Pharmacokinetics and bioequivalence of ranitidine and bismuth derived from two compound preparations

AIM： To evaluate the bioequivalence of ranitidine and bismuth derived from two compound preparations. METHODS： The bioavailability was measured in 20 healthy male Chinese volunteers following a single oral dose （equivalent to 200 mg of ranitidine and 220 mg of bismuth） of the test or reference products in the fasting state. Then blood samples were collected for 24 h. Plasma concentrations of ranitidine and bismuth were analyzed by high-performance liquid chromatography and inductively coupled plasma-mass spectrometry （ICPMS）, respectively. The non-compartmental method was used for pharmacokinetic analysis. Log-transformed Cmax, AUC（0-t） and AUC（0-∞） were tested for bioequivalence using ANOVA and Schuirmann two-one sided t-test. Tmax was analyzed by Wilcoxon＇s test. RESULTS： Various pharmacokinetic parameters of ranitidine derived from the two compound preparations, including Cmax, AUC（0-t）, AUC（0-∞）, Tmax and T1/2, were nearly consistent with previous observations. These parameters derived from test and reference drug were as follows： Cmax（0.67 ± 0.21 vs 0.68 ± 0.22 mg/L）, AUC（0-t）（3.1 ± 0.6 vs 3.0 ± 0.7 mg/L per hour）, AUC（0-∞）（3.3 ± 0.6 vs 3.2 ± 0.8 mg/L per hour）, Tmax （2.3 ± 0.9 VS 2.1 ± 0.9 h） and T1/2 （2.8 ± 0.3 vs 3.1 ± 0.4 h）. In addition, double-peak absorption profiles of ranitidine were found in some Chinese volunteers. For bismuth, those parameters derived from test and reference drug were as follows： Cmax （11.80 ± 7.36 vs 11.40 ± 6.55 μg/L）, AUC（0-t） （46.65 ± 16.97 vs 47.03 ± 21.49 μg/L per hour）, Tmax （0.50 ± 0.20 vs 0.50 ± 0.20 h） and T1/2 （10.2 ± 2.3 vs 13.0 ± 6.9 h）. Ninety percent of confidence intervals for the test/reference ratio of Cmax, AUC（0-t） and AUC（0-∞） derived from both ranitidine and bismuth were found within the bioequivalence acceptable range of 80%-125%. No significant difference was found in Tmax derived from both ranitidine and bismuth. CONCLUSION： The two compound preparations are bioequivalent and may be prescribed interchangeably.

Effects of in vitro cultivated Calculus Bovis compound on pulmonary lesions in rabbits with schistosomiasis

AIM:To explore the interventional effects and mechanism of in vitro cultivated Calculus Bovis compound preparation(ICCBco) on pulmonary lesions in portal hypertensive rabbits with schistosomiasis. METHODS:The experimental group included 20 portal hypertensive rabbits with schistosomiasis treated by ICCBco.The control group included 20 portal hypertensive rabbits with schistosomiasis treated by praziquantel. The morphological changes of the pulmonary tissues were observed under light and electron microscopy.The expression of fibronectin(FN) and laminin(LN) in the lung tissues was analyzed by immunohistochemistry. RESULTS:Under light microscope,the alveolar exudation in the lung tissue was more frequently observed in the control group,while the alveolar space was fairly dry in the lung tissue of ICCBco group.Under electron microscope,more alveolar exudation in the lung tissue,and moremacrophages,alveolar angiotelectasis and the blurred three-tier structure of alveolar-capillary barrier could be seen in the control group.In ICCBco group,fibers within the alveolar interspace slightly increased in some lung regions,and the structure of typeⅠepithelium,basement membrane and endodermis was complete,and no obvious exudation from the alveolar space,and novascular congestion could be observed.There was a positive or strong positive expression of FN and LN in the lung tissue of the control group,while there was a negative or weak positive expression of FN and LN in ICCBco group. CONCLUSION:ICCBco can effectively prevent pulmonary complications in portal hypertensive rabbits with schistosomiasis by means of improving lung microcirculation and lowering the content of extracellular matrix.

