TW201029670A - Method of auto-synthesis in I-123-IBOX - Google Patents

Method of auto-synthesis in I-123-IBOX Download PDF

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TW201029670A
TW201029670A TW98104421A TW98104421A TW201029670A TW 201029670 A TW201029670 A TW 201029670A TW 98104421 A TW98104421 A TW 98104421A TW 98104421 A TW98104421 A TW 98104421A TW 201029670 A TW201029670 A TW 201029670A
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Taiwan
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bottle
reaction
injected
drug
ethanol
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TW98104421A
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Chinese (zh)
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Kang-Wei Chang
Shih-Ying Lee
Chia-Chieh Chen
Lie-Hang Shen
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Atomic Energy Council
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Abstract

The patent is including the method of auto-synthesis in I-123-IBOX; regulate preparation, oxidizing reaction, filtration collection and sampling. According the pathway we could automatic control achieves the operation to respond completes the total reaction time to the preparation to be possible to complete the medicine preparation procedure in 15 minutes, to short half-life nuclear medicine. Not only short the reaction time, but also produces high quality product. I-123-IBOX, also may effectively reduce radiation exposure the drugs manufacture operator to reduce the injury, then may promote to the medical arena provides the clinical diagnosis use, reaches considers goal of truly the patient.

Description

201029670 六、發明說明: 【發明所屬之技術領域】 本發明係有關於一種I-123-IBOX自動化合成系統之方 法’尤指一種具有標幡放射核種1-123於ffi〇x之合成方法, 以供腦部核子醫學澱粉樣乙型斑塊(AmybidBetapiaques)造 影診斷用。 【先前技術】 ❹ 由於生活型態與生活壓力之改變,及人口結構老化等問 題,國人罹患中樞神經系統疾病係逐年增加,其中又以精神分 裂症(Schizophrenia)、焦慮症、憂鬱症等精神疾病、阿茲海 默氏症(Alzheimer’s Disease)等神經退化性疾病以及巴金森 氏症(Parkinson sDisease)等運動失調神經疾病影響國人生命 品質及社會資源最為嚴重。 阿_默氏祕-_行_退化之疾病,又稱為退化性 老年失智症,#、-種最常見且無法轉之失智症,由於阿兹海 ❹ 默氏症好發於老年人,因此年紀愈大得病機會愈高,以85歲 以上罹患率可達30〜35%。此種漸進式之疾病,其主要臨床表 現包括認知(Cognition)、行為(Behavi〇r)與精神狀態三方 面之退化。其在神經病理學上係具有特殊之變化,在外^肉眼 上可見到大腦皮質之萎縮、腦之溝迴變寬、以及腦室擴大等。 而其中診斷為阿_默氏症之最重要病理指獅係神經纖維 (Neurofibrillaiy Tangles, NFT) (Senile Plaque, 目別國内約有五萬名病患,根據研究結果顯示,在該些阿 201029670 兹海默氏症患者之腦部係發現有許多小小且圓形之沉搬或斑 塊。這些如蜘蛛網般纏結之蛋白質即為類澱粉蛋白,因此此一 腦部激粉樣乙型斑塊之形成已成為探討發生阿兹海默症之 點。 一般檢測澱粉樣乙型斑塊除有益於阿茲海默症之早期診 斷外,尚可用於治療過程之觀察,對阿茲海默症之診療將有二 大之助益’因職醫造影界積極研發可於臨床之搬粉樣乙 型斑塊造·。唯其目前有應麟力之麟樣乙型斑塊造影 ❹ 劑’如FDDNP、IB0X、TZDM及BAT-1等,其皆仍在研發 階段中,故,-般習用者係無法符合使用者於實際使用時之所 需。 I-123-IBOX係經由美國賓州孔繁淵教授逾2〇〇〇年研究發 明之。對於阿茲海默氏症利用micr〇SPECT進行核醫診斷造影 工作有所助益,雖在目前已有改善其化學結構為ΙΜργ等化合 物,但其原始組成成分仍為鑑定阿茲海默氏症染色劑 (Thioflavine-T) ’故發展該項藥物的自動合成系統,有助於減 ® 少操作人員輻射劑量,並於更短時間内即達到標幟的目的。 【發明内容】 本發明之主要目的係在於,克服習知技藝所遭遇之上述問 題並提供一種腦部醫學診斷用澱粉樣乙型斑塊造影劑 I-123-IBOX之自動合成製程,使自動合成標幟系統應用於例 行放射性藥物生產,可防止放射性物質外洩,並可推廣至醫學 界提供臨床診斷使用’以達確實照顧患者目的之合成方法。 本發明之次要目的係在於,由於製程經簡化,只需使用一 4 201029670 反,瓶即可供操作,,並可於操作時分別量測反應瓶與c_8純 化管柱放射活度,且根據實驗,在啟動操作系統後,自開始反 應至製備完成之總反應時間可於15分鐘完成藥物製備程序, 可符合以自動合成系統產製短半衰期核醫藥物之需求。 本發明之另一目的係在於,所有反應均在一全自動合成系 統内進行,係可使操作人員接受幅射劑量減低至最低劑量,不 僅反應時間短、產效尚,且操作過程簡單,可在提供醫學腦部 斷層造影用之I-123-IBOX同時,亦可有效降低製藥操作人員 〇 之輻射曝露以減少傷害。 為達以上之目的,本發明係一種1423-1^0^自動化合成 系統之方法,經由準備程序將所需藥品準備完備,並在管柱前 處理及收集瓶前置作業後,進行後續氧化反應程序、過濾收集 程序及取樣程序。首先在氧化反應程序中係先抽取放射性蛾化 銨溶液並注入於一反應瓶中,接著加入一氧化劑進行氧化反 應,於一段反應時間後再加入一還原劑,終止氧化反應;緊接 著進入過濾收集程序,將此反應瓶内反應液注入一 純化管 ® 柱進行吸附’並加入注射用水清洗該C-8純化管柱,然後以 50%乙醇流洗該C-8純化管柱,接著將95%乙醇注入該C-8純 化管柱,並再注入一空管後,進行來回流洗數次,之後注入至 一第一收集瓶,並使該第一收集瓶内產品溶液流經一過濾膜 後,注入一第二收集瓶;最後進行取樣程序,於補充95%乙醇 並更換過濾膜及無菌收集瓶後,將95%乙醇注入該C-8純化管 柱中,再注入至該第一收集瓶,使該第一收集瓶内產品溶液流 經此過濾膜後,注入於無菌收集瓶内與預先調配好之生理食鹽 水及維他命C混合液混合。 '201029670 【實施方式】 請參閱『第1圖』所示,係本發明之製作流程示意圖。如 圖所示:本發明係一種I-123-IBOX自動化合成系統之方法, 其至少包括下列程序及步驟: 準備程序 (A)準備藥品11:分別於一第一藥品瓶加入過氧化氫 (H202)溶液,於一第二藥品瓶加入亞硫酸鈉(Na2S03), 於一第三藥品瓶加入亞磷酸納(Na2HP03),於一第四及第五 〇 藥品瓶各加入注射用水(H20) ’於一第六藥品瓶加入50%乙 醇(EtOH),以及於一第七藥品瓶加入95%乙醇。並將含有放 射性碘化銨之水溶液注入一無菌反應瓶内,以輸載氣體將一溶 於乙醇之標幟前驅物SnIBOX導入該反應瓶内,用以與此含有 放射性峨化錄之水溶液混合; (B ) C-8純化管柱前處理1 2 :對一 C-8純化管柱(C-8 Sep-pakcolumn)進行前處理’加入乙醇及注射用水洗出; (C )無菌收集瓶别置作業1 3 :取維他命c (Ascorbic ❹ acid)注射液(Injection)及冰醋酸加入0.9%氣化鈉注射液, 混合均勻,並以一無菌注射針筒抽取,經一 Millip〇re Mmex GV 過濾匣注入無菌收集瓶; 氧化反應程序 (D)抽取放射性碘化銨溶液注入反應瓶丄4:將一取樣 閥旋轉至填充位置,利用氮氣壓力將放射性碘化銨溶液 ([123I]NH4I)充填至取樣環路,滿出之液體則流至一回收 瓶。之後再以氮氣壓力將取樣環路内之放射性蛾化録溶液注入 該反應瓶内,並藉氮氣壓力形成之氣泡進行授拌,於其中該反 201029670 應瓶内氣體係由一活性碳(ActiveCharcoal)管排出; (E) 注入氧化劑1 5 :將第一藥品瓶之過氧化氫溶液作 為氧化劑,注入該反應瓶,於室溢下利用氣泡進行攪拌至反應 所需時間; (F) 注入還原劑16 :將第二藥品瓶之亞硫酸鈉及第三 . 藥品瓶之飽合亞磷酸納作為還原劑,分別注入該反應瓶,並利 ’ 用氣泡先後進行攪拌至反應所需時間,終止氧化反應; 過濾收集程序 O ( G )反應液注入C-8純化管柱吸附1 7 :將此反應瓶内 反應液注入該C-8純化管柱吸附,流出之過濾液係注入一廢液 瓶; (Η )注入注射用水清洗C-8純化管柱1 8 :注入第四藥 品瓶之注射用水至反應瓶,並利用氣泡進行擾拌至反應所需時 間’繼之’將此反應瓶内反應液注入該C-8純化管柱,流出之 過濾液係注入該廢液瓶,之後再注入第五藥品瓶之注射用水至 該C-8純化管柱對其進行清洗,流出之過濾液亦注入該廢液 © 瓶; (I )注入50%乙醇流洗C-8純化管柱1 9 :將第六藥品 瓶之50%乙醇注入該C-8純化管柱’流出之過濾液係注入該廢 液瓶; (J )注入95%乙醇來回流洗C-8純化管柱2 〇 :利用氣 氣壓力將第七藥品瓶之95%乙醇注入該C-8純化管柱,並再注 入一空管後,進行來回流洗數次; (Κ)經收集並過濾至收集瓶21:最後注入至一第一收 集瓶’並使該第一收集瓶内產品溶液流經一過濾膜後,注入一 201029670 第二收集瓶; 取樣程序 (L )補充95%乙醇並更換過渡膜及無菌收集瓶2 2 :補 充第七藥品瓶之95%乙醇,且更換過濾膜,並將該第二收集瓶 更換為步驟(C)無菌收集瓶;以及 * (Μ)注入95%乙醇至C-8純化管柱經收集並過渡至無菌 • 收集瓶2 3 :以氮氣壓力將第七藥品瓶之95%乙醇注入該C_8 純化管柱,再注入該第一收集瓶,使該第一收集瓶内產品溶液 p 流經此過濾膜後,注入於該無菌收集瓶内與預先調配好之生理 食鹽水及維他命C混合液混合。 