依托红霉素 | 3521-62-8

• 物质功能分类: 原料药 - 抗生素类药物 - 大环内酯类药
• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机硫酸及其衍生物
• 中文名称: 依托红霉素
• 中文别名: 无味红霉素；红霉素丙酸酯十二烷基硫酸盐；红霉素月桂酸酯
• 英文名称: erythromycin estolate
• 英文别名: Erythromycinestolat；ilosone；O''-propionyl-erythromycin; dodecyl sulfate；O''-Propionyl-erythromycin; Dodecylsulfat；erythromycin, 2'-propanoate, dodecyl sulfate (salt)；[(2S,3R,4S,6R)-4-(dimethylamino)-2-[[(3R,4S,5S,6R,7R,9R,11R,12R,13S,14R)-14-ethyl-7,12,13-trihydroxy-4-[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy-3,5,7,9,11,13-hexamethyl-2,10-dioxo-oxacyclotetradec-6-yl]oxy]-6-methyloxan-3-yl] propanoate;dodecyl hydrogen sulfate
• CAS: 3521-62-8
• 化学式: C₁₂H₂₆O₄S*C₄₀H₇₁NO₁₄
• mdl: MFCD00084691
• 分子量: 1056.4
• InChiKey: AWMFUEJKWXESNL-JZBHMOKNSA-N

物化性质

• 熔点：
  135-140°C dec.
• 沸点：
  743℃
• 密度：
  1.0053 (rough estimate)
• 闪点：
  >110°(230°F)
• 溶解度：
  在氯仿的溶解度为4.0ML，透明，无色（200mg+4.0mL氯仿）
• 碰撞截面：
  264.4 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]

计算性质

• 辛醇/水分配系数(LogP)：
  3.74
• 重原子数：
  72
• 可旋转键数：
  22
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.942
• 拓扑面积：
  272
• 氢给体数：
  5
• 氢受体数：
  19

安全信息

• 危险品标志：
  Xn
• 安全说明：
  S22,S36
• 危险类别码：
  R22,R42/43
• WGK Germany：
  3
• 海关编码：
  29419000
• 储存条件：
  -20°C 冰箱

SDS

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Section 1. Chemical Product and Company Identification
Erythromycin Estolate
Common Name/
Trade Name
Erythromycin Estolate

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Section 3. Hazards Identification
Slightly hazardous in case of skin contact (irritant), of eye contact (irritant), of ingestion, of inhalation.
Potential Acute Health
Effects
CARCINOGENIC EFFECTS: Not available.
Potential Chronic Health
MUTAGENIC EFFECTS: Not available.
Effects
TERATOGENIC EFFECTS: Not available.
DEVELOPMENTAL TOXICITY: Not available.
The substance may be toxic to liver.
Repeated or prolonged exposure to the substance can produce target organs damage.

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Section 4. First Aid Measures
Check for and remove any contact lenses. In case of contact, immediately flush eyes with plenty of water for at least
Eye Contact
15 minutes. Get medical attention if irritation occurs.
Wash with soap and water. Cover the irritated skin with an emollient. Get medical attention if irritation develops.
Skin Contact
Not available.
Serious Skin Contact
Inhalation If inhaled, remove to fresh air. If not breathing, give artificial respiration. If breathing is difficult, give oxygen. Get
medical attention.
Serious Inhalation Not available.
Do NOT induce vomiting unless directed to do so by medical personnel. Never give anything by mouth to an
Ingestion
unconscious person. If large quantities of this material are swallowed, call a physician immediately. Loosen tight
clothing such as a collar, tie, belt or waistband.
Not available.
Serious Ingestion

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Section 5. Fire and Explosion Data
Flammability of the Product May be combustible at high temperature.
Auto-Ignition Temperature Not available.
Not available.
Flash Points
Not available.
Flammable Limits
These products are carbon oxides (CO, CO2), nitrogen oxides (NO, NO2...).
Products of Combustion
Fire Hazards in Presence of Slightly flammable to flammable in presence of heat.
Various Substances
Risks of explosion of the product in presence of mechanical impact: Not available.
Explosion Hazards in
Risks of explosion of the product in presence of static discharge: Not available.
Presence of Various
Substances
SMALL FIRE: Use DRY chemical powder.
Fire Fighting Media
LARGE FIRE: Use water spray, fog or foam. Do not use water jet.
and Instructions
Material in powder form, capable of creating a dust explosion. As with most organic solids, fire is possible at elevated
Special Remarks on
temperatures
Fire Hazards
Fine dust dispersed in air in sufficient concentrations, and in the presence of an ignition source is a potential dust
Special Remarks on
explosion hazard.
Explosion Hazards
Erythromycin Estolate

