WO2021184699A1 - 一种盐酸莫西沙星氯化钠注射液及其制备方法 - Google Patents

一种盐酸莫西沙星氯化钠注射液及其制备方法 Download PDF

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WO2021184699A1
WO2021184699A1 PCT/CN2020/113782 CN2020113782W WO2021184699A1 WO 2021184699 A1 WO2021184699 A1 WO 2021184699A1 CN 2020113782 W CN2020113782 W CN 2020113782W WO 2021184699 A1 WO2021184699 A1 WO 2021184699A1
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sodium chloride
moxifloxacin hydrochloride
injection
filter element
polyethersulfone filter
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PCT/CN2020/113782
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English (en)
French (fr)
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王立江
赵勇征
王晖
王恰茹
杨义
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石家庄四药有限公司
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/08—Solutions
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
    • 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
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B65—CONVEYING; PACKING; STORING; HANDLING THIN OR FILAMENTARY MATERIAL
    • B65D—CONTAINERS FOR STORAGE OR TRANSPORT OF ARTICLES OR MATERIALS, e.g. BAGS, BARRELS, BOTTLES, BOXES, CANS, CARTONS, CRATES, DRUMS, JARS, TANKS, HOPPERS, FORWARDING CONTAINERS; ACCESSORIES, CLOSURES, OR FITTINGS THEREFOR; PACKAGING ELEMENTS; PACKAGES
    • B65D31/00—Bags or like containers made of paper and having structural provision for thickness of contents
    • B65D31/04—Bags or like containers made of paper and having structural provision for thickness of contents with multiple walls

