Α7 Β7 經濟部中央標隼局員工消費合作社印製 五、發明説明（1 ) 發明之領域 本發明係關於一種毛髮生長增進用組成物’其包含以下 列式（I )代表之化合物做為活性成份： s ,C 0 〇 R 1ί X , (Ι) kS/ XC Ο X R ' [其中Ri代表具有1至8個碳原子之烷基，R2代表具有1至 10個碳原子之烷基，具有2至6涸碳原子之烯基或具有3至8 個碳原子之環烷基及X代表-0-或- NH-]，以及局部組合物 可接受之載劑之稀釋劑。 發明之背景 在先前技藝已知與各種翳藥組合摻合之毛髮生長增進用 組成物。舉例言之，與血管掮張劑，代謝促進劑，殺菌劑 ，角質溶解劑，激素，及維生素等摻合者被用於預防及治 療禿頭。 雖然此等組合物在預防及治療頭皮屑、搔癯、掉髮等上 據說有效，但在促進頭髮生成及生長上，效果仍不令人滿 意。 發明之簡要說祖 為了克服上述先前技藝之問題，本發明者對具有頭髮生 長增進活性之藥物進行廣泛研究，结果發現Μ下列式（I) 代表之化合物顯示優異的頭髮再生作用。本發明基於此發 琨而完成。 根據本發明，提供一種毛髮生長增進用組成物，其包含 Κ下列式（I >代表之化合物做為活性成份： (請先W绩背面之注意事項再填寫本頁) 裝· 本紙張尺度適用中國國家標準（CNS ) Λ4規格（210X297公釐） 4 S08543 Μ 經濟部中央檁準局員Η消費合作杜印裂 Β7五、發明説明（2 ) y-C Ο 0 R 'I (I) NC Ο X R * [其中R1代表具有1至8個碳原子之烷基，R2代表具有1至 10個碳原子之烷基，具有2至6個碳原子之烯基或具有3至8 個碳原子之環烷基及X代表-0-或- NH-]，Μ及局部組合物 可接受之載劑之稀釋劑。 本發明之目的及優點從下列說明當可很容易地明白。 圖之簡單說明 圖1顯示試驗化合物及對照化合物之毛髮生長增進作用 。在圖1中，-△-，-〇-及分別表示溶媒對照組，PDG 及受試化合物（化合物2號）。#及♦分別表示藉Mann-Whlteney II試驗，相對於對照組，PC0.05及Ρ<0·01。 發明之詳细說1 被用做本發明活性成份之式（I )化合物在美國專利 4,1〗8,506中已被揭示做為肝病治療劑，在《115-8-54-43506 (此處J Ρ - Α係指已被審査之日本專利申請案）中已被揭示做 為農業及園蓊用殺菌劑，在JP-B-6 3-66287中被揭示做為 抑癌_物，在JP-A-6-72871UP-A在此處係指未被審査但 巳公開之日本專利申請案）中已被揭示做為轉移抑制劑， Μ及在澳洲專利644,978中被揭示做為傷口癒合促進組成 ms —^n f^i ^^^^1 ^^^^1 I. fl^^i -^^ϋ? 1^1^1 \ ^ 0¾ 、vs (請先閱讀背面之注意事項再填寫本頁) 物 合 化 之 用 作 長 生 髮 毛 進增一一 具 C 之 、 ^ one 表 ο 代 式 通 列 下 ΜΑ7 Β7 Printed by the Employee Consumer Cooperative of the Central Standard Falcon Bureau of the Ministry of Economic Affairs 5. Description of the invention (1) Field of the invention The present invention relates to a composition for hair growth promotion 'which contains a compound represented by the following formula (I) as an active ingredient : S, C 0 〇R 1ί X, (Ι) kS / XC Ο XR '[where Ri represents an alkyl group having 1 to 8 carbon atoms, R2 represents an alkyl group having 1 to 10 carbon atoms, having 2 to A diluent of an alkenyl group of 6 carbon atoms or a cycloalkyl group having 3 to 8 carbon atoms and X represents -0- or -NH-], and a carrier acceptable for the topical composition. Background of the Invention In the prior art, it is known that a hair growth promoting composition blended with various types of paniculata in combination. For example, those blended with vasodilators, metabolism enhancers, bactericides, keratolytic agents, hormones, and vitamins are used to prevent and treat baldness. Although these compositions are said to be effective in preventing and treating dandruff, scratching, hair loss, etc., the effect on promoting hair growth and growth is still not satisfactory. Brief description of the invention In order to overcome the problems of the aforementioned prior art, the present inventors conducted extensive research on drugs having hair growth promoting activity, and as a result, it was found that the compounds represented by the following formula (I) show excellent hair regeneration effects. The present invention has been completed based on this discovery. According to the present invention, there is provided a composition for hair growth promotion, which comprises Κ as a compound represented by the following formula (I > as an active