Oxymatrine | 16837-52-8

• 物质功能分类: 原料药 - 人工合成抗感染类药 - 天然来源抗感染药
• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 羽扇豆生物碱
• 英文名称: Oxymatrine
• 英文别名: OMT；ammothamnine；(1R,2R,9S,13R,17S)-13-oxido-7-aza-13-azoniatetracyclo[7.7.1.02,7.013,17]heptadecan-6-one
• CAS: 16837-52-8
• 化学式: C₁₅H₂₄N₂O₂
• 分子量: 264.368
• InChiKey: XVPBINOPNYFXID-JARXUMMXSA-N

物化性质

• 熔点：
  208℃
• 溶解度：
  可溶于甲醇：10mg/mL，澄清，无色
• 颜色/状态：
  White to off-white powder
• 气味：
  Slight amber aroma
• 蒸汽压力：
  8.75X10-11 mm Hg at 25 °C (est)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  19
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.93
• 拓扑面积：
  38.4
• 氢给体数：
  0
• 氢受体数：
  2

ADMET

毒理性

• 相互作用

当归（Oliv.）Diels和白芍药（Ait.）在传统中医中被广泛用于治疗炎症性疾病，如痤疮、心脏病和肝炎。阿魏酸钠（SF）和苦参碱（OMT）分别是当归（Oliv.）Diels和白芍药（Ait.）的有效成分。在本研究中，作者研究了SF和OMT联合使用的协同抗炎效果，以及它们对RAW 264.7细胞中炎症相关介质的调节作用。在体内，通过二甲苯诱导的小鼠耳肿胀模型和角叉菜胶诱导的大鼠足肿胀模型评估了SF和OMT联合使用的抗炎效果。在体外，通过实时PCR（RT-PCR）微阵列分析确定脂多糖（LPS）激活的RAW 264.7细胞中趋化因子和细胞因子的mRNA表达。通过酶联免疫吸附试验（ELISA）测量LPS刺激的RAW 264.7细胞上清液中白细胞介素-11（IL-11）、C反应蛋白（CRP）和干扰素-γ（INF-γ）的水平。SF和OMT联合使用可以显著抑制二甲苯诱导的小鼠耳肿胀和角叉菜胶诱导的大鼠足肿胀，而单独使用上述剂量的每种药物时没有发现效果。联合使用在下调LPS刺激的RAW 264.7细胞中炎症相关介质的mRNA表达方面比单独使用SF或OMT更有效。ELISA结果显示，联合使用以剂量依赖性方式协同抑制LPS诱导的IL-11、CRP和INF-γ的产生。SF和OMT联合使用显示出协同抗炎效果，其活性可能与对炎症相关介质的调节作用有关，尤其是IL-11、CRP和INF-γ。

The combination of Radix Angelicae sinensis (Oliv.) Diels and Radix Sophora flavescens Ait. was extensively used in traditional Chinese medicine to treat inflammatory diseases, such as acne, heart disease, and hepatitis. Sodium ferulate (SF) and oxymatrine (OMT) were effective component of Radix Angelicae sinensis (Oliv.) Diels and Radix Sophora flavescens Ait., respectively. In this study, /the authors/ investigated the synergistic anti-inflammatory effect of the combination of SF and OMT, and its modulation on inflammation-associated mediators in RAW 264.7 cells. In vivo, the anti-inflammatory effects of the combination of SF and OMT were evaluated with the xylene-induced mouse ear edema model and the carrageenan-induced rat paw edema model. In vitro, chemokines and cytokines mRNA expressions in lipopolysaccharide (LPS)-activated RAW 264.7 cells were determined by real-time PCR (RT-PCR) microarray analysis. The levels of interleukin-11 (IL-11), C-reactive protein (CRP) and interferon-gamma (INF-gamma) in the supernatant of LPS-stimulated RAW 264.7 cells were measured by enzyme-linked immune-sorbent assay (ELISA). The combination of SF and OMT could significantly inhibit the edema in the xylene-induced mouse ear edema and carrageenan-induced rat paw edema, but no effect was found when each drug was used alone according to above doses. The combination exhibited a better effect in down-regulating mRNA expressions of inflammation-associated mediators in LPS-stimulated RAW 264.7 cells than SF or OMT alone. The ELISA results showed that the combination synergistically inhibited LPS-induced IL-11, CRP and INF-gamma production in a dose-dependent manner. The combination of SF and OMT showed synergistic anti-inflammatory effect, and the activity was probably related to its modulation on inflammation-associated mediators, especially IL-11, CRP and INF-gamma.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

