quinine; hydrogen sulfate dihydrate | 6119-70-6

• 物质功能分类: 原料药 - 抗寄生虫病药 - 抗疟药
• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 金鸡纳生物碱
• 英文名称: quinine; hydrogen sulfate dihydrate
• 英文别名: quinine sulfate dihydrate；quinine sulfate；Chinin; Hydrogensulfat-Dihydrat；Chinin; Sulfat-Dihydrat；Quinine sulfate salt monohydrate；(R)-[(2S,4S,5R)-5-ethenyl-1-azabicyclo[2.2.2]octan-2-yl]-(6-methoxyquinolin-4-yl)methanol;sulfuric acid;hydrate
• CAS: 6119-70-6
• 化学式: 2C₂₀H₂₄N₂O₂*2H₂O*H₂O₄S
• 分子量: 782.956
• InChiKey: ZYCWGZVLCXRARB-HZQSTTLBSA-N

物化性质

• 熔点：
  ~225 °C (dec.)(lit.)
• 比旋光度：
  -245 º (c=2, 0.1M HCl)
• 溶解度：
  溶于氯仿和无水乙醇（2:1）的混合物。
• LogP：
  3.44
• 稳定性/保质期：
  常温常压下稳定，是一种白色粉末。

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  130
• 氢给体数：
  4
• 氢受体数：
  9

安全信息

• TSCA：
  Yes
• 危险品标志：
  Xn
• 安全说明：
  S24,S37,S45
• 危险类别码：
  R22,R42/43
• WGK Germany：
  3
• 海关编码：
  29392000
• 危险品运输编号：
  UN 2811
• RTECS号：
  VA8440000
• 危险性防范说明：
  P280,P305+P351+P338,P310
• 危险性描述：
  H302,H315,H319,H332,H335
• 储存条件：
  避光，存于阴凉干燥处，并密封保存。

SDS

Name:	Quinine sulfate dihydrate 99+% Material Safety Data Sheet
Synonym:	Quinine sulfate; Quinine bisulfate; Quinine hydrogen sulfate
CAS:	6119-70-6

Section 1 - Chemical Product MSDS Name:Quinine sulfate dihydrate 99+% Material Safety Data Sheet
Synonym:Quinine sulfate; Quinine bisulfate; Quinine hydrogen sulfate

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Section 2 - COMPOSITION, INFORMATION ON INGREDIENTS

CAS#	Chemical Name	content	EINECS#
6119-70-6	Quinine sulfate dihydrate	> 99	unlisted

Hazard Symbols: XN
Risk Phrases: 20/21/22

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Section 3 - HAZARDS IDENTIFICATION
EMERGENCY OVERVIEW
Harmful by inhalation, in contact with skin and if swallowed.Light sensitive.
Potential Health Effects
Eye:
May cause eye irritation.
Skin:
May cause skin irritation. May be harmful if absorbed through the skin. May cause an allergic reaction in certain individuals.
Ingestion:
May cause gastrointestinal irritation with nausea, vomiting and diarrhea. May cause muscle tremor and impaired motor function. May cause systemic toxic effects on the heart, liver, and kidneys.
Exposure may cause anemia and other blood abnormalities. May cause nausea and vomiting. May cause acute hepatitis. May cause allergic reaction. Ingestion can cause blurred vision, narrowing of the visual field, or blindness.
Inhalation:
May cause respiratory tract irritation. May cause effects similar to those described for ingestion. Harmful if inhaled.
Chronic:
Prolonged or repeated skin contact may cause sensitization dermatitis and possible destruction and/or ulceration. Adverse reproductive effects have been reported in animals.

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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 immediately.
Skin:
Get medical aid. Flush skin with plenty of water for at least 15 minutes while removing contaminated clothing and shoes.
Ingestion:
Call a poison control center. If swallowed, do not induce vomiting unless directed to do so by medical personnel. Never give anything by mouth to an unconscious person. Get medical aid.
Inhalation:
Get medical aid immediately. Remove from exposure and move to fresh air immediately. If breathing is difficult, give oxygen. Do NOT use mouth-to-mouth resuscitation. If breathing has ceased apply artificial respiration using oxygen and a suitable mechanical device such as a bag and a mask.
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. Use with adequate ventilation.
Minimize dust generation and accumulation. Avoid contact with skin and eyes. Keep container tightly closed. Do not ingest or inhale.
Wash clothing before reuse.
Storage:
Store in a tightly closed container. Store protected from light.
Store in a cool, dry 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# 6119-70-6: 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:
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: Powder
Color: white to off-white
Odor: None reported.
pH: Not available.
Vapor Pressure: Not available.
Viscosity: Not available.
Boiling Point: Not available.
Freezing/Melting Point: 233.00 - 235.00 deg C
Autoignition Temperature: Not applicable.
Flash Point: Not applicable.
Explosion Limits, lower: Not available.
Explosion Limits, upper: Not available.
Decomposition Temperature: > 235 deg C
Solubility in water: 1 g/810 mL water (20C)
Specific Gravity/Density: Not available.
Molecular Formula: C40H48N4O4.H2SO4.2H2O
Molecular Weight: 782.96

