Meta-analysis of the efficacy of budesonide and ambroxol hydrochloride inhalation in children with pneumonia and their effects on inflammatory response.

Childhood pneumonia, often caused by acute upper respiratory tract infections or bronchitis, is one of the leading causes of mortality in children. Nebulized inhalation, as a low-risk treatment method, has garnered significant attention. However, its effectiveness and safety remain controversial. In this study, a systematic review of relevant literature on the use of budesonide (BUD) and ambroxol hydrochloride (AMB) inhalation in the treatment of childhood pneumonia was conducted, and a total of 10 articles were included. The meta-analysis revealed an odds ratio (OR) of 1.61 and an I2 value of 0.00 % for the effectiveness of combined BUD and AMB inhalation therapy in children with pneumonia, indicating no heterogeneity among the studies in terms of effectiveness. The OR values for BUD or AMB inhalation in alleviating cough, lung auscultation abnormalities, respiratory distress, body temperature, and cyanosis of the lips in children with pneumonia all favored the combined BUD therapy, showing significant relief of the aforementioned symptoms. However, due to variations in drug dosage and administration methods, high heterogeneity was observed. This study suggested that combined BUD and AMB inhalation therapy has better efficacy in treating childhood pneumonia, and BUD combined with AMB inhalation is more effective in alleviating symptoms such as cough, lung auscultation abnormalities, respiratory distress, normalizing body temperature, and reducing cyanosis of the lips. Nevertheless, further validation is required due to the limited sample size and substantial heterogeneity in the included studies. To sum up, this study provides the first analysis of the efficacy and inflammatory response of BUD and AMB inhalation in children with pneumonia. Future research should aim to verify and clarify these findings, considering the limitations of the existing studies in terms of sample size and heterogeneity.

Baicalin/ambroxol hydrochloride combined dry powder inhalation formulation targeting lung delivery for treatment of idiopathic pulmonary fibrosis: Fabrication, characterization, pharmacokinetics, and pharmacodynamics.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and often fatal lung disease caused by multiple factors. Currently, safe, and effective drugs for the treatment of IPF have been extremely scarce. Baicalin (BA) is used to treat pulmonary fibrosis, IPF, chronic obstructive pulmonary disease, and other lung diseases. Ambroxol hydrochloride (AH), a respiratory tract lubricant and expectorant, is often used to treat chronic respiratory diseases, such as bronchial asthma, emphysema, tuberculosis, and cough. The combination of BA and AH can relieve cough and phlegm, improve lung function, and potentially treat IPF and its symptoms. However, given the extremely low solubility of BA, its bioavailability for oral absorptions is also low. AH, on the other hand, has been associated with certain side effects, such as gastrointestinal tract and acute allergic reactions, which limit its applicability. Therefore, an efficient drug delivery system is urgently needed to address the mentioned problems. This study combined BA and AH as model drugs with L-leucine (L-leu) as the excipient to prepare BA/AH dry powder inhalations (BA/AH DPIs) using the co-spray drying method. We the performed modern pharmaceutical evaluation, which includes particle size, differential scanning calorimetry analysis, X-ray diffraction, scanning electron microscope, hygroscopicity, in vitro aerodynamic analysis, pharmacokinetics, and pharmacodynamics. Notably, BA/AH DPIs were found to be advantageous over BA and AH in treating IPF and had better efficacy in improving lung function than did the positive drug pirfenidone. The BA/AH DPI is a promising preparation for the treatment of IPF given its lung targeting, rapid efficacy, and high lung bioavailability.

Comparative Study for Spectrofluorimetric Determination of Ambroxol Hydrochloride Using Aluminum Metal Transfer Chelation Complex and Biogenic Synthesis of Aluminum Oxide Nanoparticles Using Lavandula spica Flowers Extract.

The existing study pronounces two newly developed spectrofluorimetric probes for the assay of ambroxol hydrochloride in its authentic and commercial formulations using an aluminum chelating complex and a biogenically mediated and synthesized aluminum oxide nanoparticles (Al2O3NPs) from Lavandula spica flower extract. The first probe is based on the formation of an aluminum charge transfer complex. However, the second probe is based on the effect of the unique optical characteristics of Al2O3NPs in the enhancement of fluorescence detection. The biogenically synthesized Al2O3NPs were confirmed using various spectroscopic and microscopic investigations. The fluorescence detections in the two probes were measured at a λex of 260 and 244 and a λem of 460 and 369 nm for the two suggested probes, respectively. The findings showed that the fluorescence intensity (FI) covered linear concentration ranges of 0.1-200 ng mL-1 and 1.0-100 ng mL-1 with a regression of ˃0.999 for AMH-Al2O3NPs-SDS and AMH-Al(NO3)3-SDS, respectively. The lower detection and quantification limits were evaluated and found to be 0.04 and 0.1 ng mL-1 and 0.7 and 0.1 ng/mL-1 for the abovementioned fluorescence probes, respectively. The two suggested probes were successfully applied for the assay of ambroxol hydrochloride (AMH) with excellent percentage recoveries of 99.65% and 99.85%, respectively. Excipients such as glycerol and benzoic acid used as additives in pharmaceutical preparations, several common cations, and amino acids, as well as sugars, were all found to have no interference with the approach.