sodium ferulate (SF) 和氧化苦参碱（OMT）是从中药中提取的化合物，多年来分别在中国用于临床治疗心脏病和肝病。本研究的目的是探讨SF和OMT联合治疗的镇痛效果及其机制。通过应用乙酸扭体试验和福尔马林试验的动物疼痛模型，SF和OMT的联合使用显示出剂量依赖性的显著镇痛效果。在体外，联合治疗抑制了辣椒素在背根神经节神经元上引起的细胞内钙浓度增加。重要的是，通过全细胞膜片钳技术，证明了SF和OMT对辣椒素诱导的电流具有协同抑制效果。我们的结果提示，SF和OMT引起了显著的镇痛效果，这可能与它们对瞬时受体电位香草酸-1的协同抑制有关。

Sodium ferulate (SF) and Oxymatrine (OMT) were compounds extracted from Chinese herbs, and have been used in clinical treatment of heart and hepatic diseases, respectively, in China for many years. The objective of this study was to examine the analgesic effect and the mechanism of the combined treatment of SF and OMT. Using the animal pain models by applying Acetic Acid Writhing Test and Formalin Test, the combination of SF and OMT showed significant analgesic effect in dose-dependent manner. In vitro, the combined treatment inhibited the increase in intracellular calcium concentration evoked by capsaicin in the dorsal root ganglion neurons. Importantly, a synergistic inhibitory effect of SF and OMT on the capsaicin-induced currents was demonstrated by whole-cell patch-clamp. Our results suggest that SF and OMT cause significant analgesic effect which may be related to the synergistic inhibition of transient receptor potential vanilloid-1.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

这项研究的目的是为了探讨氧化苦参碱-黄芩苷联合物（OB）对2.2.15细胞中乙型肝炎病毒（HBV）复制以及HSC-T6细胞中α平滑肌肌动蛋白（αSMA）表达和I型胶原合成的影响。2.2.15细胞和HSC-T6细胞分别培养并给予处理。通过酶联免疫吸附试验（ELISA）检测培养上清中的HBsAg和HBeAg，并利用荧光定量PCR测定HBV DNA水平。从HSC-T6细胞中提取总RNA并逆转录成cDNA，通过PCR扩增cDNA，并以β肌动蛋白的比例表示其量。从HSC-T6细胞中提取的总细胞蛋白通过电泳分离，然后将解析的蛋白电转移至硝酸纤维素膜上。通过显色显示出蛋白条带，并以β肌动蛋白进行校正。在2.2.15细胞培养系统中，OB组对HBsAg和HBeAg分泌的抑制率显著高于氧化苦参碱组（HBsAg，P = 0.043；HBeAg，P = 0.026）；OB组的HBV DNA水平显著低于氧化苦参碱组（P = 0.041）。在HSC-T6细胞中，OB组的αSMA的mRNA和蛋白表达水平显著低于氧化苦参碱组（mRNA，P = 0.013；蛋白，P = 0.042）；I型胶原的mRNA和蛋白表达水平在OB组也显著低于氧化苦参碱组（mRNA，P < 0.01；蛋白，P < 0.01）。作者们得出结论，与氧化苦参碱相比，OB联合物在体外对2.2.15细胞中HBV复制具有更好的抑制作用，并且对HSC-T6细胞中αSMA表达和I型胶原合成更加有效。

/The aim of this was/ to study the effect of oxymatrine-baicalin combination (OB) against HBV replication in 2.2.15 cells and alpha smooth muscle actin (alpha SMA) expression, type I, collagen synthesis in HSC-T6 cells. The 2.2.15 cells and HSC-T6 cells were cultured and treated respectively. HBsAg and HBeAg in the culture supernatants were detected by ELISA and HBV DNA levels were determined by fluorescence quantitative PCR. Total RNA was extracted from HSC-T6 cells and reverse transcribed into cDNA. The cDNAs were amplified by PCR and the quantities were expressed in proportion to beta actin. The total cellular proteins extracted from HSC-T6 cells were separated by electrophoresis. Resolved proteins were electrophoretically transferred to nitrocellulose membrane. Protein bands were revealed and the quantities were corrected by beta actin. In the 2.2.15 cell culture system, the inhibitory rate against secretion of HBsAg and HBeAg in the OB group was significantly stronger than that in the oxymatrine group (HBsAg, P = 0.043; HBeAg, P = 0.026; respectively); HBV DNA level in the OB group was significantly lower than that in the oxymatrine group (P = 0.041). In HSC-T6 cells the mRNA and protein expression levels of alpha SMA in the OB group were significantly lower as compared with those in the oxymatrine group (mRNA, P = 0.013; protein, P = 0.042; respectively); The mRNA and protein expression levels of type I collagen in the OB group were significantly lower as compared with those in the oxymatrine group (mRNA, P < 0.01; protein, P < 0.01; respectively). /The authors concluded that/ OB combination has a better effect against HBV replication in 2.2.15 cells and is more effective against alpha SMA expression and type I collagen synthesis in HSC-T6 cells than oxymatrine in vitro.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

