470648 A7 B7 經濟部中央標準局員工消費合作社印製 五、 發明説明（ 1 ) 1 I 枝 術 領 域 1 I 本 發 明 偽 提 供 一 種 以 白 蛋 白 作 為 有 效 成 分 之 醫 藥 組 成 1 1 I 物 〇 本 發 明 之 醫 藥 組 成 物 可 用 以 治 療 角 結 膜 障 礙 或 乾 眼 等 ，—、 1 I 請 I 病 症 0 本 發 明 之 組 成 物 具 有 使 眼 表 面 上 皮 黏 蛋 白 分 泌 增 加 无 閱 1 I 讀 1 I 的 作 用 * 此 外 亦 顯 示 出 使 油 擴 散 的 作 用 0 再 者 本 發 明 提 背 Λ 1 1 之 1 I 供 一 種 使 用 該 醫 藥 組 成 物 治 療 角 結 膜 障 礙 及 乾 眼 症 之 方 法 注 意 1 | 事 1 及 使 用 該 醫 藥 組 成 物 增 加 眼 表 面 上 皮 黏 蛋 白 分 泌 之 方 法 項 再 填 1 〇 寫 本 裝 頁 1 背 景 抟 術 1 I 角 結 膜 障 礙 傜 因 上 皮 上 生 成 缺 損 而 白 其 表 面 引 起 的 〇 1 1 此 原 因 為 例 如 乾 性 角 結 膜 症 (乾眼症） Λ 各 種 角 結 膜 炎 過 1 1 敏 、 由 於 微 生 物 (病毒、 細_、 真菌等） 之 感 染 引 起 的 疾 病 訂 1 之 要 因 由 於 藥 物 之 細 胞 毒 性 N 酸 、 鹼 引 起 的 腐 蝕 等 為 準 1 1 的 化 學 性 要 因 N 由 於 眼 表 面 乾 煙 λΡγ» 異 物 (賺形眼鏡等） 引 起 1 | 的 外 傷 、 熱 水 等 物 理 性 要 因 等 0 又 近 年 來 氣 化 苯 甲 烴 銨 、 1 線 氛 丁 醇 等 之 點 眼 藥 所 含 的 防 腐 劑 或 胺 基 糖 ¥ 類 % 抗 生 素 、 1 I 非 類 固 醇 % 消 炎 劑 IDU , 游徽素（ pi m a r i c 1 η) 等 之 點 眼 藥 1 1 等 對 角 膜 上 皮 産 生 障 害 的 情 事 亦 時 有 報 導 0 1 1 現 在 « 為 治 療 角 結 膜 障 礙 » 以 投 用 硫 酸 軟 骨 素 谷 胱 1 甘 肽 透 明 質 酸 纖 維 網 蛋 白 E G F等或補充淚液為目6 勺 1 | 實 施 人 工 淚 液 之 投 用 等 t 惟 其 效 果 仍 不 足 0 1 I 乾 眼 症 傜 予 定 義 成 厂 引 起 淚 液 量 降 低 或 性 質 異 常 的 狀 1 1 I 態 9 不 問 有 無 角 結 膜 障 礙 J (山田等人， 眼紀、 43 , 1 2 8 9 - 1 1 1293 (1 992))〇 乾眼症雖有各種原因， 惟『 每未發現有{ £已 1 1 本紙張尺度適用中國國家標準（CNS ) A4規格（210X2.97公釐） 3 3 8 8 6 2 470648 A7 B7 經濟部中央標準局員工消費合作社印製 五、 發明説明（2 ) 1 | 降 低 的 淚 液 量 回 復 正 常 之 方 法 0 現 行 乾 眼 症 之 治 療 像 由 投 1 I 用 以 補 充 淚 液 為 巨 的 之 人 工 淚 液 9 冀 圖 缓 和 患 者 之 自 覺 症 1 1 I 狀 為 巨 的 而 進 行 硫 酸 軟 骨 素 谷 胱 甘 肽 N 透 明 質 酸 纖 維 /--N 請 1 1 1 網 蛋 白 EGF等之投用， 惟其效果並不足。 先 閱 1 1 1 由 最 近 的 研 究 正 常 的 眼 表 面 上 皮 偽 於 其 表 面 上 發 現 背 之 1 1 1 有 黏 蛋 白 狀 糖 蛋 白 質 t 此 被 視 作 積 極 的 參 與 淚 液 層 之 保 持 注 意 事 1 1 〇 再 者 9 由 結 膜 之 胚 細 胞 分 泌 的 黏 蛋 白 > 已 知 有 助 於 淚 液 項 再 | 層 之 安 定 化 〇 由 於 不 知 何 種 要 因 引 起 的 眼 表 面 上 皮 之 障 礙 % 本 頁 裝 I * 若 因 黏 蛋 白 分 泌 引 起 障 礙 時 則 淚 液 層 不 穩 定 > 角 結 膜 1 1 I 上 皮 細 胞 及 淚 液 間 之 相 互 作 用 降 低 被 認 為 上 皮 障 礙 1 1 進 —- 步 引 起 所 謂 惡 化 之 惡 性 循 環 (橫井則彦 「眼科治療之 1 1 訂 1 技 法 及 策 略 J 小 篡 文 雄 等 编 輯 、 中 山 書 局 (股） (曰本、 東 京 )第26〜27頁（ 1 9 9 5年 )) 0 由 此 種 見 解 > 藉 由 增 強 黏 蛋 白 1 1 産 生 > 或 其 他 手 段 以 謀 求 淚 液 層 之 安 定 化 » 及 教 示 著 可 改 1 | 善 角 結 膜 障 礙 或 乾 眼 症 0 it 白 蛋 白 偽 廣 泛 存 在 於 人 類 血 清 或 淚 液 等 多 種 動 植 物 組 1 I m 或 體 液 中 之 蛋 白 質 9 例 如 人 類 血 清 白 蛋 白 係 被 用 於 治 療 1 1 低 白 蛋 白 血 症 或 出 血 性 休 克 〇 又 於 眼 科 領 域 1 亦 已 知 被 用 1 1 作 蛋 白 質 製 劑 > 例 如 m 維 網 蛋 白 或 干 擾 素 之 安 定 化 劑 〇 巨 1 1 前 被 提 出 串 請 者 有 使 用 纖 維 網 蛋 白 或 干 擾 素 之 製 劑 供 乾 眼 1 1 症 之 治 療 (曰本特開昭6 1 - 103838號 特 開 平 6 - 271478號 ), 1 I 惟 白 蛋 白 本 身 對 黏 蛋 白 産 生 有 任 何 影 饗 或 對 角 結 膜 障 礙 或 1 1 I 乾 眼 症 是 否 有 效 的 見 解 則 兀 全 未 予 掲 示 0 1 1 發明之捃示 1 1 本纸張尺度適用中國國家標準（CNS ) A4規格（210 X 297公釐） 4 3 8 8 6 2 470648 A7 B7 五、發明説明（3 ) 本發明條提供以白蛋白為有效成分之眼科用醫藥組成 明 發 本 ο 礙 障 膜 結 角 療 治 於 用 可 物 成 組 藥 醫 之 明 發 本 ο 物 定 限 別 特 無 並 〇 源 面來 方之 症白 眼蛋 乾白 療的 治用 以所 用物 可成 亦組 物之 成明 組發 藥本 醫 之 等血 應 類 反人 敏如 過例 成 ， 生白 會 蛋 於 白 由源 ， 起 形類 情人 之以 性 ， 原 ψα 抗而 有體 具具 白 〇 蛋宜 白不 對而 而題 然問 的 用 常 用 療 醫 至 製 精 予 已 為 若 白 蛋 白 〇 清 用血 適類 較人 白於 蛋至 白 清 電之類 經毒人 以病之 言於品 而由藥 體 ，醫 具又作 〇 〇 售 明宜市 發較以 本者 。 於白宜 用蛋為 使白者 的為理 題上處 問以熱 無 ％ 加 更 〇〇 已 可其以 則時故 , 析 ， 者分化 度法活 純 泳不 適 .亦 白 蛋 白 的 産 生 物 生 撤 的 得 而 組 C 重 用因 適基 別傳 待遣 白 用 蛋利 白 由 清 血 項蛋 該白 習的 熟需 傜所 , 有 法含 造出 製製 之先 術 ， 技之 組 ^目 重簡 因 。 基者 傳知 遣.公 依用 〇 習 明所 發士 本人 於術 用技 導 體 載 該 將 體 截 之 \1/ 因 基 傳 遣 的 碼 编 白 蛋 白 類 人 如 例 /IV 白 ---------—裝-- (請先閣讀背面之注意事項再填寫本頁) 、?τ 線 經濟部中央標隼局員工消費合作社印裝 選離 胞 單 細 ， 形胞 轉細 之或 質液 白清 蛋上 的養 目培 之其 生由 産胞 將細 〇 形 形轉 轉 的 予出 並選 胞已 細養 主培 宿 。 入出 質病生 白免産 蛋避組 生由重 産 。因 為等基 出菌傳 示腸遣 例大的 可 、關 , 母 相 胞酵以 細的則 主用 ， 宿常點 於士觀 至人之 C 術 性 白技險 蛋項危 白該的 類習入 人熟混 製為等 精而毒 佳 較 白 蛋 白 之 說 本 症 眼 乾 /•V 症 有物 出生 舉微 可 、 J 敏 礙過 障 、 膜 炎 結膜 角結 Γ 角 , 種 中各 書 、 明> 膜 結 角 性 乾 菌 細 、 毒 病 本紙張尺度適用中國國家標準（CNS ) Α4規格（210X297公釐） 5 3 8 8 6 2 470648 經濟部中央標準局0貝工消費合作社印製 A7 B7五、發明説明（4 ) 、真菌等）之感染引起的疾病性要因、藥物之細胞毒性、 因酸、鹼引起的腐蝕等所致之化學性要因，眼表面之乾燥 、異物（隱形眼鏡等）引起的外傷、熱水等之物理性要因及 氯化苯甲烴銨、氯丁醇等之點眼藥所含的防腐劑或胺基糖 苷類条抗生素、非類固醇条消炎劑、IDU、游徽素等之點 眼藥等引起的角結膜之障礙、角結膜上皮缺損、角膜糜爛 、角膜潰瘍等。 本說明書中，「乾眼症」偽除予定義成「引起淚液量 降低或性質異常的狀態而不論有無角結膜障礙」之淚液減 少症（simple dry eye)外，亦包含有缺淚症、眼乾燥症、 謝革連氏（Sjogren)徵候群、乾性角結膜炎、史帝芬-強森 氏综合徵候群（Stevens-Johnson's syndrome)、眼類天痗 胞、眼瞼緣炎症等之各種乾眼病症。再者，亦包含有白内 障術後或過敏結膜炎伴隨的乾眼症，及VDT[視覺顯示終端 機（Visual Display Terminal)]作業者之淚眼減少及冷暖 氣房内因屋内乾燥等引起之全身異常等之乾眼狀病症。 本説明書中，「治療」一詞傷包含病症之預防、治療 、症狀之減輕、症狀之減退、擴散停止等所有病症之管理 Ο 本發明人等進一步發現白蛋白具有使眼表面上皮增強 黏蛋白産生之作用。因此，本發明偽再提供以白蛋白為有 效成分而用於增進黏蛋白分泌之醫藥組成物。 再者，本發明亦發現白蛋白具有使油分散的界面活性 劑作用，此界面活性劑作用亦被視作有肋於白蛋白引起的 (請先閱讀背面之注意事項再填寫本頁) 本纸張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 6 3 8 8 6 2 470648 經濟部中央標準局員工消費合作社印製 A7 B7五、發明説明（5 ) 淚液層之安定化的可能性。 本發明之醫藥組成物之製劑形態可例示有錠劑、丸劑 、散劑、懸浮劑、膠囊劑、座劑、注射劑、軟蕾劑、點眼 劑等。其中以供局部投用的點眼劑尤佳。 將本發明之醫藥組成物製劑作成點眼用藥之情形，本 發明之組成物含有白蛋白約lms/ml〜lOOOmg/ral、以約 10mg/ml 〜1000mg/ml為較佳，以 50mg/ml 〜1000mg/ml 為更 佳，及視需要含有藥學上許可的稀釋劑。 本發明所用的「藥學上許可的稀釋劑」，可例示出熟 習該項技術人士公知習用於眼科用製劑之所有稀釋劑，例 如水、生理食塩水、人工淚液等。 於本發明之組成物内可再使用一般眼科用製劑所用之 各種成分，例如安定化劑、殺菌劑、緩衝劑、等張劑、螯 合劑、pH調整劑、採用含有界面活性劑等之組成物投用亦 可。 至於安定化劑，可例示有甘胺酸、丙胺酸等一般的L-型胺基酸、葡萄糖、甘露糖等單糖類、蔗糖、麥芽耱等二 糖類、甘露糖醇、木糖醇等糖醇類、葡聚糖等多糖類。 至於殺菌劑，可例示有苯甲羥塩、氯己啶（chlorohex dine)塩、對氧基苯甲酸酯類等。 至於缓衝劑，可例示有硼酸、磷酸、醋酸、檸檬酸或 此等之塩等D 至於等張劑，可例示有氣化鈉、氣化鉀、糖類等。 至於螯合劑，可例示有乙二胺四乙酸鈉、檸樣酸等。 (請先閱讀背面之注意事項再填寫本頁) 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 7 3 8 8 6 2 470648 A7 B7 五、發明説明（6 因係點眼用藥，pH以調整成5〜8為佳 經濟部中央標準局員工消費合作杜印製 , 眼 藥 之白 含確膜 法說眼 之 藥投 欲 、技 眼點 醫 礙之包際角 方本乾 物 醫眼 所重項 1/以 之 障量僅實及 之 。