乳糖醇 | 585-86-4

• 物质功能分类: 生物化工 - 糖类化合物 - 双糖
• 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: 乳糖醇
• 中文别名: 4-O-BETA-D-吡喃半乳糖基-D-葡萄糖醇；4-Β-D-吡喃半乳糖-D-山梨醇；拉克替醇；乳梨醇；拉克替醇
• 英文名称: lactitol
• 英文别名: 4-O-β-D-galactopyranosyl-D-glucitol；β-D-galactopyranosyl-(1->4)-D-glucitol；β-D-Galp-(1->4)-D-Glc-ol；D-lactitol；lactose；(2S,3R,4R,5R)-4-[(2S,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyhexane-1,2,3,5,6-pentol
• CAS: 585-86-4
• 化学式: C₁₂H₂₄O₁₁
• 分子量: 344.316
• InChiKey: VQHSOMBJVWLPSR-JVCRWLNRSA-N

物化性质

• 熔点：
  146°
• 比旋光度：
  D23 +14° (c = 4 in water)
• 沸点：
  788.5±60.0 °C(Predicted)
• 密度：
  1.69±0.1 g/cm3(Predicted)
• 溶解度：
  Slightly soluble in ethanol (95%) and ether. Soluble 1 in 1.75 of water at 20°C; 1 in 1.61 at 30°C; 1 in 1.49 at 40°C; 1 in 1.39 at 50°C.
• LogP：
  -3.11
• 物理描述：
  Crystalline powder or colourless solution. Crystalline products occur in anhydrous, monohydrate and dihydrate forms. Nickel is used as a catalyst.
• 颜色/状态：
  Crystals from absolute ethanol
• 味道：
  30-40% of that of sucrose. The taste is sweet and clean
• 蒸汽压力：
  6.55X10-16 mm Hg at 25 °C (est)
• 稳定性/保质期：
  Lactitol ... is stable under humid conditions. It is stable to heat and does not take part in the Maillard reaction.
• 旋光度：
  Specific optical rotation: +14 deg at 23 °C/D (c = 4 in water)
• 分解：
  In an acidic solution, lactitol slowly hydrolyzes to sorbitol and galactose. Lactitol is very resistant to microbiological breakdown and fermentation.

计算性质

• 辛醇/水分配系数(LogP)：
  -5.2
• 重原子数：
  23
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  201
• 氢给体数：
  9
• 氢受体数：
  11

ADMET

代谢

由于乳糖醇几乎不被系统吸收，它不太可能经历任何显著程度的代谢。

As it undergoes little-to-no systemic absorption, lactitol is unlikely to undergo any significant degree of metabolism.

来源:DrugBank

代谢

在旨在研究健康志愿者体内赤藓糖醇代谢的研究中，以及比较人类粪便菌群在体外对赤藓糖醇、葡萄糖和乳糖醇的发酵情况，共有四名男性和两名女性志愿者参与了此次研究，他们的年龄在21-25岁之间。志愿者在隔夜禁食后，随机接受单次剂量的25克(13)C-赤藓糖醇、(13)C-葡萄糖和(13)C-乳糖醇，溶解在250毫升水中，每种处理之间至少间隔三天。在处理前和处理后30分钟至6小时内，每隔30分钟采集一次呼气样本，用于分析(13)C-二氧化碳和氢气。通过同位素比率质谱法测量(13)C:(12)C-二氧化碳的比例。为了保持恒定的代谢率，受试者在研究期间保持休息状态。为了体外发酵实验，从六名健康志愿者（性别和年龄未指明）收集粪便样本，这些志愿者食用正常西方饮食。所有受试者均未出现胃肠道症状，过去六个月内也未使用过抗生素。样本在厌氧条件下孵育6小时，然后测量孵育小瓶顶空的氢气浓度。经过6小时的孵育后，与对照小瓶相比，粪便菌群通过赤藓糖醇产生的氢气量相当，但在葡萄糖和乳糖醇小瓶中产生的氢气量显著多于对照小瓶和赤藓糖醇小瓶（p < 0.001）。

