _ _ 苯氧基乙醇 - - - - - 純化水 剩餘暈 剩餘量 剩餘量 剩餘量 剩餘量 剩餘量 渾濁·沈澱(45°C、2個月) X X X X Δ ◎ 變色(60°C、月) 〇 〇 〇 〇 ◎ 〇 變色(於曰光下曝露1週) ◎ ◎ 〇 〇 〇 〇 防菌防黴性 ~ Δ △ 〇 〇 Δ X
如表1〜3所示,本發明之實施例之穩定性良好,相對於 此’不含本發明之(b)成分或(c)成分的比較例1〜5,可觀察 到渾濁、沈澱,在穩定性方面存在問題。又可知,本發明 之實施例之防腐、防黴性優異,相對於此,比較例id儘 管含有杜鵑醇,但由於製劑之穩定性較差,故其防腐、防 徽性無法充分發揮。實施例2雖為本案之實施例,但由於 (b)成分即特定之非離子界面活性劑相對於所有非離子性界 面活性劑之含有比率較低,結果導致製劑之穩定性稍許變 差°實施例1 5為不含火棘萃取物之情況,其關於渾濁 '沈 澱之製劑穩定性及防腐、防黴性優異,然而於高溫下或曝 137274.doc 19 1378799 露於日光下之變色穩定性差,從而可知火棘萃取物對變色 穩定性大有助益。實施例22雖然製劑穩定性優異,但由於 含有比較多之非離子性界面活性劑,故實際使用時有產生 皮膚刺激之虞。實施例24雖然製劑穩定性亦優異,但由於 含有比較多之多元醇,故實際使用時有在觸感方面感覺黏 著之虞。 進而,將對上述實施例丨、12、13、14及比較例4進行皮 膚刺激性評價之結果示於表4。可知,本發明之實施例i、 2 13對皮膚幾乎無刺激,安全性優異,但若將通常所用 之防腐劑即對錄笨甲酸甲醋或苯氧基乙醇與杜鹃醇同時 使用貝J會產生皮膚刺激(實施例14)。比較例4係使用通常 所用之非離子界面活性劑即聚氧乙烯加成型活性劑來代替 本發月特定之非離子界面活性劑其可觀察到皮膚刺激, 可知在安全性方面差。 [表4]
試驗’均可獲得優異之結果 137274.doc m *20- 1378799 [表5] 實施例25 乙醇 3 1,3-丁二醇 2 二丙二醇 5 蔗糖脂肪酸酯(註4) 0.05 聚甘油脂肪酸酯(註3) 0.05 杜鵑醇-D-葡萄糖苷(β體) 3 甘草酸二鉀 0.1 火棘萃取物 0.1 純化水 剩餘量 渾濁、沈澱(45°C、2個月) ◎ 變色(6(TC、1個月) ◎ 變色(於日光下曝露1週) ◎ 防腐、防黴評價結果 ◎ (註4)SURFH0PE SE COSME C-1216(三菱化學食品公司製造, HLB=16) [表6] 實施例26 角鯊烯 10 硬脂酸 5 鯨蠟醇 2.5 凡士林 2 蜂蠟 1 1,3-丁二醇 3 二丙二醇 5 蔗糖脂肪酸酯(註5) 1.5 蔗糖脂肪酸酯(註6) 0.5 己醯杜鵑醇 3 火棘萃取物 0.1 甘草酸二鉀 0.2 純化水 剩餘量 渾濁、沈澱(45°C、2個月) ◎ 變色(60°C、1個月) ◎ 變色(於曰光下曝露1週) ◎ 防腐、防黴評價結果 ◎
(註5)SURFHOPESECOSMEC-1816(三菱化學食品公司製造,HLB=16) (註6)3111^^〇?£3£(:〇31^(:-1807(三菱化學食品公司製造,1«3 = 7) 137274.doc •21 · 1378799 進而,依照以下配方藉由常法製備皮膚外用劑,並進行 上述各種評價試驗’可確認製劑之穩定性、防腐防黴性能 優異,不存在對皮膚之刺激性。 應用例ι(化妝水) 及料成分___調配量
1,3-丁二醇 2.0 二丙二醇 6.0 濃甘油 5.0 杜鵑醇 1.5 甘草酸二鉀 0.2 蔗糖脂肪酸酯(註4) 0.3 玻尿酸鈉 0.01 火棘萃取物 0.1 甘草黃酮(1 1) 0.01 棉子糖(1 2) 0.05 喜馬拉雅山覆盆子根萃取物(1 3) 0.05 歐洲接骨木萃取物(1 4) 0.01 黃連萃取物(氺5) 0.01 桃金孃萃取物(1 6) 0.01 純化太 剝餘 137274.doc • 22- IS1 1 1 :油溶性甘草萃取物Ρ-Τ(40)(丸善製藥公司製造) *2 : Oligo GGF(旭化成工業製造) *3 :喜馬拉雅山覆盆子萃取液BG80(丸善製藥公司製造) * 4 :接骨木萃取液BG(丸善製藥公司製造) 1378799 *5:黃連萃取液-J(丸善製藥公司製造) * 6 :桃金孃萃取液BG80(丸善製藥公司製造) 應用例2(乳液)
