isosulfan blue

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: isosulfan blue
• 英文别名: sodium;2-[[4-(diethylamino)phenyl]-(4-diethylazaniumylidenecyclohexa-2,5-dien-1-ylidene)methyl]benzene-1,4-disulfonate
• 化学式: C₂₇H₃₁N₂O₆S₂*Na
• 分子量: 566.675
• InChiKey: NLUFDZBOHMOBOE-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  0.77
• 重原子数：
  38
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  137
• 氢给体数：
  0
• 氢受体数：
  7

ADMET

毒理性

• 解毒与急救

/SRP:/ 立即急救：确保已经进行了充分的中和。如果患者停止呼吸，请开始人工呼吸，最好使用需求阀复苏器、球囊阀面罩设备或口袋面罩，按训练操作。如有必要，执行心肺复苏。立即用缓慢流动的水冲洗受污染的眼睛。不要催吐。如果患者呕吐，让患者向前倾或将其置于左侧（如果可能的话，头部向下）以保持呼吸道畅通，防止吸入。保持患者安静，维持正常体温。寻求医疗救助。 /毒物A和B/

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 基本治疗：建立专利气道（如有需要，使用口咽或鼻咽气道）。如有必要，进行吸痰。观察呼吸不足的迹象，如有需要，辅助通气。通过非循环呼吸面罩以10至15升/分钟的速度给予氧气。监测肺水肿，如有必要，进行治疗……。监测休克，如有必要，进行治疗……。预防癫痫发作，如有必要，进行治疗……。对于眼睛污染，立即用水冲洗眼睛。在运输过程中，用0.9%的生理盐水（NS）持续冲洗每只眼睛……。不要使用催吐剂。对于摄入，如果患者能吞咽、有强烈的干呕反射且不流口水，则用温水冲洗口腔，并给予5毫升/千克，最多200毫升的水进行稀释……。在去污后，用干燥的无菌敷料覆盖皮肤烧伤……。/毒药A和B/

/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 高级治疗：对于无意识、严重肺水肿或严重呼吸困难的病人，考虑进行口咽或鼻咽气管插管以控制气道。使用气囊面罩装置的正压通气技术可能有益。考虑使用药物治疗肺水肿……。对于严重的支气管痉挛，考虑给予β激动剂，如沙丁胺醇……。监测心率和必要时治疗心律失常……。开始静脉输注D5W /SRP: "保持开放"，最低流量/。如果出现低血容量的迹象，使用0.9%生理盐水（NS）或乳酸林格氏液。对于伴有低血容量迹象的低血压，谨慎给予液体。注意液体过载的迹象……。使用地西泮或劳拉西泮治疗癫痫……。使用丙美卡因氢氯化物协助眼部冲洗……。 /Poisons A and B/

/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

人体暴露研究/某些重要染料会导致脉搏血氧饱和度（Spo2）降低。作者研究了异硫蓝（IB）对Spo2的影响。研究了33名34-81岁的女性，她们正在接受乳腺癌手术。由外科医生将IB 5 mL（50 mg）注射到肿瘤周围的实质内。使用脉搏血氧计连续记录IB注射后130分钟内的Spo2值。使用Friedman重复测量等级方差分析来分析基线Spo2以及5、10、20、30、40、50和60分钟时的值。5、10、20、30、40、50和60分钟的Spo2值与基线值有显著差异（p < 0.05）。在典型患者中，可以在IB注射后25分钟内预期最大3%的Spo2下降。在肿瘤周围注射IB 50 mg后，会对Spo2产生显著的干扰。

/HUMAN EXPOSURE STUDIES/ Certain vital dyes are known to cause pulse oximetry (Spo2) desaturation. The authors studied the effect of isosulfan blue (IB) on Spo2. Thirty-three women, aged 34-81 yr, who were undergoing surgery for breast cancer were studied. IB, 5 mL (50 mg), was injected intraparenchymally around the tumor area by the surgeon. A pulse oximeter was used to continuously record Spo2 values up to 130 min after IB injection. Friedman repeated-measures analysis of ranks was used to analyze the baseline Spo2 and values at 5, 10, 20, 30, 40, 50, and 60 min. Spo2 values were significantly different from baseline values at 5, 10, 20, 30, 40, 50, and 60 min (p < 0.05). In a typical patient, a maximum Spo2 decrease of 3% can be anticipated 25 min after injection of IB. After peritumoral administration of IB, 50 mg, a significant interference with Spo2 will occur.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