Therapeutic Efficacy of Chinese Herbal Compound Preparation on Viral Diseases in Poultry

[Objective] To develop a new antiviral agent with high and long efficacy, wide spectrum, low toxicity and low cost from traditional Chinese herbal medicine and their compound. [ Method] The ＂Quxie＂ （ i. e. eliminating pathogenic factors） drugs including Hedyotis diffusa and Loni- cera japonica and ＂Fuzheng＂ （ i. e. strengthening body resistance） drugs including Radix astragali and Glycyrrhiza uralensis were taken to form an antiviral herbal compound preparation. Taking the astragalus polysaccharide monomer as control, the experiment was constructed by using the agent to treat some naturally occurring viral diseases, including Newcastle disease （ND）, infectious bursal disease （IBD）, duck viral hepatitis （DVH）, avian influenza （Al） H9 subtype and avian swollen head syndrome. [Ressult] The effective rates of the agent for treatment of the above- mentioned diseases were 87%, 87%, 69%, 100% and 100%, respectively, which were higher than that of astragalus polysaccharide monomer. The cure rates for these diseases were 33%, 37%, 13%, 69% and 75%, respectively, which were significantly higher than that of astragalus polysacchadde monomer （ P 〈 0.01 ）. The rates of poor therapeutic efficacy were 15%, 21%, 24%, 6% and 7%, respectively, which were significantly lower than that of astragalus polysaccharide monomer （P 〈 0.01 ）. [ Condusion] The Chinese herbal compound preparation shows good therapeutic effects on some avian viral diseases, which can decrease mortality rate and improve production performance of poultry more greatly than astragalus polysaccharide monomer.

The Preparation and Application of Chitosan Compound Flocculant

[Objective]The research aimed to study preparation and application of the environment-friendly compound flocculant.[Method]Chitosan（natural biological product,CTS）,ferric sulfate[Fe2（SO4） 3]and polymeric aluminum chloride（PAC） as the main raw materials,four kinds of environment-friendly flocculants were made to conduct flocculation treatment on the domestic wastewater of Wuhan Bioengineering Institute.COD and turbidity of the wastewater as the main indicators,influences of the compound flocculant formulation,flocculant dosage and pH on flocculation effect were studied.[Result]CTS/PAC and CTS/Fe2（SO4） 3 compound flocculants had better removal rates for COD and turbidity when compared with single inorganic flocculant.The best volume ratio of CTS/PAC was 1.0：5.0.The smallest dosage of CTS/PAC in each 500 ml of water sample was 4.0 ml.When pH was 7.2,removal rates of the COD and turbidity were respectively 78.5% and 98.4%,which rose by 36.5% and 21.5% respectively than that singly using PAC.[Conclusion]CTS/PAC was a kind of ideal compound flocculant and had better application prospect.

Effects of Combinations of Two of Three Different Probiotics on Pond Water Quality

In order to provide reference for probiotics application in aquaculture, Bacillus subtilis （A）, Streptococcus faecalis （B） and photosynthetic bacteria （C） were prepared according to the ratios of 9：1, 4：1, 1：1, 1：4 and 1：9 with 10^5 cfu/ml as the unit of concentration into 15 mixed microecological preparations, and their effects on COD, ammonia nitrogen, nitrite nitrogen and sulfide in pond water were investigated. The results showed that the mixed preparation of B. subtilis and photosynthetic bacteria at a ratio of 1：4 had the best effect in treating COD （P〈0.05）, the mixed preparation of B. subtilis and S. faecalis at a ratio of 4：1 showed the best effect in treating ammonia nitrogen （P〈0.05）, the mixed preparation of S. faecalis and photosynthetic bacteria at a ratio of 4：1 showed the best effect in treating nitrite nitrogen （P〈0.05）, and the mixed preparation of Streptococcus faecalis and photosynthetic bacteria at a ratio of 9：1 had the best effect of reducing sulfide （P〈0.05）.

