金黄片制备工艺及质量标准研究
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摘要
急性咽炎为常见上呼吸道感染性疾病,起病急,表现为咽喉肿痛、吞咽困难,有时伴有咳嗽和发热。如治疗不彻底而反复发作,会发展成为迁延难治的慢性咽炎。急性咽炎的起因多为病毒感染(40—60%),其它有细菌、真菌感染,也有污染物或化学物质诱发。病毒引发的疾病治疗多为对症治疗,细菌或真菌感染引发的疾病可使用抗生素治疗。中药复方在治疗急性咽炎方面发挥了不可替代的作用。金黄片组方来源于临床经验方,处方组成为金银花、黄芩、知母、桔梗和甘草,原组方对于急性咽炎的治疗疗效确切。本研究旨在通过现代制药技术,将传统方剂开发成为服用方便、质量可控的现代制剂。
本文对金黄片的最佳制备工艺及制剂的质量标准进行了初步研究,拟订了金黄片的质量标准草案,考察了制剂的初步稳定性,为今后的新药研究提供实验依据。
通过对处方药味主要有效成分的理化性质进行分析,采用正交试验法对金黄片的提取工艺和制备工艺进行了优选。方中药材金银花、知母、甘草所含主要有效成分亲水性较强,故采用水提醇沉方法进行提取。以绿原酸含量为考察指标,确定其最佳提取工艺条件为10倍水提取三次,每次提取1小时,醇沉工艺采用的乙醇浓度为60%。方中药材黄芩的主要有效成分为黄芩苷,采用了水提酸沉法进行提取,即煎煮二次,每次加水8倍,每次1小时。滤过,合并滤液,浓缩,加盐酸调pH 2,80℃保温1小时,静置,滤过,沉淀干燥,粉碎成细粉,备用。处方药味桔梗采用直接打粉,细粉直接进行制粒。确定了喷雾干燥一步制粒的工艺条件,将提取物细粉、桔梗细粉与清膏进行喷雾制粒,颗粒加入0.5%硬脂酸镁混合,压片,包薄膜衣,制得金黄片。
对制剂进行了质量标准和初步稳定性研究。采用薄层层析法鉴别金黄片中的桔梗和甘草,各薄层色谱斑点清晰、专属性强、阴性无干扰。建立了金黄片中绿原酸和黄芩苷的高效液相色谱含量测定方法并进行了方法学考察,所建立的方法检测灵敏、专属性强,可用于产品质量控制。按此标准对三批中试样品进行检测,并对三批样品进行了常温留样考察6个月的初步稳定性试验。结果表明,所制备的金黄片质量稳定,重现性好,符合中药新药的质量要求。
Acute pharyngitis is a common kind of inflammatory disease characterized by rapid onset,sore throat,and difficulty with swallowing.A chronic pharyngitis may ensue if the acute pharyngitis could not be treated satisfactorily or if it occurred repeatedly.Most cases are caused by viral infections(40%-60%),with the remainder caused by bacterial infections,fungal infections,or irritants such as pollutants and chemical substances.Treatment of viral causes are mainly symptomatic while bacterial or fungal causes may be amenable to antibiotics and anti-fungals, respectively.Compound prescriptions of Traditional Chinese Medicine(TCM) play a irreplaceable role in the treatment of acute pharyngitis.The prescription of Jinhuang Pian was derived from clinical experience.The constituents of this prescription consist of Lonicera japonica,Anemarrhena asphodeloides,Glycyrrhiza uralensis, Scutellaria baicalensis,and Platycodon grandiflorum.It has long been proved that this prescription has a reliable effect for the treatment of acute pharyngitis.This study aimed at inventing a novel medicine with the characteristics of taking conveniently and carrying easily based on the prescription of Jinhuang Pian.
In this paper the preparation technology and quality standard of Jinhuang Pian were studied and a quality control method was established for the further study as a new Chinese Traditional Medicine. According to the physicochemical properties of effective components in Chinese medicinal herbs in the prescription,the extraction conditions and preparation technology were established by the orthogonal design.The water extracting-alcohol precipitating method was used to extract the water-soluble effective components of Lonicera japonica,Anemarrhena asphodeloides,and Glycyrrhiza uralensis.The content of chlorogenic acid was taken as comprehensive index to confirm the optimal extraction conditions.The medicinal materials were decocted with 10-fold water for 3 times,1 hour per time.The optimal alcohol concentration for extraction was 60%. Scutellaria baicalensis was decocted with 8-fold water for 2 times,1 hour per time. The extracted solution should be concentrated,added with hydrochloric acid to adjust the pH to 2,keeped at 80℃for 1 hour,and then filtrated.The precipitate was rinsed using water,dried under vacuum,then ground into powder.Platycodon grandiflorum was ground into fine powder directly.The one-step spray-drying and granulating processing conditions were determined by orthogonal test.Granules were made into tablets by adding 0.5%magnesium stearate.The tablets were coated with film coating technology.
