WO2021227405A1 - 一种酚磺乙胺注射液及其制备方法 - Google Patents

一种酚磺乙胺注射液及其制备方法 Download PDF

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WO2021227405A1
WO2021227405A1 PCT/CN2020/127765 CN2020127765W WO2021227405A1 WO 2021227405 A1 WO2021227405 A1 WO 2021227405A1 CN 2020127765 W CN2020127765 W CN 2020127765W WO 2021227405 A1 WO2021227405 A1 WO 2021227405A1
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injection
solution
sulfacetamide
activated carbon
water
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PCT/CN2020/127765
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English (en)
French (fr)
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赵亭
刘长江
吴双俊
段义杰
赵海桥
刘存领
尹彩霞
王正雯
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山东方明药业集团股份有限公司
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/205—Amine addition salts of organic acids; Inner quaternary ammonium salts, e.g. betaine, carnitine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/02—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
    • A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
    • A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/20—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/08—Solutions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents

Definitions

  • the application belongs to the technical field of medicine preparation, and specifically relates to a sulphurethane injection and a preparation method thereof.
  • Ethanol injection is a colorless or almost colorless clear liquid. It can be used to prevent and treat bleeding before and after various operations. It can also be used for bleeding caused by poor platelet function and increased vascular fragility. It has a wide range of uses.
  • this application provides a sulfacetamide injection and a preparation method thereof.
  • This application is implemented through the following schemes:
  • An ethidium sulfamate injection comprising the following raw materials, 500 g of ethidium sulfamate, 2 g of disodium edetate, 1 g of sodium metabisulfite, 15 g of sodium chloride, 2000 ml of water for injection, 0.1 g of mannitol, and 1 g of potassium chloride.
  • sulfoethyl amine 480g disodium edetate 1g, sodium metabisulfite 2g, sodium chloride 14g, water for injection 2000ml, mannitol 0.2g, potassium chloride 0.8g, calcium chloride 1.5g.
  • sulfoethyl amine 450g disodium edetate 0.5g, sodium metabisulfite 0.5g, sodium chloride 15g, water for injection 2000ml, mannitol 1g, potassium chloride 1.5g, calcium chloride 1g.
  • sulfoethyl amine 520g disodium edetate 3g, sodium metabisulfite 2g, sodium chloride 15g, water for injection 2000ml, mannitol 1.5g, potassium chloride 2g, calcium chloride 0.8g.
  • a preparation method of sulfacetamide injection which is characterized in that the preparation steps are as follows: (1) Saturated solutions of sulfacetamide, disodium edetate, sodium metabisulfite, and sodium chloride are prepared separately at 25° C.
  • the activated carbon in the step (3) is medicinal activated carbon, and the usage amount of the activated carbon is 0.6-0.7% of the weight of sulfoethanamide.
  • the activated carbon in the step (4) is medicinal activated carbon, and the usage amount of the activated carbon is 0.3-0.4% of the weight of sulfoethanamide.
  • the three-stage filtration in the step (5) is: the first stage filtration, using 80-100mm pore size filter paper to filter it; the second stage, the use of 5-7mm pore size filter paper to filter the thin The liquid preparation is filtered; the third pole: a 0.1-0.5um pore size filter membrane is used to filter the dilute liquid after the secondary filtration.
  • the impurities in the raw material can be removed; through nitrogen aeration, the dissolved oxygen in the material liquid can be removed; this application has undergone multiple processing processes of preparation, impurity removal, sterilization, and lamp inspection.
  • the purity of the processed sulfacetamide injection is 99.999%, the pH is 5-6, the shelf life is 2 years, and there will be no floccules or any visible suspended matter within the shelf life, and the medicinal value and quality are equal. No change will occur; this product has good stability, and the stability of various indicators such as impurities is significantly better than that of existing products, and the preparation process provided by this application is simple, easy to control, high in production efficiency, and low in production energy consumption.
  • An ethidium sulfamate injection comprising the following raw materials, 500 g of ethidium sulfamate, 2 g of disodium edetate, 1 g of sodium metabisulfite, 15 g of sodium chloride, 2000 ml of water for injection, 0.1 g of mannitol, and 1 g of potassium chloride.
  • a preparation method of sulfacetamide injection which is characterized in that the preparation steps are as follows: (1) Saturated solutions of sulfacetamide, disodium edetate, sodium metabisulfite, and sodium chloride are prepared separately at 25° C.
  • the activated carbon in the step (3) is medicinal activated carbon, and the usage amount of the activated carbon is 0.6-0.7% of the weight of sulfoethanamide.