請參閱『第2圖』所示,係本發明標幟管路配置示意圖。 如圖所示:當本發明於操作時,於一較佳實施例中,係以110 伏特(V)之電源供應本全自動合成系統,其至少包括下列程 序及步驟: 準備程序 (A 1 )分別於一第一藥品瓶3 1加入5%過氧化氫溶 , 液’於一第二樂品瓶3 2加入濃度為300mg/inl之亞硫酸納, 於一第三藥品瓶3 3加入亞磷酸納’於一第四及第五藥品瓶3 4、3 5各加入注射用水,於一第六藥品瓶3 6加入50%乙 醇,以及於一第七藥品瓶3 7加入95%乙醇。並將含有輻射劑 量150〜300mCi之放射性碘化銨之水溶液以300微升(μΐ)注 入一 5毫升(ml)無菌反應瓶3 8内’並以40〜100微升之輸 載氣體-峡化鉀(KI)將一 100微克(pg)且溶於乙醇之標職 前驅物SnIBOX導入該反應瓶3 8内,用以與此含有放射性碘 化錄之水溶液混合; 8 201029670 (B 1 )對- C-8純化管柱3 9進行前處理,加入j如 乙醇及5 ml注射用水洗出; (C 1 )取75微升維他命G15 入20毫升G.9%氣仙注概’齡均自,並無姐射針 筒抽取5.5毫升,經一 Millip〇re難饮Gv 〇 22微米(师)過 濾匣注入一無菌收集瓶4 〇b ; 氧化反應程序 (D 1 )開啟C13接頭,使一 6 V13取樣閥旋轉至填充位 置’並開啟C12、C18及C19等接頭,利用氮氣壓力將體積 0.3毫升之放射性峨化録溶液經由V9及Vi2控制間充填至 Loop取樣環路’滿出之液體則由6V13控制閥流至一回收瓶4 1 ’於此C18接頭保持開啟直到結束。充填3秒鐘後關閉ci2 及C13接頭’並開啟C9及C20接頭,利用氮氣壓力將L〇〇p 取樣環路内之放射性碘化銨溶液經由V20控制閥注入該反應 瓶3 8内,而於該反應瓶3 8内之氣體則係經由常開式之V8 控制閥及一含氫氧化鈉(NaOH)顆粒之活性碳管4 2排出。5 秒鐘後關閉C9、C19及C20接頭,並開啟C14接頭,藉氮氣 壓力形成之氣泡攪拌10秒鐘後關閉C14接頭,其中,該充填 放射性碘化銨溶液用之氮氣係以一微型閥(Micr〇 Valve)調節 適當流量’使溶液緩慢填充至Loop取樣環路; (E 1 )開啟C1接頭,以第一藥品瓶3 1之5%過氧化 氫溶液作為氧化劑,將鱧積0.1毫升之過氧化氫溶液經由VI 控制閥注入該反應瓶3 8,5秒鐘後關閉C1接頭,並開啟C14 接頭’於室溫下利用氣泡進行攪拌5分鐘後關閉C14接頭; (F 1 )將第二藥品瓶3 2之亞硫酸鈉及第三藥品瓶3 3 9 201029670 之亞碟酸納作為還原劑。首先開啟C2接頭,將體積1毫升之 亞硫酸氫鈉經由V2控制闊注入該反應瓶3 8,5秒鐘後關閉 C2接頭,並開啟C14接頭,利用氣泡進行攪拌1〇秒鐘後關閉 C14接頭’接著開啟C3接頭,將體積2毫升之飽合亞鱗酸納 經由V3控制閥注入該反應瓶3 8,5秒鐘後關閉C3接頭,並 開啟C14接頭’利用氣泡進行攪拌1〇秒鐘後關閉ci4接頭, 終止氧化反應; 過濾收集程序 ❿ (G 1 )開啟C3、C8 (關閉V8控制閥)C15、C16及 C18接頭,將此反應瓶3 8内反應液經由V14a、V15、V22a 及V16b控制閥注入該C-8純化管柱3 9吸附,流出之過濾液 則經由V10a及VIla控制閥注入一廢液瓶4 3,並於60秒鐘 後關閉C8、C15及C16接頭; (Η 1 )開啟C4接頭’將第四藥品瓶3 4之注射用水以 體積10毫升經由V4控制閥注入至反應瓶3 8,10秒鐘後關 閉C4接頭,並開啟C14接頭,利用氣泡進行攪拌1〇秒鐘後 Ο 關閉C14接頭。繼之,開啟C4、C8 (關閉V8控制閥)C15、 C16及C18接頭’使此反應瓶3 8内反應液經由V14a、V15 及V16b控制閥注入該C-8純化管柱3 9吸附,流出之過濾液 則經由V10a及Vila控制閥注入該廢液瓶4 3。關閉C8及 C15接頭,當最終產物在該c-8純化管柱3 9吸附後,開啟 C5及C16接頭’將第五藥品瓶3 5之注射用水以體積10毫 升經由V5及V16b控制閥注入該c-8純化管柱3 9以流洗出 未標幟上之1-123射源,流出之過濾液亦經由vl〇a及Vlla控 制閥注入該廢液瓶4 3,並於300秒後關閉C5接頭; 201029670 (I 1 )開啟C6接頭,將第六藥品瓶3 6之50%乙醇以 體積1毫升經由V6 V22a、及V16b控制閥注入該08純化管 柱3 9作為梯度濃度,以去除其他不純物,流出之過濾液亦經 由VlOa及VIla控制閥注入該廢液瓶4 3,且於30秒後關閉 C6接頭; (j 1 )開啟C7、CIO及C16等接頭,利用氮氣壓力將 第七藥品瓶3 7之95%乙醇以禮積3毫升經由V7、V22a及 V16b控制閥注入該匚_8純化管柱3 9,並經由VlOb控制閥 注入一空管4 4,約30秒後關閉C16接頭,並開啟C17接頭, 使該空管4 4内乙醇反向流回,再於30秒後關閉C17接頭, 並開啟C16接頭,使該c_8純化管柱3 9内之乙醇再流至該 空管4 4 ’重覆進行來回流洗共5次; (κ 1 )待上述步驟(J 1 )來回流洗於第5次後關閉 C17及C10接頭’並開啟C11及C16接頭,使該C-8純化管 柱3 9内乙醇溶液經由¥1〇3及Vllb控制閥注入至一第一收 集瓶4 5 ’待30秒後關閉C7、C11及C16等接頭,並開啟 C21接頭,使該第一收集瓶4 5内產品溶液流經一過濾膜4 6 3後’注入一第二收集瓶4 〇a,經180秒後關閉C18及C21 接頭’藉以析出最終I-123-IBOX產物; 取樣程序 (L 1 )補充第七藥品瓶3 7之95%乙醇0.9毫升,且更 換為另一過濾臈4 6b,並將該第二收集瓶4 〇a更換為步驟 (C 1 )無菌收集瓶4 〇b ;以及 (Μ 1 )開啟C7、cu、C16及C18等接頭,利用氮氣壓 力將第七藥品瓶3 7之95%乙醇經由V7、V22a及V16b控制 11 .201029670 閥注入該C-8純化官柱3 9 ’然後經由Vl〇a及Vllb控制闕 注入該第一收集瓶4 5,待30秒後關閉C7、C11及C16等接 頭,並開啟C21接頭,使該第一收集瓶4 5内產品溶液流經 此過濾膜4 6b後,注入於該無菌收集瓶4 〇b内與預先調配 好之生理食鹽水及維他命C混合液混合,經60秒後關閉C18 及C21接頭。 經由上述執行I-123-IBOX標幟反應之操作程式,在全自 動操作下約15分鐘,反應結束,便可取出已純化收集之 ❹ I-123-IBOX 〇 如是,所有反應過程均以全自動控制操作進行,由於製程 經簡化,因此只需使用一反應瓶即可供操作。當使用本方法 時,僅需將反應藥品放入特定瓶中,打開電源及通入反應用之 氣體,利用C-8純化管柱將I-123-IBOX產品分離純化收集, 並可於操作時分別量測反應瓶與C_8純化管柱放射活度,且在 啟動操作系統後,自開始反應至製備完成之總反應時間可於 15分鐘完成樂物製備程序,可符合以自動合成系統產製短半 ® 衰期核醫藥物之需求。 由以上說明可知本發明乃提供一種輕便靈活,使用上安全 可靠且方便之腦部核子醫學診斷用殿粉樣乙型斑塊(Amyloid Beta Plaques)造影劑自動化合成方法,不僅可防止放射性物 質外沒’亦可降低製藥操作人員之ϋ侧量以減少傷害,係為 可推廣至醫學界提供臨床診斷使用,以達_實照顧患者之目 的。 、綜上所述,本發明係一種W23JBOX自動化合成系統之 方法’可有效改善習用之種種缺點,其所有反應均在一全自動 12 201029670 合成系統内進行,係可使操作人員接受幅射劑量減低至最低劑 量’不僅反應時間短、產效高’且操作過程簡單,可在提供醫 學腦部斷層造影用之I-123-IBOX同時,亦可有效降低製藥操 作人員之輻射曝露以減少傷害,進而使本發明之產生能更進 步、更實用、更符合使用者之所須,確已符合發明專利申請之 要件,爰依法提出專利申請。 惟以上所述者’僅為本發明之較佳實施例而已,當不能以 此限定本發明實施之範圍;故,凡依本發明申請專利範圍及發 明說明書Θ容所作之鮮的等效變化與修飾,冑應仍屬本發明 專利涵蓋之範圍内。 【圖式簡單說明】 第1圖’係本發明之製作流程示意圖。 第2圖’係本發明標幟管路配置示意圈。 【主要元件符號說明】 步驟(A)〜(M) 1;l〜9q 第一藥品瓶31 第二藥品瓶32 第二樂品瓶3 3 第四藥品瓶34 第五藥品瓶35 第六藥品瓶3 6 第七藥品瓶3 7 反應瓶3 8 201029670 C-8純化管柱3 9 第二收集瓶4 〇a 無菌收集瓶4 Ob 回收瓶4 1 活性碳管4 2 廢液瓶4 3 空管4 4 第一收集瓶4 5 Ο 過遽膜4 6 a、4 6 b 取樣環路Loop Cl〜C21接頭 VI〜V21控制閥 14201029670 VI. Description of the Invention: [Technical Field of the Invention] The present invention relates to a method for synthesizing an I-123-IBOX automated synthesis system, particularly a method for synthesizing a standard radioactive species 1-123 in ffi〇x, For the diagnosis of angiographic amyloid plaques (AmybidBetapiaques) in the brain. [Prior Art] ❹ Due to changes in lifestyle and life pressure, and the aging of the population structure, the number of diseases of the central nervous system in the country has increased year by year, including mental illness such as Schizophrenia, anxiety, and depression. Neurodegenerative diseases such as Alzheimer's Disease and dysfunctional neurological diseases such as Parkinson's Disease affect the quality of life and social resources of Chinese people. A_Mercemy secret-_Line_Degraded disease, also known as degenerative old-age dementia, #,- the most common and untransferable dementia, due to Azheimer's disease Therefore, the higher the age, the higher the chance of getting sick, and the attack rate of over 85 years old can reach 30~35%. The main clinical manifestations of