[Composite excipients for preparing concentrated water pills of personalized traditional Chinese medicine prescriptions by extruding-rounding method].

This study aims to optimize the composite excipients suitable for the preparation of concentrated water pills of personalized traditional Chinese medicine prescriptions by the extruding-rounding method and investigate the roles of each excipient in the preparation process. The fiber materials and powder materials were taken as the standard materials suitable as excipients in the preparation of personalized concentrated water pills without excipient. Water absorption properties and torque rheology were used as indicators for selecting the materials of composite excipients. The ratio of composite excipients was optimized by D-optimal mixture design. Moreover, to demonstrate the universal applicability of the optimal composite excipients, this study selected three traditional Chinese medicine prescriptions with low, medium, and high extraction rates to verify the optimal ratio. Finally, the effects of each selected excipient on the molding of personalized concentrated water pills were investigated with the four parameters of the pill molding quality as indicators. The optimized composite excipients were dextrin∶microcrystalline cellulose(MCC)∶low-substituted hydroxypropyl cellulose(L-HPC) at a ratio of 1∶2∶4. The composite excipients were used for the preparation of personalized concentrated water pills with stable process, good quality, and a wide range of application. Dextrin acted as a diluent and accelerated the speed of extruding. MCC mainly served as an adhesive, increasing the cohesion and viscosity of the pills. L-HPC as a water absorbent and disintegrating agent can absorb and hold the water of the concentrate and has a strong disintegration effect.

[Molding law of traditional Chinese medicine gel plaster based on physicochemical properties of raw materials and intermediates].

This paper aims to study the correlation between the physicochemical properties of raw materials and intermediates and the molding quality and law of traditional Chinese medicine(TCM) gel plaster by using TCM slices and powder as raw materials. 48 TCM compounds are selected as model prescriptions to prepare gel plasters. The rotational rheometer is used to determine the rheological parameters of the plaster, including storage modulus(G'), loss modulus(G″), yield stress(τ), and creep compliance [J(t)]. The molding quality of the prepared TCM gel plaster is evaluated by subjective and objective measures. Clustering and principal component analysis are conducted to evaluate the physical properties of the plaster. By measuring the rheological properties of the plaster, the molding quality of the TCM gel plaster can be predicted, with an accuracy of 83.72% after seven days of modeling and 88.37% after 30 days of modeling. When the parameters such as G' and G″ of the plaster are large, and the [J(t)] is small, the molding quality of the plaster is better. When the plaster coating point is no less than 3, it is difficult to be coated. In addition, when the proportion of metal ions in the prescription is higher, the 30-day forming quality of the plaster is mainly affected, and the viscosity of the plaster is poor. If the prescription contains many acidic chemical components, the 7-day forming quality of the plaster is mainly affected, with many residuals. The results suggest that the rheological properties of the plaster can be used to predict the molding quality of TCM slice and powder gel plaster. It can provide a reference for the development of TCM gel plaster prescriptions.

[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.

Isolation, bioassay and 3D-QSAR analysis of 8-isopentenyl flavonoids from Epimedium sagittatum maxim. as PDE5A inhibitors.