原料成分 調配量 乙醇 5.0 杜鵑醇 2.0 蔗糖脂肪酸酯(註1) 0.5 曱基苯基聚矽氧烷(* 7) 1.0 甲基聚矽氧烷(* 8) 1.0 三(2-乙基己酸)甘油酯 1.0 對曱氧基桂皮酸-2-乙基己酯 0.1 二丙二醇 3.0 濃甘油 2.0 羧乙稀聚合物(氺9) 0.25 氫氧化鉀 0.12 依地酸二鈉 0.01 火棘萃取物 0.15 胡蘿蔔萃取物(* 10) 0.1 西洋梨醱酵萃取物(* 11) 0.1 藍莓葉萃取物(* 12) 0.1 烯明素葡萄糠苷(* 13) 0.1 海藻萃取物(* 14) 0.01 純化水 制餘詈 * 7 : Silicon FZ-209(日本UNICAR公司製造) I37274.doc •23· 1378799 * 8 : KF-96A-200cs(信越化學工業公司製造) * 9 · CARBOPOL 941(Noveon INC.公司製造) * 10 :植物膠原(Vegetable Collagen)(高研公司製造) * 11 : FermentagePearExtract(ICHIMARUPHARCOS公司製造) * 12 : CureBerry Extract(ICHIMARU PHARCOS公司製造) *13:烯酮素葡萄糖苷(長谷川香料公司製造) * 14 : Marine Purge(ICHIMARU PHARCOS公司製造) 應用例3(乳液)
成分__調配量 乙醇 10.0 氫化大豆磷脂質(* 15) 1.0 膽固醇 0.5 聚甘油脂肪睃酯(註7) 0.2 N-曱基-L-絲胺酸 〇.〇1 聚氧乙烯甲基葡萄糖苷(*16) 2.0 角鯊烯 2.0
環戊聚矽氧烷 1.0 1,3-丁二醇 2.0 聚甘油 1.0 杜鹃醇-D-葡萄糖苷 2.0 丙稀酸甲基丙烯酸烧基酯共聚物(* 17) 0.2 氫氧化鉀 0.1 甘草酸二鉀 0.1 玻尿酸鈉 0.05 三乙醇胺 0.5 137274.doc •24- 1378799 三仙膠 o.i 火棘萃取物 0.1 白芥子水解萃取物(*1 8) 0.01 忍冬萃取物(* 19) 0.01 豆乳醱酵液(*20) 0.01 小麥胚芽萃取物(* 21) 0.01 博士草萃取物(*22) 0.01 香料 0.03 純化水_剩餘量 (註7)Sunsoft Q-12S(太陽化學公司製造,HLBM6.1) 氺15 : Lecinol S-10(日光化學公司製造) * 16 : NIKKOL BMG-20(曰光化學公司製造) * 17 : PEMULEN TR-l(Noveon INC.公司製造) * 18 : Sinablanca WH(TECHNOBLE公司製造) * 19 : Pharcolex忍冬 SB(ICHIMARU PHARCOS公司製造) 氺20 :豆乳醱酵液(三省製藥公司製造) * 21 : Clariskin(Silab公司製造) *22 : Pharcolex博士草B(N)(ICHIMARUPHARCOS公司製造) 應用例4(乳液) 原料成分_調配量 角鯊烯 2.0 親油型單硬脂酸甘油酯 1.5 硬脂酸 1.0 鯨蠟醇 0.4 137274.doc -25 聚甘油脂肪酸酯(註8) 0.2 聚甘油脂肪酸酯(註9) 2.0 1,3-丁二醇 3.0 杜鵑醇 1.5 三乙醇胺 0.2 火棘萃取物 0.05 蓮子醱酵萃取物(* 23) 0.05 印度苦楝葉萃取物(* 24) 0.05 海補血草萃取物(*25) 0.05 羽扇豆萃取物(* 26) 0.05 咖喔葉萃取物(* 27) 0.05 香料 0.02 純化水 剩餘量 1378799
(註8)RYOTO聚甘油酸酯ER-30D (三菱化學食品公司製造,HLB = 10)
