[Reflections on good manufacturing practice and quality control system of personalized traditional Chinese medicine preparations].

Personalized traditional Chinese medicine(TCM) preparations have entered a stage of rapid development. The key to the healthy development of this industry is to establish a sound manufacturing standard and quality control system. This paper analyzed the characteristics of personalized TCM preparations and drew reference from the quality management standards in the production of commissioned decoctions and oral pastes, on the basis of which the production quality management scheme and cautions for the safe production of personalized TCM preparations was put forward with consideration to various problems that may exist and occur in the production of such preparations. It provided references for formulating the production standards and quality management system of personalized TCM preparations. The production standards and quality control system should develop with the times. In the future, modern technologies such as big data and artificial intelligence should be employed to achieve the automated and intelligent production and establish a sound quality traceability system, online control strategy, and safety management mode of personalized TCM preparations, which will ensure the healthy development of this industry under requirement of good manufacturing practice(GMP).

[Application of microwave vacuum drying with process management in extract drying of personalized traditional Chinese medicine preparations].

Extracts are important intermediates in the production of traditional Chinese medicines preparations. The drying effect of extracts will directly affect the subsequent production process and the quality of the preparation. To meet the requirements of high drug loading, short time consumption, and simple production process of personalized traditional Chinese medicine preparations, this study explored the application of multi-program microwave vacuum drying process in the extract drying of personalized traditional Chinese medicine preparations. The influencing factors of microwave vacuum drying process were investigated for 5 excipients and 40 prescriptions. Taking the feasibility of drying, drying rate, drying time, and dried extract status as indicators, this study investigated the feeding requirements of microwave vacuum drying. With the dried extract status as the evaluation indicator, the three drying programs(A, B, and C) were compared to obtain the optimal drying condition. The experimental results showed that the optimal feeding conditions for microwave vacuum drying were material layer thickness of 2 cm and C program(a total of 7 drying processes), which solved the problem of easy scorching in microwave drying with process management. Furthermore, the preset moisture content of the dried extract in microwave drying should be 4%-5%, so that the dried extract of traditional Chinese medicine preparation had uniform quality, complete drying, and no scorching. This study lays a foundation for the application of microwave drying in the production of traditional Chinese medicine preparations, promoting the high-quality development of personalized traditional Chinese medicine preparations.

[Origin, development, and modern application value of Chinese herbal lozenges].

Lozenge is one of the traditional dosage forms of Chinese medicine. It has been recorded in traditional Chinese medical classics of all dynasties since the Eastern Han Dynasty and has been developing and evolving continuously. The unique pharmaceutical methods and application scope are the driving force of its emergence, existence, and development. Up to now, lozenge has been included in the Chinese Pharmacopoeia as an independent dosage form. Lozenge has been endowed with new meaning by modern Chinese medicine pharmaceutics, which is worth tracing origin and exploring value. The present study reviewed the origin and development of lozenge, compared lozenge with other similar dosage forms, analyzed the characteristics of modern and ancient dosage forms of lozenge, and discussed the development prospect and potential of lozenge in combination with the demand development of modern Chinese medicine preparation, so as to provide references for expanding the modern application of lozenge.

Research Progress of Preparation Technology of Ion-Exchange Resin Complexes.

As insoluble polymer materials, ion-exchange resins (IERs) can exchange their own ions with desirable charged ions in the solution. According to the affinity of active moieties for soluble counterions, IERs could be categorized into the following four types: strongly acidic cation, weakly acidic cation, strongly basic anion, and weakly basic anion exchange resins. Due to their relative safety and high drug-loading capacity, IERs have garnered extensive attention in the pharmaceutical field since the 1950s. As numerous investigations combine drugs with IERs, this article summarizes the technologies employed in these studies from four aspects: IER screening principles, combining technologies, characterization methods, and in vitro and in vivo release of drug-resinate complexes. In addition, the advantages and disadvantages of various technologies and their scope are expounded. The article provides new insights on the preparation of ion-exchange resin complexes.

[Quality value transmitting of volatile components in personalized preparations:a case study of Menthae Haplocalycis Herba].

