First, raw material research.
Through the comparative study on the quality of multi-source and multi-producing areas, the basic source, producing area and specification grade of Chinese herbal medicines are determined, which stabilizes the purchasing base of Chinese herbal medicines and ensures the stability of product quality.
1. Determination of the source of multi-source varieties: In order to ensure the stability of the quality of traditional Chinese medicine formula granules, determine the source and medicinal parts of medicinal materials. In the study, the quality of different sources of medicinal materials was compared, and the supply of mainstream varieties in the market was considered, and the basic sources and medicinal parts of medicinal materials were finally determined. For example, * Epimedium: The 2000 edition of Pharmacopoeia includes five sources. The content of icariin in Epimedium koreanum is high, reaching 1.08- 1.76%, so it is determined that the source of Epimedium koreanum is the aerial part of Epimedium koreanum.
2. Determination of producing areas of varieties with multiple producing areas: Some varieties have great differences in the content of effective components due to different producing areas and growth modes. By comparing the contents of effective components in medicinal materials from different origins, the origin of raw materials is finally determined to ensure the quality of raw materials. Such as Scutellaria baicalensis Georgi, the content of baicalin in Scutellaria baicalensis Georgi from different habitats was compared. Therefore, the content of baicalin in Scutellaria baicalensis Georgi produced in Pingyi, Shandong Province can reach 19.8%~22.3%. Therefore, the raw material origin of Scutellaria baicalensis formula granules is determined as Pingyi, Shandong Province.
In addition to the variety and origin confirmation mentioned above, there are also detailed regulations on collection, processing and treatment.
Second, the process research
Theoretical basis: traditional theory: following the theory of traditional Chinese medicine and according to the preparation characteristics of traditional decoction, water is used as solvent in principle. Modern theory: According to the structural characteristics of rhizome, leaf, flower, fruit, seed and whole grass and the properties of chemical components (such as alkaloids, flavonoids, anthraquinones, saponins, volatile oil, etc.). ), the classification research.
Study on extraction technology of 1.
① Extraction process of volatile oil: According to the differences of different varieties of volatile oil properties, such as polarity, boiling point, density, etc. The volatile oil was extracted by steam distillation. The volatile oil was included, and the parameters such as inclusion time, inclusion temperature and oil-water ratio were investigated.
② Study on the extraction process of water-soluble components: Orthogonal test or uniform design method was used to optimize the extraction process parameters.
A. According to the properties of chemical components, orthogonal test or uniform design method is used to optimize the technological parameters such as water addition, decocting times and decocting time. B. Through the research on the extraction technology of various representative varieties, it provides a basis for formulating the extraction technology of other varieties with similar organizational structure or chemical composition. C at the same time, when determining the extraction process of specific varieties, combined with the traditional preparation methods of decoction (such as frying first and then frying, frying for a long time, mashing and then frying), a scientific and economic extraction production process was formulated.
2. Research on separation technology: According to the characteristics of impurities to be removed, especially for medicinal materials that are difficult to filter and contain mucus, starch, pectin and other components, research and apply appropriate filtration technology and equipment to ensure product quality.
3. Study on concentration process: A vacuum membrane concentration process was developed to concentrate the extract at low temperature to a specified relative density under vacuum decompression, effectively retaining the effective components of the drug.
4. Study on spray drying process: According to the relative density, solid content and other parameters of concentrated extract, as well as the properties of components contained in the extract, the spray drying process parameters such as inlet air temperature, outlet air temperature and negative pressure in the tower were investigated.
5. Study on granulating technology: The technological parameters such as the type and dosage of auxiliary materials, main side pressure and feeding speed were investigated, especially the moisture absorption and caking, and satisfactory results were obtained.
Third, the quality standard research
The research items of quality standards include characters, identification, inspection and content determination.
1. Establishment of specific identification method: TLC, HPLC, IR and other chromatographic and spectral identification methods were used, and positive reference materials were selected to establish a specific, sensitive and reproducible identification method. TLC identification was established for 300 commonly used varieties, and in 2004, the color atlas of traditional Chinese medicine formula granules was published for the first time in China, which recorded the comprehensive atlas of 152 single varieties, 6 compound traditional Chinese medicine formula granules and 5 traditional Chinese medicine formula granules, chromatogram 188, and photos of medicinal materials and decoction pieces 156. In the process of atlas making, multiple batches of samples of each variety were taken for analysis, and the differences of TLC between different batches were compared.
2. Establishment of content determination project: According to the physical and chemical properties of the tested components, a simple and reproducible content determination method was studied and established by TLC scanning, UV spectrophotometry and HPLC. According to the content determination results of 10 batch of formula granules, the content limit is established.
For example, it is stipulated that the berberine content in Huanglian formula granules shall not be less than 15% based on berberine hydrochloride. The content of paeoniflorin in stir-fried Radix Paeoniae Alba formula granules shall not be less than 3.0%. Puerarin in Radix Puerariae formula granules shall not be less than 65438 00%. The content of gardenoside in gardenia formula granules shall not be less than 65438 00%.
Fourth, pharmacological and pharmacodynamic research.
Select Shengmai Decoction, Jiawei Shenghua Decoction, Gegen Qinlian Decoction, Huoxiang Zhengqi Powder, etc. 10, and compare the pharmacodynamics of co-decocting and sub-decocting by Institute of Traditional Chinese Medicine, Nanjing University of Traditional Chinese Medicine and China Pharmaceutical University.
Both the decoction of Shengmaiyin and the decoction of Shengmaiyin have anti-arrhythmic effects in mice induced by aconitine, and there is no difference in efficacy. All of them have anti-hemorrhagic shock effect in rats, and there is no difference in efficacy.
Jiawei Shenghua Decoction can promote uterine contraction alone or in combination. All of them have obvious hemostatic effect, and the combined decoction is better than the separate decoction.
The results of pharmacodynamics research show that all the prescriptions have obvious curative effects by single decoction or combined decoction. The pharmacodynamics of the two drugs are similar, and there is no obvious difference. In some pharmacodynamic indexes, the curative effect of formula granules is better than that of decoction pieces.
Clinical study on verb (abbreviation of verb)
10 prescriptions with clear clinical efficacy and objective test indicators were screened out. Choose a hospital with clinical research qualifications for new drugs. The clinical laboratory of Nanjing University of Traditional Chinese Medicine (the clinical pharmacology research base of new drugs of the Ministry of Health) conducted a comparative study on the clinical efficacy of separate decoction and combined decoction. The results show that both the separate decoction and the combined decoction have obvious curative effects, among which two prescriptions are better than the combined decoction, and the other eight prescriptions have no obvious difference, so the clinical prescription application is feasible.