Definitions

  • the solution relates to moxifloxacin hydrochloride and sodium chloride injection and a preparation method thereof, and belongs to the technical field of pharmaceutical preparations.
  • Moxifloxacin hydrochloride is an 8-methoxyfluoroquinolone antibacterial drug with broad spectrum and antibacterial activity. Clinically, it is mainly used to treat acute bacterial sinusitis, acute exacerbation of chronic bronchitis, community-acquired pneumonia, complicated intra-abdominal infections, and skin and skin tissue infections.
  • the moxifloxacin hydrochloride and sodium chloride injection used in clinical intravenous infusion is a 250ml large-volume injection; it is used to rescue critically ill patients with fast onset and remarkable curative effect.
  • the existing Moxifloxacin Hydrochloride and Sodium Chloride Injection is packaged in a semi-open glass bottle, and the preparation method is divided into two steps: first concentrated preparation and then diluted preparation.
  • activated carbon is first added and then filtered and removed.
  • the concentrated preparation is not easy to dissolve, and two preparation tanks are required, which consumes a lot of equipment cleaning treatment and clean control, and the risk of pollution is high.
  • Activated carbon has an adsorption effect on moxifloxacin. Excessive feeding is required to meet the quality requirements.
  • the production and quality standards of activated carbon are uneven, and there is a risk of promoting the degradation of related substances.
  • this solution provides a moxifloxacin hydrochloride and sodium chloride injection and a preparation method thereof.
  • the first aspect of this solution provides a method for preparing moxifloxacin hydrochloride and sodium chloride injection, which includes the following steps:
  • the preparation method of Moxifloxacin Hydrochloride and Sodium Chloride Injection includes the following steps:
  • the polyethersulfone filter element A in the concentration stage is used in combination with the polyethersulfone filter element B, polyethersulfone filter element C and polyethersulfone filter element D before filling in the dilute mixing stage to ensure the stability of product quality and make the obtained moxifloxacin hydrochloride
  • the product quality of sodium chloride injection is stable and the content of related substances is low, which ensures the effectiveness and safety of the medication.
  • step S1 after filtering, rinse the polyethersulfone filter element A with water for injection of 10%-20% of the total volume of the injection solution. After the rinse solution and the filtrate are combined, step S2 is entered to further ensure the product The content is stable between batches.
  • the preparation method of Moxifloxacin Hydrochloride and Sodium Chloride Injection includes the following steps:
  • the amount of moxifloxacin hydrochloride is 1.55-1.65 g/L based on moxifloxacin.
  • the dosage of moxifloxacin hydrochloride is 1.60 g/L based on moxifloxacin.
  • the sodium chloride dosage is 7.5-8.5 g/L, as an isotonic agent, suitable for direct intravenous drip in humans.
  • the sodium chloride dosage is 8.0 g/L.
  • the pore size of the polyethersulfone filter element A is 1.0 ⁇ m.
  • the pore size of the polyethersulfone filter element B is 0.45 ⁇ m
  • the pore diameter of the polyethersulfone filter element C is 0.20-0.22 ⁇ m
  • the pore diameter of the polyethersulfone filter element D is 0.10 ⁇ m.
  • the pH regulator is sodium hydroxide or hydrochloric acid
  • the pH of the injection is adjusted to 4.1-4.6, so that the system is in a relatively stable state, effectively controlling the generation of impurities, reducing the content of related substances, and improving the product Quality and stability.
  • the sterilization temperature is 121°C and the time is 12-20 min.
  • the filling adopts a multi-layer co-extruded film soft bag or a vertical soft bag with a specification of 250mL. It is a fully airtight flexible package with self-shrinking function, which can effectively avoid the need for glass bottle packaging in clinical use. Introducing air can easily cause secondary pollution, and it is more suitable for applications in hospitals and high-pollution environments.
  • the second aspect of the application provides a moxifloxacin hydrochloride and sodium chloride injection, which is prepared by the above-mentioned preparation method of moxifloxacin hydrochloride and sodium chloride injection.
  • the preparation method of moxifloxacin hydrochloride and sodium chloride injection provided by this program does not use medicinal activated carbon in the whole preparation process, which avoids the adsorption of moxifloxacin hydrochloride by activated carbon, ensures the stable content of the product between batches, and improves the product The quality also reduces the pollution to the clean production area and reduces the pressure on environmental protection.
  • 3 or 4 groups of polyethersulfone filter elements with successively reduced pore diameters are used for filtration.
