蓖麻油酸 | 141-22-0

• 物质功能分类: 化学试剂 - 有机试剂 - 脂肪酸
• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 中文名称: 蓖麻油酸
• 中文别名: 顺式-12-羟基十八碳烯-9-酸；12-羟油酸；(R)-12-羟基-顺-9-十八烯酸；蓖麻酸；12-羟基-9-十八烯酸
• 英文名称: Ricinoleic acid
• 英文别名: (Z,12R)-12-hydroxyoctadec-9-enoic acid
• CAS: 141-22-0
• 化学式: C₁₈H₃₄O₃
• 分子量: 298.466
• InChiKey: WBHHMMIMDMUBKC-QJWNTBNXSA-N

物化性质

• 熔点：
  22.5-24.5℃
• 比旋光度：
  D22 +6.67°; D26 +7.15° (c = 5 in acetone)
• 沸点：
  bp10 245°
• 密度：
  0.940 g/mL at 20 °C(lit.)
• 闪点：
  248°C
• 溶解度：
  乙醇
• LogP：
  5.607 (est)
• 物理描述：
  Liquid
• 颜色/状态：
  Colorless to yellow viscous liquid
• 蒸汽压力：
  4.49X10-3 mm Hg at 25 °C (est)
• 粘度：
  400 cSt at 25 °C
• 折光率：
  Specific optical rotation: +6.67 deg at 22 °C/D; +7.15 deg at 26 °C/D (C = 5 in acetone); index of refraction: 1.4716 at 20 °C/D
• 解离常数：
  pKa = 4.74 (est)
• 保留指数：
  2351.8

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  21
• 可旋转键数：
  15
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  57.5
• 氢给体数：
  2
• 氢受体数：
  3

ADMET

代谢

给三名健康受试者口服了蓖麻油（10到15毫升）。在给药后2到8小时内收集尿液。尿液中排泄出了以下三种环氧二羧酸：3,6-环氧辛二酸；3,6-环氧癸二酸；以及3,6-环氧十二烷二酸。这三种蓖麻酸代谢物在大鼠尿液中也有检测到...

Three healthy subjects /were/ administered castor oil (10 to 15 mL) orally. Urine was collected between 2 and 8 hr post dosing. The following three epoxydicarboxylic acids were excreted in the urine: 3,6-epoxyoctanedioic acid; 3,6-epoxydecanedioic acid; and 3,6-epoxydodecanedioic acid. These three ricinoleic acid metabolites were also detected in the urine of rats...

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

蓖麻油酸（RA）与机械切削液和其他工业配方中的许多成分一样，可能是潜在的皮肤刺激物，然而关于其透过皮肤的能力却知之甚少。将3H-蓖麻油酸与三种常用的切削液添加剂混合，分别是三嗪（TRI）、线性烷基苯磺酸盐（LAS）和三乙醇胺（TEA），然后作为水包油（MO）或聚乙二醇（PEG）混合物在体外应用于惰性硅橡胶膜和猪皮上。这些添加剂显著降低了蓖麻油酸从配方中分配到角质层（SC）的能力，尤其是在基于PEG的混合物中。除了LAS之外，所有其他添加剂都产生了更偏碱性的配方（pH = 9.3-10.3）。在硅橡胶膜和猪皮上，单独添加剂或添加剂组合显著降低了蓖麻油酸的渗透性。这两种膜中蓖麻油酸处置的趋势表明，混合物的相互作用更多是物理化学性质，可能不涉及化学诱导的生物膜变化，这种变化可能会在接触潜在刺激物配方时被假设发生。

Ricinoleic acid (RA) like many of the ingredients in machine cutting fluids and other industrial formulations are potential dermal irritants, yet very little is known about its permeability in skin. 3H-ricinoleic acid mixtures were formulated with three commonly used cutting fluid additives; namely, triazine (TRI), linear alkylbenzene sulfonate (LAS), and triethanolamine (TEA) and topically applied to inert silastic membranes and porcine skin in vitro as aqueous mineral oil (MO) or polyethylene glycol (PEG) mixtures. These additives significantly decreased ricinoleic acid partitioning from the formulation into the stratum corneum (SC) in PEG-based mixtures. Except for LAS, all other additives produced a more basic formulation (pH = 9.3-10.3). In silastic membranes and porcine skin, individual additives or combination of additives significantly reduced ricinoleic permeability. This trend in ricinoleic acid disposition in both membranes suggests that the mixture interaction is more physicochemical in nature and probably not related to the chemical-induced changes in the biological membrane as may be assumed with topical exposures to potentially irritant formulations.

