Study on essential medicine system from the perspective of coordinated with centralized volume-based procurement policy / 中国药房

OBJECTIVE To provide a reference for further improvement of the essential medicine system. METHODS Statistical analysis method and comparative analysis method were used to explain the necessity of coordination between the two systems from the direct correlation and indirect impact of centralized volume-based procurement on the essential medicine system at the present stage. The relevant suggestions were put forward for the development of the essential medicine system in the new era from the perspective of improving institutional synergy. RESULTS & CONCLUSIONS There was a direct correlation between the policy of centralized procurement and the essential medicine system in terms of policy objectives and medicines selection. However， it also indirectly affects the use of essential medicines in medical institutions through production and supply， coincidence degree between the essential medicine list and the selected variety， and the consistency evaluation of generic drugs. It is suggested that in the selection of essential medicine list in the future， priority should be given to the selection of varieties through centralized procurement， and improve the drug supply guarantee capacity under the dual policy linkage； at the same time， incentive assessments for the allocation and use of essential medicines by various entities should be further strengthened to promote the further improvement and development of the essential medicine system.

Research on Preparation Process and Quality Evaluation of Traditional Chinese Medicine Dispensing Granules and Its Consistency with Traditional Decoction： A Review / 中国实验方剂学杂志

Traditional Chinese medicine dispensing granules（TCMDGs）is the new type of decoction pieces with the development of modernization of TCM， which has received mixed opinions since its practical application. In 2021， the national departments issued Announcement on Ending the Pilot Work of TCMDGs， marking the end of the 28-year pilot work of TCMDGs， and eligible TCM enterprises can produce TCMDGs after filing. However， this does not mean that the preparation process， quality standard and efficacy research of TCMDGs have been developed and matured， on the contrary， there are still some problems that need to be solved and gradually improved. For example， in the production process， there are problems such as unclear， unified and non-standardized preparation parameters. In terms of quality control， there are some problems such as lack of producing area regulation， variety selection and processing specification. In terms of consistency evaluation with traditional decoction， there are problems such as unclear relationship between the chemical constituents and pharmacological effects of the two. Therefore， in view of some prominent problems of TCMDGs at present， this paper takes the published literature as the main data source and combines the specific requirements of the code or technical standards such as the 2020 edition of Chinese Pharmacopoeia， Publicity of the Unified Standard on the Varieties of TCMDGs， Quality Control and Standard Formulation Technical Requirements of TCMDGs. The production process of TCMDGs， the origin and variety of raw materials， the processing of decoction pieces， the quality control standard and the consistency evaluation of formula granules and traditional decoction were sorted out and visualized by literature mining， data analysis and list comparison. Based on the analysis results， the following suggestions were made. In terms of preparation process， the completeness and standardization of process parameters should be strengthened. In terms of quality evaluation， attention should be paid to the relationship between the authenticity， variety， processing and quality of medicinal materials. In the consistency evaluation of formula granules and traditional decoction， the deep difference and mechanism between TCMDGs and traditional decoction were discussed by combining structural Chinese medicine， quality marker（Q-Marker） theory and physicochemical characterization， so as to provide reference for the application and development of TCMDGs.

Application and Analysis of High-quality Evaluation for Jianwei Xiaoshi Tablets / 中国实验方剂学杂志

Jianwei Xiaoshi tablets， as a common variety of Chinese patent medicine with "one product with many manufacturers"， have many manufacturers and huge market sales. However， the phenomenon about uneven quality and discrepant price is prominent. Based on this， this study was carried out for the quality evaluation of Jianwei Xiaoshi tablets by applying the high-quality evaluation criteria with the quality as core for Chinese patent medicine， which was based on the full production cycle， from the multi-dimension including raw material selection， production process， quality control， post-marketing research and so on. The evaluation results showed that the quality evaluation scores of Jianwei Xiaoshi tablets from different manufacturers varied greatly （ranging from 35 to 66）， indicating that the quality was significantly different. In the actual production， generally inadequate attention was paid to the quality of raw materials， and the quality of raw materials was insufficient with the score ratio of 43%， especially the poor consistency control of them. The role of good manufacturing practice was obvious， and the scores of production process were generally high with the average score ratio of 62%， and the maximum up to 80%. The technological advancement of the manufacturer was outstanding. The score ratio of quality control was only 31% that the internal quality standard of each manufacture almost stayed at the qualified line， which was equal to the national standard， and the consistency of products was insufficient. The post-marketing research was lacking with the score ratio of 37%. Manufacturers with high brand awareness and market share were upper scores， while the others lagged far behind. The results of this evaluation are in line with the overall prediction， which can provide a reference for the high-quality evaluation of Chinese patent medicine， and supply the scientific data for high-quality and high-price application.

