碘克沙酸 | 59017-64-0

• 物质功能分类: 原料药 - 诊断用药 - 影象检查用药
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 碘克沙酸
• 英文名称: Ioxaglic acid
• 英文别名: Hexabrix；ioxaglate；3-[[2-[[3-[acetyl(methyl)amino]-2,4,6-triiodo-5-(methylcarbamoyl)benzoyl]amino]acetyl]amino]-5-(2-hydroxyethylcarbamoyl)-2,4,6-triiodobenzoic acid
• CAS: 59017-64-0
• 化学式: C₂₄H₂₁I₆N₅O₈
• 分子量: 1268.89
• InChiKey: TYYBFXNZMFNZJT-UHFFFAOYSA-N

物化性质

• 熔点：
  302°C
• 沸点：
  887.9±65.0 °C(Predicted)
• 密度：
  2.4120 (estimate)
• 溶解度：
  极微溶于水，微溶于乙醇（96%），极微溶于二氯甲烷。溶于碱金属氢氧化物的稀溶液。
• 蒸汽压力：
  1.83X10-39 mm Hg at 25 °C (est)
• 分解：
  When heated to decomposition it emits toxic fumes of /iodine, oxides of nitrogen, and oxides of sodium/.
• 解离常数：
  pKa = 0.99 (carboxylic acid) (est)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  43
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  194
• 氢给体数：
  6
• 氢受体数：
  8

ADMET

代谢

未改变地被排出。

Excreted unchanged.

来源:DrugBank

毒理性

• 在妊娠和哺乳期间的影响

◉ 母乳喂养期间使用概述：静脉注射的碘化对比剂不易排入乳汁中，且口服吸收不良，因此它们不太可能进入婴儿的血液循环或对哺乳婴儿产生任何不良影响。一些专业组织制定的指南指出，哺乳母亲接受含碘对比剂后，无需中断哺乳。然而，由于目前没有关于哺乳期间使用碘克酸的经验发表，其他药物可能更为首选，特别是在哺乳新生儿或早产儿时。 ◉ 对哺乳婴儿的影响：截至修订日期，未找到相关的已发布信息。 ◉ 对泌乳和乳汁的影响：截至修订日期，未找到相关的已发布信息。

◉ Summary of Use during Lactation:Intravenous iodinated contrast media are poorly excreted into breastmilk and poorly absorbed orally so they are not likely to reach the bloodstream of the infant or cause any adverse effects in breastfed infants. Guidelines developed by several professional organizations state that breastfeeding need not be disrupted after a nursing mother receives an iodine-containing contrast medium. However, because there is no published experience with ioxaglate during breastfeeding, other agents may be preferred, especially while nursing a newborn or preterm infant. ◉ Effects in Breastfed Infants:Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk:Relevant published information was not found as of the revision date.

来源:Drugs and Lactation Database (LactMed)

毒理性

• 相互作用

静脉注射碘克酸（4 g碘/千克），一种碘化的放射性对比剂，在大鼠中引起了明显的蛋白渗出、肺水肿和动脉部分氧分压的降低。所有这些对碘克酸的反应都被 gabexate mesilate（10和50 mg/kg，注射前5分钟预处理）或 nafamostat mesilate（3和10 mg/kg）逆转，后者在注射后完全抑制了反应（10 mg/kg）。Gabexate mesilate 和 nafamostat mesilate 都抑制了纯化的人肺组织蛋白酶的活性，尽管后者的效力远高于前者。碘克酸增强了大鼠腹膜肥大细胞悬浮液中细胞外液中的 nafamostat 敏感的蛋白酶活性。组织蛋白酶增强了蛋白质通过培养的人肺动脉内皮细胞单层的渗透性。当碘克酸与大鼠腹膜肥大细胞联合应用时，也产生了内皮屏障功能障碍。组织蛋白酶和碘克酸的效果被 nafamostat mesilate 逆转。与这些发现一致，免疫荧光形态学分析揭示，组织蛋白酶或碘克酸与肥大细胞联合使用增加了肌动蛋白应激纤维的形成，同时减少了 VE-钙粘蛋白的免疫反应性。组织蛋白酶和碘克酸的这两种作用都被 nafamostat mesilate 逆转。这些发现表明，从肥大细胞释放的组织蛋白酶在碘克酸诱导的肺功能障碍中起着关键作用。在这方面，nafamostat mesilate 可能成为一种用于治疗或预防放射性对比剂严重不良反应的有用药物。