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)

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，协助通气。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……。预期癫痫发作，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，如果患者能够吞咽、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

/人类暴露研究/ 202名连续患者（182名女性，20名男性）患有湿疹性唇炎，他们在1996年1月至1999年12月期间参加了新加坡的接触性和职业性皮肤病的诊所，并接受了斑贴测试。女性和男性患者的平均年龄分别为31.1岁和28.8岁。斑贴测试是按照国际接触性皮炎研究小组（ICDRG）的建议进行的。29名患者（2名男性，27名女性）对蓖麻酸产生了阳性反应。在29个反应中，有22个被认为是相关的阳性反应。

/HUMAN EXPOSURE STUDIES/ 202 consecutive patients (182 females, 20 males) with eczematous cheilitis who attended a contact and occupational dermatoses clinic in Singapore between January of 1996 and December of 1999 were patch-tested. Mean ages for female and male patients were 31.1 and 28.8 years, respectively. Patch tests were conducted according to International Contact Dermatitis Research Group (ICDRG) recommendations. Twenty-nine patients (2 males, 27 females) had positive reactions to ricinoleic acid. Of the 29 reactions, 22 were considered relevant positives.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

蓖麻油酸或甲基蓖麻油酸通过胃管给药给体重至少400克的雄性大鼠，这些大鼠的胸导管插有管子。收集了48小时的淋巴液，然后提取并分离出各种脂质类别。结果表明，蓖麻油酸存在于甘油三酯、甘油二酯、甘油一酯和游离脂肪酸部分。蓖麻油酸的最大吸收发生在给药后30分钟内。淋巴脂质中的磷脂或胆固醇酯部分没有蓖麻油酸。

Ricinoleic acid or methyl ricinoleate was administered via gastric intubation to male rats (minimum weight of 400 g) with a cannulated thoracic duct. Lymph was collected for 48 hr, and the lipids were then extracted and separated into various lipid classes. Results indicated that Ricinoleic acid was present in the triglyceride, diglyceride, monoglyceride, and free fatty acid fractions. Peak absorption of ricinoleic acid occurrred within 30 min post administration. Ricinoleic acid was not present in the phospholipid or cholesterol ester fractions of the lymph lipids.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

为了提高蓖麻酸在体内的荧光性，本研究向蓖麻酸中添加了甲基安息香酸或甲基胆蒽，比例为1：99。实验物质被温和地涂抹在已经剃毛的皮肤上。在涂抹后不同时间点进行了活组织切片检查。使用带有石英聚光镜的斯宾塞显微镜观察了样本。蓖麻酸主要保留在表皮的外层。在涂抹后2小时取的活检中，几乎没有证据表明有更深的渗透。

The skin penetration of ricinoleic acid in vivo /was investigated/ using rats that were 20 to 30 days old. In order to increase the fluorescence of ricinoleic acid, either one part of methyl anthranilate or methylcholanthrene was added to 99 parts ricinoleic acid. The test substance was gently rubbed on to skin that had been clipped free of hair. Biopsies were taken at various intervals post application. The preparations were observed using a Spencer microscope with a quartz condenser. Ricinoleic acid was retained mainly in the outer strata of the epidermis. There was little evidence of deeper penetration in biopsies that were taken at 2 hr post application.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

