Combinative Approaches of Chemistry, Pharmacology and Toxicology for the Optimal Pharmaceutical Preparation of an Anti-arthritic Chinese Medicine Formulation QFJBT

Objective Qing Fu Juan Bi Tang(QFJBT)is an anti-arthritic Chinese medicine formula consisting of five herbs:Aconiti Lateralis Radix Praeparata(Fu Zi,附子),Sinomenii Caulis(Qing Feng Teng,青风藤),Astragali Radix(Huang Qi,黄芪),Paeoniae Radix Alba(Bai Shao,白芍)and Moutan Cortex(Mu Dan Pi,牡丹皮),which have well-established histories of use for treatment of rheumatic and arthritic diseases.We intended to establish the optimized and standardized pharmaceutical procedures and manufacturing processes for the pilot production of QFJBT to develop it as a novel botanical drug product for treatment of rheumatoid arthritis(RA).Methods The combinative approaches of chemical assessment,toxicological and pharmacological evaluation were explored to define the pharmaceutical preparation of QFJBT.Results The optimized and standardized pharmaceutical procedures and manufacturing processes for the pilot production of QFJBT were established in terms of greatest chemical contents of bioactive constituents,potent anti-inflammatory and antinociceptive activities,and favorable safety profile.Quality analysis of the pilot product of QFJBT by high-performance liquid chromatography(HPLC)demonstrated that the chromatographic fingerprint profiles of three batches of QFJBT were basically identical and the contents of four characteristic and bioactive markers were relatively consistent.General toxicological studies showed a favorable safety profile of QFJBT.The maximum tolerated single dose of QFJBT was determined in both sexes of rats to be 33.63 g/kg body weight which is equivalent to 346 times of clinical dose.In the chronic oral toxicity study,the results of laboratory investigation showed that QFJBT at doses of 3.89,6.80 and 9.72 g/kg body weight(equivalent to 40,70 and 100-fold clinical doses,respectively)caused no changes in all hematological parameters and blood biochemical parameters of rats.No mortality or specific toxic responses were observed in animals after three months of repeated dosing with QFJBT.Conclusion The optimized and standardized pharmaceutical and manufacturing processes for the production of QFJBT have been successfully screened and identified through established rigorous in-process controls.

Determination of diclofenac in pharmaceutical preparations by voltammetry and gas chromatography methods

Rapid, sensitive and specific methods were developed for the determination of diclofenac in pharmaceutical preparations by linear sweep voltammetry （LSV） and gas chromatography （GC） with mass spectrometry （MS） detection. The linearity was established over the concentration range of 5- 35 μg/mL for LSV and 0.25-5 μg/mL for GC-MS method. The intra- and inter-day relative standard deviation （RSD） was less than 4.39% and 4.62% for LSV and GC-MS, respectively. Limits of quantification （LOQ） were determined as 4.8 and 0.15 μg/mL for LSV and GC-MS, respectively. No interference was found from tablet excipients at the selected assay conditions. The methods were applied for the quality control of commercial diclofenac dosage forms to quantify the drug and to check the formulation content uniformity.

Multi-functional vesicles improve Helicobacter pylori eradication by a comprehensive strategy based on complex pathological microenvironment

Helicobacter pylori(H.pylori),creating a global infection rate over 50%,presents great challenges in clinical therapies due to its complex pathological microenvironment in vivo.To improve the eradication efficacy,herein we fabricated a pharmaceutical vesicle RHL/Cl-Ch-cal where cholesterol-PEG,calcitriol and first-line antibiotic clarithromycin were co-loaded in the rhamnolipid-composed outer lipid layer.RHL/Cl-Ch-cal could quickly penetrate through gastric mucus layer to reach H.pylori infection sites,and then effectively destroyed the architecture of H.pylori biofilms,killed dispersed H.pylori and inhibited the re-adhesion of residual bacteria(called biofilms eradication tetralogy).Moreover,RHL/Cl-Ch-cal activated the host immune response to H.pylori by replenishing cholesterol to repair lipid raft on the cell membrane of host epithelial cells.Finally,RHL/Cl-Ch-cal killed the intracellular H.pylori through recovering the lysosomal acidification and assisting degradation.In experiments,RHL/Cl-Ch-cal demonstrated prominent anti-H.pylori efficacy in the classical H.pylori-infected mice model.Therefore,the study provides a“comprehensive attack”strategy for anti-H.pylori therapies including biofilms eradication tetralogy,immune activation and intracellular bacteria killing.