BACKGROUND: As known, inhibition of phosphodiesterase 5 (PDE5) has the therapeutic effect on male erectile dysfunction (ED), and the processed folium of Epimedium sagittatum Maxim. (PFES) characterized by 8-isopentenyl flavonoids is a famous herb for treating ED. However, the main flavonoids inhibitory activities, structure-activity relationship (SAR) and signaling pathway have been not systematically studied so that its pharmacodynamic mechanism is unclear. METHODS: We aimed to initially reveal the PFES efficacy mechanism for treating ED. For the first time, 6 main 8-isopentenyl flavonoids (1-6) from PFES were isolated and identified. Then based on HPLC detection, we proposed a novel method to screen inhibitors among them. We further analyze the three-dimensional quantitative structure-activity relationship (3D-QSAR) for those inhibitors. RESULTS: The results were verified by cellular effects of the screened flavonoids. Among 6 compounds, Icariin: (1), 2-O''rhamnosylicaridide II (2) and Baohuoside I (3) were identified with significant activities (IC50 = 8.275, 3.233, 5.473 µM). Then 3D-QSAR studies showed that the replacement of C8 with bulky steric groups as isopentenyl, C3 with positive charge groups and C4' with a hydrogen bond acceptor substituent could increase inhibitory effects. In contrast, the substitution of C7 with bulky steric groups or hydrophilic groups tended to decrease the efficacies. And compounds 1, 2, 3 could increase cGMP level and decrease cytoplasmic Ca2+ of rat corpus cavernosum smooth muscle cells (CCSMCs)by activating PKG. CONCLUSION: 8-isopentenyl flavonoids could be the main pharmacodynamic substances of PFES in the treatment for ED, and some had significant PDE5A1 inhibitory activities so as to activate cGMP/PKG/Ca2+ signaling pathway in CCSMCs, that was related to the substituents at the key sites such as C8, C3, C4' and C7 in the characteristic compounds.

A feasible classification method of wet masses to predict pellet formation of powdered herbal slices

The aim of the current study was to explore the correlation between physical properties of wet masses and pellet quality by using powdered herbal slices as model drugs. Wet masses with 100 formulations were prepared by taking 20 kinds of powdered herbal slices as model drugs, microcrystalline cellulose as pelletization aid and five levels of added water as liquid binder. Physical properties of the wet masses such as hardness, adhesiveness, springiness, cohesiveness, chewiness, and resilience were measured by a texture analyzer. Meanwhile, the moisture retention capacities (MRC) of powdered herbal slices and wet masses were determined. Particles were classified after they were produced during spheronization. Principal component analysis, factor analysis and classification analysis were performed on the data. Wet masses could be classified into three groups by taking Ha as the first classification index and Ha/Sp as the second classification index. The correct rate of the classification was 91.00%. If Ha value of wet masses was greater than 15610 g, pellets of type ① would form, otherwise, pellets of type ② or type ③ would form based on Ha/Sp value. Then a classification plot of wet masses was developed to predict pellet formation of powdered herbal slices. Meanwhile, the probable mechanism of pellets formation during spheronisation was concluded in this study, which provided useful information to improve pellet quality

[Development status and research strategy of traditional Chinese medicine temporary prescription preparation technology].

Temporary prescription preparation is the preparation processed into different dosage forms by relevant pharmacist according to the temporary preparation requirement and the personalized prescription made by the doctor in accordance with the syndrome differentiation and drug performance.It is an important part in personalized pharmaceutical services.Rational design of process route,production equipment and quality control method for the temporary prescription preparation,and establishment of technology research strategy and mode in accordance with the characteristics of traditional Chinese medicine temporary prescription preparations play an important role in promoting the development of the temporary prescription preparations.To promote the normalization,standardization and intelligent development of temporary prescription preparations,we would comprehensively summarize the significance,policy,technology characteristics,technology research status quo and existing problems in this paper,and put forward the research direction of temporary prescription preparation technology based on the physical properties of raw materials,equipment research strategy,and intelligent manufacturing technology.Thus it will push the inheritance and innovation of temporary prescription preparation.

Er-Miao-Fang Extracts Inhibits Adipose Lipolysis and Reduces Hepatic Gluconeogenesis via Suppression of Inflammation.

