番泻苷A | 517-43-1

• 物质功能分类: 分析化学 - 标准品 - 药典标准品和杂质标准品
• 分子结构分类: 有机化合物 - 苯类化合物 - 蒽
• 中文名称: 番泻苷A
• 中文别名: 番茄汁；桑白皮提取物10:1；番泻叶甙A；环氧(5Z,8Z,14Z)-11,14,17-二十碳三烯酸；番泻草苷A；番泻苷 A
• 英文名称: Sennoside
• 英文别名: 9-[2-carboxy-4-hydroxy-10-oxo-5-[3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-9H-anthracen-9-yl]-4-hydroxy-10-oxo-5-[3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-9H-anthracene-2-carboxylic acid
• CAS: 517-43-1；81-27-6；85085-71-8
• 化学式: C₄₂H₃₈O₂₀
• 分子量: 862.7
• InChiKey: IPQVTOJGNYVQEO-UHFFFAOYSA-N

物化性质

• 沸点：
  1144.8±65.0 °C(Predicted)
• 密度：
  1.743

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  62
• 可旋转键数：
  9
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  348
• 氢给体数：
  12
• 氢受体数：
  20

ADMET

代谢

大黄酸苷A和B通过肠道细菌代谢为番泻苷A和B。番泻苷A和B进一步通过肠道细菌利用β-葡萄糖苷酶代谢为大黄酸蒽酮[DB13175]。大黄酸蒽酮[DB13175]被吸收进入系统循环，其中2.6%通过氧化代谢为大黄酸[DB13174]和番泻苷A和B。大黄酸蒽酮[DB13175]是大黄酸苷A和B的主要活性代谢物，产生药物的泻药效果。大黄酸[DB13174]也是一种活性代谢物，已知具有多种保护作用。

Sennosides A and B are metabolised to sennidins A and B by gut bacteria. Sennidins A and B are further metabolized to rheinanthrone [DB13175] by gut bacteria using beta-glucosidase. Rheinanthrone [DB13175] is absorbed into systemic circulation where 2.6% is metabolized to rhein [DB13174] and sennidins A and B via oxidation. Rheinanthrone [DB13175] is the major active metabolite of sennosides A and B which produces the laxative effect of the medication. Rhein [DB13174] is also an active metabolite known to have many protective effects.

来源:DrugBank

毒理性

• 肝毒性

在推荐剂量下短期使用番泻叶与少数副作用有关，其中大多数副作用都是轻微且短暂的，与其泻药作用有关。然而，长期和高剂量使用番泻叶时，已经描述了不良事件，包括几例临床上明显的肝损伤。肝损伤的出现时间通常在使用后3到5个月，血清酶升高的模式是肝细胞型。肝损伤通常是轻到中度的严重程度，停药后迅速缓解。至少在一个实例中，再次接触导致了肝损伤的快速复发。已发布的病例中未出现免疫过敏特征和自身免疫标志。 此外，一种常见的被称为咖啡番泻叶或东方决明的相关植物已被联系到许多急性、严重毒性事件的实例，包括脑病、肌病和肝功能障碍。在印度北方邦，每年通常在9月到11月之间，儿童中会出现原因不明的“肝-肌-脑病”爆发。调查最终确定摄入西方决明（Cassia occidentalis）是可能的原因，通常发生在吃这种常见开花杂草的叶或豆荚的儿童中。虽然西方决明也被用来泡茶，但摄入的量是最小的。在儿童中，偶尔在成人中，病情表现急剧，伴有恶心、呕吐、颤抖、异常和暴力行为、鬼脸和自残，随后是昏睡和昏迷，此时血清转氨酶和胆红素水平通常会升高。在严重的情况下，肝损伤是进行性的，血清氨和INR水平升高，患者出现昏迷、惊厥和持续癫痫状态，对治疗无反应。尸检显示肝细胞坏死和胆汁淤积。摄入西方决明的动物也会出现类似的症状和损伤模式。这种综合征是否与罕见情况下归因于典型番泻叶（Cassia acutifolia或angustifolia）用作泻药的肝损伤具有相似的病理机制尚不清楚。 可能性评分：D（可能是临床上明显肝损伤的罕见原因）。