  • the Moxifloxacin Hydrochloride and Sodium Chloride Injection provided by this program uses moxifloxacin hydrochloride as the main drug and sodium chloride as an isotonic agent.
  • the product quality is stable, the content of related substances is low, and the effectiveness and safety are high.
  • the osmolality of the injection is 0.85-1.00, the pH is 4.1-4.6, and the total impurities are ⁇ 0.1%. It is suitable for direct intravenous drip in humans.
  • the method for preparing moxifloxacin hydrochloride and sodium chloride injection includes the following steps:
  • a preparation method of moxifloxacin hydrochloride and sodium chloride injection includes the following steps:
  • Moxifloxacin hydrochloride (calculated as moxifloxacin) 400mg, sodium chloride 2.0g, water for injection 250mL, pH adjuster (sodium hydroxide or hydrochloric acid) appropriate, the filling specification is 0.4g/250mL, based on 1000 bags.
  • a preparation method of moxifloxacin hydrochloride and sodium chloride injection includes the following steps:
  • Moxifloxacin hydrochloride (calculated as moxifloxacin) 413mg, sodium chloride 2.1g, water for injection 255mL, appropriate amount of pH regulator (sodium hydroxide or hydrochloric acid), the filling specification is 0.4g/250mL, based on 1000 bags.
  • a preparation method of moxifloxacin hydrochloride and sodium chloride injection includes the following steps:
  • Moxifloxacin hydrochloride (calculated as moxifloxacin) 400mg, sodium chloride 1.8g, water for injection 250mL, pH adjuster (sodium hydroxide or hydrochloric acid) appropriate, the filling specification is 0.4g/250mL, based on 1000 bags.
  • a preparation method of moxifloxacin hydrochloride and sodium chloride injection includes the following steps:
  • Moxifloxacin hydrochloride (calculated as moxifloxacin) 400mg, sodium chloride 2.0g, water for injection 250mL, pH adjuster (sodium hydroxide or hydrochloric acid) appropriate, the filling specification is 0.4g/250mL, based on 1000 bags.
  • a preparation method of moxifloxacin hydrochloride and sodium chloride injection includes the following steps:
  • Moxifloxacin hydrochloride (calculated as moxifloxacin) 413mg, sodium chloride 2.1g, water for injection 255mL, appropriate amount of pH regulator (sodium hydroxide or hydrochloric acid), the filling specification is 0.4g/250mL, based on 1000 bags.
  • adding activated carbon for injection during the preparation process specifically includes the following steps:
  • Moxifloxacin hydrochloride (calculated as moxifloxacin) 400mg, sodium chloride 2.0g, water for injection 250mL, pH adjuster (sodium hydroxide or hydrochloric acid) appropriate, the filling specification is 0.4g/250mL, based on 1000 bags.
  • Example 1 Using the prescription in Example 1, the polyethersulfone filter element was replaced with a polypropylene filter element during the preparation process, and the others were the same as in Example 1, to obtain moxifloxacin hydrochloride sodium chloride injection.
  • Example 4 Using the prescription in Example 4, the polyethersulfone filter element B was removed during the preparation process, and the others were the same as in Example 4 to obtain Moxifloxacin Hydrochloride Sodium Chloride Injection.
  • the content of the moxifloxacin hydrochloride and sodium chloride injection product provided by the embodiment of the present invention is stable, and the content of related substances is low.
  • the content is basically unchanged, has good stability, high effectiveness and safety, and is suitable for direct intravenous drip in the human body.
  • the polypropylene filter element used in Comparative Example 2 has a larger adsorption capacity for moxifloxacin hydrochloride, which affects the effective content of the final product.
  • Comparative Example 3 only polyethersulfone filter element C and polyether are used.
  • the sulfone filter element D is difficult to effectively remove endotoxin, so that the endotoxin content of the product does not meet the standard.
  • the present invention can effectively ensure the stability of the product quality through the use of a filter element of a specific quantity and a specific material and a pH adjuster without using activated carbon, so that the obtained moxifloxacin hydrochloride sodium chloride injection
  • the product quality is stable, and the content of related substances is low, which ensures the effectiveness and safety of the medication.
  • Example 1 the low-temperature freeze-thaw tests of Example 1 and Comparative Example 1 were carried out, and three freeze-thaw cycles were performed. It was inspected for 2 days under the condition of °C, sampled and tested, and the results are shown in Table 2.
  • the moxifloxacin hydrochloride and sodium chloride injection product provided by the examples of the present invention has no obvious change in appearance and color, and the related substances and content are basically unchanged. It has certain storage stability under the conditions of low-temperature cycle test, indicating The moxifloxacin hydrochloride and sodium chloride injection provided by the embodiment of the present invention has better stability and safety during transportation and use.