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Section 6. Accidental Release Measures
Use appropriate tools to put the spilled solid in a convenient waste disposal container. Finish cleaning by spreading
Small Spill
water on the contaminated surface and dispose of according to local and regional authority requirements.
Use a shovel to put the material into a convenient waste disposal container. Finish cleaning by spreading water on
Large Spill
the contaminated surface and allow to evacuate through the sanitary system.

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Section 7. Handling and Storage
Keep away from heat. Keep away from sources of ignition. Ground all equipment containing material. Do not
Precautions
ingest. Do not breathe dust. Wear suitable protective clothing. If ingested, seek medical advice immediately and
show the container or the label.
Keep container tightly closed. Keep container in a cool, well-ventilated area.
Storage

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Section 8. Exposure Controls/Personal Protection
Use process enclosures, local exhaust ventilation, or other engineering controls to keep airborne levels below
Engineering Controls
recommended exposure limits. If user operations generate dust, fume or mist, use ventilation to keep exposure to
airborne contaminants below the exposure limit.
Personal Protection Safety glasses. Lab coat. Dust respirator. Be sure to use an approved/certified respirator or equivalent. Gloves.
Personal Protection in Case Splash goggles. Full suit. Dust respirator. Boots. Gloves. A self contained breathing apparatus should be used to
avoid inhalation of the product. Suggested protective clothing might not be sufficient; consult a specialist BEFORE
of a Large Spill
handling this product.
Exposure Limits Not available.

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Section 9. Physical and Chemical Properties
Solid. (Crystalline powder.) Odorless.
Physical state and O dor
appearance
Not available.
Taste
1056.39 g/mole
Molecular Weight
White.
Color
Not applicable.
pH (1% soln/water)
Not available.
Boiling Point
Decomposition temperature: 135°C (275°F) - 140 C.
Melting Point
Not available.
Critical Temperature
Not available.
Specific Gravity
Not applicable.
Vapor Pressure
Not available.
Vapor Density
Not available.
Volatility
Not available.
Odor Threshold
Not available.
Water/Oil Dist. Coeff.
Not available.
Ionicity (in Water)
Not available.
Dispersion Properties
Insoluble in cold water.
Solubility
Erythromycin Estolate

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Section 10. Stability and Reactivity Data
The product is stable.
Stability
Not available.
Instability Temperature
Conditions of Instability Excess heat, dust generation
Incompatibility with various Not available.
substances
Not available.
Corrosivity
Not available.
Special Remarks on
Reactivity
Not available.
Special Remarks on
Corrosivity
Will not occur.
Polymerization

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Section 11. Toxicological Information
Inhalation. Ingestion.
Routes of Entry
Acute oral toxicity (LD50): 1447 mg/kg [Rat].
Toxicity to Animals
Chronic Effects on Humans May cause damage to the following organs: liver.
Other Toxic Effects on Slightly hazardous in case of skin contact (irritant), of ingestion, of inhalation.
Humans
Not available.
Special Remarks on
Toxicity to Animals
May cause adverse reproductive effects.
Special Remarks on
Chronic Effects on Humans
Special Remarks on other Acute Potential Health Effects:
Toxic Effects on Humans Skin: May cause skin irritation.
Eyes: May cause eye irritation.
Inhalation: May cause respiratory tract irritation.
Ingestion: May cause nausea, vomiting, abdominal cramps, diarrhea. May affect the liver. May cause hearing loss.
Chronic Potential Health Effects:
Ingestion: May cause symtoms similar to acute ingestion. May cause weight loss. May affect the liver.
Medical Conditions Aggravated by Exposure: Hypersensitivity to material; impaired liver function; hearing loss;
history of cardiac arrhythmias or QT prolongation.

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Section 12. Ecological Information
Not available.
Ecotoxicity
Not available.
BOD5 and COD
Products of Biodegradation Possibly hazardous short term degradation products are not likely. However, long term degradation products may
arise.
The products of degradation are less toxic than the product itself.
Toxicity of the Products
of Biodegradation
Not available.
Special Remarks on the
Products of Biodegradation
Erythromycin Estolate

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Section 13. Disposal Considerations
Waste must be disposed of in accordance with federal, state and local environmental control
Waste Disposal
regulations.

