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OBJECTIVE:To evaluate the effects and safety of Bencycloquidium bromide nasal spray in the treatment of acute rhinitis after a cold. METHODS:A multicenter,dose parallel controlled,randomized,double-blind,placebo-controlled clinical tri-al was conducted. Two hundred and thirty-eight patients with acute rhinitis after a cold were selected and divided into group A(24 cases),B(24 cases),C(24 cases),D(24 cases),E(23 cases),F(24 cases),G(23 cases),H(24 cases),I(24 cases),J (24 cases). Group A-C were given Bencycloquidium bromide nasal spray 22.5μg,45μg,90μg,respectively,bid,spraying it once for each nostril. Group D-F were given Bencycloquidium bromide nasal spray 22.5 μg,45 μg,90 μg,respectively,tid,spraying it once for each nostril. Group G-I were given Bencycloquidium bromide nasal spray 22.5 μg,45 μg,90 μg,respectively,qid,spray-ing it once for each nostril. Group J was given placebo. All groups were treated for(4±1)d. Rhinorrhea score and continuous rhi-norrhea duration were compared among 10 groups,and the safety was evaluated. RESULTS:The rhinorrhea score and continuous rhinorrhea duration of 10 groups were improved significantly,with statistical significance (P0.05). There was no statistical significance in the incidence of ADR among 10 groups(P>0.05). CONCLUSIONS:Bencycloquidium bromide nasal spray with 90 μg,qid times significantly improves rhinorrhea score and continuous rhinorrhea duration with good safety.
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Aim Toinvestigatetheeffectofbencyclo-quidium bromide(BCQB)on mucus MUC5AC expres-sion induced by lipopolysaccharide in cultured human nasalepithelialcells(HNECs).Methods Primary culture of human nasal epithelial cells (HNECs)was randomly divided into control group (C,with no treat-ment),LPS group (LPS,with LPS 1 mg · L-1 added in),BCQB low dose group(BCQBL,with LPS 1 mg· L-1 and BCQB 10 -8 mol·L-1 added in),BCQB mid-dle dose group(BCQBM,with LPS 1 mg·L-1 and BC-QB 10 -7 mol·L-1 added in),BCQB high dose group (BCQBH,with LPS 1 mg·L-1 and BCQB 10 -6 mol· L-1 added in)and ipratropium bromide group(IB,with LPS 1 mg·L-1 and IB 10 -6 mol·L-1 added in).Af-ter incubation at 37 ℃with 5% CO2 for 24 h,the ex-pression of MUC5 AC mRNA was detected with Real-time PCR and the expression of MUC5 AC protein in HNECs was detected with Western blot,while the ex-pression of MUC5 AC protein in supernatant was detec-tedwithELISAineachgroup.Results Ascompared with control group,the expression of MUC5 AC mRNA and protein increased significantly in LPS group (each P0. 05 ). Conclusion Bencycloquidiumbromidecansuppress MUC5 AC expression induced by LPS in cultured hu-man nasal epithelial cells,indicating that BCQB may be a new drug for nasal mucous hypersecretion diseases.
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OBJECTIVE: To establish an HPLC assay to determine the uptake characteristics of bencycloquidium bromide (BCQB) in Calu-3 cells. METHODS: The samples were analyzed with a Discovery C18 column (4.6 mm×250 mm, 5μm) at 25°C. The mobile phase was acetonitrile-water containing 0.27% KH2PO4 and 0.3% triethylamine (pH adjusted to 3.0 with H3PO4) (35:65). The flow rate was 1.0 mL·min-1. The concentrations of BCQB in Calu-3 cells at various time were measured. RESULTS: The linearity of BCQB calibration curve was good in the range of 0.0102-1.0220 μg·mL-1 (r=0.9998). The minimal quantitation limit was 0.0102 μg·mL-1. The uptake of BCQB increased rapidly during the first 30 min. When the concentration of BCQB increased from 20 to 500 μmol·L-1, the uptake increased almost linearly. However, the curve showed saturation when the concentration of BCQB reached 500 μmol·L-1. CONCLUSION: This assay is rapid, sensitive and specific, and can be applied to determine BCQB concentrations in Calu-3 cells. BCQB can be uptaken by Calu-3 cells rapidly, and the uptake shows saturation with increase of dosage.
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OBJECTIVE: To study the induction effect of bencycloquidium bromide (BCQB) on rat liver cytochrome P450 enzymes. METHODS: Rats were divided into solvent control group, positive control (phenobarbital) group and BCQB group. The rats in BCQB groups were intranasally administered with 1, 3, and 9 mg · kg-1 BCQB, respectively. After multiple-dose administration, the rats were sacrificed, and the livers were weighed and prepared to microsomes. Then the liver coefficients were calculated, and the total content of CYP450 enzymes in liver microsomes was determined by spectrophotometer. HPLC-MS/MS method was adopted and validated to simultaneously determine the productive velocity of 6β-hydroxyl testosterone and paracetamol after incubation of rat liver microsomes. The activities of CYP1A1/2 and CYP3A1/2 were measured according to the productive velocity. RESULTS: The liver coefficients, total content of CYP450 enzymes, and activity of CYP1A1/2 were significantly different (P0.05) between solvent control group and BCQB groups. The activity of CYP3A1/2 in BCQB groups was not higher than solvent control group. CONCLUSION: Phenobarbital has induction effect on rat liver CYP450 enzymes. The test system can be used to evaluate the induction effect of BCQB on rat liver CYP450 enzymes. BCQB has no induction effect on liver CYP450 enzymes in rats.