[Synchronous evaluation of continuous dynamic dissolution and absorption of Compound Danshen Dropping Pills based on cellular bioelectrical effect].

The real-time cell-based assay(RTCA) was used to establish the bioelectrical sensing model of Compound Danshen Dripping Pills with rat cardiomyocytes(H9 c2). The time/dose-dependent cell response profiles(TCRPs) of in vitro dissolution and absorption of the pills were determined to establish the continuous dynamic dissolution and absorption kinetic models. Thereby, the cell index(CI)-based dissolution and absorption kinetic curves and kinetic models of Compound Danshen Dripping Pills were obtained. The optimal dissolution kinetic model was Weibull model. The similarity factors f_2 of dissolution curves were greater than 50 and the correlation coefficients of absorption curves were larger than 0.95. With the experiment about the efficacy on mice, percentages of the bleeding time of mice administrated with Compound Danshen Dripping Pills were calculated, and there was a correlation among dissolution, absorption, and efficacy curves(r > 0.9). RTCA is applicable to the study of the dissolution and absorption kinetics of solid compound Chinese medicine preparations. Thus, it is an innovative and feasible method to evaluate the quality and batch consistency of compound Chinese medicine preparations.

[Quality evaluation of Ginseng Radix et Rhizoma based on UPLC characteristic chromatogram and quantitative analysis of multi-components by single marker (QAMS)].

Based on UPLC characteristic chromatogram and quantitative analysis of multi-components by single marker(QAMS), the content of seven types of ginsenosides in Ginseng Radix et Rhizoma was simultaneously determined, and the quality of Ginseng Radix et Rhizoma was evaluated by the principal component analysis(PCA). The chromatographic separation was performed on the Acquity UPLC BEH C_(18) column(2.1 mm×100 mm, 1.7 µm) with the mobile phase of acetonitrile-water for gradient elution at the flow rate of 0.3 mL·min~(-1), the column temperature of 30 ℃, the detection wavelength of 203 nm, and the injection volume of 2 µL. The UPLC chromatogram was established with 19 batches of Ginseng Radix et Rhizoma samples from three producing areas by Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine(version 2012). Thirteen characteristic peaks were determined and seven components were identified. SPSS 26.0 was used to conduct PCA on the characteristic peak areas. With the peak of ginsenoside Rb_1 as reference peak S, ginsenoside Rb_1 showed good durability of relative correction factor as compared with other ginsenosides. The QAMS method for the determination of seven ginsenosides in Ginseng Radix et Rhizoma was established. There was no significant difference in results between the QAMS method and the external standard method. As revealed by the results of PCA and the determination of the total content of seven ginsenosides, the four batches of Ginseng Radix et Rhizoma numbered S19, S18, S1, and S2 were of superior quality. The characteristic chromatogram and QAMS method for the determination of seven ginsenosides in this study were convenient and accurate, which greatly shortened the analysis time and improved the analysis efficiency. The findings of this study are expected to provide a basis for the overall quality evaluation of Ginseng Radix et Rhizoma.

[Mechanism of Qingwei Powder in treatment of periodontitis based on UPLC-Q-TOF-MS, GC-MS, network pharmacology and molecular docking].

The present study explored the mechanism of Qingwei Powder(QP) in the treatment of periodontitis based on chromatography-mass spectrometry and network pharmacology-molecular docking techniques. UPLC-Q-TOF-MS and GC-MS were used to identify the chemical constituents of QP. The active components and targets were screened out through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), and their targets were predicted using SwissTargetPrediction. Targets related to periodontitis were obtained from GeneCards, OMIM, and DisGeNET. Venn diagram was constructed using Venny 2.1 to obtain the intersection targets. Cytoscape 3.7.2 was used to construct the "chemical component-target-disease" network. The targets were analyzed for Gene Ontology(GO) function and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment by clusterProfiler R, and the "chemical component-target-pathway" network was constructed. The binding activity of the active components to the target proteins was verified by molecular docking. A total of 189 chemical components were obtained by UPLC-Q-TOF-MS and GC-MS, including 39 active components with 180 potential targets related to periodontitis. Target enrichment analysis of the active components yielded 92 KEGG pathways. Twenty KEGG pathways, 34 active components, and 99 targets were involved in the "chemical component-target-pathway" network. Molecular docking verified a good binding ability of the key targets to the key compounds. This study preliminarily indicates that QP is effective in treating periodontitis through multiple components, multiple targets, and multiple pathways, which reflects the complex system of Chinese medicine. This study provides the theoretical foundation for the subsequent research on the material basis and key quality attributes of QP.