有 成 述點 指體該 3 予 明 膜效 不及者 症白般 組 上以 偽 、習 00眼 發 結有 J，患 眼蛋述 述 用惟 J 別熟 '11/本 角用象患之 乾白上 上 使， 量性之 ^ U 述 療投對病病。療之如 於 以定 效 、域 1-50上 治，之之該者治量指 用 藥限 有龄領 約~ 造 種象礙 礙有患種效意 以 投別 r 年學 以30製 一對障障疑之一有傺 白 之特 之 、醫 時約 供 供之膜 膜含礙 供用， 蛋 白予 白狀他 藥為 供 提礙結結包障提投 J 白 蛋未 蛋症其 投宜 提 明 障角角 又膜明 ，象 。中 白並 白之及 次較 亦 。發膜 療有，結發象 對患其 ，徑 ，者上 毎， 明途本 結治疑 外角本 對的病 ， 。中路 中患藥 係眼 發用 ，角需 或以之 ，的 症之法用法用 法應醫 物1/本之點療 Γ 患患發點症眼症方適方投 方因他 成 3 ，白 觀治 内病病 併觀眼乾眼等 可等於 等 ，其 組50點蛋外需書之之能外乾療乾此均此至 此量慮 之約 觀白另 對明礙 礙可另 療治有 之白之 。 之需考 明~ 他 之在括 說障障 後在治 需疑明 蛋明可 明所併 發10其用者包本膜膜術者需 Γ 或發白發即 。發 之合 本約 。在 物再 ， 。結結手再對内狀本種本物 宜本上 、 為可 成 法白 角角植 括書症 一 成為 療食 宜即 組 方蛋 有有移 包明之 任 組用 治飲 (請先閱讀背面之注意事項再填寫本頁) 本纸張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 8 3 8 8 6 2 470648 A7 B7 五、發明説明（7 ) 經濟部中央標準局員工消費合作社印製 量藥 藥為 1 乾蛋般 皮.白泌 蛋上 組以 白重項 效醫 醫宜約 或白一 上的分 黏面 藥惟 蛋體該 有為 之 ，日 療 。與 面量白 有表 醫， 黏 、習 此則 明眼每so治藥以 表效蛋 ..眼 的定 之別熟 ,, 發1/,<^礙投， 眼有黏 括、 述限 皮性之 又定 本 W 量 障時藥 進與皮 包等 上別 上 、域 。 決 述00之 U 膜同投 增投上 J 礙 。以特 面龄領 量之 上 1 眼1¾結白之 種 ，面 象障患 傜予 表年學 约 厂 受 適量 ，1/1 角蛋液 一者表 對膜病藥未 眼 、醫 最效 。言1"3 彡 的白淚 供患之 。之結 之投並 使狀他 擇有業而約50U 用與工 提之眼化藥角礙之徑 為症其 選 C 作體如 ~ 習可人 明藥加 定投、障白路 J 之及 可異的具例30夂 ，亦 ， 發投增安 需眼泌蛋藥 量者上 而而行 ，為約0-中液際 本需 ，的 r 乾 分白投 效患藥 , 性例 法可為-1法淚之 。 ，對 法層 ，有白 ，於 有應醫 因活士方 ，宜5~方工 藥可上 傜方液中及 蛋中至 r 因他 要或 人等 量 較日 等 人投即 點 ，之 淚法 、黏法 。 ， ，其 種類 術此用 ，每此 之時行 觀法明 之方者 有方可 中可慮 各種技之投 眼指之 用同進他方發 面此患 測此即 。法即考 的之 項明之1/尤明所 液程其 之本表 明之預 明行宜 方量併 知白 該發次 W ，發時 淚療在 生由眼 發礙被 發施較 明之合 所蛋習本每50次本療 Η 及者産藉求本障 且本式 用發加 、 士白 熟於物 一20於治人 量再白 。謀 於泌礙 於方投 本增食 人依之 成10約 症與同 蛋白並 分障 物眼 生飲 術傜界 組約 ~ 眼白相 黏蛋， 白皮 成點 産、 (請先閱讀背面之注意事項再填寫本頁) 本紙張尺度適用中國國家標準（CNS ) Α4規格（2丨0 X 297公釐） 9 3 8 8 6 2 470648 A7 B7 經濟部中央標準局員工消費合作社印製 五、 發明説明（8 ) 1 1 技 術 人 士 所 知 的 各 種 要 因 而 可 選 擇 最 適 量 0 又 依 白 蛋 白 1 1 f 之 種 類 或 活 性 而 異 〇 有 效 量 之 決 定 9 刖 為 醫 藥 界 之 熟 習 該 1 1 項 技 術 人 士 例 行 的 作 業 0 1 請 1 1 於 本 發 明 之 此 等 方 法 中 具 體 而 » 上 述 本 發 明 之 醫 閱 1 I 藥 組 成 物 每 次 之 投 用 量 1 可 為 例 如 約 1至約100 u 1/眼 宜 讀 背 1 1 面 1 為 10 50 U 1/眼 較 宜 為 約 30 50 U 1/眼 之 量 9 每 B 約 1 之 注 1 I 意 1 1 約20次 » 尤 指 每 B 5 λ -1 0 次， 惟並非受此两 〒限定。 事 項 1 於 本 發 明 之 治 療 方 法 中 9 習 用 的 角 結 膜 障 礙 治 療 或 乾 再 填 1 眼 症 治 療 時 所 用 之 人 工 淚 液 亦 可 與 白 蛋 白 同 時 投 藥 0 白 蛋 寫 本 頁 裝 1 白 與 人 工 淚 液 同 時 投 藥 人 工 淚 液 之 投 用 t 以 與 一 般 相 同 量 1 1 及 療 程 進 行 即 可 0 1 I 製 劑 例 1 1 訂 本 發 明 之 試 驗 係 採 用 綠 十 字 股 份 有 限 公 司 製 造 的 捐 血 1 白 蛋 白 製 劑 0 此 白 蛋 白 製 劑 9 偽 以 損 血 者 之 血 漿 為 原 料 1 1 利 用 Co hn 之 低 溫 乙 醇 分 盡 化 法 分 離 純 化 的 白 蛋 白 區 份 9 調 1 I 整 成 下 述 製 劑 例 1及2, 及 在 60 ^ 進 行 1 0小 時 之 加 埶 處 理 所 1 it 1 得 者 〇 製割1 1 | (白蛋白含量25 % ) 1 I 人 類 血 清 白 蛋 白 2 5 0 m g / m 1 1 I 乙 醯 色 胺 酸 鈉 5 . 37 in g / 1 1 1 1 癸 酸 鈉 3 . 3 2 in g / m 1 1 I m m 2 1 1 (白蛋白含量5 % ) 1 1 乙 醯 色 胺 酸 鈉 1 . 07 m g / m 1 1 I 癸 酸 鈉 0 66 m g /扭 1 1 本紙張尺度適用中國國家標準（CNS ) A4規格（210'〆297公釐） 10 38862 470648 A7 B7五、發明説明（9 ) 試_.驗例L 對角結膜有障礙之3名乾眼症患者（64歲女性、61歲女 性及34歲女性）以每次30〜50；u 1/眼、每日點眼10次繼缅 投用製劑例1之25%人類血清白蛋白（白蛋白含量250ms/ ml)。與白蛋白之投用同時繼缠進行人工淚液之點眼。 於投用開始前及投用後，進行生體染色檢査，判定角 結膜障礙之程度。至於生體染色檢査，偽進行二碘瞎紅及 螢光染色。二碘曙紅染色（RB)偽成為角結膜障礙之指標的 檢査，就球結膜之释側、耳側、角膜各以〇〜3分_合計9點 將染色程度予以評分而成者。螢光染色（F)傜成為檢査角 膜障礙之指標，以0〜3分評分角膜之障礙程度而成者。任 一者均偽以Van Bijsterreld之評估方法予以評分。任一 種情況中，數值愈高則表示障礙愈嚴重。結果示於表1。 表1投用白蛋白之效果 (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 患 者 投藥期間 64歲女性 14天 右眼 左眼 61歲女性 14天 右眼 左眼 34歲女性s 7天 RB 投用前 投用後 7 7 3 3 8 8 5 5 上輪部染色較深 上輪部約略無染色 F 投用前 投用後 2 2 1 1 3 2 1 1 上輪部染色較深 上輪部約略無染色 *此患者僳於乾眼上併發有上輪部角結膜炎。__ 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） U 38862 470648 Μ Β7 五、發明説明（10 ) 試驗例2 皮後 上術)( 膜手標 角之商 後膜i( 膜角in 角層 e 植全eη 移眼ar ..右Hy 性植 9ί 男移 1 歲 ο 2 3J 6 用 者 患 損 缺 損 缺} % 續 1 繼ο 皮酸 上質 膜明 角透 , 有 含 已 療 台 91 g. ο 身 5 效 ~ 現 3 發次 未每 並以 L… 惟 ， 止 中 故 艮 ηπρ /470648 A7 B7 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the Invention (1) 1 I Branch Field 1 I The present invention provides a medicinal composition with albumin as an active ingredient 1 1 I. The medicine of the present invention The composition can be used to treat corneal and conjunctival disorders or dry eyes, etc., 1 I Please I Illness 0 The composition of the present invention has the effect of increasing the secretion of mucous epithelium on the surface of the eye without reading 1 I reading 1 I * The role of oil diffusion 0 Furthermore, the present invention provides a method of Λ 1 1 1 I to provide a method for treating corneal and conjunctival disorders and dry eye using the pharmaceutical composition. Attention 1 | Incident 1 and the use of the pharmaceutical composition to increase epithelial adhesion on the surface of the eye Fill in the method of protein secretion 1 〇 Written book page 1 Background surgery 1 I Keratoconjunctival disorder 引起 Caused by the formation of defects on the epithelium and whitening the surface 〇1 1 This cause is, for example, dry keratoconjunctivitis (dry eye disease) Λ Various keratoconjunctivitis is sensitive, due to Diseases caused by infection with microorganisms (viruses, bacteria, fungi, etc.) The main reason for order 1 is due to the cytotoxicity of drugs due to acid, alkali, etc. The chemical nature of 1 1 due to dry smoke on the surface of the eye λPγ »Foreign matter ( Ear-shaped glasses, etc.) cause physical injuries such as trauma, hot water, etc. 0 and preservatives or amine sugars contained in ophthalmic ophthalmic drugs that have been vaporized in recent years, such as benzyl ammonium, 1-line butanol, etc. % Antibiotics, 1 I non-steroids% anti-inflammatory agents IDU, pi maric 1 η, etc. eye drops 1 1 etc. have also been reported to cause damage to the corneal epithelium. 