200301142 E6 __ F6 五T發明之詳細説明: ' 技術領域 . τΓ 本發明係有關於，用糖類除去肉毒素之技術；關於除去 含糖類之肉毒素用組成物、及使用該組成物的肉毒素除去方 法與卒取方法的g羊細內容，係有關於從醫療用具、醫藥品製 器具、醫樂品製造裝置等固體表面中去除肉毒素之有效技 技術背景 肉毒素屬於主要存在於革蘭式陰性菌細胞壁外膜的一種 脂多糖，因身爲發熱性物質（Pyrogen)而成爲眾所皆知的物質。 當注射劑或導管等受到肉毒素所汙染，而讓發熱性物質 侵入體內時，有可能會發生發燒、休克、廣泛性血管內凝固 (DIC : Disseminated Intravascular Coagulation)等症狀，因此 必須嚴格管理，以防肉毒素汙染到注射劑等醫藥品、注射器 或導管等醫療用具、醫藥品製造器具及裝置等。 大部分的醫療用具或醫藥品製造器具及裝置等，都是由 各種合成樹脂、玻璃、金屬及天然谶維等所構成，而且可能 會因附著或吸附肉毒素而遭受汙染。 通常，肉毒素在250°C環境下加熱30分鐘以上，或者在 170°C環境下加熱120分鐘以上就會呈現不活化的狀態，因此 玻璃或金屬等材質，可藉由這種加熱處理方式避免感染肉毒 素；此外，在含有氫氧化鈉的3(TC乙醇或二甲亞颯等有機溶 劑中，肉毒素會呈現不活化狀態，因此即使用這種溶劑淸洗 玻璃％ ’也可去除肉毒素；但是若用不適用於适種加熱處理、 或有機溶劑處理方式的材質所構成的醫療用具或醫藥品製造 器具及裝置等，或屬於在構造上無法用這種加熱處理方式的 醫療用具或醫藥品製造器具及裝置等，就必須採用其他去除 汙染的方式。 4 _ _. — . — _________' -____—— -- 本紙張尺度適用中國國家標準（CNS ) A4規格（210x297公瘦） (請先閱讀背面之注意事項再行繪製) •裝· .泉 經濟部中央標準局員工消費合作社印製 經濟部中央標準局員工消費合作社印製 200301142 E6 F6 五、發明之詳細説明「 舉例來說，要除去這些醫療用具或醫藥品製造器具及裝 置等所含的肉毒素，可用不含肉毒素的水或生理食鹽水以進 行淸洗，但這些淸洗方法需用到大量的水或生理食鹽水，而 且也有可能發生無法完全去除醫療用具或醫藥品製造器具及 裝置上所附著或吸附的肉毒素。 在專利第2884975公報有效萃取附著或吸附於容器、器 具等固體表面的肉毒素方法上有記載，可用淸蛋白、人體血 淸白蛋白、球蛋白等蛋白溶劑，以取代水或生理食鹽水等， 當淸洗完容器、器具等後，再萃取出溶劑中.的肉毒素。 但是，血液蛋白屬於來自於生體的成份，若要用來去除 存在於醫療用具或醫藥品製造器具及裝置等的肉毒素，並不 算是値得推薦的淸洗方式；若要用於這些用途上，最好不使 用含有生體來源成份的溶劑，而是最好能採用方便調製與使 用的組成物。 用方便調製與使用之組成物以淸洗或除去肉毒素的技 術’則適用於例如：爲了縮短有效期間，而視其需要高頻度 製造的醫藥品，或者用短半衰期放射性核種來製造出放射性 醫藥品；其中最適合用來製造出，在數小時半衰期內用超短 半哀期釋放陽電子核種之釋放陽電子放射斷層影像（P ◦ s i t r ο η Emission Tomography，以下簡稱爲「PET」）診斷法所用的藥 劑。 本發明之目的在於，利用除去醫療用具或醫藥品製造器 具及裝置等固體表面上所附著或吸附的肉毒素技術，及非生 體來源的化學試劑、且可進行殺菌處理的成份，提供出比水 或生理食鹽水更能有效除去肉毒素的方法。 公開發明 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） ---------A------IT-------1 (請先閲讀背面之注意事項再行繪製) 經濟部中央標準局員工消費合作社印製 200301142 E6 —F6 五、發明之詳細説明： PET診斷法的代表性藥劑2-〔 18F〕-氟代-2-脫氧-D-葡萄 糖（以下簡稱爲「18F-FDG」），大多是利用哈馬克（Hamacher) 等方法（Hamacher, Κ· et al·, J· Nuclear Medicine, 27: 235-238, 1986)所做成；經由這些發明人屢次使用這些製造方法，並 精心硏究除去離子阻滯樹脂上所附著或吸附的肉毒素方法 後’終於發現到無法用一般的水或生理食鹽水所去除的肉毒 素’竟然可使用含糖類成份的溶劑，極爲有效的溶解析出或 萃取出肉毒素，而且可用於去除醫療用具或醫藥品製造器具 及裝置等固體表面上所附著或吸附的肉毒素，因而完成本發 明。 如此一來，本發明的特徵便在於提供，將糖類視爲有效 成份後’以去除吸附或附著於固體表面之肉毒素的專用組成 物。 換言之，讓本發明的除去肉毒素用組成物溶劑，接觸需 除去肉毒素的醫療用具或醫藥品製造器具及裝置等各種固體 表面後，再藉由回收方式以有效去除肉毒素。 根據本發明的另一個角度來說，其特徵在於提供讓應去 除肉毒素的固體表面，接觸前述組成物溶劑，以去除該固體 表面所附著或吸附之肉毒素的方法。 讓本發明之除去肉毒素用組成物溶劑，接觸前述固體表 面的方法，可依據該固體表面的種類進行適當的選擇；舉例 來說’其使用方式可分爲，將固體表面浸漬於本發明除去肉 毒素用組成物溶劑內、或用該溶劑淸洗固體表面、或用適當 方法讓該溶劑浸漬於已殺菌的布，再用該布擦拭固體表面等。 此外，用本發明組成物溶劑，執行上述浸漬、淸洗、擦 拭等操作’可讓醫療用具或醫藥品製造器具及裝置等固體表 面上所附著或吸附的肉毒素轉移到前述溶劑中，並可溶解析 6 本紙張尺度適用中國國家標準（CNS ) A4規格（210 X 297公兹） ---------^------1T-------多 (請先閱讀背面之注意事項再行繪製) 經濟部中央標準局員工消費合作社印製 200301142 E6 F6 五、發明之詳細説明： ~： 出或萃取出該溶劑中的肉毒素，因此本發明組成物可獲得能 有效檢測及測量該固體表面受到肉毒素之汙染程度的檢測 液。 換言之，以另一個角度來看’本發明之特徵在於提供， §襄已吸附或附著肉毒素的固體表面接觸前述組成物溶劑，以 獲得含有自該固體表面脫離或解離之肉毒素的前述組成物萃 取方法。 以下將說明本發明的實施型態。 本發明組成物所用的糖類，則有單糖、寡（〇丨丨g 〇 )糖、該 衍生物；此外’這些糖類也可以是鹽或水合物；再者，糖類 也可以是D體或L體；具體而言，單糖最好是一般的六碳糖 例如：葡萄糖、半乳糖、甘露糖、果糖等、葡糖胺、半乳糖 胺、葡糖胺氫氯化物、半乳糖胺氫氯化物、N-乙銑葡糖胺、 N-乙銑半乳糖胺等氨基酸、衍生物及鹽；寡（〇ng〇)糖方面則 有二糖到六糖，最好是採用麥芽糖、蔗糖、乳糖等二糖；其 中適用的糖類爲葡萄糖、葡糖胺氫氯化物、N-乙銑-D半乳糖 胺及麥芽糖，最好的糖類則是葡萄糖。 使用本發明之除去肉毒素用組成物時，需調製成已溶解 於適當溶劑內的溶劑，但也可提供用於已事先溶解於溶劑內 的溶劑型態；此外，也提供凍結乾燥的型態，等到要使用時 再溶解於溶劑中即可；再者，也提供本發明組成物之凍結乾 燥品與溶劑的組合套件。 只要是生理學、藥物學、化學得以容許，便不特別限定 溶劑，例如：生理食鹽水、林格式液（Ringer’s solution :改 良的生理食鹽水）般的電解質組成物、注射用劑.等各種緩衝 劑；緩衝劑方面則有磷酸緩衝液、檸檬酸緩衝液等、鄰苯二 酸、磷酸、硼酸、檸檬酸、琥珀酸、洒石酸、乳酸、醋酸、 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 裝 訂 ^A (請先閲讀背面之注意事項再行繪製) 經濟部中央標準局員工消費合作社印製 200301142 E6 F6 五、發明之詳細説明： 氯化銨、碳酸、三（羥筹甲基）氨甲烷、及由這些氯系所構 成的緩衝液。 此外，本發明組成物可視其需要，含有生理學、藥學、 化學所容許的各種添加劑；添加劑方面則有酸、鹼等各種pH 調製劑、各種緩衝溶劑、葡聚糖10、葡聚糖40、糊精、環糊 精、乳酸鈉、各種胺基酸、甲醇、乙醇、二甲亞楓、N, N-二 甲基甲銑胺、乙腈、氧染環戊烷等。 雖然本發明的溶劑內糖類濃度，會因糖及溶劑等種類、 固體表面所吸附或附著肉毒素的程度等而異，但通常都在0.1 〜15公克/毫升（g/ 100ml)(以下簡稱爲「w/ν%」），其中最好 能在0.5〜10w/v%範福內；當濃度過低，就會降低除去肉毒 素的效果；濃度過高時，就必須使用大量的淸洗劑，以淸洗 除去後所殘留的糖類，而且會形成出操作的繁雜性。 本發明組成物溶劑，可視其需要隨著添加劑，調製出溶 解於溶劑內的糖類，但在性質上務必調製出不含肉毒素或失 去活性的糖類溶劑；利用本發明組成物以去除肉毒素的方法 上則有，藉由糖類溶劑超濾膜或肉毒素吸附體等以除去肉毒 素的方法，或者使用已藉由超濾膜等事先去除肉毒素的水， 以調製出糖類溶劑；此外，也可直接使用已殺菌的市售糖類 溶劑，例如：日本藥局方的葡萄糖注射液（5w/v%、l〇w/v% 等），此時不須再特別調製因此極具便利性；再者，也可利用 上述溶劑，將相關市售糖類溶劑稀釋成無菌狀態後再使用。 如此一來，將適當固體浸漬於本發明組成物溶劑內，或 用該溶劑淸洗該固體表面，就可讓已附著或吸附於該固體表 面的肉毒素，脫離或解離於該表面再轉移到該溶劑內，而得 以獲得有效的除去效果；再者，可藉由回收浸漬或淸洗之用 的溶劑，以檢測或測量出附著於固體表面的肉毒素量；換言 之，本發明組成物也可作用肉毒素檢測液之用。 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） ---------A------IT------- (請先閲讀背面之注意事項再行繪製) 200301142 E6 F6 _ 五、發明之詳細説明： (請先閱讀背面之注意事項再行繪製) 利用已公開的肉毒素測量法，例如：將兜蟹的血球成份 卒取液（以下簡稱爲「A L丨谷劑」）提供用於測量嚳試驗（l i m u 1 u s Test)法等之用的樣本，就可正確測量出固體表面遭受肉毒素 汙染的程度；AL溶劑是從鱟族（Limulus)、準鱟族（Tachypleus) 等兜蟹血球中所萃取而成，可使用因肉毒素或卢-1，3-葡聚糖 反應所產生的凝固物；一般而言，可使用生化學工業（株） 及和光純藥工業（株）等調製而成的市售凍結乾燥品；藉由 Limulus Test法以測量樣本中肉毒素濃度的方法，只要是日本 藥局方所記載的一般方法，就能毫無限定的使用。 本發明用以去除肉毒素或萃取對象的固.體表面則爲，醫 療用具、醫藥品製造器具、醫藥品製造裝置等固體表面；醫 療用具方面則有，拋棄式注射針、拋棄式注射筒、拋棄式輸 血器具及輸液器具、拋棄式採血專用器具、人工心肺用拋棄 式組.、醫療用人工血管、人工心臟瓣、心臟起搏器、透析型 人工腎臟裝置等、測試肉毒素所用的拋棄式實驗器具（已殺 菌滴管、已殺菌實驗管、已殺菌吸管片等）等；醫藥品製造 器具及醫藥品製造裝置則有，用於離子交換樹脂等精製或分 離而成的樹脂、逆滲透膜、奈米過濾膜、超濾膜、精密過濾 膜、電氣透析膜等精製或分離之用的膜等；此外，由於有效 期限較短，因此本發明可視其需要，有效去除高頻度製造的 醫藥品製造器具及裝置上的肉毒素，尤其是能有效去除附著 或吸附於2-〔 18F〕-氟代-2-脫氧-D-葡萄糖的合成裝置及/或 器具上的肉毒素。 實施例 以下將列舉出實施例，以更具體的說明本發明內容；但 本發明並不偏限於這些實施例；再者，只要沒有特別標示， 以下實施例皆以「w/v%」作爲糖類溶劑的濃度標示。 實驗所用之試劑與器具 本紙張尺度適用中國國家標準（CNS ) A4規格（210 X 297公釐） 經濟部中央標準局員工消費合作社印製 200301142 E6 F6 五、發明之詳細説明： 注射筒、三方活栓及柱塔等，都是使用已殺菌的市售拋 棄型器具；玻璃器具則用已經過注射用水淸洗後，在250°C、 90分鐘環境下進行乾熱殺菌處理的器具。 關於糖類溶劑方面，則使用適當稀釋過後的市售品，或 將市售特級試劑溶解於注射用冰內，再依據下列實施例注入 離子阻滯樹脂，以做成除去肉毒素溶劑·，這些溶劑都是以無 菌操作方式所調製而成。 基於日本藥局方的肉毒素實驗用試劑，則採用以下試劑。 肉毒素標準溶劑（l〇〇〇〇EU/ml) :將適量的肉毒素實驗用 水溶解於肉毒素10000標準品（日本藥局方標準品），調製成 肉毒素標準溶劑（10000EU/ml )，將、此視爲原劑後再予以適當 稀釋；再者，「EU」表示肉毒素的單位。 凝膠化法：Limulus ES-II Test WAKO (和光純藥製） 比濁法：Limulus ES-II Test WAKO 或 Limulus ES-J Test WAKO (和光純藥製） 離子阻滯樹脂則採用BIORAT製離子阻滯樹脂AG 11 A8。 實施例1 , 藉由葡萄糖溶劑淸洗離子阻滯樹脂Μ 在已用咼壓签殺菌（120°C、20分鐘）的柱塔內，無菌塡 充離子阻滯樹脂，以做成2根柱塔。 在二根柱塔內注入100ml注射用水再進行調節；接下來， 在1根柱塔（以下稱之爲「柱塔1」）內注入1 〇〇ml注射用水， 並在另一根（以下稱之爲「柱塔2」）內注入l〇ml的0.175w/v %葡萄糖溶劑，再針對各柱塔的溶解析出液執行肉毒素實驗 (凝膠化法）；依照日本藥局方法實施凝膠化法的結果則如表 1所示。 