人类暴露研究/两名患有乳腺癌的女性患者在手术过程中疑似出现过敏性休克，这些手术是为了进行前哨淋巴结活检，期间她们接受了1%的异硫氰酸蓝以可视化淋巴管。第一个案例中，患者出现了低血压和缺氧，需要插管。在第二个案例中，患者出现了持续的低血压。两名患者均无后遗症恢复。对患者进行了/检查/，并进行了异硫氰酸蓝的皮肤测试，以及患者在麻醉期间接受的其他药物的皮肤测试。在这两个案例中，患者对异硫氰酸蓝的皮肤测试呈阳性。没有任何其他用于皮肤测试的药物对患者产生阳性反应。对九名对照者进行了异硫氰酸蓝的皮肤测试，所有对照者的皮肤测试均为阴性。异硫氰酸蓝可能是过敏性反应的原因，这似乎是通过阳性皮肤测试证实的免疫球蛋白E介导的事件。

/HUMAN EXPOSURE STUDIES/ Two female patients with breast cancer were evaluated ... after suspected intraoperative anaphylactic episodes during sentinel lymph node biopsies in which they had received isosulfan blue 1% for the purpose of visualization of the lymph vessels. In the first case, the patient suffered hypotension and hypoxia requiring intubation. In the second case, the patient suffered prolonged hypotension. Both patients recovered without sequelae. The patients were /examined/ and skin tests were performed to isosulfan blue in addition to other agents the patients had received during anesthesia. In both cases, the patients demonstrated positive skin tests to isosulfan blue. Neither patient had positive skin tests to any other agent used for skin testing. Isosulfan blue skin tests were performed in nine control subjects and all skin tests in the control subjects were negative. Isosulfan blue may be a cause of anaphylactic reactions and this seems to be an immunoglobulin E-mediated event as confirmed by positive skin tests.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

皮下注射后，1%的异硫蓝注射液会与血清蛋白结合，并被淋巴管吸收。因此，蓝色染料勾勒出淋巴管的轮廓。

Following subcutaneous administration, isosulfan blue injection 1% binds to serum proteins and is picked up by the lymphatic vessels. Thus, the lymphatic vessels are delineated by the blue dye.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

这种药物是否排泄入人乳中尚不清楚。

It is not known whether this drug is excreted in human milk.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

皮下注射的1%异硫蓝注射液在24小时内，人体中有高达10%的剂量未改变地通过尿液排出。

Up to 10% of the subcutaneously administered dose of isosulfan blue injection 1% is excreted unchanged in the urine in 24 hours in humans.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

皮下注射后，1%的isosulfan蓝注射液会与血清蛋白结合，并被淋巴管吸收。因此，淋巴管通过蓝色染料被描绘出来。

Following subcutaneous administration, isosulfan blue injection 1% binds to serum proteins and is picked up by the lymphatic vessels. Thus, the lymphatic vessels are delineated by the blue dye.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

这种药物是否排泄入人乳中尚不清楚。

It is not known whether this drug is excreted in human milk.

来源:Hazardous Substances Data Bank (HSDB)

反应信息

• 作为产物：
  描述：

  N,N-二乙基苯胺 在 溶剂黄146 、 silver(l) oxide 作用下， 以 甲醇 、 水 为溶剂， 生成 isosulfan blue
  参考文献：
  名称：

  [EN] METHOD FOR PREPARATION OF ISOSULFAN BLUE
  [FR] PROCÉDÉ DE PRÉPARATION D'D'ISOSULFANE BLEU

  摘要：

  提供一种制备异磺酸蓝的方法。

  公开号：

  WO2017218764A1

文献信息

• PROCESS FOR PREPARATION OF ISOSULFAN BLUE
  申请人：Kovi Ravishanker

  公开号：US20080281127A1

  公开（公告）日：2008-11-13

  A process for the preparation of isosulfan blue (Active Pharmaceutical Ingredient) is provided. A process is also provided for preparation of the intermediate, 2-chlorobenzaldehyde-5-sulfonic acid, sodium salt of formula (2), used in the preparation thereof and a procedure for the isolation of benzaldehyde-2,5-disulfonic acid, di-sodium salt of the formula (3). Also provided is a process for the preparation of an isoleuco acid of formula (4), which upon mild oxidation gives rise to isosulfan blue of pharmaceutical grade which can be used for preparation of pharmaceutical formulations. The isolation and purification procedures provided in the process provide substantially pure isosulfan blue with HPLC purity 99.5% or greater.

