Journal of Chinese Pharmaceutical Sciences

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2010, 19(2): 83-86.

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Development of Hong Kong Chinese Materia Medica (HKCMM) standards

Hu-Biao Chen^*, Tao Yi

2010, 19(2): 87-94.

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The development of HKCMM standards is one of the achievements of developing Hong Kong into an international centre for Chinese medicine. In order to enable more people concerned to have an intimate knowledge of this standard, the author was invited to introduce the development of HKCMM standards to readers, including: 1) the history of the project and the basis for legislative supports; 2) the composition and operation of the regulatory division, the research institution and the evaluation committee; 3) the progress of HKCMM standards; 4) the contents and features of HKCMM standards.

Chemical ingredients isolated from the aerial parts of Artemisia anomala

Ke Zan, Xiao-Qing Chen, Qiang Fu, Si-Xiang Zhou, Mei-Tian Xiao, Jing Wen, Peng-Fei Tu^*

2010, 19(2): 95-99.

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Fourteen known compounds were isolated from the aerial parts of Artemisia anomala and identified as follows: zhepiresinol (1), (-)-lariciresinol (2), ficusal (3), medioresinol (4), (+)-syringaresinol (5), 1β,2β-epoxy-3β,4α,10α-trihydroxyguaian-6α,12-olide (6), 5β,10α-dihydroxy-1αH-dehydroleucodin (7), 3α-chloro-8α-acetoxy-4β,10α-dihydroxy-1β,2β-epoxy-5α,7αH-guai-11(13)-en-12,6α-olide (8), 13-O-desacetyleudesma-afraglaucolide (9), 1,10-seco-4ξ-hydroxy-muurol-5-ene-1,10-diketone (10), 1α-hydroxyafraglaucolide (11), aurantiamide (12), indole-3-aldehyde (13), loliolide (14). All these compounds were isolated from this plant for the first time and compounds 1–4, 8, 10, 13 were obtained from genus Artemisia for the first time.

Isolation and structural elucidation of an unstable isoflavonoid glycoside malonate from Radix hedysari

Yi Liu, Yu-Ying Zhao, Hu-Biao Chen, Qing-Ying Zhang^*

2010, 19(2): 100-103.

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Based on the stability results of Radix hedysari extract, an unstable compound was extracted using acidic methanol and purified by rapid chromatographic methods successfully from Radix hedysari for the first time guided by HPLC analysis. Its structure was identified as formononetin 7-O-β-D-(6''-O-malonyl)-glucopyranoside by spectroscopic analyses.

Reversed-phase high-performance liquid chromatographic analysis of seven pairs of chiral drug enantiomers in transport medium after chiral derivatization

Ying He, Xiao-Juan Chai, Su Zeng^*

2010, 19(2): 104-109.

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A reversed-phase high-performance liquid chromatographic (RP-HPLC) method was established for the determination of the enantiomers of 7 aryloxy aminopropanol drugs (atenolol, sotalol, celiprolol, carvedilol, metoprolol, propranolol and propafenone) in transport medium. The method involved liquid-liquid extraction of chiral drugs from transport medium, and employed 2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl isothiocyanate (GITC, 1.0 mg/mLin acetonitrile) as a pre-column chiral derivatization reagent. After derivatization, the products were separated on an Agilent Zorbax C8 column (150 mm×4.6 mm, 5 µm) at 25 °C. The mobile phase consisted of a mixture of acetonitrile and 0.01 M phosphate buffer (pH 3.5). The present methods were specific for the determination of enantiomers of each chiral drug. The absolute recoveries of the enantiomers and internal standards were >78%. The relative recoveries of the enantiomers were approximately 100%. The intra- and inter-day variations were <15%. The method was reproducible and sufficiently sensitive to determine the enantiomers of seven aryloxy aminopropanol drugs in transport medium. The method could be used to study the transport of atenolol, sotalol, celiprolol, carvedilol, metoprolol, propranolol and propafenone.

Preparation and evaluation of sinomenine hydrochloride patch

Xin-Ru Li, Yan-Qing Huang, Xiao-Yan Li, Yan-Xia Zhou, Yan Liu^*, Ming Guo, Qing-Fen Zhu, Yuan-Chao Xie, Zhi-Yun Fan

2010, 19(2): 110-114.