從表1柱塔2的結果可知，將〇. Π5w/v%葡萄糖溶記注 本紙張尺度適用中國國家標準（CNS ) Λ4規格（210 X 297公釐） (請先閲讀背面之注意事項再行繪製) 訂200301142 E6 __ F6 Five-T invention details: 'Technical field. ΤΓ The present invention relates to a technique for removing botulinum toxin by sugar; a composition for removing botulinum toxin containing sugar, and a botulinum toxin removal using the composition Methods and details of the method of extracting g are related to effective techniques and techniques for removing botulinum toxin from solid surfaces such as medical appliances, medical devices, and medical equipment manufacturing equipment. Background Botoxin is mainly found in Gram-negative A kind of lipopolysaccharide on the outer membrane of bacterial cell wall, which is known as Pyrogen. When injectables or catheters are contaminated with botulinum, and feverish substances are allowed to invade the body, symptoms such as fever, shock, and widespread intravascular coagulation (DIC) may occur. Therefore, strict management must be taken to prevent Botoxin contaminates pharmaceuticals such as injections, medical appliances such as syringes and catheters, pharmaceutical manufacturing equipment and devices, and the like. Most medical appliances or pharmaceutical manufacturing appliances and devices are made of various synthetic resins, glass, metals, and natural chemicals, and they may be contaminated by adhesion or adsorption of botulinum toxin. Generally, botulinum toxin is heated at 250 ° C for more than 30 minutes, or heated at 170 ° C for more than 120 minutes. It will appear inactive. Therefore, materials such as glass or metal can be avoided by this heat treatment. Infected with botulinum; in addition, botulinum toxin will appear in an inactive state in organic solvents such as 3 (TC ethanol or dimethylarsine) containing sodium hydroxide, so even if the glass is washed with this solvent, it can also remove botulinum toxin ; But if it is made of materials that are not suitable for a variety of heat treatment or organic solvent treatment, medical appliances or pharmaceutical manufacturing equipment and devices, or medical appliances or medicine that are not structurally applicable to this heat treatment Products and equipment, etc., other methods of decontamination must be adopted. 4 _ _. —. — _________ '-____——-This paper size applies to China National Standard (CNS) A4 (210x297 thin) (please (Please read the notes on the back before drawing) • Install · Printed by the Consumer Standards Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs Manufacturing 20031142 E6 F6 5. Detailed description of the invention "For example, to remove the botulinum toxin contained in these medical appliances or pharmaceutical manufacturing equipment and devices, botulinum-free water or physiological saline can be used for rinsing. However, these washing methods require a large amount of water or physiological saline, and botulinum toxins attached or adsorbed on medical devices or pharmaceutical manufacturing devices and devices may not be completely removed. In Patent No. 2884975, effective extraction or adhesion The method of botulinum adsorption on solid surfaces such as containers and utensils is described. Protein solvents such as prion protein, human serum albumin, globulin can be used instead of water or physiological saline. After washing the containers and utensils, etc. Then, the botulinum toxin in the solvent is extracted. However, blood protein is a component derived from the living body. If it is used to remove the botulinum toxin that exists in medical appliances or pharmaceutical manufacturing equipment and devices, it is not recommended. Cleansing methods; for these purposes, it is best not to use solvents containing biogenic ingredients, but to use methods Compositions to be prepared and used. Techniques for washing and removing botulinum toxins with ingredients that are easy to prepare and use are applicable to, for example, pharmaceuticals manufactured at high frequency as needed to shorten the effective period, or with a short half-life Radionuclide species are used to produce radiopharmaceuticals; the most suitable of which is to produce positron emission tomography (P ◦ sitr ο η Emission Tomography, hereinafter referred to as "PET" ”) Medicaments used in diagnostic methods. The object of the present invention is to remove botulinum toxins attached to or adsorbed on solid surfaces such as medical appliances, pharmaceutical manufacturing equipment and devices, and chemical reagents of non-biological origin. Sterilized ingredients provide a more effective way to remove botulinum toxins than water or physiological saline. The invention discloses that the paper size applies to the Chinese National Standard (CNS) A4 specification (210X297 mm) --------- A ------ IT ------- 1 (Please read the Note for re-drawing) Printed by the Consumer Cooperatives of the Central Bureau of Standards, Ministry of Economic Affairs, 200301142 E6 —F6 V. Detailed description of the invention: Representative drug for PET diagnostic method 2- [18F] -Fluoro-2-deoxy-D-glucose (Hereinafter referred to as "18F-FDG"), most of them are made by methods such as Hamacher (Hamacher, K. et al., J. Nuclear Medicine, 27: 235-238, 1986); through these inventions People have repeatedly used these manufacturing methods and carefully studied the method to remove the botulinum toxin attached or adsorbed on the ion-blocking resin 'finally found that botulinum toxin that cannot be removed by ordinary water or physiological saline' can use sugars The solvent of the component is extremely effective for dissolving or extracting botulinum toxin, and can be used to remove botulinum toxin attached or adsorbed on solid surfaces such as medical appliances, pharmaceutical manufacturing equipment and devices, etc., thus completing the present invention. In this way, the present invention is characterized by providing a special composition that removes botulinum toxin adsorbed or attached to a solid surface after treating saccharides as effective ingredients. In other words, the botulinum toxin-removing composition solvent of the present invention is brought into contact with various solid surfaces such as medical appliances, pharmaceutical manufacturing equipment, and devices to be removed, and then the botulinum toxin is effectively removed by a recovery method. According to another aspect of the present