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Section 14. Transport Information
Not a DOT controlled material (United States).
DO T Cl assi fi cati on
Not applicable.
Identification
Not applicable.
Special Provisions for
Transport
DO T (Pi ctograms)

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Section 15. Other Regulatory Information and Pictograms
No products were found.
Federal and State
Regulations
California prop. 65: This product contains the following ingredients for which the State of California has found to
California
cause cancer which would require a warning under the statute: No products were found.
Proposition 65
Warnings
California prop. 65: This product contains the following ingredients for which the State of California has found to
cause birth defects which would require a warning under the statute: No products were found.
Other Regulations EINECS: This product is on the European Inventory of Existing Commercial Chemical Substances (EINECS No.
222-532-4).
Canada: Not listed on Canadian Domestic Substance List (DSL) or Candian Non-Domestic Substances List (NDSL)
China: Not listed on National Inventory.
Japan: Not listed on National Inventory (ENCS).
Korea: Listed on National Inventory (KECI).
Philippines: Not listed on National Inventory (PICCS).
Australia: Listed on AICS.
WHMIS (Canada) Not controlled under WHMIS (Canada).
Other Classifications
R22- Harmful if swallowed. S46- If swallowed, seek medical advice
DSCL (EEC)
immediately and show this container or label.
Health Hazard
HMIS (U.S.A.) 1 National Fire Protection
1 Flammability
1 Association (U.S.A.)
Fire Hazard
1 0 Reactivity
Health
Reactivity 0
Specific hazard
Personal Protection
E
WHMIS (Canada)
(Pictograms)
DSCL (Europe)
(Pictograms)
Erythromycin Estolate
TDG(Canada)
(Pictograms)
ADR (Europe)
(Pictograms)
Protective Equipment
Gloves.
Lab coat.
Dust respirator. Be sure to use an
approved/certified respirator or equivalent.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

简介

依托红霉素以红霉素丙酸酯的十二烷基硫酸盐形式存在，胃酸中较红霉素稳定。空腹或食后口服均可快速吸收，蛋白结合率高达90～99%。口服后在胃肠中分解为红霉素丙酸酯，部分在血液中水解成游离的红霉素。不良反应较小。

理化性质

依托红霉素现有生产工艺以硫氰酸红霉素为主要原料，采用丙酮为溶剂、碳酸钾脱硫分层过滤后再加碳酸钾吸附脱水过滤，与丙酸酐成酯后加入十二烷基硫酸盐溶液合成依托红霉素。依托红霉素片通常通过普通压片制成，脆碎度控制不佳时容易断裂、龟裂和粉碎，会影响片剂质量。溶出度取决于依托红霉素片颗粒的结实程度，控制不好也会导致片剂质量不均一稳定，影响药效。

应用

依托红霉素临床上作为青霉素过敏患者治疗以下感染的替代用药：由溶血性链球菌、肺炎链球菌等引起的急性扁桃体炎、急性咽炎、鼻窦炎；溶血性链球菌所致的猩红热、蜂窝织炎；白喉及白喉带菌者；气性坏疽、炭疽、破伤风；放线菌病；梅毒；李斯特菌病等。依托红霉素为红霉素丙酸酯的十二烷基硫酸盐，对葡萄球菌属、各组链球菌和革兰阳性杆菌均具抗菌活性。奈瑟菌属、流感嗜血杆菌、百日咳鲍特氏菌等也可对该品呈现敏感。此外，对除脆弱拟杆菌和梭杆菌属以外的各种厌氧菌亦有抗菌活性；对军团菌属、胎儿弯曲菌、某些螺旋体、肺炎支原体、立克次体属和衣原体属也有抑制作用。该品系抑菌剂，在高浓度时对某些细菌也具杀菌作用。