ingredient: (please pay attention to the matters on the back of this page before filling in this page) China National Standards (CNS) Λ4 specifications (210X297mm) 4 S08543 Μ The Central Purification Bureau of the Ministry of Economy Η Consumer Cooperation Du Yinpai VII. Invention Description (2) yC Ο 0 R 'I (I) NC Ο XR * [ Where R1 represents an alkyl group having 1 to 8 carbon atoms, R2 represents an alkyl group having 1 to 10 carbon atoms, an alkenyl group having 2 to 6 carbon atoms or a cycloalkyl group having 3 to 8 carbon atoms and X represents -0- or -NH-], M and a diluent acceptable to the carrier of the topical composition. The purpose and advantages of the present invention can be easily understood from the following description. Brief description of the drawings Figure 1 shows the test compound And the control compound's hair growth promotion effect. In Figure 1,-△-, -〇- and respectively represent the vehicle control group, PDG and the test compound (Compound No. 2). # And ♦ respectively represent the Mann-Whlteney II test , Relative to the control group, PC0.05 and Ρ < 0.01. Invention of Detail 1 The compound of formula (I) used as the active ingredient of the present invention has been disclosed as a therapeutic agent for liver disease in US Patent No. 4,1〗 8,506, in "115-8-54-43506 (here J Ρ-Α Refers to the Japanese patent application that has been examined) has been disclosed as a fungicide for agriculture and gardening, and it has been disclosed as a cancer suppressor in JP-B-6 3-66287, in JP-A-6 -72871UP-A here refers to the unexamined but published Japanese patent application) has been disclosed as a transfer inhibitor, M and disclosed in Australian Patent 644,978 as a wound healing promoting composition ms — ^ nf ^ i ^^^^ 1 ^^^^ 1 I. fl ^^ i-^^ ϋ? 1 ^ 1 ^ 1 \ ^ 0¾, vs (please read the precautions on the back before filling in this page) Used as a long-haired hair to increase one by one with C, ^ one table
RR
o R r3M s s// c :o 本紙張尺度適用中國國家標隼（CMS ) Α4規格（210Χ 297公釐） 5 A7 B7 五、發明説明（3 ) 被揭示於對懕於JP-A-63-10131之EP 170748A1中。不過該 化合物由於不安定及於使用時會被分解，所Μ無法產生明 顯的作用。 在式（I)中，具有1至8個碳原子之烷基之說明例包括甲 基、乙基、正-丙基、異丙基、正-丁基、異丁基、正-戊 基、正-己基等，具有1至10個碳原子之烷基之說明例包括 甲基、乙基、正-丙基、異丙基、正-丁基、異丁基、正_ 戊基、正-己基、正-庚基、正-辛基、及正-癸基等；具有 2至6個碳原子之烯基之說明例包括乙烯基、烯丙基、2 -丁 烯基、及3-戊烯基等，Κ及具有3至8個碳原子之環烷基之 說明例包括環丙基、環戊基、環己基及環庚基等。R1及 R2較好各為具有1至6個碳原子之烷基Μ及X為氧。較佳化 合物例包括亞1,3-二噻茂-2-基丙二酸二異丙酯。 其次，用於本發明之化合物之典型例被示於表1中，但 非限於此。 ---------^------ΪΤ------線 (請先閱讀背面之注意事項再填寫本頁) 經濟部中央標準局員工消費合作社印^ 本紙張尺度適用中國國家標隼（CNS ) /\4说格（210Χ.297公t ) -6- 奮正買 308543 Μ Β7 五、發明説明（4 經濟部中央檍隼局員工消費合作杜印製 編號 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 CH 3 i-C 3 Η 7 i-C 3Η 7 i-C a Η 7 i-C a H 7 i-C 3H 7 i-C 3H 7 表 XR2 OCH 3 0 - i C 3 H 7 OH 〇-Π-('βΗι3 O-CH ?CH = CH 2 N H <1 物理性質 hi. P. 1 2 5 - 1 2 9 ¾ m . p . 5 9 - 6 0 °C 10 , P , 5 4 °C m . P . 6 8 - 6 9 °C m . p . 4 0 t m . p . 4 8 "C m.p.70-72 ¾ C3H7 NH-n-CeH , 3 CH 3 0 -i-C 4 U 2 Π 5 I-C4H3 i-C 5C ! 1 n-C 3H 7 n - C 4 H 9 s-C 4 H 9 n-C5H1! 0 C 2 H 5 0-i-C 4 H g 0 - i - C 5 H 1 1 O-n-CaH? 0_n - C4H3 O-s-C 4 H s Q - n - C 5 H 1 , 23 23 .5 7 2 8 .5928 m . p . 