[Research model integrating "both medicinal and adjuvant properties" for essential oils from Chinese medicinal: based on characterization of medicinal properties].

Essential oils(EOs) from Chinese medicinals, which can be used as adjuvants and exert certain therapeutic effect, are directly used in Chinese medicine formulas. Conventional research strategy for EOs from Chinese medicinals is to compare the efficacy of the prescriptions before and after the addition of EOs, and the penetration-enhancing mechanisms of EOs remain unclear. In modern research on EOs from Chinese medicinals, the method for studying chemical penetration enhancers is often used, which fails to reflect the overall efficacy of EOs. This study clarified the property regularity of EOs from Chinese medicinals as transdermal penetration enhancers, and thereby proposed a research model which integrated the medicinal and adjuvant properties of EOs from Chinese medicinals via "component-delivery-effect" characterization route. The core concept is that constituents of EOs from Chinese medicinals and their delivery process play a key role in their external application. This research model is expected to serve as a reference for further research on EOs from Chinese medicinals for transdermal application.

[Quality value transmitting of substance benchmarks in Danggui Buxue Decoction].

To clarify the key quality attributes of substance benchmarks in Danggui Buxue Decoction(DBD), this study prepared 21 batches of DBD substance benchmarks, and established two methods for detecting their fingerprints, followed by the identification of peak attribution and similarity range as well as the determination of extract and transfer rate ranges and contents of index components ferulic acid, calycosin-7-O-ß-D-glucoside, and astragaloside Ⅳ. The mass fractions and transfer rates of DBD substance benchmarks from different batches were calculated as follows: ferulic acid(index component in Angelicae Sinensis Radix): 0.037%-0.084% and 31.41%-98.88%; astragaloside Ⅳ(index component in Astragali Radix): 0.021%-0.059% and 32.18%-118.57%; calycosin-7-O-ß-D-glucoside: 0.002%-0.023% and 11.51%-45.65%, with the extract rate being 18.4%-36.1%. The similarity of fingerprints among 21 batches of DBD substance benchmarks was all higher than 0.9. The quality control method for DBD substance benchmarks was preliminarily established based on the HPLC fingerprint analysis and index component determination, which has provided a basis for the subsequent development of DBD and the quality control of novel related preparations.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal metastasis from breast cancer: a preliminary report of 4 cases.

BACKGROUND: Breast cancer (BC) has the highest morbidity and the fifth-highest mortality rate among women in China. Peritoneal metastases from BC are rare, and presently, there are no guidelines or international consensus on its treatment. Patients with a prognosis of peritoneal carcinomatosis (PC) have poorer survival rates than patients with other regional metastases from BC. METHODS: Four BC PC patients, who had undergone cytoreductive surgery (CRS) + hyperthermic intraperitoneal chemotherapy (HIPEC), participated in this study. Clinicopathologic characteristics and overall survival (OS) data were collected and analyzed. RESULTS: Patients' average age when they underwent CRS + HIPEC was 59.8 years. The average time of CRS + HIPEC was 8.8 h. The median number of resected organ areas was 7. Following CRS + HIPEC, each of the 4 patients survived for 31, 28, 16 and 52 months, respectively. There were no serious adverse events during the perioperative period. CONCLUSIONS: The study examined the detailed process of CRS + HIPEC and found that patients with BC PC may benefit from this treatment. The 4 cases provided evidence that the integrated therapy of CRS + HIPEC is a promising strategy that could improve outcomes for BC PC patients. Further, no serious adverse events (SAEs) occurred during the CRS + HIPEC perioperative period.

Development of curcumin-loaded composite phospholipid ethosomes for enhanced skin permeability and vesicle stability.