Herb induced liver injury by Xianling Gubao Tablets: A case assessed for causality using updated RUCAM and integrated evidence chain

Objective:A typical case of Xianling Gubao(XLGB)Tablets-induced liver injury was systematically studied in the clinic and the laboratory.Methods:A patient with herb-induced liver injury(HILI)and a history of taking XLGB Tablets before disease onset was engaged as the study subject,and the case was diagnosed according to the updated Roussel Uclaf Causality Assessment Method(RUCAM)and the integrated evidence chain(iEC)method recommended by the Guidelines for Diagnosis and Treatment of Herb-induced Liver Injury(HILI Guidelines).Results:Clinical history,biochemical indexes and imaging tests were used to exclude the influence of fundamental diseases and confusing liver diseases such as viral,alcoholic and autoimmune liver diseases on the diagnosis.Based on an investigation of the patient’s medication history,she was suspected to have HILI caused by XLGB Tablets,as the patient was only taking an oral preparation of XLGB Tablets,and the influence of other drugs on the diagnosis was excluded.This patient with alanine aminotransferase(ALT)3 upper limit of normal(ULN)and a calculated R of 6 was diagnosed with possible acute drug-induced hepatocellular injury.The relationship was considered“highly probable”(score of 9)using the updated RUCAM of 2016.Moreover,the fingerprint similarity between the preparation taken by the patient and a commercially available preparation was 0.99,suggesting that the patient was consuming XLGB Tablets rather than another drug.LC-MS technology and the Agilent Fake TCM-Drugs database were used to investigate the drug,and no chemical additions were found.Examination of the drug for pesticide residues,heavy metals,aflatoxins and other exogenous substances indicated compliance with the content limits of the Chinese Pharmacopoeia.Conclusion:In summary,the final diagnosis of XLGB-induced liver injury reached the clinical diagnosis of HILI and was acute severe hepatocellular injury type by the updated RUCAM and iEC.Therefore,this study provides scientific evidence regarding the causality evaluation of compound preparations of traditional Chinese medicines-induced liver injury.

Preparation of some new arylseleno compounds and application in the oxidation of olefins

Fifteen pyridine and substituted benzene diselenides,seleninic acids and seleninic anhydrides have been synthesized.Among them,4,4'-dipyridinediselenide,bis(2,4-dimethoxyphenyl)diselenide, 2,4-dimethoxyphenyl seleninic acid,2-pyridineseleninic acid,2-pyridineseleninic anhydride,4-pyridine- seleninic anhydride,2-nitrophenyl seleninic anhydride and 4-nitrophenyl seleninic anhydride were new compounds.Their regioselective oxidation or dehydrogenation of β-pinene,3β-benzoyloxycholest- 5-ene and androstan-3-one have been studied and compared.2-Pyridineseleninic anhydride is a more efficient oxidant than the others;most of the substituted benzeneseleno derivatives did not give the expected products.

Identification and differentiation of Panax ginseng,Panax quinquefolium, and Panax notoginseng by monitoring multiple diagnostic chemical markers

To differentiate traditional Chinese medicines(TCM) derived from congeneric species in TCM compound preparations is usually challenging. The roots of Panax ginseng(PG), Panax quinquefolium(PQ) and Panax notoginseng(PN) are used as popular TCM. They contain similar triterpenoid saponins(ginsenosides) as the major bioactive constituents. Thus far, only a few chemical markers have been discovered to differentiate these three species. Herein we present a multiple marker detection approach to effectively differentiate the three Panax species, and to identify them in compound preparations. Firstly, 85 batches of crude drug samples(including 32 PG, 30 PQ, and 23 PN) were analyzed by monitoring 40 major ginsenosides in the extracted ion chromatograms(EICs) using a validated LC–MS fingerprinting method. Secondly, the samples were clustered into different groups by pattern recognition chemometric approaches using PLS-DA and OPLS-DA models, and17 diagnostic chemical markers were discovered. Aside from the previously known Rf and p-F11, ginsenoside Rs1 could be a new marker to differentiate PG from PQ. Finally, the above multiple chemical markers were used to identify the Panax species in 60 batches of TCM compound preparations.