薄荷脑 | 1490-04-6

• 物质功能分类: 原料药 - 人工合成抗感染类药 - 消毒防腐药
• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 中文名称: 薄荷脑
• 英文名称: menthol
• 英文别名: DL-menthol；2-isopropyl-5-methylcyclohexan-1-ol；(±)-menthol；5-methyl-2-propan-2-ylcyclohexan-1-ol
• CAS: 1490-04-6
• 化学式: C₁₀H₂₀O
• mdl: MFCD00001484
• 分子量: 156.268
• InChiKey: NOOLISFMXDJSKH-UHFFFAOYSA-N

物化性质

• 熔点：
  34-36 °C(lit.)
• 沸点：
  216 °C(lit.)
• 密度：
  0.89 g/mL at 25 °C(lit.)
• 闪点：
  200 °F
• 溶解度：
  Very soluble in ethanol (95%), chloroform, ether, fatty oils and liquid paraffin; freely soluble in glacial acetic acid;soluble in acetone and benzene; very slightly soluble in glycerin; practically insoluble in water.
• 介电常数：
  3.2（Ambient）
• LogP：
  3.3-3.79 at 25℃
• 物理描述：
  D,l-menthol is a white crystalline solid with a peppermint odor and taste. (NTP, 1992)
• 颜色/状态：
  White crystals /89-78-1/
• 气味：
  Peppermint odor /dl-Menthol/
• 味道：
  Peppermint taste /dl-Menthol/
• 蒸汽密度：
  5.4 (NTP, 1992) (Relative to Air)
• 蒸汽压力：
  7.67X10-3 mm Hg at 25 °C (est)
• 稳定性/保质期：
  Stable under recommended storage conditions.
• 旋光度：
  Specific rotation: -45 to -51 deg (25 °C; l-menthol); -2 to +2 deg (dl-menthol) /89-78-1/
• 分解：
  When heated to decomposition it emits acrid smoke and irritating fumes.
• 折光率：
  Index of refraction: 1.4674 at 18 °C/D
• 保留指数：
  1158;1155;1161;1156;1152;1157;1157;1153;1152.8;1153;1160;1157;1154;1151;1169;1159;1156;1165.1;1157;1156;1159;1154;1154;1159

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  20.2
• 氢给体数：
  1
• 氢受体数：
  1

ADMET

代谢

在美国，除了薄荷醇之外，禁止使用香烟调味剂。薄荷醇的冷却效果可能促进烟草毒素的吸收。我们检查了美国吸食薄荷醇香烟和非薄荷醇香烟的吸烟者体内烟草暴露生物标志物的水平。我们研究了1999年至2010年参与国家健康和营养调查（NHANES）的4,603名白人、非裔美国人和墨西哥裔美国人当前吸烟者，这些吸烟者年龄在20岁或以上，并且有关于香烟类型和血清可替宁、血镉和血铅浓度的数据。在1,607名有可用测量的参与者中研究了尿液总4-(甲基亚硝胺基)-1-(3-吡啶基)-1-丁醇 (NNAL)。共有3,210名（74.3%）参与者吸食非薄荷醇香烟，而1,393名（25.7%）参与者吸食薄荷醇香烟。与非薄荷醇香烟吸烟者相比，薄荷醇香烟吸烟者的血清可替宁几何平均浓度分别为163.1与175.9 ng/mL；血镉为0.95与1.02 ug/L；血铅为1.87与1.75 ug/dL；尿液NNAL为0.27与0.23 ng/mL。在多变量调整后，与非薄荷醇香烟吸烟者相比，薄荷醇香烟吸烟者的比率（95%置信区间）分别为可替宁1.03（0.95-1.11）、镉1.10（1.04-1.16）、铅0.95（0.90-1.01）和NNAL 0.81（0.65-1.01）。在一个代表性的美国成年吸烟者样本中，当前使用薄荷醇香烟与血液镉浓度的增加有关，镉是一种已知的致癌物和高度有毒金属，但与其他生物标志物无关。这些发现提供了关于薄荷醇香烟吸烟者与非薄荷醇香烟吸烟者之间可能存在的暴露于有毒成分差异的信息。

In the United States, cigarette flavorings are banned, with the exception of menthol. The cooling effects of menthol could facilitate the absorption of tobacco toxicants. We examined levels of biomarkers of tobacco exposure among U.S. smokers of menthol and nonmenthol cigarettes. We studied 4,603 White, African-American, and Mexican-American current smokers 20 years of age or older who participated in the National Health and Nutrition Examination Survey (NHANES) from 1999 through 2010 and had data on cigarette type and serum cotinine, blood cadmium, and blood lead concentrations. Urinary total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol) (NNAL) was studied in 1,607 participants with available measures. A total of 3,210 (74.3%) participants smoked nonmenthol cigarettes compared with 1,393 (25.7%) participants who smoked menthol cigarettes. The geometric mean concentrations comparing smokers of nonmenthol with menthol cigarettes were 163.1 versus 175.9 ng/mL for serum cotinine; 0.95 versus 1.02 ug/L for blood cadmium; 1.87 versus 1.75 ug/dL for blood lead; and 0.27 versus 0.23 ng/mL for urine NNAL. After multivariable adjustment, the ratios [95% confidence interval (CI)] comparing smokers of menthol with nonmenthol cigarettes were 1.03 (0.95-1.11) for cotinine, 1.10 (1.04-1.16) for cadmium, 0.95 (0.90-1.01) for lead, and 0.81 (0.65-1.01) for NNAL. In a representative sample of U.S. adult smokers, current menthol cigarette use was associated with increased concentration of blood cadmium, an established carcinogen and highly toxic metal, but not with other biomarkers. These findings provide information regarding possible differences in exposure to toxic constituents among menthol cigarette smokers compared with nonmenthol cigarette smokers./L-Menthol/