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Abstract

一种盐酸莫西沙星氯化钠注射液及其制备方法。所述制备方法包括如下步骤：将盐酸莫西沙星、氯化钠和pH调节剂加入注射用水中，搅拌溶解，通过3或4组且孔径依次减小的聚醚砜滤芯过滤，灌装，灭菌，得盐酸莫西沙星氯化钠注射液。盐酸莫西沙星氯化钠注射液采用上述制备方法制得。提供的注射液批次间含量稳定，有关物质含量低，有效性和安全性高，且具有良好的稳定性。

Description

一种盐酸莫西沙星氯化钠注射液及其制备方法
本申请要求于2020年03月19日提交的中国专利申请CN202010196194.2的优先权。在先申请的公开内容通过整体引用并入本申请。
技术领域
本方案涉及盐酸莫西沙星氯化钠注射液及其制备方法，属于药物制剂技术领域。
 背景技术
盐酸莫西沙星是广谱和具有抗菌活性的8-甲氧基氟喹诺酮类抗菌药。临床上主要用于治疗急性细菌性鼻窦炎、慢性支气管炎急性发作、社区获得性肺炎、复杂性腹腔内感染以及皮肤和皮肤组织感染等。临床上静脉输注应用的盐酸莫西沙星氯化钠注射液为250ml大容量注射剂；用于抢救危重病患，起效快，疗效显著。
现有的盐酸莫西沙星氯化钠注射液为半开放式玻瓶包装，制备方法分为先浓配再稀配两步，在浓配时先加入活性炭再过滤去除。然而，两步配制时，浓配不易溶解，且需要两个配制罐，设备清洁处理和洁净控制消耗量大，污染风险高。活性炭对莫西沙星有吸附作用，需要过量投料才能达到质量要求，且活性炭生产和质量标准参差不齐，存在促进有关物质降解的风险，同时，在称量和投料活性炭时极易造成活性炭飞扬，污染洁净区。使用后的活性炭的回收及处理也会对环保造成压力。
 技术问题
针对现有盐酸莫西沙星氯化钠注射液制备过程中存在的上述技术问题，本方案提供一种盐酸莫西沙星氯化钠注射液及其制备方法。
 技术解决方案
本方案的第一方面提供一种盐酸莫西沙星氯化钠注射液的制备方法，包括如下步骤：
将盐酸莫西沙星、氯化钠和pH调节剂加入注射用水中，搅拌溶解，通过3或4组且孔径依次减小的聚醚砜滤芯过滤，灌装，灭菌，得盐酸莫西沙星氯化钠注射液。
作为本方案的一种改进，所述的盐酸莫西沙星氯化钠注射液的制备方法，包括如下步骤：
S1：将盐酸莫西沙星和氯化钠加入注射液总体积30%-70%的注射用水中，搅拌溶解，通过聚醚砜滤芯A进行过滤，得滤液；
S2：向滤液中加入剩余的注射用水，加入pH调节剂，依次通过聚醚砜滤芯B、聚醚砜滤芯C和聚醚砜滤芯D过滤，灌装，灭菌，得盐酸莫西沙星氯化钠注射液。
浓配阶段的聚醚砜滤芯A与稀配阶段灌装前的聚醚砜滤芯B、聚醚砜滤芯C和聚醚砜滤芯D联合使用，保证产品质量的稳定性，使所得盐酸莫西沙星氯化钠注射液产品质量稳定，有关物质含量低，保证了用药的有效性和安全性。
作为本方案的一种改进，步骤S1中，过滤后用注射液总体积10%-20%的注射用水冲洗聚醚砜滤芯A，将冲洗液与滤液合并后，进入S2步骤，进一步地保证产品批次间含量稳定。
作为本方案的一种改进，所述的盐酸莫西沙星氯化钠注射液的制备方法，包括如下步骤：
将盐酸莫西沙星、氯化钠和pH调节剂加入注射液总体积100%的注射用水中，搅拌溶解，依次通过聚醚砜滤芯B、聚醚砜滤芯C和聚醚砜滤芯D过滤，灌装，灭菌，得盐酸莫西沙星氯化钠注射液。采用一步法配制，与传统的先浓配再稀配两步法相比，盐酸莫西沙星溶解速度快，工艺简单，投资少，配制罐清洁和处理量小，成本低。
作为本方案的一种改进，以注射液总体积计，所述盐酸莫西沙星的用量以莫西沙星计为1.55-1.65g/L。
作为本方案的一种改进，所述盐酸莫西沙星的用量以莫西沙星计为1.60g/L。
作为本方案的一种改进，以注射液总体积计，所述氯化钠用量为7.5-8.5g/L，作为等渗剂，适用于人体直接静脉滴注。
作为本方案的一种改进，所述氯化钠用量为8.0g/L。
作为本方案的一种改进，所述聚醚砜滤芯A的孔径为1.0μm。
作为本方案的一种改进，所述聚醚砜滤芯B的孔径为0.45μm，所述聚醚砜滤芯C的孔径为0.20-0.22μm，所述聚醚砜滤芯D的孔径为0.10μm，滤除内毒素和微生物。
作为本方案的一种改进，所述pH调节剂为氢氧化钠或盐酸，调节注射液pH值为4.1-4.6，使体系处于相对稳定状态，有效控制杂质的产生，降低有关物质含量，提高产品质量和稳定性。
作为本方案的一种改进，所述灭菌温度为121℃，时间为12~20min。