0 1 1 Now «for the treatment of corneal and conjunctival disorders» With the administration of chondroitin sulfate glutathione 1 glycin hyaluronan fibronectin EGF or tear supplement 6 scoops 1 | Implementation of artificial tears, etc. t but the effect is still Less than 0 1 I dry eye syndrome is defined as a condition that causes a decrease in the amount of tears or abnormal properties of the plant. 1 1 State 9 regardless of the presence of corneal and conjunctival disorders. J (Yamada et al. Ophthalmology, 43, 1 2 8 9-1 1 1293 ( 1 992)) 〇 Although there are various causes of dry eye disease, but "{£ has not been found 1 1 This paper size applies to the Chinese National Standard (CNS) A4 specification (210X2.97 mm) 3 3 8 8 6 2 470648 A7 B7 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the Invention (2) 1 | Method for reducing the amount of tears to return to normal 0 Current treatment of dry eye is treated by casting 1 I to supplement the artificial tears Tears 9 in an attempt to ease the patient's subjective symptoms 1 1 I Chondroitin glutathione glutathione N translucent acid fiber /-N Please use 1 1 1 net protein EGF, etc., but its effect is not sufficient. Read 1 1 1 According to recent research, the normal epithelial surface of the eye is found on the surface of the back. 1 1 1 has mucin-like glycoprotein t. This is considered to be actively involved in maintaining the tear layer. 1 1 〇 Further 9 Mucin secreted by conjunctival germ cells > Known to help regenerate tears | Stabilization of the layer 〇 Ocular epithelial disorders due to unknown cause% This page contains I * If caused by mucin secretion Tear layer instability at the time of the disorder > Corneal and conjunctival 1 1 I The reduction in the interaction between epithelial cells and tears is considered to be an epithelial disorder 1 1 Progression --- causes a so-called worsening vicious cycle (Yokoi Nobuhiko "Ophthalmic Treatment 1 1 Order 1 Techniques and Strategies J Xiaojian Wenxiong and other editors, Zhongshan Book Co., Ltd. (Japanese, Tokyo, pp. 26 ~ 27 (195)) 0 This insight > produced by enhancing mucin 1 1 > or other means Stabilization of the tear layer »and teachings can be changed 1 | Good corneal and conjunctival disorders or dry eye 0 it Albumin is widely present in various animal and plant groups such as human serum or tears 1 I m or protein in body fluids 9 For example, human serum white The protein line is used to treat 1 1 hypoalbuminemia or hemorrhagic shock. It is also known in the ophthalmology field. 1 1 is also used as a protein preparation. For example, m-dimensional reticulin or interferon stabilizers. Ju 1 1 Those who have been asked before have used fibronectin or interferon preparations for the treatment of dry eye 1 1 (Japanese Patent Publication No. 6 1-103838, Japanese Patent Application No. 6-271478), 1 I only albumin itself No opinion on the effectiveness of mucin production or on corneal and conjunctival disorders or whether 1 1 I dry eye disease is effective 0 1 1 Inventions 1 1 This paper applies Chinese national standards (CN S) A4 size (210 X 297 mm) 4 3 8 8 6 2 470648 A7 B7 V. Description of the invention (3) The article of the present invention provides an ophthalmic medicine composition with albumin as the active ingredient. The corner treatment is used in the Mingfa version of the medicine group. There is no specific limit to the material. The source of the disease is the white eye egg dry white treatment. The treatment can be used in the Cheng Ming group. The blood of the medicine and the medicine should be as anti-human as normal. The raw white will be the egg and the white, the nature of the lover, the original ψα, but the body is white. The egg should not be white. Of course, the commonly used medical treatment to refinement has been used for drugs such as albumin, blood, and blood, which are more suitable for humans than white for eggs to white for electricity. Make 〇〇 sale Mingyi City issued more than the person. Yu Bai should use the egg as the reason for the white person's question. It is not necessary to add heat to the %%, but it can be changed from time to time. Analysis, the differentiation method is not suitable for pure swimming. Also the production of albumin is produced. The retired group C reused because of Shijibei's transfer of white eggs to be used to clear the blood of the white eggs of the familiar needs of the practice, there are methods to create the system's first technique, the technical group of ^ eyes reiterate the reasons. The base is circulated by the public. The public has used it. Xi Mingfa sent himself to the technical conductor to carry the body section of the body. -----— Equipment— (Please read the precautions on the back before filling out this page),? Τ Line Ministry of Economic Affairs, Central Bureau of Standards, Employee