WO2016045530A1 - 一种高复溶性及高稳定性的绿原酸冻干粉针 - Google Patents

一种高复溶性及高稳定性的绿原酸冻干粉针 Download PDF

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WO2016045530A1
WO2016045530A1 PCT/CN2015/089772 CN2015089772W WO2016045530A1 WO 2016045530 A1 WO2016045530 A1 WO 2016045530A1 CN 2015089772 W CN2015089772 W CN 2015089772W WO 2016045530 A1 WO2016045530 A1 WO 2016045530A1
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chlorogenic acid
parts
injection
freeze
mannitol
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PCT/CN2015/089772
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French (fr)
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张洁
黄望
张亮
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四川九章生物科技有限公司
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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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
    • 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
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/216—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
    • 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
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    • 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
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin

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  • the invention relates to a chlorogenic acid freeze-dried powder needle.
  • Chlorogenic acid is a polyphenolic compound. Experimental studies have shown that it is unstable under acid, alkali, light and high temperature conditions. Zhou Hongqi, Olthof MR and Gonthir MP reported that chlorogenic acid is an unstable polyphenolic compound. Moreover, it is susceptible to factors such as digestive flora, and the bioavailability of oral administration is low, and it is preferable to use a blood vessel administration method, so that the injection dosage form is a better dosage form of the drug. Chlorogenic acid is unstable in aqueous solution, so it is not suitable to use a liquid dosage form.
  • the technical solution of the present invention provides a chlorogenic acid freeze-dried powder needle.
  • the invention provides a chlorogenic acid lyophilized powder needle which is prepared from the following raw materials by weight ratio:
  • the invention also provides a preparation method for preparing a chlorogenic acid lyophilized powder needle, which comprises the following steps:
  • a, dosing in order according to sodium bisulfite, chlorogenic acid, mannitol dissolved in 50-55 ° C water for injection, formulated into a solution containing 15-90mg / ml chlorogenic acid;
  • activated carbon adsorption adding 0.03% activated carbon to the chlorogenic acid aqueous solution, and stirring at 45-50 ° C for 30 minutes in the dark;
  • pre-freezing temperature is below -45 °C
  • pre-freezing time is more than 3 hours
  • drying temperature is raised from -45 °C to 30 °C
  • heating time is 6h-9h
  • drying time is further 2h-5h at 30 °C.
  • the degree of vacuum during lyophilization is 200mPa-400mPa;
  • the packaging material is brown borosilicate glass controlled injection bottle, medicinal butyl rubber stopper or The sterile powder for injection was filled with a halobutyl rubber.
  • the advantages of the freeze-dried powder injection of the invention are: a, good stability, no obvious change in the dark place for 36 months; b good resolubility, rapid dissolution, solubility up to 40%; c, good formability, no collapse , no shrinkage, uniform texture.
  • Solution in accordance with 3 parts of sodium hydrogen sulfite, 30 parts of chlorogenic acid, 90 parts of mannitol dissolved in water for injection at 55 ° C, and prepared into a solution containing 15 mg / ml of chlorogenic acid;
  • Activated carbon adsorption 0.03% activated carbon is added to the chlorogenic acid aqueous solution, and stirred at 50 ° C for 30 minutes in the dark;
  • freeze-dried pre-heating temperature is -45 ° C, pre-freezing time is 3 hours, drying temperature is raised from -45 ° C to 30 ° C, heating time is 9 h, re-drying time is 30 h at 30 ° C, vacuum degree is 200 mPa during freeze-drying -400mPa;
