Preparation of Curcumin-Lysine Cocrystal and Solubility Comparison of Different Crystal Forms / 中国药师

Objective:To develop a new cocrystal form to improve bioavailability and druggability of curcumin. Methods:Solvent crystallization was used to prepare curcumin-lysine cocrystal, and two crystal forms ( a and b) were obtained. The two cocrystal forms were characterized by elemental analysis, differential scanning calorimetry and X-ray diffraction. The dissolution profiles of the two crystal forms were detected and compared with that of curcumin. Results:Curcumin combined with lysine at a stoichiometry of 1: 1 to form the cocrystal with much better solubility than curcumin. Conclusion: Curcumin-lysine cocrystal has ideal druggability, which means the cocrystal can be a new chemical entity used for subsequent development.

Identification and differentiation of major components in three different "Sheng-ma" crude drug species by UPLC/Q-TOF-MS

Cimicifugae Rhizoma (Sheng ma) is a Ranunculaceae herb belonging to a composite family and well known in China. has been widely used in traditional Chinese medicine. Thecontains three varieties ((Turcz.),L. andKom.) which have been used clinically as "Sheng-ma". However, the chemical constituents of three components of "Sheng-ma" have never been documented. In this study, a rapid method for the analysis of the main components of "Sheng-ma" was developed using ultra-high performance liquid chromatography with quadrupole-time-of-flight mass spectrometry (UPLC/Q-TOF-MS). The present study reveals the major common and distinct chemical constituents of,andand also reports principal component and statistical analyses of these results. The components were identified by comparing the retention time, accurate mass, mass spectrometric fragmentation characteristic ions and matching empirical molecular formula with that of the published compounds. A total of 32 common components and 8 markers for different "Sheng-ma" components were identified. These findings provide an important basis for the further study and clinical utilities of the three "Sheng-ma" varieties.

Screening technologies of pharmaceutical cocrystals:research advances / 国际药学研究杂志

Recently,the screening technologies of pharmaceutical cocrystals have become a research focus of improving drug solubility and stability. The technique changes medicine properties by intermolecular forces without changing the molecular structure , which provides new ways for the development of the insoluble drug. In addition,the formation of cocrystal gives new properties to drugs and intellectual property rights are effectively protected. This review focuses on screening technique ,which provides references for fur?ther studies of pharmaceutical cocrystal.

Study on Preparation and Releasing Characteristics in vitro of Weiyoukang Intragastric Floating Tablet / 中国药房

OBJECTIVE:To prepare Weiyoukang intragastric floating tablet,and to investigate in vitro releasing characteristics of it. METHODS:Weiyoukang intragastric floating tablet was prepared by full powder compression method using HPMC-K15M (framework material),octadecanol(low density bleaching promoter),sodium bicarbonate(foaming agent),PVP-K30(release reg-ulator)and magnesium stearate(lubricant)as excipients. The amounts of HPMC-K15M,octadecanol and PVP-K30 were optimized by orthogonal test and validated with 2 h,4 h and 8 h accumulative release rate of berberine (Y2 h,Y4 h,Y8 h) as index,start time (T1)and duration(T2)of floating as adjunctive index. The releasing regularity of berberine,tetrahydropalmatine,baicalin and glyc-yrrhizic acid in Coptis chinensis,Corydalis vanhus,Scatellaria baicalensis and Glycyrrhiza uralensis were measured by release model fitting method and Peppas equarion fitting method. Similar factor(f2)method was used to investigate the similarity of 4 com-ponents. RESULTS:The optimized formulation was as follows as HPMC-K15M 40 g,octadecanol 14 g,PVP-K30 2 g for 200 tab-lets. Y2 h,Y4 h and Y8 h of berberine of preparations were 31.94%,55.88%,93.34%(RSDs were 1.2%,1.5% and 1.5%,n=3),re-spectively. T1 and T2 were about 1 min and 13 h. The drug release of four ingredients all fitted Higuchi models,and were synergis-tic action of diffusion and matrix erode. The f2 were all more than 80,indicating that the release of four ingredients were similar. CONCLUSIONS:Weiyoukang intragastric floating tablet is prepared successfully,showing fast onset,long floating,sustained-re-lease and balanced release of multiple indigents.