使用Bronaugh流通扩散细胞系统，评估了标记有放射性同位素（^3H）的ricinoleic酸（比活性=20.0 mCi/mmol）混合物通过猪皮膜或硅橡胶（聚二甲基硅氧烷）膜的经皮吸收。在水中制备了含有5%矿物油或5%PEG 200的^3H标记的ricinoleic酸（5%）混合物。其他^3H标记的ricinoleic酸混合物采用了以下三种常用的切削液添加剂：三嗪、线性烷基苯磺酸盐和三乙醇胺。在局部暴露8小时后，ricinoleic酸的吸收（基于受体液中回收的量）在硅橡胶膜中从1%到13%，在猪皮膜中从0.1%到0.3%。对于大多数混合物，ricinoleic酸的吸收峰出现在3小时内。在两种膜中，含有PEG的控制混合物与ricinoleic酸的最高峰浓度相关。

The percutaneous absorption of a radiolabeled (3H)ricinoleic acid (specific activity = 20.0 mCi/mmol) mixture was evaluated using porcine skin membranes or silastic (polydimethylsioloxane) membranes in the Bronaugh flow-through diffusion cell system. [3H]Ricinoleic acid (5%) mixtures were prepared in water containing either 5% mineral oil or 5% PEG 200. Other (3H)Ricinoleic acid mixtures were formulated with the following three commonly used cutting fluid additives: triazine, linear alkylbenzene sulfonate, and triethanolamine. At 8 hr after topical exposure, Ricinoleic acid absorption (based on amount recovered in receptor fluid) ranged from 1% to 13% in silastic membranes and 0.1% to 0.3% in porcine skin membranes. For most mixtures, peak absorption of ricinoleic acid occurred within 3 hr. The greatest ricinoleic acid peak concentrations were associated with the control mixtures containing PEG in both membranes.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

调查人员在两个实验中研究了在大鼠被喂食麻酸后在脂肪库中羟基酸的积累情况。在第一个实验中，成年雄性大鼠（数量、品系和体重未说明）被喂食麻酸（5%乳液，20毫升）7天。在第二个实验中，动物被喂食了27天。从脂肪组织中提取脂质后，通过水解得到一种脂肪酸混合物。气液色谱图显示，与麻酸链长较短的以下羟基脂肪酸含量显著：10-羟基十六碳烯酸（实验1：占总脂肪酸的0.60%；实验2：占总脂肪酸的0.33%），8-羟基十四碳烯酸（实验1：占总脂肪酸的0.03%；实验2：占总脂肪酸的0.08%），以及6-羟基十二碳烯酸（实验2：占总脂肪酸的0.03%）。麻酸在实验1中占总脂肪酸的0.51%，在实验2中占总脂肪酸的3.85%。

/Investigators/ studied the accumulation of hydroxyl acids in depot fat after rats were fed with ricinoleic acid in two experiments. In the first experiment, adult male rats (number, strain, and weights not stated) were fed ricinoleic acid (5% emulsion, 20 mL) for 7 days. In the second experiment, the animals were fed for 27 days. Lipid extraction from the fat tissue was followed by hydrolysis to yield a fatty acid mixture. A gas-liquid chromatogram indicated appreciable amounts of the following hydroxy fatty acids with shorter chain lengths than ricinoleic acid: 10-hydroxyhexadecenoic acid (experiment 1: 0.60% of total fatty acids; experiment 2: 0.33% of total fatty acids), 8-hydroxytetradecenoic acid (experiment 1: 0.03% of total fatty acids; experiment 2: 0.08% of total fatty acids), and 6-hydroxydodecenoic acid (experiment 2: 0.03% of total fatty acids). Ricinoleic acid comprised 0.51% of total fatty acids in experiment 1 and 3.85% of total fatty acids in experiment 2.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险品标志：
  Xi
• 安全说明：
  S26,S36
• 危险类别码：
  R36/37/38
• WGK Germany：
  3
• 海关编码：
  29181990
• 危险品运输编号：
  NONH for all modes of transport
• RTECS号：
  VJ3150000
• 危险标志：
  GHS07
• 危险性描述：
  H315,H319,H335
• 危险性防范说明：
  P261,P305 + P351 + P338