Considering the characteristic chromatograms and quality value transmitting of three volatile components, this study investigated the changes in volatile components of Menthae Haplocalycis Herba in each heating process of personalized preparations and identified the critical control points for the application of volatile components from traditional Chinese medicine in such preparations. The characteristic chromatograms of volatile components in Menthae Haplocalycis Herba were established by gas chromatography, followed by the quantitative determination of three volatile components menthone, menthol, and piperitone and the comparison of retention rates of volatile components during the crushing, extraction, concentration and drying of preparation products and their change rules in characteristic peaks. The results showed that the volatile components of Menthae Haplocalycis Herba were reduced in each process. The loss rate was low in the crushing process when the volatile component peaks were present, but high in the extraction and concentration processes, manifested as the absence of partial component peaks and the presence of new component peaks. The changes in volatile components of Chuanxiong Chatiao Granule in the drying process were compared with those in Chuanxiong Chatiao Pill, both of which were prepared from the raw Menthae Haplocalycis Herba powder, and the findings demonstrated that Chuanxiong Chatiao Pill was superior to Chuanxiong Chatiao Granule. This study confirmed that the retention rates of volatile components in Menthae Haplocalycis Herba were mostly affected by the extraction and concentration processes, and the packing of preparations helped to reduce the loss of volatile components in Menthae Haplocalycis Herba powder, which has provided reference for the application of Chinese medicinal materials containing volatile components in the personalized preparations.

[Exploratory study on preparation of high drug loading granules with traditional Chinese medicine raw powder as carriers].

With Sangtang Yin granule as model drug,and based on the strategy of " unification of medicines and excipients",the feasibility of preparing high drug loading granules with traditional Chinese medicine( TCM) raw powder as carrier was explored. The powder yield,particle size and particle size distribution,fillibility,flowability,hygroscopicity,reconstituability and other key physical properties relating to preparations of 8 herbs( Dioscoreae Rhizoma,Euryales Semen,Atractylodis Macrocephalae Rhizoma,Coicis semen,Poria,Puerariae Lobatae Radix,Puerariae Thomsonii Radix and Coicis Semen by stir-frying with bran) were studied after being smashed,and the feasibility of taking them as excipients of TCM granules was evaluated by co-spray drying,dry granulation and other preparation techniques. According to the results of the physical properties of raw powders,raw powders of Dioscoreae Rhizoma,Euryales Semen and Puerariae Thomsonii Radix had a high powder yield,uniform particle size distribution,good fillibility,poor hygroscopicity and good reconstitutability,with the feature of assisting granule forming. Compared with the prescription of spray dry powder Sangtang Yin without any excipient,the co-sprayed powder had a high yield,good fillibility and compressibility. The yield of dry granules prepared by co-spraying dry powder was increased by more than 10%,and the particles had a uniform color,good fluidity and dissolubility with the drug-loading rate up to 100%. Based on the physical characteristics of TCM raw powder combined with the analysis of the preparation process,Dioscoreae Rhizoma and Puerariae Thomsonii Radix raw powder were selected as the carriers of granule preparations,and Sangtang Yin granule without any excipient was successfully prepared. The findings provide a feasible idea for the preparation of TCM granules with a high drug loading capacity.

[Application,problems,and development strategies of personalized traditional Chinese medicine preparations].

With the continuous improvement of people's living standards and the greatly accelerated pace of life, patients' requirements for traditional Chinese medicine(TCM) pharmaceutical care are constantly raised, and personalized TCM preparations used are increasing year by year. However, a series of problems, such as the bottleneck of preparation technology, the lack of preparation specifications, and the weak legal basis for supervision, have become prominent, leading to the uneven product quality of personalized pre-parations. This paper systematically summarized and analyzed the current situation and existing problems of personalized TCM preparations, including dosage form application, preparation technology, production equipment, quality standard, clinical application, and administration mode. Additionally, it put forward an inheritance and innovation research mode of personalized TCM preparation technology based on the physical fingerprint of raw materials and innovation research and intellectual property protection mode of "research-patent-technology-equipment-standard". Furthermore, innovative development strategies were proposed, such as the production standard system of clinical preparations based on the whole process traceability and the regional processing service mode of clinical preparations based on industry 4.0. The present study is expected to provide beneficial references for the inheritance and innovation development of personalized TCM preparations.