1 1 3 Ό m . p . 7 6 - 7 8 °C m.p.55-56 Ό m.p.7 3 -7 5 r m.p.74-75t m . p . 6 3 - 6 5 C m.P.70-70. 5¾ 本紙張尺度適用中國國家標隼（CNS ) A4規格（210X 297公釐） 批衣 訂 (請先閱讀背面之注意Ϋ項再填寫本頁) A7 B7 經濟部中央標準局員工消費合作社印繁 五、發明説明（ 4 ) 1 1 本 發 明 增 進 頭 髮 生長 之 組 合 物 可 Μ 常 用 方 式 藉 與 局 部 組 1 1 I 合 物 可 接 受 之 載 劑 或稀 釋 劑 摻 合 而 被 製 成 美 髮 劑 t 髮 乳 Λ 1 1 I 髮 霜 Λ 髮 爱 洗 髮 精及 濶 絲 精 等 〇 請 I 1 I 酵 類 > 油 脂 及 界 面活 性 劑 等 可 被 用 做 摻 合 的 基 本 物 質 » 讀 背 | 面 I Μ 及 血 管 擴 張 劑 殺菌 劑 角 質 溶 解 劑 Λ 代 謝 促 進 劑 激 之 1 I 意 1 I 素 及 維 生 素 等 亦 可 被摻 入 做 為 其 他 活 性 組 份 9 以 及 可 摻 入 禀 ή 1 I 再 1 薄 荷 等 香 料 〇 填 1 根 據 本 發 明 被 摻入 之 活 性 成 份 之 量 通 常 為 組 合 物 總 量 寫 本 頁 裝 1 之 0 . 01 -1 〇重量％ Μ 0 .1-5 重 量 S!為較佳c 1 1 現 提 供 下 列 合 成 例， 實 施 例 及 試 驗 例 Μ 進 一 步 說 明 本 發 1 1 明 0 不 過 懕 了 解 此等 例 子 僅 係 用 於 說 明 非 意 圖 界 定 本 1 玎 發 明 之 範 圍 〇 1 I 式 (I)化合物之合成例如下C 1 1 合 成 例 1 1 1 亞 1 , 3- 二 噻 茂 -2 -基丙二酸二甲_ (化 合 物 1號） 1 將 5 . 28克 份 丙 二 酸二 甲 酯 (0 .04莫耳） 及 3 . 66克 二 硫 化 碳 1 I (0 .048 萁 耳 )溶於25奄升二甲基亞碾 ，將1 0 . 9克4 5 S：氯 氧 化 1 I 鉀 水 溶 液 逐 滴 加 到 在冰 浴 中 被 冷 卻 之 溶 液 内 並 將 生 成 的 1 1 混 合 物 在 室 溫 下 攪 拌20小 時 〇 將 得 到 的 反 應 溶 液 逐 滴 加 到 1 1 由 1 9 . 6克 4 0 3!氯乙醛及2 .88克冰乙酸組成之混合物溶液中 1 1 9 將 其 在 51C或更低之溫度下冷卻以及將混合物於相同溫 1 I 度 下 m 拌 30分 鐘 〇 將反 應 溶 液 倒 人 冰 水 中 用 乙 酸 乙 酯 萃 1 1 1 取 二 次 > 然 後 用 水 洗滌 〇 於 硫 酸 m 上 乾 燥 後 釁 熔 劑 藉 於 滅 1 1 壓 下 蒸 m 移 除 t 得 到4- 羥 基 -亞-1 , 3- 二 m m -2 -基丙二酸 1 1 本紙張尺度適州中國國家標準（CNS ) Λ4規格（210〕< 297公釐） ^ ^ „ 5 着it頁 A7 B7 經濟部中央標準扃負工消费合作社印奴 五、發明説明（6 酷。將所得到的化合物及12.2克三乙胺<0.12莫耳）溶於20 毫升二啤烷，然後於01C下將6.9克甲磺醯氣（0.06莫耳）加 入其中。逐滴加入完成後，將生成的混合物於室溫下授拌 10分鐘，然後回流加熱10分鐘。將反懕溶液倒入冰水中， 用乙酸乙酯萃取，然後用水洗滌。於硫酸鎂上乾燥後，藉 減壓蒸皤移除溶劑，生成之殘餘物藉矽膠柱層析純化（正-己烷：乙酸乙酯=2 : 1 )，得到4 . 0克為结晶形式之標鼴化 合物，熔點為125-129T (產率= 433!)。 合成例2 亞1,3 -二噻茂-2 -基丙二酸乙酯異丙酯（化合物3號） 將14.4克1,3-二噻茂-2-基丙二酸二異丙酯（0.05莫耳） 溶於50毫升異丙酵，於3〇υ下將2.95克氳氧化鉀（0.05莫 耳）加到該溶液中，然後將生成的混合物攪拌1小時。將溶 液用6Ν鹽酸酸化及用200毫升二氛甲烷萃取，然後用水及 飽和鹽水依次洗滌。在硫酸鎂上乾煉後，藉減®蒸餾移除 溶劑，生成之殘餘物自乙醚中结晶，得到8 . 5克亞1 , 3 -二 唾茂基丙二酸單異丙酷，其為白色結晶形式（產率：75¾) 。然後將2 . 7克（0 . 0 1 1莫耳）得到的结晶及3 . 6克（0 . 0 1 2莫 耳）2 -氛-1-甲基咁錠對甲苯磺酸豳溶於20毫升二氛甲烷， 然後於10T：下將0.51克（0.011莫耳）乙酵及3.46克（0.034 莫耳）三乙胺之二氛甲烷溶液逐滴加入其中，繼而將生成 之混合物於室溫下攪拌2小時。將反應溶液倒入冰水中， 用二氛甲烷萃取*然後用2N18酸，10S：碳酸氫納水溶液及 水依次洗滌。於硫酸鎂上乾煉後，賴減懕蒸餾移除溶劑， 本紙張尺度適用中國國家標準（CNS ) /U規格（210 < 297公埯） (請先閲讀背面之注意事項再填寫本頁) _裝· 訂 經濟部中央標準局員工消費合作社印製 A7 B7 五、發明説明（7 ) 生成之殘餘物藉矽膠柱式層析（正-己烷：乙酸乙酯=2: 1 )純化，得到1.0克為结晶形式之檷題化合物，熔點： (產率：35¾)。 合成例3 亞1,3 -二噻茂-2 -基丙二酸0 -異丙酯N -環丙酯（化合物7號） 將2.46克份亞1,3-二噻茂-2-基丙二酸單異丙酷（0.01莫 耳），0.80克（0.014萁耳）環丙胺及3.25克（0.02莫耳）偶磷 丨批衣 訂 線 (#先閱讀背面之注意事項再填寫本頁) 氰 酸 二 乙 m 溶 於 20 毫 升 二 甲基 甲 醮 胺 9 將 3 . 03 克 三 乙 胺 (0 .03莫耳） 逐 滴 加 到 被 冷 卻至 10 'η 之 溶 液 中 0 將 生 成 的 混 合 物 於 相 同 溫 度 下 攪 拌 1小時， 然後於室溫下攪拌3小 時 〇 將 反 應 溶 液 倒 入 冰 水 中 f 用乙 酸 乙 酿 萃 取 ，然 後 用 1N 鹽 酸 9 飽 和 碳 酸 氫 納 水 溶 液 及 水依 次 洗 滌 0 於 硫酸 鎂 上 乾 燥 後 t 藉 減 壓 蒸 m 移 除 溶 劑 9 生成 之 殘 餘 物 藉 矽膠 柱 式 層 析 ( 乙 酸 乙 m ： 正 -己烷=1 ♦ • 1 )純 化 * 得 到 2 . 6克為结晶形式 之 標 題 化 合 物 9 熔 點 70 -72V ( :產 率 9 1 % ) 實 施 例1 本 發 明 化 合 物 0 .5克 水 楊 酸 1 .0克 間 苯 二 酚 2 .0克 甘 油 2 .0克 酚 1 .0克 篦 麻 子 油 1 .0克 m 衣 草 油 10 .0¾ 升 總體積為1〇〇蠹升之洗麵藉將上述組份溶於乙酵中而製 本紙張尺度適用中國國家標隼（CNS ) Λ4現格（210x2<)7公聲_ ) -10- 修正荑 ^08543 Μ Β7 五、發明説明（8 備 實施例 本發明化合物 薄荷油 甘 油 薰衣草油 1 . 0克 0 . 6克 1 5 . 0毫升 10 . 