(註9)RYOTO聚甘油酸酯SWA-10D (三菱化學食品公司製造,HLB=15) * 23 :蓮釀果(TECHNOBLE公司製造) 氺24 :印度苦楝葉萃取液B(ICHIMARUPHARCOS公司製造) * 25 : Sea Lavender SC(SECMA公司製造) * 26 : Structurine(Silab公司製造) 氺27 :咖喱葉萃取液(禦木本公司製造) 應用例5(0/W型(水中油)霜) 原料成分_調配量 137274.doc -26- 1378799 角鯊烯 1〇_〇 棕櫊酸異丙酯 20 親油型單硬脂酸甘油酷 1 · 〇 硬脂酸 7·〇 蜂蟻 1〇 蔗糖脂肪酸酯(註5) 2-5 蔗糖脂肪酸酯(註6) 0.5 甲基苯基聚矽氧烷(氺7) 0.5
1,3-丁二醇 1〇.〇 杜鵑醇-D-葡萄糖苷 3.0 產鹼桿菌B16聚合物 〇·〇5 火棘萃取液 0.1 胡蘿蔔液汁(* 28) 〇.1 橘子果汁(氺29) 0.1 山藥萃取物(*30) 〇-1
酵母萃取物(*31) 〇.1 珊瑚草萃取物(* 32) 〇.1 氫氧化If 0.5 香料 0.03 純化皮__剩餘量 * 28 : Hormo Fruit Carrot N(ESPERIS公司製造) * 29 : Hormo Fruit Orange N(ESPERIS公司製造) *30:山藥根萃取物(三井化學公司製造) *31 :酵母萃取液ZB(ICHIMARU PHARCOS公司製造) 137274.doc -27· [S] 1378799
* 32 :珊瑚草(TECHNOBLE公司製造) 應用例6(W/0型(油中水)霜) 原料成分 調配量 山梨糖醇酐單異硬脂酸酯 1.0 曱基環聚矽氡烷(* 33) 10.0 二曱石夕氧共聚醇(dimethicone copolyol) 2.0 角鯊烯 3.0 蔗糖脂肪酸酯(註10) 0.2 氯化納 1.0 氯化鎂 1.0 二丙二醇 7,0 己醯杜鵑醇 2.0 甘草次酸硬脂酸酯 0.1 微粒子氧化鈦(* 34) 2.0 對甲氧基桂皮酸-2-乙基己酯 0.1 火棘萃取液 0.05 杏果汁(* 35) 0.01 七葉樹萃取物(* 36) 0.01 β-胡蘿蔔素(* 37) 0.01 香料 適量 純化水 劍餘詈 (註 10)SURFHOPE SE COSME C-1811 (三菱化學食品公司製造,HLB = 11) * 33 : TSF405(GE-TOSHIBA SILICONE公司製造) 137274.doc -28-
I SI 1378799 * 34 : Tipaque ΤΤΟ-55(Α)(石原產業公司製造) *35:杏子萃取物K(ESPERIS公司製造) *36:七葉樹萃取液BG-J(丸善製藥公司製造) * 37 : β胡蘿蔔素(ROCHE公司製造) 應用例7(美容液) 原料成分_調配詈 乙醇 5.0 脫脂酸卵磷脂 〇·5
聚甘油脂肪酸酯(註3) 0.1 曱基苯基聚矽氧烷(*7) 2.0 1,3-丁二醇 3.0 聚氧乙烯曱基葡萄糖苷(*16) 0.5 聚乙二醇1000 1.0 杜鵑醇 3 · 0 丙烯酸曱基丙烯酸烷基酯共聚物(註1) 〇.1 2-甲基丙烯醯氧基乙基磷醢膽鹼 0.5
•曱基丙烯酸共聚物(* 38) 甘草酸二鉀 0.2 菸鹼醯胺 1.0 氯化左旋肉鹼 0.3 N-曱基-L-絲胺酸 0.1 氫氧化鉀 〇·〇7 火棘萃取物 0.1 岩白菜萃取物 0.01 137274.doc -29- 1378799 乳酸菌醱酵液(* 39) 0.1 γ-胺基丁酸(*40) 0.02 茶果萃取物(*41) 0.01 山茶萃取物(*42) 0.01 薏苡萃取物(*43) 0.01 虎耳草萃取物(*44) 0.01 地黃萃取物(*45) 0.01 扁柏水(*46) 0.01 苦橙皮萃取物(*47) 〇.〇1 甲瓦龍酸内酯(* 48) 0.01 厚樸樹皮萃取物(* 49) 〇.