来源:Hazardous Substances Data Bank (HSDB)

代谢

研究人员最近提出，通过生物标志物（如可替宁和4-（甲基亚硝基）-1-（3-吡啶基）-1-丁醇（NNAL））测量的尼古丁和致癌物暴露量与黑人吸烟者每天吸烟量（CPD）无关。研究人员还提出，薄荷烟和非薄荷烟吸烟者的尼古丁暴露量没有差异。在本研究中，我们检查了美国吸烟者按种族、CPD和薄荷香烟使用的NNAL暴露量。我们从2007-2010年参与国家健康和营养检查调查的1500多名日常吸烟者中分析了尿液中的NNAL浓度。为了比较，我们还分析了这些吸烟者的血清可替宁浓度。我们使用线性回归分析来估计按CPD和种族/族裔群体划分的平均生物标志物浓度，并检查按种族/族裔群体划分的生物标志物浓度与薄荷香烟使用之间的关系，同时控制其他人口统计和吸烟特征。生物标志物浓度随着CPD的增加而增加，对于白人、黑人和西班牙裔吸烟者，尽管与非黑人吸烟者相比，黑人吸烟者的NNAL浓度在较低的CPD水平上趋于平稳。总的来说，薄荷烟吸烟者的平均NNAL浓度低于非薄荷烟吸烟者（beta = -0.165，p = .032），在白人吸烟者中也是如此（beta = -0.207，p = .048）。我们发现在国家健康调查数据中有证据表明，尼古丁和致癌物暴露量通常随着CPD的增加而增加，尽管在高CPD水平上NNAL暴露量的模式因种族/族裔群体而异。我们还发现薄荷烟吸烟者与非薄荷烟吸烟者之间NNAL暴露量的差异。

Researchers have recently suggested that nicotine and carcinogen exposure as measured by biomarkers such as cotinine and (4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol) (NNAL) does not vary with cigarettes smoked per day (CPD) among Black smokers. Researchers have also suggested that nicotine exposure does not differ between menthol and nonmenthol smokers. In this study, we examine NNAL exposure for U.S. smokers by race, CPD, and menthol cigarette use. We analyzed urinary NNAL concentrations for more than 1500 everyday smokers participating in the National Health and Nutrition Examination Survey from 2007-2010. For purposes of comparison, we also analyzed serum cotinine concentrations for these smokers. We used linear regression analysis to estimate mean biomarker concentrations by CPD and race/ethnicity group and to examine the association between biomarker concentrations and menthol cigarette use by race/ethnicity group, controlling for other demographic and smoking characteristics. Biomarker concentrations increased with CPD for White, Black, and Hispanic smokers although NNAL concentrations leveled off for Black smokers at lower CPD levels compared with other smokers. Mean NNAL concentrations were lower among menthol smokers compared with nonmenthol smokers among smokers overall (beta = -0.165, p = .032) and White smokers (beta = -0.207, p = .048). We find evidence in national health survey data that nicotine and carcinogen exposure generally increases with CPD across race/ethnicity groups although the pattern of NNAL exposure differs by race/ethnicity group at high CPD levels. We also find evidence of differences in NNAL exposure for menthol smokers compared with nonmenthol smokers among smokers overall and White smokers /L-Menthol/

来源:Hazardous Substances Data Bank (HSDB)

代谢

枯草杆菌RWM1菌株能够以(-)-薄荷醇、(-)-薄荷酮和其他非环单萜作为唯一的碳源生长。在薄荷醇上的生长非常缓慢，其倍增时间超过24小时，而在(-)-薄荷酮上的生长也不是很快（倍增时间为12小时）。当碳源的浓度超过0.025%时，会抑制生长。在(-)-薄荷酮上生长的培养物在生长过程中暂时积累了3,7-二甲基-6-羟基辛酸酯，而(-)-薄荷醇上生长的细胞则氧化了(-)-薄荷醇、(-)-薄荷酮、3,7-二甲基-6-内酯和3,7-二甲基-6-羟基辛酸酯。尽管在(-)-薄荷醇或(-)-薄荷酮生长的细胞提取物中没有检测到薄荷醇氧化酶或薄荷醇脱氢酶，但是很容易检测到对(-)-薄荷酮有活性的诱导型NADPH依赖性单加氧酶。使用粗细胞提取物时，仅检测到3,7-二甲基-6-羟基辛酸酯作为反应产物。当通过羟基磷灰石色谱将(-)-薄荷酮单加氧酶与诱导型3,7-二甲基-6-内酯水解酶分离时，显示内酯3,7-二甲基-6-内酯是氧化的产物。/L-薄荷醇/

Corynebacterium sp. strain RWM1 grew with (-)-menthol, (-)-menthone and other acyclic monoterpenes as sole carbon sources. Growth on menthol was very slow, with a doubling time of more than 24 hr, and was not rapid with (-)-menthone (doubling time 12 hr). Concentrations of either carbon source greater than 0.025% inhibited growth. (-)-Menthone-grown cultures transiently accumulated 3,7-dimethyl-6-hydroxyoctanoate during growth, and (-)-menthol-grown cells oxidized (-)-menthol, (-)-menthone, 3,7-dimethyl-6-octanolide and 3,7-dimethyl-6-hydroxyoctanoate. Although neither a menthol oxidase nor a menthol dehydrogenase could be detected in extracts of (-)-menthol- or (-)-menthone-grown cells, an induced NADPH-linked monooxygenase with activity towards (-)-menthone was readily detected. With crude cell extracts, only 3,7-dimethyl-6-hydroxyoctanoate was detected as the reaction product. When the (-)-menthone monooxygenase was separated from an induced 3,7-dimethyl-6-octanolide hydrolase by chromatography on hydroxyapatite, the lactone 3,7-dimethyl-6-octanolide was shown to be the product of oxygenation. /L-Menthol/