invention, a method for removing a botulinum toxin attached to or adsorbed on a solid surface from which a botulinum toxin is removed is brought into contact with the solvent of the aforementioned composition. The method of allowing the composition solvent for removing botulinum toxin of the present invention to contact the aforementioned solid surface can be appropriately selected according to the type of the solid surface; for example, 'the method of use can be divided into immersing the solid surface in the present invention to remove The composition of the botulinum toxin is used in the solvent, or the solid surface is washed with the solvent, or the solvent is immersed in a sterilized cloth by an appropriate method, and the solid surface is wiped with the cloth. In addition, using the composition solvent of the present invention to perform the above-mentioned operations such as impregnation, rinsing, wiping, etc., can transfer the botulinum toxin attached or adsorbed on solid surfaces such as medical appliances, pharmaceutical manufacturing appliances and devices to the aforementioned solvents, and Solvent analysis 6 This paper size is applicable to China National Standard (CNS) A4 specifications (210 X 297 kilometers) --------- ^ ------ 1T ------- multiple (please first Read the notes on the back of the book and draw it again.) Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs, 200301142 E6 F6. 5. Detailed description of the invention: ~: The botulinum toxin in the solvent is extracted or extracted. Detection liquid for effectively detecting and measuring the degree of contamination of the solid surface by botulinum toxin. In other words, from another perspective, the present invention is characterized in that § a solid surface on which a botulinum toxin has been adsorbed or adhered is contacted with the aforementioned composition solvent to obtain the aforementioned composition containing botulinum toxin that is detached or dissociated from the solid surface Extraction method. Embodiments of the present invention will be described below. The saccharides used in the composition of the present invention include monosaccharides, oligo (〇 丨 丨 g 〇) sugars, and the derivatives; in addition, these saccharides may also be salts or hydrates; furthermore, the saccharides may also be D form or L form. In particular, the monosaccharide is preferably a general six-carbon sugar such as: glucose, galactose, mannose, fructose, etc., glucosamine, galactosamine, glucosamine hydrochloride, galactosamine hydrochloride , N-ethyl glucosamine, N-ethyl glucosamine and other amino acids, derivatives and salts; oligo (0ng〇) sugars are disaccharides to hexasaccharides, preferably maltose, sucrose, lactose, etc. Disaccharides: Among them, glucose, glucosamine hydrochloride, N-ethyl milling-D galactosamine and maltose, the best sugar is glucose. When using the botulinum toxin-removing composition of the present invention, it is necessary to prepare a solvent that has been dissolved in an appropriate solvent. However, a solvent type that has been dissolved in a solvent in advance can also be provided. In addition, a freeze-dried type is also available. It is only necessary to dissolve it in a solvent when it is to be used. Furthermore, a combination kit of a freeze-dried product and a solvent of the composition of the present invention is also provided. As long as physiology, pharmacology, and chemistry allow it, solvents are not particularly limited, such as physiological saline, Ringer's solution (improved physiological saline) electrolyte composition, injection agents, and other buffers. For buffering agents, there are phosphate buffer solution, citric acid buffer solution, phthalic acid, phosphoric acid, boric acid, citric acid, succinic acid, tartaric acid, lactic acid, acetic acid, etc. This paper applies Chinese national standards (CNS) A4 specification (210X297 mm) Binding ^ A (Please read the precautions on the back before drawing) Printed by the Staff Consumer Cooperative of the Central Bureau of Standards, Ministry of Economic Affairs, 200301142 E6 F6 5. Detailed description of the invention: Ammonium chloride, carbonic acid, three ( Hydroxymethyl) aminomethane and a buffer solution composed of these chlorine systems. In addition, the composition of the present invention may contain various additives allowed by physiology, pharmacy, and chemistry as required; in terms of additives, various pH adjusting agents such as acid and alkali, various buffer solvents, dextran 10, dextran 40, Dextrin, cyclodextrin, sodium lactate, various amino acids, methanol, ethanol, dimethyl sulfene, N, N-dimethylmethanamine, acetonitrile, and oxygen dyed cyclopentane. Although the concentration of saccharides in the solvent of the present invention varies depending on the type of sugar and solvent, and the degree of botulinum toxin adsorbed or attached to the solid surface, it is usually 0.1 to 15 g / ml (g / 100ml) (hereinafter referred to as "W / ν%"), which is preferably within 0.5 ~ 10w / v% Fanfu; when the concentration is too low, the effect of removing botulinum toxin will be reduced; when the concentration is too high, a large amount of lotion must be used The saccharides remaining after removal by rinsing, and the complexity of the operation will be formed. The solvent of the composition of the present invention can be prepared with the additives according to the needs, and the saccharides dissolved in the solvent can be prepared, but the saccharide solvent that does not contain botulinum toxin or loses its activity must be prepared in nature; Methods include saccharide solvent ultrafiltration membranes or botulinum toxins to remove botulinum toxin, or water that has been botulinum toxin removed by ultrafiltration membranes or the like in advance to prepare saccharide solvents; You can directly use sterilized commercially available sugar solvents, such as the glucose injection (5w / v%, 10w / v%, etc.) of the Japanese Pharmacy, which does