ambroxol hydrochloride | 23828-92-4

• 物质功能分类: 原料药 - 呼吸系统用药 - 祛痰药
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: ambroxol hydrochloride
• 英文别名: trans-4-[(2-amino-3,5-dibromobenzyl)amino]cyclohexanol hydrochloride；ambroxol；Mucosolvan
• CAS: 23828-92-4
• 化学式: C₁₃H₁₈Br₂N₂O*ClH
• 分子量: 414.568
• InChiKey: QNVKOSLOVOTXKF-PFWPSKEQSA-N

物化性质

• 熔点：
  233-234.5°C
• 溶解度：
  微溶于水，溶于甲醇，几乎不溶于二氯甲烷。

计算性质

• 辛醇/水分配系数(LogP)：
  3.61
• 重原子数：
  19.0
• 可旋转键数：
  3.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  58.28
• 氢给体数：
  3.0
• 氢受体数：
  3.0

安全信息

• 危险品标志：
  Xn
• 安全说明：
  S36
• 危险类别码：
  R22
• WGK Germany：
  3
• 海关编码：
  2922199090
• 危险品运输编号：
  NONH for all modes of transport
• RTECS号：
  GV8423000
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H315,H319,H335
• 储存条件：
  库房应保持通风、低温和干燥。

SDS

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Section 1. IDENTIFICATION OF THE SUBSTANCE/MIXTURE
Product identifiers
Product name : Ambroxol hydrochloride
CAS-No. : 23828-92-4
Relevant identified uses of the substance or mixture and uses advised against
Identified uses : Laboratory chemicals, Manufacture of substances

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Section 2. HAZARDS IDENTIFICATION
Classification of the substance or mixture
Not a hazardous substance or mixture according to Regulation (EC) No. 1272/2008.
This substance is not classified as dangerous according to Directive 67/548/EEC.
Label elements
The product does not need to be labelled in accordance with EC directives or respective national laws.
Other hazards - none

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Section 3. COMPOSITION/INFORMATION ON INGREDIENTS
Substances
Synonyms : 2-Amino-3,5-dibromo-N-(trans-4-hydroxycyclohexyl)benzylamine
Formula : C13H18Br2N2O · HCl
Molecular Weight : 414,56 g/mol

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Section 4. FIRST AID MEASURES
Description of first aid measures
General advice
Consult a physician. Show this safety data sheet to the doctor in attendance.
If inhaled
If breathed in, move person into fresh air. If not breathing, give artificial respiration. Consult a physician.
In case of skin contact
Wash off with soap and plenty of water. Consult a physician.
In case of eye contact
Flush eyes with water as a precaution.
If swallowed
Never give anything by mouth to an unconscious person. Rinse mouth with water. Consult a physician.
Most important symptoms and effects, both acute and delayed
To the best of our knowledge, the chemical, physical, and toxicological properties have not been
thoroughly investigated.
Indication of any immediate medical attention and special treatment needed
no data available

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Section 5. FIREFIGHTING MEASURES
Extinguishing media
Suitable extinguishing media
Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.
Special hazards arising from the substance or mixture
Carbon oxides, nitrogen oxides (NOx), Hydrogen chloride gas, Hydrogen bromide gas
Advice for firefighters
Wear self contained breathing apparatus for fire fighting if necessary.
Further information
no data available

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Section 6. ACCIDENTAL RELEASE MEASURES
Personal precautions, protective equipment and emergency procedures
Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Avoid
breathing dust.
Environmental precautions
Do not let product enter drains.
Methods and materials for containment and cleaning up
Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed
containers for disposal.
Reference to other sections
For disposal see section 13.

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Section 7. HANDLING AND STORAGE
Precautions for safe handling
Avoid formation of dust and aerosols.
Provide appropriate exhaust ventilation at places where dust is formed.
Conditions for safe storage, including any incompatibilities
Store in cool place. Keep container tightly closed in a dry and well-ventilated place.
Recommended storage temperature: 2 - 8 °C
Specific end uses
no data available

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Section 8. EXPOSURE CONTROLS/PERSONAL PROTECTION
Control parameters
Components with workplace control parameters
Exposure controls
Appropriate engineering controls
Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and
at the end of workday.
Personal protective equipment
Eye/face protection
Use equipment for eye protection tested and approved under appropriate government standards
such as NIOSH (US) or EN 166(EU).
Skin protection
Handle with gloves. Gloves must be inspected prior to use. Use proper glove removal technique
(without touching glove's outer surface) to avoid skin contact with this product. Dispose of
contaminated gloves after use in accordance with applicable laws and good laboratory practices.
Wash and dry hands.
The selected protective gloves have to satisfy the specifications of EU Directive 89/686/EEC and
the standard EN 374 derived from it.
Body Protection
Choose body protection in relation to its type, to the concentration and amount of dangerous
substances, and to the specific work-place., The type of protective equipment must be selected
according to the concentration and amount of the dangerous substance at the specific workplace.
Respiratory protection
Respiratory protection is not required. Where protection from nuisance levels of dusts are desired,
use type N95 (US) or type P1 (EN 143) dust masks. Use respirators and components tested and
approved under appropriate government standards such as NIOSH (US) or CEN (EU).