Ethosomes are widely applied as the carriers for the transdermal delivery of hydrophobic and hydrophilic drugs. Herein, curcumin-loaded ethosomes (CE) with different phospholipid composition were formulated and thoroughly compared. A significant interaction between the unsaturated phosphatidylcholine (PC) and saturated hydrogenated phosphatidylcholine (HPC) was found by molecular simulation and differential scanning calorimetry (DSC), which led to the reduction of PC peroxidation with the presence of HPC. Subsequently, the composite phospholipid ethosomes containing curcumin were prepared for the first time to evaluate their properties in comparison with the conventional ethosomes composed of PC (CE-P) or HPC (CE-H). CE with PC/HPC ratio of 1:1 (CE-P1H1) with the best vesicle stability and flexibility significantly decreased the uptake by HaCaT cells compared to CE-H and free curcumin, indicating reduced skin cell toxicity. Compared with free curcumin, CE-P1H1 had the highest transdermal efficiency (p < 0.001), followed by CE-P (p < 0.05), partly due to the fact that CE-P1H1 could disturb lipid domain of stratum corneum (SC). Moreover, CE-P1H1 was found to promote curcumin for deep penetration of the skin via the hair follicles route. Our study has shown that using composite phospholipid ethosomes as lipid vesicular carriers could enhance transdermal penetration of drugs and increase in the vesicle stability.

Peritoneal cancer index (PCI) based patient selecting strategy for complete cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy in gastric cancer with peritoneal metastasis: A single-center retrospective analysis of 125 patients.

OBJECTIVE: The role of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) in gastric cancer with peritoneal metastasis (GCPM) is still controversial, mainly due to the limited survival benefit and uncertain patient selection. This study aims to construct a selecting strategy in GCPM for CRS + HIPEC. METHODS: From a prospective established database, 125 patients were enrolled. All these patients were pathologically confirmed as GCPM and treated with CRS + HIPEC with or without preoperative or postoperative chemotherapy. The clinical documents and follow-up results were collected and analyzed with the primary endpoint of overall survival (OS) and the secondary endpoint of perioperative serious adverse events (SAEs). RESULTS: The median OS of 125 GCPM patients treated with CRS + HIPEC was 10.7 months, with 1-, 2-, 3-, and 5-year survival rates of 43.8%, 24.7%, 18.6%, and 15.7%, respectively. The multivariate analysis identified completeness of cytoreduction (CC), SAEs, HIPEC drugs, and adjuvant chemotherapy as independent prognostic factors on OS. The median OS was 30.0 (95%CI: 16.8-43.3) months in CC-0 group, significantly better than 7.3 (95%CI: 5.8-8.8) months in CC1-3 group (P < 0.001). The median OS showed no significant difference among CC-1 (8.5, 95%CI: 6.7-10.2, months), CC-2 (5.6, 95%CI: 3.0-8.2, months) and CC-3 (6.5, 95%CI: 5.2-7.7, months) groups (P > 0.05 for all pairwise comparations). The nomogram based on peritoneal metastasis timing, preoperative tumor marker (TM), and peritoneal cancer index (PCI), with AUC of 0.985, showed a good accuracy and consistency between actual observation and prediction of the probability of complete CRS. The cutoffs of PCI were 16 for synchronous GCPM with normal TM, 12 for synchronous GCPM with abnormal TM, 10 for metachronous GCPM with normal TM, and 5 for metachronous GCPM with abnormal TM, setting the probability to achieve complete CRS as 50%. CONCLUSIONS: Only complete CRS + HIPEC (CC-0) could improve survival for high selected GCPM patients with acceptable safety. An incomplete CRS (CC1-3) should be avoided for GCPM patients. Synchronous GCPM with PCI ≤16 and normal TM, synchronous GCPM with PCI ≤12 and abnormal TM, metachronous GCPM with PCI ≤10 and normal TM, or metachronous GCPM with PCI ≤5 and abnormal TM maybe potential indications for complete CRS + HIPEC treatment.

CRS + HIPEC combined with IP + IV chemotherapy for gastric signet-ring cell carcinoma: Case report of long-term survival.