来源:Hazardous Substances Data Bank (HSDB)

代谢

L-Menthol被迅速但不完全地葡萄糖醛酸化。在使用了氧化药物代谢抑制剂西咪替丁（1克/天，持续1周）预处理的所有受试者中，除了1人外，L-薄荷醇葡萄糖醛酸酯的产量增加，并且在所有使用了药物代谢酶诱导剂苯巴比妥（每晚60毫克，持续10天）预处理的受试者中也都增加了。

L-Menthol was rapidly but incompletely glucuronidated. The output of l-menthol glucuronide was incr in all but 1 subject pretreated with cimetidine (1 g/day for 1 wk), an inhibitor of oxidative drug metabolism, & in all subjects pretreated with a drug-metabolizing enzyme inducer, phenobarbitone (60 mg nightly for 10 days). /L-Menthol/

来源:Hazardous Substances Data Bank (HSDB)

代谢

(2S,3S,4S,5R,6R)-3,4,5-三羟基-6-(5-甲基-2-异丙基环己基)氧杂环己烷-2-羧酸。

Neomenthol has known human metabolites that include (2S,3S,4S,5R,6R)-3,4,5-Trihydroxy-6-(5-methyl-2-propan-2-ylcyclohexyl)oxyoxane-2-carboxylic acid.

来源:NORMAN Suspect List Exchange

毒理性

• 毒性总结

识别和使用：薄荷醇以晶体或颗粒形式生产。DL-薄荷醇用作糖果制品、利口酒、口香糖、牙膏、化妆品以及用于人类用途的普通感冒软膏和药品中的调味剂、消毒剂和冷却化合物。L-薄荷醇大量用于香烟、化妆品、牙膏、口香糖、糖果和药品中。D-薄荷醇仅用于研究。人类暴露和毒性：对25名志愿者进行了最大程度测试。该物质在凡士林中的浓度为8%，未产生致敏反应。摄入高剂量的薄荷醇可能会导致腹痛、抽搐、恶心、呕吐、眩晕、共济失调、嗜睡和昏迷。薄荷醇可能会在某些个体中引起过敏反应（例如接触性皮炎、潮红和头痛）。在极少数情况下，全部发生在1岁以下的儿童中，将薄荷醇涂抹在鼻孔或靠近鼻子的地方会引起反射性呼吸暂停。在对美国成人的代表性样本中，吸食薄荷醇香烟与增加的全因、心血管和癌症死亡率有关，与非薄荷醇香烟相比没有差异。在系统回顾中，薄荷醇香烟的使用与非薄荷醇香烟的使用相比，与癌症风险的逆相关性，并有心血管疾病风险增加的证据。流行病学研究表明，使用薄荷醇的美国吸烟者与非薄荷醇香烟使用者之间的依赖性没有差异。动物研究：所有研究的薄荷醇同分异构体，如果未经稀释使用，对皮肤都有中等刺激性。薄荷醇异构体对眼睛有轻微刺激性。在实验动物中，薄荷醇通过口服、注射和皮肤途径的急性毒性较低。在多种动物中，主要是通过口服给药，看到了肝脏和肾脏的变化。吸入薄荷醇可能会对呼吸道造成伤害。在大鼠和小鼠中没有令人信服的致癌性证据。L-薄荷醇在多种物种（大鼠、小鼠、兔和仓鼠）的灌胃研究中没有表现出胚胎或胎儿毒性，也没有致畸性。在细菌和哺乳动物体外测试系统中，薄荷醇异构体被认为不具有遗传毒性。在体内，L-和D/L-薄荷醇在显性致死和细胞遗传学测试以及小鼠的骨髓微核测试中未表现出突变潜力。

IDENTIFICATION AND USE: Menthol is produced as crystals or granules. DL-Menthol is used as flavoring, disinfectant and cooling compound in confectionery products, liqueurs, chewing gums, toothpastes, cosmetics and common cold ointments and medications for human purposes. L-Menthol is used in large quantities in cigarettes, cosmetics, toothpastes, chewing gum, sweets, and medicines. D-Menthol is used only in research. HUMAN EXPOSURE AND TOXICITY: A maximization test was carried out on 25 volunteers. The material was tested at a concentration of 8% in petrolatum and produced no sensitization reactions. Ingestion of high menthol doses may cause abdominal pain, convulsions, nausea, vomiting, vertigo, ataxia, drowsiness and coma. Menthol may cause allergic reactions (e.g. contact dermatitis, flushing, and headache) in certain individuals. In very few cases, all in children younger than 1 year, menthol applied to the nostrils or near the nose caused reflex apnea. In a representative sample of U.S. adults, menthol cigarette smoking was associated with increased all-cause, cardiovascular and cancer mortality with no differences compared to nonmenthol cigarettes. In the systematic review, menthol cigarette use was associated with inverse risk of cancer compared to nonmenthol cigarette use with some evidence of an increased risk for cardiovascular disease. Epidemiological studies indicate no difference in dependence among U.S. smokers who use menthol compared to non-menthol cigarettes. ANIMAL STUDIES: All studied isomers of menthol are, if applied undiluted, moderately irritating to skin. The menthol isomers are slightly irritating to the eye. In experimental animals, menthol was of low acute toxicity by oral, injection, and dermal routes. Liver and kidney changes have been seen in a number of animals mainly involving oral administration. Inhalation of menthol may produce respiratory tract injury. There was no convincing evidence of carcinogenicity in rats and mice. L-Menthol was not embryo- or fetotoxic and had no teratogenic properties in gavage studies in various species (rat, mouse, rabbit, and hamster) at not maternally toxic doses. The menthol isomers are considered non-genotoxic in bacterial and mammalian test systems in vitro. In vivo, L- and D/L-menthol have demonstrated no mutagenic potential in dominant lethal and cytogenetic tests and in a bone marrow micronucleus test in mice.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 副作用