In studies designed to investigate the metabolism of erythritol in vivo in healthy volunteers and to compare the fermentation of erythritol by human fecal flora in vitro with that of glucose and lactitol, four male and two female volunteers aged 21-25 undertook an overnight fast and were then chosen at random to receive a single dose of 25 g (13)C-erythritol, (13)C-glucose, and (13)C-lactitol in 250 mL of water with at least three days between each treatment. Breath samples were taken for analysis of (13)C-carbon dioxide and hydrogen gas before treatment and at 30 min intervals up to 6 hrs after treatment. The ratio of (13)C: (12)C-carbon dioxide was measured by isotope-ratio mass spectrometry. ... In order to maintain a constant metabolic rate, the subjects remained at rest during the study. For the assay of fermentation in vitro, fecal samples were collected from six healthy volunteers (sex and age not specified) who ate a normal western diet. None of the subjects complained of gastrointestinal symptomsand none had used antibiotics in the past six months. The samples were incubated under anaerobic conditions for 6 hr, and then the hydrogen gas concentration was measured in the head-space of the incubation vials. ... After a 6 hr incubation with erythritol, the amount of hydrogen gas formed by the fecal flora was comparable to that in control vials, but significantly (p < 0.001) more hydrogen gas was produced in the glucose and lactitol vials than in either control or erythritol.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 紧急急救：确保已经进行了充分的中和。如果患者停止呼吸，请开始人工呼吸，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。 /高醇（大于3个碳）及相关化合物/

/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 as necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on 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. /Higher alcohols (>3 carbons) and related compounds/

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。密切观察呼吸不足的迹象，如有必要，进行辅助通气。通过非重复呼吸面罩以10至15升/分钟的速度给予氧气。监测休克迹象并在必要时进行治疗……监测肺水肿迹象并在必要时进行治疗……预期可能出现癫痫并在必要时进行治疗……对于眼睛污染，立即用水冲洗眼睛。在转运过程中，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、有强烈的呕吐反射并不流口水，则用水冲洗口腔，并给予5毫升/千克，最多200毫升的水进行稀释。给予活性炭……/高醇（大于3个碳）及相关化合物/

/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 necessary. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for shock and treat if necessary ... . Monitor for pulmonary edema 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. Administer activated charcoal ... . /Higher alcohols (>3 carbons) and related compounds/

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。正压通气技术，使用球囊阀面罩装置可能有益。考虑使用药物治疗肺水肿……。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）或乳酸钠林格氏液（LR）。对于伴有低血容量迹象的低血压，谨慎给予液体。如果病人在正常血容量下出现低血压，考虑使用血管加压药。注意液体过载的迹象……。监测低血糖的迹象（意识水平下降、心动过速、苍白、瞳孔扩大、出汗和/或葡萄糖试纸或血糖仪读数低于50毫克）并在必要时给予50%葡萄糖……。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……。/高级醇（>3个碳）及相关化合物/

/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 ... . 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 (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Consider vasopressors if patient is hypotensive with a normal fluid volume. Watch for signs of fluid overload ... . Monitor for signs of hypoglycemia (decreased LOC, tachycardia, pallor, dilated pupils, diaphoresis, and/or dextrose strip or glucometer readings below 50 mg) and administer 50% dextrose if necessary ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Higher alcohols (>3 carbons) and related compounds/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

/HUMAN EXPOSURE STUDIES/ 相等量的蔗糖、乳糖、乳糖醇以及乳糖醇和蔗糖的负荷测试已经在八名健康成人中进行。不同负荷后血糖浓度平均最大增加值分别为63、43、6和40毫克%。所有受试者在摄入乳糖醇（50克）以及乳糖醇和蔗糖后都出现了腹泻。

/HUMAN EXPOSURE STUDIES/ Loading tests with equal amounts of sucrose, lactose, lactitol, and lactitol and sucrose have been carried out on eight healthy adults. The average maximal increases in blood glucose concentration after the different loadings were 63, 43, 6 and 40 mg% respectively. All subjects experienced diarrhea after lactitol (50 g) as well as lactitol and sucrose ingestion.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