RATIONALE: Signet ring cell carcinoma of the stomach is prone to relapse and metastasis after traditional surgical treatment, and the prognosis is also poor. We improved the concept of treatment and conducted cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) combined with intraperitoneal (IP) and intravenous (IV) chemotherapy for a gastric signet-cell carcinoma patient. PATIENT CONCERNS: A 65-year-old male patient with complaint of intermittent hematemesis for over 10 days was referred to our hospital for treatment. The patient developed hematemesis of 800 mL without obvious causes on May 27, 2015, accompanied by dizziness and amaurosis fugax. After the bleeding was stopped with medicinal treatment, diagnostic gastroscopy revealed an ulcer at the less curvature of the stomach, with biopsy pathology diagnosis as severe atypical hyperplasia, which was confirmed to be poorly differentiated adenocarcinoma by a second biopsy. In past medical history, the patient had 5 coronary stents implanted because of coronary atherosclerotic heart disease 3 years ago. DIAGNOSIS: Gastric cancer (cT4NxMx) according to the patient's history and biopsy pathology. INTERVENTIONS: the patient was treated surgery-based multidisciplinary treatments integrating CRS + HIPEC and IP + IV adjuvant chemotherapy. The CRS was curative distal gastrectomy with D2 lymphadenectomy, and HIPEC was cisplatin 120 mg plus mitomycin C 30 mg at 43 °C, for 60 minutes. Final pathological diagnosis of after surgery was: poorly differentiate adenocarcinoma with signet-ring cells, with invasion beyond the serosal layer and into the duodenum, 10/23 lymph nodes positive, nerve invasion, vascular tumor thrombi, Borrmann type IV, Lauren type diffuse. TNM stage was pT4aN3M0, IIIC. After operation, the patient received 6 courses of IV chemotherapy with oxaliplatin and 5-fluorouracil/Tegafur Gimeracil Oteracil Potassium capsules, and IP chemotherapy with docetaxel and carboplatin. OUTCOMES: Regular follow-up till July 20, 2020, revealed that the patient has a disease-free survival of over 61+ months. LESSONS: CRS + HIPEC combined with IP + IV chemotherapy achieved long-term disease-free survival for this patient with gastric signet-ring cell carcinoma and deserve further study. This new treatment modality deserves appropriate consideration in routine clinical practice for patients with advanced gastric cancer.

[Opportunities and challenges in development of compound preparations of traditional Chinese medicine: problems and countermeasures in research of ancient classical prescriptions].

As an outstanding representative of traditional Chinese medicine( TCM),ancient classical prescriptions carry the profound accumulation of the splendid civilization of Chinese medicine for thousands of years. It is the best part of the great treasure-house of Chinese medicine after thousands of years' training of TCM theory. It condenses the wisdom of all generations of doctors,and as the summary of clinical experience,it is the most brilliant pearl in the treasure house of TCM. The in-depth research and development of ancient classic prescriptions is a golden key to excavate the treasure house of TCM,which not only conforms to the development trend of TCM industry,but also brings unprecedented opportunities and challenges for the inheritance and innovation of contemporary Chinese herbal compound preparations. However,as a " new member" in the national drug research and development system,classic prescriptions have no specific implementation rules although the guidance is given by macro policies,and there is no successful case of research and development according to the registration requirements. Therefore,unified consensus and standards have not yet been formed for some key issues in the process of the development of the classic prescriptions,and much work is still in the exploration stage,so it is necessary to conduct in-depth research and discussion on these issues. In this paper,the problems in the research process of classical prescriptions were summarized,such as the resources of medicinal materials,the processing of decoction pieces,the prescription dosage,the molding technology and the quality evaluation,and the research strategy was put forward after analysis,hoping to provide a reference for the research and development of classical prescriptions.

[Study on quality of standard decoction of Coptidis Rhizoma based on traditional decoction process].

In order to determine the quality evaluation method for standard decoction of Coptidis Rhizoma,15 batches of standard decoction of Coptidis Rhizoma were prepared by using standardized process. Parameters such as traits,p H value,indicative component content,fingerprint similarity,composition transfer rate and dry extract rate were selected as the indexes for quality evaluation. Similarity evaluation and cluster analysis were performed for HPLC fingerprint of standard decoction,and mathematical model was used to study the correlation between dry extract rate,berberine content,berberine transfer rate in standard decoction and berberine content in decoction pieces. The results showed that the similarity of fingerprints was greater than 0. 99 for these 15 batches of standard decoctions of Coptidis Rhizoma. In cluster analysis,the standard decoctions of Coptidis Rhizoma from 4 producing areas were classified into 3 categories,consistent with the content determination results,indicating that there were quality differences among different producing areas.R2 in three linear regression mathematical models established was all greater than 0. 9,with significant difference. The validation of three batches of data showed that the models had good accuracy. Therefore,this model can be used to predict the quality of standard decoction prepared from different Coptidis Rhizoma pieces. In the standard decoction process established in this study,the integrity of the traditional process was greatly preserved,and the established quality evaluation method could be used to comprehensively examine the quality of the standard decoction,which can provide a demonstration for the related research of water extraction preparation containing Coptidis Rhizoma pieces.