Use of senna in the recommended doses for a limited period of time has been associated with few side effects, most of which are mild and transient and related to its laxative action. With longer term and higher dose use of senna, however, adverse events have been described including several cases of clinically apparent liver injury. The time to onset of liver injury was usually after 3 to 5 months of use, and the pattern of serum enzyme elevations was hepatocellular. The liver injury was usually mild-to-moderate in severity and resolved rapidly with discontinuation. In at least one instance, reexposure led to rapid recurrence of liver injury. Immunoallergic features and autoimmune markers were not present in the published cases. In addition, a related plant commonly known as coffee senna or Cassia orientalis has been linked to many instances of acute, severe toxicity with encephalopathy, myopathy and hepatic dysfunction. Outbreaks of “hepato-myo-encephopathy” of unknown cause among children occurred yearly in Uttar Pradesh, India typically between September and November. Investigation eventually identified Cassia occidentalis ingestion as the probable cause, typically occurring in children who eat the leaves or pods of the common flowering weed. While Cassia occidentalis has also been used to prepare tea, the amount ingested was minimal. In children, and rarely in adults, the presentation was precipitous with nausea, vomiting, tremor, abnormal and violent behavior, grimacing and self-mutilation followed by stupor and coma at which time serum aminotransferase and bilirubin levels were typically elevated. In severe instances, the liver injury was progressive, serum ammonia and INR levels rose and patients developed coma, convulsions and status epilepticus that was unresponsive to therapy. Autopsies revealed hepatic necrosis and cholestasis. A similar pattern of symptoms and injury occurs in animals that consume Cassia occidentalis. Whether this syndrome has a similar pathogenesis to the rare instance of hepatic injury attributed to typical senna (Cassia acutifolia or angustifolio) that is used as a laxative is unknown. Likelihood score: D (possible rare cause of clinically apparent liver injury).

来源:LiverTox

毒理性

• 在妊娠和哺乳期间的影响

哺乳期使用的总结：尽管早期一项使用旧的大黄产品的非控制性报告发现哺乳婴儿腹泻频率增加，但使用现代大黄产品的几项控制性研究发现对婴儿没有影响。通常剂量的大黄在哺乳期间是可以接受的。 对哺乳婴儿的影响：在分娩后第5天给予3.6毫升大黄流浸膏后，观察到10名婴儿中有6名对肠道有泻药作用。 在另一项观察性研究中，148名在分娩后第3天服用两茶匙Senokot（相当于700毫克大黄豆荚）的母亲中，没有观察到哺乳婴儿出现腹泻的情况。 50名在分娩后第一天的母亲服用了相当于450毫克大黄豆荚的大黄。如果需要，在随后的几天里可以给予额外的剂量。他们哺乳的婴儿中没有注意到明显异常的大便，尽管所有婴儿也接受了补充喂养。 在一项随机、非盲的研究中，35位母亲在分娩后立即开始每天服用一次含有总共14毫克标准化大黄提取物的片剂，持续2周。37名哺乳婴儿中有6名据报道出现腹泻，这比研究中其他非吸收性泻药的比例要高。 16名妇女服用了含有24毫克大黄苷的大黄粉800毫克。他们哺乳的婴儿都没有异常大便。 一项随机、双盲试验比较了商业大黄片剂（Senokot）的剂量，每天两次，每次2片（14毫克大黄苷a和b），共8剂，从分娩后第一天开始，与安慰剂进行比较。在研究中，126名妇女在服用大黄的同时哺乳她们的婴儿，而155名对照组的母亲哺乳她们的婴儿。在活动组和对照组中，有大便稀疏或腹泻的婴儿百分比没有差异。 20名产后母亲在分娩后第2至4天服用了一种含有车前子种子（欧车前）和大黄的大黄，相当于每天15毫克大黄苷a和b。在11名哺乳的婴儿中，没有一个有大便稀疏。 对泌乳和母乳的影响：截至修订日期，没有找到相关的已发布信息。