神经毒素 - 急性溶剂综合征

Neurotoxin - Acute solvent syndrome

来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases

毒理性

• 相互作用

薄荷脑（l-薄荷脑）与乙醇（酒精）结合对模型药物经皮吸收的影响进行了研究，使用了两个方程式和一个两层体外皮肤模型。采用非线性最小二乘法，通过两个方程式和实验获得的全层皮肤透过率系数以及全层皮肤/载体浓度比来确定6个系数。将薄荷脑添加到水和40%乙醇中，增加了药物在角质层脂质和毛孔途径中的扩散系数。将乙醇添加到水和5%薄荷脑中，增加了药物在载体中的溶解度，降低了皮肤的极性，并增加了毛孔途径在整个皮肤渗透中的作用。结论是，薄荷脑和乙醇对体外药物经皮吸收的影响是协同的。/L-薄荷脑/

The effects of l-menthol ((-)-menthol) combined with ethyl alcohol (ethanol) on the percutaneous absorption of model drugs were studied using 2 equations and a 2-layer in vitro skin model. A nonlinear least-squares method was employed to determine 6 coefficients using the 2 equations and experimentally obtained permeability coefficient through full-thickness skin and full-thickness skin/vehicle concentration ratio. Adding menthol to water and 40% ethyl alcohol increased the diffusion coefficient of drugs in lipid and pore pathways of stratum corneum. Adding ethyl alcohol to water and 5% menthol increased drug solubility in the vehicle, decreased skin polarity, and increased the role of the pore pathway to whole-skin permeation. It was concluded that the effects of l-menthol and ethyl alcohol on percutaneous drug absorption in vitro are synergistic. /L-Menthol/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

大多数药物通过眼睛的渗透性非常有限，因此在当前的眼科学研究中，找到安全有效的渗透增强剂具有很高的重要性。在本文中，我们采用了一种新的方法，将中西医药相结合，以提高黄芩苷（一种水和脂溶性目标药物）的体外角膜渗透性。将兔子分为三组。第一组分别给予冰片（0.05%，0.1%）、薄荷醇（0.1%，0.2%）或Labrasol（1%，2%）单独用药，第二组给予Labrasol与冰片或薄荷醇的组合用药，第三组接受对照治疗。与对照治疗相比，单独使用冰片、薄荷醇或Labrasol明显提高了黄芩苷的体外渗透性。此外，将Labrasol与薄荷醇或冰片联合应用，穿透效果显著增加。在各种联合渗透增强剂中，0.1%冰片与2%Labrasol的组合获得了最佳表观渗透性，约为对照组的16.35倍。此外，角膜水合水平的计算和Draize测试证明了这些渗透增强剂对活体兔角膜的安全性。本研究证实，将冰片或薄荷醇（均来源于中草药）与Labrasol联合使用可以提高水和脂不溶性药物的角膜渗透性。/DL-薄荷醇/

The permeability of most drugs through the eyes is very limited, so finding safe and effective penetration enhancers is of high importance in current ophthalmology research. In this paper, we use a new approach that integrates Chinese and Western medicine to improve the corneal permeability of baicalin, a water- and fat-insoluble target drug, in vitro. Rabbits were divided into three groups. The first group was dosed with borneol (0.05%, 0.1%). menthol (0.1%, 0.2%), or Labrasol (1%, 2%) individually, the second was dosed with a combination of Labrasol with either borneol or menthol, and the third group received a control treatment. Compared with the control treatment, borneol, menthol, or Labrasol alone clearly improved the permeability of baicalin in vitro. Furthermore, the penetrating effects were significantly increased by combining the application of Labrasol withmenthol or borneol. Among the various combined penetration enhancers, 0.1% borneol with 2% Labrasol achieved the best apparent permeability, approximately 16.35 times that of the control. Additionally, the calculation of corneal hydration level and the Draize test demonstrated the safety of these penetration enhancers to the rabbit corneas in vivo. This study confirms that the combined use of borneol or menthol, compounds both derived from Chinese herbs, with Labrasol can improve the corneal permeability of water- and fat-insoluble drugs. /DL-Menthol/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

炎症和氧化应激在各种病理过程中起着关键作用，包括皮肤肿瘤发生。皮肤癌是最常见的一种癌症，尽管治疗进展缓慢，但仍造成了相当大的发病率和死亡率。因此，人们正在考虑化学预防和其它策略。薄荷醇对各种人类癌症显示出高抗肿瘤活性，但其对皮肤癌的影响从未被评估过。我们在本研究中调查了薄荷醇对雌性ICR小鼠9,10-二甲基苯并[a]蒽（DMBA）/12-O-十四烷基佛波醇-13-醋酸（TPA）诱导的炎症、氧化应激和皮肤癌变的化学预防潜力。以不同剂量的薄荷醇预处理显著抑制了肿瘤的形成和生长，并显著减少了肿瘤的发生率和体积。此外，薄荷醇抑制了TPA诱导的皮肤增生和炎症，显著抑制了环氧合酶-2（COX-2）的表达。进一步地，薄荷醇预处理抑制了活性氧种类的形成，并影响了皮肤中一系列抗氧化酶的活性。薄荷醇给药下调了NF-kappaB、Erk和p38的表达。因此，炎症和氧化应激在薄荷醇对小鼠皮肤肿瘤发生的化学预防效果中共同发挥了关键作用。/DL-薄荷醇/