Skin Electrical Resistance Measurement of Oxygen-Containing Terpenes as Penetration Enhancers: Role of Stratum Corneum Lipids.

The measurement of skin electrical resistance (SER) has drawn a great deal of attention for the rapid screening of transdermal penetration enhancers (PEs). However, the mechanisms underlying the SER measurement are still unclear. This study was to investigate the effects and mechanisms of seven oxygen-containing terpenes on the SER kinetics. Stratum corneum (SC) lipids were proved to play a key role in SER measurement. Then, the factors affecting the SER measurement were optimized. By the determination of SER kinetics, cyclic terpenes (1,8-cineole, terpinen-4-ol, menthol and α-terpineol) were demonstrated to possess higher enhancement ratio (ER) values compared with linear terpenes (linalool, geraniol and citral). For the first time, the linear correlation was found between ER of terpenes and the interaction energy of terpene⁻ceramide complexes revealed by molecular simulation. The attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) analysis revealed that the effect of cyclic terpenes on SC lipid arrangement was obviously stronger than that of linear terpenes. In addition, by evaluating HaCaT skin cell viability, little difference was found between the toxicities of cyclic and linear terpenes. In conclusion, measurement of SER could be a feasible approach for the efficient evaluation of the PEs that mainly act on SC lipids.

Development of phospholipid vesicle-based permeation assay models capable of evaluating percutaneous penetration enhancing effect.

OBJECTIVES: The phospholipid vesicle-based permeation assay (PVPA) model has recently been introduced as an in vitro model which can mimic stratum corneum (SC) barriers to estimate the skin permeability of drugs. The aim of this study was to evaluate whether the PVPA model was suitable for the evaluation of penetration enhancing effect of skin penetration enhancers (PE). METHODS: The PVPA model was optimized by changing the lipid composition of both small liposomes (SL), and large liposomes (LL). The barrier properties of the PVPA model were monitored by electrical resistance and permeability measurement of the fluorescent marker Rhodamine B (RB). Then the permeation studies of the five active compounds with different physicochemical properties, namely, ferulic acid, paeoniflorin, albiflorin, tetrahydrocolumbamine, and tetrahydropalmatine, were performed directly on PVPA model to evaluate the penetration enhancing effect of menthol. RESULTS AND DISCUSSIONS: The enhancement ratio (ER) ranking of the five active compounds observed using the optimized PVPA model was in accordance with what observed with Franz diffusion cell device using porcine ear skin. Attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) analysis of PVPA model and porcine ear skin after treatment with menthol has shown similar mechanism of menthol which perturbs the SC lipid arrangement and extracts the SC lipids. CONCLUSIONS: In summary, the optimized PVPA model was used for the first time for the evaluation of the permeation enhancing effect. The optimized PVPA model has shown potential to be applied in a more standardized, cheaper, and ethical way for the screening of PE.

Preparation and pharmacokinetics in beagle dogs of ganershu sustained-release pellets.

BACKGROUND: The active ingredients of Ganershu compound recipe, which are effective for hepatitis treatment in liver protection and transaminase reduction. However, the active ingredients of Ganershu compound recipe are poor absorption, which conduct it has a low oral bioavailability. OBJECTIVE: We prepared Ganershu sustained-release pellets (GSPs) by fluidized-bed on central composite design-response surface methodology and increase its bioavailability in beagle dogs. MATERIALS AND METHODS: In this study, GSPs were successfully prepared. The Drug-loaded pellets and sustained-release coated were carried out in fluidized-bed machine. GSP was optimized for fitting release, roundness, and the overall desirability by central composite design-response surface methodology. RESULTS: To optimize cumulative release profile, the outermost ethyl cellulose coating layer and the hydroxypropyl methyl cellulose (HPMC) swelling layer were employed, which were respectively given coating levels in terms of weight gain of 22% and 6%, the concentration of HPMC is 4.5% (g/ml). The pharmacokinetics of Ganershu normal pellets (GNPs) and GSP was studied in beagle dogs after oral administration. The naringenin as an index, the area under the curve0-∞ of naringenin in GSP was 1.38 times greater than that of GNP. Meanwhile, Tmax of GSP was prolonged for about 74%. CONCLUSION: This study can clearly indicate that we enhanced the oral bioavailability of Ganershu by preparing the GSP, which had the sustained dissolution and improved the potential of it for clinical application.