High-fat-diet (HFD) feeding induces adipose dysfunction. This study aims to explore whether the Traditional Chinese Medical prescription Er-Miao-Fang could ameliorate adipose dysfunction and prevent hepatic glucose output. Short-term HFD feeding induced adipose lipolysis accompanied with enhanced hepatic glucose output in mice. Adipose lipolysis is initiated by cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling. Oral administration Er-Miao-Fang inhibited inflammation in adipose tissue by dephosphorylation of JNK and reducing TNF-α and IL-1ß production, and thus preserved phosphodiesterase 3B (PDE3B) induction, contributing to preventing cAMP accumulation. As a result, from suppression of PKA activation, Er-Miao-Fang reduced fatty acids and glycerol release from adipose tissue due to the inhibition hormone-sensitive lipase (HSL). By blocking the traffic of fatty acids and inflammatory mediators from adipose tissue to the liver, Er-Miao-Fang attenuated hepatic cAMP/PKA signaling by protecting phosphodiesterase 4B (PDE4B) induction from inflammatory insult, and thereby reduced hepatic glucose production by suppression of hepatic glucagon response in HFD-fed mice. In conclusion, Er-Miao-Fang prevented adipose lipolysis by suppression of inflammation, contributing to reducing excessive hepatic glucose output. These findings present a new view of regulating gluconeogenesis and provide the guiding significance for the regulation of multi-link targets with Traditional Chinese Medicine.

[Wetting agent dosage screening for traditional Chinese medicine pellet based on torque rheological property].

With lubricant and bonding effect simultaneously, wetting agent has direct effect on properties of wet mass and extrudate, thus affecting the forming quality of pellets in extrusion-spheronization process. In this research, 25 representative kinds of traditional Chinese medicine(TCM) were selected as model drugs and 20%, 30% and 40% drug loading were set with MCC as their balling agent. The torque rheological curves were measured to get parameters such as maximum torque (Tmax) and corresponding water addition (WTmax) for these 75 raw materials by a mixer torque rheometer (MTR).The results showed that among 75 representative raw materials, 74 ones could be obtained for spherical pellets under the water addition of WTmax-2. corresponding to the second largest torque in torque rheological curve, suggesting that MTR could be used to select the optimal wetting agent dosage of TCM pellets. So the tedious and expensive pre-production work could be considerably reduced when TCM pellets were prepared.

[Discussion on research and development of new traditional Chinese medicine preparation process based on idea of QbD].

Traditional processes are mostly adopted in traditional Chinese medicine (TCM) preparation production and the quality of products is mostly controlled by terminal. Potential problems of the production in the process are unpredictable and is relied on experience in most cases. Therefore, it is hard to find the key points affecting the preparation process and quality control. A pattern of research and development of traditional Chinese medicine preparation process based on the idea of Quality by Design (QbD) was proposed after introducing the latest research achievement. Basic theories of micromeritics and rheology were used to characterize the physical property of TCM raw material. TCM preparation process was designed in a more scientific and rational way by studying the correlation among enhancing physical property of raw material, preparation process and product quality of preparation. So factors affecting the quality of TCM production would be found out and problems that might occur in the pilot process could be predicted. It would be a foundation for the R&D and production of TCM preparation as well as support for the "process control" of TCMIs gradually realized in the future.

A protocol for the classification of wet mass in extrusion-spheronization.

In this study, a structured protocol for the classification of wet mass in extrusion-spheronization was developed to predict formation and pellet quality. The wet masses of 120 formulae were prepared taking microcrystalline celluloses as pelletization aid and lactose, hydroxypropyl methylcellulose grades, herbal medicines as model drugs. Physical properties of the wet masses such as hardness, adhesiveness, springiness, cohesiveness, chewiness, and resilience were tested, respectively, using a texture analyzer. Particles were produced by spheronization process, and the quality of spherical pellets was also evaluated. Data were analyzed by principal component analysis, factor analysis, and classification analysis. The wet masses could be classified into five groups taking the ratio of hardness to springiness (Ha/Sp) as the first classification index and chewiness, resilience as the second and the third classification index. The wet masses of different classification could correspondingly form the different shapes. So, a new protocol could be devised, for example, if the range of Ha/Sp of the wet masses was 30,992-47,689 g, at the same time, the value of chewiness was less than 4842, and the value of resilience was no more than 0.139; it would form spherical pellets under the experimental condition. These results demonstrate that the proposed protocol could be a valuable asset in a formulation development project to assess the physical properties of wet masses and to predict formation and pellet quality. So, the tedious and expensive pre-production (pre-formulation and optimization) work could be considerably reduced.

