To compare the efficacy of two kinds of Zhizhu pills in the treatment of functional dyspepsia of spleen-deficiency and qi-stagnation syndrome:a randomized group sequential comparative trial

<p>Abstract</p> <p>Background</p> <p>In Traditional Chinese Medicine (TCM) theory, functional dyspepsia (FD) can be divided into different syndromes according to different clinical symptoms and signs, and the most common one is spleen-deficiency and qi-stagnation syndrome that can be treated by Chinese traditional patent medicine ---- two kinds of Zhizhu pills, between which the primary difference in ingredients is that one contains immature orange fruit of Citrus aurantium L.(IFCA) and the other contains that of Citrus sinensis Osbeck (IFCS). The trial's objective was to compare the efficacy of two kinds of Zhizhu pills on symptom changes in patients with FD of spleen-deficiency and qi-stagnation syndrome.</p> <p>Methods</p> <p>A randomized, group sequential, double-blinded, multicenter trial was conducted in patients with FD of spleen-deficiency and qi-stagnation syndrome at 3 hospitals in Beijing between June 2003 and May 2005. Participants were randomly allocated into two groups (IFCA group and IFCS group) in a 1:1 ratio, and respectively took one of the two kinds of Zhizhu pills orally, 6 g each time, 3 times a day, for 4 weeks. Statistical analysis was performed with use of a group sequential method, the triangular test (TT).</p> <p>Results</p> <p>A total of 163 patients were randomized, and 3 patients were excluded from analysis because of early dropouts, leaving 160 patients (IFCA group: n = 82; IFCS group: n = 78) for statistical analysis. Three interim analyses were done after 62, 116, and 160 patients had completed their 4-week treatment, respectively. At the third interim analysis, the sample path crossed the upper boundary and the trial was stopped, the cure-markedly effective rates were 45% for IFCS group and 67% for IFCA group, respectively, the one-sided <it>p</it>-value was 0.0036, the median unbiased estimate of the odds ratio (OR) for the benefit of IFCA relative to IFCS was 2.91 with 95%CI: 1.40 to 6.06.</p> <p>No adverse events were observed in the two groups.</p> <p>Conclusions</p> <p>Zhizhu pills containing IFCA was superior to Zhizhu pills containing IFCS in the treatment of FD of spleen-deficiency and qi-stagnation syndrome. The application of group sequential analysis in clinical trials of TCM may offer some financial and ethical benefits.</p> <p>Trial Registration</p> <p>Chinese Clinical Trial Registry (ChiCTR): ChiCTR-TRC-00000485</p

Tannin extracts from immature fruits of Terminalia chebula Fructus Retz. promote cutaneous wound healing in rats

<p>Abstract</p> <p>Background</p> <p>Tannins extracted from immature fruits of <it>Terminalia chebula Fructus Retz</it>. are considered as effective components promoting the process of wound healing. The objective of this study is to explore the optimal extraction and purification technology (OEPT) of tannins, while studying the use of this drug in the treatment of a cutaneous wound of rat as well as its antibacterial effects.</p> <p>Methods</p> <p>The content of tannin extracts was measured by the casein method, and antibacterial ability was studied by the micro-dilution method in vitro. In wound healing experiment, animals in group Ⅰ, Ⅱ and Ⅲ were treated with vaseline ointment, tannin extracts (tannin content: 81%) and erythromycin ointment, respectively (5 mg of ointment were applied on each wound). To evaluate the process of wound healing, selected pharmacological and biochemical parameters were applied.</p> <p>Results</p> <p>After optimal extraction and purification, content of tannin extracts was increased to 81%. Tannin extracts showed the inhibition of <it>Staphylococcus aureus </it>and <it>Klebsiella Pneumonia </it>in vitro. After excision of wounds, on days 7 and 10, the percent of wound contraction of group Ⅱ was higher than that of group Ⅰ. After being hurt with wounds, on days 3, 7, and 10, the wound healing quality of group Ⅱ was found to be better than that of group Ⅰ in terms of granulation formation and collagen organization. After wound creation, on day 3, the vascular endothelial growth factor expression of group Ⅱ was higher than that of group Ⅰ.</p> <p>Conclusion</p> <p>The results suggest that tannin extracts from dried immature fruits of <it>Terminalia chebula Fructus Retz</it>. can promote cutaneous wound healing in rats, probably resulting from a powerful anti-bacterial and angiogenic activity of the extracts.</p

Molecular Characterisation of Long-Acting Insulin Analogues in Comparison with Human Insulin, IGF-1 and Insulin X10