[Characteristics and development assumptions of personalized traditional Chinese medicine granules].

Personalized traditional Chinese medicine(TCM) granules are positioned as a solid dosage form of TCM decoctions, boasting strong applicability and wide application range. The market prospect of personalized TCM granules is promising in that their preparation by mixed decoction makes up for the shortcoming of formula granules like the Chinese patent medicine granules and classical TCM prescription granules whose components cannot be changed flexibly. However, such factors as insufficient basic research, equipment mismatch, and low process commonality have limited their clinical application. After analyzing the characteristics of perso-nalized TCM granules, their production status, and the bottlenecks restricting their development, this paper pointed out the meaning and key points of developing a generalized preparation process for personalized TCM granules and affirmed the vital roles of the preparation and process prediction system and the on-line detection technology in improving the productivity of granulation. Finally, some assumptions on technology development for solving the specific problems of personalized TCM granules were shared to provide some ideas for the application and development of personalized TCM granules in clinical practice.

[Establishment of prediction model for personalized water-paste pills based on classification of traditional Chinese medicine materials].

The purpose of the present study was to investigate the relationship of the classification of traditional Chinese medicine(TCM) materials with the suitable binder concentration and dosage in the preparation of personalized water-paste pills and establish a model for predicting the binder concentration and dosage. Five representative TCM materials were selected, followed by mixture uniform design. The water-paste pills were prepared by extrusion and spheronization with hypromellose E5(HPMC E5) as the binder. The quality of intermediates and final products was evaluated, and the resulting data were subjected to multivariate statistical analysis. The prediction models for binder concentration and dosage were established as follows: binder concentration: Y_1=0.378 6 + 0.570 1X_A + 2.271 2X_B-0.894 5X_C-0.458 2X_D-1.145 4X_E(when Y_1 < 0, 10% HPMC E5 was required; when Y_1 > 0, 20% HPMC E5 was required), with the accuracy reaching up to 100%; binder dosage: Y_2=32.38 + 0.25X_A + 1.85X_B-0.013X_B~2-0.002 5X_C~2(R~2=0.932 6, P < 0.001). The results showed that the binder concentration and dosage were correlated positively with the proportion of fiber material but negatively with the proportions of sugar material and brittle material. Then the validation experiments were conducted with the prediction models and all the prescriptions could be successfully prepared at one time. These demonstrated that following the classification of TCM materials and the calculation of their proportions in the prescription, the established mathematical model could be adopted for predicting the binder concentration and dosage required in the preparation of personalized water-paste pills, which contributed to reducing the pre-formulation research and guiding the actual production of personalized water-paste pills.

[Preparation of personalized traditional Chinese medicine condensed water pill without excipients based on correlation between concentrate viscosity and molding quality].

To explore the correlation between concentrate viscosity and molding quality of personalized traditional Chinese medicine(TCM) condensed water pill, this study established a concentrate viscosity characterization method with rotational rheometry. Seven model prescriptions were respectively concentrated to different degrees and the viscosity of each concentrate was determined. The pre-sence of 'viscosity jump' in the middle stage of 'flag hanging' of all the model prescriptions implied that there might be an ideal viscosity range in the preparation of condensed water pill. The further study of 22 model prescriptions demonstrated that the optimum viscosity range of concentrate was 5-15 Pa·s(25 ℃) for approximately 82% of the prescriptions. About 18% of the prescriptions had a wide range, which might be caused by the high proportions of mineral and crustacean drugs in the crushing part and sugar and fibrous drugs in the decocting part. This study clarified the optimum viscosity range for concentrates of personalized TCM condensed water pills and achieved a preparation technology without any excipient, laying a foundation for the on-line control of the preparation.

[Physiochemical property variation in traditional Chinese medicine decoction before or after precipitation in alcohol and its relationship with wall stickiness in spray drying].