苦参碱已被证实能够保护肝脏、肠道和心脏免受缺血和再灌注损伤，这种效果是通过抗炎和抗凋亡实现的。作者们因此调查了苦参碱在大脑缺血损伤中的潜在神经保护作用及其作用机制。雄性Sprague-Dawley大鼠被随机分配到四个组：永久性大脑中动脉闭塞（pMCAO），高剂量（pMCAO+苦参碱120 mg/kg），低剂量（pMCAO+苦参碱60 mg/kg）和假手术组。作者们使用永久性大脑中动脉闭塞模型，在大脑缺血后立即腹腔注射苦参碱，并在随后几天每天给药一次。在MCAO后24小时，使用改良的六点量表评估神经缺陷；测量脑水分含量；通过免疫组化、Western印迹和RT-PCR测量NF-kappaB表达。在72小时时使用2,3,5-三苯基四氮唑氯化物（TTC）染色分析梗死体积。与pMCAO组相比，高剂量组的神经缺陷有所改善（P < 0.05），梗死体积减少（P < 0.001）和脑水肿减轻（P < 0.05）。与这些指标一致，免疫组化、Western印迹和RT-PCR分析表明高剂量组中NF-kappaB表达显著降低。低剂量的苦参碱对pMCAO大鼠的NF-kappaB表达没有影响。苦参碱减少了由pMCAO诱导的梗死体积，这种效果可能是通过降低NF-kappaB表达实现的。

Oxymatrine is proven to protect ischemic and reperfusion injury in liver, intestine and heart, this effect is via anti-inflammation and anti-apoptosis. Whether this protective effect applies to ischemic injury in brain, /the authors/ therefore investigate the potential neuroprotective role of oxymatrine and the underlying mechanisms. Male, Sprague-Dawley rats were randomly assigned to four groups: permanent middle cerebral artery occlusion (pMCAO), high dose (pMCAO+oxymatrine 120 mg/kg), low dose (pMCAO+oxymatrine 60 mg/kg) and sham operated group. /The authors/ used a permanent middle cerebral artery occlusion model and administered oxymatrine intraperitoneally immediately after cerebral ischemia and once daily on the following days. At 24 hr after MCAO, neurological deficit was evaluated using a modified six point scale; brain water content was measured; NF-kappaB expression was measured by immunohistochemistry, Western blotting and RT-PCR. Infarct volume was analyzed with 2, 3, 5-triphenyltetrazolium chloride (TTC) staining at 72 hr. Compared with pMCAO group, neurological deficit in high dose group was improved (P < 0.05), infarct volume was decreased (P < 0.001) and cerebral edema was alleviated (P < 0.05). Consistent with these indices, immunohistochemistry, Western blot and RT-PCR analysis indicated that NF-kappaB expression was significantly decreased in high dose group. Low dose of oxymatrine did not affect NF-kappaB expression in pMCAO rats. Oxymatrine reduced infarct volume induced by pMCAO, this effect may be through the decreasing of NF-kappaB expression.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 立即急救：确保已经进行了充分的中毒物清除。如果患者停止呼吸，开始人工呼吸，最好使用需求阀复苏器、袋阀面罩装置或口袋面罩，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。如果发生呕吐，让患者前倾或置于左侧（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。寻求医疗帮助。 /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)

安全信息

• 危险品标志：
  Xn
• 安全说明：
  S24/25
• 危险类别码：
  R22,R20/22
• WGK Germany：
  3
• 海关编码：
  29399990
• 危险品运输编号：
  NONH for all modes of transport