0毫升 總體積為100毫升之洗劑藉將上述組份溶於乙酵中而製 備 經濟部中央標隼局Μ工消費合作社印製 賁施例 3 總 備 本 發 明 化合物 0 . 1克 卡 拉 明 (calamine ) 8 . 0克 海 藻 酸 納 1 . 25克 甘 油 4 . 0克 對 -羥基芏酸甲酗 0 . 2克 氧 化 鋅 8 . 0克 Tw e e η 20 0 . 0 1克 體 積 為 100奄升之 洗劑藉將 上述組份溶 於純 實 胞例 4 本 發 明 化合物 0 . 5克 鉀 肥 皂 8 . 0克 薄 荷 油 0 . 6克 m 衣 草 油 10 .0毫 總體積為100毫升之洗劑藉將上述組份溶於乙酵而製備 本紙張尺度適用中國國家標準（CNS ) Λ4規格（210X297公釐） m Atl m^i ^^^^1 mV— n^i t 1^^^ fttn n^i \ V -9 (請先M讀背面之注意事項再填寫本頁) -11- ^08543 A7 B7五、發明説明（9 ) 實施例 5 本發明化合物 〇.5克 對羥基芏酸乙酯 0 . 0 2 5克 對羥基芏酸丙酯 0.0] 5克 硫酸月桂酷納 1 . 5克 丙二酵 1 2 . 0克 硬脂酵 2 2 . 0克 白a 士林 2 5 . 0克 鈍水 38.96克 總重為100克之軟齋藉將上述組份溶解及混合而製備。 實施例 6 本發明化合物 〇 . 5克 聚乙二酵400 57.5克 聚乙二酵1500 20.0克 聚乙二酵4000 22.0克 總重為100克之軟晉藉將上述組份溶解及混合而製備。 簧施例一7 (請先閱讀背面之注意事項再填寫本頁) 經濟部中央標準局員工消費合作社印製 本發明化合物 0.5克 純羊毛脂 5 . 0克 白蜂蠘 5 . 0克 白凡士林 89.5克 總重為100克之軟脅藉將上述組份溶解及混合而製備。 試驗例 將在毛髮生長循環靜止期之C3H糸雄鼠之背部修剪並將 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） -12- 30B543 A7 經濟部中央標隼局員工消費合作社印製 B7五、發明説明（！ 〇 ) 其分組，每組δ隻動物。將試驗化合物（化合物2號）溶於 70!K(V/V)乙酵。十五碳酸單甘油酯（PDG)被用做陽性對照 組。每日將溶於溶劑（70UV/V)乙酵）之3!ϋ(ν/ν)試驗溶液 局部塗敷至鼠之背部皮虜，其體積為0.1毫升/鼠/日。根 據表2所示之計分法評估試驗化合物之毛髮生長促進作用 ，結果被示於圖1中。 如圖1所示，與溶劑對照組相較，塗敷本發化合物之試 驗組動物被觀察到毛生長明顧增進。再者，與已知為毛髮 生長促進劑之PDG相較，本發明化合物顯示較強的毛髮生 長增進作用。 表 2 頭髮生長之分數 分數 標準 _ 0 無毛（毛髮周期為靜止期） 1 覼察到毛生長 (毛髮周期變為生長期） 2 ^ 25¾之背部皮虜區覆蓋有再長之毛 3 2 50¾之背部皮膚區覆蓋有再長之毛 4 275¾之背部皮虜區覆蓋有再長之毛 5 背部皮虜完全覆蓋再長之毛 因此·本發明之毛髮生長增進用組成物顯然具有毛髮再 生促進功能，所以為有用的毛髮生長增進製劑。 雖然本發明已參照特殊實施例詳细說明*熟悉本技藝之 人士顯而易知可在不偏離本發明之精神及範圍下做各種改 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 1 „ (請先閲讀背面之注意事項再填寫本頁) ^^8543 A7 B7 五、發明説明（1 i) 飾 修及變 (請先閱讀背面之注意事項再填寫本頁 裝· 經濟部中央標隼局員工消f合作社印製 本紙張尺度適用中國國家橾準（CNS ) A4規格（210X 297公釐）o R r3M ss // c: o The paper size is applicable to the Chinese National Standard Falcon (CMS) Α4 specification (210Χ 297 mm) 5 A7 B7 5. The description of the invention (3) was revealed in JP-A-63- 10131 of EP 170748A1. However, the compound is not stable and will be decomposed during use, so it cannot produce a significant effect. In the formula (I), illustrative examples of alkyl groups having 1 to 8 carbon atoms include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, n-pentyl, Illustrative examples of n-hexyl and the like, alkyl groups having 1 to 10 carbon atoms include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, n-pentyl, and n- Hexyl, n-heptyl, n-octyl, n-decyl, etc .; illustrative examples of alkenyl groups having 2 to 6 carbon atoms include vinyl, allyl, 2-butenyl, and 3-pentyl Examples of alkenyl and the like, K and cycloalkyl having 3 to 8 carbon atoms include cyclopropyl, cyclopentyl, cyclohexyl and cycloheptyl. R1 and R2 are each preferably an alkyl group having 1 to 6 carbon atoms and X is oxygen. Examples of preferred compounds include diisopropylidene 1,3-dithien-2-ylmalonate. Next, typical examples of the compounds used in the present invention are shown in Table 1, but are not limited thereto. --------- ^ ------ ΪΤ ------ Line (please read the precautions on the back before filling in this page) Printed by the Staff Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs ^ This paper size Applicable to the Chinese National Standard Falcon (CNS) / \ 4 said grid (210Χ.297g) -6- Fenzheng buy 308543 Μ Β7 5. Invention description (4 Employee's consumption cooperation of the Central Bureau of Peregrine Falconry No. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 CH 3 iC 3 Η 7 iC 3Η 7 iC a Η 7 iC a H 7 iC 3H 7 iC 3H 7 Table XR2 OCH 3 0-i C 3 H 7 OH 〇 -Π-('βΗι3 O-CH? CH = CH 2 NH < 1 Physical properties hi. P. 1 2 5-1 2 9 ¾ m. P. 5 9-6 0 ° C 10, P, 5 4 ° C m. P. 6 8-6 9 ° C m. P. 4 0 tm. P. 4 8 " C mp70-72 ¾ C3H7 NH-n-CeH, 3 CH 3 0 -iC 4 U 2 Π 5 I-C4H3 iC 5C! 1 nC 3H 7 n-C 4 H 9 sC 4 H 9 n-C5H1! 0 C 2 H 5 0-iC 4 H g 0-i-C 5 H 1 1 On-CaH? 0_n- C4H3 OsC 4 H s Q-n-C 5 H 1, 23 23 .5 7 2 8 .5928 m. P. 1 1 3 Ό m. P. 7 6-7 8 ° C mp55-56 Ό mp7 3 -7 5 r mp74-75t m. P. 6 3-6 5 C mP70-70. 5¾ This paper size is applicable to Chinese national standard (CNS) A4 specification (210X 297mm) Approved clothing order (please read the note Ϋ on the back side and fill in this page) A7 B7 Central Government Bureau of Economic Affairs Employee's Consumer Cooperative Printed V. V. Invention Description (4) 1 1 copy The hair growth-promoting composition of the invention can be made into a hairdressing agent by blending with a carrier or diluent acceptable to the composition of the topical group 1 1 I in the usual way. Hair cream Λ 1 1 I Hair cream Λ Hair love shampoo Essence and sperm extract etc. Please I 1 I Enzymes> Oils and surfactants can be used as basic materials for blending »Read back | Face I Μ and vasodilator fungicides keratolytic agent Λ metabolic accelerator 1%, 1%, 1%, vitamins, etc. can also be incorporated as other active ingredients 9 and can be incorporated into 1 1 and 1 mint and other spices. 1 according to the present invention The amount of the active ingredient added is usually 0. 01 -1 〇% by weight of the total composition of this page. 0.001 -1 〇% by weight Μ 0.1-5 weight S! For the better c 1 1 now provides the following synthesis examples, examples and Test Example Μ Further description of the present invention 1 1 Ming 0 However, understanding these examples is only for the purpose of not intending to define the scope of the present invention. 1 I Synthesis of compounds of formula (I) For example C 1 1 Synthesis Example 1 1 1 Methylene 1,3-dithiol-2-ylmalonic acid dimethyl _ (Compound No. 1) 1 5.28 grams of dimethyl malonate (0.04 mole) and 3.66 grams of carbon disulfide 1 I (0.048 cylinoleum) was dissolved in 25 liters of dimethyl sub-milling, and 1 0.9 g of 4 5 S: 1 1 potassium chloride aqueous solution was added dropwise to the solution cooled in an ice bath and The resulting 1 1 mixture was stirred at room temperature for 20 hours. The resulting reaction solution was added dropwise to 1 1 to 19. 