制备

在140g丙酮中加入20g水、50g硫氰酸红霉素，升温至35～38℃，搅拌5分钟，加入9g三乙胺使硫氰酸红霉素脱硫为游离红霉素碱，体系溶清；

在35～38℃条件下加入13.5g丙酸酐，反应120分钟，生成红霉素丙酸酯；过滤；

再加入十二烷基硫酸盐溶液（十二烷基硫酸盐∶水＝17g∶90g）保温反应60分钟，生成依托红霉素；

在35～38℃条件下加50g水使溶液浑浊，搅拌60分钟，使依托红霉素大量析出；

加500g水降温至5～10℃结晶60分钟离心，滤饼水洗后干燥，即得61g依托红霉素。重量收率为61/50=122%。

按此工艺生产的产品为白色结晶性粉末，几乎无味，熔点为132-138℃，在乙醇或氯仿中易溶，在水中几乎不溶。通过元素分析证明，该物质的元素测试值与理论计算值接近。

副作用

1. 用药后可能出现恶心、呕吐、腹泻、中上腹痛、口舌疼痛、食欲减退等胃肠道症状，发生率与剂量大小相关。
2. 偶见乏力、黄疸及肝功能损害，通常在服药10～14日后发生。本药引起的肝毒性反应比其他红霉素制剂多见。少数患者用药后可出现血清碱性磷酸酶、胆红素、谷丙转氨酶等指标升高。
3. 少数患者可能出现嗜酸粒细胞增多、过敏反应等过敏症状，如皮疹、荨麻疹或严重时全身过敏反应（史蒂文斯-约翰逊综合征）。
4. 大剂量应用时尤其肝、肾疾病患者或老年患者可能引起听力减退，主要与血药浓度过高有关。停药后大多可恢复。

生物活性

Erythromycin estolate是红霉素衍生物，是一种大环内酯类抗生素，在多种细菌感染研究中表现出良好的抗菌效果。其引起的肝损伤主要包括胆汁淤积性肝炎。Erythromycin estolate的毒性与其对胆汁酸运输的抑制作用有关。

用途

用于耐青霉素的金葡菌感染及对青霉素过敏的金葡菌感染。

反应信息

• 作为产物：
  描述：

  红霉素丙酸酯 、 sodium dodecyl-sulfate 生成 依托红霉素
  参考文献：
  名称：

  BIEDRZYCKI, MAREK;CHMIELNICKI, PIOTR;DRZEWNSKI, WIESLAW;MARSZALEK, JAN;SE+

  摘要：

  DOI：

文献信息

• [EN] PEPTIDE-BASED MULTIPLE-DRUG DELIVERY VEHICLE<br/>[FR] VÉHICULE D'ADMINISTRATION DE MÉDICAMENTS MULTIPLES À BASE DE PEPTIDES
  申请人：ARIEL-UNIVERSITY RES AND DEV COMPANY LTD

  公开号：WO2017068577A1

  公开（公告）日：2017-04-27

  A molecular structure comprising a targeting moiety, a multi-functional peptide platform and a plurality of controllably released bioactive agents attached thereto is provided herein.

  本文提供了一种包括靶向基团、多功能肽平台和附着在其上的多种可控释放的生物活性剂的分子结构。
• [EN] ISOTHIAZOLOQUINOLONES AND RELATED COMPOUNDS AS ANTI-INFECTIVE AGENTS<br/>[FR] ANTI-INFECTIEUX A BASE D'ISOTHIAZOLOQUINOLONES ET DE SELS CORRESPONDANTS
  申请人：ACHILLION PHARMACEUTICALS INC

  公开号：WO2005019228A1

  公开（公告）日：2005-03-03

  The invention provides compounds and salts of Formula (I) and Formula (II): which possess antimicrobial activity. The invention also provides novel synthetic intermediates useful in making compounds of Formula (I) and Formula (II). The variables A1, R2, R3, R5, R6, R7, A8 and R9 are defined herein. Certain compounds of Formula (I) and Formula (II) disclosed herein are potent and selective inhibitors of bacterial DNA synthesis and bacterial replication. The invention also provides antimicrobial compositions, including pharmaceutical compositions, containing one or more compounds of Formula (I) or Formula (II) and one or more carriers, excipients, or diluents. Such compositions may contain a compound of Formula (I) or Formula (II) as the only active agent or may contain a combination of a compound of Formula (I) or Formula (II) and one or more other active agents. The invention also provides methods for treating microbial infections in animals.