  • Solution in accordance with 1 part of sodium hydrogen sulfite, 30 parts of chlorogenic acid, 60 parts of mannitol dissolved in 50 ° C water for injection, formulated into a solution containing 90 mg / ml of chlorogenic acid;
  • Activated carbon adsorption 0.03% activated carbon was added to the aqueous chlorogenic acid solution, and the mixture was stirred at 45 ° C for 30 minutes in the dark;
  • pre-heating temperature is below -50 °C
  • pre-freezing time is more than 3 hours
  • drying temperature is -50 °C
  • Raised to 30 ° C, heating time 6h, re-drying time 5h at 30 ° C, vacuum degree during lyophilization is 200mPa-400mPa;
  • activated carbon adsorption adding 0.03% activated carbon to the chlorogenic acid solution, avoiding light at 45 ° C Mix for 30 minutes;
  • Freeze-drying pre-station temperature is -48 °C, pre-freezing time is 4 hours, drying temperature is raised from -48 °C to 30 °C, heating time is 7 h, re-drying time is 30 h at 30 °C, and vacuum degree is 200 mPa during freeze-drying. -400mPa;
  • Activated carbon adsorption 0.03% activated carbon was added to the chlorogenic acid aqueous solution, and the mixture was stirred at 448 ° C for 30 minutes in the dark;
  • the pre-heating temperature is -48 °C
  • the pre-freezing time is 4 hours
  • the drying temperature is raised from -48 °C to 30 °C
  • the heating time is 8 h
  • the drying time is 30 h at 30 °C
  • the vacuum degree is 200 mPa during lyophilization. -400mPa;
  • Activated carbon adsorption 0.03% activated carbon was added to the chlorogenic acid aqueous solution, and the mixture was stirred at 46 ° C for 30 minutes in the dark;
  • freeze-dried pre-station temperature is -48 ° C, pre-freezing time 4 hours, drying temperature from -48 ° C to 30 ° C, heating time 9h, 30 ° C re-drying time 5h, freeze-drying period of 200mPa -400mPa;
  • Example 1 The lyophilized powder injection samples prepared in Example 1, Example 2, and Example 3 and Comparative Example 1 were dissolved in 0.1 g, 0.2 g, 0.3 g, 0.4 g, and 0.5 g, respectively, using glucose injection and 0.9 ml of 0.9% physiological saline. Sample, examine the resolubility of the sample, the results are shown in Table 1:
  • the preparation method of the comparative example 1 freeze-dried powder injection is:
  • Activated carbon adsorption 0.03% activated carbon is added to the chlorogenic acid solution, and stirred at 45 ° C for 30 minutes;
  • freeze-dried pre-heating temperature is -38 ° C, pre-freezing time 3 hours, drying temperature is raised from -38 ° C to 28 ° C, heating time is 6.5 h, initial vacuum is 450 mbar, the end vacuum is 200 mbar, and then dried 30 ° C, 3 h.
  • the chlorogenic acid crystal form used in the invention has a good resolubility by preparing a lyophilized powder injection with a ratio of mannitol and sodium hydrogen sulfite in a certain weight ratio, and the solubility can reach 40 mg at 25 ° C. Ml, the solubility of 20 mg/ml of the comparative example is 100% higher.
  • the chlorogenic acid crystal form used in the invention has a good stability by preparing a lyophilized powder injection by a ratio of mannitol and sodium hydrogen sulfite in a certain weight ratio.
  • Example 1-3 the amount of individual related substances increased in 36 months, and the increase rate was not large, which increased by 7.87%-110.81% compared with that of 0. Among them, the most stable example was increased by 7.87%-63.91%.
  • the sum of other related substances except caffeic acid increased, but the increase was small, which increased by 13.29%-76.48% compared with that of 0, which was the most stable in Example 1, which increased by 13.29%; Reduced, but not obvious, decreased by 0.08%-0.61% compared with 0 month, of which the most stable in Example 1, only 0.08%.
  • the individual related substances increased by 166.18%-2200% in 36 months, the total of other related substances except caffeic acid increased by 451.20%, and the labeled content decreased by 3.67%.
  • the stability of the proportional preparation is not good.