制备方法与用途

天然生物碱——氧化苦参碱（oxymatrine）是一种广泛存在于豆科槐属植物中的天然生物碱，主要存在于苦参（Sophora flavescens Ait.）、越南槐（S. tonkinensis Gagnep）和白刺花（S. viciifolia Hance）中。氧化苦参碱属于喹诺里西啶类生物碱，具有广泛的生物活性，如抗炎、抗肿瘤、镇痛、调节心率、镇咳和杀菌等作用。

其氮原子以配位键与氧结合，研究表明，在某些条件下，氧化苦参碱可转化为苦参碱。此外，这类生物碱还广泛应用于农业，用于防治松毛虫、茶毛虫、菜青虫等多种害虫，并具有杀虫、杀菌及调节植物生长等功能。

性质

• 外观：白色结晶性粉末；气微，味苦。

应用

• 苦参素被广泛应用于医药、农药和兽药等领域。它具有抗肿瘤、抗菌、抗寄生虫、抗炎、消肿利尿及减轻环磷酰胺引起的白细胞减少等作用。在抗肿瘤方面，氧化苦参碱能够降低谷-丙转氨酶水平，并有助于治疗慢性乙型肝炎（CHB），调节机体免疫状态和改善肝功能。

生物活性

• 氧化苦参碱是一种从Sophora flavescens的根部分离出的喹唑啉生物碱，具有抗炎症、抗纤维化及抗肿瘤活性。它能抑制iNOS表达并阻断TGF-β/Smad通路，用于治疗病毒性肝炎、癌症、病毒性心肌炎和皮肤疾病（如阴道炎、银屑病和湿疹）。

体外研究

• 氧化苦参碱能够保护小鼠免受GalN/LPS诱导的爆发性肝炎，并通过下调肝脏中血清肿瘤坏死因子α的产生及Fas和Fas配体的表达，抑制肝细胞凋亡及其随后的坏死。此外，它还表现出对乙型肝炎病毒的体外抗作用。

体内研究

• 氧化苦参碱的半数致死剂量（LD50）为小鼠腹腔注射521毫克/千克、静脉注射150毫克/公斤。

化学性质

• 外观：无色块状结晶，易溶于氯仿和甲醇，难溶于石油醚和丙酮。来源于山豆根及苦参。

用途

• 主要用于含量测定、鉴定以及药理实验等。具有利尿作用，并对肺癌和胃癌细胞诱导的血管内皮细胞增殖有抑制作用。

类别

• 毒性：属于有毒物质，属中毒类。
• 急性毒性：
  • 腹腔注射小鼠 LD50：521 毫克/公斤；
  • 静脉注射小鼠 LD50: 150 毫克/公斤。

危险特性

• 可燃性：可燃；火场分解产生有毒氮氧化物烟雾。
• 储运特性：库房低温通风、干燥保存。

灭火剂

• 可用水、二氧化碳、干粉或砂土进行灭火。

反应信息

• 作为反应物：
  描述：

  Oxymatrine 在 一水合肼 作用下， 以 乙醇 、 水 为溶剂， 反应 48.0h， 以409.5 g的产率得到苦参碱
  参考文献：
  名称：

  一种利用转移氢化法由氧化苦参碱制备苦参碱的方法

  摘要：

  本发明涉及一种利用转移氢化法由氧化苦参碱制备苦参碱的方法，属于天然药物化学技术领域。该方法是先向氧化苦参碱的极性溶液中加入氢源和催化剂，于40℃‑100℃回流5小时‑48小时；减压浓缩至50℃热测相对密度为1.02‑1.06；浓缩液采用极性2.0‑4.5的不溶于水的有机溶剂进行萃取；萃取液经蒸发、结晶、离心分离、干燥，得到白色晶体苦参碱。本发明工艺方法操作简便，成本低廉，适合工业化生产；可以避免产生金属还原法带来的固体废弃物对环境造成的污染，环保效益显著；采用固体催化剂，反应后易于从反应体系中分离；采用本发明适用的氢源，反应中除了目标产物，其它产物都是气体，随时从体系中溢出，提高反应效率。