  • the activated carbon in the step (4) is medicinal activated carbon, and the usage amount of the activated carbon is 0.3-0.4% of the weight of sulfoethanamide.
  • the three-stage filtration in the step (5) is: the first stage filtration, using 80-100mm pore size filter paper to filter it; the second stage, the use of 5-7mm pore size filter paper to filter the thin The liquid preparation is filtered; the third pole: a 0.1-0.5um pore size filter membrane is used to filter the dilute liquid after the secondary filtration.
  • An ethidium sulfamate injection comprising the following raw materials, sulfasulfame 480g, disodium edetate 1g, sodium metabisulfite 2g, sodium chloride 14g, water for injection 2000ml, mannitol 0.2g, potassium chloride 0.8g , Calcium chloride 1.5g.
  • a preparation method of sulfacetamide injection which is characterized in that the preparation steps are as follows: (1) Saturated solutions of sulfacetamide, disodium edetate, sodium metabisulfite, and sodium chloride are prepared separately at 25° C.
  • the activated carbon in the step (3) is medicinal activated carbon, and the usage amount of the activated carbon is 0.6-0.7% of the weight of sulfoethanamide.
  • the activated carbon in the step (4) is medicinal activated carbon, and the usage amount of the activated carbon is 0.3-0.4% of the weight of sulfoethanamide.
  • the three-stage filtration in the step (5) is: the first stage filtration, using 80-100mm pore size filter paper to filter it; the second stage, the use of 5-7mm pore size filter paper to filter the thin The liquid preparation is filtered; the third pole: a 0.1-0.5um pore size filter membrane is used to filter the dilute liquid after the secondary filtration.
  • An ethidium sulfamate injection comprising the following raw materials, 450 g of ethidium sulfamate, 0.5 g of disodium edetate, 0.5 g of sodium metabisulfite, 15 g of sodium chloride, 2000 ml of water for injection, 1 g of mannitol, and 1.5 of potassium chloride. g, calcium chloride 1g.
  • a preparation method of sulfacetamide injection which is characterized in that the preparation steps are as follows: (1) Saturated solutions of sulfacetamide, disodium edetate, sodium metabisulfite, and sodium chloride are prepared separately at 25° C.
  • the activated carbon in the step (3) is medicinal activated carbon, and the usage amount of the activated carbon is 0.6-0.7% of the weight of sulfoethanamide.
  • the activated carbon in the step (4) is medicinal activated carbon, and the usage amount of the activated carbon is 0.3-0.4% of the weight of sulfoethanamide.
  • the three-stage filtration in the step (5) is: the first stage filtration, using 80-100mm pore size filter paper to filter it; the second stage, the use of 5-7mm pore size filter paper to filter the thin The liquid preparation is filtered; the third pole: a 0.1-0.5um pore size filter membrane is used to filter the dilute liquid after the secondary filtration.
  • An ethidium sulfamate injection including the following raw materials, sulfamethine 520g, disodium edetate 3g, sodium metabisulfite 2g, sodium chloride 15g, water for injection 2000ml, mannitol 1.5g, potassium chloride 2g, Calcium chloride 0.8g.
  • a preparation method of sulfacetamide injection which is characterized in that the preparation steps are as follows: (1) Saturated solutions of sulfacetamide, disodium edetate, sodium metabisulfite, and sodium chloride are prepared separately at 25° C.
  • the activated carbon in the step (3) is medicinal activated carbon, and the usage amount of the activated carbon is 0.6-0.7% of the weight of sulfoethanamide.
  • the activated carbon in the step (4) is medicinal activated carbon, and the usage amount of the activated carbon is 0.3-0.4% of the weight of sulfoethanamide.
  • the three-stage filtration in the step (5) is: the first stage filtration, using 80-100mm pore size filter paper to filter it; the second stage, the use of 5-7mm pore size filter paper to filter the thin The liquid preparation is filtered; the third pole: a 0.1-0.5um pore size filter membrane is used to filter the dilute liquid after the secondary filtration.
  • the sulfacetamide injections that have been stored for 7 days, March, June, and December are subjected to pH test and lamp test.
  • the conditions of the lamp test are: the light intensity of the colorless product is 1200Lx, and the light intensity of the colored product is 1800Lx. There was no flocculation, and no visible foreign matter suspended during lamp inspection.
  • the pH is as shown in Table 1:
  • the sulfacetamide injections of Examples 1-4 were respectively placed in an environment of 60°C, minus 20°C, and sunlight for 1 year, and then subjected to pH test and light inspection.
  • the conditions of the light inspection were: colorless product light The intensity is 1200Lx, the light intensity of colored products is 1800Lx, no flocs appear after inspection, and there is no visible foreign matter suspended in light inspection.
  • the pH is as follows: Table 2:

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  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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Abstract

一种酚磺乙胺注射液及其制备方法，制备步骤如下：配制酚磺乙胺，依地酸二钠，焦亚硫酸钠，氯化钠的饱和溶液备用；将甘露醇、氯化钾和氯化钙溶于10ml注射用水中得微量元素液备用；将酚磺乙胺，依地酸二钠，焦亚硫酸钠，氯化钠的饱和溶液、微量元素液混合均匀得原料浓液；将原料浓液至于浓配罐中，吸附，过滤至浓液澄清；浓液置于稀配罐中，加入注射用水，吸附，过滤得稀配液；将稀配液进行三级过滤处理得成品原液；向成品原液中补加注射用水至最终溶液重量；封口；灭菌10min；检测经过灭菌的安瓿瓶中是否存在可见异物悬浮及微粒数量；贮存。

Description

一种酚磺乙胺注射液及其制备方法 技术领域
本申请属于药品制备技术领域，具体涉及一种酚磺乙胺注射液及其制备方法。
背景技术
酚磺乙胺注射液为无色或几乎无色的澄明液体。用于防治各种手术前后的出血，也可用于血小板功能不良、血管脆性增加而引起的出血，具有广泛的用途，
然而，酚磺乙胺注射液存放几个月后，会发生pH不稳定的现象，导致产品出现絮状物，进而导致可见异物不合格。
技术问题
由于这种现象的存在，会造成用户退货，这些退货均需要做报废处理。这不仅造成很大浪费，而且给客户造成不良影响，生产厂商的信誉遭到质疑。
技术解决方案
为了解决上述技术的问题，本申请提供了一种酚磺乙胺注射液及其制备方法，本申请是通过下述方案实现的：
一种酚磺乙胺注射液，包括下述原料，酚磺乙胺500g，依地酸二钠2g，焦亚硫酸钠1g，氯化钠15g，注射用水2000ml，甘露醇0.1g，氯化钾1g，氯化钙2g。
优选的，酚磺乙胺480g，依地酸二钠1g，焦亚硫酸钠2g，氯化钠14g，注射用水2000ml，甘露醇0.2g，氯化钾0.8g，氯化钙1.5g。
优选的，酚磺乙胺450g，依地酸二钠0.5g，焦亚硫酸钠0.5g，氯化钠15g，注射用水2000ml，甘露醇1g，氯化钾1.5g，氯化钙1g。
优选的，酚磺乙胺520g，依地酸二钠3g，焦亚硫酸钠2g，氯化钠15g，注射用水2000ml，甘露醇1.5g，氯化钾2g，氯化钙0.8g。
一种酚磺乙胺注射液的制备方法，其特征在于，制备步骤如下：(1)在25℃下分别配置酚磺乙胺，依地酸二钠，焦亚硫酸钠，氯化钠的饱和溶液备用；在25℃下将甘露醇、氯化钾和氯化钙溶于10ml注射用水中得微量元素液备用；(2)将酚磺乙胺，依地酸二钠，焦亚硫酸钠，氯化钠的饱和溶液，微量元素液于25℃下混合均匀得原料浓液；(3)将原料浓液至于浓配罐中，向浓配罐中加入活性炭，在38℃下吸附25min，过滤至浓液澄清；(4)将步骤(3)得到的浓液置于稀配罐中，加入注射用水1000ml，于1000r/min的速度下搅拌3min，后向稀配罐中加入活性炭，于45℃下吸附15min，过滤得稀配液；(5)将稀配液进行三级过滤处理得成品原液；(6)向成品原液中补加注射用水至最终溶液重量，调节总料液的pH为5-6，后将总料液于25℃下氮气曝气45min 得成品；(7)将成品置于安瓿瓶中，封口；(8)将封口后的安瓿瓶正放，于100℃的流通蒸汽下灭菌10min；(9)检测经过灭菌的安瓿瓶中是否存在可见异物悬浮及微粒数量，灯检的条件为：无色产品光照强度为1200Lx，有色产品光照强度为1800Lx；(10)对灯检合格的安瓿瓶进行包装，贮存。