作为本方案的一种改进，灌装采用多层共挤膜软袋或直立式软袋，规格为250mL，是具有自收缩功能的全密闭软包装，可以有效避免采用玻瓶包装在临床使用时需要导入空气，易造成二次污染的问题，更适用于医院与高污染环境下应用。
本申请的第二方面提供一种盐酸莫西沙星氯化钠注射液，由上述盐酸莫西沙星氯化钠注射液的制备方法制得。
 有益效果
与现有技术相比，本方案具有如下优点：
（1）本方案提供的盐酸莫西沙星氯化钠注射液的制备方法，整个配制过程不使用药用活性炭，避免了活性炭对盐酸莫西沙星吸附，保证产品批次间含量稳定，提高了产品质量，同时也降低了对生产洁净区污染，减轻环保压力。此外，灌装前采用3或4组且孔径依次减小的聚醚砜滤芯进行过滤，通过特定数量和特定材质的滤芯与pH调节剂的配合使用，进一步地保证产品质量的稳定性，使所得盐酸莫西沙星氯化钠注射液产品质量稳定，有关物质含量低，保证了用药的有效性和安全性。
（2）本方案提供的盐酸莫西沙星氯化钠注射液，以盐酸莫西沙星为主药，氯化钠作为等渗剂，产品质量稳定，有关物质含量低，有效性和安全性高，注射液渗透压摩尔浓度在0.85-1.00，pH值为4.1-4.6，总杂质≤0.1%，适用于人体直接静脉滴注。
 本发明的实施方式
本方案提供的一种盐酸莫西沙星氯化钠注射液的制备方法，包括如下步骤：
将盐酸莫西沙星、氯化钠和pH调节剂加入注射用水中，控制温度为65-75℃，搅拌10-15min，溶解均匀后，按中间体质量标准检测，检测含量、pH值、可见异物，检测合格后，通过3或4组且孔径依次减小的聚醚砜滤芯过滤，灌装，灭菌，灯检合格包装，得盐酸莫西沙星氯化钠注射液产品。
实施例1
一种盐酸莫西沙星氯化钠注射液的制备方法，包括如下步骤：
处方：盐酸莫西沙星（以莫西沙星计）400mg，氯化钠2.0g，注射用水250mL，pH调节剂（氢氧化钠或盐酸）适量，装量规格0.4g/250mL，以1000袋计。
S1：在浓配罐中加入注射液总体积50%的注射用水，控制温度为65℃，依次加入处方量的盐酸莫西沙星和氯化钠，搅拌溶解后，通过孔径为1.0μm的聚醚砜滤芯A进行过滤，并用注射液总体积15%的注射用水冲洗聚醚砜滤芯A，将冲洗液与滤液一起输送至稀配罐；
S2：向稀配罐中补加剩余注射用水，加入pH调节剂，检测含量、pH值（4.3）、可见异物，检测合格后过滤，依次通过孔径为0.45μm的聚醚砜滤芯B、孔径为0.22μm的聚醚砜滤芯C和孔径为0.10μm的聚醚砜滤芯D过滤，灌装至多层共挤膜软袋（规格为250mL），封口，于121℃灭菌15min，灯检合格包装，得盐酸莫西沙星氯化钠注射液产品。
实施例2
一种盐酸莫西沙星氯化钠注射液的制备方法，包括如下步骤：
处方：盐酸莫西沙星（以莫西沙星计）413mg，氯化钠2.1g，注射用水255mL，pH调节剂（氢氧化钠或盐酸）适量，装量规格0.4g/250mL，以1000袋计。
S1：在浓配罐中加入注射液总体积30%的注射用水，控制温度为75℃，依次加入处方量的盐酸莫西沙星和氯化钠，搅拌溶解后，通过孔径为1.0μm的聚醚砜滤芯A进行过滤，并用注射液总体积20%的注射用水冲洗聚醚砜滤芯A，将冲洗液与滤液一起输送至稀配罐；
S2：向稀配罐中补加剩余注射用水，加入pH调节剂，检测含量、pH值（4.1）、可见异物，检测合格后过滤，依次通过孔径为0.45μm的聚醚砜滤芯B、孔径为0.20μm的聚醚砜滤芯C和孔径为0.10μm的聚醚砜滤芯D过滤，灌装至多层共挤膜软袋（规格为250mL），封口，于121℃灭菌12min，灯检合格包装，得盐酸莫西沙星氯化钠注射液产品。
实施例3
一种盐酸莫西沙星氯化钠注射液的制备方法，包括如下步骤：
处方：盐酸莫西沙星（以莫西沙星计）400mg，氯化钠1.8g，注射用水250mL，pH调节剂（氢氧化钠或盐酸）适量，装量规格0.4g/250mL，以1000袋计。
S1：在浓配罐中加入注射液总体积70%的注射用水，控制温度为70℃，依次加入处方量的盐酸莫西沙星和氯化钠，搅拌溶解后，通过孔径为1.0μm的聚醚砜滤芯A进行过滤，并用注射液总体积10%的注射用水冲洗聚醚砜滤芯A，将冲洗液与滤液一起输送至稀配罐；
S2：向稀配罐中补加剩余注射用水，加入pH调节剂，检测含量、pH值（4.6）、可见异物，检测合格后过滤，依次通过孔径为0.45μm的聚醚砜滤芯B、孔径为0.22μm的聚醚砜滤芯C和孔径为0.10μm的聚醚砜滤芯D过滤，灌装至多层共挤膜软袋（规格为250mL），封口，于121℃灭菌20min，灯检合格包装，得盐酸莫西沙星氯化钠注射液产品。