[Evaluating method of the characteristic physical properties of the wetting mass using texture analyser].

To build the evaluating method of the characteristic physical properties of the wetting mass, this study reported the preparation of wetting mass by adding water into microcrystalline cellulose, and using texture analyser texture profile analysis to test its physical properties, including hardness, adhesiveness, springness, cohesiveness, chewiness, resilience and so on, then finding out the better method and parameters. The method was evaluated and used to test wetting mass, which was made of microcrystalline cellulose of different types and polyvinylpyrrolidone. When running texture profile analysis whose trigger force was 1500 g, the relative standard deviation was under 10%, and the trend of every characteristic physical property tallied with the theory result by water ratio increase. Testing result of the same excipient with the same water ratio had a higher precision, while characteristic physical properties of wetting mass who was made of the same excipient with different water ratios and different excipients had a great difference. Using texture analyser to test physical properties of wetting mass could get a result which tallied with the theory by water ratio increase, and had a well precision, accuracy and sensitivity, and thus it could also evaluate the characteristic physical properties of wetting mass relatively well.

[Correlation between physical characteristics of sticks and quality of traditional Chinese medicine pills prepared by plastic molded method].

OBJECTIVE: To quantify the physical characteristics of sticks of traditional Chinese medicine (TCM) honeyed pills prepared by the plastic molded method and the correlation of adhesiveness and plasticity-related parameters of sticks and quality of pills, in order to find major parameters and the appropriate range impacting pill quality. METHOD: Sticks were detected by texture analyzer for their physical characteristic parameters such as hardness and compression action, and pills were observed by visual evaluation for their quality. The correlation of both data was determined by the stepwise discriminant analysis. RESULT: Stick physical characteristic parameter l(CD) can exactly depict the adhesiveness, with the discriminant equation of Y0 - Y1 = 6.415 - 41.594l(CD). When Y0 < Y1, pills were scattered well; when Y0 > Y1, pills were adhesive with each other. Pills' physical characteristic parameters l(CD) and l(AC), Ar, Tr can exactly depict smoothness of pills, with the discriminant equation of Z0 - Z1 = -195.318 + 78.79l(AC) - 3 258. 982Ar + 3437.935Tr. When Z0 < Z1, pills were smooth on surface. When Z0 > Z1, pills were rough on surface. CONCLUSION: The stepwise discriminant analysis is made to show the obvious correlation between key physical characteristic parameters l(CD) and l(AC), Ar, Tr of sticks and appearance quality of pills, defining the molding process for preparing pills by the plastic molded and qualifying ranges of key physical characteristic parameters characterizing intermediate sticks, in order to provide theoretical basis for prescription screening and technical parameter adjustment for pills.

[Research for thermal stability of fructose, glucose, 5-hydroxymethyl-2-furfural during the process of refining honey of honeyed pill].

OBJECTIVE: To research the thermal stability of Fructose, Glucose, 5-Hydroxymethyl-2-furfural (5-HMF) during the process of refining honey. METHODS: The refined honey was placed under different temperature and time. High Performance of Liquid Chromatography (HPLC) coupled with Evaporative Light Scattering Detection (ELSD) were used for the determination of fructose and glucose content and HPLC-UV detector was used to detect the content of 5-HMF in refined honey. RESULTS: The contents of fructose and glucose decreased meanwhile the amount of 5-HMF conversion increased with the temperature increasing and the time extension. CONCLUSION: Temperature is the main factor and the content of fructose, glucose and 5-HMF has no significant change below 8 degrees C. Therefore, low-temperature method is recommended for the process of increasing the viscosity of honey.