6 g 4 0 3! Chloroacetaldehyde and 2.88 g of glacial acetic acid in a mixture solution 1 1 9 It was cooled at a temperature of 51C or lower and the mixture was stirred at the same temperature of 1 I for 30 minutes. The reaction solution was poured into ice water, extracted with ethyl acetate 1 1 1 and taken twice> then washed with water. After drying on sulfuric acid m, the flux was quenched with 1 1 and steamed under m to remove t to obtain 4-hydroxy-sub -1, 3-dimm -2 -ylmalonic acid 1 1 The paper size is suitable for the Chinese National Standard (CNS) Λ4 specification (210) < 297mm) ^ ^ „5 page it A7 B7 Central Ministry of Economic Affairs Standard labor contract consumer cooperative Inno V. Invention description (6 cool. The obtained compound and 12.2 g of triethylamine (0.12 mol) were dissolved in 20 ml of dibrane, and then 6.9 g of mesylate (0.06 mol) was added thereto at 01C. After the dropwise addition was completed, the resulting mixture was stirred at room temperature for 10 minutes, and then heated under reflux for 10 minutes. The inverted solution was poured into ice water, extracted with ethyl acetate, and then washed with water. After drying over magnesium sulfate, the solvent was removed by evaporation under reduced pressure, and the resulting residue was purified by silica gel column chromatography (n-hexane: ethyl acetate = 2: 1) to obtain 4.0 g of the crystalline form Standard mole compound, melting point 125-129T (yield = 433!). Synthesis Example 2 Isopropyl 1,3-dithiol-2-ylmalonate (Compound No. 3) 14.4 g of diisopropyl 1,3-dithiol-2-ylmalonate ( 0.05 mol) was dissolved in 50 ml of isopropanol, 2.95 g of potassium oxide (0.05 mol) was added to the solution at 30 °, and the resulting mixture was stirred for 1 hour. The solution was acidified with 6N hydrochloric acid and extracted with 200 ml of dichloromethane, then washed successively with water and saturated brine. After being dried over magnesium sulfate, the solvent was removed by minus® distillation, and the resulting residue was crystallized from diethyl ether to obtain 8.5 g of sub-l, 3-disialylmalonic acid monoisopropyl chloride, which was white crystals. Form (yield: 75¾). Then, 2.7 g (0.0 1 1 mol) of the obtained crystals and 3.6 g (0.0 1 2 mol) of 2-amino-1-methylzine in toluene p-toluenesulfonate were dissolved in 20 ML of dichloromethane, then at 10T: add 0.51 g (0.011 mol) of ethyl yeast and 3.46 g (0.034 mol) of triethylamine in dichloromethane solution drop by drop, and then the resulting mixture at room temperature Stir for 2 hours. The reaction solution was poured into ice water, extracted with dichloromethane * and then washed sequentially with 2N18 acid, 10S: aqueous sodium bicarbonate solution and water. After drying on magnesium sulfate, Lai Jianguo distills to remove the solvent. The paper size is in accordance with Chinese National Standard (CNS) / U specifications (210 < 297 gong) (please read the precautions on the back before filling this page) _Filled and printed A7 B7 printed by the Staff Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economy V. Description of the invention (7) The resulting residue is purified by silica gel column chromatography (n-hexane: ethyl acetate = 2: 1) to obtain 1.0 g of the title compound in crystalline form, melting point: (yield: 35¾). Synthetic Example 3 1,3-Dithiol-2-ylmalonic acid 0-isopropyl ester N-cyclopropyl ester (Compound No. 7) 2.46 g parts of 1,3-dithiol-2-ylpropylene Monoisopropyl diacid (0.01 mol), 0.80 g (0.014 ear) cyclopropylamine and 3.25 g (0.02 mol) phosphorous 丨 Approved clothes line (#Read the precautions on the back before filling this page) Diethylmethane acid was dissolved in 20 ml of dimethylmethanamine 9 3. 