Consumer Cooperatives, printed out the list of detached cells, The culture of the cultured egg on the white egg of the white liquid was carried out by the germ cells, and the cells were finely shaped. Import and export of germplasm disease, avoiding egg production and avoiding egg production. Because of the presence of equal bacteria, the intestines are large, and the mother's yeast is mainly used in small ones. It is often used in C-level technical white eggs of Shiguan to people. It is cooked into humans and is mixed with equal sperm, which is better than albumin. This disease is dry in the eye / V syndrome. There is a slight birth, J sensitivity hinders obstacles, meningitis, conjunctival angle, and Γ angle. Ming > Membrane keratophytic bacteria, toxic disease The paper size is applicable to Chinese National Standard (CNS) A4 specification (210X297 mm) 5 3 8 8 6 2 470648 Central Standards Bureau of the Ministry of Economic Affairs 0 Printed by ABC Consumer Cooperative B7 V. Description of the invention (4), fungal factors, disease-caused factors, cytotoxicity of drugs, chemical factors caused by acid and alkali corrosion, dry eye surface, foreign bodies (contact lenses, etc.) ) The physical causes of trauma, hot water, etc., and the preservatives contained in ophthalmic drugs such as benzyl chloride, chlorobutanol, or aminoglycoside strip antibiotics, non-steroid strip anti-inflammatory agents, IDU, swimmers, etc. Corneal and conjunctival barrier caused by eye drops, etc. Obstacles, corneal and conjunctival epithelial defects, corneal erosion, corneal ulcers, etc. In this specification, "dry eye syndrome" is defined as "simple dry eye" which is defined as "a state that causes a decrease in the amount of tears or abnormal properties, regardless of the presence or absence of corneal and conjunctival disorders." Syndromes, Sjogren's syndrome, dry keratoconjunctivitis, Stevens-Johnson's syndrome, ocular cells, inflammation of the eyelid margin, and other dry eye disorders. Furthermore, it also includes dry eye syndrome associated with cataract surgery or allergic conjunctivitis, and reduced tears in the eyes of VDT [Visual Display Terminal] operators, and systemic abnormalities caused by dryness in the heating and cooling rooms. Dry eye condition. In the present specification, the term "treatment" includes the prevention, treatment of symptoms, alleviation of symptoms, reduction of symptoms, and management of all diseases such as cessation of spread. The present inventors have further discovered that albumin has the ability to enhance the epithelium of the eye surface to enhance mucin. The effect. Therefore, the present invention further provides a pharmaceutical composition that uses albumin as an effective ingredient to enhance mucin secretion. In addition, the present invention also found that albumin has a surfactant effect that disperses oil, and this surfactant effect is also considered to be caused by ribbed albumin (please read the precautions on the back before filling this page) Zhang scale is applicable to Chinese National Standard (CNS) A4 specification (210X297 mm) 6 3 8 8 6 2 470648 A7 B7 printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention (5) Possibility of stabilization of the tear layer . Examples of the form of the pharmaceutical composition of the present invention include lozenges, pills, powders, suspensions, capsules, bases, injections, soft buds, eye drops, and the like. Eye drops for topical administration are particularly preferred. When the pharmaceutical composition preparation of the present invention is used as an ophthalmic medicine, the composition of the present invention contains about 1 mg / ml to 1000 mg / ral of albumin, preferably about 10 mg / ml to 1000 mg / ml, and 50 mg / ml to 1000 mg / ml is more preferred and contains a pharmaceutically acceptable diluent as needed. The "pharmacologically acceptable diluent" used in the present invention can be exemplified by all diluents known to those skilled in the art for ophthalmic preparations, such as water, physiological food water, artificial tears, and the like. In the composition of the present invention, various components used in general ophthalmic preparations can be reused, such as stabilizers, bactericides, buffers, isotonic agents, chelating agents, pH adjusting agents, and compositions containing surfactants. Put into use. Examples of stabilizing agents include general L-type amino acids such as glycine and alanine, monosaccharides such as glucose and mannose, disaccharides such as sucrose and malt, sugars such as mannitol and xylitol, and the like. Polysaccharides such as alcohols and dextran. Examples of the bactericide include benzoxamine, chlorohex dine, and parabens. As the buffering agent, boric acid, phosphoric acid, acetic acid, citric acid, or the like can be exemplified. As for the isotonicity agent, sodium vaporizing, potassium vaporizing, sugars, and the like can be exemplified. Examples of the chelating agent include sodium ethylenediamine tetraacetate, citric acid, and the