优选的，所述步骤(3)的活性炭为药用活性炭，所述活性炭的使用量为酚磺乙胺重量的0.6-0.7％。
优选的，所述步骤(4)的活性炭为药用活性炭，所述活性炭的使用量为酚磺乙胺重量的0.3-0.4％。
优选的，所述步骤(5)中的三级过滤为：第一级过滤，采用80-100mm孔径滤纸对其进行过滤处理；第二级，采用5-7mm孔径滤纸对一级过滤后的稀配液进行过滤处理；第三极：采用0.1-0.5um孔径滤膜对二级过滤后的稀配液进行过滤处理。
有益效果
通过两次活性炭吸附和三级过滤，可除去原料中的杂质；通过氮气曝气，可除去料液中的溶解氧；本申请历经多次调配、、除杂、杀菌、灯检的加工工艺，使得加工出的酚磺乙胺注射液的纯度为99.999％，pH为5-6，保质期为2年，且在保质期内不会出现絮状物或任何可见悬浮物，且药用价值和品质均不会发生任何改变；本产品稳定性好，杂质等各项指标的稳定性显著优于现有产品，且本申请提供的制备工艺简单、易控、生产效率高、生产能耗低。
本发明的最佳实施方式
实施例1
一种酚磺乙胺注射液，包括下述原料，酚磺乙胺500g，依地酸二钠2g，焦亚硫酸钠1g，氯化钠15g，注射用水2000ml，甘露醇0.1g，氯化钾1g，氯化钙2g。
一种酚磺乙胺注射液的制备方法，其特征在于，制备步骤如下：(1)在25℃下分别配置酚磺乙胺，依地酸二钠，焦亚硫酸钠，氯化钠的饱和溶液备用；在25℃下将甘露醇、氯化钾和氯化钙溶于10ml注射用水中得微量元素液备用；(2)将酚磺乙胺，依地酸二钠，焦亚硫酸钠，氯化钠的饱和溶液、微量元素液于25℃下混合均匀得原料浓液；(3)将原料浓液至于浓配罐中，向浓配罐中加入活性炭，在38℃下吸附25min，过滤至浓液澄清；(4)将步骤(3)得到的浓液置于稀配罐中，加入注射用水1000ml，于1000r/min的速度下搅拌3min，后向稀配罐中加入活性炭，于45℃下吸附15min，过滤得稀配液；(5)将稀配液进行三级过滤处理得成品原液；(6)向成品原液中补加注射用水至最终溶液重量，调节总料液的pH为5-6，后将总料液于25℃下氮气曝气45min得成品；(7)将成品置于安瓿瓶中，封口；(8)将封口后的安瓿瓶正放，于100℃的流通 蒸汽下灭菌10min；(9)检测经过灭菌的安瓿瓶中是否存在可见异物悬浮及微粒数量，灯检的条件为：无色产品光照强度为1200Lx，有色产品光照强度为1800Lx；(10)对灯检合格的安瓿瓶进行包装，贮存。
优选的，所述步骤(3)的活性炭为药用活性炭，所述活性炭的使用量为酚磺乙胺重量的0.6-0.7％。
优选的，所述步骤(4)的活性炭为药用活性炭，所述活性炭的使用量为酚磺乙胺重量的0.3-0.4％。
优选的，所述步骤(5)中的三级过滤为：第一级过滤，采用80-100mm孔径滤纸对其进行过滤处理；第二级，采用5-7mm孔径滤纸对一级过滤后的稀配液进行过滤处理；第三极：采用0.1-0.5um孔径滤膜对二级过滤后的稀配液进行过滤处理。
实施例2