To explore the relationship between the variations of the physiochemical properties of traditional Chinese medicine(TCM) decoction before or after precipitation in alcohol and the wall stickiness in spray drying. In this study, widely used TCMs in clinic were selected to determine the physiochemical properties of TCM decoction before or after precipitation in alcohol separately.Afterwards, the principle component analysis(PCA),Hierarchical cluster analysis(HCA),and orthogonal partial least squares-discriminate analysis(OPLS-DA) were used to evaluate the relationship between the variations of those liquid before or after precipitation in alcohol and hot-melt stickiness in spray drying.Three types of statistical analysis methods all indicated that ethanol precipitation affected physiochemical properties of TCM decoction, and the variations of physical properties showed significant association with hot-melt stickiness in spray drying.The results of PCA-X and HCA suggested that the dynamic surface tension(DST) was impacted most by the alcohol deposition treatment,at the same time,the other 5 physiochemical properties were also affected.OPLS-DA verified that PCA-X and HCA results, and revealed that DST,equilibrium surface tension(EST) and pH were significantly affected by alcohol deposition treatment,and the order of the affecting factors from high to low was DST,EST and pH.Therefore,the downward trend of DST and pH were the important factors that directly affected the hot-melt stickiness of TCM after precipitation in alcohol,which would be probably caused by losing macromolecules alcoholic insoluble components and increasing relative proportions of organic acid and small molecule sugar.

[Correlation between chemical compositions of traditional Chinese medicine extracts and phenomenon of wall stickiness in spray drying].

To explore the correlation between chemical compositions (organic acids, small molecule sugars, protein and others) of traditional Chinese medicine extracts and the wall stickiness in spray drying. In this study, 55 types of most common used Chinese herbs were selected to determine the content of 7 chemical components such as citric acid and fructose from plant extraction. The status of wall stickiness was observed during the drying process. The principle component analysis (PCA-X), hierarchical clustering analysis(HCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) were then used to evaluate the correlation between each chemical compositions and wall stickiness, so as to look for the essential chemical compositions associated with the wall stickiness. All of the above 3 statistical analysis methods showed significant results in distinguishing the two groups (sticky or non-sticky). PCA-X score chart and HCA clustering scatter plot suggested that the small molecular substance was the main factor causing wall stickiness, which was then proved by the reality where some of the traditional herb extracts were in non-sticky state after drying but in sticky state after alcohol precipitation. OPLS-DA results revealed that L-malic acid, citric acid, fructose and glucose were the difference factors for the wall stickiness of the extracts. Under small molecular components, L-malic acid, citric acid, fructose and glucose were the crucial factors that directly led to the hot melt sticky wall of the herbal extracts, and macromolecular substances might ameliorate the function of wall stickiness.

[A new device for determination of adhesive force and its application in predicting hot-melt sticking in spray drying of traditional Chinese medicine].

A new device was designed to measure adhesive force and predict whether traditional Chinese medicine extracts would appear hot-melt sticking in spray drying process．Based on the physical property tester as fundamental test platform, the device was fixed with a camera, a temperature and humidity sensor probe and a set of equipment for hot air. This device could simulate the dry environment of spray dryer and analyze the variables of testing solutions' adhesiveness against drying time. To establish and validate a model of predicting hot-melt sticking in spray drying, data was collected by using data mining. The results of this study proved that the device could be used to predict the hot-melt sticking in spray drying based on the adhesive force of materials (testing solutions). In addition, the study also found that the adhesiveness of the hot-melt sticking materials gradually increased with the evaporation of water, while that of non-sticking materials first increased and then rapidly decreased.

[Research on bitter components from Coptis chinensis based on electronic tongue].

Isolated alkaloids from Coptis chinensis Franch. The compounds were identified as berberine, columbamine, groenlandicine, jatrorrhizine, magnoflorine, corydaldine and ferulic acid methylester. Then measured their bitter degree based on the electronic tongue and evaluated the antibacterial. The results based on the Electronic Tongue showed that berberine, columbamine, groenlandicine and jatrorrhizine have higher bitter degree than magnoflorine and corydaldine. And they also appeared better antibacterial activity on E. coli and S. aureus. The correlation coefficients between bitter degree and the two bacteria antibacterial activity were 0.983 and 0.911. So there was close relationship between the bitter degree and antibacterial activity of bitter components. Thus, it is confirmed further that bitter components are the material foundation of medicinal effectiveness of bitter herbs.