like. (Please read the precautions on the back before filling this page) This paper size is applicable to the Chinese National Standard (CNS) A4 specification (210X 297 mm) 7 3 8 8 6 2 470648 A7 B7 V. Description of the invention Medication, the pH is adjusted to 5 ~ 8. It is best produced by the consumer cooperation of the Central Standards Bureau of the Ministry of Economic Affairs. Dubai, white medicine with eye drops contains the film method. The eye weight 1 / the barrier amount is only achievable. The tangible point refers to the body of the 3 Yuming film that is ineffective, with a false, Xi 00 eye knot with J, and the affected eye is described. Yongwei J Bieshu '11 / This corner is used to cure the disease in quantitative terms. U Quantitative treatment is used to treat the disease. The treatment is as if the effect is fixed and the range is 1-50. The amount of treatment refers to the age-limited agreement with the use of drugs. ~ The appearance of the image hinders the effectiveness of the disease. Membrane contains obstacles for use, protein to white-like drugs is provided for the purpose of improving the knot and encapsulation barrier. Membrane, elephant. Medium white and white, and lesser. Hair mask treatment is available, and the hair and the elephant are affected by the path, the path, the upper part of the head, and the path of the disease is treated by the suspected external angle. It is used for eye hair. The method of how to treat the symptoms of the eye needs to be used. The medicine should be treated with 1 / the point of treatment. Viewing the dry eye can be equal to the equivalent. The group of 50-point egg external need book can be used for external dry treatment. All the considerations mentioned here can be treated in addition to the obvious obstacles. Ming ~ He needs to be doubted after the treatment of the obstacles. It is necessary to know that the egg can be cleared. The user who covers the membrane needs surgery or white hair. The hair is about the same. Knot the hands and then apply the internal shape of this species to the original, in order to be able to form the white angle horn plantar syndrome. Once it becomes a therapeutic diet, the group of eggs should be prescribed for any group. (Please read the back Please fill in this page for the matters needing attention) This paper size is applicable to China National Standard (CNS) A4 specification (210X297 mm) 8 3 8 8 6 2 470648 A7 B7 V. Description of the invention (7) The amount of medicine printed by the Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs is 1 dried egg-like skin. The white secreted egg group is treated with white heavy medicine and should be treated as a medicine or a sticky surface medicine on the white one. The body deserves to be done, and the day treatment. There is a doctor with the face, the sticky, and the habit is to treat the eyes with the effect of the egg .. The eye's definition is familiar ,, hair 1 /, < Eyes are sticky, and the limitation of the skin is fixed. The amount of medicine and the bag are different when the amount of obstacles. It is stated that the U film of 00 is the same as that of J. With a special age-aged amount of 1 eye, 1¾ whitening seeds, patients with facial disorders have been given an appropriate amount by the chronology school, and 1/1 horny egg liquid is the most effective for the treatment of membrane diseases. Words 1 & 3 The result of the investment is that he chooses to have a career and about 50U uses the eye-catching medicine of the industrial medicine. The choice of the C body such as ~ Xi Keren Ming Yao plus scheduled investment, barrier white road J The specific case 30 is different. Also, those who need to increase the amount of egg secretion required to increase the safety of the eye, which is about 0-intermediate interstitial demand, r dry whitening effective drugs, the sex case law can be- 1 method of tears. For the legal level, there is white, if there is a medical prescription, it should be 5 ~ prescription medicine can be applied in the recipe and the egg to r. Because he wants to equal the amount of people to vote, click Tear method, stick method. The types of technology are used for this purpose, and at this time, those who have a good understanding of the method can consider the investment of various skills and use it for other people's problems. According to the law, the item 1 of the Ming Ming 1 / You Ming Sui's original course indicated the appropriate amount and know the hair W. When the hair tears are caused by the eyes, it is blocked by the brighter eggs. Every 50 times, this treatment should be done by the patient and the formula should be made with hair, and the person should be familiar with the material and 20 to the amount of treatment. It is planned to prevent the development of the diet by increasing the number of people, and the same protein and the obstacles of the eye and drinking. The circle of the world is about ~ The white eyes are sticking to the eggs, the white skin is the point of production, (Please read the back