Fingerprint of Shenmai Injection based on ~1H-NMR technique / 中国中药杂志

Shenmai Injection is a Chinese medicinal injection prepared from Ginseng Radix et Rhizoma Rubra and Ophiopogonis Radix, which is widely used in clinical practice for the treatment and adjuvant therapy of cardiovascular diseases with significant pharmacological effects. Proton nuclear magnetic resonance spectroscopy(~1H-NMR) has the advantages of simple and nondestructive sample pretreatment, fast analysis, abundant chemical information, quantification and no need to follow the standard curve. It is widely used in the analysis and research of complex mixtures of traditional Chinese medicine, clinical blood and urine samples. In this study, the ~1H-NMR fingerprint of Shenmai Injection was established. Thirty-two chemical components were identified, including seven amino acids, eight small molecular organic acids, one alkaloid, four sugars, two nucleosides, seven saponins, and three other components. Pearson's correlation coefficient and multivariate analysis of variance(principal component analysis combined with hierarchical cluster analysis) were applied based on the ~1H-NMR fingerprint to evaluate the quality consistency. The results showed high-quality consistency of 82 batches of Shenmai Injection. This study confirms that the ~1H-NMR fingerprint has great potential in the application of quality control of Chinese medicinal injection.

Analysis on the linkage of 415 generic medicines passing consistency evaluation and essential medicine list ， medical insurance list and centralized procurement list from the perspective of medicine accessibility / 中国药房

OBJECTIV E To in vestigate the situation ，achievements and proble ms of consistency evaluation policy of generic medicines in China. METHODS The descriptive analysis was performed after collecting and sorting out the information of generic medicine passing consistency evaluation （GMPCE） published on the official website of the National Medical Products Administration. The basic information ，the distribution and changes of GMPCE were analyzed statistically in National Essential Medicine List （hereinafter refer to as “essential medicine list ”），Medicine List for National Basic Medical Insurance ，Industrial Injury Insurance and Maternity Insurance （hereinafter refer to as “medical insurance list ”）and the result of the successful selection of centralized medicine procurement organized by the state （hereinafter refer to as “centralized procurement list ”）. RESULTS From 2017 to 2021，415 chemical generic drugs had passed consistency evaluation in China ，including 309 varieties，1 822 specifications， 6 dosage forms ，and 17 pharmacological mechanisms ，basically belonging to 30 provinces，and 492 drug manufacturers （except 12 products had not been found the manufacturers ）；the proportion of GMPCE in essential medicine list increased from 0.96％ in 2012 edition to 25.40％ in 2018 edition；that of GMPCE in medical insurance list increased f rom 2.13％ in 2017 edition to 11.68％ in 2021 edition；in the first 5 batches of centralized procurement list，GMPCE accounted for 81.65％，and the maximum price drop after entering the list was 97.52％. CONCLUSIONS The policy linkage has been achieved with the continual increase of the number of GMPCE and their total amount in three lists in China. The accessibility and affordability of related medicines have been improved with the apparent decrease of the price of those medicines. H owever，total number of GMPCE is a little small，with the higher repetition rate of variety and the low proportion in the three lists ；the guarantee measures of those medicine supply need to be strengthened.