一种酚磺乙胺注射液，包括下述原料，酚磺乙胺480g，依地酸二钠1g，焦亚硫酸钠2g，氯化钠14g，注射用水2000ml，甘露醇0.2g，氯化钾0.8g，氯化钙1.5g。
一种酚磺乙胺注射液的制备方法，其特征在于，制备步骤如下：(1)在25℃下分别配置酚磺乙胺，依地酸二钠，焦亚硫酸钠，氯化钠的饱和溶液备用；在25℃下将甘露醇、氯化钾和氯化钙溶于10ml注射用水中得微量元素液备用；(2)将酚磺乙胺，依地酸二钠，焦亚硫酸钠，氯化钠的饱和溶液、微量元素液于25℃下混合均匀得原料浓液；(3)将原料浓液至于浓配罐中，向浓配罐中加入活性炭，在38℃下吸附25min，过滤至浓液澄清；(4)将步骤(3)得到的浓液置于稀配罐中，加入注射用水1000ml，于1000r/min的速度下搅拌3min，后向稀配罐中加入活性炭，于45℃下吸附15min，过滤得稀配液；(5)将稀配液进行三级过滤处理得成品原液；(6)向成品原液中补加注射用水至最终溶液重量，调节总料液的pH为5-6，后将总料液于25℃下氮气曝气45min得成品；(7)将成品置于安瓿瓶中，封口；(8)将封口后的安瓿瓶正放，于100℃的流通蒸汽下灭菌10min；(9)检测经过灭菌的安瓿瓶中是否存在可见异物悬浮及微粒数量，灯检的条件为：无色产品光照强度为1200Lx，有色产品光照强度为1800Lx；(10)对灯检合格的安瓿瓶进行包装，贮存。
优选的，所述步骤(3)的活性炭为药用活性炭，所述活性炭的使用量为酚磺乙胺重量的0.6-0.7％。
优选的，所述步骤(4)的活性炭为药用活性炭，所述活性炭的使用量为酚磺乙胺重量的0.3-0.4％。
优选的，所述步骤(5)中的三级过滤为：第一级过滤，采用80-100mm孔径滤纸对其进行过滤处理；第二级，采用5-7mm孔径滤纸对一级过滤后的稀配液进行过滤处理；第三极：采用0.1-0.5um孔径滤膜对二级过滤后的稀配液进行过滤处理。
本发明的实施方式
实施例3
一种酚磺乙胺注射液，包括下述原料，酚磺乙胺450g，依地酸二钠0.5g，焦亚硫酸钠0.5g，氯化钠15g，注射用水2000ml，甘露醇1g，氯化钾1.5g，氯化钙1g。
一种酚磺乙胺注射液的制备方法，其特征在于，制备步骤如下：(1)在25℃下分别配置酚磺乙胺，依地酸二钠，焦亚硫酸钠，氯化钠的饱和溶液备用；在25℃下将甘露醇、氯化钾和氯化钙溶于10ml注射用水中得微量元素液备用；(2)将酚磺乙胺，依地酸二钠，焦亚硫酸钠，氯化钠的饱和溶液、微量元素液于25℃下混合均匀得原料浓液；(3)将原料浓液至于浓配罐中，向浓配罐中加入活性炭，在38℃下吸附25min，过滤至浓液澄清；(4)将步骤(3)得到的浓液置于稀配罐中，加入注射用水1000ml，于1000r/min的速度下搅拌3min，后向稀配罐中加入活性炭，于45℃下吸附15min，过滤得稀配液；(5)将稀配液进行三级过滤处理得成品原液；(6)向成品原液中补加注射用水至最终溶液重量，调节总料液的pH为5-6，后将总料液于25℃下氮气曝气45min得成品；(7)将成品置于安瓿瓶中，封口；(8)将封口后的安瓿瓶正放，于100℃的流通蒸汽下灭菌10min；(9)检测经过灭菌的安瓿瓶中是否存在可见异物悬浮及微粒数量，灯检的条件为：无色产品光照强度为1200Lx，有色产品光照强度为1800Lx；(10)对灯检合格的安瓿瓶进行包装，贮存。