of the first Note: Please fill in this page again.) This paper size is applicable to China National Standard (CNS) Α4 size (2 丨 0 X 297 mm) 9 3 8 8 6 2 470648 A7 B7 Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs Explanation (8) 1 1 Various techniques known to the skilled person can therefore choose the optimal amount 0 and vary depending on the type or activity of albumin 1 1 0 The effective amount is determined 9 刖 Those who are familiar with the 1 1 technical person in the medical field Routine homework 0 1 Please 1 1 Be specific in these methods of the present invention »The above-mentioned medical reading of the present invention I The dosage of the pharmaceutical composition 1 per time 1 may be, for example, about 1 to about 100 u 1 / eye is appropriate Read Back 1 1 Side 1 is 10 50 U 1 / eye, preferably about 30 50 U 1 / eye 9 Note 1 about 1 per B I means 1 1 about 20 times »especially 5 times λ-10 times per B, but not limited by these two terms. Matter 1 In the treatment method of the present invention 9 conventional corneal and conjunctival disorder treatment or dry refilling 1 artificial tears used in the treatment of eye diseases can also be administered with albumin at the same time 0 white eggs written on this page 1 white and artificial tears are administered at the same time The administration of artificial tears can be performed in the same amount as usual 1 1 and the course of treatment can be carried out. 0 1 I Formulation Example 1 1 The test of the present invention is a blood donation made by Green Cross Co., Ltd. 1 albumin preparation 0 this albumin preparation 9 The blood plasma of the injured person was used as a raw material. 1 1 The albumin fractions separated and purified by Co hn's low-temperature ethanol depletion method were prepared. 9 Transcription I was prepared into the following formulation examples 1 and 2, and it was performed at 60 ^ for 10 hours. Additive treatment 1 it 1 winner 0 system cut 1 1 | (albumin content 25%) 1 I human serum albumin White 2 5 0 mg / m 1 1 I Sodium acetamidine sodium 5. 37 in g / 1 1 1 1 Sodium caprate 3.3 2 in g / m 1 1 I mm 2 1 1 (Albumin content 5% ) 1 1 Sodium Acetate Tryptophan 1.07 mg / m 1 1 I Sodium Decanoate 0 66 mg / Twisted 1 1 This paper size applies to Chinese National Standard (CNS) A4 (210'〆297 mm) 10 38862 470648 A7 B7 V. Description of the invention (9) Test _. Test Example L Three patients with dry eye syndrome (64-year-old woman, 61-year-old woman, and 34-year-old woman) with corneal and conjunctival disorders with 30 ~ 50 each time; u 1 25% of human serum albumin (albumin content 250ms / ml) of the formulation example 1 administered to Myanmar / eye, 10 eyes per day. Simultaneously with the administration of albumin, the point of artificial tears was followed. Before and after administration, a biopsy examination was performed to determine the degree of corneal and conjunctival disorders. As for the biological staining, diiodine and fluorescent staining were performed. In the examination of diiodine eosin staining (RB), which is pseudo-indicated as an index of corneal and conjunctival disorders, the release side, ear side, and cornea of the bulbar conjunctiva were scored with 0 to 3 points and a total of 9 points. Fluorescent staining (F) 傜 is used as an index for examining corneal disorders, and the degree of corneal disorders is scored on a scale of 0 to 3. Each of them was scored in a pseudo-Van Bijsterreld evaluation method. In either case, the higher the value, the more severe the obstacle. The results are shown in Table 1. Table 1 Effects of using albumin (please read the precautions on the back before filling out this page) Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs Patients during the administration of 64-year-old women 14 days right eye Left eye 61-year-old women 14 days right eye 34-year-old female in the left eye 7 days before RB 7 7 3 3 8 8 5 5 After the application, the upper part is slightly stained The upper part is slightly stained F Before the application 2 2 1 1 3 2 1 1 The upper round is darker and the upper round is slightly non-staining. * This patient had keratoconjunctivitis of the upper round on the dry eye. __ This paper size is in accordance with Chinese National Standard (CNS) A4 (210X297 mm) U 38862 470648 Μ B7 V. Description of the invention (10) Test example 2 Post-epithelial surgery) (Financial film i) Horn in cornea e implantation eη eye shift ar .. right Hy sex plant 9ί male shift 1 year old ο 2 3J 6 user with defect defect}% continued 1 follow ο epidermal epithelium with bright corners, with treatment台 91 g. Ο Body 5 effects ~ now 3 rounds and each with L ... However, stop and stop ηπρ /