Views on Key Technical Problems in Research and Development of Famous Classical Formulas / 中国实验方剂学杂志

In this paper， the key technical problems in the research and development of famous classical formulas are analyzed. Firstly， the puzzled problem for a long-time， which is conversion relationship from medicinal metrology of Han dynasty （HD） to that of modern （gram，g）， is comprehensively expounded that one Liang （两） of HD=3 g is more appropriate. Secondly， the model and principles of quality consistency evaluation are given for the transformation from the quality of authoritative basic sample prepared by casserole （ABS-C） to the quality consistency in Laboratory process， pilot-scale process and industrial production. The consistency evaluation model is ξABS-X=K1（Q1ABS-X/Q1ABS-C）+K2（Q2ABS-X/Q2ABS-C）+……+Ki（QiABS-X/QiABS-C）=∑Ki（QiABS-X/QiABS-C）（i=1，2，3……n）. In the formula， ABS-X means laboratory reference sample ABS-C （ABS-L）， pilot-scale ABS-C （ABS-mP） or industrial production ABS-C （ABS-P）， ξABS-X means the quality consistency rate or similarity degree of ABS-L， ABS-mP and ABS-P processes with ABS-C， Ki means the weight of each quality evaluation index （i）， QiABS-X is the data of i in ABS-L， ABS-mP， ABS-P samples， and QiABS-C is the data （or mean） of i in ABS-C sample. Thirdly， in order to control the quality of the herbal medicines whose active ingredients were unknown， their chemical constituents should be studied deeply， and if necessary， the bioassay research should be carried out according to the main efficacy or indication of famous classical formulas. Finally， for the special processing of some herbal medicines， it is difficult to formulate the processing method， technology and standard of prepared slices. It is suggested that the scientific connotation and historical evolution of the special processing method should be thoroughly sorted out， and its technological characteristics are summarized， the modern processing technology and production processes are simulated， and then the corresponding processing methods and quality standards are formulated.

The analysis of unconventional research projects and common problems in the in vitro consistency evaluation of oral solid generic drugs / 药学学报

Based on the "requirements on the submitted documents for consistency evaluation of generic oral solid dosage forms of chemical drugs" and relevant guidance, this article summarized and formulated the decision tree of in vitro consistency evaluation of oral solid generic drugs, discussed the differences and common problems of in vitro evaluation research projects under different conditions, selective analyzed the technical requirements and concern problems of unconventional research projects, and proposed corresponding recommendations for concern problems, in order to provide more references for the follow-up study on consistency evaluation of oral solid generic drugs.

Determination of five saponins in Xuesaitong Dropping Pills by micellar electrokinetic chromatography and evaluation method of between-batch consistency / 中国中药杂志

The present study determined five saponins in Xuesaitong Dropping Pills(XDP) by micellar electrokinetic chromatography(MEKC), and evaluated between-batch consistency by MEKC fingerprints and similarity analysis. A background buffer was composed of 20 mmol·L~(-1) sodium tetraborate-20 mmol·L~(-1) boric acid solution(pH 8.5), 55 mmol·L~(-1) sodium dodecyl sulfate(SDS), 23 mmol·L~(-1) β-cyclodextrin, and 13% isopropyl alcohol. All separations were performed at 25 ℃,20 kV and the detection wavelength was set at 203 nm. The separation channel was a fused silica capillary with a dimension of 75 μm I.D. and a total length of 50.2 cm(effective length of 40.0 cm). The contents of notoginsenoside R_1, and ginsenosides Rg_1, Re, Rb_1, Rd were determined with their quality control ranges set. The fingerprints of XDP were established and the between-batch consistency was evaluated by similarity analysis. The contents of five saponins from the 19 batches of XDP were stable in the fixed ranges. Statistical analysis was carried out on the results of multiple batches of samples, and the specific quality control ranges were recommended as follows: notoginsenoside R_1 21.92-34.16 mg·g~(-1), ginsenosides Rg_1 83.54-131.78 mg·g~(-1), ginsenosides Re 13.58-19.82 mg·g~(-1), ginsenosides Rb_1 89.40-129.90 mg·g~(-1), and ginsenosides Rd 22.34-35.67 mg·g~(-1). Eleven characteristic peaks were identified in the fingerprints. Five peaks, notoginsenoside R_1 and ginsenosides Rg_1, Re, Rb_1, Rd, were identified with reference standards. The similarities of the 19 batches of samples were all above 0.988, indicating good between-batch consistency. This method is green and simple, and can be used for the quantitative determination and quality evaluation of XDP. It can also provide references for the quality control of other Chinese medicinal dripping pills.