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The sinomenine hydrochloride (SH) patch, a topical drug delivery system, was prepared and characterized. The in vitro release was studied according to the paddle-over-disk method in the appendix of Chinese Pharmacopeia (appendix XD, 2005). Stability of SH patch was evaluated at accelerated testing conditions (40 °C, 75% RH). Pharmacological and pharmacokinetics study were also performed. It was found that the release of SH from patches depended on pH value of the release medium. There were no significant differences between SH patches stored for 6 mon and those stored for 0 mon in the drug content, initial adhesion, lasting stickiness, peeling strength and in vitro release. SH patches exhibited better anti-inflammatory activity as well as analgesic efficacy. More importantly, primary pharmacokinetic parameters of SH patch, such as Cmax and AUC, were much lower than those of SH solution dosed orally. In conclusion, the patch might be a promising delivery system for SH, which bypassed the gastrointestinal tract and was a convenient, efficacious, safe and non-invasive delivery method.

Vasorelaxant effect of 7-[2-(4-morpholinyl)ethoxy] chroman hydrochloride (HEF-04) and possible mechanisms

Bing Wang, Shou-Ting Fu^*, Chun Hu, Lan Zhu, Yuan-Yuan Wei

2010, 19(2): 115-119.

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This study aimed to investigate the relaxant effect of chroman compound HEF-04 on isolated vascular smooth muscle (VSM) and the possible underlying mechanisms involved. Isolated rabbit thoracic aorta was used as the in vitro model and the relaxant effects of HEF-04 on endothelium-intact (+EC) and endothelium-denuded (-EC) thoracic aortic rings were compared. Potassium channel blockers, guanylate cyclase inhibitors, and COX-inhibitors were used to explore associations between the relaxant effects of HEF-04 with potassium channels, NO, and prostaglandin-like substances and endothelial hyperpolarizing factor (EDHF), respectively. The results indicated that HEF-04 (1×10^–5 mol/L to 3×10^–3mol/L) had no significant impact on basal vascular tension, but could relax the contraction of vascular smooth muscle caused by high-K⁺ solution in a dose-dependent manner. Indomethacin (5.6×10^–6mol/L) had no effect on vasorelaxation effect of HEF-04. In contrast, the vasorelaxant effect of HEF-04 was enhanced by methylene blue, which was significantly inhibited by calcium-dependent potassium channel blocker TEA. The vasorelaxant effect of HEF-04 on +EC thoracic aortic rings was significantly stronger than that on -EC thoracic aortic rings. The endothelium dependent relaxant effect of HEF-04 on VSM might be attributed to the interaction of HEF-04 with vascular relaxing factors or the increased release of EDHF.

Cyclovirobuxine D inhibits blood coagulation and venous thrombosis

Xiu-Mei Liu, Xiao-Yan Liu, Yin-Ye Wang^*, Shi-Zhong Chen

2010, 19(2): 120-124.

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Cyclovirobuxine D (CVB-D) is a compound extracted from Chinese traditional plant Buxus microphylla, which has been used for treating arrhythmia and myocardial ischemia in China. In this study, we investigated its effect on blood coagulation and thrombotic formation in mouse and rat models. The doses of CVB-D used in this study (5-20 mg/kg) prolonged clotting time (CT) in a dose-dependent manner (P<0.01). It also significantly prolonged thrombin time (TT), prothrombin time (PT) and activated partial thromboplast time (aPTT) (P<0.05 or P<0.01) at the doses of 10-20 mg/kg. CVB-D did not affect the bleeding time (BT) compared with the control group, while warfarin significantly prolonged the bleeding time. CVB-D at the doses of 5-20 mg/kg reduced wet weight of thrombosis (P<0.01). This study demonstrated the anti-coagulation effect and anti-thrombosis effect of orally administered CVB-D without substantially increasing bleeding. These findings suggest that CVB-D probably can be used as an oral anti-coagulant in addition to its current applications.

Influence of different intravenous injection containers on residual liquid volume and its economic impact

Xin Zhou, Li-Hua Chen, Suo-Di Zhai^*

2010, 19(2): 125-129.

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The objective of this study was to evaluate the influence of infusion container design on the volume of residual drug solution following use in a clinical setting. 0.9% (w/v) NaCl infusion solution containers (5 types, each of three capacities: 100 mL, 250 mL and 500 mL) following clinical use for in-patients at Peking University Third Hospital were collected during Sept. and Oct. 2007. The volume of residual drug solution was determined. Hospital pharmacy records were used to determine the potential economic implications of discarding residual drug solutions. The mean residual volumes ranged from 0.38 mL to 4.80 mL and, in general, residual volume increased with increasing container capacity. The residual volumes for one type of double-port soft bag were significantly lower than the residual volumes for all other containers of the same capacity (P<0.05), including glass and semi-rigid plastic bottles. Highest residual volumes were observed for the single-port soft bag. Estimates of the value of discarded residual drug solution ranged from approximately US $15,000 to US $150,000 per annum in our hospital. Infusion container design has a major influence on residual drug solution volumes following intravenous infusion. Appropriate choice of bag design remains an important consideration for the economics and efficacy of infusion treatment in Chinese hospitals.