Inflammation and oxidative stress have been implicated in various pathological processes including skin tumorigenesis. Skin cancer is the most common form of cancer responsible for considerable morbidity and mortality, the treatment progress of which remains slow though. Therefore, chemoprevention and other strategies are being considered. Menthol has shown high anticancer activity against various human cancers, but its effect on skin cancer has never been evaluated. We herein investigated the chemopreventive potential of menthol against 9,10-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation, oxidative stress and skin carcinogenesis in female ICR mice. Pretreatment with menthol at various doses significantly suppressed tumor formation and growth, and markedly reduced tumor incidence and volume. Moreover, menthol inhibited TPA-induced skin hyperplasia and inflammation, and significantly suppressed the expression of cyclooxygenase-2 (COX-2). Furthermore, pretreatment with menthol inhibited the formation of reactive oxygen species and affected the activities of a battery of antioxidant enzymes in the skin. The expressions of NF-kappaB, Erk and p38 were down-regulated by menthol administration. Thus, inflammation and oxidative stress collectively played a crucial role in the chemopreventive efficacy of menthol on the murine skin tumorigenesis./DL-Menthol/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

剂量较大的L-薄荷脑在兔子体内与葡萄糖醛酸结合排出的百分比取决于剂量的多少；剂量越大，结合越少。

...The percentage of a dose of l-menthol that is excreted combined with glucuronic acid in the rabbit depends on the magnitude of the dose; the larger the dose, the less is the conjugation. /L-Menthol/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

并非所有的葡萄糖苷酸都通过肾小管分泌排出...较高分子量的结合物，如雄酮的葡萄糖苷酸...仅通过肾小球滤过消除，而较低分子量的薄荷醇的葡萄糖苷酸...除了通过肾小球滤过外，还通过肾小管排出... /DL-薄荷醇/

Not all glucuronides are excreted by tubular secretion... conjugates of higher mol wt such as glucuronides of androsterone...are eliminated by glomerular filtration alone, whereas those of menthol...of lower mol wt...by tubules in addition to glomerular filtration... /DL-Menthol/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

许多具有不同结构的物质已知会分泌到胆汁中；这些包括薄荷脑的葡萄糖苷酸酯... /DL-薄荷脑/

Many substances with diverse structures are known to be excreted into bile; these incl glucuronides of menthol... /DL-Menthol/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

吸收可以发生在局部使用时。/DL-薄荷醇/

Absorption can occur from topical use. /DL-Menthol/

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险品标志：
  Xi
• 安全说明：
  S26,S36,S36/37/39
• 危险类别码：
  R48/20/22,R40,R22,R37/38,R41
• WGK Germany：
  1,2
• 海关编码：
  29061100
• 危险品运输编号：
  UN 1888 6.1/PG 3
• RTECS号：
  OT0525000

SDS

Name:	DL-Menthol 99% Material Safety Data Sheet
Synonym:	p-Menthan-3-o
CAS:	1490-04-6

Section 1 - Chemical Product MSDS Name:DL-Menthol 99% Material Safety Data Sheet
Synonym:p-Menthan-3-o

---

Section 2 - COMPOSITION, INFORMATION ON INGREDIENTS

CAS#	Chemical Name	content	EINECS#
1490-04-6	DL-Menthol	99	216-074-4

Hazard Symbols: XI
Risk Phrases: 36/37/38

---

Section 3 - HAZARDS IDENTIFICATION
EMERGENCY OVERVIEW
Irritating to eyes, respiratory system and skin.The toxicological properties of this material have not been fully investigated.
Potential Health Effects
Eye:
May cause eye irritation. The toxicological properties of this material have not been fully investigated.
Skin:
May cause skin irritation. The toxicological properties of this material have not been fully investigated.
Ingestion:
May cause gastrointestinal irritation with nausea, vomiting and diarrhea. The toxicological properties of this substance have not been fully investigated.
Inhalation:
May cause respiratory tract irritation. The toxicological properties of this substance have not been fully investigated.
Chronic:
Not available.

---

Section 4 - FIRST AID MEASURES
Eyes: Flush eyes with plenty of water for at least 15 minutes, occasionally lifting the upper and lower eyelids. Get medical aid immediately.
Skin:
Get medical aid. Flush skin with plenty of water for at least 15 minutes while removing contaminated clothing and shoes.
Ingestion:
If victim is conscious and alert, give 2-4 cupfuls of milk or water.
Never give anything by mouth to an unconscious person. Get medical aid.
Inhalation:
Remove from exposure and move to fresh air immediately. If not breathing, give artificial respiration. If breathing is difficult, give oxygen. Get medical aid.
Notes to Physician:

---

Section 5 - FIRE FIGHTING MEASURES
General Information:
As in any fire, wear a self-contained breathing apparatus in pressure-demand, MSHA/NIOSH (approved or equivalent), and full protective gear. During a fire, irritating and highly toxic gases may be generated by thermal decomposition or combustion.
Extinguishing Media:
Use water fog, dry chemical, carbon dioxide, or regular foam.

---

Section 6 - ACCIDENTAL RELEASE MEASURES
General Information: Use proper personal protective equipment as indicated in Section 8.
Spills/Leaks:
Clean up spills immediately, observing precautions in the Protective Equipment section. Sweep up or absorb material, then place into a suitable clean, dry, closed container for disposal.