实施例4
一种盐酸莫西沙星氯化钠注射液的制备方法，包括如下步骤：
处方：盐酸莫西沙星（以莫西沙星计）400mg，氯化钠2.0g，注射用水250mL，pH调节剂（氢氧化钠或盐酸）适量，装量规格0.4g/250mL，以1000袋计。
在配制罐中加入注射液总体积100%的注射用水，依次加入处方量的盐酸莫西沙星、氯化钠和pH调节剂，搅拌10min，溶解均匀后，按中间体质量标准检测，检测含量、pH值（4.3）、可见异物，检测合格后，依次通过孔径为0.45μm的聚醚砜滤芯B、孔径为0.22μm的聚醚砜滤芯C和孔径为0.10μm的聚醚砜滤芯D过滤，灌装至多层共挤膜软袋（规格为250mL），封口，于121℃灭菌15min，灯检合格包装，得盐酸莫西沙星氯化钠注射液产品。
实施例5
一种盐酸莫西沙星氯化钠注射液的制备方法，包括如下步骤：
处方：盐酸莫西沙星（以莫西沙星计）413mg，氯化钠2.1g，注射用水255mL，pH调节剂（氢氧化钠或盐酸）适量，装量规格0.4g/250mL，以1000袋计。
在配制罐中加入注射液总体积100%的注射用水，依次加入处方量的盐酸莫西沙星、氯化钠和pH调节剂，搅拌15min，溶解均匀后，按中间体质量标准检测，检测含量、pH值（4.6）、可见异物，检测合格后，依次通过孔径为0.45μm的聚醚砜滤芯B、孔径为0.22μm的聚醚砜滤芯C和孔径为0.10μm的聚醚砜滤芯D过滤，灌装至直立式软袋（规格为250mL），封口，于121℃灭菌20min，灯检合格包装，得盐酸莫西沙星氯化钠注射液产品。
对比例1
采用实施例1中处方，在制备过程中添加注射用活性炭，具体包括如下步骤：
处方：盐酸莫西沙星（以莫西沙星计）400mg，氯化钠2.0g，注射用水250mL，pH调节剂（氢氧化钠或盐酸）适量，装量规格0.4g/250mL，以1000袋计。
在配制罐中加入注射液总体积100%的注射用水，依次加入处方量的盐酸莫西沙星、氯化钠和pH调节剂，搅拌12min，溶解均匀后，加入注射液总体积0.05（w/v）%的注射用活性炭，继续搅拌20min，通过孔径为1.0μm的聚醚砜滤芯过滤，检测含量、pH值（4.5）、可见异物，检测合格后，依次通过孔径为0.45μm的聚醚砜滤芯和孔径为0.22μm的聚醚砜滤芯过滤，灌装至多层共挤膜软袋（规格为250mL），封口，于121℃灭菌12min，灯检合格包装，得盐酸莫西沙星氯化钠注射液产品。
对比例2
采用实施例1中处方，在制备过程中将聚醚砜滤芯替换为聚丙烯滤芯，其他与实施例1相同，得到盐酸莫西沙星氯化钠注射液。
对比例3
采用实施例4中处方，在制备过程中去掉聚醚砜滤芯B，其他与实施例4相同，得到盐酸莫西沙星氯化钠注射液。
参照药物稳定性指导原则，对盐酸莫西沙星氯化钠注射液进行稳定性考察，将实施例1-5及对比例1-3所得的盐酸莫西沙星氯化钠注射液产品进行影响因素考察试验，在温度60℃的条件下分别进行0天、5天、10天的初步影响因素试验，结果如表1所示。
表1
Figure dest_path_image001
由以上数据可得，与对比例1中添加注射用活性炭的制备工艺相比，本发明实施例提供的盐酸莫西沙星氯化钠注射液产品批次间含量稳定，有关物质含量低，有关物质、含量基本未变，具有良好的稳定性，有效性和安全性高，适用于人体直接静脉滴注。通过与对比例2、3比较，对比例2中采用了聚丙烯滤芯对盐酸莫西沙星的吸附量较大，影响最终产品的有效含量，对比例3中仅仅采用聚醚砜滤芯C和聚醚砜滤芯D难以有效去除内毒素，使产品内毒素含量不达标。进一步地说明，本发明在未使用活性炭的情况下，通过特定数量和特定材质的滤芯与pH调节剂的配合使用，能够有效保证产品质量的稳定性，使所得盐酸莫西沙星氯化钠注射液产品质量稳定，有关物质含量低，保证了用药的有效性和安全性。
此外，根据化学药物制剂研究技术指导原则，将实施例1与对比例1进行低温冻融试验，做三次冻融循环，每次循环在-10℃~-20℃条件下2天，然后在40℃条件下考察2天，取样检测，结果如表2所示。
表2
Figure dest_path_image002
由以上数据可得，本发明实施例提供的盐酸莫西沙星氯化钠注射液产品外观颜色无明显变化，有关物质、含量基本未变，在低温循环试验条件下具有一定的放置稳定性，说明本发明实施例提供的盐酸莫西沙星氯化钠注射液在运输和使用过程中具有较好的稳定性和安全性。