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Section 9. PHYSICAL AND CHEMICAL PROPERTIES
Information on basic physical and chemical properties
a) Appearance Form: solid
b) Odour no data available
c) Odour Threshold no data available
d) pH no data available
e) Melting point/freezing no data available
point
f) Initial boiling point and no data available
boiling range
g) Flash point no data available
h) Evaporation rate no data available
i) Flammability (solid, gas) no data available
j) Upper/lower no data available
flammability or
explosive limits
k) Vapour pressure no data available
l) Vapour density no data available
m) Relative density no data available
n) Water solubility no data available
o) Partition coefficient: n- no data available
octanol/water
p) Autoignition no data available
temperature
q) Decomposition no data available
temperature
r) Viscosity no data available
s) Explosive properties no data available
t) Oxidizing properties no data available
Other safety information
no data available

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Section 10. STABILITY AND REACTIVITY
Reactivity
no data available
Chemical stability
no data available
Possibility of hazardous reactions
no data available
Conditions to avoid
no data available
Incompatible materials
no data available
Hazardous decomposition products
Other decomposition products - no data available

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Section 11. TOXICOLOGICAL INFORMATION
Information on toxicological effects
Acute toxicity
LD50 Oral - rat - 4.203 mg/kg
Remarks: Behavioral:Ataxia. Behavioral:Somnolence (general depressed activity). Lungs, Thorax, or
Respiration:Dyspnea.
Skin corrosion/irritation
no data available
Serious eye damage/eye irritation
no data available
Respiratory or skin sensitization
no data available
Germ cell mutagenicity
no data available
Carcinogenicity
IARC: No component of this product present at levels greater than or equal to 0.1% is identified as
probable, possible or confirmed human carcinogen by IARC.
Reproductive toxicity
no data available
Specific target organ toxicity - single exposure
no data available
Specific target organ toxicity - repeated exposure
no data available
Aspiration hazard
no data available
Potential health effects
Inhalation May be harmful if inhaled. May cause respiratory tract irritation.
Ingestion May be harmful if swallowed.
Skin May be harmful if absorbed through skin. May cause skin irritation.
Eyes
May cause eye irritation.
Signs and Symptoms of Exposure
To the best of our knowledge, the chemical, physical, and toxicological properties have not been
thoroughly investigated.
Additional Information
RTECS: GV8425000

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Section 12. ECOLOGICAL INFORMATION
Toxicity
no data available
Persistence and degradability
no data available
Bioaccumulative potential
no data available
Mobility in soil
no data available
Results of PBT and vPvB assessment
no data available
Other adverse effects
no data available

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Section 13. DISPOSAL CONSIDERATIONS
Waste treatment methods
Product
Offer surplus and non-recyclable solutions to a licensed disposal company. Dissolve or mix the material
with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber.
Contaminated packaging
Dispose of as unused product.

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Section 14. TRANSPORT INFORMATION
UN number
ADR/RID: - IMDG: - IATA: -
UN proper shipping name
ADR/RID: Not dangerous goods
IMDG: Not dangerous goods
IATA: Not dangerous goods
Transport hazard class(es)
ADR/RID: - IMDG: - IATA: -
Packaging group
ADR/RID: - IMDG: - IATA: -
Environmental hazards
ADR/RID: no IMDG Marine pollutant: no IATA: no
Special precautions for user
no data available

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SECTION 15 - REGULATORY INFORMATION
N/A

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SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

盐酸氨溴索简介

盐酸氨溴索（Ambroxol Hydrochloride）是祛痰药溴己新的活性代谢物，N-去甲基化后环己基对位引入反式羟基。与溴己新相比，其毒性较低而疗效更优。

盐酸氨溴索的药理作用 止咳化痰作用

盐酸氨溴索主要作用于呼吸道分泌细胞，调节黏液性及浆液性物质的分泌。它能够增加浆液分泌，降低痰液粘稠度，并裂解痰液中的酸性糖蛋白多糖纤维。此外，该药物还能抑制粘液腺和杯状细胞中酸性蛋白的合成，从而促进痰液排出。