Intravenous injection of ioxaglate (4 g iodine kg(-1)), an iodinated radiographic contrast medium, caused a marked protein extravasation, pulmonary edema and a decrease in the arterial partial oxygen pressure in rats. All of these reactions to ioxaglate were reversed by the pretreatment with gabexate mesilate (10 and 50 mg kg(-1), 5 min prior to injection) or nafamostat mesilate (3 and 10 mg kg(-1)), in which the inhibition was complete after injection of nafamostat mesilate (10 mg kg(-1)). Both gabexate mesilate and nafamostat mesilate inhibited the activity of purified human lung tryptase, although the latter compound was far more potent than the former. Ioxaglate enhanced the nafamostat-sensitive protease activity in the extracellular fluid of rat peritoneal mast cell suspensions. Tryptase enhanced the permeability of protein through the monolayer of cultured human pulmonary arterial endothelial cells. Ioxaglate, when applied in combination with rat peritoneal mast cells, also produced the endothelial barrier dysfunction. These effects of tryptase and ioxaglate were reversed by nafamostat mesilate. Consistent with these findings, immunofluorescence morphological analysis revealed that tryptase or ioxaglate in combination with mast cells increased actin stress fiber formation while decreasing VE-cadherin immunoreactivity. Both of these actions of tryptase and ioxaglate were reversed by nafamostat mesilate. These findings suggest that tryptase liberated from mast cells plays a crucial role in the ioxaglate-induced pulmonary dysfunction. In this respect, nafamostat mesilate may become a useful agent for the cure or prevention of severe adverse reactions to radiographic contrast media.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

肝脏功能不全的患者在服用口服胆囊造影剂后接着使用血管内碘化造影剂，以及在患有隐匿性肾脏疾病的患者中，尤其是糖尿病和高血压患者中，已经报道了肾功能衰竭的情况。在这些类型的患者中，在给予对比剂之前，不应有限制液体的措施，并且应尽一切努力维持正常的液体平衡，因为脱水是影响进一步肾功能损害的最重要因素。

Renal failure has been reported in patients with liver dysfunction who were given an oral cholecystographic agent followed by an intravascular iodinated radiopaque agent and also in patients with occult renal disease, notably diabetics and hypertensives. In these classes of patients there should be no fluid restriction and every attempt made to maintain normal hydration, prior to contrast medium administration, since dehydration is the single most important factor influencing further renal impairment.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

ioxaglate 盐可以通过透析去除。

Ioxaglate salts are dialyzable.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

对于有强烈过敏史、之前对对比剂有反应或预测试阳性的患者，应考虑预防性治疗，包括使用皮质类固醇和抗组胺药。由于这些患者的反应发生率是普通人群的两到三倍，因此应足够早期开始给予足量的皮质类固醇，以在注射对比剂之前生效，并在注射期间及注射后24小时内持续使用。抗组胺药应在注射对比剂前30分钟内给药。最近的报告表明，这种预处理并不能预防严重威胁生命的反应，但可能降低它们的发生率和严重程度。这些注射应使用单独的注射器。

Prophylactic therapy including corticosteroids and antihistamines should be considered for patients who present with a strong allergic history, a previous reaction to a contrast medium, or a positive pre-test since in these patients the incidence of reaction is two to three times that of the general population. Adequate doses of corticosteroids should be started early enough prior to contrast medium injection to be effective and should continue through the time of injection and for 24 hours after injection. Antihistamines should be administered within 30 minutes of the contrast medium injection. Recent reports indicate that such pre-treatment does not prevent serious life-threatening reactions, but may reduce both their incidence and severity. A separate syringe should be used for these injections.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

• 吸收

静脉注射后，碘克酸迅速通过循环系统传输到肾脏。静脉给药的放射性对比剂的药代动力学可以用一个双室模型来描述，其中有一个快速分布的阿尔法阶段和一个慢速消除的贝塔阶段。在10名健康志愿者中静脉注射50毫升碘克酸后，平均血浆峰浓度在2分钟（1-3分钟）出现，达到2.1毫克/毫升（1.8-2.8毫克/毫升）。大约50%的静脉给药剂量在两小时内通过尿液回收，到24小时时点回收率达到90%。

Following the intravascular route of injection, Ioxaglic acid is rapidly transported through the circulatory system to the kidneys. The pharmacokinetics of radiopaque contrast media given by the IV route are described by a two-compartment model with a rapid alpha phase for drug distribution and a slow beta phase for the elimination of the drug. Following the intravenous administration of 50 mL of ioxaglic acid in 10 healthy volunteers, the mean peak plasma concentration occurred at two (1-3) minutes, reaching a concentration of 2.1 (1.8-2.8) mg/mL. Approximately 50 percent of the intravenously administered dose was recovered in the urine at two hours, and 90% percent was recovered at the 24 hour time point.