制备方法与用途

作用

蓖麻油酸具有镇痛和抗炎作用，并可特异性激活前列腺素E2的EP3前列腺素受体。

简介

Ricinoleic acid 主要来源于蓖麻油 (Ricinus communis) 种子油，是一种具有广泛应用价值的羟基脂肪酸。它不仅是生产高性能润滑剂、化妆品、聚合物、表面活性剂和涂料的重要原料，还在工业上发挥着重要作用。

用途

Ricinoleic acid 广泛用于制备表面活性剂、增塑剂及润滑油添加剂，并可作为合成癸二酸和庚酸的原料。

反应信息

• 作为反应物：
  描述：

  蓖麻油酸 在 potassium permanganate 、 水 、 potassium hydroxide 、 硫酸 作用下， 以 水 为溶剂， 反应 2.0h， 生成 壬二酸
  参考文献：
  名称：

  [EN] PROCESS FOR PREPARATION OF AZELAIC ACID
  [FR] PROCÉDÉ DE PRÉPARATION D'ACIDE AZÉLAÏQUE

  摘要：

  提供了一种制备癸二酸的过程。

  公开号：

  WO2016067160A1
• 作为产物：
  描述：

  O-乙酰基蓖麻酸甲酯 在 lithium hydroxide 、 水 作用下， 以 四氢呋喃 为溶剂， 反应 6.0h， 以83%的产率得到蓖麻油酸
  参考文献：
  名称：

  BoC₂O Mediated Macrolactonisation: Syntheses of R-(+)-Ricinoleic Acid Lactone and (±)-12-OH-Stearic Acid Lactone

  摘要：

  An efficient chemoenzymatic synthesis of R-(+)-ricinoleic acid lactone and (+/-)-12-OH-stearic acid lactone using Boc(2)O mediated macrolactonisation is reported.

  DOI：

  10.1080/00397919908086253

文献信息

• [EN] QUINOLINE AND QUINAZOLINE COMPOUNDS<br/>[FR] COMPOSÉS QUINOLÉINE ET QUINAZOLINE
  申请人：ACERTA PHARMA BV

  公开号：WO2016055982A1

  公开（公告）日：2016-04-14

  In some embodiments, the invention relates to quinazoline and quinoline compounds of Formula I: (I) or a pharmaceutically acceptable salt thereof, or to pharmaceutical compositions comprising these compounds and to their use in therapy. In particular, in some embodiments, the present invention relates to quinazoline and quinoline compounds, pharmaceutical compositions thereof, and the use of the compounds and pharmaceutical compositions in the treatment of Bruton's tyrosine kinase (BTK) mediated disorders.

  在某些实施例中，该发明涉及式I的喹唑啉和喹啉化合物：(I)或其药用可接受盐，或者涉及包含这些化合物的药物组合物以及它们在治疗中的应用。具体而言，在某些实施例中，本发明涉及喹唑啉和喹啉化合物、其药物组合物以及这些化合物和药物组合物在治疗布鲁顿氨基酸激酶（BTK）介导的疾病中的应用。
• Bna Conjugates and Methods of Use
  申请人：James Kenneth D.

  公开号：US20080207505A1

  公开（公告）日：2008-08-28

  Modified natriuretic compounds and conjugates thereof are disclosed in the present invention. In particular, conjugated forms of hBNP are provided that include at least one modifying moiety attached thereto. The modified natriuretic compound conjugates retain activity for stimulating cGMP production, binding to NPR-A receptor, decreasing arterial blood pressure and in some embodiments an improved half-life in circulation as compared to unmodified counterpart natriuretic compounds. Oral, parenteral, enteral, subcutaneous, pulmonary, and intravenous forms of the compounds and conjugates may be prepared as treatments and/or therapies for heart conditions particularly congestive heart failure. Modifying moieties comprising oligomeric structures having a variety of lengths and configurations are also disclosed. Analogs of the hBNP compound are also disclosed, having an amino acid sequence that is other than the native sequence.