this progressive disease include the degradation of cognition, behavior (Behavi〇r) and mental state. It has a special change in neuropathology. The atrophy of the cerebral cortex, the widening of the sulcus of the brain, and the enlargement of the ventricles can be seen on the external eye. Among them, the most important pathological diagnosis of A-Mer's disease is Neurofibrillaiy Tangles (NFT) (Senile Plaque, about 50,000 patients in the country, according to the results of the study, in those A. 201029670 The brains of patients with Alzheimer's disease have found many small and rounded sinks or plaques. These spider-like tangled proteins are amyloid-like proteins, so this brain is a kind of brain-like type B. The formation of plaque has become a point to explore the occurrence of Alzheimer's disease. General detection of amyloid plaques in addition to benefiting the early diagnosis of Alzheimer's disease, can also be used for the observation of the treatment process, for Alzheimer The diagnosis and treatment of the disease will have two major benefits. Because the occupational medicine imaging industry is actively researching and developing the clinically possible powder-like type B plaque. Only the current lining force type B-type plaque contrast agent Such as FDDNP, IB0X, TZDM and BAT-1, etc., which are still in the research and development stage, so the general users can not meet the needs of users in actual use. I-123-IBOX is through the United States of Pennsylvania Kong Fanyuan Professor over 2 years of research and invention. For Alzheimer The use of micr〇SPECT for nuclear diagnostic imaging has been helpful. Although the chemical structure of ΙΜργ has been improved, its original composition is still used to identify Alzheimer's disease stain (Thioflavine-T). 'Therefore, the development of the automatic synthesis system of the drug helps to reduce the radiation dose of the operator and achieve the purpose of the logo in a shorter time. SUMMARY OF THE INVENTION The main object of the present invention is to overcome the conventional knowledge. The above problems encountered in the art and provide an automatic synthesis process for amyloid beta plaque contrast agent I-123-IBOX for brain medical diagnosis, which enables the automatic synthesis of the marker system to be applied to routine radiopharmaceutical production, preventing radioactive substances. Leakage, and can be extended to the medical community to provide clinical diagnosis using a synthetic method for the purpose of taking care of the patient. The secondary purpose of the present invention is that, since the process is simplified, only one 4 201029670 is used, the bottle is available. Operation, and can measure the radioactivity of the reaction bottle and the c_8 purification column separately during operation, and according to the experiment, after starting the operating system, start from the beginning The total reaction time to the completion of the preparation can complete the drug preparation procedure in 15 minutes, which can meet the requirement of producing a short half-life nuclear medicine by an automatic synthesis system. Another object of the present invention is that all the reactions are in a fully automatic synthesis. In the system, the operator can reduce the radiation dose to the lowest dose, not only the reaction time is short, the production efficiency is still good, and the operation process is simple. It can also provide I-123-IBOX for medical brain tomography. It can effectively reduce the radiation exposure of pharmaceutical operators to reduce the damage. For the above purposes, the present invention is a method of 1423-1^0^ automated synthesis system, through the preparation process to prepare the required drugs, and in the column After the pretreatment and collection of the bottle pre-operation, a subsequent oxidation reaction procedure, a filtration collection procedure, and a sampling procedure are performed. First, in the oxidation reaction process, the radioactive molybdenum ammonium solution is firstly extracted and injected into a reaction bottle, followed by adding an oxidant for oxidation reaction, and then adding a reducing agent after a reaction time to terminate the oxidation reaction; Procedure, the reaction solution in the reaction flask is injected into a purification tube® column for adsorption' and the C-8 purification column is washed by adding water for injection, and then the C-8 purification column is washed with 50% ethanol, followed by 95%. Ethanol is injected into the C-8 purification column, and after an empty tube is injected, it is washed back several times, then injected into a first collection bottle, and the product solution in the first collection bottle is passed through a filtration membrane. Injecting a second collection bottle; finally, a sampling procedure is performed, after 95% ethanol is added and the filter membrane and the sterile