[Study on HPLC fingerprint of Ganershu intermediate and determination of three active components].

OBJECTIVE: To establish the fingerprint analysis method of Ganershu intermediate by HPLC. METHODS: An analysis was performed on a sunFire C18 (4. 6 mm x 250 mm, 5 microm) column with acetonitrile-0.1% phosphate aqueous as the mobile phase by gradient elution. The flow rate was 1.0 mL/min, the detection wavelength was 320 nm and detection time was 80 min. The column temperature was 35 degrees C. In the recorded chromatogram of Ganershu intermediate, neohesperidin was used as reference substance, and RSD of the relative retention time and the relative peak areas of all peaks compared with its peak were measured. The similarity of 10 batches of Ganershu intermediate was appraised by the similarity evaluation system. Using the external standard method, the contents of chlorogenic acid, neohesperidin and naringin were determined in 10 batches of intermediate. RESULTS: Tweenty-three peaks were separated on HPLC fingerprint in Ganershu intermediate, degree of similarity of fingerprint for ten batches of Ganershu intermediate were greater than 0.90. Three compounds' contents were almost the same in each batch of intermediate sample. CONCLUSION: The method is stable, accurate, reliable and can be used as a quality control for Ganershu intermediate and sustained-release capsules.

Improved pharmacokinetics and reduced toxicity of brucine after encapsulation into stealth liposomes: role of phosphatidylcholine.

OBJECTIVE: Brucine was encapsulated into stealth liposomes using the ammonium sulfate gradient method to improve therapeutic index. MATERIALS AND METHODS: Four brucine stealth liposomal formulations were prepared, which were made from different phosphatidylcholines (PCs) with different phase transition temperatures (T(m)). The PCs used were soy phosphatidylcholine (SPC), dipalmitoyl phosphatidylcholine (DPPC), hydrogenated soy phosphatidylcholine (HSPC), and distearoyl phosphatidylcholine (DSPC). The stabilities, pharmacokinetics, and toxicities of these liposomal formulations were evaluated and compared. RESULTS: Size, zeta potential, and entrapment efficiency of brucine-loaded stealth liposomes (BSL) were not influenced by PC composition. In vitro release studies revealed that drug release rate increased with decreased T(m) of PCs, especially with the presence of rat plasma. After intravenous administration, the area under the curve (AUC) values of BSL-SPC, BSL-DPPC, BSL-HSPC, and BSL-DSPC in plasma were 7.71, 9.24, 53.83, and 56.83-fold as large as that of free brucine, respectively. The LD(50) values of brucine solution, BSL-SPC, BSL-DPPC, BSL-HSPC, and BSL-DSPC following intravenous injection were 13.17, 37.30, 37.69, 51.18, and 52.86 mg/kg, respectively. It was found in calcein retention experiments that the order of calcein retention in rat plasma was SPC < DPPC << HSPC < DSPC stealth liposomes. CONCLUSION: PC composition could exert significant influence on the stabilities, pharmacokinetics, and toxicities of brucine-loaded stealth liposomes. DSPC or HSPC with T(m) above 50°C should be used to prepare the stealth liposomal formulation for the intravenous delivery of brucine. However, it was found in the present paper that the pharmacokinetics and toxicity of BSL were not influenced by the PC composition when the T(m) of the PC was in the range of -20°C to 41°C.

HPLC determination of strychnine and brucine in rat tissues and the distribution study of processed semen strychni.