not require special preparation at this time, so it is very convenient; Alternatively, the above-mentioned solvents may be used after diluting the relevant commercially available saccharide solvents to a sterile state. In this way, by immersing an appropriate solid in the solvent of the composition of the present invention, or washing the solid surface with the solvent, the botulinum toxin that has been attached or adsorbed on the solid surface can be detached or dissociated from the surface and then transferred to In this solvent, an effective removal effect can be obtained. Furthermore, the amount of botulinum toxin attached to a solid surface can be detected or measured by recovering the solvent used for dipping or rinsing; in other words, the composition of the present invention can also Used for the detection of botulinum toxin. This paper size applies to China National Standard (CNS) A4 (210X297 mm) --------- A ------ IT ------- (Please read the precautions on the back before Line drawing) 200301142 E6 F6 _ V. Detailed description of the invention: (Please read the precautions on the back before drawing) Use the published botulinum toxin measurement method, for example: take the crab's blood cell component puff fluid (hereinafter referred to as "AL 丨 Grain") provides samples for measuring the limu 1 us Test method, etc., which can accurately measure the degree of botulinum toxin contamination on solid surfaces; AL solvents are from the Lizu (Limulus), Extracted from crab blood cells such as Tachypleus, coagulum produced by the reaction of botulinum toxin or Lu-1,3-glucan can be used; in general, Biochemical Industry Co., Ltd. can be used And commercially available freeze-dried products prepared by Wako Pure Chemical Industries, Ltd .; and the method of measuring the concentration of botulinum toxin in a sample by the Limulus Test method, as long as it is a general method described by the Japan Pharmaceutical Agency Limited use. The solid surface of the present invention for removing botulinum toxin or extraction objects is solid surfaces such as medical appliances, pharmaceutical manufacturing equipment, and pharmaceutical manufacturing equipment; for medical appliances, there are disposable needles, disposable syringes, Disposable blood transfusion devices and infusion devices, disposable blood collection devices, disposable sets for artificial heart and lungs, medical artificial blood vessels, artificial heart valves, pacemakers, dialysis type artificial kidney devices, etc., disposable types used for testing botulinum toxin Laboratory equipment (sterilized dropper, sterilized experimental tube, sterilized straw pipette, etc.); pharmaceutical manufacturing equipment and pharmaceutical manufacturing equipment, including resins and reverse osmosis membranes used for purification or separation of ion exchange resins, etc. , Nanofiltration membrane, ultrafiltration membrane, precision filtration membrane, electrical dialysis membrane and other refining or separation membranes; etc. In addition, because the effective period is short, the present invention can effectively remove high-frequency pharmaceutical products according to their needs Botoxins on manufacturing equipment and devices, especially those that can effectively remove or adhere to 2- [18F] -fluoro-2-deoxy-D-glucose Botulinum toxin into the device and / or apparatus. EXAMPLES Examples will be listed below to more specifically explain the content of the present invention; however, the present invention is not limited to these examples; moreover, unless otherwise specified, the following examples all use "w / v%" as the sugar solvent The concentration indicator. Reagents and apparatus used in the experiment The paper size is in accordance with Chinese National Standard (CNS) A4 (210 X 297 mm). Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs, 200301142 E6 F6. 5. Detailed description of the invention: Syringes, three-way stopcocks The columns and towers are sterilized and commercially available disposable appliances. The glass appliances are sterilized by dry heat sterilization at 250 ° C for 90 minutes after being rinsed with water for injection. For carbohydrate solvents, use commercially available products after proper dilution, or dissolve commercially available premium reagents in ice for injection, and then inject ion blocking resin according to the following examples to make botulinum-removing solvents. These solvents They are prepared by aseptic operation. The following reagents are used for the botulinum toxin test based on the Japanese Pharmacy. Botulinum standard solvent (1000 EU / ml): Dissolve an appropriate amount of botulinum toxin in botulinum toxin 10,000 standard (Japanese Pharmacopoeia standard) to prepare a botulinum standard solvent (10000 EU / ml). Think of this as the original and then dilute it appropriately; moreover, "EU" means a unit of botulinum toxin. Gelation method: Limulus ES-II Test WAKO (manufactured by Wako Pure Chemicals) Turbidimetry method: Limulus ES-II Test WAKO or Limulus ES-J Test WAKO (manufactured by Wako Pure Chemical) Ion-blocking resins use BIORAT ion-resistance Resin AG 11 A8. Example 1 Ion-blocking resin was washed with a glucose solvent. In a column that had been sterilized with a rubbing pressure (120 ° C, 20 minutes), the ion-blocking resin was aseptically filled to form two columns. . 100 ml of water for injection is injected into two columns and then adjusted; next, 100 ml of water for injection is injected into one column (hereinafter referred to as "column 1"), and the other (hereinafter referred to as "column 1") is injected. This is "Column 2") 10 ml of 0.175 w / v% glucose solvent was injected, and then a botulinum toxin test (gelation method) was performed on the eluate of each column; the gel was performed according to the method of the Japan Pharmacy The results of the chemical method are shown in Table 1. From the results of column 2 in Table 1, it can be known that the Π5w / v% glucose is dissolved. Note that the paper size applies the Chinese National Standard (CNS) Λ4 specification (210 X 297 mm) (please read the precautions on the back first) Draw) order