〇1 純化水 剩餘量 * 38 : Lipidure PMB(PhlO)(曰本油脂公司製造) * 39 ··乳清 CPA(ICHIMARU PHARCOS公司製造) *40:810 0八8八(協和醱酵公司製造) 氺41:茶果萃取物(丸善製藥公司製造) *42:山茶籽萃取物(丸善製藥公司製造) 氺43:薏苡仁萃取液BG-S(丸善製藥公司製造) * 44 :虎耳草萃取物(ICHIMARU PHARCOS公司製造) 氺45 :地黃萃取液BG-J(丸善製藥公司製造) * 46 :扁柏水B(丸善製藥公司製造) * 47 :苦橙皮萃取液B(ICHIMARU PHARCOS公司製造) * 48 :甲瓦龍酸内酯(旭電化公司製造) * 49 : Pharcolex 厚樸 B(ICHIMARU PHARCOS 公司製造) 137274.doc •30· 1378799 應用例8(防曬霜) 8.0 1.0 0.1 10.0 3.0 .0 0 0 0 0 0 0 0.1 0.05 0.01 0.01 剩餘量 3 乙醇 山梨糖醇酐單異硬脂酸酯 聚甘油脂肪酸酿(註2) 對甲氧基桂皮酸-2-乙基己酯 甲基聚矽氧烷8) 微粒子氧化鈦(* 50) 微粒子氧化鋅(* 51) 無水ί夕酸 低黏度甲基氫化聚矽氧烷 全氟烷基二甲基-三甲基矽烷氧基矽酸 交聯型聚矽氧粉 1,3-丁二醇 濃甘油 己醯杜鵑醇 甘草次酸硬脂酯 火棘萃取物 絲綢萃取液 水解蠶絲液(* 52) 純化水 * 50 : ZnO-350(SUMITOMO OSAKA CEMENT公司製造) * 5 1 : Tipaque TTO-55(A)(石原產業公司製造) * 52 : Silkgen G Soluble S(ICHIMARU PHARCOS公司製造) 137274.doc 31 1378799
應用例9(面膜) 原料成公 調配詈 乙醇 10.0 聚乙稀醇 13.0 1,3-丁二醇 1.0 二丙二醇 2.0 甘油 2.0 甲基笨基聚矽氧炫(氺7) 0.2 肉豆蔻酸辛基十二烷基酯 .0.2 蔗糖脂肪酸酯(註1) 0.05 角鯊烯 0.2 杜鵑醇 2.0 羧乙烯聚合物 0.1 玻尿酸鈉 0.01 羥乙基纖維素 0.05 胺基甲基丙醇 0.05 火棘萃取物 0.05 歐洲白柳葉萃取物(氺53) 0.05 純化水 剩餘詈 * 53 : ASTRESSYL(Silab公司製造) 再者,上述應用例中所使用之香料之組成示於表7。 [表7] 香料配方 成分 質量% 成分 質量% 松油醇 10.00 香蘭素 2.00 乙酸松油腦酯 2.00 6基香蘭素 0.10 137274.doc •32- 1378799 表二氫茉莉酮酸曱酯(Cepionate) 60.00 麝香網(muscone) 0.50 二氫茉莉鲷酸甲酯 250.00 巴西酸亞乙酯 42.00 吲哚 0.05 4,6,6,7,8,8-六甲基-1,3,4,6,7,8-六氫環 戊苯并吼喃 60.00 2-甲基-3-(3,4-亞甲基二氧基苯基)丙醛 3.00 環十五内_ 20.00 羥基香茅醛 20.00 黃葵内酯 1.00 羥基香茅醇 10.00 γ·十一炫内醋 0.40 對第三丁基-α-甲基氫桂皮醛 35.00 γ-癸内酯 0.10 4-(4-羥基-4-甲基-戊基)-3-環己烯-1 -甲醛 75.00 4·(4-羥基笨基)-2-丁明 0.50 3-甲基-5-苯基戊醇 20.00 麝香綢 (musk ketone) 0.10 苯基乙醇 10.00 糞臭素 0.01 α-紫羅蘭明 10.00 順式茉莉明 0.05 β-紫羅蘭明 20.00 乙酸苯基乙酯 0.10 y-甲基紫羅蘭酮 10.00 香貓酮 0.20 二氫-P-紫羅蘭酮 25.00 γ-壬内酯 0.05 水楊酸苄酯 150-00 α-檀香醇 0,20 順式-3-己烯基水楊酸酯 30.00 β-檀香醇 0.20 丁香酚 0.80 乙酸丁香酯 0.10 桂皮醇 5.00 α-己基桂皮醛 20.00 桂皮醛 0.50 α-突厥明 0.04 愈創木醇乙酸酯 1.00 β-突厥酮 0.02 愈創木醇 0.50 β-突厥烯酮 0.01 乙酸柏木烯酯 5.00 δ-突厥酮 0.01 曱基柏木酮 30.00 玫瑰原精 0.50 6,7-二氫-1,1,2,3,3-五甲基-4(5H)-茚滿 2.00 玫瑰油 4.50 乙酸香根酯 10.00 檀香木油 2.00 3-曱基-5-(2,3,3-三曱基-3-環戊烯-1-基)-戊烷-2-醇 2.00 岩玫瑰原精 0.05 2-乙基-4-(2,3,3-三曱基-3-環戊烯-1 -基)-2-丁烯小醇 0.80 岩薔薇原精 0.01 異掐基環己醇 35.00 岩蘭油 0.50 向日花香醛 10.00 癒瘡木油 0.10 香豆素 2.00 總計 1000.00