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Section 10 - STABILITY AND REACTIVITY
Chemical Stability:
Stable under normal temperatures and pressures. May decompose when exposed to light. Light sensitive.
Conditions to Avoid:
Light, dust generation.
Incompatibilities with Other Materials:
Strong oxidizing agents, direct light, ammonia, bases.
Hazardous Decomposition Products:
Carbon monoxide, oxides of nitrogen, oxides of sulfur, carbon dioxide.
Hazardous Polymerization: Will not occur.

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Section 11 - TOXICOLOGICAL INFORMATION
RTECS#:
CAS# 6119-70-6 unlisted.
LD50/LC50:
Not available.
Oral, woman: LDLo = 220 mg/kg. Oral, rat: LDLo = 800 mg/kg.
Carcinogenicity:
Quinine sulfate dihydrate - Not listed by ACGIH, IARC, or NTP.

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Section 12 - ECOLOGICAL INFORMATION
Other No information available.

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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: XN
Risk Phrases:
R 20/21/22 Harmful by inhalation, in contact with
skin and if swallowed.
Safety Phrases:
S 22 Do not breathe dust.
S 36 Wear suitable protective clothing.
WGK (Water Danger/Protection)
CAS# 6119-70-6: 2
Canada
None of the chemicals in this product are listed on the DSL/NDSL list.
CAS# 6119-70-6 is not listed on Canada's Ingredient Disclosure List.
US FEDERAL
TSCA
CAS# 6119-70-6 is not on the TSCA Inventory because it is a hydrate.
It is considered to be listed if the CAS number for the anhydrous form
is on the inventory (40CFR720.3(u)(2)).

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SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

药理作用

奎宁是一种喹啉类衍生物，能够与疟原虫的DNA结合形成复合物，抑制DNA复制和RNA转录，进而抑制原虫的蛋白质合成。其作用较氯喹弱。此外，奎宁还能降低疟原虫的耗氧量，并干扰疟原虫内的磷酸化酶活性，从而影响其糖代谢。在某些情况下，奎宁还会引起疟色素聚集，但这种聚集发展缓慢，很少形成大团块，并且往往伴随着细胞死亡。通过电子显微镜观察可见到原虫核和外膜的肿胀以及含有血细胞颗粒的小空泡。此外，在血液中一定浓度的奎宁可导致寄生红细胞提前破裂，从而阻止裂殖体成熟。

本品对红外期疟疾无效，但长期使用可以根治恶性疟疾，但它并不能直接作用于恶性疟原虫的配子体，因此不能中断传播。

药物相互作用

1. 制酸药和含铝制剂：会延缓或减少奎宁的吸收。
2. 抗凝血药物：与奎宁合用后，抗凝作用增强。
3. 肌肉松弛剂（如琥珀胆碱、筒箭毒碱）：与奎宁同用可能会引起呼吸抑制。
4. 奎尼丁：与奎宁合用时，金鸡纳反应增加。
5. 尿液碱化剂（如碳酸氢钠）：可增加肾小管对奎宁的重吸收，导致血药浓度和毒性上升。
6. 维生素K：与奎宁合用能增加其吸收。
7. 某些药物组合（布克利嗪、赛克利嗪、美克利嗪、吩噻嗪类、噻吨类、曲美苄胺及氨基苷类抗生素）：可导致耳鸣和眩晕。
8. 硝苯地平：与奎宁合用时，游离的奎宁浓度增加。

不良反应

1. 奎宁每日用量超过1g或连续使用较长时间常会引起金鸡纳反应，包括耳鸣、头痛、恶心、呕吐及视力听力减退等症状。严重者可能会出现暂时性耳聋，停药后通常可以恢复。
2. 24小时内剂量大于4g时，可直接损害神经组织并收缩视网膜血管，导致视野缩小、复视和弱视等现象。
3. 大剂量中毒时，上述症状会进一步加重，并可能出现心肌抑制、传导延迟、心肌收缩力减弱以及外周血管扩张等症状。血压骤降、呼吸减慢或变浅、发热、烦躁及谵妄等情况也可能出现，最终因呼吸麻痹而死亡。
4. 奎宁的致死剂量约为8g。
5. 少数患者对奎宁高度敏感，即使少量使用也会引起严重的金鸡纳反应。孕妇应禁用。