  公开号：

  CN112047946A

文献信息

• 一种葡萄糖醛酸或葡醛内酯与苦参碱和/或苦参素形成的复盐的制备方法及用途
  申请人：刘兆平

  公开号：CN108997449A

  公开（公告）日：2018-12-14

  本发明公开了一种由葡萄糖醛酸或葡醛内酯与苦参素和/或苦参碱形成的复盐的制备方法，具体步骤如下：将葡萄糖醛酸或葡醛内酯与苦参素和/或苦参碱的混合物中加入水和有机溶剂，在20～60℃水浴条件下搅拌回流至澄清；将获得的澄清液体在40～80℃下蒸发浓缩；将浓缩产物冷却冷藏后过滤，洗涤，真空干燥。本发明还公开了含有上述复盐及药学上可接受的辅料的药物组合物，用于治疗肝脏疾病。通过动物试验证明葡萄糖醛酸或葡醛内酯与苦参素和/或苦参碱具有协同增效作用，并且对动物体不具有毒害作用。
• Cocrystals of Oxymatrine: Reducing Hygroscopicity and Affecting the Dissolution Rate
  作者：Ming-Hui Qi、Heng Li、Bin Zhu、Minghuang Hong、Guo-Bin Ren

  DOI：10.1021/acs.cgd.1c00205

  日期：2021.7.7

  Oxymatrine (OMT) is mainly used for the treatment of hepatitis B. In this work, one anhydrous form and three hydrates of OMT are reported and their transformational relationship is clarified. It is revealed that OMT has high hygroscopicity and fast release characteristics. In order to improve these physical properties, cocrystallization of OMT was performed. Five cocrystals of OMT with urea (OMT-Urea-DH), sulfanilamide (OMT-SUA), theophylline (OMT-THP), 2-ketoglutaric acid (OMT-KTA-MH), and 3-hydroxy-2-naphthoic acid (OMT-HNA) were obtained and characterized. According to the DVS tests, OMT-SUA, OMT-KTA-MH, and OMT-HNA enhance the hydroscopic stability of OMT by forming new hydrogen bonds. The dissolution rate of OMT has been drastically reduced through cocrystallization with THP and HNA.

  本研究报告了 OMT 的一种无水物和三种水合物，并阐明了它们之间的转化关系。研究发现，OMT 具有高吸湿性和快速释放特性。为了改善这些物理特性，研究人员对 OMT 进行了共晶体化。获得了 OMT 与尿素（OMT-Urea-DH）、磺胺（OMT-SUA）、茶碱（OMT-THP）、2-酮戊二酸（OMT-KTA-MH）和 3-羟基-2-萘乙酸（OMT-HNA）的五种共晶体，并对其进行了表征。根据 DVS 试验，OMT-SUA、OMT-KTA-MH 和 OMT-HNA 通过形成新的氢键增强了 OMT 的水相稳定性。通过与 THP 和 HNA 共结晶，OMT 的溶解速率大大降低。
• An innovative extraction strategy for herbal medicine by adopting p‐sulphonatocalix[6]/[8]arenes
  作者：Xuan Yu、Teng‐hui Liang、Meng Wang、Xiao‐liang Ren、Zhen‐yu Zhou、Miao‐miao Jiang、De‐qin Zhang

  DOI：10.1002/pca.3160

  日期：2022.10

  Alkaloids exist in various herbal medicine widely and exhibit diverse biological and pharmacological activities. p-Sulphonatocalix[6]arenes (SC6A) and p-sulphonatocalix[8]arenes (SC8A) are water-soluble supramolecular macrocycles and are applied to the extraction of alkaloids from herbal products.

  生物碱广泛存在于各种草药中，具有多种生物和药理活性。p-Sulphonatocalix[6] 芳烃 (SC6A) 和 p-sulphonatocalix[8] 芳烃 (SC8A) 是水溶性超分子大环化合物，适用于从草药产品中提取生物碱。
• 一种利用转移氢化法由氧化苦参碱制备苦参碱的方法
  申请人：北方民族大学

  公开号：CN112047946A

  公开（公告）日：2020-12-08

  本发明涉及一种利用转移氢化法由氧化苦参碱制备苦参碱的方法，属于天然药物化学技术领域。该方法是先向氧化苦参碱的极性溶液中加入氢源和催化剂，于40℃‑100℃回流5小时‑48小时；减压浓缩至50℃热测相对密度为1.02‑1.06；浓缩液采用极性2.0‑4.5的不溶于水的有机溶剂进行萃取；萃取液经蒸发、结晶、离心分离、干燥，得到白色晶体苦参碱。本发明工艺方法操作简便，成本低廉，适合工业化生产；可以避免产生金属还原法带来的固体废弃物对环境造成的污染，环保效益显著；采用固体催化剂，反应后易于从反应体系中分离；采用本发明适用的氢源，反应中除了目标产物，其它产物都是气体，随时从体系中溢出，提高反应效率。