Effects of pharmaceutical excipients on CYP3A activity and its guiding effects on quality and efficacy consistency evaluation of generic drugs / 中国临床药理学与治疗学

The prescription and technology of pharmaceutical preparations are the basis for ensuring the quality and efficacy of medicines. Pharmaceutical excipients are important part of pharmaceutical preparations. As it's known to all that some pharmaceutical excipients can affect the activity of CYP3A, and then may influence the metabolism and bioavailability of its substrates in vivo. Relative bioavailability is a key element of generic drug research in China and the United States. Our country is advancing the quality and efficacy consistency evaluation of generic drugs. Therefore, it is of great practical significance to understand the impact of pharmaceutical excipients on CYP3A and its guiding role in consistency evaluation.

Study on batch consistency evaluation techniques of Xiaoyao Tablets based on UPLC fingerprint / 中草药

Objective: A fingerprint similarity evaluation method was optimized, and combined with multivariable statistical analysis technology to evaluate the quality consistency of Xiaoyao Tablets comprehensively, systematically, and scientifically. Methods: UPLC fingerprint data of multiple batches of Xiaoyao Tablets were collected, and its similarities were performed by correlation coefficients, angle cosine, euclidean distance, macro qualitative and quantitative similarity, and equivalent coefficient. A similarity evaluation method was selected for product quality evaluation, according to the characteristics of various calculation methods. At the same time, pattern recognition technologies such as principal component analysis (PCA) was used to analyze and evaluate the overall quality of Xiaoyao Tables. Hotelling's T2 and DModX statistics were used to monitor the quality of different batches of products. The similarity calculation and multivariate statistical analysis were combined to evaluate the consistency of the quality of different batches of samples. Results: By analyzing the fingerprint data of 22 common peaks of 14 batches of Xiaoyao Tablets, the quality of products had high consistency evaluated by traditional similarity calculation method. The weighted equivalent coefficient evaluation method was more suitable for product quality evaluation comparing with the traditional similarity evaluation method, as different weight coefficients were set for different indicators according to the peak area information and pharmacological effect and the information reflected was more comprehensive and reasonable. There were no abnormal batches in the 14 batches of samples in the PCA analysis, indicating the quality of products were relatively stable. The upper control limits of Hotelling's T2 and DModX were 25.145 3 and 1.75, respectively. The equivalent coefficient method evaluates the quality of different batches of samples from a macro perspective, and the multivariate statistical analysis analyzes the contribution of each chromatographic peak based on evaluation results. The combination of the two methods can comprehensively evaluate the quality consistency of samples. Conclusion: The similarity evaluation and multivariate statistical analysis method based on fingerprints established in this study can evaluate the quality consistency of samples comprehensively and systematically. The study also provides a reference for the research on quality control of traditional Chinese medicine.

Research Strategies for Quality Standards of Famous Classical Formula Based on Standard Decoction (Material Reference) / 中国实验方剂学杂志

The inheritance of traditional clinical value of famous classical formulae is an important direction for the development of traditional Chinese medicine industry.Compared with the previous research and development of new drugs, the management requirement of " material reference" was introduced into the famous classical formulae research, which is used as the reference of process optimization and quality control.The characteristics of compound preparation of famous classical formulae are also reflected in the core concept of " quality inheritance of classics" in the road of industrial development.How to implement the above requirements and concepts into product development and industrial production? There are many specific common problems to be solved in practical research.How to effectively establish the " material reference" of famous classical formulae of different dosage forms? How to use " material reference" to guide the process optimization of compound preparation of famous classical formulae? How to determine the daily dose of famous classical formulae? How to take effective measures in the selection of raw material to reduce quality fluctuation range? This paper discusses the key issues such as production process and quality evaluation from the following aspects.Firstly, the management regulations and research and development guidelines are analyzed, and the specific implementation methods are given.Then, the possible problems in the Requirements for Declaration Documents (Draft for Opinions) are pointed out, and relevant suggestions are given.Finally, based on the research experience of standard decoction and famous classical formulae in the laboratory, an example is given to provide reference for the development of compound preparation of famous classical formulae.