---

Section 7 - HANDLING and STORAGE
Handling:
Wash thoroughly after handling. Remove contaminated clothing and wash before reuse. Use only in a well-ventilated area. Avoid contact with eyes, skin, and clothing. Avoid ingestion and inhalation.
Storage:
Keep container closed when not in use. Store in a cool, dry, well-ventilated area away from incompatible substances.

---

Section 8 - EXPOSURE CONTROLS, PERSONAL PROTECTION
Engineering Controls:
Use adequate ventilation to keep airborne concentrations low.
Exposure Limits CAS# 1490-04-6: Personal Protective Equipment Eyes: Wear appropriate protective eyeglasses or chemical safety goggles as described by OSHA's eye and face protection regulations in 29 CFR 1910.133 or European Standard EN166.
Skin:
Wear appropriate protective gloves to prevent skin exposure.
Clothing:
Wear appropriate protective clothing to prevent skin exposure.
Respirators:
Follow the OSHA respirator regulations found in 29 CFR 1910.134 or European Standard EN 149. Use a NIOSH/MSHA or European Standard EN 149 approved respirator if exposure limits are exceeded or if irritation or other symptoms are experienced.

---

Section 9 - PHYSICAL AND CHEMICAL PROPERTIES

Physical State: Solid
Color: white
Odor: None reported.
pH: Not available.
Vapor Pressure: Not available.
Viscosity: Not available.
Boiling Point: Not available.
Freezing/Melting Point: 28.00 - 30.00 deg C
Autoignition Temperature: Not available.
Flash Point: 93 deg C ( 199.40 deg F)
Explosion Limits, lower: Not available.
Explosion Limits, upper: Not available.
Decomposition Temperature:
Solubility in water: soluble in alcohol, chloroform and ether
Specific Gravity/Density: .8900g/cm3
Molecular Formula: C10H20O
Molecular Weight: 156.27

---

Section 10 - STABILITY AND REACTIVITY
Chemical Stability:
Stable under normal temperatures and pressures.
Conditions to Avoid:
Incompatible materials.
Incompatibilities with Other Materials:
Strong oxidizing agents.
Hazardous Decomposition Products:
Carbon monoxide, carbon dioxide.
Hazardous Polymerization: Has not been reported.

---

Section 11 - TOXICOLOGICAL INFORMATION
RTECS#:
CAS# 1490-04-6: GW0554000 LD50/LC50:
Not available.
Carcinogenicity:
DL-Menthol - Not listed by ACGIH, IARC, or NTP.
Other:
See actual entry in RTECS for complete information.

---

Section 12 - ECOLOGICAL INFORMATION

---

Section 13 - DISPOSAL CONSIDERATIONS
Dispose of in a manner consistent with federal, state, and local regulations.

---

Section 14 - TRANSPORT INFORMATION

IATA
Not regulated as a hazardous material.
IMO
Not regulated as a hazardous material.
RID/ADR
Not regulated as a hazardous material.

---

Section 15 - REGULATORY INFORMATION

European/International Regulations
European Labeling in Accordance with EC Directives
Hazard Symbols: XI
Risk Phrases:
R 36/37/38 Irritating to eyes, respiratory system
and skin.
Safety Phrases:
S 24/25 Avoid contact with skin and eyes.
WGK (Water Danger/Protection)
CAS# 1490-04-6: 1
Canada
CAS# 1490-04-6 is listed on Canada's DSL List.
CAS# 1490-04-6 is not listed on Canada's Ingredient Disclosure List.
US FEDERAL
TSCA
CAS# 1490-04-6 is listed on the TSCA inventory.

---

SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

化学性质

薄荷脑源自薄荷植物，其主要成分是右旋薄荷酮（又称右旋薄荷醇），具有清凉感和特殊的芳香气味。其分子式为C10H20O，相对密度约为0.875，熔点约43°C。在常温下为白色结晶性粉末或片状晶体，在室温及压力环境下易升华。薄荷脑可溶于乙醇、丙酮等有机溶剂，微溶于冷水，几乎不溶于热水。

精制工艺

1. 熔化

   • 将原料放入熔化间进行熔化，形成薄荷原油。
   • 保持熔化温度80-90°C（冬季可适当调整）。

2. 脱水

   • 打入脱水釜后启动真空泵，降低脱水压力；开启蒸汽阀门加热薄荷原油至85-90°C。
   • 维持此状态1-1.5小时，确保油温及真空度稳定。

3. 配料

   • 根据高度油和低度油的含脑量比例进行计算，确定加入量并分别打入配料罐中搅拌。

4. 压滤

   • 使用泵将混合油打入压滤机过滤杂质。
   • 控制压力小于0.6MPa，必要时更换滤纸。

5. 精馏与结晶

   • 将压滤后的油料进行减压精馏（400-500Pa），温度控制在75-80°C。
   • 精馏直至无液体馏出后浓缩至含薄荷醇≥77%的浓度，流入结晶桶冷冻20-24小时。