天 1X 後 其 ο 用% 投25 之之 *1 t—H in例 em劑 e 製 Γ Ϊ a 用 ^次 血 類 人 量 含 白 蛋 白 /IV 白 蛋 白 清 後 期 星 ix 〇 期 星 ix 眼 點 續 繼 善 改 經 已 損 缺 皮 上 膜 角 皮 上 出 長 3 膜例 角駿 , 試 螢 由 後 膜 羊 植 者移 患 、 損部 缺 輪 皮植 上移 膜之 角膜 後角 膜層 角全 植 眼 移左 : 植 性移 女 經 歲 次 每 以 ο 礙 障 皮 上 膜 角 有 現 發 色 染 光After 1X day ο ο 25% of the * 1 t-Hin in the case of em agent e Γ Ϊ a a human blood serum containing albumin / IV albumin late stage ix 〇stage ix eye point continued Following the improvement of the damaged corneal epithelium on the corneal surface, 3 cases of horned cornea were tested, and the test was transplanted by the posterior lamb transplanter, and the corneal layer of the corneal layer was transplanted after the corneal layer was transplanted on the defect. Shift left: Transplantation of women's menstruation every year
艮 JJ· / U 量 含 白 蛋 白 /fv 白 蛋 白 0 •νί 血 類 人 % 5 之 2 例 劑 製 用 次 星 4 眼 粘 績 繼 (請先閱讀背面之注意事項再填寫本頁 予 色 染 光 螢 由 藉 後 期 ο ， 星 2 善色 用改染 投有所 始礙色 開障染 。 皮 光 期上螢 現為 發未 , 全 時完 査 ， 檢時 以査 檢 後 期 星 4 的 顯 明 有 礙 用障 投皮 始上 開現 在發 善 改 經濟部中央標隼局員工消費合作社印裂 例 驗 試 以 者 患 損 缺 皮 上 膜 者角 患 的 群發 候併 徽群 氏候 連徽 革氏 tin .1ΤΠ1— 譁 遵 : 革 .Ξ fJJ 諸 女對 歲 鈉 酸 甘 色 有 含 /1\ \)/ 標 商 e /fv \i/ 標 商 有 含 Γ ο 角 現 發 未 仍 惟 後 療 台 液 淚 Η 人 及 次 每 以 、 用 停 方 處 療 台 此 將 〇 善 改 之 損 缺 皮 上 膜 w 含 白 蛋 白 /__' 白 蛋 白 青 •yt 血 類 人 之 2 例 劑 製 用 次 6 天 眼 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 2 3 8 8 6 2 470648 A7 B7五、發明説明（11 ) 量50mg/ml)繼缠點眼4星期。在4星期後檢査時，未發現有 角膜上皮缺損。 試，驗例5 45歲女性謝革連氏擻候群患者 對謝革連氏歡候群併發的角結膜上皮障礙患者，以每 次30〜50U1/眼，1天10次，用製劑例2之5%人類血清白 蛋白（白蛋白含量50mg/ml)繼绩點眼4星期。 開始投用前及投用後進行生體染色檢査（二碘曙紅染 色及螢光染色），以判定角結膜障礙之程度，生體染色檢 査係以微移液管正確的將1 %二碘曙紅及1 %螢光之混合液 2wl點眼入下眼瞼結膜囊内、俟數次眨眼後，以細縫燈之 白色光觀察二碘曙紅染色狀態（RB),以轱藍光觀察螢光染 色狀態（F),對各自的染色狀態以0〜9分予以評分而成者 。結果不於表2。 表2 投用白蛋白之效果 (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 投用前 投用後 (4週内） R B評分右眼 7 2 左眼 7 2 F評分右眼 9 2 左眼 9 2 本纸張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 3 8 8 6 2 470648Gen JJ · / U Amount of albumin / fv Albumin 0 • νί Blood human% 5 of 2 Example of preparation of secondary stars 4 Eye stickiness (Please read the precautions on the back before filling in this page to color and dye Fluorescent from the late period ο, Star 2 good color with the change of dyeing has begun to hinder the color to open the barrier. Fluorescence in the skin light phase is not yet developed, complete the investigation, check the late phase of the star 4 to check Barrier investment has begun to be developed now and it is necessary to reform the Central Government Bureau of Standards of the Ministry of Economic Affairs of the Consumer Cooperative Co-operative Seal of the People's Republic of China. — Wa Zun: Leather.Ξ fJJ The girls have a sodium natrium content / 1 \ \) / standard e / fv \ i / standard y ο ο 角 corners have not been found, but only after treatment liquid tears The person and time of the treatment should be used at the treatment station. This will improve the damaged skin defect membrane w / albumin / __ 'albumin blue • yt blood type of 2 cases of preparation for humans for 6 days. Applicable to China National Standard (CNS) A4 specification (210X 297 male (Centre) 2 3 8 8 6 2 470648 A7 B7 V. Description of the invention (11) Amount 50mg / ml) Follow the eye for 4 weeks. On examination 4 weeks later, no corneal epithelial defect was found. Test, test example 5: A 45-year-old female Shegerian's syndrome group of patients with corneal and conjunctival epithelial disorders complicated by Shegerian's syndrome group, each time 30 ~ 50U1 / eye, 10 times a day, using 5% of the preparation example 2 human Serum albumin (albumin content of 50 mg / ml) continued for 4 weeks. Before and after the administration, a biostaining test (diiodine eosin staining and fluorescent staining) is performed to determine the degree of corneal and conjunctival disorders. The biostaining test is performed with a micropipette to accurately apply 1% diiodide. 2wl of eosin and 1% fluorescent mixture was spotted into the lower eyelid conjunctival sac. After blinking several times, the diiodine eosin staining state (RB) was observed with white light under a slit lamp, and the fluorescence was observed with osmium blue light. The dyeing state (F) is obtained by scoring each dyeing state on a scale of 0 to 9. The results are not in Table 2. Table 2 Effect of applying albumin (please read the precautions on the back before filling this page) Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs before use (within 4 weeks) RB score right eye 7 2 left eye 7 2 F-score right eye 9 2 left eye 9 2 This paper size applies Chinese National Standard (CNS) A4 size (210X297 mm) 3 8 8 6 2 470648
7 7 A B 五、發明説明（1 2 ) 試驗例R 對3名乾眼症患者（64歲女性、61歲女性及34歲女性）， 以每天30〜50W1/眼，1天10次，用製劑例1之25%人類血 清白蛋白（白蛋白含量250mg/inl)繼鑛點眼。白蛋白投用之 同時繼鑲進行人工淚液之點眼。 判定投用開始前及投用後患者之自覺症狀。自覺症狀 傜以眼痛、眼之乾澀及眼之異物感為中心的最惡劣狀態為 1 0 0 ,以最佳狀態為0 ,由患者本身自行判斷。結果示於表 3 〇 表3 投用白蛋白之自覺症狀的改善 (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 患 者 投用期間 64歲女性 14天 6 1歲女性 14天 3 4歲女性s 7天 右眼 左眼 右眼 左眼 投用前 100 100 100 100 100 投用後 0 30 50 50 20 *此患者係於乾眼上併發有上輪部角結膜炎。 試驗例7 對謝革連氏徵候群併發的乾眼症患者（72歲、女性）， 以每次3 0〜5 0 w 1 /眼，1天6次，用製劑例2之5 %人類血清 白蛋白（白蛋白含量50mg/ml)繼鑲點眼8星期。 本纸張尺度適用中國國家標準（CNS ) A4規格（2丨OX297公釐） 14 3 8 8 6 2 470648 A 7 B7 經濟部中央標準局員工消費合作社印製 五、發明説明（13 ) 8星期後，患者之以眼痛、眼之乾澀及眼之異物感為 中心的乾眼症之自覺症狀幾乎消失，故中止的白蛋白之投 用。 試驗例8 調査白蛋白對眼上皮細胞之黏蛋白生産之增強作用。 以溶解CCL細胞（結膜上皮細胞株）於人類血清白蛋白（ SIGMA公司）而成10% (W/V)之TCM 199培養基（GIBC0公司） 以常法培養24小時。另僅以TCM 199培養基同法培養作為 對照組。 以胰蛋白酶-EDTA剝離已培養的細胞後，於三聚甲醛 内固定30分鐘，以PBS(磷酸塩缓衝塩水）清洗3次後，於正 常山羊血清内封阻（4 °C , 3 0分鐘）後，使與小白鼠抗黏蛋 白抗體（Hue 1)反應（4C, 30分鐘），其後用PBS清洗3次。 