1,4;3,6-Dianhydro-D-glucitol-2-nitrat | 16051-77-7

• 物质功能分类: 原料药 - 循环系统用药 - 防治心绞痛药
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 呋喃类
• 英文名称: 1,4;3,6-Dianhydro-D-glucitol-2-nitrat
• 英文别名: [(3R,6S)-3-hydroxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl] nitrate
• CAS: 16051-77-7；16106-20-0；16908-90-0；16908-91-1；35993-37-4；38709-03-4；114718-64-8；127001-76-7
• 化学式: C₆H₉NO₆
• 分子量: 191.141
• InChiKey: YWXYYJSYQOXTPL-GWVKGMJFSA-N

物化性质

• 熔点：
  88-93 °C
• 比旋光度：
  170 º (c=1, EtOH)
• 沸点：
  326.86°C (rough estimate)
• 密度：
  1.5784 (rough estimate)
• 溶解度：
  未稀释的单硝酸异山梨醇酯易溶于水、丙酮、乙醇（96%）和二氯甲烷。稀释产品的溶解度取决于稀释剂及其浓度。

计算性质

• 辛醇/水分配系数(LogP)：
  -1.28
• 重原子数：
  13.0
• 可旋转键数：
  2.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  91.06
• 氢给体数：
  1.0
• 氢受体数：
  6.0

安全信息

• 危险等级：
  4.1
• 危险品标志：
  F
• 安全说明：
  S15,S16,S37/39
• 危险类别码：
  R36/37/38,R11
• 海关编码：
  2932999099
• 危险品运输编号：
  3251
• 危险类别：
  1.1A
• RTECS号：
  LZ4386500
• 包装等级：
  III
• 储存条件：
  -20°C冷冻室

SDS

Name:	Isosorbide-2-mononitrate Material Safety Data Sheet
Synonym:	1,4:3,6-Dianhydro-D-glucitol-2-mononitrate; 2-ISMN; 2-Nitro-1,4,3,6-dianhydrosorbitol
CAS:	16106-20-0

Section 1 - Chemical Product MSDS Name:Isosorbide-2-mononitrate Material Safety Data Sheet
Synonym:1,4:3,6-Dianhydro-D-glucitol-2-mononitrate; 2-ISMN; 2-Nitro-1,4,3,6-dianhydrosorbitol

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Section 2 - COMPOSITION, INFORMATION ON INGREDIENTS

CAS#	Chemical Name	content	EINECS#
16106-20-0	Isosorbide-2-mononitrate	100.0	240-271-4

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

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Section 3 - HAZARDS IDENTIFICATION
EMERGENCY OVERVIEW
Irritating to eyes, respiratory system and skin.
Potential Health Effects
Eye:
Causes eye irritation. May cause chemical conjunctivitis.
Skin:
Causes skin irritation. May be harmful if absorbed through the skin.
Ingestion:
May cause gastrointestinal irritation with nausea, vomiting and diarrhea. May be harmful if swallowed.
Inhalation:
Causes respiratory tract irritation. May be harmful if inhaled.
Chronic:
No information found.

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Section 4 - FIRST AID MEASURES
Eyes: Immediately flush eyes with plenty of water for at least 15 minutes, occasionally lifting the upper and lower eyelids. Get medical aid.
Skin:
Get medical aid. Flush skin with plenty of water for at least 15 minutes while removing contaminated clothing and shoes. Wash clothing before reuse.
Ingestion:
Get medical aid. Do NOT induce vomiting. If conscious and alert, rinse mouth and drink 2-4 cupfuls of milk or water.
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:
Treat symptomatically and supportively.

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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 spray, dry chemical, carbon dioxide, or appropriate foam.

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Section 6 - ACCIDENTAL RELEASE MEASURES
General Information: Use proper personal protective equipment as indicated in Section 8.
Spills/Leaks:
Vacuum or sweep up material and place into a suitable disposal container. Clean up spills immediately, observing precautions in the Protective Equipment section. Avoid generating dusty conditions.
Provide ventilation.