抗氧化作用

盐酸氨溴索具有明显的抗氧化作用。研究表明，它能够对中性粒细胞产生的H2O2产生强烈抑制，并激活细胞内的谷胱甘肽系统以对抗氧自由基破坏。

合成方法

以邻－硝基苯甲醛为起始原料，与反式－4－氨基环己醇反应得到化合物(3)，然后用特殊的催化剂如改性Pd/C同时还原硝基和C=N基团得到化合物(2)。最后，使用HBr/H2O2进行氧化处理生成盐酸氨溴索。

应用领域 慢性呼吸道疾病

用于急、慢性呼吸道疾病的治疗，尤其是慢性支气管炎的祛痰治疗。

新生儿呼吸窘迫综合征（NRDS）

促进内源性表面活性物质（PS）的生物合成与分泌，提高肺泡Ⅱ型细胞释放内源性PS，从而降低肺泡的表面张力，改善肺功能。

体外循环心脏术后肺保护作用

有效促进胸外科术后表面活性物质的合成与分泌，抑制活化的中性粒细胞反应，降低呼吸道阻力及气道高反应性。

注意事项 禁忌症

• 对盐酸氨溴索过敏者。
• 妊娠前3个月。

警惕使用

• 恶性纤毛综合征患者。
• 肝、肾功能不全者。
• 胃溃疡患者。
• 青光眼患者。
• 妊娠中晚期或哺乳期妇女。

与其他药物的协同作用

与抗生素（如阿莫西林、头孢呋辛、红霉素等）联合使用可提高抗生素在肺组织中的浓度。

不良反应

偶见轻微胃肠道不良反应，剂量减少后可缓解。

物理化学性质

• 类别：有毒物品。
• 毒性分级：中毒。
• 急性毒性（口服）：
  • 大鼠 LD50: 4203 毫克/公斤
  • 小鼠 LD50: 2380 毫克/公斤

危险性

• 可燃；燃烧时产生有毒氮氧化物、氯化氢和溴化物烟雾。
• 库房应保持通风并处于低温干燥环境中。

灭火方法

使用干粉、泡沫、砂土或二氧化碳灭火器以及雾状水。

反应信息

• 作为反应物：
  描述：

  ambroxol hydrochloride 在 sodium hydroxide 作用下， 以 水 为溶剂， 生成 trans-4-[(2-Amino-3,5-dibromobenzyl)amino]cyclohexanol
  参考文献：
  名称：

  三种新型反式-4-[(2-氨基-3,5-二溴苄基)氨基]环己醇与羟基苯甲酸共晶的合成、结构表征和Hirshfeld分析研究

  摘要：

  摘要 活性药物成分，反式-4-[（2-氨基-3,5-二溴苄基）氨基]环己醇（AMB）和一些有机酸如对羟基苯甲酸（PHBA）、间羟基苯甲酸（MHBA）的组合) 和 3,4-二羟基苯甲酸 (DHBA)，产生三种新型共晶，通过 X 射线单晶、荧光光谱和热分析（DSC 和 TGA）表征，其中包括 2:2 的共晶 1 ：AMB、PHBA 和 H 2 O 的 1 化学计量，AMB 和 MHBA 的化学计量为 1:1 的共晶 2，AMB、DHBA 和 CH 3 OH 的化学计量为 1:1:1 的共晶 3。还根据 Hirshfeld 表面研究了共晶相的成分。在晶格中，观察到三维氢键网络，包括二维分子支架基序的形成。三个共晶的 Hirshfeld 表面和指纹图表明结构通过 H⋯H、N-H⋯O、H⋯Br 和 C⋯H 分子间相互作用稳定。此外，溶解度的研究表明，这种共晶策略可以促进AMB的溶解度并遵循以下顺序：共晶1

  DOI：

  10.1016/j.molstruc.2014.11.026
• 作为产物：
  描述：

  trans-4-[(2-Amino-3,5-dibromobenzyl)amino]cyclohexanol 在 盐酸 作用下， 以 水 、 丙酮 为溶剂， 反应 1.0h， 以97%的产率得到ambroxol hydrochloride
  参考文献：
  名称：

  一种盐酸氨溴索的合成方法

  摘要：

  本发明属于药物合成领域，具体公开了一种盐酸氨溴索的合成方法。本发明主要以邻硝基苯甲醛为起始原料，经溴化后得到2‑硝基‑3，5‑二溴苯甲醛，所得2‑硝基‑3，5‑二溴苯甲醛再与反式‑4‑氨基环己醇反应，再经还原、盐酸盐成盐最终制得盐酸氨溴索。本发明所采用的合成方法原料成本低、操作简单、安全环保、简化了生产工序，且提高了产品收率及产品纯度，适合工业化生产。

  公开号：

  CN104788326B

文献信息

• Substituted 1,3-thiazole compounds, their production and use
  申请人：——

  公开号：US20040053973A1

  公开（公告）日：2004-03-18

  (1) A 1,3-thiazole compound of which the 5-position is substituted with a 4-pyridyl group having a substituent including no aromatic group or (2) a 1,3-thiazole compound of which the 5-position is substituted with a pyridyl group having at the position adjacent to a nitrogen atom of the pyridyl group a substituent including no aromatic group has an excellent p38 MAP kinase inhibitory activity.