再使與F I T C標幟抗小白鼠I g G抗體反應（4 C， 3 0分鐘） ,其後用P B S清洗3次。 對所得的細胞採用Epics(Colter公司）以流動細胞計 測定黏蛋白産生（陽性）細胞於全部細胞中之比率（％)。結 果示於表4。 表4 由白蛋白引起的黏蛋白産生之增強作用 黏蛋白産生（陽性）細胞（％) 對照組（未添加） 白蛋白1 0 %組 15.2¾ 3 5.5¾ 本紙張尺度適用中國國家標準（CNS ) A4規格（210X29?公釐） 15 3 8 8 6 2 (請先閱讀背面之注意事項再填寫本頁) 470648 A7 B7 五、發明説明（14 ) 可得知由添加白蛋白明顯的增強結膜上皮細胞之黏蛋 白産生能力。 例 驗 試 時 油 麻 % 蓖 5 之加 % 添 積液 體淚 10H 加人 添對 液中 淚其 工於 人若 對 。 若 在 存 式 形 滴 油 以 會 成 使 液 溶 白 蛋 白 此面 由表 〇 眼 失防 消預 滴有 油具 使而 , 劑 散 性 擴活 上面 面界 表為 水作 於僳 會白 。 油蛋用 麻白作 蓖示的 > 顯 散 時即蒸 ¥ ，液 積果淚 體結之 倌 儅 用 利 之 業 産 及亦 礙 -障途 膜用 結及 角法 療方 治 、 在物 , 成 途組 用藥 及醫 法之 方明 、 發 物本 成 〇 S 勺 之用 明有 發傷 本症 眼 乾 用 .作 的 加 增 泌 分 白 蛋 黏 之 皮 上 面 表 眼 使 可 有 具 示 表 步 1 進 (請先閲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 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 6 1i 3 8 8 6 27 7 AB V. Description of the invention (1 2) Test example R For 3 dry eye patients (64-year-old woman, 61-year-old woman, and 34-year-old woman), 30 to 50 W / eye per day, 10 times a day, using the preparation In Example 1, the 25% human serum albumin (albumin content 250mg / inl) was followed by eye drops. The use of albumin was followed by the placement of artificial tears. Determine the patient's subjective symptoms before and after administration. Self-conscious symptoms 傜 The worst state centered on eye pain, dryness of the eyes, and foreign body sensation is 100, and the best state is 0, which is judged by the patient himself. The results are shown in Table 3 〇 Table 3 Improvement of the subjective symptoms of the administration of albumin (please read the precautions on the back before filling this page) Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs Patients 64-year-old women 14 days 6 1 year old female 14 days 3 4 years old females 7 days right eye left eye right eye left eye before administration 100 100 100 100 100 after administration 0 30 50 50 20 * This patient is on dry eyes with upper corners Conjunctivitis. Test Example 7 For patients with dry eye syndrome (72 years old, female) complicated by Schelenian's syndrome, 30 to 50 w 1 / eye, 6 times a day, using 5% of human serum albumin of Preparation Example 2 (Albumin content 50mg / ml) followed by eye fixation for 8 weeks. This paper size applies Chinese National Standard (CNS) A4 specification (2 丨 OX297 mm) 14 3 8 8 6 2 470648 A 7 B7 Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of invention (13) 8 weeks later The patient's conscious symptoms of dry eye, centered on eye pain, dryness of the eyes, and foreign body sensation almost disappeared, so the administration of albumin was suspended. Test Example 8 The effect of albumin on mucin production of ocular epithelial cells was investigated. CCM cells (conjunctival epithelial cell line) were lysed in 10% (W / V) TCM 199 medium (GIBC0) in human serum albumin (SIGMA), and cultured for 24 hours in a conventional manner. In addition, only TCM 199 medium was cultured in the same way as a control group. After the cultured cells were detached with trypsin-EDTA, they were fixed in paraformaldehyde for 30 minutes, washed with PBS (phosphate buffered 塩 water) 3 times, and then blocked in normal goat serum (4 ° C, 30 minutes). ), Reacted with mouse anti-mucin antibody (Hue 1) (4C, 30 minutes), and then washed 3 times with PBS. Then reacted with F I T C-labeled anti-mouse I g G antibody (4 C, 30 minutes), and then washed 3 times with P B S. The ratio (%) of mucin-producing (positive) cells to total cells was measured on the obtained cells using a flow cytometer using Epics (Colter). The results are shown in Table 4. Table 4 Enhancement of mucin production by albumin Mucin-producing (positive) cells (%) Control group (not added) Albumin 10% Group 15.2¾ 3 5.5¾ This paper size applies Chinese National Standards (CNS) A4 specification (210X29? Mm) 15 3 8 8 6 2 (Please read the precautions on the back before filling out this page) 470648 A7 B7 V. Description of the invention (14) It can be seen that the addition of albumin significantly enhances the conjunctival epithelial cells Mucin production capacity. For example, linseed%, castor 5 plus%, effusion, body tears, 10H, plus people, add tears in the liquid, and it works. If a drop of oil is stored in the form to make the liquid soluble protein, this surface is caused by the drop of oil on the surface of the eye, and the surface of the upper surface is dispersed as the water is used for the whitening. Oil egg with sesame white as castor > steamed when it is scattered, the spleen fruit tear body knots should be used for profitable production and also hinder-barrier membrane and knot treatment method, The formula and medicine of Chengtu group, the prescription of the hair product is 0S, the use of the spoon is known to have hair injury, dry eyes. It is used to increase the secretion of albumin and the surface of the skin Step 1 (Please read the notes on the back before filling out this page) Printed by the Central Consumers Bureau of the Ministry of Economic Affairs, Consumer Cooperatives This paper is printed in accordance with China National Standard (CNS) A4 (210X297 mm) 6 1i 3 8 8 6 2