[產業上之可利用性] 藉由本發明,可提供對皮膚之刺激性較小、長期保存穩 定性優異、且美肌及美白效果較高之皮膚外用劑。 137274.doc -33- m
Claims (1)
1378799 十、申請專利範圍: 第097150734號專利申請案 中文申請專利範圍替換本(〗〇1年6月) 一種皮膚外用劑,其特徵在於含有ya)選自下述通式(ι) 所表示之杜鵑醇及其衍生物中之〖種或2種以上;(b)選自 蔗糖脂肪酸酯及聚甘油脂肪酸酯中之1種或2種以上;以 及(c)多元醇’且以皮膚外用劑之總量為基準, (a)成分之含量係於R為氫原子時為〇1〜3質量%,於r為 石厌數2〜20之酸基時為〇·ι〜5質量°/〇,於R為膽殘基時為 0·1〜5質量%, [化1] 0Η
(式中,R為氫原子、碳數2〜20之醯基、或者單醣類或二 醣類之醣殘基)。 2. 如請求項1之皮膚外用劑,其中(a)成分為杜鵑醇。 3. 如清求項1之皮膚外用劑,其中(b)成分為選自HLB為1 〇 以上之蔗糖脂肪酸酯及聚甘油脂肪酸酯中之1種或2種以 上。 4. 如請求項1至3中任一項之皮膚外用劑’其含有(d)為薔薇 科火棘屬(Rosaceae Pyracantha)中之1種的中文名稱「火 棘」(Pyracantha fortuneana)之果實的溶劑萃取物9 5 ·如請求項1至3中任一項之皮膚外用劑,其中, (b) 成分之含量為〇.〇1〜8質量%, (c) 成分之含量為〇.1〜30質量%。 137274-1010622.doc 1378799 6. 如請求項1至3中任一項之皮膚外用劑,其實質上不含有 對羥基苯甲酸酯及/或苯氧基乙醇。 7. 如請求項1至3中任一項之皮膚外用劑,其實質上不含有 聚氧乙烯加成型非離子界面活性劑。 137274-1010622.doc 2-
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| FR2950885B1 (fr) * | 2009-10-01 | 2011-12-23 | Oreal | Utilisation de derives de vanilline comme conservateur, procede de conservation, compose et composition. |
| JP2012031125A (ja) * | 2010-08-03 | 2012-02-16 | Nikko Chemical Co Ltd | 紫外線吸収剤を含有する微細エマルション組成物並びに化粧料 |
| FR2968657B1 (fr) * | 2010-12-13 | 2013-03-15 | Oreal | Utilisation comme conservateur de derives dimethoxy-hydroxyphenyl-alkyl substitues, procede de conservation, compose et composition |
| WO2012131177A1 (fr) * | 2011-03-31 | 2012-10-04 | L'oreal | Utilisation de dérivés hydroxylés de vanilline comme conservateur, procédé de conservation, composés et composition |
| JP2012224623A (ja) * | 2011-04-08 | 2012-11-15 | Kao Corp | 水中油型乳化組成物 |