A simple and low-cost HPLC method with UV absorbance detection was developed and validated to simultaneously determine strychnine and brucine, the most abundant alkaloids in the processed Semen Strychni, in rat tissues (kidney, liver, spleen, lung, heart, stomach, small intestine, brain and plasma). The tissue samples were treated with a simple liquid-liquid extraction prior to HPLC. The LOQs were in the range of 0.039-0.050 µg/ml for different tissue or plasma samples. The extraction recoveries varied from 71.63 to 98.79%. The linear range was 0.05-2 µg/ml with correlation coefficient of over 0.991. The intra- and inter-day precision was less than 15%. Then the method was used to measure the tissue distribution of strychnine and brucine after intravenous administration of 1 mg/kg crude alkaloids fraction (CAF) extracted from the processed Semen Strychni. The results revealed that strychnine and brucine possessed similar tissue distribution characterization. The highest level was observed in kidney, while the lowest level was found in brain. It was indicated that kidney might be the primary excretion organ of prototype strychnine and brucine. It was also deduced that strychnine and brucine had difficulty in crossing the blood-brain barrier. Furthermore, no long-term accumulation of strychnine and brucine was found in rat tissues.

[The determination of aristolochic acid A in different processed Aristolochia manshuriensis and the test of influence about renal function in rats].

OBJECTIVE: To study and approach the processing methods and mechanism which can markedly reduce the content of aristolochic acid in Aristolochia manshuriensis and lighten the nephrotoxicity of aristolochic acid. METHODS: A traditional "attenuation" processing method was used and 30 types of samples which contain one crude and 29 types of processed sample were obtained. The contents of aristolochic acid A in every sample were determined by HPLC. According to the Rat's acute renal injury test, the influence of animal's renal function was investigated for representative samples. RESULTS: The content of aristolochic acid in six types of samples depressed markedly (30% or more depressed) which processing with boiling in the limewater, steaming with limewater, boiling in the juice of liquorice, boiling in the decoction of black soybean, boiling in the soda water and stir-baked with talcum powder, the content of aristolochic acid in other processed samples also depressed with a large discrepancy. The toxicology test results showed that the above-mentioned 6 samples all can relieve renal injury of rats. There could be some associativity between the degree of renal injury relieving and the content of aristolochic acid A in the samples. CONCLUSION: The content of aristolochic acid can be reduced and the nephrotoxicity for animals can be lightened with some eligible processing methods for the traditional Chinese medicines containing aristolochic acid with the representative of Aristolochia manshuriensis.

[Study on the technology of ultra-fine pulverization for Flos Caryophylli].

OBJECTIVE: To study the technology of ultra-fine pulverization of Flos Caryophylli. METHODS: A single factor experiment was used to choose the method of ultra-fine pulverization for Flos Caryophylli. An orthogonal test was used to optimize the technology of ultra-fine aeropulverization of Flos Caryophylli. The preliminary powder fineness, the quantities and the types of accessories were optimized by the test, according to the indices such as ultra-fine powder yield, the average particle size and the powder flowbility. RESULTS: The super-fine powder made by the method of aeropulverization was the best, but the shape and properties were not stable. In the orthogonal test, factor A (the preliminary powder fineness) and B (the types of accessories) had little effect on all indices; Factor C (the ratio of accessories) had significant effect on the powder flowbility. The best technology was A1 B3 C3. CONCLUSION: In this study, the obtained powder has good flowbility, average size and quality stability, so it can be promoted as the technology of ultra-fine pulverization condition for Flos Caryophylli.

Sputtering ZnO films on langasite and its SAW properties.

C-axis-oriented ZnO films were sputtered on Langasite substrate (LGS, La(3)Ga(5)SiO(14)). The crystalline structure of the films was determined by grazing incident angle X-ray diffraction, the surface microstructure of films was investigated by scanning electron microscopy and atomic force microscopy, the atom composition ratio O/Zn of films was determined by energy dispersive X-ray spectroscopy, and the resistivity of films was determined by the four-point probe instrument. The measurement results showed those films prepared were all polycrystalline hexagonal ZnO films. By analyzing the microstructure of the ZnO films, those prepared at the oxygen flow rate (O(2)/O(2)+Ar) of 20%, the RF power of 200 W, and the substrate temperature of 200 degrees C had the best performance: highly c-axis-oriented microstructures, dense surface morphology, and the atom composition ratio 1.02. The measured scattering parameters of the SAW device fabricated on the composite substrate (ZnO/LGS) with film thickness 1.76 microm showed an average shifted velocity around 2741 m/s at 57.1 MHz and a electromagnetic coupling coefficient greater than 1%.