酒石酸溴莫尼定 | 70359-46-5

• 物质功能分类: 生物化工 - 抑制剂 - 神经信号通路(Neuronal Signaling)
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 中文名称: 酒石酸溴莫尼定
• 中文别名: 溴莫尼定酒石酸盐；5-溴-6-(咪唑啉-2-基)氨基喹喔啉酒石酸盐
• 英文名称: 5-bromo-6-(2-imidazolylamino)quinoxaline L-tartrate
• 英文别名: brimonidine L-tartrate；brimonidine tartarate；brimonidine tartrate；Lumify；5-bromo-N-(4,5-dihydro-1H-imidazol-2-yl)quinoxalin-6-amine;(2R,3R)-2,3-dihydroxybutanedioic acid
• CAS: 70359-46-5
• 化学式: C₄H₆O₆*C₁₁H₁₀BrN₅
• 分子量: 442.226
• InChiKey: QZHBYNSSDLTCRG-LREBCSMRSA-N

物化性质

• 熔点：
  207-208°C (dec.)
• 溶解度：
  DMSO：1 mg/ml； PBS（pH 7.2）：3 mg/ml

计算性质

• 辛醇/水分配系数(LogP)：
  -0.36
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  177
• 氢给体数：
  6
• 氢受体数：
  9

安全信息

• 海关编码：
  2933990090
• 安全说明：
  S36/37
• WGK Germany：
  3
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  -20°C freezer

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: Brimonidine L-Tartrate
Synonyms: Brimonidine Tartrate

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Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.

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Section 3. Composition/information on ingredients.
Ingredient name: Brimonidine L-Tartrate
CAS number: 70359-46-5

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Section 4. First aid measures
Skin contact: Immediately wash skin with copious amounts of water for at least 15 minutes while removing
contaminated clothing and shoes. If irritation persists, seek medical attention.
Eye contact: Immediately wash skin with copious amounts of water for at least 15 minutes. Assure adequate
flushing of the eyes by separating the eyelids with fingers. If irritation persists, seek medical
attention.
Inhalation: Remove to fresh air. In severe cases or if symptoms persist, seek medical attention.
Ingestion: Wash out mouth with copious amounts of water for at least 15 minutes. Seek medical attention.

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Section 5. Fire fighting measures
In the event of a fire involving this material, alone or in combination with other materials, use dry
powder or carbon dioxide extinguishers. Protective clothing and self-contained breathing apparatus
should be worn.

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Section 6. Accidental release measures
Personal precautions: Wear suitable personal protective equipment which performs satisfactorily and meets local/state/national
standards.
Respiratory precaution: Wear approved mask/respirator
Hand precaution: Wear suitable gloves/gauntlets
Skin protection: Wear suitable protective clothing
Eye protection: Wear suitable eye protection
Methods for cleaning up: Mix with sand or similar inert absorbent material, sweep up and keep in a tightly closed container
for disposal. See section 12.
Environmental precautions: Do not allow material to enter drains or water courses.

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Section 7. Handling and storage
Handling: This product should be handled only by, or under the close supervision of, those properly qualified
in the handling and use of potentially hazardous chemicals, who should take into account the fire,
health and chemical hazard data given on this sheet.
Store in closed vessels, under −20◦C.
Storage:

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Section 8. Exposure Controls / Personal protection
Engineering Controls: Use only in a chemical fume hood.
Personal protective equipment: Wear laboratory clothing, chemical-resistant gloves and safety goggles.
General hydiene measures: Wash thoroughly after handling. Wash contaminated clothing before reuse.

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Section 9. Physical and chemical properties
Appearance: Not specified
Boiling point: No data
No data
Melting point:
Flash point: No data
Density: No data
Molecular formula: C15H16BrN5O6
Molecular weight: 442.2

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Section 10. Stability and reactivity
Conditions to avoid: Heat, flames and sparks.
Materials to avoid: Oxidizing agents.
Possible hazardous combustion products: Carbon monoxide, nitrogen oxides, hydrogen bromide.

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Section 11. Toxicological information
No data.

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Section 12. Ecological information
No data.

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Section 13. Disposal consideration
Arrange disposal as special waste, by licensed disposal company, in consultation with local waste
disposal authority, in accordance with national and regional regulations.

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Section 14. Transportation information
Non-harzardous for air and ground transportation.