  本发明提供了具有抗菌活性的公式(I)和公式(II)的化合物及盐类：本发明还提供了用于制造公式(I)和公式(II)化合物的新的合成中间体。变量A1、R2、R3、R5、R6、R7、A8和R9在此文中定义。本文披露的某些公式(I)和公式(II)化合物是细菌DNA合成和细菌复制的强效和选择性抑制剂。本发明还提供了含有一种或多种公式(I)或公式(II)化合物以及一种或多种载体、辅料或稀释剂的抗菌组合物，包括药物组合物。这样的组合物可以只含有公式(I)或公式(II)的化合物作为唯一的活性成分，也可以含有公式(I)或公式(II)的化合物与一种或多种其他活性成分的组合。本发明还提供了用于治疗动物微生物感染的方法。
• Compositions and Methods for Preventing or Treating Diseases, Conditions, or Processes Characterized by Aberrant Fibroblast Proliferation and Extracellular Matrix Deposition
  申请人：MOERAE MATRIX, INC.

  公开号：US20160136234A1

  公开（公告）日：2016-05-19

  The described invention provides compositions and methods for reducing progression of a fibrosis in a tissue of a subject selected from liver, kidney or vascular fibrosis, the progression of the fibrosis being characterized by aberrant fibroblast proliferation and extracellular matrix deposition in the tissue. The method includes administering a therapeutic amount of a pharmaceutical composition containing a polypeptide having the amino acid sequence YARAAARQARAKALARQLGVAA (SEQ ID NO: 1) or functional equivalent thereof, and a pharmaceutically acceptable carrier, wherein the therapeutic amount of the polypeptide is effective to reduce progression of the fibrosis, to treat remodeling of the tissue, or a combination thereof.

  描述的发明提供了一种用于减少主体选定组织中的纤维化进展的组成和方法，该选定组织来自肝纤维化、肾纤维化或血管纤维化，纤维化的进展在组织中以异常成纤维细胞增殖和细胞外基质沉积为特征。该方法包括施用含有具有氨基酸序列YARAAARQARAKALARQLGVAA（SEQ ID NO: 1）或其功能等效物的多肽的药物治疗量，以及药学上可接受的载体，其中多肽的治疗量有效于减少纤维化的进展，治疗组织的重塑，或其组合。
• [EN] THERANOSTIC CONJUGATES<br/>[FR] CONJUGUÉS THÉRANOSTIQUES
  申请人：ARIEL SCIENT INNOVATIONS LTD

  公开号：WO2021009759A1

  公开（公告）日：2021-01-21

  Provided herein is a drug delivery (DD) system for ratiometric luminescence determination of drug release degree in drug delivery monitoring, which includes a drug, a switchable reporter and non-switchable reporter providing two distinguishable signals for detection; or a single switchable reporter providing two distinguishable signals for detection, and a cleavable linker connecting a drug to a switchable reporter, as well as a method for ratiometric luminescence determination of drug release in a target in vivo or in vitro), which is effected by administering the DD system provided herein that is capable of releasing a drug from the DD system, measuring two luminescent signals provided by the switchable reporter and the non-switchable reporter, or the single switchable reporter, determining the ratio between these two luminescence signals, and determining the drug release degree through the ratio between the two luminescence signals.

  本文提供了一种药物递送（DD）系统，用于药物递送监测中药物释放程度的比例荧光测定，该系统包括一种药物、一种可切换的报告物和一种不可切换的报告物，用于提供两种可区分的信号以进行检测；或者一种单一可切换的报告物，用于提供两种可区分的信号以进行检测，以及一种可切割的连接剂，连接药物和可切换的报告物，以及一种比例荧光测定方法，用于在目标（体内或体外）中测定药物释放，通过给予本文提供的能够从DD系统中释放药物的DD系统，测量可切换的报告物和不可切换的报告物提供的两个发光信号，或者单一可切换的报告物，确定这两个发光信号之间的比例，并通过这两个发光信号之间的比例确定药物释放程度。
• FUNCTIONALLY-MODIFIED OLIGONUCLEOTIDES AND SUBUNITS THEREOF
  申请人：Sarepta Therapeutics, Inc.

  公开号：US20140330006A1

  公开（公告）日：2014-11-06

  Functionally-modified oligonucleotide analogues comprising modified intersubunit linkages and/or modified 3′ and/or 5′-end groups are provided. The disclosed compounds are useful for the treatment of diseases where inhibition of protein expression or correction of aberrant mRNA splice products produces beneficial therapeutic effects.

  提供了包含修改的亚单位间连接和/或修改的3'和/或5'-末端基团的功能修饰寡核苷酸类似物。所公开的化合物对于治疗需要抑制蛋白质表达或纠正异常mRNA剪接产物以产生有益治疗效果的疾病是有用的。