AIMS/HYPOTHESIS: There is controversy with respect to molecular characteristics of insulin analogues. We report a series of experiments forming a comprehensive characterisation of the long acting insulin analogues, glargine and detemir, in comparison with human insulin, IGF-1, and the super-mitogenic insulin, X10. METHODS: We measured binding of ligands to membrane-bound and solubilised receptors, receptor activation and mitogenicity in a number of cell types. RESULTS: Detemir and glargine each displayed a balanced affinity for insulin receptor (IR) isoforms A and B. This was also true for X10, whereas IGF-1 had a higher affinity for IR-A than IR-B. X10 and glargine both exhibited a higher relative IGF-1R than IR binding affinity, whereas detemir displayed an IGF-1R:IR binding ratio of ≤ 1. Ligands with high relative IGF-1R affinity also had high affinity for IR/IGF-1R hybrid receptors. In general, the relative binding affinities of the analogues were reflected in their ability to phosphorylate the IR and IGF-1R. Detailed analysis revealed that X10, in contrast to the other ligands, seemed to evoke a preferential phosphorylation of juxtamembrane and kinase domain phosphorylation sites of the IR. Sustained phosphorylation was only observed from the IR after stimulation with X10, and after stimulation with IGF-1 from the IGF-1R. Both X10 and glargine showed an increased mitogenic potency compared to human insulin in cells expressing many IGF-1Rs, whereas only X10 showed increased mitogenicity in cells expressing many IRs. CONCLUSIONS: Detailed analysis of receptor binding, activation and in vitro mitogenicity indicated no molecular safety concern with detemir

A systematic review of the use of dosage form manipulation to obtain required doses to inform use of manipulation in paediatric practice

This study sought to determine whether there is an evidence base for drug manipulation to obtain the required dose, a common feature of paediatric clinical practice. A systematic review of the data sources, PubMed, EMBASE, CINAHL, IPA and the Cochrane database of systematic reviews, was used. Studies that considered the dose accuracy of manipulated medicines of any dosage form, evidence of safety or harm, bioavailability, patient experience, tolerability, contamination and comparison of methods of manipulation were included. Case studies and letters were excluded. Fifty studies were eligible for inclusion, 49 of which involved tablets being cut, split, crushed or dispersed. The remaining one study involved the manipulation of suppositories of one drug. No eligible studies concerning manipulation of oral capsules or liquids, rectal enemas, nebuliser solutions, injections or transdermal patches were identified. Twenty four of the tablet studies considered dose accuracy using weight and/or drug content. In studies that considered weight using adapted pharmacopoeial specifications, the percentage of halved tablets meeting these specifications ranged from 30% to 100%. Eighteen studies investigated bioavailability, pharmacokinetics or clinical outcomes following manipulations which included nine delayed or modified release formulations. In each of these nine studies the entirety of the dosage form was administered. Only one of the 18 studies was identified where drugs were manipulated to obtain a proportion of the dosage form, and that proportion administered. The five studies that considered patient perception found that having to manipulate the tablets did not have a negative impact on adherence. Of the 49 studies only two studies reported investigating children. This review yielded limited evidence to support manipulation of medicines for children. The results cannot be extrapolated between dosage forms, methods of manipulation or between different brands of the same drug

From Scutellaria barbata to BZL101 in Cancer Patients: Phytochemistry, Pharmacology, and Clinical Evidence

Scutellaria barbata D.Don is a popular Chinese medicinal plant documented to treat cancer patients in traditional Chinese medicine (TCM). A botanical new investigational drug for breast cancer BZL101 (FDA IDN# 59521) was previously developed in the United States from the aqueous extract of the aerial parts from S. barbata. The early phase 1A and 1B clinical trials show its favorable toxicity profiles, good clinical tolerance, and promising efficacy for patients with metastatic breast cancer. To further evidence the phytopharmacology research, drug development, and anticancer use of this herb, a systematic literature review was performed herein on the phytochemistry, pharmacology, and specifically anticancer clinical evidence. A systematic review of the literature on phytochemical and pharmacological properties of the plant related to cancer treatment employed several web-based scientific databases including Wanfang (Chinese), Pubmed, Web of Science, and Elsevier. Key words included Scutellaria barbata, Ban Zhi Lian, cancer, and tumor. Based on critical quality criteria, only 8 out of 69 reports related to clinical studies of cancer patients in China. This review covered the available literature up to July 2019. The anticancer effects of S. barbata can be explained by the presence of various flavonoids and diterpenoids alkaloids. The underlying mechanisms are primarily summarized as cyclin/cyclin-dependent kinase (CDK)-modulated cell cycle arrest and mitochondria-mediated apoptotic death. The highly cancer-cell selective cytotoxicity and detoxifying effects of S. barbata contribute to a favorable clinical profile and enhanced quality of life for the cancer patient, thereby demanding further study as an adjuvant or alternative to conventional chemotherapy. The phytochemical and pharmacological studies reviewed strongly underpin a fundamental understanding of the anticancer activity of S. barbata and support ongoing clinical trials. The further safety verification and clinical trials are expected to progress S. barbata-based development to finally transform the traditional TCM herb S. barbata to the valuable anticancer drug

Transcriptome analysis of Bupleurum chinense focusing on genes involved in the biosynthesis of saikosaponins