来源:DrugBank

吸收、分配和排泄

• 消除途径

在尿液中以不变的形式排泄，肝脏和小肠提供了主要的替代排泄途径。在严重肾损害的患者中，这种对比剂的排泄通过胆囊进入小肠急剧增加。

Excreted unchanged in the urine The liver and small intestine provide the major alternate route of excretion. In patients with severe renal impairment, the excretion of this contrast medium through the gallbladder and into the small intestine sharply increases.

来源:DrugBank

吸收、分配和排泄

• 分布容积

ioxaglate 盐类会穿过人类胎盘屏障，并以未改变的形式在人类乳汁中排出。

Ioxaglate salts cross the placental barrier in humans and are excreted unchanged in human milk.

来源:DrugBank

吸收、分配和排泄

• 清除

245毫升/千克

245 ml/kg

来源:DrugBank

吸收、分配和排泄

注入血管后，HEXABRIX迅速通过循环系统传输到肾脏，并以不变的形式在尿液中排出。静脉内给药的放射性对比剂的药代动力学通常最好通过一个双室模型来描述，其中快速alpha阶段用于药物分布，较慢的beta阶段用于药物消除。

Following intravascular injection, HEXABRIX is rapidly transported through the circulatory system to the kidneys and is excreted unchanged in the urine. The pharmacokinetics of intravascularly administered radiopaque contrast media are usually best described by a two compartment model with a rapid alpha phase for drug distribution and a slower beta phase for drug elimination.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 海关编码：
  2924296000
• WGK Germany：
  3

反应信息

• 作为反应物：
  描述：

  碘克沙酸 在 氯化亚砜 、 N,N-二甲基甲酰胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成
  参考文献：
  名称：

  CATIONIC NANOSTRUCTURES FOR INTRA-CARTILAGE DELIVERY OF THERAPEUTICS AND CONTRAST AGENTS

  摘要：

  本发明提供了一种将小分子药物或造影剂输送到关节和其他软组织的平台。该平台通过利用阳离子平台与阴离子软骨基质之间的静电相互作用，使药物穿透软骨的全部厚度，并具有长时间的软骨内滞留时间。本发明描述了符合该平台的化合物和复合物。还提供了使用本发明中的化合物和复合物治疗关节疾病的方法，以及成像关节和其他软组织的方法。

  公开号：

  US20210154307A1

文献信息

• [EN] GEL FORMULATIONS FOR ENHANCING THE EFFECT OF RADIOTHERAPY<br/>[FR] FORMULATIONS DE GEL POUR AMÉLIORER L'EFFET DE RADIOTHÉRAPIE
  申请人：UNIV DENMARK TECH DTU

  公开号：WO2016079331A1

  公开（公告）日：2016-05-26

  The present invention relates to a composition comprising: a. non-water soluble carbohydrates b. a contrast agent for imaging, wherein at least 60% of the contrast agent remains within 10 cm from the injection site after 24h, for use in local co-administration into a human or animal body, and wherein the composition is a liquid before administration into the human or animal body and increases in viscosity by more than 1,000 centipoise (cP) after administration.

  本发明涉及一种包含以下成分的组成物：a. 非水溶性碳水化合物 b. 成像的对比剂，其中至少60%的对比剂在24小时后保持在注射部位10厘米范围内，用于在人体或动物体内局部共同给药，并且该组成物在给药前为液态，在给药后在粘度上增加超过1,000厘泊（cP）。
• [EN] CONTRAST AGENTS<br/>[FR] AGENTS DE CONTRASTE
  申请人：GE HEALTHCARE AS

  公开号：WO2009060021A1

  公开（公告）日：2009-05-14

  Compounds of formula (I) RA-CO-N(R2)-(CR12)n-N(R5)-RB and salts or optical active isomers thereof, wherein each R1 independently are the same or different and denotes a hydrogen atom, a hydroxyl group, a C1 to C4 straight of branched alkyl group or a C1 to C4 straight of branched oxyalkyl group; R2 denotes a hydrogen atom or a C1 to C4 straight of branched alkyl group; R5 independently are the same or different and denotes a acyl moiety; RA and RB independently are the same or different and denote a triiodinated phenyl group, preferably a 2,4,6-triiodinated phenyl group further substituted by two groups R3 in the 3 and 5 positions wherein each R3 are the same or different and denote a hydrogen atom or a non-ionic hydrophilic moiety, provided that at least one R3 group in the compound of formula (I) is a hydrophilic moiety; and n denotes a positive integer of 1 to 6. The invention also relates to the use of such diagnostic compositions as contrast agents in diagnostic imaging and in particular in X-ray imaging, and to contrast media containing such compounds.