Claims (10)

  1. 一种盐酸莫西沙星氯化钠注射液的制备方法，其特征在于：包括如下步骤：
    将盐酸莫西沙星、氯化钠和pH调节剂加入注射用水中，搅拌溶解，通过3或4组且孔径依次减小的聚醚砜滤芯过滤，灌装，灭菌，得盐酸莫西沙星氯化钠注射液。
  2. 如权利要求1所述的盐酸莫西沙星氯化钠注射液的制备方法，其特征在于：包括如下步骤：
    S1：将盐酸莫西沙星和氯化钠加入注射液总体积30%-70%的注射用水中，搅拌溶解，通过聚醚砜滤芯A进行过滤，得滤液；
    S2：向滤液中加入剩余的注射用水，加入pH调节剂，依次通过聚醚砜滤芯B、聚醚砜滤芯C和聚醚砜滤芯D过滤，灌装，灭菌，得盐酸莫西沙星氯化钠注射液。
  3. 如权利要求1所述的盐酸莫西沙星氯化钠注射液的制备方法，其特征在于：包括如下步骤：
    将盐酸莫西沙星、氯化钠和pH调节剂加入注射液总体积100%的注射用水中，搅拌溶解，依次通过聚醚砜滤芯B、聚醚砜滤芯C和聚醚砜滤芯D过滤，灌装，灭菌，得盐酸莫西沙星氯化钠注射液。
  4. 如权利要求1至3任一项所述的盐酸莫西沙星氯化钠注射液的制备方法，其特征在于：所述盐酸莫西沙星的用量以莫西沙星计为1.55-1.65g/L。
  5. 如权利要求1至3任一项所述的盐酸莫西沙星氯化钠注射液的制备方法，其特征在于：所述氯化钠用量为7.5-8.5g/L。
  6. 如权利要求2所述的盐酸莫西沙星氯化钠注射液的制备方法，其特征在于：所述聚醚砜滤芯A的孔径为1.0μm。
  7. 如权利要求2或3所述的盐酸莫西沙星氯化钠注射液的制备方法，其特征在于：所述聚醚砜滤芯B的孔径为0.45μm，所述聚醚砜滤芯C的孔径为0.20-0.22μm，所述聚醚砜滤芯D的孔径为0.10μm。
  8. 如权利要求1至3任一项所述的盐酸莫西沙星氯化钠注射液的制备方法，其特征在于：所述pH调节剂为氢氧化钠或盐酸，调节注射液pH值为4.1-4.6。
  9. 如权利要求1至3任一项所述的盐酸莫西沙星氯化钠注射液的制备方法，其特征在于：灌装采用多层共挤膜软袋或直立式软袋。
  10. 一种盐酸莫西沙星氯化钠注射液，其特征在于：由权利要求1至9任一项所述的盐酸莫西沙星氯化钠注射液的制备方法制得。
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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115282116A (zh) * 2022-08-19 2022-11-04 浙江和沐康医药科技有限公司 一种阿米卡星注射液及其制备方法
CN115444857A (zh) * 2022-08-30 2022-12-09 安徽丰原药业股份有限公司 一种氰化物解毒剂注射液的制备方法