Consistency Evaluation on the Dissolution Behavior and Related Indicators between Generic and Original Pre- parations of Oxcarbazepine Scored Tablets / 中国药房

OBJECTIVE：To evaluate the dissolution behavior consistency between the generic drugs and original drugs of Oxcarbazepine scored tablets ，and to compare the appearance ，the friability of the split portions ，loss of mass of the split portions as well as crystal form and morphology of raw material from different enterprises. METHODS ：HPLC method was adopted. The paddle method （rotation speed of 60 r/min，the temperature of 37.0℃）was adopted to determine accumulative dissolution rate of generic and original drugs in 4 mediums [ 0.6％ SDS hydrochloric acid solution （pH＝1.2），0.6％ SDS acetate buffer solution （pH＝4.5），0.6％ SDS phosphate buffer solution （pH＝6.8）and 0.6％ SDS water solution]. The similarity factor method was used to evaluate the similarity of dissolution curves as well as intra-batch uniformity of the split portions and whole tablets. The friability tester and electronic balance were used to determine the friability and the loss of mass of the split portions. X-ray diffractometer and scanning electron microscope were used to observe the crystal form and crystal morpho logy of the raw materials of different enterprises. RESULTS ：The linear range of oxcarbazepine was LOD was 0.04 μg/mL；RSDs of precision ，stability，reprodu- cibility and durability tests were lower than 2.0％；the reco- veries were 99.80％-101.63％（RSD＝0.37％-0.91％，n＝3）. The average cumulati ve dissolution rate of generic drug A ， generic drug B and original drug in 4 different dissolution media at 90 min were 92％，87％，90％ [0.6％ SDS hydrochloric acid solution（pH＝1.2）]；94％，94％，90％ [0.6％ SDS acetate buffer solution （pH＝4.5）]；95％，95％，91％ [0.6％ SDS phosphate buffer solution （pH 6.8）]；97％，98％，95％（0.6％ SDS water solution ）. The similarity factors of generic drug A ，generic drug B and original drug in 4 kinds of different dissolution media were 66 and 81，71 and 69，71 and 61，59 and 39. In the first 15 min，the difference of dissolution rate of split portions and whole tablets were －3％-13％，－2％-24％ and －3％-7％ for generic drug A ， generic drug B and original drug ，respectively. RSDs of accumulative dissolution rate of split portions and whole tablets were 6％-14％ and 2％-9％ for generic drug A （n＝12），4％-10％ and 1％-8％ for generic drug B （n＝12）and 2％-7％ and 2％-8％ for original drug. The appearance of the original drug was fusiform ，and the notch was deep ；the shape of the generic drug was different from each other ，and the notch of the generic drug was significantly shallower than that of original drug. The friability ， the loss of mass of the split portions for generic drug A and generic drug B ，original drug were 0.62％and 0.67％，0.12％ and 0.11％，0.08％ and 0.05％. The domestic raw materials possessed irregular lumps and debris ，while the raw materials produced by original drug enterprises possessed regular flat cuboids and regular strips with little debris ；but X-ray diffraction peaks of them were basically the same. CONCLUSIONS ：The dissolution behavior of generic drug A in 4 medium is consistent with that of the original drug；dissolution behavior of generic drug B in water containing 0.6％SDS is different from that of the original drug ；there is no significant change in the homogeneity of the original drug before and after splitting ，but the homogeneity of the generic drug A and B after splitting is lower than that of the whole tablet ；the fragility of generic drugs and loss of mass of split portions are higher than those of the original drugs ；two kinds of raw material have the same crystal form but different crystal morphology.

Effects of source difference of sodium carboxymethyl starch on its properties and function / 药学学报