A 經濟部中央標準局員工消費合作社印製 200301142 E6 F6 __ 五、發明之詳細説明： 入柱1T內—苛溶—解析出肉毒素；另一方面，從已注入注射用水 的柱塔1溶解析出液中，並沒有檢測出肉毒素；由此可見’ 用100ml注射用水進行調節時，並沒有從柱塔中溶解析出肉 毒素，然而接下來注入l〇ml的0.1 75 w/v%葡萄糖溶劑後’就 會溶解析出肉毒素。 表1 將注射用水、0.175w/v%葡萄糖溶劑注入離子阻滯樹脂時，各 溶解析出液的肉毒素實驗結果 樣本 . 判定 柱塔1溶解析出液：注射用水 陰性 柱塔2溶解析出液：0.175w/v%葡萄糖溶 劑 陽性 實施例2 藉由葡萄糖溶劑淸洗離子阻滯樹脂-2 在已用高壓釜殺菌（12(TC、20分鐘）的柱塔內，無菌塡 充離子阻滯樹脂，以做成2根柱塔 在1根柱塔（以下稱之爲「柱塔3」）內注入注射用水， 並在另1根（以下稱之爲「柱塔4」）內注入0.175w/v%葡萄 糖溶劑；在已溶解析出100ml、200ml、500ml及、1000ml時 採樣各溶解析出液，並將各採樣編號訂爲1、2、3、4 ;關於 採樣後的溶解析出液，則藉由比濁法以測量出肉毒素的濃 度；此時，則依照日本藥局方法實施比濁法的結果則如表2 所示。 如表2所示，從柱塔4的結果中可得知，注入0.175w/v %葡萄糖溶劑，可在最初的餾分中（採樣編號1 )溶解析出肉 毒素；此外，從肉毒素柱塔萃取的速度較快，而且也在採樣 11 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） ----------^裝------訂----------線 (請先閱讀背面之注意事項再行繪製) 200301142 E6 _ F6 五、發明之詳細説明： 編號2〜4觀察到，幾乎沒有出現肉毒素濃度；另二.方面，如 柱塔3的結果所示’即使注入注射用水，也沒有溶解析出肉 毒素。 表2 將注射用水（柱塔3 )及0 · Π 5 w /v %葡萄糖溶劑（柱塔4 )視 爲溶解析出液，以測量各溶解析出液的肉毒素濃度 量，採樣編號 100ml 200ml 5 0 0ml 1000ml 溶解析出液 1 2 3 4 柱塔3 注射用水 0 .〇 0 0 柱塔4 0.1 7 5 w/ V %葡萄糖溶劑 0.14EU/ml 0 0 0 (請先閲讀背面之注意事項再行繪製) 參考例 製作混入肉毒素的離子阳滯樹脂柱（column) 在燒杯內取出20g離子阻滯樹脂（AG11A8)後，添加適 量的注射用水以便於膨脹，接下來則如上述所示，添加〇.41ml 已調製的肉毒素標準溶劑（lOOOOEU/ml·);攪拌一夜的同時保 管於4°C環境下；最後再將適量的離子阻滯樹脂，無菌塡充於 已進行高壓釜殺菌（120°C，20分鐘）的柱塔內。 實施例3 經濟部中央標準局員工消費合作社印製 測量離子阻滯樹脂中所含的除去肉毒素效果：從離子阳滯樹 脂中除去肉毒素之操作-1 準備2隻依照參考例所做成的離子阻滯樹脂柱塔，將5ml 注射用水注入1根柱塔（以下稱之爲「柱塔5」）內，再將5ml 的.10w/v%葡萄糖溶劑注入另1根柱塔（以下稱之爲「柱塔6」） 內；將各柱塔內所餾分的各0.5ml (合計10 )溶解析出液，注 12 本紙張尺度逍用中國國家摞準（CNS〉A4規格（210X297公釐） 經濟部中央標隼局員工消費合作社印製 200301142 E6 _ F6 五、發明之詳細説明·· ' _ 入已殺菌的燒杯內後，依據餾分No.] > 1 〇編號對這些餾分進 行標示。 執行淸洗，以確認殘留於柱內的肉羞窜 接下來，將7.5ml的l〇w/v%葡萄糖溶劑注入上述柱塔5 及6內；再將各柱塔內所餾分的各〇.5ml (合計15)溶解析出 液’注入到已殺菌的實驗管內後，依據餾分No. 1 1〜25編號 對這些飽分進行標示。 測量各i留分（fraction)的肉毒素濃度 '針對柱塔5及6依據上述方式所獲得的餾分No.4、5、6、 7、10、13、16、19、22及25溶劑，測量其肉毒素濃度；此 時’則依照日本藥局方的比濁法測試肉毒素。 修正肉毒素濃度測量値 關於溶解析出液的肉毒素測試値，也以下列方式執行過 阻礙修正；爲了讓採樣劑達〇.25EU/ml，而在各糖類溶劑內添 加肉毒素標準溶劑稀釋液（0.5EU/ml )，再測量該溶劑的肉毒 素濃度；另一方面，也以相同方式在注射用水內，添加肉毒 素標準溶劑稀釋液（0.5EU/ml)後測量出該溶劑的肉毒素濃 度；再針對已添加肉毒素標準溶劑稀釋液（0.5EU/ml)的各糖 類溶劑的肉毒素濃度，求出將已添加肉毒素標準溶劑稀釋液 (0.5EU/ml )的注射用水肉毒素濃度視爲1〇〇時的百分比（％ ) 後，再將此視爲阻礙率（％ );用此阻礙率修正各餾分的肉毒 素濃度；關於注射用水的肉毒素測試値，則不執行修正。 表3表示柱塔5及6之各餾分No.4、5、6、7及10中所 含的肉毒素濃度（修正後的數値）。 13 本紙張尺度適用中國國家橾準（CNS ) A4規格（210 X 297公釐） ---------裝------、玎-------Λ (請先閱讀背面之注意事項再行繪製) 200301142 E6 F6 I 五、發明之詳細説明: 表3 利用1 Ow/v%葡萄糖溶劑及注射用水，從離子阻滯樹脂中除去 肉毒素的肉毒素濃度變化 扁號(No.) 溶解析出液 4 5 6 7 10 柱塔5 注射用水 45.8 40.8 28.5 23.0 3.23 柱塔6 10w/v%葡萄糖溶劑 65.9 47.3 28.2 12.0 0.55 (EU/ml ) 從表3可觀察到，將1 〇w/v%葡萄糖溶劑注入到柱塔時， 正如餾分No.4〜7的肉毒素濃度變化所示，.各餾分所溶解析 出的肉毒素量會急速減少；由此可見，可藉由10 w/v%葡萄糖 溶劑快速去除肉毒素。 從這個結果已確認出，與採用注射用水相較之下，反倒 是採用10w/v%葡萄糖溶劑，更能快速溶解析出柱塔內的肉毒 素。 爲了顯示出柱塔內有無殘留的肉毒素，而將柱塔5及6 之各餾分No. 13、16、19、22及25中所含的肉毒素濃度（修 正後的數値）顯示於表4上。 表4 利用10w/v%葡萄糖溶劑淸洗柱塔的肉毒素濃度變化 --------!,裝------、訂|------^ (請先閲讀背面之注意事項再行繪製) 經濟部中央標準局員工消費合作社印製 分編號（No.) 溶解析出液 13 16 19 22 25 柱塔 餾分No.1〜10 眞留分No.11〜25的溶 No.. 的溶解析出液 解析出液 1.38 1.00 0.50 0.14 0.00 柱塔5 注射用水 10 w / v %葡萄糖溶劑 柱塔6 1 0 w/v %葡萄 1 0 w/v %葡萄.糖溶劑 0.14 0.06 0..01 0.00 0.00 糖溶劑 本紙張尺度適用中國國家標準（CNS〉A4規格（210X297公釐） 200301142 E6 F6 ____ 五、發明之詳細説明·· (EU/ml) (請先閲讀背面之注意事項再行繪製) 在餾分1〜10溶解析出液中使用注射用水的柱塔5後， 會將10w/v%葡萄糖溶劑視爲溶解析出液，並在餾分11〜25 內溶解析出肉毒素，因此用餾分1〜10注射用水可說是不足 以充分去除肉毒素。 另一方面，在餾分1〜10溶解析出液中使用10w/v%葡萄 糖溶劑的柱塔6，則將lOw/v%葡萄糖溶劑視爲溶解析出液， 並在餾分11以後幾乎沒有發現到溶解析出的肉毒素。 由此已確認出，從上述離子阻滯樹脂中.除去肉毒素的溶 劑方面，使用10w/v%葡萄糖溶劑比使用注射用水，更能有效 溶解析出肉毒素。 實施例4 測量離子阻滯樹脂中所含的除去肉毒素效果：從離子阻、滯棱[ 脂中除去肉毒素之橾作-2 將5ml的lw/v%葡萄糖溶劑，注入依照參考例所做成的 離子阻滯樹脂柱塔（以下稱之爲「柱塔7」）；再將柱塔:內所：|留 分的各0.5ml(合計10 )溶解析出液，注入已殺菌的燒杯內（飽 分 No. 1 〜10 ) 〇 經濟部中央標準局員工消費合作社印製 測量各餾分的肉毒素濃度 已針對所獲得的態分N 〇 · 4、5、6、7及1 〇溶劑，'測量其 肉毒素濃度；並依據同於實施例3的方法，執行肉毒素_〶 及測量値的阻礙修正；其結果如表5所示。 ~ ~ ° 表5 利用lw/v%葡萄糖溶劑，從離子阻滯樹脂中除去肉毒素的內 $氏張尺度適用中國國家標準（CNS ) A4規格（210X297公疫) ~ - 200301142 E6 F6 經濟部中央標準局員工消費合作社印製 五、發明之詳細説明: 毒素濃度變化 分編號（No.) 溶解析出液 4 5 6 7 10 柱塔7 lw/v%葡萄糖溶劑 621 533 384 180 12.7 (EU/ml ) 從表5可觀察到，將lw/v%葡萄糖溶劑注入到柱塔時， 離子阻滯樹脂中的肉毒素，會被各餾分所溶解析出，而且正 如餾分4〜7的肉毒素濃度變化所示，各餾分所溶解析出的肉 毒素量會急速減少，因此能從離子阻滯樹脂柱塔中，迅速去 除與萃取肉毒素。 . 實施例5 測量離子附滯樹脂中所含的除去肉毒素效果：從離子阳滯樹 月旨中除去肉毒素之操作-3 將5ml的lw/v% D-( + )葡糖胺氫氯化物溶劑，注入依照 參考例所做成的離子阻滯樹脂柱塔（以下稱之爲「柱塔8」）； 再將此柱塔內所餾分的各0.5ml (合計1 〇 )溶解析出液，注入 已殺菌的燒杯內（餾分No· 1〜10)。 測量各餾分的肉毒素濃度 已針對所獲得的鶴分N 〇 · 4 ' 5、6、7及1 〇溶劑，測量其 肉毒素濃度；並依據同於實施例3的方法，執行肉毒素測試 及測量値的阻礙修正；其結果如表6所示。 表6 利用lw/v% D-( + )葡糖胺氫氯化物溶劑，從離子阻滯樹脂中 除去肉毒素的肉毒素濃度變化 16 本紙張尺;^適用中國國家標準（CNS ) A4規格(210 X 297公婕) _~" ----------症------1T------β (請先閱讀背面之注意事項再行繪製) 200301142 經濟部中央標準局員工消費合作社印製 ! 五、發明之詳細説明： E6 __ F6 分編號（Ν 〇 ·) 溶解析出液 4 5 6 7 .4 0 柱塔8 lw/v% D-( + )葡糖胺氫 氯化物溶劑 8066 2944 960 468 224 (EU/ml) 實施例 子阻滯樹脂中所含的除去肉毒素效果：從離子姐滯樹 脂中除去肉毒素之操作-4 準備2隻依照參考例所做成的離子阻滯樹脂柱塔，將5ml 的1 w/v %麥芽糖溶劑注入1根柱塔（以下稱之爲「柱塔9」） 內’再將5ml的lOw/ν%麥芽糖溶劑注入另1根柱塔（以下稱 之爲「柱塔10」）內；將各柱塔內所餾分的各〇.5ml(合計10) 溶解析出液’注入已殺菌的燒杯內後，再依據餾分No.l〜10 編號對這些餾分進行標示。 測量各I留分的肉毒素濃度. 已針對所獲得的餾分No.4、5、6、7及10溶劑，測量其 肉毒素濃度；並依據同於實施例3的方法，執行肉毒素測試 及測量値的阻礙修正；其結果如表7所示。 表7 利用lw/v%麥芽糖溶劑及i〇w/v%麥芽糖溶劑，從離子阻滯樹 脂中除去肉毒素的肉毒素濃度變化 編號（No.) 溶解析出液 4 5 6 7 10 柱塔9 1 w/v%麥芽糖溶劑 597 247 131 73.0 9.03 柱塔10· 10w/v%麥芽糖溶劑 851 466 130 26.6 2.22 (EU/ml) 17 (請先閲讀背面之注意事項再行繪製) 訂 Λ 張 _紙 本 尺度適用中國國家榡準（亡奶）八4規格（210\297公楚） 200301142 E6 _ F6 發明之詳細説明: 實施例7 . IL量離子阻滯樹脂中所含的除去肉毒素效果：從離子阻滯樹 脂__中除去肉毒素之橾作-5 準備2隻依照參考例所做成的離子阻滯樹脂柱塔，將5ml 的lw/v%N-乙銑-D半乳糖胺溶劑注入1根柱塔（以下稱之爲 「柱塔11」）內’再將5ml的10w/v%N-乙銑-D半乳糖胺溶劑 注入另1根柱塔（以下稱之爲「柱塔12」）內；將各柱塔內所 倉留分的各0 · 5 m 1 (合g十10 )溶解析出液，注入已殺菌的燒杯內 後，再依據餾分No· 1〜10編號對這些餾分進行標示。 測量各餾分的肉毒素濃度 已針對所獲得的餾分No·4、5、6、7及10溶劑，測量其 肉毒素濃度；並依據同於實施例3的方法，執行肉毒素測試 及測量値的阻礙修正；其結果如表8所示。 表8 利用lw/v%及10w/v%N-乙銑-D半乳糖胺溶劑，從離子阻滯 (請先閲讀背面之注意事項再行繪製) 訂 經濟部中央標準局員工消費合作社印製 樹脂中除去肉毒秦的肉毒素濃度變化 分編號（N〇 ·) 溶解析出液 4 5 6 7 10 柱塔 11 lw/v%N-乙銑-D半乳糖 胺溶劑 684 276 37.6 7.46 0.32 柱塔 12 10w/v%N-乙銑-D半乳 糖胺溶劑 1014 211 18.0 4.06 0.14 • (EU/ml) 從表6、7及表8可得知，將1 w/v% D-( + )葡糖胺氫氯化 物溶劑、lw/v%麥芽糖溶劑、i〇w/v%麥芽糖溶劑、iw/v%N_ 18 本紙張尺度適用中國國家標準（CNS ) A4規格（210 X 297公釐） 200301142 E6 _ F6 五、發¥?詳細説明： 一 一 (請先閱讀背面之注意事項再行繪製) 乙銑-D半乳糖胺溶劑及i〇y/.v% N_乙銑_D半乳糖胺溶劑，視 爲除去肉毒素溶劑之用時，可同於獲得表丨〜5所示之葡萄糖 溶劑的結果；換言之，將這些溶劑注入柱塔內後，各餾分會 溶解析出離子阻滯樹脂中的肉毒素，而且正如餾分4〜7的肉 毒素濃度變化所示，各餾分所溶解析出的肉毒素量會急速減 少，因此能從上述離子阻滯樹脂柱塔中，迅速去除與萃取肉 毒素。 而且，與lw/v%麥芽糖溶劑相較之下，將i〇w/v%麥芽糖 溶劑、以及與1 w/v% N-乙銑-D半乳糖胺溶劑相較之下，將 10〜/〃％1^乙銑-〇半乳糖胺溶劑用作除去肉.