  式(I)的化合物RA-CO-N(R2)-(CR12)n-N(R5)-RB及其盐或光学活性异构体，其中每个R1独立地相同或不同，并表示氢原子、羟基、C1到C4的直链或支链烷基或C1到C4的直链或支链氧烷基；R2表示氢原子或C1到C4的直链或支链烷基；R5独立地相同或不同，并表示酰基；RA和RB独立地相同或不同，并表示三碘苯基，优选为在3和5位进一步取代两个R3基团的2,4,6-三碘苯基，其中每个R3相同或不同，并表示氢原子或非离子亲水基团，但化合物中至少有一个R3基团是亲水基团；n表示1到6的正整数。本发明还涉及将这种诊断组合物用作诊断成像中的造影剂，特别是在X射线成像中的造影剂，以及含有这种化合物的造影剂。
• [EN] ACTIVITY BASED PROBE AND USES THEREOF FOR IMAGING<br/>[FR] SONDE BASÉE SUR L'ACTIVITÉ ET SES UTILISATIONS POUR L'IMAGERIE
  申请人：YISSUM RES DEV CO

  公开号：WO2017141251A1

  公开（公告）日：2017-08-24

  The present application provides a compound comprising at least one carrier moiety associated with a plurality of CT imaging moieties, and with at least one enzyme interacting moiety as well as uses thereof in diagnosis.

  本申请提供了一种化合物，其中至少包括一个载体基团与多个CT成像基团相关联，并且至少包括一个与酶相互作用的基团，以及在诊断中的用途。
• [EN] PREPARATION OF INTERMEDIATES OF X-RAY CONTRAST AGENTS<br/>[FR] PRÉPARATION D'INTERMÉDIAIRES D'AGENTS DE CONTRASTE DE RAYONS X
  申请人：GE HEALTHCARE AS

  公开号：WO2014074315A1

  公开（公告）日：2014-05-15

  The present invention relates to a process for the preparation of iodinated X-ray contrast agents and in particular to key intermediates thereof. It particularly relates to an improved process for preparation of 5-acetamido-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide (Compound A) or N,N'-bis(2,3-dihydroxypropyl)-5-formamido-2,4,6-triiodoisophthalamide (Compound C), which are intermediates in the industrial preparation of non-ionic X-ray contrast agents. More particularly the invention provides a process for deacylation of the acylated hydroxyl groups of an intermediate compound of Compound A and Compound C.

  本发明涉及碘化X射线造影剂的制备方法，特别是涉及其关键中间体的制备方法。本发明特别涉及一种改进的制备5-乙酰氨基-N,N'-双(2,3-二羟丙基)-2,4,6-三碘异酞酰胺（化合物A）或N,N'-双(2,3-二羟丙基)-5-甲酰氨基-2,4,6-三碘异酞酰胺（化合物C）的方法，这两种化合物是工业制备非离子型X射线造影剂的中间体。更具体地，本发明提供了一种用于脱除化合物A和化合物C中间体中羰基化羟基的工艺。
• Contrast Agents
  申请人：Priebe Hanno

  公开号：US20080199404A1

  公开（公告）日：2008-08-21

  The present invention relates to a class of compounds and to diagnostic compositions containing such compounds where the compounds are iodine containing compounds. More specifically the iodine containing compounds are chemical compounds containing an aliphatic central moiety allowing for the arrangement of three iodinated phenyl groups bound thereto. The invention also relates to methods of diagnosis and imaging employing such diagnostic compositions as contrast agents in particular in X-ray imaging, and to contrast media containing such compounds.

  本发明涉及一类化合物以及含有此类化合物的诊断组合物，其中所述化合物为含碘化合物。更具体地，所述含碘化合物是化学化合物，包含一个可连接三个碘化的苯基基团的脂肪族中心部分。本发明还涉及使用此类诊断组合物作为对比剂，特别是在X射线成像中的诊断和成像方法，以及包含此类化合物的对比介质。