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Section 7 - HANDLING and STORAGE
Handling:
Wash thoroughly after handling. Minimize dust generation and accumulation. Avoid contact with eyes, skin, and clothing. Keep container tightly closed. Avoid ingestion and inhalation. Use with adequate ventilation.
Storage:
Store in a tightly closed container. Store in a cool, dry, well-ventilated area away from incompatible substances.

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Section 8 - EXPOSURE CONTROLS, PERSONAL PROTECTION
Engineering Controls:
Facilities storing or utilizing this material should be equipped with an eyewash facility and a safety shower. Use adequate ventilation to keep airborne concentrations low.
Exposure Limits CAS# 16106-20-0: 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:
A respiratory protection program that meets OSHA's 29 CFR 1910.134 and ANSI Z88.2 requirements or European Standard EN 149 must be followed whenever workplace conditions warrant respirator use.

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Section 9 - PHYSICAL AND CHEMICAL PROPERTIES

Physical State: Crystalline powder
Color: white to off-white
Odor: odorless
pH: Not available.
Vapor Pressure: Not available.
Viscosity: Not available.
Boiling Point: Not available.
Freezing/Melting Point: > 51.5 deg C
Autoignition Temperature: Not applicable.
Flash Point: Not applicable.
Explosion Limits, lower: Not available.
Explosion Limits, upper: Not available.
Decomposition Temperature:
Solubility in water:
Specific Gravity/Density:
Molecular Formula: C6H9NO6
Molecular Weight: 191.16

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Section 10 - STABILITY AND REACTIVITY
Chemical Stability:
Stable at room temperature in closed containers under normal storage and handling conditions.
Conditions to Avoid:
Light, ignition sources, dust generation, excess heat.
Incompatibilities with Other Materials:
Oxidizing agents.
Hazardous Decomposition Products:
Carbon monoxide, oxides of nitrogen, carbon dioxide.
Hazardous Polymerization: Will not occur.

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Section 11 - TOXICOLOGICAL INFORMATION
RTECS#:
CAS# 16106-20-0: LZ4385500 LD50/LC50:
CAS# 16106-20-0: Oral, rat: LD50 = 2300 mg/kg.
Carcinogenicity:
Isosorbide-2-mononitrate - Not listed by ACGIH, IARC, or NTP.
Other:
See actual entry in RTECS for complete information.

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Section 12 - ECOLOGICAL INFORMATION

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

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Section 14 - TRANSPORT INFORMATION

IATA
Shipping Name: Not regulated.
Hazard Class:
UN Number:
Packing Group:
IMO
Shipping Name: Not regulated.
Hazard Class:
UN Number:
Packing Group:
RID/ADR
Shipping Name: Not regulated.
Hazard Class:
UN Number:
Packing group:

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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 26 In case of contact with eyes, rinse immediately
with plenty of water and seek medical advice.
S 37/39 Wear suitable gloves and eye/face
protection.
WGK (Water Danger/Protection)
CAS# 16106-20-0: No information available.
Canada
None of the chemicals in this product are listed on the DSL/NDSL list.
CAS# 16106-20-0 is not listed on Canada's Ingredient Disclosure List.
US FEDERAL
TSCA
CAS# 16106-20-0 is not listed on the TSCA inventory.
It is for research and development use only.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

简介

单硝酸异山梨酯（Isosorbide Mononitrate）是1,4:3,6-二脱水-D-山梨醇-5单硝酸酯的通用名，又名5-硝酸异山梨酯，是二硝酸异山梨酯的主要生物活性代谢物。主要药理作用是松弛血管平滑肌，临床使用的剂型包括普通片剂、缓释制剂和注射剂。主要用于：冠心病的长期治疗；预防心绞痛；心肌梗死后持续心绞痛的治疗；与洋地黄或利尿剂联合应用，用于治疗慢性充血性心力衰竭；以及用于治疗老年单纯性收缩期高血压、高血压危象及围手术期急性高血压。