毒素溶劑時，能呈 現出快速溶解析出肉毒素的情況，而且也確認出濃度較高的 溶劑，能以低比率快速溶解析出。 用於產業上的可能性 經濟部中央標準局員工消費合作社印製 從本發明已明確出，利用糖類溶劑可去除附著或吸附於 固體表面的肉毒素；換言之，讓已殺菌的糖類溶劑接觸醫療 用具、醫藥品製造器具及裝置的表面，能有效去除附著或吸 附於該表面的肉毒素；從本發明可得知，能有效且方便去除 難以用傳統方式進行去除、溶解析出或萃取的肉毒素，而且 去除後也不須執行繁雜的後續處理，因此能有效運用於醫藥 品製造現場等。 19 ^紙張尺度適用>國國家標準（CNS ) A4規格(21〇Χ297公煃）A Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 200301142 E6 F6 __ V. Detailed description of the invention: Enter column 1T-harsh solution-resolve botulinum toxin; on the other hand, dissolve from column 1 which has been injected with water for injection In the liquid, no botulinum toxin was detected; it can be seen that when adjusted with 100ml of water for injection, botulinum toxin was not dissolved from the column, but after injecting 10ml of 0.1 75 w / v% glucose solvent, 'It will dissolve botulinum toxin. Table 1 Samples of botulinum toxin test results for each eluate when water for injection and 0.175 w / v% glucose solvent were injected into the ion-blocking resin. Judgment column elution solution: negative column water for injection 2 elution solution: 0.175 w / v% glucose solvent positive Example 2 Ion-blocking resin was washed with glucose solvent-2 In a column that had been sterilized in an autoclave (12 (TC, 20 minutes)), the ion-blocking resin was aseptically filled with Make two columns and inject water for injection into one column (hereinafter referred to as "column 3"), and inject 0.175 w / v% into the other (hereinafter referred to as "column 4"). Glucose solvent; when 100ml, 200ml, 500ml, and 1000ml have been eluted, each elution solution is sampled, and each sampling number is set to 1, 2, 3, 4; for the eluted solution after sampling, the turbidimetric method is used In order to measure the concentration of botulinum toxin; at this time, the results of the turbidimetric method according to the Japanese Pharmacopoeia method are shown in Table 2. As shown in Table 2, from the results of column 4, the injection of 0.175w / v% glucose solvent, can be dissolved in the first fraction (sampling number 1) In addition, botulinum toxin is extracted from the botulinum toxin column faster, and 11 paper sizes are also applicable to China National Standard (CNS) A4 (210X297 mm) ---------- ^ Install ------ order ---------- line (please read the notes on the back before drawing) 200301142 E6 _ F6 V. Detailed description of the invention: No. 2 ~ 4 observed, almost No botulinum toxin concentration appeared; on the other hand, as shown in the results of column 3, botulinum toxin was not dissolved even when water for injection was injected. Table 2 Water for injection (column 3) and 0 · Π 5 w / v % Glucose solvent (column tower 4) was regarded as the eluate to measure the botulinum concentration of each eluate. Sampling number 100ml 200ml 50 0ml 1000ml eluate 1 2 3 4 column 3 water for injection 0.0 0 Column 4 0.1 7 5 w / V% glucose solvent 0.14EU / ml 0 0 0 (Please read the precautions on the back before drawing) Reference Example Make an ion-positive resin column (column) mixed with botulinum toxin in a beaker After taking out 20g of ion blocking resin (AG11A8), add an appropriate amount of water for injection for swelling. Then, as shown above, add 0.41 ml of the prepared botulinum toxin standard solvent (1000OOEU / ml ·); store it at 4 ° C while stirring overnight; and finally, fill an appropriate amount of ion blocking resin in a sterile solution. The autoclave has been sterilized (120 ° C, 20 minutes) in the column. Example 3 Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs to measure the effect of removing botulinum toxin contained in ion blocking resin: Operation for removing botulinum toxin-1 Prepare two ion-blocking resin column towers made according to the reference example, inject 5ml of water for injection into one column (hereinafter referred to as "column tower 5"), and then 5ml .10w / v% glucose solvent was injected into another column (hereinafter referred to as "column column 6"); each 0.5ml (total 10) of the fractions in each column was dissolved in the eluate, and 12 papers were injected. Standards are in accordance with China ’s National Standards (CNS> A4 (210X297 mm). Printed by the Consumer Cooperatives of the Central Bureau of Standards, Ministry of Economic Affairs, 200301142 E6 _ F6. 5. Detailed description of the invention ... _ _ After entering the sterilized beaker, These fractions were added according to Fraction No.] > 10 Line labeling. Rinse was performed to confirm the flesh remaining in the column. Next, 7.5 ml of 10 w / v% glucose solvent was injected into the above-mentioned column 5 and 6; and each of the fractions in each column was injected. After 5 ml (15 in total) of the eluted solution was injected into the sterilized experimental tube, these contents were labeled according to the fraction No. 1 1 to 25. Measure the concentration of botulinum toxin in each fraction. 'For the solvents No. 4, 5, 6, 7, 10, 13, 16, 19, 22, and 25 obtained from the columns 5 and 6 according to the above method, measure Its botulinum toxin concentration; at this time, botulinum toxin was tested according to the turbidimetric method of the Japanese Pharmacy. Corrected the measurement of botulinum toxin concentration (the botulinum toxin test for the elution solution) has also been performed in the following way. In order to make the sampling agent reach 0.25EU / ml, a botulinum standard solvent dilution solution is added to each saccharide solvent ( 0.5EU / ml), and then measure the botulinum toxin concentration of the solvent; on the other hand, in the same manner, the botulinum toxin standard solvent dilution solution (0.5EU / ml) was added to the water for injection in the same manner to measure the botulinum toxin concentration of the solvent ; And then for the botulinum toxin concentration of the botulinum toxin standard solvent dilution solution (0.5EU / ml), the botulinum toxin concentration of the water for injection to which the botulinum toxin standard solvent dilution solution (0.5EU / ml) has been added is determined as After the percentage (%) at 100, this is regarded as the blocking rate (%); the blocking rate is used to correct the botulinum toxin concentration of each fraction; for the botulinum toxin test water for injection, the correction is not performed. Table 3 shows the concentration of botulinum in each of fractions Nos. 4, 5, 6, 7, and 10 of column 5 and column 6 (corrected values). 