During the process of consistency evaluation, it was found that the consistency of drug release between generic and original brands in vitro was not sufficient to demonstrate their same release in vivo. The disintegration of tablets, as a premise for the release of tablet drugs, greatly affects the release of drugs, depending on the structure and properties of disintegrants. Hence the systematic research on disintegrants would be very important for the evaluation of generic consistency. In this experiment, the physicochemical properties and application of 11 different sodium carboxymethyl starch (CMS-Na) from 9 manufacturers were investigated. This provides the reference for selection of excipients for consistency evaluation. The particle morphology of CMS-Na was observed by scanning electron microscope. The particle size distribution was determined by dry particle size analyzer. The determination of pH and loss on drying was carried out according to the 2015 edition of Chinese pharmacopoeia method. The powder fluidity was evaluated with Carr's index, Hausner ratio and angle of repose. The disintegration performance of CMS-Na was evaluated through determining the water absorption and swelling. The disintegration effect of CMS-Na tablets was studied using lactose and microcrystalline cellulose as fillers. The results showed that pH values and weight loss on drying of all samples met the requirements, whereas the particle morphology, fluidity, water swell-ability and disintegration time had a large variation, which leads to the large differences the properties of CMS-Na depending on the sources. Therefore in order to ensure that the reproducibility of generic drugs from their name brand, our studies indicate that only a sizable choice of disintegrants could ensure good inter batch reproducibility.

Application of reverse engineering in the development of caffeine tablets / 国际药学研究杂志

Objective: The reverse engineering technology was used to analyze the prescription and process of Good Sense Stay Awake®, the reference listed drug of caffeine tablets, in order to provide guidance for the development of generic caffeine tablets. Methods: Firstly, the prescription information of the reference listed drug was obtained by literature research. Then, quantitative analysis of the composition of the prescription was achieved by the high-performance liquid chromatography with a crystal refractive index detection and the gravimetric analysis method;the particle size of raw and auxiliary materials was analyzed by Raman imaging technology;the crystal habit and crystal form of active pharmaceutical ingredient(API)were characterized by the optical microscope and X-ray powder diffraction technology, respectively;the preparation process of reference listed drug was determined by disintegration method;and finally, the package material was identified by the morpholine reagent. Moreover, three batches of samples were pre-pared according to the determined prescription and process, and the quality was compared with the reference listed drug. Results: By the reverse engineering analysis of the reference listed drug, the prescription composition of the reference listed drug was determined to be composed of glucose, microcrystalline cellulose, pregelatinized starch, maltodextrin, magnesium stearate, colloidal silica and yellow lake, in which the glucose content was 32% and the microcrystalline cellulose content was <23%. The API crystal form of the reference listed drug was consistent with that of the self-made preparation. The average particle size of caffeine, microcrystalline cellulose, glucose, maltodextrin and pregelatinized starch was approximately 206, 112, 172 and 61 μm, respectively. The tablet preparation process was the direct compression method, and the packaging material was polyvinyl chloride aluminum foil. The quality of the three batches of home-made preparations was the same as that of the reference listed drug. Conclusion: Caffeine tablets with the same quality as Good Sense Stay Awake® were successfully prepared by reverse engineering of the reference listed drug, which provides a reference for the application of reverse engineering in the generic drug development and consistency evaluation.

Determination of saponins in Xuesaitong Drop Pills and study on batch consistency evaluation techniques / 中草药

Objective: To establish the fingerprint of Xuesaitong Dropping Pills (XDP) using ultra-high pressure liquid chromatography (UPLC), determine the content of its main components and propose a chemometrics method for the systemic, comprehensive and scientific quality evaluation. Methods: The Agilent 1290 UPLC and Acquity UPLC BEH C18 column were used for the establishment of the UPLC fingerprints of 14 batches of XDP with acetonitrile and water as mobile phase for gradient elution, and the content of five kinds of notoginsenosides wsa determined. Then, the further quality assessment of XDP was carried out with similarity evaluation, principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA). Meanwhile, the Hotelling’s T2 and DModX control ranges were set for the different batches of samples. Results: Among the 14 batches, the content of five kinds of notoginsenosides was relatively stable, and the quality control ranges for notoginsenosides R, ginsenoside Rg1, Re, Rb1, Rd were set at 24.69-30.03 mg/g, 102.60-122.44 mg/g, 12.93-15.45 mg/g, 99.74-112.12 mg/g, and 23.35-31.75 mg/g, respectively. In this research, 15 chromatographic peaks were recognized as common peaks in the fingerprints, five peaks were identified with standard references compounds, which were notoginsenoside R1, ginsenoside Rg1, ginsenoside Re,ginsenoside Rb1 and ginsenoside Rd. The similarity values of the drugs were all above 0.998. In the PCA analysis, 14 batches of samples had no abnormal batch, indicating that the quality was relatively stable, however, the difference of the storage time was reflected in the fingerprint. According to the OPLS-DA result, the quantitative ginsenoside Rb1 and ginsenoside Rd had greater influence on the variables causing the gradual trend in 14 batches of samples. The upper limit of control for Hotelling’s T2 and DModX was 31.17 and 1.82, respectively. Conclusion: The established method was accurate, reliable, and simple. It can be used not only for the quality control of XDP, but also for the comprehensive evaluation of batch consistency. The study also provides a reference for solving the common problem of the consistency evaluation of Chinese materia medica.

