| Non-erosive gastroesophageal reflux disease is a type of gastroesophageal reflux disease.It is a gastro-intestinal disease with main symptoms of acid reflux,heartburn or food reflux.The etiology and pathogenesis of this disease is still unclear.It is generally believed that it is related to acid reflux and non-acid reflux,abnormal esophageal motility,high sensitivity of esophageal visceral mucosa,decreased resistance of esophageal mucosal tissue,and psychological or mental abnormalities.At present,the treatment of NERD mostly stays at the control of symptoms and cannot be completely cured,and its incidence in China is increasing year by year,which seriously affects the life and work of patients.The treatment of NERD has become a hot topic in clinical research.Hewei Jiangni Formula is a clinical prescription that originates from Professor Li Junxiang who inherited the clinical experience and academic thoughts of Academician Dong Jianhua,combined with many years of clinical experience to continuously improve the composition of the component prescription.Hewei Jiangni Formula has a significant effect in experimental research and clinical validation,and it is better than the current clinical drug proton pump inhibitors(PPI).Hewei Jiangni Formula composed of Baikal skullcap,Coptis chinensis,Dried ginger,Alum processed pinellia[tuber],Immature bitter orange,Thunberg fritillary bulb,Mongolian dandelion herb,Rough gentian root,Mongolian snakegourd fruit,and Fried Glycyrrhizae ten herbs in all.The prescription is rigorous and the medication is peaceful.In the light of NERD,it has the efficacy of balancing fever and chills,lowering the stomach vomit effect.Objective:Decoction is one of the earliest and most widely used dosage forms in China,but it needs immediate preparation before using,and it has the features of bitter taste,large amount,inconvenience in oral administration and taking,easy to mould after long storage,so decoction is not in line with modern drug habits.In order to overcome the shortcomings of traditional decoctions,and make up for the lack of Chinese patent medicine with NERD as an indication for treatment and exact efficacy,Hejiang granule in line with modern drug habits had been made.This study uses traditional Chinese medicine extraction and enrichment techniques combined with modern preparation techniques to develop the Hewei Jiangni prescription into granules,and conduct preliminary evaluation and control of the safety,effectiveness,and stability of the granules.Methods:This subject mainly includes the research on the extraction and molding process of HeweiJiangni prescription,the study of quality standards,stability,and the preliminary pharmacy and pharmacodynamic evaluation of Hejiang granule.The specific methods are as follows:Extraction process research:HeweiJiangni prescription was divided into three parts,including the volatile oil extraction part,the water extraction part,and the ethanol extraction part.In the volatile oil extraction part Dried ginger and Immature bitter orange were included,and the single factor experiment was used to determine the three factors such as grind degree,merge extraction and extraction time that affect the extraction of volatile oil by using volatile oil extraction amount and 6-gingerol extraction rate as indexes.After inspection,uniform design was used to optimize the factors that had a greater impact.Finally,a single factor study was performed to determine the extraction times.The water extraction part mainly aimed at the extraction of Baikal skullcap,Alum processed pinellia[tuber],Mongolian dandelion herb,Rough gentian root,Mongolian snakegourd fruit,and Fried Glycyrrhizae.The number of extractions,the extraction time,and the amount of water were three factors.The baicalin extraction rate and dry ointment rate were used as indicators to measure the three factors of water extraction process by using orthogonal test.In the alcohol extraction part Coptis chinensis and Thunberg fritillary bulb were included,and single factor experiment was used to determin the ethanol concentration by using the coptis alkaloid extraction rate,Fritillaria alkaloids extraction amount and dry ointment rate as index.The extraction times,solvent amount,and extraction time of the alcohol extraction process were investigated by using orthogonal test.Molding process research:The moisture absorption rate,molding rate,melting rate,soft material and grain properties and the difficulty level of granulation were used as indicators to assess the proper excipient,the amount of the excipient and the wetting agent concentration of wet granulation excipients.In addition,the fluidity,critical relative humidity,and melt ability were examined.Quality standard study:referring to the methods under the Granule Principle 0104 in the Chinese Pharmacopoeia 2015 edition,the moisture content and dissolubility examination was conducted;Referring to the determination of extractives method under the preparations Principle and Notopterygii Bolus of Nine Ingredients,Danxiang Qingzhi Granules,Anzhong Tablets in the Chinese Pharmacopoeia 2015 edition,the ethyl ether extract of HeJiang Granule was measured and its standard was formulated;Adopting