Content Determination of 4 Ingredients in Ligustrum lucidum Decoration Piece by Reference Extract Method / 中国药房

OBJECTIVE:To establish a method for the contents determination of 4 ingredients in Ligustrum lucidum decoration piece by reference extract method. METHODS:HPLC was performed on the column of XBridge C18 with mobile phase of acetoni-trile-0.1% formic acid(gradient elution) at flow rate of 1.0 ml/min,detection wavelength was 254 nm,column temperature was 30℃and volume injection was 10μl. RESULTS:The linear range was 0.037-0.598 mg for neonuezhenide,0.006-0.101 mg for ac-teoside,0.189-3.023 mg for nuezhenide and 0.314-5.027 mg for specnuezhenide(r≥0.999 0);RSDs of precision,reproducibility and stability tests were no more than 3.8%;recoveries were 98.46%-104.83%(RSD=2.43,n=6),95.55%-104.57%(RSD=3.63, n=6),100.09%-104.39%(RSD=1.45,n=6)and 98.84%-104.97%(RSD=2.02,n=6). CONCLUSIONS:The method is simple, good reproducibility,and can be used for the contents determination of 4 ingredients in L. lucidum decoration piece.

Some Key Problems during Quality Standard Research of Pieces of Chinese Crude Drugs / 世界科学技术-中医药现代化

Quality standard research of pieces of Chinese crude drugs is the important content of research of Chinese medicine processing, and it is also the key point of the whole standardization system of Chinese medicine. Although we have set up a preliminary quality standard system of pieces of Chinese crude drugs, it still under a low level. During the research of quality standard of pieces of Chinese crude drugs, we still face some problems, such as how to set up a more comprehensive, scientific, and reasonable quality standard. In this paper, we proposed some advices that we should pay more attention to traditional processing theories, processing mechanisms and effective substances during research of quality standard research of pieces of Chinese crude drugs.

Identification of metabolites of arbidol by ultra-high performance liquid chromatography tandem mass spectrometry / 药学学报

UPLC-MS-MS system was used for the identification of arbidol metabolites in the rat feces, urine and plasma samples. The system was so powerful a way with high ability of separation and analysis, based on both chromatography and mass properties. The isotope of Br was also a good indicator for metabolites finding. There were altogether 9 metabolites detected and identified, including 2 phase I biotransformation products and 7 phase II ones. It is concluded that arbidol mainly undergo metabolic reactions such as N-demethylation, S-oxidation, glucuronidation and sulfation in rats.

Simultaneous determination of five main index components and specific chromatograms analysis in Xiaochaihu granules / 药学学报

Reversed phase high performance liquid chromatography with diode array detector was employed for simultaneous determination of five main index components and specific chromatograms analysis in Xiaochaihu granules with a linear gradient elution of acetonitrile-water (containing 0.1% phosphoric acid) as mobile phase. The results showed that five main index components (baicalin, baicalein, wogonoside, wogonin, enoxolone) were separated well under the analytical condition. The linear ranges of five components were 0.518 - 16.576, 0.069 - 2.197, 0.167 - 5.333, 0.009 - 0.297 and 0.006 - 0.270 mg x g(-1), respectively. The correlation coefficients were 0.999 9, and the average recoveries ranged from 95% to 105%. Twelve common peaks were selected as the specific chromatograms of Xiaochaihu granules with baicalin as the reference peak. There were good similarities between the reference and the ten batches of samples. The similarity coefficients were no less than 0.9. The analytical method established is highly sensitive with strong specificity and it can be used efficiently in the quality control of Xiaochaihu granules.