collection bottle are replaced, 95% ethanol is injected into the C-8 purification column, and then injected into the first collection bottle. The product solution in the first collection bottle is passed through the filter membrane, and then injected into a sterile collection bottle and mixed with a pre-mixed physiological saline solution and a vitamin C mixture. '201029670 EMBODIMENT> Please refer to FIG. 1 for a schematic diagram of the production process of the present invention. As shown in the figure: The present invention is a method for an I-123-IBOX automated synthesis system, which comprises at least the following procedures and steps: Preparation procedure (A) Preparation of a drug 11: Hydrogen peroxide is added to a first drug bottle (H202) Solution, adding sodium sulfite (Na2S03) to a second drug bottle, adding sodium phosphite (Na2HP03) to a third drug bottle, and adding water for injection (H20) in a fourth and fifth drug bottles. Six drug bottles were added to 50% ethanol (EtOH), and 95% ethanol was added to a seventh drug bottle. And injecting an aqueous solution containing radioactive ammonium iodide into a sterile reaction bottle, and introducing a reagent precursor SnIBOX dissolved in ethanol into the reaction bottle with a carrier gas for mixing with the aqueous solution containing radioactive cesium; (B) C-8 purification column pretreatment 1 2: pretreatment of a C-8 purification column (C-8 Sep-pakcolumn) 'added ethanol and water for injection; (C) sterile collection bottle Assignment 1 3: Add vitamin C (Ascorbic ❹ acid) injection (Injection) and glacial acetic acid to 0.9% sodium sulphate injection, mix well, and extract with a sterile syringe and filter through a Millip〇re Mmex GV. Inject the sterile collection bottle; Oxidation reaction procedure (D) Inject the radioactive ammonium iodide solution into the reaction flask. 4: Rotate a sampling valve to the filling position and fill the radioactive ammonium iodide solution ([123I]NH4I) to the sampling with nitrogen pressure. In the loop, the liquid that flows out flows to a recycling bottle. Then, the radioactive moth recording solution in the sampling loop is injected into the reaction bottle under nitrogen pressure, and the bubbles formed by the pressure of nitrogen are mixed, wherein the anti-201029670 internal gas system of the bottle is composed of an activated carbon (ActiveCharcoal). (E) Injecting the oxidizing agent 1 5: injecting the hydrogen peroxide solution of the first drug bottle as an oxidizing agent into the reaction bottle, and stirring the chamber to a time required for the reaction by using a bubble; (F) injecting the reducing agent 16 : the sodium sulfite of the second drug bottle and the saturated sodium phosphite of the third drug bottle are used as reducing agents, respectively, and are respectively injected into the reaction bottle, and the bubbles are successively stirred until the reaction takes time to terminate the oxidation reaction; The process O ( G ) reaction solution is injected into the C-8 purification column to adsorb 1 7 : the reaction liquid in the reaction bottle is injected into the C-8 purification pipe column for adsorption, and the discharged filtrate is injected into a waste liquid bottle; (Η) injection Washing the C-8 purification column with water for injection 1 8: Injecting the injection water of the fourth drug bottle into the reaction bottle, and using a bubble to disturb the reaction to the time required for the reaction 'following' the reaction liquid in the reaction bottle is injected into the C- 8 pure a column, the effluent filtrate is injected into the waste bottle, and then injected into the C-8 purification column by the injection water of the fifth drug bottle, and the effluent filtrate is also injected into the waste liquid bottle; (I) injecting 50% ethanol to wash the C-8 purification column 19. Injecting 50% ethanol of the sixth drug bottle into the C-8 purification column, the filtrate flowing out is injected into the waste bottle; (J) Inject 95% ethanol to reflux and wash the C-8 purification column 2 〇: 95% ethanol of the seventh drug bottle is injected into the C-8 purification column by gas pressure, and then injected into an empty tube, and then refluxed. Several times; (Κ) is collected and filtered to the collection bottle 21: finally injected into a first collection bottle 'and the product solution in the first collection bottle is passed through a filter membrane, and then injected into a second collection bottle of 201029670; sampling Procedure (L) supplement 95% ethanol and replace the transition membrane and sterile collection bottle 2 2: replenish the 95% ethanol of the seventh drug bottle, replace the filter membrane, and replace the second collection bottle with the step (C) sterile collection bottle ; and * (Μ) inject 95% ethanol into the C-8 purification column and collect and transition to sterile • Collection bottle 