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Abstract

一种绿原酸冻干粉针及其制备方法。所述绿原酸冻干粉针由下述重量配比的原辅料制备而成：绿原酸30份，甘露醇60-90份，亚硫酸氢钠1-3份；其中，绿原酸的晶型为正交晶系，空间群为P2 12 12 1，晶胞参数为a=7.7291(2)Å，b=10.9808(2) Å，c=36.5334(7) Å，α＝β＝γ＝90°，Z=8，晶胞体积为3100.65（11）Å 3。

Description

一种高复溶性及高稳定性的绿原酸冻干粉针 技术领域
本发明涉及一种绿原酸冻干粉针。
背景技术
绿原酸为多酚类化合物，实验研究证明，在酸、碱、光照和高温条件下不稳定，周宏灏、Olthof MR和Gonthir MP等文献报道表明，绿原酸属不稳定的多酚类化合物，且易受到消化道菌群等因素的影响，口服给药的生物利用度较低，最好是采用血管给药方式，故注射剂型为该药物的较好剂型。绿原酸在水溶液中不稳定性，故不宜采用液体剂型。
发明内容
本发明的技术方案是提供了一种绿原酸冻干粉针。
本发明提供了一种绿原酸冻干粉针，它是由下述重量配比的原辅料制备而成：
绿原酸30份，甘露醇60-90份，亚硫酸氢钠1-3份；
其中，绿原酸的晶型为正交晶系，空间群为P212121，晶胞参数为
Figure PCTCN2015089772-appb-000001
α＝β＝γ＝90°，Z＝8，晶胞体积为
Figure PCTCN2015089772-appb-000002
绿原酸是按专利申请号：201410193699.8所述的方法制备。
进一步优选地，它是由下述重量配比的原辅料制备而成：
绿原酸30份、甘露醇90份、亚硫酸氢钠3份。
本发明还提供了一种制备绿原酸冻干粉针的制备方法，它包括如下步骤：
a、配液：依次按照亚硫酸氢钠、绿原酸、甘露醇溶解于50-55℃注射用水中，配制成含15-90mg/ml绿原酸的溶液；
b、活性炭吸附：向绿原酸水溶液加入0.03％活性炭，于45-50℃条件下避光搅拌30分钟；
c、脱碳及精滤：用0.22μm滤膜过滤，检测滤液不溶性微粒；
d、灌装：滤液不溶性微粒检测合格后，按每瓶含10-60mg绿原酸灌装；
e、冻干：预冻温度为-45℃以下，预冻时间3小时以上，干燥温度由-45℃以下升至30℃，升温时间6h-9h，在30℃下再干燥时间2h-5h，冻干期间真空度为200mPa-400mPa；
f、包装。
其中，包装材料为棕色低硼硅玻璃管制注射剂瓶、药用丁基橡胶瓶塞或 注射用无菌粉末用卤化丁基橡胶塞。
本发明冻干粉针剂的优点：a、稳定性良好，阴暗处存放36个月内无明显变化；b复溶性良好，溶解迅速，溶解度较大可达40％；c、成型性良好，无塌陷，不皱缩，质地均匀。
具体实施方式
实施例1本发明冻干粉针剂的制备方法
1、配液：依次按照3份亚硫酸氢钠、30份绿原酸、90份甘露醇溶解于55℃注射用水中，配制成含15mg/ml绿原酸的溶液；
2、活性炭吸附：向绿原酸水溶液加入0.03％活性炭，于50℃条件下避光搅拌30分钟；
3、脱碳及精滤：用0.22μm滤膜过滤，检测滤液不溶性微粒，不溶性微粒合格；
4、灌装：按每瓶含30mg绿原酸灌装，半加注射用无菌粉末用卤化丁基橡胶塞；
5、冻干：预栋温度为-45℃，预冻时间3小时，干燥温度由-45℃升至30℃，升温时间9h，在30℃下再干燥时间2h，冻干期间真空度为200mPa-400mPa；
6、轧盖；
实施例2本发明冻干粉针剂的制备方法
1、配液：依次按照1份亚硫酸氢钠、30份绿原酸、60份甘露醇溶解于50℃注射用水中，配制成含90mg/ml绿原酸的溶液；
2、活性炭吸附：向绿原酸水溶液加入0.03％活性炭，于45℃条件下避光搅拌30分钟；
3、脱碳及精滤：用0.22μm滤膜过滤，检测滤液不溶性微粒，不溶性微粒合格；
4、灌装：按每瓶含60mg绿原酸灌装，半加药用丁基橡胶瓶塞；
5、冻干：预栋温度为-50℃以下，预冻时间3小时以上，干燥温度由-50℃
升至30℃，升温时间6h，在30℃下再干燥时间5h，冻干期间真空度为200mPa-400mPa；
6、轧盖；
实施例3本发明冻干粉针剂的制备方法
1、配液：依次按照2份亚硫酸氢钠、30份绿原酸、80份甘露醇溶解于50℃注射用水中，配制成含30mg/ml绿原酸的溶液；