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Section 15. Regulatory information
No chemicals in this material are subject to the reporting requirements of SARA Title III, Section
302, or have known CAS numbers that exceed the threshold reporting levels established by SARA
Title III, Section 313.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

降眼压药物

溴莫尼定 溴莫尼定是一种高选择性α2-受体阻滞剂，由美国Allergan公司研发成功。该药可降低眼内压(IOP)，适用于开角型青光眼和高眼压患者的慢性治疗，还可用于氩激光术后眼压增高者。

酒石酸溴莫尼定滴眼液是其酒石酸形式，具有双重的作用机制：通过减少房水的生成和增加色素上皮层巩膜液外流来降低眼内压。本品滴入眼中后，起效迅速，在2小时后达到峰值，并可在12小时内维持疗效。血中只能检测到微量药物，它在肝脏进行首过代谢并经肾脏排出。

与α-受体阻滞剂相比，酒石酸溴莫尼定滴眼液具有较低的脂溶性，不易穿过血脑屏障，不会产生镇静或低血压等中枢神经系统的不良反应。此外，本品对α2-肾上腺素受体的选择性极高，长期使用不会引起快速减敏现象。

与β-受体阻滞剂相比，酒石酸溴莫尼定滴眼液对心血管的影响轻微，不影响肺功能，因此适用于禁用β-受体阻滞剂的患者。当单独使用β-受体阻滞剂不能达到治疗目的时，可以同时加用本品。

临床研究

临床试验表明，酒石酸溴莫尼定滴眼液能有效降低青光眼病人的眼内压，且仅有轻微的心血管影响。与0.5%的噻吗洛尔相比，两者疗效相当。两药分别单独使用时，每日2次，每次1滴，达峰值时眼内压平均降低值分别为本品0.79～1.01 kPa、0.5%的噻吗洛尔为0.8～0.88kPa；用药12小时后，眼内压平均降低值分别为0.49～0.67kPa和0.79～0.88kPa。滴眼液建议采用每日3次方案，但有些研究显示，每日2次与每日3次疗效无显著差异。

不良反应

常见的不良反应包括嗜睡、头痛等。儿童使用本品时可能表现为嗜睡及反应力下降，不推荐用于2岁以下的儿童。

生物活性

Brimonidine Tartrate是一种高选择性α-肾上腺素能受体激动剂，EC50为0.45 nM，用于治疗开角型青光眼或高眼压症。

目标	值
α2a-受体	0.45 nM (EC50)

体内研究

在实验中发现，Brimonidine能显著保护视网膜神经节细胞免于进一步损失，并且在缺血条件下能够提高视网膜神经节细胞的存活率。

研究类型	操作	结果
体外研究	0.5 和1 mg/kg	防止神经节细胞进一步丧失
		BDNF阳性的视网膜神经节细胞数量增加至166%
体内研究	1 mg/kg	显著保护高眼压诱导的视网膜神经节细胞死亡
	0.0001%, 0.001%或0.01%	视网膜神经节细胞存活率分别为76%或90%，完全阻止细胞死亡

以上信息展示了溴莫尼定作为一种高效、安全的降眼压药物，具有广泛的临床应用前景。

反应信息

• 作为反应物：
  描述：

  酒石酸溴莫尼定 在 sodium hydroxide 作用下， 以 水 为溶剂， 反应 0.25h， 以60%的产率得到溴莫尼定
  参考文献：
  名称：

  [EN] DRUGS AND COMPOSITIONS FOR THE TREATMENT OF OCULAR DISORDERS
  [FR] COMPOSÉS ET COMPOSITIONS POUR LE TRAITEMENT DE TROUBLES OCULAIRES

  摘要：

  本发明提供了治疗活性化合物的新前药，包括寡聚前药，以及用于治疗医学疾病的组合物，例如青光眼，一种与眼压增高有关的疾病或异常，需要神经保护的疾病，年龄相关性黄斑变性，或糖尿病性视网膜病变。

  公开号：

  WO2018175922A1

文献信息

• Compounds, formulations, and methods for treating or preventing rosacea
  申请人：——

  公开号：US20040242588A1

  公开（公告）日：2004-12-02

  In methods, compounds, and topical formulations for treatment of rosacea incorporating compounds represented by the formulas below: 1 wherein each of R 1 , R 2 , and R 3 is independently hydrogen, hologen, alkyl, or alkoxy; each of R 4 and R 5 is independently hydrogen, alkyl, or alkoxy; and each of R 6 and R 7 is independently hydrogen, nitro, alkyl, or alkoxy; wherein each of A 1 , A 3 , and A 4 is independently hydrogen or alkyl; and A 2 is independently hydrogen or hydroxy; and wherein each of B 1 , B 2 , and B 3 is independently hydrogen, hydroxy, or alkoxy; and each of B 4 and B 5 is independently hydrogen or alkyl, applying such compounds topically as sprays, mists, aerosols, solutions, lotions, gels, creams, ointments, pastes, unguents, emulsions, and suspensions to treat rosacea and its symptoms.