Comparison of the Quality of Generic and Original Preparations of Thioctic Acid Injection and Study on Its Acute Toxicity Test in Mice / 中国药房

OBJECTIVE： To compare the quality of original preparations of Thioctic acid injection and generic preparations from 2 domestic manufacturers， discuss the acute toxicity test of mice and to investigate the project of consistency evaluation methods. METHODS： According to the quality standard that stated in Chinese Pharmacopeia， physicochemical properties （characters， pH， osmotic pressure， etc.， contents and related substances of samples of Thioctic acid injection as well as LD50 in acute toxicity test （n＝10）， and mortality of mice after administration of injection solution （n＝30） were compared among 3 manufacturers. RESULTS： The physicochemical properties as and related substances of the original drug and 2 generic drugs were all in line with the quality standard； the contents of 3 samples ranged 95％-105％. The acute toxicity test results showed that the LD50 values of 2 generic drugs （LD50： 247.911 mg/kg， 95％ confidence interval： 222.209-277.999 mg/kg；LD50： 215.291 mg/kg， 95％ confidence interval： 196.637-235.053 mg/kg） were smaller than that of original drug （LD50： 266.534 mg/kg， 95％ confidence interval： 250.597-283.418 mg/kg）， but there was no statistical difference （P＞0.05）. The results of 3 repeated experiments showed that there was statistical significance in the number of animal death caused by the 2 generic drugs （26， 28） was more than that of the original drug （19） （all P＜0.05）， when injection solution was injected into mice in a single dose. After administration of the original drug， mice showed excitatory reactions such as movement and squeal， while 2 generic drugs showed inhibitory reactions. CONCLUSIONS： 2 generic drugs of Thioctic acid injection and the original drug all conform to the relevant regulations of Chinese Pharmacopoeia in terms of preparation quality standards， but the results of acute toxicity test are quite different， so it is difficult to prove the consistency between the 2 generic drugs and the original drug. Therefore， acute toxicity test is necessary for the consistency evaluation of injections.

Evaluation of the Process Control Capability of Lorazepam Tablets by Near-Infrared Spectroscopy / 中国药学杂志

OBJECTIVE: To evaluate the process control capability of lorazepam tablets produced in China. METHODS: Near-infrared spectroscopy combined with cluster analysis(CLA) and principal component analysis(PCA) were used to characterize the different processes and process control space of lorazepam tablets produced in China. Universal quantitative model was built to obtain the content predictions of individual units(tablets), on base of which process mean value,intra-batch and inter-batch differences and distribution status were calculated by univariate statistics analysis methods. RESULTS: Three different manufacturing processes of lorazepam tablets were characterized by both CLA and PCA. The process control spaces reconstructed by the second and third principal components indicated that the process of manufacturer B had smaller variation than that of manufacturer A. The universal quantitative model had a principal component number of 5, r2 square value of 93.89% and bias of -0.008 56. The statistic distribution of API contents showed that 9 batches out of the total 27 batches had relative lager intra-batch differences and manufacturer B had better inter-batch differences than manufacturer A. CONCLUSION: The method this study established can reveal the control levels of different processes of lorazepam tablets, which provide an efficient quality consistency evaluation means for generic drug consistency assessment.