2、活性炭吸附：向绿原酸溶液加入0.03％活性炭，于45℃条件下避光搅 拌30分钟；
3、脱碳及精滤：用0.22μm滤膜过滤，检测滤液不溶性微粒，不溶性微粒合格；
4、灌装：按每瓶含30mg绿原酸灌装，半加药用丁基橡胶瓶塞；
5、冻干：预栋温度为-48℃，预冻时间4小时，干燥温度由-48℃升至30℃，升温时间7h，在30℃下再干燥时间5h，冻干期间真空度为200mPa-400mPa；
6、轧盖。
实施例4本发明冻干粉针剂的制备方法
1、配液：依次按照3份亚硫酸氢钠、30份绿原酸、70份甘露醇溶解于53℃注射用水中，配制成含20mg/ml绿原酸的溶液；
2、活性炭吸附：向绿原酸水溶液加入0.03％活性炭，于448℃条件下避光搅拌30分钟；
3、脱碳及精滤：用0.22μm滤膜过滤，检测滤液不溶性微粒，不溶性微粒合格；
4、灌装：按每瓶含10mg绿原酸灌装，半加药用丁基橡胶瓶塞；
5、冻干：预栋温度为-48℃，预冻时间4小时，干燥温度由-48℃升至30℃，升温时间8h，在30℃下再干燥时间2h，冻干期间真空度为200mPa-400mPa；
6、轧盖。
实施例5本发明冻干粉针剂的制备方法
1、配液：依次按照2份亚硫酸氢钠、30份绿原酸、60份甘露醇溶解于52℃注射用水中，配制成含50mg/ml绿原酸的溶液；
2、活性炭吸附：向绿原酸水溶液加入0.03％活性炭，于46℃条件下避光搅拌30分钟；
3、脱碳及精滤：用0.22μm滤膜过滤，检测滤液不溶性微粒，不溶性微粒合格；
4、灌装：按每瓶含50mg绿原酸灌装，半加药用丁基橡胶瓶塞；
5、冻干：预栋温度为-48℃，预冻时间4小时，干燥温度由-48℃升至30℃，升温时间9h，在30℃下再干燥时间5h，冻干期间真空度为200mPa-400mPa；
6、轧盖。
实施例1-5所述的绿原酸是按专利申请号：201410193699.8所述的方法制备。
实施例6复溶性
取实施例1、实施例2及实施例3、对比例1制备的冻干粉针剂样品，分别用葡萄糖注射液及0.9％生理盐水1ml溶解0.1g、0.2g、0.3g、0.4g及0.5g样品，考察样品的复溶性，结果见表1：
其中，对比例1冻干粉针剂的制备方法为：
1、配液：依次按照2份亚硫酸氢钠、30份绿原酸、80份甘露醇溶解于50℃注射用水中，控制溶液pH值为3，其中绿原酸原料为市售绿原酸，绿原酸含量为99.3％；
2、活性炭吸附：向绿原酸溶液加入0.03％活性炭，于45℃条件下搅拌30分钟；
3、脱碳及精滤：用0.22μm滤膜过滤，检测滤液不溶性微粒，不溶性微粒合格；
4、灌装：按每瓶含60mg绿原酸灌装，半加药用丁基橡胶瓶塞；
5、冻干：预栋温度为-38℃，预冻时间3小时，干燥温度由-38℃升温至28℃，升温时间为6.5h，初始真空度为450mbar，结束真空度为200mbar，再干燥30℃，3h。
6、轧盖。
本发明采用的绿原酸晶型，通过与甘露醇、亚硫酸氢钠按一定的重量比例配比，制备成的冻干粉针剂具有良好的复溶性，在25℃条件下溶解度可达40mg/ml，比对比例的20mg/ml溶解度高出100％。
实施例7稳定性
取冻干粉针剂，摇散，倒置于18±2℃，相对湿度60±10％的条件下，于3月、6月、9月、12月、18月、24月、36月末取样检测。结果见下表2及表3：
本发明采用的绿原酸晶型，通过与甘露醇、亚硫酸氢钠按一定的重量比例配比，制备成的冻干粉针剂具有良好的稳定性。实施例1-3在36个月内单个有关物质有所增加，增加幅度不大，与0月相比增加了7.87％-110.81％，其中以实施例1最稳定，增加了7.87％-63.91％；除咖啡酸外的其它有关物质总和有所增加，但增加幅度较小，与0月相比增加了13.29％-76.48％，其中以实施例1最稳定，增加了13.29％；标示含量有所降低，但不明显，与0月相比降低了0.08％-0.61％，其中以实施例1最稳定，只降低了0.08％。
对比例中，在36个月内单个有关物质比0月增加了166.18％-2200％，除咖啡酸外的其它有关物质总和增加451.20％，标示含量降低3.67％，说明对 比例制剂的稳定性欠佳。
Figure PCTCN2015089772-appb-000003
Figure PCTCN2015089772-appb-000004
Figure PCTCN2015089772-appb-000005
表3长期稳定性试验分析结果
Figure PCTCN2015089772-appb-000006