优选的，所述步骤(3)的活性炭为药用活性炭，所述活性炭的使用量为酚磺乙胺重量的0.6-0.7％。
优选的，所述步骤(4)的活性炭为药用活性炭，所述活性炭的使用量为酚磺乙胺重量的0.3-0.4％。
优选的，所述步骤(5)中的三级过滤为：第一级过滤，采用80-100mm孔径滤纸对其进行过滤处理；第二级，采用5-7mm孔径滤纸对一级过滤后的稀配液进行过滤处理；第三极：采用0.1-0.5um孔径滤膜对二级过滤后的稀配液进行过滤处理。
实施例4
一种酚磺乙胺注射液，包括下述原料，酚磺乙胺520g，依地酸二钠3g，焦亚硫酸钠2g，氯化钠15g，注射用水2000ml，甘露醇1.5g，氯化钾2g，氯化钙0.8g。
一种酚磺乙胺注射液的制备方法，其特征在于，制备步骤如下：(1)在25℃下分别配置酚磺乙胺，依地酸二钠，焦亚硫酸钠，氯化钠的饱和溶液备用；在25℃下将甘露 醇、氯化钾和氯化钙溶于10ml注射用水中得微量元素液备用；(2)将酚磺乙胺，依地酸二钠，焦亚硫酸钠，氯化钠的饱和溶液，微量元素液于25℃下混合均匀得原料浓液；(3)将原料浓液至于浓配罐中，向浓配罐中加入活性炭，在38℃下吸附25min，过滤至浓液澄清；(4)将步骤(3)得到的浓液置于稀配罐中，加入注射用水1000ml，于1000r/min的速度下搅拌3min，后向稀配罐中加入活性炭，于45℃下吸附15min，过滤得稀配液；(5)将稀配液进行三级过滤处理得成品原液；(6)向成品原液中补加注射用水至最终溶液重量，调节总料液的pH为5-6，后将总料液于25℃下氮气曝气45min得成品；(7)将成品置于安瓿瓶中，封口；(8)将封口后的安瓿瓶正放，于100℃的流通蒸汽下灭菌10min；(9)检测经过灭菌的安瓿瓶中是否存在可见异物悬浮及微粒数量，灯检的条件为：无色产品光照强度为1200Lx，有色产品光照强度为1800Lx；(10)对灯检合格的安瓿瓶进行包装，贮存。
优选的，所述步骤(3)的活性炭为药用活性炭，所述活性炭的使用量为酚磺乙胺重量的0.6-0.7％。
优选的，所述步骤(4)的活性炭为药用活性炭，所述活性炭的使用量为酚磺乙胺重量的0.3-0.4％。
优选的，所述步骤(5)中的三级过滤为：第一级过滤，采用80-100mm孔径滤纸对其进行过滤处理；第二级，采用5-7mm孔径滤纸对一级过滤后的稀配液进行过滤处理；第三极：采用0.1-0.5um孔径滤膜对二级过滤后的稀配液进行过滤处理。
工业实用性
将放置7天、3月、6月、12月的酚磺乙胺注射液进行pH检测和灯检，灯检的条件为：无色产品光照强度为1200Lx，有色产品光照强度为1800Lx，经检测均无无絮状物出现，灯检无可见异物悬浮，pH如下表1：
分别将实施例1-4的酚磺乙胺注射液分别置于60℃、零下20℃、太阳光照的环境中1年后，进行pH检测和灯检，灯检的条件为：无色产品光照强度为1200Lx，有色产品光照强度为1800Lx，经检测均无无絮状物出现，灯检无可见异物悬浮，pH如下表2：
表1
7天3个月6个月9个月实施例1 5.90 5.89 5.89 5.88实施例2 5.82 5.82 5.82 5.81实施例3 5.71 5.70 5.70 5.70实施例4 5.69 5.68 5.68 5.67
表2
Figure PCTCN2020127765-appb-000001