  (1) 一种1,3-噻唑化合物，其5位被取代为含有一个取代基的4-吡啶基团，该取代基不包括芳香基，或者(2) 一种1,3-噻唑化合物，其5位被取代为一个吡啶基团，该吡啶基团的氮原子邻近位置有一个取代基，该取代基不包括芳香基，具有出色的p38 MAP激酶抑制活性。
• TROPAN COMPOUND
  申请人：ONO PHARMACEUTICAL CO., LTD.

  公开号：EP1785421A1

  公开（公告）日：2007-05-16

  The conventional anticholinergic drugs for administration through inhalation have been considered to have the possibility of aggravating dysuria associated with prostatic hyperplasia mediated by blood, and it has been demanded that the conventional anticholinergic drugs for administration through inhalation will have to show reduced side effects or adverse ractions. The present invention relates to a compound represented by the general formula (I): (wherein A represents; and R1, R2, R3 and R1 each a hydrogen atom or a substituent; R5 is a substituent; X- is an anion;the symbol: denotes an exo-form or endo-form, or their mixture), its salt or solvation product thereof. They are useful as a prophylactic and/or therapeutic agent with reduced side effects or adverse reactions for the diseases mediated by the muscarinic receptor.

  传统的抗胆碱药物通过吸入给药被认为可能加重与前列腺增生相关的排尿困难，并要求传统的抗胆碱药物通过吸入给药必须显示减少副作用或不良反应。 本发明涉及一种由通式（I）表示的化合物： （其中A代表; 和R1、R2、R3和R1分别是氢原子或取代基; R5是取代基; X-是阴离子;符号: 表示外向型或内向型，或它们的混合物），其盐或溶剂化产物。它们可用作通过胆碱受体介导的疾病的预防和/或治疗剂，具有减少副作用或不良反应。
• BENZAZEPINE DERIVATIVE, PROCESS FOR PRODUCING THE SAME, AND USE
  申请人：Takeda Chemical Industries, Ltd.

  公开号：EP1422228A1

  公开（公告）日：2004-05-26

  The present invention provides a novel benzazepine derivative represented by formula : wherein, R1 is a 5- or 6-membered aromatic ring, R2 is lower alkyl group, etc., Y is an optionally substituted imino group, ring A and ring B are independently an optionally substituted aromatic ring, W is formula -W1-X2-W2- (W1 and W2 are independently S(O)m1 (m1 is 0, 1 or 2), etc., and X2 is an optionally substituted alkylene groupetc. ), a preparation method and use thereof.

  本发明提供了一种新型的苯并氮杂环衍生物，其由以下公式表示： 其中，R1是一个5-或6-成员的芳香环，R2是低级烷基团等，Y是可选地取代的亚氨基，环A和环B是独立地选自一个可选地取代的芳香环，W是公式-W1-X2-W2-（W1和W2是独立地为S(O)m1（m1是0、1或2）等，X2是一个可选地取代的亚烷基团等），其制备方法及其用途。
• [EN] HETEROCYCLIC COMPOUNDS AND THEIR USE AS RETINOID-RELATED ORPHAN RECEPTOR (ROR) GAMMA-T INHIBITORS<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES ET LEUR UTILISATION EN TANT QU'INHIBITEURS GAMMA-T DU RÉCEPTEUR ORPHELIN APPARENTÉ AUX RÉCEPTEURS DES RÉTINOÏDES (ROR) )
  申请人：TAKEDA PHARMACEUTICAL

  公开号：WO2016002968A1

  公开（公告）日：2016-01-07

  Provided are heterocyclic compounds having a RORγt inhibitory action represented by the formula (I): wherein each symbol is as defined in the specification, or a salt thereof.

  提供的是具有RORγt抑制作用的杂环化合物，其由公式(I)表示：其中每个符号如说明书中定义，或其盐。
• MEDICINAL COMPOSITIONS
  申请人：Takeda Chemical Industries, Ltd.

  公开号：EP1402900A1

  公开（公告）日：2004-03-31

  The present invention relates to an agent for the prophylaxis or treatment of pain, an agent for suppressing activation of osteoclast, and an inhibitor of osteoclast formation, which contains a p38 MAP kinase inhibitor and/or a TNF-α production inhibitor.

  本发明涉及一种用于预防或治疗疼痛的药剂，一种用于抑制破骨细胞活化的药剂，以及一种包含p38 MAP激酶抑制剂和/或TNF-α产生抑制剂的破骨细胞形成抑制剂。