人类暴露研究/长期使用乳糖醇作为食品添加剂或泻药可能会不利地影响钙稳态。在一项公开交叉研究中，对12名志愿者每天服用20-40克乳糖醇一个月的钙代谢进行了研究。与对照组（不服用乳糖醇）相比，这种双糖并没有改变尿液中钙、无机磷酸盐或羟基脯氨酸的排泄量，也没有改变血液中钙、磷酸盐、碱性磷酸酶、甲状旁腺激素和骨钙素的水平。长期使用乳糖醇作为泻药剂量对人类的钙代谢没有可测量的影响。

/HUMAN EXPOSURE STUDIES/ The chronic use of lactitol as a food additive or laxative might adversely affect calcium homeostasis. Its effect on calcium metabolism has been examined in an open cross-over study in 12 volunteers given 20-40 g lactitol per day for one month. Compared to a control period without lactitol, the disaccharide did not alter the urinary excretion of calcium, inorganic phosphate or hydroxyproline, nor did it alter the circulating levels of calcium, phosphate, alkaline phosphatase, parathormone and osteocalcin. Chronic treatment with lactitol in laxative doses had no measurable effect on calcium metabolism in man.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

• 吸收

在健康受试者进食状态下，口服20克乳糖醇导致平均达峰时间（Tmax）为3.6 ± 1.2小时，最大浓度（Cmax）为776 ± 253纳克/毫升，平均药时曲线下面积（AUC）为6,019 ± 1,771纳克*小时/毫升。

In healthy subjects under fed conditions, oral administration of 20 grams of lactitol resulted in a mean Tmax of 3.6 ± 1.2 hours, Cmax of 776 ± 253 ng/mL, and a mean AUC of 6,019 ± 1,771 ng*hr/mL.

来源:DrugBank

吸收、分配和排泄

• 消除途径

乳糖醇在胃肠道的吸收非常有限。摄入的大部分剂量可能会在结肠中降解成有机酸，并通过粪便排出体外。

Lactitol is not absorbed in the gastrointestinal tract to any significant extent. The vast majority of an ingested dose is likely degraded into organic acids in the colon and eliminated in the feces.

来源:DrugBank

吸收、分配和排泄

• 分布容积

关于乳糖醇的分布体积的数据是不可用的。

Data regarding the volume of distribution of lactitol are unavailable.

来源:DrugBank

吸收、分配和排泄

• 清除

关于乳糖醇清除的数据是不可用的。

Data regarding the clearance of lactitol are unavailable.

来源:DrugBank

吸收、分配和排泄

三只雄性大鼠（体重150-200克；年龄六到八周；一只未经预处理，两只适应了含有7%乳糖醇的饮食）口服给予了大约2毫克的D-(山梨醇-1-(14)C)乳糖醇。在适应乳糖醇的大鼠研究中，0-5小时内呼出的空气中有9-15%的放射性活性被回收，0-24小时内呼出的空气中有48%的放射性活性被回收。尿液和粪便中含有少量给予的放射性活性（尿液，5小时后2.3%，24小时后6.8%；粪便，24小时后11.7%）。5小时后，消化道中含有33%的放射性活性，24小时后为5%；5小时后，身体的其余部分含有20%，24小时后为9%。结论是，乳糖醇在大鼠口服给药后在大鼠体内广泛降解，这主要是通过肠道微生物群，并且大鼠对未标记乳糖醇的适应并没有本质上影响降解的速率和程度。

Three male rats (150-200 g; six to eight weeks of age; one not pretreated and two habituated to a diet containing 7% lactitol) were orally intubated with about 2 mg D-(sorbitol-1-(14)C) lactitol. In the studies with the rats habituated to lactitol, 9-15% of the radioactivity was recovered from the air exhaled in the period 0-5 hours and 48% from the air exhaled in the period 0-24 hours. The urine and the feces contained a minor proportion of the administered radioactivity (urine, 2.3% after five hours and 6.8% after 24 hours; feces, 11.7% after 24 hours). The gastrointestinal tract contained 33% of the radioactivity after five hours and 5% after 24 hours; the remainder of the body contained 20% after five hours and 9% after 24 hours. It was concluded that lactitol is extensively degraded in the rat after oral administration presumably mainly by the intestinal microflora and that habituation of the rats to unlabelled lactitol did not essentially affect the rate and extent of degradation.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 储存条件：
  密封保存