03 g of triethylamine (0.03 mol) was added dropwise to the solution cooled to 10′η 0 The resulting mixture was the same Stir at temperature for 1 hour, then at room temperature for 3 hours. Pour the reaction solution into ice water. Extract with ethyl acetate, then wash with 1N hydrochloric acid, 9 saturated aqueous sodium bicarbonate solution and water. After drying on magnesium sulfate t Removal of solvent 9 by distillation under reduced pressure 9 The residue formed was purified by silica gel column chromatography (ethyl acetate m: n-hexane = 1 ♦ • 1) * to obtain 2.6 g of the title compound 9 in crystalline form. Melting point 70 -72V (: yield 9 1%) Example 1 Compound of the present invention 0.5 g salicylic acid 1.0 g resorcinol 2.0 g glycerol 2.0 g phenol 1.0 g grate oil 1.0 g m lavender oil 10.0 liters The cleansing face with a total volume of 100 liters is prepared by dissolving the above components in ethyl yeast. The paper size is applicable to the Chinese National Standard Falcon (CNS) Λ4 present grid (210x2 <) 7 public voices _) -10- Amendments ^ 08543 Μ Β7 5. Description of the invention (8 alternate examples of the compound of the present invention peppermint oil glycerin lavender oil 1.0 g 0.6 g 15.0 ml 10.0 ml total volume of 100 ml lotion borrow the above group The portion was dissolved in ethyl yeast and prepared by the Ministry of Economic Affairs, Central Standard Falcon Bureau, Mgong Consumer Cooperative Printed Ben Example 3 Total preparation of the compound of the present invention 0.1 g calamine 8.0 g sodium alginate 1.25 g glycerol 4.0 grams of para-hydroxy hexanoic acid methyl alcohol 0.2 grams of zinc oxide 8.0 grams Tw ee η 20 0 .01 gram volume is 100 am Liter of lotion by dissolving the above components in pure solid cells Example 4 Compound of the present invention 0.5 g potassium soap 8.0 g peppermint oil 0.6 g m lavender oil 10.0 milliliter total volume 100 ml This paper is prepared by dissolving the above components in ethyl yeast. The paper size is applicable to the Chinese National Standard (CNS) Λ4 specification (210X297mm) m Atl m ^ i ^^^^ 1 mV— n ^ it 1 ^^^ fttn n ^ i \ V -9 (please read the precautions on the back before filling in this page) -11- ^ 08543 A7 B7 V. Description of the invention (9) Example 5 Compound 0.5 of the present invention 0.5 g ethyl p-hydroxypyranate 0. 