[Discrimination of traditional Chinese medicinal materials with different tastes based on electronic tongue].

OBJECTIVE: To investigate the use of the electronic tongue in the evaluation of traditional Chinese medicinal materials with sour, bitter, sweet or salty tastes, and assess the possible application of the sensor in the evaluation of different tastes of traditional Chinese medicinal materials. METHOD: Aqueous extracts of 22 traditional Chinese medicinal materials were measured by the electronic tongue. The data collected with the tongue was evaluated for discrimination of the samples with multivariate statistical methods: principal component analysis (PCA) and discriminant factor analysis (DFA). RESULT: The electronic tongue was capable of discriminating between samples with different taste modalities and could also distinguish different samples eliciting the same basic taste. Twenty-two traditional Chinese medicinal materials could be classified into five clusters based on PCA. These differences seem to derive from the different tastes. DFA was applied to construct a model to discriminate traditional Chinese medicinal materials with different tastes. And the samples yielded about 88.2% accuracy for cross-validation. CONCLUSION: We confirmed that the electronic tongue may provide an analytical procedure for classification of the samples with respect to tastes of the traditional Chinese medicinal materials.

Associations of prenatal exposure to bisphenols with BMI growth trajectories in offspring within the first two years: evidence from a birth cohort study in China.

BACKGROUND: Prenatal bisphenol exposure has been reported to be associated with lower birth weight and obesity-related indicators in early childhood. These findings warrant an investigation of the relationship between prenatal bisphenol exposure and the dynamic growth of offspring. This study aimed to evaluate the relationship of maternal bisphenol concentration in urine with the body mass index (BMI) growth trajectory of children aged up to two years and to identify the critical exposure periods. METHODS: A total of 826 mother-offspring pairs were recruited from Wuhan Children's Hospital between November 2013 and March 2015. Maternal urine samples collected during the first, second, and third trimesters were analyzed for bisphenol A (BPA), bisphenol S, and bisphenol F (BPF) concentrations. Measurements of length and weight were taken at 0, 1, 3, 6, 8, 12, 18, and 24 months. Children's BMI was standardized using the World Health Organization reference, and group-based trajectory modeling was used to identify BMI growth trajectories. The associations between prenatal bisphenol exposure and BMI growth trajectory patterns were assessed using multinomial logistic regression models. RESULTS: The BMI growth trajectories of the 826 children were categorized into four patterns: low-stable (n = 134, 16.2%), low-increasing (n = 142, 17.2%), moderate-stable (n = 350, 42.4%), and moderate-increasing (n = 200, 24.2%). After adjusting for potential confounders, we observed that prenatal exposure to BPA during the second trimester [odds ratio (OR) = 2.20, 95% confidence interval (CI) = 1.09-4.43] and BPF during the third trimester (OR = 3.28, 95% CI = 1.55-6.95) at the highest quartile concentration were associated with an increased likelihood of the low-increasing BMI trajectory. Furthermore, in the subgroup analysis by infant sex, the positive association between the highest quartile of prenatal average urinary BPF concentration during the whole pregnancy and the low-increasing BMI trajectory was found only in girls (OR = 2.82, 95% CI = 1.04-7.68). CONCLUSION: Our study findings suggest that prenatal exposure to BPA and BPF (a commonly used substitute for BPA) is associated with BMI growth trajectories in offspring during the first two years, increasing the likelihood of the low-increasing pattern. Video Abstract (MP4 120033 kb).

[Influence of combination on the specific chromatogram of Glycyrrhiza in sini decoctions by HPLC].