标准溶液

硫酸奎宁荧光标准物质主要用于荧光光谱类仪器的校准与检验、分析方法的确证评价以及材料荧光性能评估等。

用途

• 校准仪器和装置
• 评价方法
• 工作标准
• 质量保证/质量控制
• 其他用途

反应信息

• 作为反应物：
  描述：

  quinine; hydrogen sulfate dihydrate 生成 维喹地尔
  参考文献：
  名称：

  Howard; Chick, Chemisches Zentralblatt, 1918, vol. 89, # I, p. 552

  摘要：

  DOI：
• 作为产物：
  描述：

  奎宁硫酸盐 在 水 作用下， 以 甲醇 为溶剂， 反应 120.0h， 生成 quinine; hydrogen sulfate dihydrate
  参考文献：
  名称：

  US2009/163540

  摘要：

  公开号：

文献信息

• Multiple phase cross-linked compositions and uses thereof
  申请人：——

  公开号：US20020076443A1

  公开（公告）日：2002-06-20

  The present invention is directed to pharmaceutical compositions, and method for preparing pharmaceutical compositions, comprising a cross-linked matrix physically entrapping at least one therapeutic agent. The matrix may comprise one or more phases in addition to an aqueous phase, such as a solid and/or oil phase. The matrix of the invention has at least one controlled release in-vivo kinetic profile, and may have additional profiles for the same agent. The matrix may also comprise more than one therapeutic agent, and each additional therapeutic agent may have one or more controlled release in-vivo kinetic profile.

  本发明涉及制备药物组合物和制备药物组合物的方法，其中药物组合物包括至少一种治疗剂物理上被包裹在交联基质中。该基质可能包括除水相外的一个或多个相，例如固体和/或油相。本发明的基质具有至少一个体内控制释放动力学特性，并且可能具有相同药物的其他特性。基质还可以包括多种治疗剂，每种附加治疗剂可能具有一个或多个体内控制释放动力学特性。
• Growth and characterisation of crystals of a new organic complex of thiourea with quinine sulphate dihydrate: An NLO material
  作者：Lekshmi P. Nair、B.R. Bijini、S. Prasanna、C.M.K. Nair、M. Deepa、K. Rajendra Babu

  DOI：10.1016/j.saa.2013.09.090

  日期：2014.2

  of thiourea and quinine sulphate dihydrate (TQS) has been grown for the first time by gel method. The structure determination was done by the single crystal XRD technique. The crystal belongs to monoclinic system, P21 space group with cell dimensions a=6.228 (3) Å, b=20.4051 (4) Å, c=11.0600 (6) Å, β=101.9811(2)°. The crystal structure is stabilized by the hydrogen bonding. The functional groups present

  硫脲和奎宁硫酸盐二水合物（TQS）的有机复合物首次通过凝胶法生长。通过单晶XRD技术完成结构确定。晶体属于单斜晶系，P21空间群的晶胞尺寸为a = 6.228（3）Å，b = 20.4051（4）Å，c = 11.0600（6）Å，β= 101.9811（2）°。通过氢键使晶体结构稳定。通过傅立叶变换红外光谱法分析复合物中存在的官能团。通过元素分析证实了配合物的化学计量。通过TGA和DTA方法测定复合物的热性质，并且该复合物在222.53℃下熔融。使用紫外可见吸收光谱研究了晶体的光学透明性。发现光学带隙为2.5eV。
• Biddle, Journal of the American Chemical Society, 1912, vol. 34, p. 503
  作者：Biddle

  DOI：——

  日期：——
• Boettcher; Horowitz, Monatshefte fur Chemie, 1911, vol. 32, p. 794
  作者：Boettcher、Horowitz

  DOI：——

  日期：——
• MULTIPLE PHASE CROSS-LINKED COMPOSITIONS AND USES THEREOF
  申请人：Stein Stanley

  公开号：US20110135732A1

  公开（公告）日：2011-06-09

  The present invention is directed to pharmaceutical compositions, and method for preparing pharmaceutical compositions, comprising a cross-linked matrix physically entrapping at least one therapeutic agent. The matrix may comprise one or more phases in addition to an aqueous phase, such as a solid and/or oil phase. The matrix of the invention has at least one controlled release in-vivo kinetic profile, and may have additional profiles for the same agent. The matrix may also comprise more than one therapeutic agent, and each additional therapeutic agent may have one or more controlled release in-vivo kinetic profile.