2 5 g propyl para-hydroxy acetonate 0.0] 5 g lauryl sulfate 1.5 g malonate 1 2 0 g stearic acid 2 2 0 g white a Shihlin 2 5 0 g dull 38.96 grams of water with a total weight of 100 grams is made by dissolving and mixing the above components. Example 6 Compound of the present invention 0.5 g Polyoxirane 400 57.5 g Polyoxirane 1500 20.0 g Polyoxirane 4000 22.0 g A total weight of 100 g is prepared by dissolving and mixing the above components. Spring Example 1 (Please read the precautions on the back before filling this page) The Ministry of Economic Affairs Central Standards Bureau employee consumer cooperative printed the compound of the present invention 0.5 g pure lanolin 5.0 g white bee worm 5.0 g white petrolatum 89.5 A soft gram with a total weight of 100 grams is prepared by dissolving and mixing the above components. The test example will trim the back of the male C3H Mito rat during the hair growth cycle and apply this paper to the Chinese National Standard (CNS) A4 specification (210X 297 mm) -12- 30B543 A7 Employee consumption of the Central Standard Falcon Bureau of the Ministry of Economic Affairs Cooperatives printed B7 V. Description of invention (! 〇) Its grouping, δ animals in each group. The test compound (Compound No. 2) was dissolved in 70! K (V / V) yeast. Pentacarbonate (PDG) was used as a positive control group. Daily apply 3! Ϋ (ν / ν) test solution dissolved in solvent (70UV / V) yeast to the back of the rat, the volume is 0.1ml / rat / day. The hair growth promoting effect of the test compound was evaluated according to the scoring method shown in Table 2, and the results are shown in FIG. As shown in Fig. 1, compared with the solvent control group, the animals of the test group to which the compound of the present invention was applied were observed to have a clear increase in hair growth. Furthermore, the compound of the present invention shows a stronger hair growth promoting effect compared to PDG known as a hair growth promoter. Table 2 Score criteria for hair growth score _ 0 Hairless (hair cycle is stationary) 1 Hair growth is observed (hair cycle becomes growth phase) 2 ^ 25¾ The back skin area is covered with regrown hair 3 2 50¾ The back skin area is covered with regrowth hair 4 275¾ The back skin area is covered with regrowth hair 5 The back skin area is completely covered with regrowth hair Therefore, the hair growth promoting composition of the present invention obviously has a hair regeneration promoting function , So it is a useful hair growth promotion agent. Although the present invention has been described in detail with reference to specific embodiments, it is obvious to those familiar with the art that various changes can be made without departing from the spirit and scope of the present invention. The paper standard is applicable to the Chinese National Standard (CNS) A4 specification (210X297 1) (Please read the precautions on the back before filling in this page) ^^ 8543 A7 B7 V. Invention description (1 i) Decoration and changes (please read the precautions on the back before filling in this page · Ministry of Economic Affairs The standard paper printed by the Central Standard Falcon Bureau ’s employee consumer cooperative is applicable to the Chinese National Standard (CNS) A4 (210X 297mm)