Simultaneous determination of four components in sini tang by HPLC / 中国中药杂志

<p><b>OBJECTIVE</b>To develop an HPLC method for determining four components in Sini Tan, benzoylmesaconine, liquiritin, glycyrrhizic acid and 6-gingerol.</p><p><b>METHOD</b>The Hypersil BDS column was adopted with gradient elution program at a flow rate of 1.0 mL x min(-1) and the detection wavelength of 235 nm.</p><p><b>RESULT</b>Benzoylmesaconine, liquiritin, glycyrrhizic acid and 6-gingerol showed good separation, with the linear range of 0.006-0.12, 0.021-0.42, 0.012-0.24 and 0.018-0.36 g x L(-1), respectively. Their average recoveries were 99.3%, 96.9%, 100% and 100%, respectively; and RSD of the above four components were 1.5%, 0.6%, 1.3% and 2.1%, respectively.</p><p><b>CONCLUSION</b>The method is proved to be so easy and accurate and practical that it can be used to determine the four components in Sini Tang.</p>

Quick identification of sun-dried and sulfur-fumigated angelicae sinensis radix by Fourier transform infrared spectroscopy / 中国中药杂志

<p><b>OBJECTIVE</b>To develop a quick identification method for the sun-dried and sulfur-fumigated Angelicae Sinensis Radix used by Fourier transform infrared spectroscopy (FTIR) combined with second derivative infrared spectroscopy.</p><p><b>METHOD</b>The alcoholic and aqueous extracts of sun-dried and sulfur-fumigated Angelicae Sinensis Radix were analyzed by using FTIR, the further analysis was used by second derivative infrared spectroscopy.</p><p><b>RESULT</b>There existed differences between their infrared spectra either extracted by ethanol or water, while the distinctions were more obvious after analyzing their alcoholic and aqueous extracts through high resolution of second derivative infrared spectroscopy. Infrared spectra showed that the absorption peaks of Angelicae Sinensis Radix were significantly reduced and a new absorption peak appeared after sulfur-fumigated process in alcoholic extracts, while both of them changed markedly in the "fingerprint region" ranging from 1 000 to 400 cm(-1) in aqueous extracts. Second derivative spectra showed that the absorption peaks of sulfur-fumigated Angelicae Sinensis Radix extracted by ethanol weakened and disappeared at about 3 578 cm(-1) and 3 541 cm(-1), while both of them differed significantly from each other ranging from 1 400 to 1 200 cm(-1) as well as 800 cm(-1) to 600 cm(-1), difference also existed between them extracted by water ranging from about 3 900 to 3 850 cm(-1) and 3 800 to 3 750 cm(-1).</p><p><b>CONCLUSION</b>The FTIS method combined with second derivative can be utilized to distinguish sun-dried and sulfur-fumigated Angelicae Sinensis Radix efficiently, conveniently and accurately, and provide a basis for identification and quality control of Angelicae Sinensis Radix.</p>

Comparison on in vivo pharmacokinetics of brucine, total alkaloids of Strychni Semen and Strychni Semen pulveratum in rats / 中国中药杂志

<p><b>OBJECTIVE</b>To study different in vivo pharmacokinetic regularity of brucine, total alkaloids of scorched sand-prepared Strychni Semen products and Strychni Semen pulveratum in rats, and probe into mutual impact between single component and compound.</p><p><b>METHOD</b>Rats in each group were orally administered with brucine, total alkaloids of scorched sand-prepared Strychni Semen products and Strychni Semen pulveratum suspension. The in vivo plasma concentrations of brucine in rats were determined by HPLC. A compartment model was made for the blood drug concentration-time curve using 3P97 software package and the pharmacokinetic parameters of each group were calculated and compared.</p><p><b>RESULT</b>The in vivo metabolic process of brucine in rats complied with the two-compartment model, weight W = 1/C2. The results of variance analysis showed that among three existing forms of brucine with same dosage, the brucine solution group and the total alkaloids group of scorched sand-prepared Strychni Semen products showed significant differences in C(max), MRT (P < 0.05); and the brucine solution group and the Strychni Semen pulveratum suspension group showed significant differences in C(max), AUC(0-t), and AUC(0-infinity), in which the latter displayed minimum C(max), AUC(0-t) and AUC(0-infinity).</p><p><b>CONCLUSION</b>The total alkaloids group of scorched sand-prepared Strychni Semen products showed a relatively longer retention time of effective components of brucine in plasma, while the Strychni Semen pulveratum suspension group showed a lower bioavailability.</p>