  提供了一种制备异磺蓝（活性药用成分）的方法。还提供了一种制备中间体2-氯苯甲醛-5-磺酸钠盐（式（2））的方法，该中间体用于制备，并提供了一种分离苯甲醛-2,5-二磺酸二钠盐（式（3））的程序。还提供了一种制备异亮氨酸的方法（式（4）），经轻度氧化后可得到药用级别的异磺蓝，可用于制备药物配方。在该过程中提供的分离和纯化程序可提供具有HPLC纯度为99.5%或更高的几乎纯净的异磺蓝。
• A PROCESS FOR THE PREPARATION OF ISOSULPHAN BLUE
  申请人：KULKARNI K. BALKRISHNA

  公开号：US20060224003A1

  公开（公告）日：2006-10-05

  A process for the preparation of Isosulphan Blue is disclosed. The process comprises the following steps: Sulphonating orthochlorobenzaldehyde, treatment with sodium sulphite, basification, condensation and oxidation to obtain Isosulphan Blue.

  公开了一种制备伊索苏尔凡蓝的方法。该方法包括以下步骤：磺化邻氯苯甲醛，用亚硫酸钠处理，碱化，缩合和氧化以获得伊索苏尔凡蓝。
• [EN] METHOD FOR THE PREPARATION OF DIARLYMETHANE DYES AND TRIARYLMETHANE DYES INCLUDING ISOSULFAN BLUE<br/>[FR] PROCÉDÉ DE PRÉPARATION DE COLORANTS À BASE DE DIARYLMÉTHANE ET DE COLORANTS À BASE DE TRIARYLMÉTHANE COMPRENANT DU BLEU ISOSULFAN
  申请人：NJ BIOPHARMACEUTICALS LLC

  公开号：WO2021011440A1

  公开（公告）日：2021-01-21

  Disclosed herein is a method for the preparation of diarylmethane dyes and triarylmethane dyes, such as Isosulfan Blue, using electrochemistry. Further disclosed is Isosulfan Blue prepared from a process employing electrochemistry, compositions comprising the same, and use of the prepared Isosulfan Blue as an imaging agent.

  本文披露了一种使用电化学方法制备二芳基甲烷染料和三芳基甲烷染料（如异砜蓝）的方法。进一步披露了通过采用电化学的过程制备的异砜蓝，包括相同成分，并将制备的异砜蓝用作成像剂。
• [EN] ISOSULFAN BLUE, ITS CRYSTALLINE FORM AND PROCESS FOR PREPARATION THEREOF<br/>[FR] BLEU D'ISOSULFANE, SA FORME CRISTALLINE ET SON PROCÉDÉ DE PRÉPARATION
  申请人：BIOPHORE INDIA PHARMACEUTICALS PVT LTD

  公开号：WO2018008040A1

  公开（公告）日：2018-01-11

  The invention relates to an improved process for the preparation N-[4-[[4-(diethyl amino) phenyl] (2,5-disulfophenyl)methylene]-2,5-cyclohexadien-1-ylidene]-N- ethylethanaminium inner salt sodium salt (Isosulfan blue) of formula I. The invention also relates to highly pure novel crystalline form of Isosulfan blue (I) hydrate and its process for the preparation thereof. The invention also relates to an improved process for the preparation of Isosulfan blue sodium hydrate having not more than 0.2% of desethyl impurity of formula A.

  该发明涉及一种改进的制备N-[4-[[4-(二乙基氨基)苯基](2,5-二磺苯基)亚甲基]-2,5-环己二烯-1-基]-N-乙基乙酰胺内盐钠盐（异磺青）的方法，其化学式为I。该发明还涉及异磺青（I）水合物的高纯度新结晶形式及其制备方法。该发明还涉及一种改进的制备异磺青钠水合物的方法，其不含超过0.2%的A式脱乙基杂质。
• [EN] AN IMPROVED PROCESS FOR THE PREPARATION OF ISOSULFAN BLUE<br/>[FR] PROCÉDÉ AMÉLIORE DE PRÉPARATION DE BLEU ISOSULFANE
  申请人：DISHMAN PHARMACEUTICALS AND CHEMICALS LTD

  公开号：WO2017118882A1

  公开（公告）日：2017-07-13

  The present invention relates to process for preparation of Isosulfan blue (Formula I) substantially free from desethyl impurity. (I)

  本发明涉及一种制备基本不含去乙基杂质的异硫氰蓝（化学式I）的方法。