6. 烘脑

   • 进行冰油放净操作后推进烘脑房，温度控制在42-45°C。
   • 烘房中心刻度下降1.5-2cm时停止烘脑并保温1-2小时。

7. 晾脑与整脑

   • 将结晶桶有序排列，在桶上加盖滤网纱网。
   • 晾脑后将结晶脑倒入整脑台上疏松，挑出脑根或并晶。

8. 包装、储存

   • 称重并按标准称量结晶体送入包装桶内。
   • 储存在阴凉干燥通风仓库内，确保避光及远离火源。烘油和脑根可用于再生产薄荷脑。

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  L-薄荷醇	(-)-menthol	2216-51-5	C10H20O	156.268
  ——	menthyl methyl ether	75326-21-5	C11H22O	170.295
  小茴香醇	(1R)-endo-(+)-fenchol	2217-02-9	C10H18O	154.252
  甲酸薄荷酯	menthyl formate	2230-90-2	C11H20O2	184.279
  ——	rac-(1R,2S,5R)-2-isopropyl-5-methylcyclohexyl vinyl ether	——	C12H22O	182.306
  ——	menthyl vinyl ether	46173-76-6	C12H22O	182.306
  1-异丙基-2-(甲氧基甲氧基)-4-甲基环己烷	2-(Methoxymethoxy)-4-methyl-1-propan-2-ylcyclohexane	91898-14-5	C12H24O2	200.321
  ——	Menthol allyl ether	144266-44-4	C13H24O	196.333
  异蒲勒醇	Isopulegol	7786-67-6	C10H18O	154.252
  异胡薄荷醇	isopulegol	89-79-2	C10H18O	154.252
• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  ——	(R)-menthol	904840-84-2	C10H20O	156.268
  D-薄荷醇	(+)-Menthol	15356-60-2	C10H20O	156.268
  L-薄荷醇	(-)-menthol	2216-51-5	C10H20O	156.268
  ——	2-(1-hydroxypropan-2-yl)-5-methylcyclohexan-1-ol	——	C10H20O2	172.268
  氢化松油醇	p-menthan-8-ol	498-81-7	C10H20O	156.268
  ——	menthyl methyl ether	75326-21-5	C11H22O	170.295
  ——	O-ethylmenthol	164351-97-7	C12H24O	184.322
  甲酸薄荷酯	menthyl formate	2230-90-2	C11H20O2	184.279
  ——	menthyl vinyl ether	46173-76-6	C12H22O	182.306
  薄荷基氯甲基醚	Menthyl chloromethyl ether	96662-07-6	C11H21ClO	204.74

反应信息

• 作为反应物：
  描述：

  薄荷脑 在 platinum-chromium (III)-oxide catalyst 、 苯 作用下， 生成 4-异丙基甲苯
  参考文献：
  名称：

  Catalytic Dehydrogenation of Hydroaromatic Compounds with Benzene¹

  摘要：

  DOI：

  10.1021/ja01850a050
• 作为产物：
  描述：

  百里酚 在 氢气 作用下， 以 叔丁醇 为溶剂， 150.0 ℃ 、3.0 MPa 条件下， 以94 %的产率得到薄荷脑
  参考文献：
  名称：

  地球储量丰富的多相钴催化剂用于（杂）芳烃的选择性环加氢和医药中间体的克级合成

  摘要：

  开发可以替代贵金属基催化剂的非贵金属基加氢催化剂是非常理想的，但在科学和技术上都具有挑战性。在此，我们提出了一种简便且环保的方法来合成松针生物质衍生的氮掺杂碳负载Co 3 O 4纳米粒子（Co 3 O 4 /PNC）。整个过程包括用硝酸钴盐浸渍松针，然后在氮气气氛下在 500°C 下热解。应用这种 Co 3 O 4 /PNC 纳米催化剂，可产生多种取代酚和功能性有机化学品，包括N - 和O-杂芳烃，可以有效地转化为其相应的环氢化产物，产率从良好到优异（> 55个例子）。此外，这种催化方法已被证明可用于制备克级的七种关键药物中间体，这些中间体通常用于批量生产活性药物成分。有利地，环己烷甲酸，吡喹酮的关键药物结构单元，是由聚苯乙烯以两步法合成的。通过高分辨率透射电子显微镜、X 射线光电子能谱、X 射线衍射、N 2彻底研究了新鲜和废 Co 3 O 4 /PNC 纳米催化剂的关键物理化学性质。吸附-解吸、拉曼分析、H

  DOI：

  10.1021/acscatal.3c02084
• 作为试剂：
  描述：

  苯戊醇 在 薄荷脑 、 戴斯-马丁氧化剂 作用下， 以 二氯甲烷 为溶剂， 反应 0.33h， 以95%的产率得到苯戊酮
  参考文献：
  名称：

  Diospongins A 和 B 的全合成

  摘要：

  描述了使用 2,6-二取代二氢吡喃酮作为关键中间体的 diospongins A 和 B 的全合成。

  DOI：

  10.1055/s-0028-1083518

文献信息

• Additives and products including oligoesters
  申请人：——

  公开号：US20030199593A1

  公开（公告）日：2003-10-23

  The present invention relates to oligoesters and their use or the creation of additives. Oligoester containing additives and/or oligoesters themselves may be used for formulating pharmaceutical preparations, cosmetics or personal care products such as shampoos and conditioners. These oligoesters are particularly useful for the creation of multi-purpose additives that can impart conditioning, long substantivity and/or UV protection. Individual oligoesters and oligoester mixtures are described.

  本发明涉及寡酯及其用途或添加剂的制备。含有寡酯的添加剂和/或寡酯本身可用于配制药物制剂、化妆品或个人护理产品，如洗发水和护发素。这些寡酯对于制备能够赋予调理、长效性和/或紫外线保护的多功能添加剂特别有用。描述了单独的寡酯和寡酯混合物。
• [EN] INHIBITORS OF BRUTON'S TYROSINE KINASE<br/>[FR] INHIBITEURS DE TYROSINE KINASE DE BRUTON
  申请人：BIOCAD JOINT STOCK CO