13 This paper size is applicable to China National Standard (CNS) A4 (210 X 297 mm) --------- install ------, 玎 ------- Λ (please first Read the notes on the back and draw again.) 200301142 E6 F6 I V. Detailed description of the invention: Table 3 Changes in the concentration of botulinum toxin that removes botulinum from ion blocking resin using 1 Ow / v% glucose solvent and water for injection. (No.) Eluent 4 5 6 7 10 Column 5 Water for injection 45.8 40.8 28.5 23.0 3.23 Column 6 10w / v% glucose solvent 65.9 47.3 28.2 12.0 0.55 (EU / ml) It can be observed from Table 3 that 1 〇w / v% glucose solvent injected into the column, as shown in the changes in the concentration of botulinum toxins in fractions 4 to 7, the amount of botulinum toxin dissolved in each fraction will decrease rapidly; w / v% glucose solvent for rapid removal of botulinum toxin. From this result, it has been confirmed that, compared with the use of water for injection, 10w / v% glucose solvent is used instead, and the botulin in the column can be quickly dissolved out. In order to show the presence or absence of residual botulinum toxin in the column, the botulinum toxin concentrations (corrected numbers) contained in the respective fractions Nos. 13, 16, 19, 22, and 25 of column 5 and 6 are shown in the table. 4 on. Table 4 Changes in the concentration of botulinum toxin in a column washed with 10w / v% glucose solvent -------- !, install ------, order | ------ ^ (Please read the back first Note for re-drawing) Print out the branch number (No.) of the employee's cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 13 16 19 22 25 Dissolve No. 1 to 10 of column fraction No. 11 to 25 of retention fraction .. eluent solution 1.38 1.00 0.50 0.14 0.00 Column 5 Water for injection 10 w / v% glucose solvent Column 6 6 0 w / v% grape 1 0 w / v% grape. Sugar solvent 0.14 0.06 0. .01 0.00 0.00 Sugar solvent This paper size is in accordance with Chinese national standard (CNS> A4 specification (210X297 mm) 200301142 E6 F6 ____ V. Detailed description of the invention ... (EU / ml) (Please read the precautions on the back before proceeding) (Drawing) After using column 5 for injection of water in the elution solution of fractions 1 to 10, the 10w / v% glucose solvent is regarded as the elution solution, and the botulinum toxin is dissolved in the fractions 11 to 25. Therefore, fraction 1 is used. It can be said that ~ 10 water for injection is not sufficient to sufficiently remove botulinum toxin. On the other hand, 10 w / v% is used in the elution solution of fractions 1 to 10. In the column 6 of the glucose solvent, 10w / v% glucose solvent was regarded as the eluate, and the eluted botulinum toxin was hardly found after the fraction 11. From this, it has been confirmed that from the ion blocking resin described above, In terms of the solvent for removing botulinum toxin, using 10w / v% glucose solvent can dissolve botulinum toxin more effectively than using water for injection. Example 4 Measurement of the effect of removing botulinum toxin contained in ion blocking resin: from ion blocking, blocking [The operation of removing botulinum toxin from fat-2] Inject 5 ml of lw / v% glucose solvent into an ion-blocking resin column prepared in accordance with the reference example (hereinafter referred to as "column column 7"); Column Tower: Internal Office: | 0.5ml (10 in total) of each of the remaining fractions is dissolved and injected into a sterilized beaker (saturation No. 1 to 10) 〇 Printed by the Consumers Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs to measure each fraction The concentration of botulinum toxin has been measured for the obtained fractions No. 4, 5, 6, 7, and 10, and the botulinum toxin concentration is measured; and the botulinum toxin and the measurement are performed according to the same method as in Example 3. Obstacle correction for 値; the results are shown in Table 5. ~ ~ ° Table 5 Internal ligament scale for removing botulinum toxin from ion blocking resin using lw / v% glucose solvent Applicable to China National Standard (CNS) A4 specification (210X297 public epidemic) ~-200301142 E6 F6 Central Standard of Ministry of Economic Affairs Printed by the Consumer Cooperative of the Bureau of the People's Republic of China 5. Detailed description of the invention: Toxin concentration change number (No.) Eluate 4 5 6 7 10 Column 7 lw / v% glucose solvent 621 533 384 180 12.7 (EU / ml) from In Table 5, it can be observed that when lw / v% glucose solvent is injected into the column, the botulinum toxin in the ion-blocking resin will be dissolved by each fraction, and as shown by the change in the concentration of botulinum toxin in fractions 4 to 7, The amount of botulinum toxin dissolved in each fraction will decrease rapidly, so it can be quickly removed and extracted from the ion-blocking resin column. Example 5 Measurement of the effect of removing botulinum toxin contained in the ion-adherent resin: the operation of removing botulinum toxin from the ionic stagnant tree month-3-5ml of lw / v% D-(+) glucosamine hydrochloride An ion-blocking resin column (hereinafter referred to as "column column 8") prepared in accordance with the reference example is injected into a compound solvent; and 0.5 ml (total 10) of each of the fractions distilled in the column is dissolved. Fill the sterilized beaker (fraction No. 1 to 10). Measurement of the botulinum concentration of each fraction The botulinum toxin concentration of the obtained crane fractions No. 4 '5, 6, 7 and 10 was measured; according to the same method as in Example 3, a botulinum test was performed and Measure the obstruction correction of radon; the results are shown in Table 6. Table 6 Changes in the concentration of botulinum toxin that removes botulinum toxin from ion-blocking resin using lw / v% D-(+) glucosamine hydrochloride solvent 16 paper rulers; ^ Applicable to China National Standard (CNS) A4 specifications ( 210 X 297 Gongjie) _ ~ " ---------- Symptom ------ 1T ------ β (Please read the notes on the back before drawing) 200301142 Ministry of Economic Affairs Printed by the Consumer Standards Cooperative of the Central Standards Bureau! V. Detailed description of the invention: E6 __ F6 Sub-number (N 〇 ·) Eluate 4 5 6 7. 