临床应用

1. 在心脑血管疾病方面，该药物能改善心肌缺血程度，减少心肌耗氧量，并改善心脏功能。其不良反应少且轻微。

2. 在肝硬化治疗上，在消化性溃疡治疗的基础上加用单硝酸异山梨酯治疗肝性溃疡，结果显示其愈合率和有效率明显优于未使用该药物的情况。

药理学

5-单硝酸异山梨酯在血管平滑肌与细胞内的硫基结合后产生一氧化氮（NO）或S－亚硝基巯基化合物。两者可激活鸟苷酸环化酶，增加环鸟苷酸（cGMP）含量，加速钙离子从细胞内释放，抑制钙离子内流，从而舒张血管平滑肌。5-单硝酸异山梨酯的血管扩张作用呈剂量依赖性，随着剂量的增加，依次扩张静脉血管、冠状动脉和阻力小动脉。

其主要作用机制包括：

1. 静脉扩张使血液潴留在外周，减少回心血量，降低心脏前负荷，降低心肌张力。
2. 扩张动脉血管，降低外周血管阻力，从而降低收缩期动脉压和平均动脉压（后负荷），进而降低心肌耗氧量并提高心排出量。
3. 扩张冠状动脉，改善心肌供血，增强心肌对负荷的顺应性和收缩力，促进衰竭心肌细胞功能恢复，并增加心脏排血量。在临床常用剂量范围内，不扩张微动脉，避免发生“冠状动脉窃血”现象。
4. 扩张肺血管，降低肺血管床压力和肺毛细血管压，改善肺淤血，同时降低体循环阻力，进一步改善心功能。
5. 有效促进机体的血管内皮细胞合成前列腺素（PG），抑制合成血小板血栓素A2，并同时抑制血小板的功能。这可以避免血管内形成粥样斑块，从而减少血管狭窄。

上述作用共同促使降低心肌耗氧量，增加供氧量，增强心肌收缩力，改善缺血组织器官的灌注量，从而缓解心绞痛、心力衰竭及高血压的症状。

药代动力学

注射用5-单硝酸异山梨酯是一种强效、长效抗心绞痛药物。口服不受肝代谢效应的影响，以原形药物进入全身循环。其半衰期长达约5小时，生物利用度较高。临床上用于预防和治疗心绞痛。

该药物适用于冠心病的长期治疗、预防血管痉挛和混合型心绞痛，以及心肌梗死后的心脏保护和慢性心力衰竭的长期管理。

生产方法

以山梨醇为原料，在10～15℃条件下与硝酸及乙酐反应2.5小时后即可得到单硝酸异山梨醇酯。此化学反应步骤生成的产品具有较高的生物利用度，半衰期较长，适用于多种心血管疾病的治疗。

毒理学

小鼠经口、静脉注射和腹腔注射的LD50分别为3231.7mg/kg、2215.5mg/kg和2224.6mg/kg。狗长期毒性试验显示每日口服50mg/kg单硝酸异山梨酯连续六月未出现任何毒副作用；而500mg/kg被认为是狗的中毒剂量。

化学性质

单硝酸异山梨酯熔点为52-53℃，主要化学性质表明该物质具有良好的生物利用度和长效特性。临床应用中用于预防及治疗心绞痛。

用途方面，单硝酸异山梨酯主要用于冠心病的长期管理、预防血管痉挛以及混合型心绞痛，并且也适用于心肌梗死后的心脏保护以及慢性心脏衰竭患者的长期治疗。

生产方法包括以山梨醇为原料，在低温条件下与硝酸和乙酐反应制备单硝酸异山梨酯，此过程简单高效。

反应信息

• 作为反应物：
  描述：

  1,4;3,6-Dianhydro-D-glucitol-2-nitrat 、 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 以47.1 %的产率得到
  参考文献：
  名称：

  CN115894596

  摘要：

  公开号：
• 作为产物：
  描述：

  (6-nitrooxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-yl) 4-methylbenzoate 生成 1,4;3,6-Dianhydro-D-glucitol-2-nitrat
  参考文献：
  名称：

  STOSS, P.

  摘要：

  DOI：

文献信息

• STOSS, P.
  作者：STOSS, P.

  DOI：——

  日期：——
• CN115894596
  申请人：——

  公开号：——

  公开（公告）日：——