Variation regularity of chemical constituents contained in Euphorbia ebracteolata before and after roasting with vinegar / 中国中药杂志

<p><b>OBJECTIVE</b>To study the variation regularity of chemical constituents contained in Euphorbia ebracteolata after vinegar processing.</p><p><b>METHOD</b>The colorimetric method was adopted for determining the variation of total lactone content in toxic constituents contained in E. ebracteolata decoction, with Kedde as the coloring reagent. The HPLC method was used for detecting the content variation of jolkinolide B and jolkinolide C, both were active constituents contained in E. ebracteolata decoction, before and after roasting with vinegar, in which Kromasil-ODS column (4.6 mm x 250 mm, 5 microm) was adopted, with the detection wavelength of 290 nm, column temperature at 25 degrees C , gradient elution with acetonitrile and water and the flow rate of 1.0 mL x min(-1).</p><p><b>RESULT</b>After roasting with vinegar, the total lactone content in E. ebracteolata was reduced from 0.60 to 0.45 mg x g(-1) , with active constituents, jolkinolide B and jolkinolide C, increased to varying degrees. The established chromatographic fingerprint contained risk information and could reflect the overall variation regularity of chemical constituents after roasting with vinegar.</p><p><b>CONCLUSION</b>The chemical constituents of E. ebracteolata show significantly changes, especially a reduced toxicity, after roasting with vinegar. The increase in its efficacy may be related to the variation of these constituents.</p>

Effect of Zingiber offiicinale and Aconitum cainichaeli before and after compatibility on contents of four gingerols / 中国中药杂志

<p><b>OBJECTIVE</b>To discuss the synergistic mechanism of compatible use of two medicinal herbs, Zingiber offiicinale and Aconitum cainichaeli, by determining single decoction of Z. offiicinale and four gingerols (6-gingerol, 8-gingerol, 6-shogaol, 10-gingerol) contained in compound decoction of Z. offiicinale and A. cainichaeli of different compatibility ratio using HPLC.</p><p><b>METHOD</b>Kromasil-C18 column (4.6 mm x 250 mm, 5 microm) was adopted. The mobile phase was acetonitrile (B) and 0.1% aqueous acetic acid (A) for gradient elution (0-30 min, 40%-90% B; 30-35 min, 90%-40% B). The flow rate was 1.0 mL x min(-1). The detection wavelength was set at 275 nm. The column temperature was 30 degrees C.</p><p><b>RESULT</b>The four gingerols were in baseline separation, with a good linearity (r > 0.999), an average recovery of 100.9% -103.5% and RSD < 3.0%. Compared with the single decoction of Z. offiicinale, the content of gingerols in the compound decoction of Z. offiicinale and A. cainichaeli was on the rise and in direct proportion with the increase in the volume of A. cainichaeli.</p><p><b>CONCLUSION</b>The synergistic mechanism of the compatibility of Z. offiicinale and A. cainichaeli can be proved with the increased release of gingerols from Z. offiicinale.</p>

Simultaneous determination of three steroidal alkaloids from Solanum Nigrum by RP-HPLC / 中国中药杂志

<p><b>OBJECTIVE</b>A new method for simultaneous determination of solasonine (1), solamargine (2) and khasianine (3) in Solanum Nigrum by reversed-phase HPLC was developed.</p><p><b>METHOD</b>The samples were separated at 30 degrees C on Agilent Zorbax SB C18 (4.6 mm x 150 mm, 5 microm) column with acetonitrile-water-phosphoric as mobile phase. Flow rate was 1.0 mL x min(-1) and the detection wavelength was 205 nm.</p><p><b>RESULT</b>There was good linearity between the peak area and concentration at the ranges of 0.860-10.320 microg (r = 0.999 7), 0.726-8.710 microg (r = 0.999 7), 0.856-10.270 microg (r = 0.999 7) for 1, 2 and 3 respectively. The average recoveries of 1, 2 and 3 were 101.04%, 99.65%, 100.17%.</p><p><b>CONCLUSION</b>The method is rapid, simple and accurate, and it can be used for the evaluation of Solanum Nigrum L.</p>