2 3 : with nitrogen pressure 95% ethanol of the seventh medicine bottle is injected into the C_8 purification column, and then injected into the first collection bottle, so that the product solution p in the first collection bottle flows through the filtration membrane, and is injected into the sterile collection bottle and pre-distributed Mix well with physiological saline and vitamin C mixture. Please refer to FIG. 2, which is a schematic diagram of the configuration of the flag pipeline of the present invention. As shown, when the present invention is in operation, in a preferred embodiment, the fully automated synthesizing system is supplied with a power supply of 110 volts (V), which includes at least the following procedures and steps: Preparation procedure (A1) Adding 5% hydrogen peroxide solution to a first drug bottle 31, respectively, adding sodium sulfite at a concentration of 300 mg/inl to a second bottle 3, and adding phosphorous acid to a third drug bottle 3 3 Na's fourth and fifth drug bottles 3 4, 3 5 were each added with water for injection, 30% ethanol was added to a sixth drug bottle 36, and 95% ethanol was added to a seventh drug bottle 37. And injecting an aqueous solution containing radioactive ammonium iodide having a radiation dose of 150 to 300 mCi into a 5 ml (ml) sterile reaction bottle 38 at 300 μl (μΐ) and using 40 to 100 μl of the carrier gas-gorging Potassium (KI) introduces a 100 microgram (pg) and ethanol-soluble standard precursor SnIBOX into the reaction flask 38 for mixing with the aqueous solution containing radioactive iodine; 8 201029670 (B 1 ) C-8 purification column 3 9 pre-treatment, add j such as ethanol and 5 ml of water for injection; (C 1 ) take 75 microliters of vitamin G15 into 20 ml of G.9% gas extracts There is no syringe pumping 5.5 ml, which is injected into a sterile collection bottle 4 〇b through a Millip〇re refractory Gv 〇 22 micron (strain) filter; the oxidation reaction program (D 1 ) opens the C13 connector to make a 6 V13 The sampling valve is rotated to the filling position' and the joints such as C12, C18 and C19 are opened. The volume of 0.3 ml of the radioactive sputum recording solution is filled into the Loop sampling loop through the V9 and Vi2 control chambers under nitrogen pressure. The liquid is filled by 6V13. The control valve flows to a recovery bottle 4 1 'the C18 joint remains open until the end. After filling for 3 seconds, close the ci2 and C13 joints' and open the C9 and C20 joints. The radioactive ammonium iodide solution in the L〇〇p sampling loop is injected into the reaction flask 38 through the V20 control valve by nitrogen pressure. The gas in the reaction flask 38 is discharged through a normally open V8 control valve and an activated carbon tube 42 containing sodium hydroxide (NaOH) particles. After 5 seconds, the C9, C19 and C20 joints were closed, and the C14 joint was opened, and the bubble formed by the nitrogen pressure was stirred for 10 seconds, and then the C14 joint was closed, wherein the nitrogen-filled radioactive ammonium iodide solution was used as a micro valve ( Micr〇Valve) adjust the appropriate flow rate to make the solution slowly fill the Loop sampling loop; (E 1 ) open the C1 joint, and use the 5% hydrogen peroxide solution of the first drug bottle 31 as the oxidant, which will accumulate 0.1 ml. The hydrogen peroxide solution is injected into the reaction vial via a VI control valve for 3,8,5 seconds, then the C1 connector is closed, and the C14 connector is opened. The mixture is stirred at room temperature for 5 minutes with a bubble and the C14 connector is closed. (F 1 ) The second drug is opened. The bottle of sodium sulfite and the third drug bottle 3 3 9 201029670 are used as a reducing agent. First open the C2 joint, inject 1 ml of sodium bisulfite into the reaction vial via V2 control for 3,8,5 seconds, then close the C2 joint, open the C14 joint, stir with bubbles for 1 〇 second, then close the C14 joint. 'The C3 joint was then opened, and 2 ml of saturated sodium sulphate was injected into the reaction vial via a V3 control valve for 3,8,5 seconds, the C3 joint was closed, and the C14 joint was opened. Close the ci4 connector to terminate the oxidation reaction; Filter the collection procedure ❿ (G 1 ) to open the C3, C8 (close the V8 control valve) C15, C16 and C18 joints, and the reaction solution in the reaction flask 38 via V14a, V15, V22a and V16b The control valve is injected into the C-8 purification column 39, and the filtered filtrate is injected into a waste bottle 43 through the V10a and VIla control valves, and the C8, C15 and C16 joints are closed after 60 seconds; Open the C4 connector'. Inject the fourth drug vial 34 into the reaction vial via a V4 control valve in a volume of 10 ml. After 10 seconds, close the C4 connector and open the C14 connector. Stir for 1 second with air bubbles. After the clock Ο Close the C14 connector. Then, open C4, C8 (close V8 control valve) C15, C16 and C18 joints' so that the reaction liquid in the reaction flask 38 is injected into the C-8 purification column through the V14a, V15 and V16b control valves. The filtrate is injected into the waste bottle 43 via the V10a and Vila control valves. Close the C8 and C15 joints, and open the C5 and C16 joints after the final product is adsorbed on the c-8 purification column 39. 