Claims (9)

  1. 一种酚磺乙胺注射液，其特征在于，包括下述原料，酚磺乙胺500g，依地酸二钠2g，焦亚硫酸钠1g，氯化钠15g，注射用水2000ml，甘露醇0.1g，氯化钾1g，氯化钙2g。
  2. 如权利要求1所述的一种酚磺乙胺注射液，其特征在于，包括下述原料，酚磺乙胺480g，依地酸二钠1g，焦亚硫酸钠2g，氯化钠14g，注射用水2000ml，甘露醇0.2g，氯化钾0.8g，氯化钙1.5g。
  3. 如权利要求1所述的一种酚磺乙胺注射液，其特征在于，包括下述原料，酚磺乙胺450g，依地酸二钠0.5g，焦亚硫酸钠0.5g，氯化钠15g，注射用水2000ml，甘露醇1g，氯化钾1.5g，氯化钙1g。
  4. 如权利要求1所述的一种酚磺乙胺注射液，其特征在于，包括下述原料，酚磺乙胺520g，依地酸二钠3g，焦亚硫酸钠2g，氯化钠15g，注射用水2000ml，甘露醇1.5g，氯化钾2g，氯化钙0.8g。
  5. 如权利要求1或2或3或4所述的一种酚磺乙胺注射液的制备方法，其特征在于，制备步骤如下：(1)在25℃下分别配置酚磺乙胺，依地酸二钠，焦亚硫酸钠，氯化钠的饱和溶液备用；在25℃下将甘露醇、氯化钾和氯化钙溶于10ml注射用水中得微量元素液备用；(2)将酚磺乙胺，依地酸二钠，焦亚硫酸钠，氯化钠的饱和溶液、微量元素液于25℃下混合均匀得原料浓液；(3)将原料浓液至于浓配罐中，向浓配罐中加入活性炭，在38℃下吸附25min，过滤至浓液澄清；(4)将步骤(3)得到的浓液置于稀配罐中，加入注射用水1000ml，于1000r/min的速度下搅拌3min，后向稀配罐中加入活性炭，于45℃下吸附15min，过滤得稀配液；(5)将稀配液进行三级过滤处理得成品原液；(6)向成品原液中补加注射用水至最终溶液重量，调节总料液的pH为5-6，后将总料液于25℃下氮气曝气45min得成品；(7)将成品置于安瓿瓶中，封口；(8)将封口后的安瓿瓶正放，于100℃的流通蒸汽下灭菌10min；(9)检测经过灭菌的安瓿瓶中是否存在可见异物悬浮及微粒数量，灯检的条件为：无色产品光照强度为1200Lx，有色产品光照强度为1800Lx；(10)对灯检合格的安瓿瓶进行包装，贮存。
  6. 如权利要求5所述的一种酚磺乙胺注射液的制备方法，其特征在于，所述步骤(3)的活性炭为药用活性炭，所述活性炭的使用量为酚磺乙胺重量的0.6-0.7％。
  7. 如权利要求5所述的一种酚磺乙胺注射液的制备方法，其特征在于，所述步骤(4)的活性炭为药用活性炭，所述活性炭的使用量为酚磺乙胺重量的0.3-0.4％。
  8. 如权利要求5所述的一种酚磺乙胺注射液的制备方法，其特征在于，所述步骤(5)中的三级过滤为：第一级过滤，采用80-100mm孔径滤纸对其进行过滤处理；第二 级，采用5-7mm孔径滤纸对一级过滤后的稀配液进行过滤处理；第三极：采用0.1-0.5um孔径滤膜对二级过滤后的稀配液进行过滤处理。
  9. 如权利要求5所述的一种酚磺乙胺注射液的制备方法，其特征在于，所述步骤(6)中调节pH所用的溶液为1mol/L的盐酸溶液或1mol/L的NaOH溶液。
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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN117443251A (zh) * 2023-11-01 2024-01-26 安徽宏业药业有限公司 一种缩宫素注射液的生产工艺及其配液生产系统

