ABSTRACT
OBJECTIVE：To study the mecha nism of Bambuterol hydrochloride in the improvement of chronic obstructive pulmonary disease （COPD）model rats ，and to find the potential biomarker. METHODS ：Totally 30 rats were randomly divided into normal group ，model group and bambuterol hydrochloride group （3.3 mg/kg），with 10 rats in each group ；COPD model was established by lipopolysaccharide （LPS）infusion combined with smoking in model group and bambuterol hydrochloride group. After modeling ，bambuterol hydrochloride group was given relevant medicine intragastrically ，normal group and model group were given constant volume of normal saline intragastrically ，once a day ，for consecutive 45 d. After last medication ，the serum sample and alveolar lavage fluid of rats were collected. The levels of interleukin- 6（IL-6）and tumor necrosis factor-α（TNF-α）in alveolar lavage fluid were detected by ELISA. The serum metabolites were detected by LC-MS and analyzed by metabolomics. Orthogonal partial least squares discriminant analysis （OPLS-DA）was used to screen out the differential metabolites. The potential biomarkers were identified based on the related literature ，and the metabolic pathway enrichment analysis was carried out by MetPA analysis platform. RESULTS ：Compared with normal group ，the levels of IL- 6 and TNF-α in alveolar lavage fluid of rats were increased significantly in model group （P＜0.05）. Compared with model group ，the levels of IL- 6 and TNF-α in alveolar lavage fluid of rats were decreased significantly in bambuterol hydrochloride group （P＜0.05）. Results of metabolomics and OPLS-DA showed that 21 differential metabolites and 12 potential biomarkers were found （including maleylpyruvate ， hydroxypyruvate， tartronate semialdehyde，etc.）. Bambuterol hydrochloride can significantly reduce the levels of maleylpyruvate ，methylselenocysteine and 5-deoxy-D-glucuronic acid （P＜0.05）， while increase the levels of hydroxypyruvate ， tartronate semialdehyde and. These biomarkers were mainly @163.com concentrated in pentose phosphoric acid pathway ，glyoxyli acid and tricarboxylic acid metabolism pathway ，followed by 开发。E-mail：pn333@163.com inositol phosphoric acid metabolism pathway ，arginine and tyrosine metabolism pathway ，glycine，serine and threonine metabolism pathway. CONCLUSIONS ：The mechanism of bambuterol hydrochloride improving COPD may be associated with the decrease of the levels of TNF-α and IL-6，as well as the pathway of amino acid metabolism ，energy metabolism and lipid metabolism.
ABSTRACT
Objective: To establish a rapid and accurate method for the determination of 15 chemical drugs which were illegally added into the slimming Chinese patent medicines (CPM) and health foods. Methods: The UPLC-MS/MS method was adopted. The samples were extracted with methanol by ultrasonic processing and separated on a Waters Acquity BEH C18 column (100 mm × 2.1 mm, 1.7 μm) with 0.1% formic acid methanol (A) -0.1% formic acid water (B) as mobile phase by gradient elution (0-3 min, 33%-45% A; 3-5 min, 45%-55% A; 5-7 min, 55%-70% A; 7-9 min, 70%-80% A; 9-10 min, 80%-90% A; 10-11 min, 90%-33% A; 11-13 min, 33% A at a flow rate of 0.2 mL/min, and the column temperature was 40℃. A positive-ion (ESI+) source and an MRM mode were used to separate and quantitatively determine 15 chemical drugs. The obtained molecular ions, fragment ions, and retention time for MRM channels were used to identify the 15 kinds of drugs by comparison with those of reference substances. The obtained peak areas were used to determine the accurate contents of chemical drugs in CPM and the health foods. Results: A good resolution of 15 kinds of chemical drugs, including terbutaline hydrochloride, ephedrine hydrochloride, theophylline, caffeine, doxofylline, clenbuterol hydrochloride, tulobuterol hydrochloride, bambuterol hydrochloride, fenfluramine hydrochloride, furosemide, indapamide, phenolphthalein, sibutramine hydrochloride, N-demethylated sibutramine hydrochloride, and hydrochloric acid N,N-dinor sibutraminel, was obtained under this UPLC and MS/MS condition. The limits of qualitation and quantitation were in the range of 0.1-5.0 ng/g and 0.3-15.0 ng/g. The standard addition recoveries were in the range of 91.8%-110.8%. In the 86 batches of samples (including capsules, granules, and other different matrix types) were detected in the 74 batches of added chemicals, the positive rate was 86.0%. Sibutramine hydrochloride (39 batches), furosemide (20 batches), phenolphthalein (23 batches), theophylline (1 batch), and caffeine (15 batches) were checked out in the samples, 22 batches of which two kinds were checked out, one batch of which three kinds were checked out. By contrast, the products which were not clearly marked manufacturer illegally added more seriously. Conclusion: The method is simple, accurate, and highly sensitive, which can be used for the determination of illegally added chemical drugs in slimming CPM and health foods.
ABSTRACT
The construction and electrochemical response characteristics of polyvinyl chloride (PVC) membrane sensors for determination of bambuterol hydrochloride (BH) in presence of its degradation products are described. The sensors are based on the ion association complexes of BH cation with sodium tetraphenyl borate (BH-TPB) [sensor 1] or ammonium reineckate (BHRNC) [sensor 2] counter anions as ion exchange sites in PVC matrix. Fast and stable Nernstian responses in the range 10-5-10-2 M for BH over the pH range 5–8 revealed the performance characteristics of these electrodes, which were evaluated according to International Union of Pure and Applied Chemistry recommendations. The two proposed sensors are used for determination of BH, in pure form, in presence of its degradation product and in pharmaceutical formulations. Validation of the method according to the quality assurance standards showed suitability of the proposed electrodes for use in the quality control assessment of BH. The recoveries for determination of BH by the two proposed selective electrodes were 100.07 ± 1.008, 99.93 ± 0.920, for sensor 1 and sensor 2, respectively. Statistical comparison between the results obtained by this method and the official non-a method of BH was done, and no significant difference was found.
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Objective To evaluate the efficacy and safety of oral liquid of bambuterol hydrochloride in treatment children with asthma. Methods One hundred and fifty cases as study group treated with oral liquid of bambuterol hydrochloride,50.cases as control group treated with etinoline. Results Two groups had good efficacy, however, gasp and lung wheezing were better improved in study group compared with control group after 1 week treatment(P