| JP2012224624A (ja) * | 2011-04-08 | 2012-11-15 | Kao Corp | 水中油型乳化組成物 |
| JP2012224622A (ja) * | 2011-04-08 | 2012-11-15 | Kao Corp | 水中油型乳化組成物 |
| CN103222944B (zh) * | 2011-09-27 | 2014-11-26 | 沈志荣 | 一种含植物提取物的瞬透生肌水组合物的制备方法 |
| GB2500585A (en) | 2012-03-23 | 2013-10-02 | Univ Manchester | Use of oligosaccharides to reduce skin pigmentation |
| WO2014098264A1 (en) | 2012-12-21 | 2014-06-26 | L'oreal | Cosmetic composition |
| CN103083210A (zh) * | 2013-01-25 | 2013-05-08 | 王恩瀚 | 具有美白皮肤作用的药物组合物及其制备方法和应用 |
| WO2015118625A1 (ja) * | 2014-02-05 | 2015-08-13 | 株式会社マンダム | ジケトン作用抑制剤 |
| CN103792302B (zh) * | 2014-02-17 | 2014-12-31 | 苏州出入境检验检疫局检验检疫综合技术中心 | 一种检测化妆品中杜鹃醇的方法 |
| CN106137811B (zh) * | 2015-04-03 | 2020-08-25 | 伽蓝(集团)股份有限公司 | 一种植物提取物组合物及其用途 |
| CN107049824A (zh) * | 2017-06-27 | 2017-08-18 | 上海新高姿化妆品有限公司 | 一种具有美白功效的组合物及其在化妆品中的应用 |
| DE102018001761A1 (de) * | 2018-03-06 | 2019-09-12 | 4Gene Gmbh | Zusammensetzung mit einem Aromaglykosid und einem Wirkstoff |
| CN111394192B (zh) * | 2019-12-31 | 2022-09-16 | 纳爱斯浙江科技有限公司 | 一种温和无刺激的全食品级洗涤剂组合物及其制备方法 |
| WO2022133715A1 (en) * | 2020-12-22 | 2022-06-30 | L'oreal | Composition for brightening and/or whitening keratin materials |
| CN118307688B (zh) * | 2024-04-26 | 2025-01-21 | 广州青岚生物科技有限公司 | 火棘果纯化多糖及其制备方法与应用 |
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| JP3340935B2 (ja) * | 1997-03-26 | 2002-11-05 | カネボウ株式会社 | メラニン生成抑制剤及び美白化粧料 |
| JP3455406B2 (ja) * | 1997-12-22 | 2003-10-14 | カネボウ株式会社 | 皮膚化粧料 |
| JP2003321488A (ja) * | 2002-04-24 | 2003-11-11 | Hajime Ikegai | 抗菌性抽出物及びその製造方法並びに抗菌剤組成物 |
| JP4681512B2 (ja) * | 2006-06-27 | 2011-05-11 | 花王株式会社 | 皮膚外用剤 |
| JP5049638B2 (ja) * | 2007-04-26 | 2012-10-17 | 花王株式会社 | 皮膚外用剤 |
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