TLC and HPLC methods,the qualitative and quantitative research of HeJiang Granule was conducted to formulate its quality standards.Stability:Referring to the Guidelines for Stability Testing of Raw Material Drugs and Preparations(9001)of Pharmacopoeia 2015 edition in order to investigate factors affecting HeJiang Granule stability.Comparative study of pharmacy and pharmacodynamics of traditional decoction,formula granules,and HeJiang Granule(The pharmacodynamic experiment was completed by the research group of Professor Li Junxiang of DongFang Hospital of Beijing University of Chinese Medicine):The enzyme-linked immunosorbent assay(ELISA)was used to determine this three preparations relative protein content in a rat model of NERD induced by basic sensitization combined with esophageal acid perfusion.Adopting HPLC to measure index component in this three preparations and study preliminarily of the dose-effect relationship.Results:Extraction process:Dried ginger and Immature bitter orange were extracted together,dry ginger crushed over 4 mesh,12 times water,2.5 hours the extraction of volatile oil,and then added 10 times water in dregs,extract 1h,combined this twice filtrate,set aside.Baikal skullcap,Alum processed pinellia[tuber],Mongolian dandelion herb,Rough gentian root,Mongolian snakegourd fruit,and Fried Glycyrrhizae,were reflux extracted with 12 times water(considering water absorption of medicinal materials,15 times of water was needed for the first time),for 3 times,each time 2h,combined this three times filtrate,and the volatile oil portion.Coptis chinensis and Thunberg fritillary bulb(Thunberg fritillary bulb crushed to a degree that can pass through 6 meshes,but mixed with 24 objects not exceeding 20%),were extracted with 12 folds(considering solvent absorption of medicinal materials,15 folds of solvent was needed for the first time)of 50%ethanol was for 3 times,each time for 1.5 hours.The filtrate was decompressed and recovered at 60℃ until no alcohol was found,and combining with the filtrate of water extract proportion,volatile oil extract proportion,being concentrated to a relative density of 1.15-1.20(60℃).After that,thick extract drying under reduced pressure(70℃),crushed into fine powder.Molding process:dextrin as excipient,the ratio of drug to excipient was 2:1,and 85%ethanol was used for wet granulation.The extracted volatile oil was dissolved in an appropriate amount of 95%ethanol,and evenly sprayed on the granules and sealed,swelling 24h.Quality standards:The total content of epiberberine,coptisine chloride,palmatin hydrochloride should not be lower than 2.50 mg·g-1.The content of berberine hydrochloride should not be lower than 4.20 mg·g-1.The content of baicalin should not be less than 14.4 mg·g-1.With volatile ether extracts shall not be less than 0.29%.Besides,the TLC method of six herbs,which was of good specificity.Stability:Strong light illumination and high temperature had no obvious effect on the appearance,solubility and main content determination of the granule,but the volatile oil was adopted the process of ethanol dissolving and spraying,it bound to be affected by strong light and high temperature.So in the process of packaging,storage and transportation should be avoided strong light as much as possible,stored in a cool place.Comparative study of traditional decoction,formula granules,and HeJiang Granule in pharmacy and pharmacodynamics:The pharmacodynamics study showed that Hejiang Granule has a significant effect,besides,the daily dose dropped to 1/2.The main content determination index study found that the total content of epiberberine,coptisine chloride,palmatin hydrochloride in the three preparations from high to low was HeJiang Granule>formula granules>traditional decoction;berberine hydrochloride content from high to low was He Jiang Granule>formula granules>traditional decoction;baicalin content from high to low was HeJiang Granule>traditional decoction>formula granules.The above research shows that choosing the chemical composition as an indicator to control the quality of the process and drug was scientific.The efficacy of Chinese medicine compound was the result of multiple components.We should use multiple indicators and multi components to control the quality of the granule.Conclusion:Through the research on extraction and forming process,the stable and feasible preparation of HeJiang Granule for is established,and qualified HeJiang Granules has been prepared.Through the research on quality standard,the content limit of volatile ether extract,method of qualitative standard and quantitative determination are established.These methods can be repeated and of good precision and accuracy,and lay the foundation for the quality control of HeJiang Granule in the future;Through the study of the stability of HeJiang Granule,the influence factors of stability is clarified,it can provide a reference for the study of stability in the future;Through the pharmacy and pharmacodynamics comparative study between traditional decoction,formula granule,and HeJiang Granule,a preliminary assessment of the efficacy of HeJiang Granule was conducted,and lays a foundation for further development. |
PDF Full Text Request