Analysis of harmful heavy metals, sulfur and main trace elements from Paeoniae Radix Alba before and after sulfur-fumigated process by ICP-AES method / 中国中药杂志

<p><b>OBJECTIVE</b>To analyze the contents of harmful heavy metals, sulfur and trace elements from Paeoniae Radix Alba before and after sulfur-fumigated process.</p><p><b>METHOD</b>Samples were pretreated by wet digestion and then subjected to elements analysis by inductively coupled plasma-atomic emission spectrometry (ICP-AES).</p><p><b>RESULT</b>The contents of Cu and S elements were increased, while the content of Zn element was decreased in Paeoniae Radix Alba after sulfur-fumigated process compared with the samples dried in the sun. Moreover, heavy metallic elements, such as As and Hg, were detected in Paeoniae Radix Alba after sulfur-fumigated process.</p><p><b>CONCLUSION</b>Sulfur fumigated process may cause residual of heavy metals and sulfur which are harmful to human body and change the contents of some trace elements.</p>

Effects of glycyrrhiza extract on pharmacokinetics property of daphnetin in rats / 中国中药杂志

<p><b>OBJECTIVE</b>To research the influence of glycyrrhiza extract on the pharmacokinetics characteristic parameters of daphnetin, which was aimed to explore the rationality of concert application of drugs.</p><p><b>METHOD</b>The rats received intragastric administration of daphnetin and glycyrrhiza extract containing the same daphnetin respectively. The blood concentration of daphnetin was assayed by LC-MS. The data was processed by program DAS2.1.1.</p><p><b>RESULT</b>Glycyrrhiza extract can reduce the t(1/2), tmax and Ke of daphnetin, while increased the Ka and AUC(0-infinity).</p><p><b>CONCLUSION</b>Glycyrrhiza extract promoted the oral absorption of daphnetin, slowed down the elimination and increased the biological availability.</p>

Pharmacokinetics of brucine in rats after intravenous administration of liposomes containing total alkaloids from seed of Strychnos nux-vomica / 中国中药杂志

<p><b>OBJECTIVE</b>To compare the pharmacokinetic characteristics of brucine following intravenous administration of liposomes, containing total alkaloids from seed of Strychnos nux-vomica, to rats with different phospholipids composition.</p><p><b>METHOD</b>Liposomes containing the total alkaloids were prepared by the method of ammonium sulfate transmembrane gradients and stealth liposome technique. The contents of total alkaloids and brucine in liposomes were determined and compared after free drug being removed. After intravenous administration of total alkaloids solution or liposomes with different composition, plasma samples were drawn at predetermined time points and the concentrations of brucine were determined by a validated method of HPLC. Pharmacokinetic analysis was performed by 3P97 program.</p><p><b>RESULT</b>The ratios of brucine to total alkaloids in liposomes hardly varied with phospholipids composition. Compared with SPC liposome, AUC of brucine was increased 13.3-fold and apparent volume of distribution was decreased to only 3.6% following intravenous administration of HSPC liposome. In addition, besides that AUC of brucine was slightly increased, most pharmacokinetic parameters were not significantly changed after administration of the novel liposome compared with those of SPC liposome.</p><p><b>CONCLUSION</b>Phospholipids composition has a significant influence on the pharmacokinetics of brucine after intravenous administration of liposomes containing total alkaloids from seed of S. nux-vomica.</p>

Study on apoptosis of SMMC-7721 hepatocarcinoma cells induced by Oxytropis falcata and its preliminary mechanism / 中国中药杂志