The quality control standard of Jinghuang Pian was also established in this paper. The thin layer chromatography(TLC) methods were established to identify Platycodon grandiflorum and Glycyrrhiza uralensis.A high performance liquid chromatography(HPLC) method was established to determine the content of chlorogenic acid and baicalin in Jinghuang Pian.Three consecutive batches of pilot products were analyzed using the established quality standard.The results of stability test showed that Jinhuang Pian was stable when stored at room temperature for 6 months.The results showed that the prepation and quality control methods were feasible and stable.
本文对金黄片的最佳制备工艺及制剂的质量标准进行了初步研究,拟订了金黄片的质量标准草案,考察了制剂的初步稳定性,为今后的新药研究提供实验依据。
通过对处方药味主要有效成分的理化性质进行分析,采用正交试验法对金黄片的提取工艺和制备工艺进行了优选。方中药材金银花、知母、甘草所含主要有效成分亲水性较强,故采用水提醇沉方法进行提取。以绿原酸含量为考察指标,确定其最佳提取工艺条件为10倍水提取三次,每次提取1小时,醇沉工艺采用的乙醇浓度为60%。方中药材黄芩的主要有效成分为黄芩苷,采用了水提酸沉法进行提取,即煎煮二次,每次加水8倍,每次1小时。滤过,合并滤液,浓缩,加盐酸调pH 2,80℃保温1小时,静置,滤过,沉淀干燥,粉碎成细粉,备用。处方药味桔梗采用直接打粉,细粉直接进行制粒。确定了喷雾干燥一步制粒的工艺条件,将提取物细粉、桔梗细粉与清膏进行喷雾制粒,颗粒加入0.5%硬脂酸镁混合,压片,包薄膜衣,制得金黄片。
对制剂进行了质量标准和初步稳定性研究。采用薄层层析法鉴别金黄片中的桔梗和甘草,各薄层色谱斑点清晰、专属性强、阴性无干扰。建立了金黄片中绿原酸和黄芩苷的高效液相色谱含量测定方法并进行了方法学考察,所建立的方法检测灵敏、专属性强,可用于产品质量控制。按此标准对三批中试样品进行检测,并对三批样品进行了常温留样考察6个月的初步稳定性试验。结果表明,所制备的金黄片质量稳定,重现性好,符合中药新药的质量要求。
Acute pharyngitis is a common kind of inflammatory disease characterized by rapid onset,sore throat,and difficulty with swallowing.A chronic pharyngitis may ensue if the acute pharyngitis could not be treated satisfactorily or if it occurred repeatedly.Most cases are caused by viral infections(40%-60%),with the remainder caused by bacterial infections,fungal infections,or irritants such as pollutants and chemical substances.Treatment of viral causes are mainly symptomatic while bacterial or fungal causes may be amenable to antibiotics and anti-fungals, respectively.Compound prescriptions of Traditional Chinese Medicine(TCM) play a irreplaceable role in the treatment of acute pharyngitis.The prescription of Jinhuang Pian was derived from clinical experience.The constituents of this prescription consist of Lonicera japonica,Anemarrhena asphodeloides,Glycyrrhiza uralensis, Scutellaria baicalensis,and Platycodon grandiflorum.It has long been proved that this prescription has a reliable effect for the treatment of acute pharyngitis.This study aimed at inventing a novel medicine with the characteristics of taking conveniently and carrying easily based on the prescription of Jinhuang Pian.
In this paper the preparation technology and quality standard of Jinhuang Pian were studied and a quality control method was established for the further study as a new Chinese Traditional Medicine. According to the physicochemical properties of effective components in Chinese medicinal herbs in the prescription,the extraction conditions and preparation technology were established by the orthogonal design.The water extracting-alcohol precipitating method was used to extract the water-soluble effective components of Lonicera japonica,Anemarrhena asphodeloides,and Glycyrrhiza uralensis.The content of chlorogenic acid was taken as comprehensive index to confirm the optimal extraction conditions.The medicinal materials were decocted with 10-fold water for 3 times,1 hour per time.The optimal alcohol concentration for extraction was 60%. Scutellaria baicalensis was decocted with 8-fold water for 2 times,1 hour per time. The extracted solution should be concentrated,added with hydrochloric acid to adjust the pH to 2,keeped at 80℃for 1 hour,and then filtrated.The precipitate was rinsed using water,dried under vacuum,then ground into powder.Platycodon grandiflorum was ground into fine powder directly.The one-step spray-drying and granulating processing conditions were determined by orthogonal test.Granules were made into tablets by adding 0.5%magnesium stearate.The tablets were coated with film coating technology.
The quality control standard of Jinghuang Pian was also established in this paper. The thin layer chromatography(TLC) methods were established to identify Platycodon grandiflorum and Glycyrrhiza uralensis.A high performance liquid chromatography(HPLC) method was established to determine the content of chlorogenic acid and baicalin in Jinghuang Pian.Three consecutive batches of pilot products were analyzed using the established quality standard.The results of stability test showed that Jinhuang Pian was stable when stored at room temperature for 6 months.The results showed that the prepation and quality control methods were feasible and stable.
引文
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