'Inject the fifth vial 35 water for injection into the volume of 10 ml via the V5 and V16b control valves. The c-8 purification column 3 9 washes out the 1-123 source on the unlabeled stream, and the effluent filtrate is also injected into the waste bottle 4 3 via the vl〇a and Vlla control valves, and is turned off after 300 seconds. C5 joint; 201029670 (I 1 ) open the C6 joint, and inject the sixth drug bottle 36% ethanol into the volume of 1 ml via V6 V22a, and V16b control valve into the 08 purification column 3 9 as a gradient concentration to remove other Impure, the filtrate that flows out is also injected into the waste bottle 43 through the VlOa and VIla control valves, and the C6 joint is closed after 30 seconds; (j 1 ) the joints such as C7, CIO and C16 are opened, and the seventh drug is used under nitrogen pressure. Bottle 7 7 of 95% ethanol is injected into the 匚_8 purification column 3 through the V7, V22a and V16b control valves through a V3, V22a and V16b control valve, and an empty tube 4 4 is injected via the VlOb control valve, and the C16 joint is closed after about 30 seconds. And open the C17 connector, so that the ethanol in the empty tube 4 4 flows back, and then close the C17 connector after 30 seconds, and open the C16 connection. Head, the ethanol in the c_8 purification column 3 9 is re-flowed to the empty tube 4 4 'overflow and reflux washing for 5 times; (κ 1 ) to the above step (J 1 ) to be refluxed and washed 5 times After closing the C17 and C10 joints' and opening the C11 and C16 joints, the ethanol solution in the C-8 purification column is injected into the first collection bottle via the ¥1〇3 and Vllb control valves. Close the joints such as C7, C11 and C16, and open the C21 joint, so that the product solution in the first collection bottle 45 flows through a filter membrane 463, and then injects a second collection bottle 4 〇a, and closes after 180 seconds. The C18 and C21 joints' were used to precipitate the final I-123-IBOX product; the sampling procedure (L 1 ) supplemented the seventh drug vial 37 with 95% ethanol 0.9 ml and was replaced with another filter 臈 4 6b, and the second The collection bottle 4 〇a is replaced with the step (C 1 ) aseptic collection bottle 4 〇b; and (Μ 1 ) the joints such as C7, cu, C16 and C18 are opened, and the seventh drug bottle 37% of the 95% ethanol is passed through the nitrogen pressure. V7, V22a and V16b control 11.201029670 Valve is injected into the C-8 purification column 3 9 ' and then injected into the first collection bottle 4 5 via Vl〇a and Vllb control, and closed C7, C after 30 seconds 11 and C16 and other joints, and open the C21 joint, so that the product solution in the first collection bottle 45 flows through the filter membrane 46b, and is injected into the sterile collection bottle 4 〇b and the pre-mixed physiological saline solution and The vitamin C mixture was mixed and the C18 and C21 connectors were closed after 60 seconds. Through the above-mentioned operation program for performing the I-123-IBOX label reaction, about 15 minutes under the fully automatic operation, the reaction can be completed, and the purified collected I-123-IBOX can be taken out. For example, all the reaction processes are fully automatic. The control operation is carried out, and since the process is simplified, it is only necessary to use a reaction bottle for operation. When using this method, it is only necessary to put the reaction drug into a specific bottle, turn on the power supply and pass the gas for reaction, and use the C-8 purification column to separate and purify the I-123-IBOX product, and during operation, The reaction activity of the reaction flask and the C_8 purification column are separately measured, and after the start of the operating system, the total reaction time from the start of the reaction to the completion of the preparation can be completed in 15 minutes, which can be consistent with the production of the automatic synthesis system. The need for semi-virtual nuclear medicine. It can be seen from the above description that the present invention provides a method for automatically synthesizing an amyloid Beta Plaques contrast agent which is light and flexible, safe and reliable, and convenient for use in brain nuclear medicine diagnosis, and can prevent not only radioactive substances but also radioactive substances. 