4 0 Column 8 lw / v% D- (+) glucose Amine hydrochloride solvent 8066 2944 960 468 224 (EU / ml) Implementation example Blocking of botulinum toxin removal effect in resin: operation of removing botulinum toxin from ionomer resin-4 Prepare 2 according to the reference example Into an ion-blocking resin column, 5 ml of 1 w / v% maltose solvent is injected into one column (hereinafter referred to as "column column 9"), and then 5 ml of lw / ν% maltose solvent is injected into another column. In the root column (hereinafter referred to as "column column 10"), 0.5 ml (total 10) of the eluate from each of the fractions in each column is injected into the sterilized beaker, and then based on the fraction No. The l to 10 numbers indicate these fractions. The botulinum toxin concentration of each fraction was measured. The botulinum toxin concentration of the obtained fractions Nos. 4, 5, 6, 7, and 10 had been measured; and the botulinum toxin test was performed according to the same method as in Example 3 and Measure the obstruction correction of radon; the results are shown in Table 7. Table 7 Variation of botulinum toxin concentration (No.) for removing botulinum toxin from ion-blocking resin using lw / v% maltose solvent and i0w / v% maltose solvent. Eluate 4 5 6 7 10 Column 9 1 w / v% maltose solvent 597 247 131 73.0 9.03 Column 10 · 10w / v% maltose solvent 851 466 130 26.6 2.22 (EU / ml) 17 (Please read the notes on the back before drawing) Order Λ Sheet_Paper The scale is applicable to China National Standard (Dead Milk) 8-4 specification (210 \ 297 Gongchu) 200301142 E6 _ F6 Detailed description of the invention: Example 7. The effect of removing botulinum toxin contained in the ion blocking resin of IL content: from ion The operation of removing botulinum toxin from blocking resin __- 5 Prepare 2 ion blocking resin column towers made according to the reference example, and inject 5 ml of lw / v% N-ethyl milling-D galactosamine solvent into 1 Into one column (hereinafter referred to as "column 11"), 5 ml of 10w / v% N-ethyl milling-D galactosamine solvent was injected into another column (hereinafter referred to as "column 12"). ); Dissolve each 0 · 5 m 1 (g 10) of the aliquots stored in each column into the sterilized beaker, and then according to the fraction No. 1 ~ 1 The 0 number identifies these fractions. Measurement of the botulinum concentration of each fraction The botulinum toxin concentration of the obtained fractions No. 4, 5, 6, 7, and 10 has been measured; according to the same method as in Example 3, the botulinum toxin test and the measurement of radon were performed. Obstacle correction; the results are shown in Table 8. Table 8 Use of lw / v% and 10w / v% N-ethyl milling-D galactosamine solvent, from ion blocking (please read the precautions on the back before drawing). Variation of botulinum toxin concentration in resin (No.) Eluent 4 5 6 7 10 Column 11 lw / v% N-ethyl milling-D galactosamine solvent 684 276 37.6 7.46 0.32 Column 12 10w / v% N-ethyl-D-galactosamine solvent 1014 211 18.0 4.06 0.14 • (EU / ml) As can be seen from Tables 6, 7, and 8, 1 w / v% D-(+) glucose Glycosamine hydrochloride solvent, lw / v% maltose solvent, i0w / v% maltose solvent, iw / v% N_ 18 This paper size applies to Chinese National Standard (CNS) A4 specification (210 X 297 mm) 200301142 E6 _ F6 Five, send ¥? Detailed description: one by one (please read the precautions on the back before drawing) E-milling-D galactosamine solvent and i〇y / .v% N_ethyl milling_D-galactosamine solvent When used as a solvent to remove botulinum toxin, the results can be the same as those obtained from the glucose solvents shown in Tables 5 to 5; in other words, after these solvents are injected into the column, each fraction will dissolve and resolve the ion resistance. The botulinum toxin in the stagnant resin, and as the concentration of botulinum toxin in fractions 4 to 7 shows, the amount of botulinum toxin dissolved in each fraction will decrease rapidly, so it can be quickly removed and extracted from the ion-blocking resin column. Botox. In addition, compared with lw / v% maltose solvent, i〇w / v% maltose solvent, and 1 w / v% N-ethyl milling-D galactosamine solvent, 10 ~ / 〃% 1 ^ ethyl milling-0 galactosamine solvent can be used to remove meat. Toxin solvent, can show the rapid dissolution of botulinum toxin, and also confirmed that a higher concentration of the solvent can be quickly dissolved at a low ratio. Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs. It is clear from the present invention that the use of sugar solvents can remove botulinum toxins attached to or adsorbed on solid surfaces; in other words, let sterilized sugar solvents contact medical appliances. The surface of pharmaceutical manufacturing equipment and devices can effectively remove botulinum toxins attached to or adsorbed on the surface; it can be known from the present invention that it can effectively and conveniently remove botulinum toxins that are difficult to remove, dissolve or extract by traditional methods, In addition, it does not need to perform complicated subsequent processing after removal, so it can be effectively used in pharmaceutical manufacturing sites. 19 ^ Applicable paper size> National Standard (CNS) A4 specification (21〇 × 297 cm)