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111388415A (zh) * 2020-03-19 2020-07-10 石家庄四药有限公司 一种盐酸莫西沙星氯化钠注射液及其制备方法
CN112516082A (zh) * 2020-12-31 2021-03-19 常州兰陵制药有限公司 氨基己酸注射液及其制备方法
CN112957322B (zh) * 2021-03-23 2023-08-15 回音必集团江西东亚制药有限公司 一种乳酸左氧氟沙星氯化钠注射液及其制备方法
CN113069411B (zh) * 2021-04-02 2022-08-09 石家庄四药有限公司 一种己酮可可碱注射液及其制备方法
CN114569550A (zh) * 2022-03-08 2022-06-03 石家庄四药有限公司 一种曲克芦丁注射液及其制备方法

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101884613A (zh) * 2010-07-28 2010-11-17 陕西合成药业有限公司 一种盐酸莫西沙星氯化钠注射液及其制备方法和用途
CN102000024A (zh) * 2010-11-17 2011-04-06 陕西合成药业有限公司 一种盐酸莫西沙星氯化钠注射液及其制备方法和用途
CN103181892A (zh) * 2013-02-20 2013-07-03 南京恒道医药科技有限公司 盐酸莫西沙星滴眼液及其制备方法
CN109431987A (zh) * 2018-12-17 2019-03-08 江西润泽药业有限公司 盐酸莫西沙星氯化钠注射液及其制备方法
US10265312B1 (en) * 2018-02-01 2019-04-23 Jason Ahee Antibiotic solution and method of injection to prevent ophthalmic infections
CN110721153A (zh) * 2019-10-08 2020-01-24 四川太平洋药业有限责任公司 一种盐酸莫西沙星氯化钠注射液及制备工艺
CN111388415A (zh) * 2020-03-19 2020-07-10 石家庄四药有限公司 一种盐酸莫西沙星氯化钠注射液及其制备方法

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE19937116A1 (de) * 1999-08-06 2001-02-08 Bayer Ag Moxifloxacin Kochsalzformulierung
CN1704057A (zh) * 2004-06-02 2005-12-07 上海医药科技发展有限公司 注射用盐酸莫西沙星的制备方法
CN105640876B (zh) * 2016-01-07 2019-04-12 天津红日药业股份有限公司 一种盐酸莫西沙星氯化钠注射液的制备工艺

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101884613A (zh) * 2010-07-28 2010-11-17 陕西合成药业有限公司 一种盐酸莫西沙星氯化钠注射液及其制备方法和用途
CN102000024A (zh) * 2010-11-17 2011-04-06 陕西合成药业有限公司 一种盐酸莫西沙星氯化钠注射液及其制备方法和用途
CN103181892A (zh) * 2013-02-20 2013-07-03 南京恒道医药科技有限公司 盐酸莫西沙星滴眼液及其制备方法
US10265312B1 (en) * 2018-02-01 2019-04-23 Jason Ahee Antibiotic solution and method of injection to prevent ophthalmic infections
CN109431987A (zh) * 2018-12-17 2019-03-08 江西润泽药业有限公司 盐酸莫西沙星氯化钠注射液及其制备方法
CN110721153A (zh) * 2019-10-08 2020-01-24 四川太平洋药业有限责任公司 一种盐酸莫西沙星氯化钠注射液及制备工艺
CN111388415A (zh) * 2020-03-19 2020-07-10 石家庄四药有限公司 一种盐酸莫西沙星氯化钠注射液及其制备方法

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115282116A (zh) * 2022-08-19 2022-11-04 浙江和沐康医药科技有限公司 一种阿米卡星注射液及其制备方法
CN115282116B (zh) * 2022-08-19 2023-04-18 浙江和沐康医药科技有限公司 一种阿米卡星注射液及其制备方法
CN115444857A (zh) * 2022-08-30 2022-12-09 安徽丰原药业股份有限公司 一种氰化物解毒剂注射液的制备方法
CN115444857B (zh) * 2022-08-30 2023-08-01 安徽丰原药业股份有限公司 一种氰化物解毒剂注射液的制备方法

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