◉ Summary of Use during Lactation:Although an early uncontrolled report using an old senna product found increased frequency of diarrhea in breastfed infants, several controlled studies using modern senna products found no effect on the infant. Usual doses of senna are acceptable to use during breastfeeding. ◉ Effects in Breastfed Infants:After administration of 3.6 mL of senna fluidextract on day 5 postpartum, a laxative effect on the bowels was observed in 6 of 10 infants. In another observational study, no cases of diarrhea were observed among the breastfed infants of 148 mothers who received 2 teaspoonfuls of Senokot (equivalent to 700 mg of senna pod) on day 3 postpartum. Fifty mothers who were in the first day postpartum received senna equal to 450 mg of senna pod. Additional doses were given on subsequent days if needed. None of their breastfed infants were noted to have any markedly abnormal stools, although all of the infants also received supplemental feedings. In a randomized, nonblinded study, 35 mothers were given tablets containing a total of 14 mg of standardized senna extract once daily for 2 weeks starting in the immediate postpartum period. Six of the 37 breastfed infants were reported to have diarrhea which was a higher percentage than with other nonabsorbable laxatives in the study. Sixteen women were given 800 mg of powdered senna containing 24 mg of sennosides. None of their breastfed infants had any abnormal stools. A randomized, double-blind trial compared commercial senna tablets (Senokot) in a dose of 2 tablets (14 mg sennosides a and b) twice daily for 8 doses started on the first day postpartum to placebo. Of the women in the study, 126 breastfed their infants and took senna while 155 control mothers breastfed their infants. There was no difference in the percentages of infants in the active and control groups with loose stools or diarrhea. Twenty postpartum mothers were given a laxative containing plantango seeds (psyllium) and senna equivalent to 15 mg of sennosides a and b daily on days 2 to 4 postpartum. Of the 11 infants who were breastfed, none had any loose stools. ◉ 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

• 蛋白质结合

因为泻药苷是在肠道中被摄入并发挥作用，所以通常认为它们不会与蛋白质结合。

Because sennosides are ingested and their action occurs in the gut, it is generally not thought to be protein bound.

来源:DrugBank

吸收、分配和排泄

• 吸收

10%从肠道吸收，主要是以活性代谢物大黄酸 [DB13175] 的形式。

<10% is absorbed from the gut mostly in the form of the active metabolite rheinanthrone [DB13175].

来源:DrugBank

吸收、分配和排泄

• 消除途径

3-6%的代谢物通过尿液排出，其中一些通过胆汁排出。大于90%的番泻苷以聚合物的形式通过粪便排出，2-6%的母化合物未发生变化排出。

3-6% of metabolites are excreted in urine with some in bile. >90% of sennosides are excreted in the feces as polymers with 2-6% of the parent compounds excreted unchanged.

来源:DrugBank

吸收、分配和排泄

• 分布容积

静脉注射放射性标记的大黄酸B在大鼠体内的分布体积为0.802±0.124L/kg。

The volume of distribution of radiolabelled intravenous sennoside B in rats was 0.802±0.124L/kg.

来源:DrugBank

吸收、分配和排泄

• 清除

静脉注射放射性标记的番泻苷B在大鼠体内的清除率为0.065±0.007升/小时/千克。

The clearance of radiolabelled intravenous sennoside B in rats was 0.065±0.007L/h/kg.

来源:DrugBank

安全信息

• WGK Germany：
  3

制备方法与用途

理化性质

番泻苷是从番泻叶中提取的番泻苷甲（Sennoside A）与乙（Sennoside B）的钙盐等量混合物，也可以直接使用番泻叶。该物质对大肠壁具有刺激作用，反射性地增加其蠕动，从而引起排便。适用于治疗便秘，尤其适合在服用驱虫药后需要导泻的情况。

文献信息

• [EN] PHOSPHAMIDE DERIVATIVE, METHOD FOR MANUFACTURING THE SAME, AND USES THEREOF<br/>[FR] DÉRIVÉ DE PHOSPHAMIDE, SON PROCÉDÉ DE FABRICATION ET SES UTILISATIONS<br/>[ZH] 一种磷酰胺衍生物及制备方法和用途
  申请人：SICHUAN HAISCO PHARMACEUTICAL CO LTD

  公开号：WO2017133517A1

  公开（公告）日：2017-08-10

  公开了一种磷酰胺衍生物及制备方法和用途。特别公开了一种通式(I)所示化合物及其药学上可接受的盐或立体异构体 (I)，其中，G、L、Q、s如说明书中所定义。