'It can also reduce the amount of the side of the pharmaceutical operator to reduce the damage, which can be extended to the medical community to provide clinical diagnosis and use. In summary, the present invention is a method of the W23JBOX automated synthesis system, which can effectively improve various disadvantages of the conventional use, and all the reactions are carried out in a fully automatic 12 201029670 synthesis system, which enables the operator to receive the radiation dose reduction. The lowest dose 'not only short reaction time, high productivity' and simple operation process, but also can provide I-123-IBOX for medical brain tomography, and can also effectively reduce the radiation exposure of pharmaceutical operators to reduce the damage. The invention can be made more progressive, more practical, and more in line with the needs of the user. It has indeed met the requirements of the invention patent application, and has filed a patent application according to law. However, the above description is only a preferred embodiment of the present invention, and the scope of the invention is not limited thereto; therefore, the equivalent changes and modifications made by the scope of the invention and the description of the invention are Modifications, which are still within the scope of the invention patents. BRIEF DESCRIPTION OF THE DRAWINGS Fig. 1 is a schematic view showing the production process of the present invention. Fig. 2 is a schematic circle diagram of the present invention. [Description of main component symbols] Steps (A) to (M) 1; l to 9q First drug bottle 31 Second drug bottle 32 Second bottle 3 3 Fourth drug bottle 34 Fifth drug bottle 35 Sixth drug bottle 3 6 Seventh drug bottle 3 7 Reaction bottle 3 8 201029670 C-8 purification column 3 9 Second collection bottle 4 〇a Aseptic collection bottle 4 Ob Recycling bottle 4 1 Activated carbon tube 4 2 Waste bottle 4 3 Empty tube 4 4 First collection bottle 4 5 Ο Over the diaphragm 4 6 a, 4 6 b Sampling loop Loop Cl~C21 connector VI~V21 control valve 14

Claims (1)

、201029670 七、申請專利範圍: 1 · 一種I-123-IBOX自動化合成系統之方法,係至少包含下列程 序及步驟: 準備程序 (A )分別於一第一藥品瓶加入過氧化氫(H202 )溶液, 於一第二藥品瓶加入亞硫酸鈉(Na2S03),於一第三藥品瓶 加入亞破酸納(Na2HP03),於一第四及第五藥品瓶各加入注 射用水(H20),於一第六藥品瓶加入50%乙醇(EtOH),以 © 及於一第七藥品瓶加入95%乙醇。並將含有放射性碘化銨之 水溶液注入一無菌反應瓶内,以輸載氣體將一溶於乙醇之標 幟前驅物SnIBOX導入該反應瓶内,用以與此含有放射性峨 化銨之水溶液混合; (B )對一 C-8純化管柱(08 Sep-pak column)進行前 處理,加入乙醇及注射用水洗出; (C )取維他命 C (Ascorbic acid)注射液(Injection) 及冰醋酸加入0.9%氣化納注射液’混合均勻,並以一無菌注 ® 射針筒抽取,經一 Millipore Millex GV過濾匣注入無菌收集 瓶; 氧化反應程序 (D)將一取樣閥旋轉至填充位置,利用氮氣壓力將放 射性蛾化銨溶液([123I]NH4I)充填至取樣環路,滿出之液體 則流至一回收瓶。之後再以氮氣壓力將取樣環路内之放射性 碟化録溶液注入該反應瓶内,並藉氮氣壓力形成之氣泡進行 搜拌’於其中該反應瓶内氣體係由一活性碳(Active Charcoal) 管排出; 15 4201029670 (E) 將第一藥品瓶之過氧化氫溶液作為氧化劑,注入 該反應瓶,於室溫下利用氣泡進行攪拌至反應所需時間; (F) 將第二藥品瓶之亞硫酸鈉及第三藥品航之飽合亞 磷酸鈉作為還原劑,分別注入該反應瓶,並利用氣泡先後進 行攪拌至反應所需時間,終止氧化反應; 過濾收集程序 (G) 將此反應瓶内反應液流經該c-8純化管柱吸附, 流出之過濾液係注入一廢液瓶; (H) 注入第四藥品瓶之注射用水至反應瓶,並利用氣 泡進行攪拌至反應所需時間’繼之,將此反應瓶内反應液注 入該C-8純化管柱’流出之過濾液係注入該廢液瓶,之後再 注入第五藥品瓶之注射用水至該c_8純化管柱對其進行清 洗’流出之過濾液亦注入該廢液^(; (I )將第六藥品瓶之50%乙醇注入該C-8純化管柱, 流出之過濾液係注入該廢液瓶; (J )利用氮氣壓力將第七藥品瓶之95%乙醇注入該C-8 純化管柱’並再注入一空管後,進行來回流洗數次; (K)最後注入至一第一收集瓶’並使該第一收集瓶内 產品溶液流經一過濾膜後,注入一第二收集瓶; 取樣程序 (L )補充第七藥品瓶之95%乙醇,且更換過濾膜,並 將該第二收集瓶更換為步驟(C)無菌收集瓶;以及 (M)以氮氣壓力將第七藥品瓶之95%乙醇注入該C-8 純化管柱,再注入該第一收集瓶,使該第一收集瓶内產品溶 液流經此過濾膜後’注入於該無菌收集瓶内與預先調配好之 201029670 生理食鹽水及維他命c混合液混合。 2 ·依據申請專利範園第1項所述ij^m-roox自動化合成系統 之方法’其中’該輸載氣體係為碘化鉀(KI)。 3 ·依據申請專利範圍第1項所述之j-ojbox自動化合成系統 之方法’其中,該氧化反應程序中,氮氣係以一微型閥(Micro Valve)調節其流量。 4 ·依據中請專利範圍第!項所述之^业⑽自動化合成系統 之方法,其中,該步驟(D)放射性蛾化録溶液之充填時間 係為3秒鐘。 5 ·依據申請專利範圍第2項所述之卜心齡乂自動化合成系統 之方法,其中,該步驟(D)氮氣攪拌時間為1〇秒鐘。 6 ·依據申請專利範圍第工項所述之Ι123 ΙΒ〇χ自動化合成系統 之方法,其中,該步驟(Ε )敗氣勝時間為5分鐘。 •依據申請專利範圍第丄項所述之Ι-123·ΙΒ〇χ自動化合成系統 之方法’其中’該步驟(F)亞硫酸鈉及亞鱗酸納其各別氮 氣攪拌時間皆為10秒鐘。 8 ·依據申請專利範圍第!項所述之卜觀職自動化合成系統 •之方法’其中’該步驟(Η)氮氣授拌時間為10秒鐘。 依據申4專利範®第1項所述之Ι123 ΙΒ〇χ自動化合成系統 之方法,其中’該步驟⑴係進行共5次來回流洗。 *依據申請專利範圍第工項所述之[必迅敗自動化合成系 、先之方法’其巾,經由全自_狀狀麟_、為15分鐘。, 201029670 VII, the scope of application for patents: 1 · A method of I-123-IBOX automated synthesis system, including at least the following procedures and steps: Preparation procedure (A) separately add hydrogen peroxide (H202) solution to a first drug bottle Adding sodium sulfite (Na2S03) to a second drug bottle, adding sodium succinate (Na2HP03) to a third drug bottle, and adding water for injection (H20) to a fourth and fifth drug bottles. The bottle was filled with 50% ethanol (EtOH), and 95% ethanol was added to and from a seventh drug bottle. And injecting an aqueous solution containing radioactive ammonium iodide into a sterile reaction bottle, and introducing a reagent precursor SnIBOX dissolved in ethanol into the reaction bottle with a carrier gas for mixing with the aqueous solution containing radioactive ammonium hydride; (B) pre-treating a C-8 purification column (08 Sep-pak column), adding ethanol and washing water for injection; (C) taking vitamin C (Injection) and glacial acetic acid to 0.9. The % gasification injection was 'mixed evenly and extracted with a sterile injection® syringe, injected into a sterile collection via a Millipore Millex GV filter; Oxidation reaction procedure (D) rotated a