<p><b>OBJECTIVE</b>To examine apoptosis of SMMC-7721 hepatocarcinoma cells induced by total flavonoids of Oxytropis falcata (TFOF) and its preliminary mechanism.</p><p><b>METHOD</b>SMMC-7721 cells were treated for 24 h with TFOF in different concentrations. Inhibition on proliferation of SMMC-7721 cells was assessed by MTT assay. The morphology of treated SMMC-7721 cells was observed by optical microscope. Effect of TFOF on the nuclear morphology of cells was analyzed using Hoechst 33258 staining by fluorescence microscope. Annexin V-FITC/PI staining and flow cytometric measurement were used for investigating the effect of TFOF on induction of apoptosis in SMMC-7721 cells and cell cycle analysis.</p><p><b>RESULT</b>The results of MTT assay showed that TFOF could induce cytotoxicity in SMMC-7721 cells in a dose-dependent manner. Hoechst 33258 staining analysis indicated that TFOF caused typical characteristics of apoptotic programmed cell death, such as cell shrinkage, apoptotic body formation etc. Flow cytometric analysis demonstrated that TFOF caused a dose-dependent apoptosis of SMMC-7721 cells and arrested cell cycle in G1 phase.</p><p><b>CONCLUSION</b>It suggested that TFOF inhibit proliferation of SMMC-7721 cells by inducing apoptosis of the cells and arresting cell cycle in G1 phase.</p>

Effects of different excipients on properties of Tongsaimai mixture and pellet molding / 中国中药杂志

<p><b>OBJECTIVE</b>To study preliminarily on the relationship between properties of the mixture composed of Tongsaimai extract and different excipients and pellet molding.</p><p><b>METHOD</b>The multivariate regression analysis was used to investigate the correlation of different mixture and pellet molding by measuring the cohesion, liquid-plastic limit of mixture, and the powder properties of pellets. The weighted coefficients of the powder properties were determined by analytic hierarchy process combined with criteria importance through intercriteria correlation.</p><p><b>RESULT</b>The results showed that liquid-plastic limit seemed to be a major factor, which had positive correlation with pellet molding, while cohesion had negative correlation with pellet molding in the measured range.</p><p><b>CONCLUSION</b>The physical properties of the mixture has marked influence on pellet molding.</p>

Determination and comparison of plasma protein binding rate of alkaloids from seed of Strychnou nux-vomica / 中国中药杂志

<p><b>OBJECTIVE</b>To determine the plasma protein binding rates of brucine and strychnine in total alkaloids from the seed of Strychnou nux-vomica, and make comparison with the single components at the same concentration.</p><p><b>METHOD</b>Ultrafiltration was employed to determine the rat the plasma protein binding rate of the alkaloids from the seed of S. nux-vomica. The plasma concentrations were measured by RP-HPLC.</p><p><b>RESULT</b>The protein binding rates of brucine were (65.60 3.01)%, (68.20 +/- 7.80)%, (59.58 +/- 3.78)% when the plasma concentrations was 0.520, 1.300, 2.600 mg x L(-1), respectively. The protein binding rates of strychnine was (66.17 +/- 6.36)%, (67.10 +/- 2.52)%, (57.21 +/- 0.79)% when the plasma concentrations were 0.936, 2.340, 4.680 mg x L(-1) respectively. As to the total alkaloids from the seed of S. nux-vomica, The protein binding rate of brucine was (62.19 +/- 2.45)%, (69.55 +/- 5.84)%, (61.76 +/- 3.68)% when the plasma concentrations were 0.519, 1.288, 2.607 mg x L(-1), respectively. And the protein binding rates of strychnine were (54.79 +/- 3.55)%, (57.13 +/- 4.49)%, (59.31 +/- 3.65)% when the plasma concentrations were 0.940, 2.338, 4.674 mg x L(-1), respectively.</p><p><b>CONCLUSION</b>Brucine and strychnine have medium capacity in binding to plasma protein. In comparison with the single component of the same concentration, the protein binding rate of brucine in total alkaloids shows little difference, while there seems to be an obvious decrease for strychnine.</p>