制备方法与用途

根据提供的信息，乳糖醇是一种常用的食品添加剂，具有以下特点：

物理性质：

• 白色结晶或结晶性粉末或无色液体：通常以白色粉末的形式存在。
• 无臭味甜：甜度大约为蔗糖的一半（约8.4kJ/g）。
• 水溶性：10%的乳糖醇水溶液pH值在4.5～7.0之间，且极易溶解于水中。

化学性质：

• 乳糖醇由乳糖经加氢还原反应制得。
• 分为二水物和单水物两种形式。二水物熔点约为70~80℃，单水物的熔点则为115～125℃。

生产方法：

主要通过将30%～40%乳糖在镍催化剂作用下加压氢化制备而成。

用途与应用领域：

• 甜味剂：可用于冰淇淋、饮料（如果汁型）、乳制品和糕点等食品中，作为替代蔗糖的甜味来源。
• 组织改进剂：对于某些食品来说，可以改善其质地或口感。
• 在医学上，也可用作口服降血氨药物治疗急性和慢性肝门脉系统脑病。

安全性与法规要求：

• 按照我国现行标准（GB 2760—96及更新版），乳糖醇属于食品添加剂的一种，并允许在特定食品中按需添加。
• 食品添加剂使用标准规定，冰淇淋、饮料、乳制品和糕点等均可使用乳糖醇作为甜味剂成分。

毒性与ADI（每日允许摄入量）：

• 由于其安全性和广泛的应用背景，乳糖醇被FAO/WHO认定无需特别规定ADI值。
• 具体而言，在中国相关法规中，对于GB 2760—96及GB 2760—2002等标准下对口香糖、冰淇淋和其他多种食品类型有明确的限量要求。

分析检测方法：

• 高压液相色谱法用于分析乳糖醇及其副产品（如山梨糖醇、甘露糖醇等）含量，以确保产品质量符合国家标准。

反应信息

• 作为反应物：
  描述：

  乳糖醇 在 galactose oxidase 、 氧气 、 copper(II) sulfate 、 catalase 、 D,L-histidine 作用下， 生成 4-O-(β-D-galacto-hexodialdo-1,5-pyranosyl)-(1->4)-β-D-sorbitol
  参考文献：
  名称：

  化学酶法制备5-C-（羟甲基）己糖的方法。

  摘要：

  描述了5-C-（羟甲基）己糖的合成，碳水化合物抗代谢。这些化合物是在己糖6-醛与甲醛反应中获得的。使用半乳糖氧化酶通过两步化学合成，可以从D-半乳糖苷有效地获得5-C-（羟甲基）-L-阿拉伯糖-己糖，以制备所需的己糖6-醛。该方法是不使用保护基的碳水化合物合成的一个例子。其他5-C-（羟甲基）己糖是通过典型的化学方法制备的，该方法需要对己糖羟基进行特殊保护。

  DOI：

  10.1021/jo970232p
• 作为产物：
  描述：

  Lactose 在 1-甲基吡咯烷 、 Ru-MACHO-BH 、 氢气 作用下， 以 乙醇 为溶剂， 150.0 ℃ 、5.0 MPa 条件下， 反应 6.0h， 生成 乳糖醇
  参考文献：
  名称：

  Ru-MACHO-BH 催化的糖的高效选择性加氢：糖醇的实用合成

  摘要：

  通过使用均相催化剂的选择性氢化实现了糖醇的高效合成。PN H P-钌催化剂Ru-MACHO-BH以极高的反应性和选择性促进氢化。该反应可应用于各种单糖和双糖，并已成功在几十克的规模上运行。

  DOI：

  10.1021/acs.oprd.2c00047

文献信息

• [EN] A CONJUGATE OF A CYTOTOXIC AGENT TO A CELL BINDING MOLECULE WITH BRANCHED LINKERS<br/>[FR] CONJUGUÉ D'UN AGENT CYTOTOXIQUE À UNE MOLÉCULE DE LIAISON CELLULAIRE AVEC DES LIEURS RAMIFIÉS
  申请人：HANGZHOU DAC BIOTECH CO LTD

  公开号：WO2020257998A1

  公开（公告）日：2020-12-30

  Provided is a conjugation of cytotoxic drug to a cell-binding molecule with a side-chain linker. It provides side-chain linkage methods of making a conjugate of a cytotoxic molecule to a cell-binding ligand, as well as methods of using the conjugate in targeted treatment of cancer, infection and immunological disorders.