  在治疗酒渣鼻的方法、化合物和局部制剂中，包含以下公式所代表的化合物：其中R1、R2和R3中的每一个独立地是氢、卤素、烷基或烷氧基；R4和R5中的每一个独立地是氢、烷基或烷氧基；R6和R7中的每一个独立地是氢、硝基、烷基或烷氧基；A1、A3和A4中的每一个独立地是氢或烷基；A2独立地是氢或羟基；B1、B2和B3中的每一个独立地是氢、羟基或烷氧基；B4和B5中的每一个独立地是氢或烷基。将这些化合物作为喷雾、薄雾、气雾剂、溶液、乳液、凝胶、霜、药膏、糊剂、乳膏和悬浮液局部涂抹，以治疗酒渣鼻及其症状。
• NOVEL COMPOUNDS AND THEIR USE RELATED TO COMPOSITIONS FOR TREATING DISEASE
  申请人：Ruckmick Stephen

  公开号：US20070093494A1

  公开（公告）日：2007-04-26

  Novel compounds and their uses are disclosed herein.

  本文披露了新化合物及其用途。
• Brimonidine Compositions for Treating Erythema
  申请人：Theobald Klaus P.

  公开号：US20090061020A1

  公开（公告）日：2009-03-05

  The present invention is directed to a pharmaceutical composition including brimonidine tartrate in an amount from about 0.17 percent by weight to about 0.19 percent by weight in a pharmaceutically acceptable carrier such as a gel or cream. The invention also relates to a method of treating erythema in a patient with rosacea by administering the composition of the invention to the site of erythema on the skin of the patient.

  本发明涉及一种制药组合物，其中包括酒石酸布里莫尼定，其含量约为0.17%至0.19%的质量百分比，以药学上可接受的载体（如凝胶或乳霜）为基础。该发明还涉及一种治疗鲁米病患者皮肤红斑的方法，即通过将本发明的组合物用于患者皮肤上的红斑处进行治疗。
• Compounds, formulations, and methods for treating or preventing inflammatory skin disorders
  申请人：DeJovin A. Jack

  公开号：US20050276830A1

  公开（公告）日：2005-12-15

  In methods, compounds, and topical formulations for treatment of inflammatory skin disorders incorporating compounds represented by the formulas below: wherein each of R 1 , R 2 , and R 3 is independently hydrogen, hologen, alkyl, or alkoxy; each of R 4 and R 5 is independently hydrogen, alkyl, or alkoxy; and each of R 6 and R 7 is independently hydrogen, nitro, alkyl, or alkoxy; wherein each of A 1 , A 3 , and A 4 is independently hydrogen or alkyl; and A 2 is independently hydrogen or hydroxy; and wherein each of B 1 , B 2 , and B 3 is independently hydrogen, hydroxy, or alkoxy; and each of B 4 and B 5 is independently hydrogen or alkyl, applying such compounds topically as sprays, mists, aerosols, solutions, lotions, gels, creams, ointments, pastes, unguents, emulsions, and suspensions to treat inflammatory skin disorders and the symptoms associated therewith.

  在治疗炎性皮肤疾病的方法、化合物和局部制剂中，包含由以下公式表示的化合物：其中R1、R2和R3中的每一个独立地表示氢、卤素、烷基或烷氧基；R4和R5中的每一个独立地表示氢、烷基或烷氧基；R6和R7中的每一个独立地表示氢、硝基、烷基或烷氧基；其中A1、A3和A4中的每一个独立地表示氢或烷基；A2独立地表示氢或羟基；B1、B2和B3中的每一个独立地表示氢、羟基或烷氧基；B4和B5中的每一个独立地表示氢或烷基。将这些化合物作为喷雾、雾、气溶胶、溶液、乳液、凝胶、霜、软膏、糊剂、乳膏和悬浮液局部涂抹，以治疗炎性皮肤疾病及其相关症状。
• Compounds, formulations, and methods for ameliorating telangiectasias
  申请人：Dejovin A. Jack

  公开号：US20060264515A1

  公开（公告）日：2006-11-23

  Methods, compounds, and topical formulations for treatment of telangiectasias are disclosed. The methods comprise topically applying a composition comprising an α-adrenergic receptor agonist to telangiectatic skin. Amelioration of telangiectasia symptoms begins within minutes after topical application of a disclosed composition. A single application can significantly lessen telangiectasia discoloration for at least about 2 hours.

  本文揭示了治疗毛细血管扩张的方法、化合物和局部制剂。该方法包括将含有α-肾上腺素受体激动剂的组合物局部涂抹于毛细血管扩张的皮肤上。使用揭示的组合物局部涂抹后，毛细血管扩张症状的改善在几分钟内开始。单次应用可以显著减轻毛细血管扩张的色素沉着，持续至少约2小时。