  公开号：WO2018092047A1

  公开（公告）日：2018-05-24

  The present invention relates to a new compound of formula I: or pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein: V1 is C or N, V2 is C(R2) or N, whereby if V1 is C then V2 is N, if V1 is C then V2 is C(R2), or if V1 is N then V2 is C(R2); each n, k is independently 0, 1; each R2, R11 is independently H, D, Hal, CN, NR'R", C(O)NR'R", C1-C6 alkoxy; R3 is H, D, hydroxy, C(O)C1-C6 alkyl, C(O)C2-C6 alkenyl, C(O)C2-C6 alkynyl, C1-C6 alkyl; R4 is H, Hal, CN, CONR'R", hydroxy, C1-C6 alkyl, C1-C6 alkoxy; L is CH2, NH, O or chemical bond; R1 is selected from the group of the fragments, comprising: Fragment 1, Fragment 2, Fragment 3 each A1, A2, A3, A4 is independently CH, N, CHal; each A5, A6, A7, A8, A9 is independently C, CH or N; R5 is H, CN, Hal, CONR'R", C1-C6 alkyl, non-substituted or substituted by one or more halogens; each R' and R" is independently selected from the group, comprising H, C1-C6 alkyl, C1-C6 cycloalkyl, aryl; R6 is selected from the group: [formula II] each R7, R8, R9, R10 is independently vinyl, methylacetylenyl; Hal is CI, Br, I, F, which have properties of inhibitor of Bruton's tyrosine kinase (Btk), to pharmaceutical compositions containing such compounds, and their use as pharmaceuticals for treatment of diseases and disorder.

  本发明涉及一种新的化合物，其化学式为I：或其药学上可接受的盐、溶剂化合物或立体异构体，其中：V1为C或N，V2为C(R2)或N，如果V1为C，则V2为N，如果V1为C，则V2为C(R2)，或者如果V1为N，则V2为C(R2)；每个n，k独立地为0或1；每个R2，R11独立地为H，D，Hal，CN，NR'R"，C(O)NR'R"，C1-C6烷氧基；R3为H，D，羟基，C(O)C1-C6烷基，C(O)C2-C6烯基，C(O)C2-C6炔基，C1-C6烷基；R4为H，Hal，CN，CONR'R"，羟基，C1-C6烷基，C1-C6烷氧基；L为CH2，NH，O或化学键；R1从包括的片段组中选择：片段1，片段2，片段3，每个A1，A2，A3，A4独立地为CH，N，CHal；每个A5，A6，A7，A8，A9独立地为C，CH或N；R5为H，CN，Hal，CONR'R"，C1-C6烷基，未取代或被一个或多个卤素取代；每个R'和R"独立地从包括H，C1-C6烷基，C1-C6环烷基，芳基的组中选择；R6从组中选择：[化学式II]每个R7，R8，R9，R10独立地为乙烯基，甲基乙炔基；Hal为CI，Br，I，F，具有布鲁顿酪氨酸激酶（Btk）抑制剂的性质，以及含有这种化合物的药物组合物，以及它们作为治疗疾病和紊乱的药物的用途。
• Eflornithine Prodrugs, Conjugates and Salts, and Methods of Use Thereof
  申请人：Xu Feng

  公开号：US20100120727A1

  公开（公告）日：2010-05-13

  In one aspect, the present invention provides a composition of a covalent conjugate of an eflornithine analog with an anti-inflammatory drug. In another aspect, the present invention provides a composition of an eflornithine prodrug. In another aspect, the present invention provides a composition of an eflornithine or its derivatives aspirin salt. In another aspect, the present invention provides methods for treating or preventing cancer using the conjugates or salts of eflornithine analogs or eflornithine prodrugs.

  在一个方面，本发明提供了一种氟硝西汀类似物与抗炎药物的共价结合物的组合物。在另一个方面，本发明提供了一种氟硝西汀前药的组合物。在另一个方面，本发明提供了一种氟硝西汀或其衍生物水杨酸盐的组合物。在另一个方面，本发明提供了使用氟硝西汀类似物或氟硝西汀前药的共轭物或盐来治疗或预防癌症的方法。
• [EN] CALPAIN MODULATORS AND THERAPEUTIC USES THEREOF<br/>[FR] MODULATEURS DE CALPAÏNE ET LEURS UTILISATIONS THÉRAPEUTIQUES
  申请人：BLADE THERAPEUTICS INC

  公开号：WO2019190885A1

  公开（公告）日：2019-10-03

  Small molecule calpain modulator compounds, including their pharmaceutically acceptable salts, can be included in pharmaceutical compositions. The compounds can be useful in inhibiting calpain, or competitive binding with calpastatin, by contacting them with CAPN1, CAPN2, and/or CAPN9 enzymes residing inside a subject. The compounds and composition can also be administered to a subject in order to treat a fibrotic disease or a secondary disease state or condition of a fibrotic disease.

  小分子钙蛋白酶调节剂化合物，包括其药用可接受的盐，可以包含在药物组合物中。这些化合物可以通过与主体内的CAPN1、CAPN2和/或CAPN9酶接触来抑制钙蛋白酶，或与钙蛋白酶抑制剂竞争性结合。这些化合物和组合物也可以被用于治疗纤维化疾病或纤维化疾病的继发疾病状态或病情。
• H₅IO₆/KI: A New Combination Reagent for Iodination of Aromatic Amines, and Trimethylsilylation of Alcohols and Phenols through<i>in situ</i>Generation of Iodine under Mild Conditions
  作者：Mohammad Ali Zolfigol、Ardeshir Khazaei、Eskandar Kolvari、Nadiya Koukabi、Hamid Soltani、Maryam Behjunia

  DOI：10.1002/hlca.200900259

  日期：2010.3

  A simple method for the in situ generation of iodine using H5IO6/KI has been developed, and its application in silylation of OH group and iodination of aromatic amines is described.

  已开发出一种使用H 5 IO 6 / KI原位生成碘的简单方法，并描述了其在OH基甲硅烷基化和芳族胺碘化中的应用。

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