Study on Clinical Consistency Evaluation in TCM Practice Guidelines for Prevention and Treatment of Biqiu (Allergic Rhinitis) / 中国中医药信息杂志

Zhangjiagang Hospital of Traditional Chinese Medicine, as a collaborative unit of the project, participated in the clinical consistency evaluation in project of TCM Practice guidelines for Prevention and Treatment of Biqiu (allergic rhinitis) organized by the State Administration of Traditional Chinese Medicine. The evaluation results showed that the guideline met the clinical practice requirements. This article summarized the clinical evaluation experience from the three aspects: The diagnosis in TCM and Western medicine is clear and definite, but the English translation needs to be considered; The definition of remission phase of Biqiu (allergic rhinitis) is difficult, to interfere by identifying the constitution is innovative; The advantages of "preventive treatment of diseases" in TCM should be fully played in role, improving the satisfaction of patients.

Relative bioavailability of terpene lactones in Beagle dogs after ig administration of domestic and imported Ginkgo Leaf Tablets / 中草药

Objective To compare the pharmacokinetic parameters and bioavailability of terpene lactones in Beagle dogs between domestic and imported Ginkgo Leaf Tablets. Methods Beagle dogs were ig administrated demestic and imported Ginkgo Leaf Tablets, and then the plasma of Beagle dogs were detected. LC-MS was used to determine the contents of terpene lactones (including ginkgolide A, ginkgolide B, and ginkgo lactone) in plasma of Beagle dogs. Plasma concentration-time curves were drawn and analyzed by DAS software to obtain pharmacokinetics parameter. Results The area under curve (AUC0-t) of GA, GB, and BB in Beagle dogs after ig administration domestic Ginkgo Leaf Tablets was 51.64, 19.86, and 72.90 ng∙h/mL, while it was 69.98, 24.35, and 169.60 ng∙h/mL after ig administration imported G. biloba leaf extract tablets, respectively. According to the contents of three components in two preparations, the relative bioavailability of GA, GB, and BB of domestic Ginkgo Leaf Tablets respectively was 37.77%, 33.70%, and 95.98%. Conclusion The oral bioavailability of the terpene lactones in imported Ginkgo Leaf Tablets was significantly higher than that of domestic tablets.

Simultaneous determination of 10 components in Paidu Yangyan Capsules by HPLC wavelength change method / 中草药

Objective The contents of sennoside A, sennoside B, echinacoside, verbascoside, hesperidin, aloe-emodin, rhein, emodin, chrysophanol, and rheochrysidin in Paidu Yangyan Capsules (PYC) were determined by HPLC. The quality of different batches of psoralen were evaluated by chemical pattern recognition. Methods HPLC was established for the simultaneous determination of 10 components in 15 batches of PYC with variable wavelength detector, and the results were analyzed by principal component analysis and cluster analysis to comprehensively evaluate the difference in quality of PYC which is available in the market. Results The contents of sennoside A, sennoside B, echinacoside, verbascoside, hesperidin, aloe-emodin, rhein, emodin, chrysophanol, and rheochrysidin in PYC had good linear relationship in the ranges of 0.167 4—2.093 0, 0.093 5—1.177 0, 0.075 9—0.948 6, 0.049 9—0.623 7, 0.109 0—1.363 0, 0.033 5—0.418 4, 0.079 7—0.996 1, 0.013 9—0.174 3, 0.025 2—0.315 6, and 0.012 3—0.061 4 μg/mL, the average sample recovery rate range were 99.84%, 99.15%, 99.34%, 99.81%, 100.6%, 99.36%, 99.86%, 100.1%, 100.1%, and 99.76% (RSD < 2.0%), the detection limits were 0.64—2.18 ng/mL, quantitative limits were 3.19—9.55 ng/mL, the content of 10 active ingredients in 15 batches of samples respectively were 0.712 7—1.118 0, 0.403 9—0.522 0, 0.236 4—0.320 3, 0.671 1—1.183 0, 0.0580—0.1467, 0.108 7—0.2592, 0.0147—0.0501, 0.5173—0.5828, 0.2754—0.3051, and 0.1621—0.1853 mg/grain and there were some differences among the samples in different batches, mainly due to different rhubarb dosages. Conclusion The established method is simple, accurate and reproducible, and can be used to control the quality of PYC. It is suggested that the quality control of Rhei Radix et Rhizoma should be strengthened in the process of preparation production for providing a reference of PYC follow-up quality improvement.