The paper is to report the establishment of an HPLC specific chromatogram of Glycyrrhiza in Sini decoctions and the influence of combination on the specific chromatogram. The RP-HPLC method was used with a Phenomenex Gemini C18 column (250 mm x 4.6 mm ID, 5 microm), and acetonitrile-0.05% trifluoroacetic acid (gradient elution) as mobile phase. Flow rate was 0.8 mL x min(-1) and the detection wavelength was set at 232 nm. The temperature of column was 30 degrees C. The method is stable and reliable with a good reproducibility, it can be used to determine the specific chromatogram of Glycyrrhiza in Sini Decoctions. Twenty peaks were selected as specific peaks in Sini Decoction with liquiritin peak as the reference peak. Six of them were from Glycyrrhiza and the other 6 peaks were from both Glycyrrhiza and Ganjiangfuzi Decoction. The areas of specific peaks of Sini Decoctions were smaller than those in the chromatogram of Glycyrrhiza. The specific chromatogram of Glycyrrhiza in Sini Decoctions is markedly influenced by Radix Aconiti Carmichaeli and Rhizoma Zingiberis. The areas of the specific peaks in Sini Decoctions were reduced obviously. The method is stable and reliable with a good reproducibility, it can be used to determine the specific chromatogram of Glycyrrhiza in Sini Decoctions.

Protective effect of C(60) -methionine derivate on lead-exposed human SH-SY5Y neuroblastoma cells.

Oxidative stress has been considered as one of the possible mechanisms leading to the neurotoxicity of lead. One of the effective ways to prevent cellular damage after lead exposure is using antioxidants. In this paper, a novel C(60) -methionine derivate (FMD), a fullerene molecule modified with methionine, was synthesized. The protective effect of FMD on lead-exposed human SH-SY5Y neuroblastoma cells was investigated. In this research, after incubating with 500 µm Pb acetate alone for 72 h, the cells had undergone a series of biological changes including viability loss, apoptotic death, the depletion of glutathione (GSH), the peroxidation of membrane lipid and DNA damage. Pretreatment with FMD before lead exposure could improve cell survival, increase the GSH level, reduce malondialdehyde content and attenuate DNA damage without obvious toxicity. In addition, the protective effects of FMD were proven to be greater than those of other two C(60) -amino acid derivates, ß-alanine C(60) derivate and cystine C(60) derivate, which have been confirmed in our previous work to be able to protect rat pheochromocytoma PC12 cells from hydrogen dioxide-induced oxidative injuries. These observations suggest that FMD may serve as a potential antioxidative and neuroprotective agent in the prevention of lead intoxication.

Effect of Physical Activity on Hospital Service Use and Expenditures of Patients with Coronary Heart Disease: Results from Dongfeng-Tongji Cohort Study in China.

The intervention of behaviors, including physical activity (PA), has become a strategy for many hospitals dealing with patients with chronic diseases. Given the limited evidence available about PA and healthcare use with chronic diseases, this study explored the association between different levels of PA and annual hospital service use and expenditure for inpatients with coronary heart disease (CHD) in China. We analyzed PA information from the first follow-up survey (2013) of the Dongfeng-Tongji cohort study of 1460 CHD inpatients. We examined factors such as PA exercise volume and years of PA and their associations with the number of inpatient visits, number of hospital days, and inpatient costs and total medical costs. We found that the number of hospital days and the number of inpatient visits were negatively associated with intensity of PA level. Similarly, total inpatient and outpatient costs declined when the PA exercise volume levels increased. Furthermore, there were also significant associations between the number of hospital days, inpatient costs or total medical costs and levels of PA years. This study provides the first empirical evidence about the effects of the intensity and years of PA on hospital service use and expenditure of CHD in China. It suggests that the patients' PA, especially the vigorous PA, should be promoted widely to the public and patients in order to relieve the financial burden of CHD.

[Establishment of bitterness appraisal method of Chinese drugs and preparation].

OBJECTIVE: Bitterness appraisal method of Chinese drugs and preparation is established. METHOD: The investigation table was designed by analogical epidemiology investigation. Then the statistical analysis was made for the data, and berberine bitter taste threshold was calculated. Verification experiment was made by two kinds of complex prescription. RESULT: Berberine is determined as the standard bitter material. Statistics results about verification experiment are significant. CONCLUSION: The system could be bitterness appraisal method of Chinese drugs and preparation.