<p>Abstract</p> <p>Background</p> <p><it>Bupleurum chinense </it>DC. is a widely used traditional Chinese medicinal plant. Saikosaponins are the major bioactive constituents of <it>B. chinense</it>, but relatively little is known about saikosaponin biosynthesis. The 454 pyrosequencing technology provides a promising opportunity for finding novel genes that participate in plant metabolism. Consequently, this technology may help to identify the candidate genes involved in the saikosaponin biosynthetic pathway.</p> <p>Results</p> <p>One-quarter of the 454 pyrosequencing runs produced a total of 195, 088 high-quality reads, with an average read length of 356 bases (NCBI SRA accession SRA039388). A <it>de novo </it>assembly generated 24, 037 unique sequences (22, 748 contigs and 1, 289 singletons), 12, 649 (52.6%) of which were annotated against three public protein databases using a basic local alignment search tool (E-value ≤1e-10). All unique sequences were compared with NCBI expressed sequence tags (ESTs) (237) and encoding sequences (44) from the <it>Bupleurum </it>genus, and with a Sanger-sequenced EST dataset (3, 111). The 23, 173 (96.4%) unique sequences obtained in the present study represent novel <it>Bupleurum </it>genes. The ESTs of genes related to saikosaponin biosynthesis were found to encode known enzymes that catalyze the formation of the saikosaponin backbone; 246 cytochrome P450 (<it>P450</it>s) and 102 glycosyltransferases (<it>GT</it>s) unique sequences were also found in the 454 dataset. Full length cDNAs of 7 <it>P450</it>s and 7 uridine diphosphate <it>GT</it>s (<it>UGT</it>s) were verified by reverse transcriptase polymerase chain reaction or by cloning using 5' and/or 3' rapid amplification of cDNA ends. Two <it>P450</it>s and three <it>UGT</it>s were identified as the most likely candidates involved in saikosaponin biosynthesis. This finding was based on the coordinate up-regulation of their expression with <it>β-AS </it>in methyl jasmonate-treated adventitious roots and on their similar expression patterns with <it>β-AS </it>in various <it>B. chinense </it>tissues.</p> <p>Conclusions</p> <p>A collection of high-quality ESTs for <it>B. chinense </it>obtained by 454 pyrosequencing is provided here for the first time. These data should aid further research on the functional genomics of <it>B. chinense </it>and other <it>Bupleurum </it>species. The candidate genes for enzymes involved in saikosaponin biosynthesis, especially the <it>P450</it>s and <it>UGT</it>s, that were revealed provide a substantial foundation for follow-up research on the metabolism and regulation of the saikosaponins.</p

Titanium nanoparticles (TiO2)/graphene oxide nanosheets (GO): an electrochemical sensing platform for the sensitive and simultaneous determination of benzocaine in the presence of antipyrine.

An effective electrochemical sensing platform for the simultaneous determination of benzocaine (BEN) and antipyrine (ANT) based upon titanium dioxide nanoparticle (TiO2)/graphene oxide nanosheet (GO) bulk modified carbon paste electrodes (TiO2-GO/CPE) is reported. The TiO2-GO/CPE electrochemical sensing platform is found to exhibit linear ranges from 1.0 × 10-6 to 1.0 × 10-4 M and 1.2 × 10-8 to 8.0 × 10-5 M for BEN and ANT, respectively. The TiO2-GO/CPE sensor is explored towards the analysis of BEN and ANT in oral fluid (saliva) and pharmaceutical products. The synergy between the graphene oxide nanosheets and titanium dioxide nanoparticles results in a dramatic enhancement in the sensitivity of the sensor through a combination of increased surface area and improved electron transfer kinetics compared to other electrode alternatives. The fabricated TiO2-GO/CPE exhibits high sensitivity and good stability towards the sensing of BEN and ANT and has the potential to be utilised as a clinical assay and QA in pharmaceutical products

Mixed solvent system as binder for the production of silicified microcrystalline cellulose-based pellets

ABSTRACT: Silicified microcrystalline cellulose pellets with hydroxypropyl methylcellullose (HPMC) as modifier were prepared using a mixed solvent as liquid binder. Pellets were produced using extrusion-spheronization with a mixed solvent consisting of water and isopropanol as liquid binder. The key spheronization aid was Prosolv® SMCC 90. Low viscosity grade HPMC was incorporated aiming to modify release of indometacin. Physical characteristics including breaking load, apparent density and flow properties, particle size distribution and shape were determined. Drug loaded pellets were also tested for dissolution profiles. By adjusting liquid binder property, at isopropanol to water ratio of 3.5 to 6.5, pellets of desirable size and shape with reasonable yields were obtained. Pellets exhibited good flow property and they were mechanically strong. Pellet with higher HPMC content displayed a faster drug dissolution profile. This was because low viscosity grade HPMC was not enough to create strong gel. Instead hydration of HPMC molecules increased matrix’s hydrophilicity and weakened the structure of pellet faster. The release of indometacin was partly based on the erosion of hydrated matrix. The presence of HPMC in the pellets would require a mixed solvent to produce desirable shape. Incorporation of HPMC had modified drug release from the pellets without further coating. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 47924