Claims (4)

  1. 一种绿原酸冻干粉针，其特征在于：它是由下述重量配比的原辅料制备而成：
    绿原酸30份，甘露醇60-90份，亚硫酸氢钠1-3份；
    其中，绿原酸的晶型为正交晶系，空间群为P212121，晶胞参数为
    Figure PCTCN2015089772-appb-100001
    α＝β＝γ＝90°，Z＝8，晶胞体积为
    Figure PCTCN2015089772-appb-100002
  2. 根据权利要求1所述的绿原酸冻干粉针，其特征在于：它是由下述重量配比的原辅料制备而成：
    绿原酸30份、甘露醇90份、亚硫酸氢钠3份。
  3. 一种制备权利要求1或2所述的绿原酸冻干粉针的制备方法，它包括如下步骤：
    a、配液：依次按照亚硫酸氢钠、绿原酸、甘露醇溶解于50-55℃注射用水中，配制成含15-90mg/ml绿原酸的溶液；
    b、活性炭吸附：向绿原酸溶液加入0.03％活性炭，于45-50℃条件下避光搅拌30分钟；
    c、脱碳及精滤：用0.22μm滤膜过滤，检测滤液不溶性微粒；
    d、灌装：滤液不溶性微粒检测合格后，按每瓶含10-60mg绿原酸灌装；
    e、冻干：预冻温度为-45℃以下，预冻时间3小时以上，干燥温度由-45℃以下升至30℃，升温时间6h-9h，在30℃下再干燥时间2h-5h，冻干期间真空度为200mPa-400mPa；
    f、包装。
  4. 根据权利要求3所述的制备方法，其特征在于：包装材料为棕色低硼硅玻璃管制注射剂瓶、药用丁基橡胶瓶塞或注射用无菌粉末用卤化丁基橡胶塞。
PCT/CN2015/089772 2014-09-22 2015-09-16 一种高复溶性及高稳定性的绿原酸冻干粉针 WO2016045530A1 (zh)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111103375A (zh) * 2018-10-25 2020-05-05 四川九章生物科技有限公司 一种绿原酸衍生物在药品质量控制中的应用

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111100006B (zh) * 2018-10-25 2022-04-26 四川九章生物科技有限公司 一种3-咖啡酰奎尼酸衍生物及其制备方法和用途
CN111346061B (zh) * 2018-12-21 2022-02-18 北京科莱博医药开发有限责任公司 绿原酸组合物及其制备方法
CN111728945A (zh) * 2020-08-18 2020-10-02 四川九章生物科技有限公司 一种治疗带状疱疹的注射剂

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1568960A (zh) * 2004-05-08 2005-01-26 四川九章生物化工科技发展有限公司 高纯度绿原酸制剂
CN103446064A (zh) * 2013-08-21 2013-12-18 四川九章生物化工科技发展有限公司 一种绿原酸粉针剂及其制备方法
CN103951562A (zh) * 2014-05-09 2014-07-30 四川九章生物化工科技发展有限公司 一种绿原酸晶型及其制备方法

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1813705A (zh) * 2005-11-23 2006-08-09 广东大光药业有限公司 一种注射用绿原酸粉针剂及其制备方法及其用途
CN102391119A (zh) * 2011-11-14 2012-03-28 肖文辉 高纯度绿原酸制剂的制备及临床应用

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1568960A (zh) * 2004-05-08 2005-01-26 四川九章生物化工科技发展有限公司 高纯度绿原酸制剂
CN103446064A (zh) * 2013-08-21 2013-12-18 四川九章生物化工科技发展有限公司 一种绿原酸粉针剂及其制备方法
CN103951562A (zh) * 2014-05-09 2014-07-30 四川九章生物化工科技发展有限公司 一种绿原酸晶型及其制备方法

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111103375A (zh) * 2018-10-25 2020-05-05 四川九章生物科技有限公司 一种绿原酸衍生物在药品质量控制中的应用
CN111103375B (zh) * 2018-10-25 2022-04-08 四川九章生物科技有限公司 一种绿原酸衍生物在药品质量控制中的应用

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