  提供了一种将细胞毒性药物与一个侧链连接分子结合的共轭物。它提供了制备细胞毒性分子与细胞结合配体的共轭物的侧链连接方法，以及在靶向治疗癌症、感染和免疫性疾病中使用该共轭物的方法。
• [EN] CROSS-LINKED PYRROLOBENZODIAZEPINE DIMER (PBD) DERIVATIVE AND ITS CONJUGATES<br/>[FR] DÉRIVÉ DE DIMÈRE DE PYRROLOBENZODIAZÉPINE RÉTICULÉ (PBD) ET SES CONJUGUÉS
  申请人：HANGZHOU DAC BIOTECH CO LTD

  公开号：WO2020006722A1

  公开（公告）日：2020-01-09

  A novel cross-linked cytotoxic agents, pyrrolobenzo-diazepine dimer (PBD) derivatives, and their conjugates to a cell-binding molecule, a method for preparation of the conjugates and the therapeutic use of the conjugates.

  一种新型的交联细胞毒剂，吡咯苯并二氮杂环二聚体（PBD）衍生物，以及它们与细胞结合分子的结合物，一种制备这些结合物的方法以及这些结合物的治疗用途。
• [EN] N-OPTIONALLY SUBSTITUTED ARYL-2-OLIGOMER-3-ALKOXYPROPIONAMIDES<br/>[FR] ARYL-2-OLIGOMÈRE-3-ALCOXYPROPIONAMIDES ÉVENTUELLEMENT SUBSTITUÉS EN N
  申请人：NEKTAR THERAPEUTICS

  公开号：WO2012051551A1

  公开（公告）日：2012-04-19

  The invention relates to (among other things) N-optionally substituted aryl- 2-oligomer-3-alkoxypropionamides and compositions comprising the same. A compound of the invention, when administered by any of a number of administration routes, exhibits one or more advantages over corresponding compounds lacking the oligomer.

  这项发明涉及（其他事项之一）N-选择性取代芳基-2-寡聚体-3-烷氧基丙酰胺和包含其的组合物。根据本发明的化合物，当通过多种给药途径之一给予时，表现出比缺乏寡聚体的相应化合物更多的优点。
• [EN] PRMT5 INHIBITORS CONTAINING A DIHYDRO- OR TETRAHYDROISOQUINOLINE AND USES THEREOF<br/>[FR] INHIBITEURS DE LA PRMT5 CONTENANT UNE DIHYDRO- OU TÉTRAHYDRO-ISOQUINOLÉINE ET LEURS UTILISATIONS
  申请人：EPIZYME INC

  公开号：WO2014100730A1

  公开（公告）日：2014-06-26

  Described herein are compounds of Formula (A), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity. Methods of using the compounds for treating PRMT5- mediated disorders are also described.

  本文描述了式（A）的化合物，其药学上可接受的盐以及药物组合物。本发明的化合物对抑制PRMT5活性是有用的。还描述了利用这些化合物治疗PRMT5介导的疾病的方法。
• PRMT5 INHIBITORS AND USES THEREOF
  申请人：Duncan Kenneth W.

  公开号：US20190083482A1

  公开（公告）日：2019-03-21

  Described herein are compounds of Formula (I), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity. Methods of using the compounds for treating PRMT5-mediated disorders are also described.

  本文描述了式（I）的化合物，其药学上可接受的盐以及药物组合物。本发明的化合物对抑制PRMT5活性是有用的。还描述了利用这些化合物治疗PRMT5介导的疾病的方法。

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