sampling valve to the filling position with nitrogen The pressure fills the radioactive molybdenum solution ([123I]NH4I) into the sampling loop, and the filled liquid flows to a recovery bottle. Then, the radioactive recording solution in the sampling loop is injected into the reaction bottle under nitrogen pressure, and the bubbles formed by the pressure of nitrogen are mixed. The gas system in the reaction flask is made up of an activated carbon (Active Charcoal) tube. 15 4201029670 (E) Inject the hydrogen peroxide solution of the first drug bottle as an oxidant into the reaction flask, and stir it at room temperature with a bubble until the reaction takes time; (F) the sodium sulfite of the second drug bottle and The third drug is saturated with sodium phosphite as a reducing agent, and is respectively injected into the reaction bottle, and the bubble is successively stirred until the reaction takes time to terminate the oxidation reaction; the filtration collection procedure (G) is carried out in the reaction bottle. After being adsorbed by the c-8 purification column, the effluent filtrate is injected into a waste liquid bottle; (H) injecting the injection water of the fourth drug bottle into the reaction bottle, and stirring with a bubble until the reaction takes time, The reaction solution in the reaction flask is injected into the C-8 purification column, and the filtrate flowing out is injected into the waste liquid bottle, and then the injection water of the fifth medicine bottle is injected into the c_8 purification tube column. The cleaning solution is also injected into the waste liquid ^ (; (I) injecting 50% ethanol of the sixth drug bottle into the C-8 purification column, and the flowing filtrate is injected into the waste bottle; Applying 95% ethanol of the seventh drug bottle to the C-8 purification column by nitrogen pressure and then injecting an empty tube, and performing a reflux washing several times; (K) finally injecting into a first collection bottle' After the product solution in the first collection bottle is passed through a filter membrane, a second collection bottle is injected; the sampling procedure (L) supplements the 95% ethanol of the seventh drug bottle, and the filter membrane is replaced, and the second collection bottle is replaced. Replace with step (C) sterile collection bottle; and (M) inject 95% ethanol of the seventh drug bottle into the C-8 purification column under nitrogen pressure, and then inject the first collection bottle to make the first collection bottle After the product solution flows through the filter membrane, it is injected into the sterile collection bottle and mixed with the pre-mixed 201029670 physiological saline solution and vitamin C mixture. 2 · According to the patent application, the ij^m-roox automation A method of synthesizing a system 'where the carrier gas system is potassium iodide (KI). 3 · According to the method of the j-ojbox automated synthesis system described in claim 1, wherein in the oxidation reaction process, the nitrogen gas is regulated by a micro valve. 4 · According to the scope of the patent application! The method for automatically synthesizing a system according to the item (10), wherein the filling time of the step (D) of the radioactive moth recording solution is 3 seconds. 5 · The automatic synthesis of Buxinling according to the second item of the patent application scope The method of the system, wherein the step (D) nitrogen agitation time is 1 〇 second. 6 · According to the method of the Ι123 ΙΒ〇χ automated synthesis system described in the scope of the patent application, wherein the step (Ε) is defeated The gas win time is 5 minutes. • According to the method of the Ι-123·ΙΒ〇χAutomatic Synthetic System described in the scope of the patent application, wherein the step (F) sodium sulfite and sulphite are each stirred for 10 seconds. 8 · According to the scope of patent application! The method described in the item is a method of 'automatically synthesizing the system' wherein the step (Η) nitrogen gas mixing time is 10 seconds. According to the method of the Ι123 ΙΒ〇χ automated synthesis system described in claim 1, wherein the step (1) is carried out a total of 5 times for reflux washing. * According to the application of the scope of the patent application, the "Must be the automatic synthesis system, the first method", the towel, through the _ _ _ _, for 15 minutes.
TW98104421A 2009-02-12 2009-02-12 Method of auto-synthesis in I-123-IBOX TW201029670A (en)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
TWI488645B (en) * 2013-05-14 2015-06-21 Inst Nuclear Energy Res A method for synthesizing rhenium-188-micro-fat and its device

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
TWI488645B (en) * 2013-05-14 2015-06-21 Inst Nuclear Energy Res A method for synthesizing rhenium-188-micro-fat and its device

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