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111437253A (zh) * 2020-05-15 2020-07-24 山东方明药业集团股份有限公司 一种酚磺乙胺注射液及其制备方法

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3167881A1 (en) * 2015-10-19 2017-05-17 Cuevas Sánchez, Pedro Locally administered ethamsylate as a medicament
CN106963729A (zh) * 2017-04-16 2017-07-21 李孝国 一种用于预防手术出血的药物制剂及其制备方法
CN107308105A (zh) * 2017-06-26 2017-11-03 北京立时达药业有限公司 一种酚磺乙胺注射液及其制造方法
CN108926538A (zh) * 2018-07-24 2018-12-04 江苏金丝利药业股份有限公司 一种注射用酚磺乙胺及其制备方法
CN109010266A (zh) * 2018-09-10 2018-12-18 贵州天地药业有限责任公司 一种安乃近注射液的制备方法
CN111437253A (zh) * 2020-05-15 2020-07-24 山东方明药业集团股份有限公司 一种酚磺乙胺注射液及其制备方法

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3167881A1 (en) * 2015-10-19 2017-05-17 Cuevas Sánchez, Pedro Locally administered ethamsylate as a medicament
CN106963729A (zh) * 2017-04-16 2017-07-21 李孝国 一种用于预防手术出血的药物制剂及其制备方法
CN107308105A (zh) * 2017-06-26 2017-11-03 北京立时达药业有限公司 一种酚磺乙胺注射液及其制造方法
CN108926538A (zh) * 2018-07-24 2018-12-04 江苏金丝利药业股份有限公司 一种注射用酚磺乙胺及其制备方法
CN109010266A (zh) * 2018-09-10 2018-12-18 贵州天地药业有限责任公司 一种安乃近注射液的制备方法
CN111437253A (zh) * 2020-05-15 2020-07-24 山东方明药业集团股份有限公司 一种酚磺乙胺注射液及其制备方法

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN117443251A (zh) * 2023-11-01 2024-01-26 安徽宏业药业有限公司 一种缩宫素注射液的生产工艺及其配液生产系统

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