A study of the impact of pharmaceutical care on medication compliance in asthmatic children

Xiao-Hui Xie, Li-Hua Hu, Xiao-Ling Wang, Lu-Wen Shi, Li Xiang^*

2010, 19(2): 130-135.

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The objective of the study is to study the impact of pharmaceutical care on medication compliance in asthmatic children. The results will be used to further develop the pharmaceutical care delivered by pharmacists for asthmatic children, and to promote children's asthma control in China. The study was conducted in outpatient department of Beijing Children's Hospital from Mar. to Sept., 2009. Asthmatic children (101) were randomly divided into two groups: the intervention group that received routine treatment and complete pharmaceutical care provided by pharmacists and the control group that received routine treatment only. Questionnaires were distributed to both groups and responses were analyzed statistically. Our results showed that the percentage of children using medication following doctor's instructions in the intervention group was significantly higher than that in the control group (66.67% and 36.00%, respectively); the percentage of children correctly using inhaler devices in the intervention group was significantly higher than that in the control group (78.26% and 32.84%, respectively); children and care givers of the intervention group had significantly more knowledge about medication compliance. In conclusion, the pharmaceutical care provided by pharmacists could improve medication compliance of asthmatic children, and it would be desirable to further develop the pharmaceutical care for asthmatic children across China.

Synthesis of 3-(4-hydroxyphenyl)-4-methyl-6-methoxy-7-hydroxycoumarin and its analogues as angiogenesis inhibitors

Hao Zou, Hao Jiang, Jie-Yun Zhou, Yan Zhu^*, Lin Cao, Peng Xia, Qian Zhang^*

2010, 19(2): 136-140.

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3-(4-Hydroxyphenyl)-4-methyl-6-methoxy-7-hydroxycoumarin (2a) and its analogues with different substituents at the p-position of 3-phenyl group were designed and synthesized as the non-steroidal analogues of 2-methoxyestradiol (2-ME 1). The desired compounds were synthesized via a novel and simple route and the effects of specific substituents on their anti-angiogenesis activities were investigated with Human umbilical vein endothelial cells (HUVECs) proliferation assays. Preliminary biological screening showed that compounds 2a and 2d (IC50 = 61.0 and 76.7 μM, respectively) have potential anti-angiogenesis activities. The bulk of the group at the p-position of 3-phenyl group likely play an important role in their activities.

Efficient synthesis of ethyl 4-[N-methyl-N-(2,3-aziridinyl)amino]benzoate and diethyl N-{4-[N-methyl-N-(2,3-aziridinyl)amino]benzoyl}-L-glutamate

Xi-Ling Deng, Zhi-Li Zhang, Xiao-Wei Wang, Jun-Yi Liu^*

2010, 19(2): 141-145.

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Aziridine and its N-substituted derivatives could undergo nucleophilic ring opening reaction with biological molecules, leading to their alkylation and the loss of their biological activities. For this purpose, ethyl 4-[N-methyl-N-(2,3-aziridinyl)amino]benzoate and diethyl N-{4-[N-methyl-N-(2,3-aziridinyl)amino]benzoyl}-L-glutamate, as the key intermediates in the synthesis of new anticancer agents, were designed and synthesized via four steps of reactions in good yields.

Study on the iodination of uracil derivatives

Li Li, Hua Qin, Liang Zhang, Xiao-Wei Wang, Jun-Yi Liu^*

2010, 19(2): 146-150.

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5-Iodouracil derivatives have interesting biological activities and can serve as important substrates for the metal-catalyzed cross-coupling reactions to introduce alkyl, alkenyl, and alkynyl groups to the C-5 position of uracil derivatives. In order to find a good method to iodinate directly the C-5 of uracil derivatives, we investigated three methods, which included iodine/lead (IV) dioxide, iodine/ammonium hexanitratocerate (CAN) and iodine chloride, and examined their reactivity to different types of uracil and thiouracil derivatives.

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Journal of Chinese Pharmaceutical Sciences

2010, 19(2): 151-158.

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