  本发明公开了改性利钠肽化合物及其共轭物。具体而言，提供了至少连接有一个修饰基团的hBNP的共轭形式。这些改性利钠肽化合物共轭物保留了刺激cGMP产生、结合NPR-A受体、降低动脉血压以及在某些实施例中相对于未经改性的对应利钠肽化合物具有改善的循环半衰期的活性。这些化合物和共轭物的口服、静脉注射、肠内、皮下、肺部和静脉形式可作为治疗和/或治疗心脏病症，特别是充血性心力衰竭的治疗。还公开了包含具有各种长度和构型的寡聚结构的修饰基团。此外，还公开了hBNP化合物的类似物，其氨基酸序列与天然序列不同。
• UNSATURATED FATTY ACID MONOESTERS AND DIESTERS ON ASCORBIC ACID AND COSMETIC USES THEREOF
  申请人：Poigny Stéphane

  公开号：US20120076744A1

  公开（公告）日：2012-03-29

  The present invention relates to a compound with the following general formula (I): in which: R 1 is a hydrocarbon chain of an unsaturated fatty acid from C 12 to C 24 including at least one unsaturation; and R 2 and R 3 are, independently or simultaneously: a hydrogen or a C 1 -C 3 alkyl or a phenyl; and R 4 : a hydrogen atom or COR 1′ , where R 1′ is a hydrocarbon chain of an unsaturated fatty acid from C 12 to C 24 including at least one unsaturation, advantageously 1 to 6 and preferably 1 to 4.

  本发明涉及具有以下一般式（I）的化合物： 其中：R1是来自C12到C24的不饱和脂肪酸的烃链，包括至少一个不饱和度；而R2和R3是独立或同时的：氢或C1-C3烷基或苯基；而R4：氢原子或COR1'，其中R1'是来自C12到C24的不饱和脂肪酸的烃链，有利地为1到6，优选为1到4。
• [EN] HETEROAROMATIC AND HETEROBICYCLIC AROMATIC DERIVATIVES FOR THE TREATMENT OF FERROPTOSIS-RELATED DISORDERS<br/>[FR] DÉRIVÉS AROMATIQUES HÉTÉROBICYCLIQUES ET HÉTÉROAROMATIQUES POUR LE TRAITEMENT DE TROUBLES LIÉS À LA FERROPTOSE
  申请人：COLLABORATIVE MEDICINAL DEV LLC

  公开号：WO2020185738A1

  公开（公告）日：2020-09-17

  The present application discloses heteroaromatic and heterobicyclic aromatic derivative compounds and compositions, and methods for treating ferroptosis-related disorders and diseases in patients using the compounds and compositions as disclosed herein.

  本申请公开了杂芳和杂双环芳香衍生物化合物和组合物，以及利用所公开的化合物和组合物治疗患者的铁死亡相关疾病和疾病的方法。
• [EN] LYMPHATIC SYSTEM-DIRECTING LIPID PRODRUGS<br/>[FR] PROMÉDICAMENTS LIPIDIQUES ORIENTANT VERS LE SYSTÈME LYMPHATIQUE
  申请人：ARIYA THERAPEUTICS INC

  公开号：WO2019046491A1

  公开（公告）日：2019-03-07

  The present invention provides lymphatic system-directing lipid prodrugs, pharmaceutical compositions thereof, methods of producing such prodrugs and compositions, as well as methods of improving the bioavailability or other properties of a therapeutic agent that comprises part of the lipid prodrug. The present invention also provides methods of treating a disease, disorder, or condition such as those disclosed herein, comprising administering to a patient in need thereof a provided lipid prodrug or a pharmaceutical composition thereof.

  本发明提供了淋巴系统定向脂质前药，其制药组合物，制备这种前药和组合物的方法，以及改善作为脂质前药一部分的治疗剂的生物利用度或其他性质的方法。本发明还提供了治疗疾病、紊乱或症状的方法，包括向需要的患者施用所提供的脂质前药或其制药组合物。

表征谱图