Ambroxol, a mucolytic agent, boosts HO-1, suppresses NF-κB, and decreases the susceptibility of the inflamed rat colon to apoptosis: A new treatment option for treating ulcerative colitis.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease of unknown etiology that increases the risk of developing colorectal cancer and imposes a lifelong healthcare burden on millions of patients worldwide. Current treatment strategies are associated with significant risks and have been shown to be fairly effective. Hence, discovering new therapies that have better efficacy and safety profiles than currently exploited therapeutic strategies is challenging. It has been well delineated that NF-κB/Nrf2 crosstalk is a chief player in the interplay between oxidative stress and inflammation. Ambroxol hydrochloride, a mucolytic agent, has shown antioxidant and anti-inflammatory activity in humans and animals and has not yet been examined for the management of UC. Therefore, our approach was to investigate whether ambroxol could be effective to combat UC using the common acetic acid rat model. Interestingly, a high dose of oral ambroxol (200 mg/kg/day) reasonably improved the microscopic and macroscopic features of the injured colon. This was linked to low disease activity and a reduction in the colonic weight/length ratio. In the context of that, ambroxol boosted Nrf2 activity and upregulated HO-1 and catalase to augment the antioxidant defense against oxidative damage. Besides, ambroxol inactivated NF-κB signaling and its consequent target pro-inflammatory mediators, IL-6 and TNF-α. In contrast, IL-10 is upregulated. Consistent with these results, myeloperoxidase activity is suppressed. Moreover, ambroxol decreased the susceptibility of the injured colon to apoptosis. To conclude, our findings highlight the potential application of ambroxol to modify the progression of UC by its anti-inflammatory, antioxidant, and antiapoptotic properties.

Efficacy, Safety and Mechanism of Jinzhen Oral Liquid in the Treatment of Acute Bronchitis in Children: A Randomized, Double-Blind, Multicenter Clinical Trial Protocol.

Background: Acute bronchitis (AB) is a common disease in pediatrics. Prolonged AB may develop into chronic bronchitis. Bronchitis caused by the influenza virus can lead to severe hypoxia or insufficient ventilation, causing great harm to patients and increasing the burden on children and society. Presently, there is no specific treatment for AB except symptomatic supportive treatment. It is urgent to find an effective treatment for AB. Jinzhen Oral Liquid (JZOL) has been found to have a broad spectrum of anti-inflammatory and antiviral effects in previous clinical and basic studies and has a good effect on AB in children. However, the large-sample, randomized, double-blind, head-to-head, evidence-based studies are lacking. The purpose of this protocol is to evaluate the efficacy, safety, and mechanism of JZOL in the treatment of AB in children. Methods: This is a randomized, double-blind, parallel-controlled multi-center clinical trial. The sample size is 500 participants in the intervention group and the control group respectively, with a total of 1000 participants. They will be recruited by 10 hospitals in China. The Intervention group takes JZOL and Ambroxol Hydrochloride and Clenbuterol Hydrochloride Oral Solution (AHCHOS) placebo, while the control group receives AHCHOS and JZOL placebo. The dosage of the two drugs varies according to age and weight. The medication lasts for 7 days. The disappearance time of cough is adopted as the primary outcome. Quality control will be carried out at every stage of data management and processing to ensure that all data are reliable and processed correctly. SAS is used for statistical analysis. Intention-to-treat analysis will be carried out in this trial. All statistical tests are conducted using a two-sided test, and p <0.05 would be considered statistically significant. Discussion: We hypothesized that children with AB could get good health benefits from JZOL. This study not only evaluates the clinical efficacy and safety of JZOL but also conducts metagenomics analysis and metabolomics analysis of feces and saliva of participants to study the mechanism of JZOL against AB. Therefore, this protocol evaluates the efficacy, safety, and mechanism of JZOL from a comprehensive perspective, so as to obtain a more solid evidence chain, which will enhance the credibility of the evidence. If successful, this study will provide a high-level evidence-based reference for the treatment of AB in children and future relevant studies.

Efficacy and safety of ambroxol hydrochloride in the treatment of secretory otitis media: a systematic review and meta-analysis.

Background: Secretory otitis media is a very common nonsuppurative inflammatory disease in otorhinolaryngology. Ambroxol hydrochloride helps to improve ciliary movement in the ear canal and promote the dissolution and discharge of secretions. However, its effect still lacks systematic evaluation. We conducted a meta-analysis of clinical studies to systematically evaluate the application effect of ambroxol hydrochloride. Methods: A computer-based search of the Chinese Biomedical Database (CBM), China National Knowledge Infrastructure (CNKI), PubMed, and Web of Science databases was conducted using the keywords "Ambroxol hydrochloride" & "secretory otitis media". Randomized controlled trials published after 2015 were selected and then screened and analyzed using RevMan 5.4 software. Results: Ten studies involving a total of 998 patients were included. Meta-analysis showed that adding ambroxol hydrochloride to the original glucocorticoid treatment improved therapeutic efficacy [odds ratio (OR) =4.95, 95% confidence interval (CI): 3.27, 7.50, P<0.00001], reduced tympanic pressure after treatment [mean difference (MD) =-19.04, 95% CI: -22.72, -15.36, P<0.00001], and increased the pure tone threshold (MD =6.37, 95% CI: 5.36, 7.37, P<0.00001), without increasing adverse reactions (OR =0.51, 95% CI: 0.14, 1.85, P=0.30). Discussion: On the basis of the original treatment of secretory otitis media, adding ambroxol hydrochloride treatment improved the therapeutic effect, reduced tympanic pressure after treatment, and improved the pure tone threshold (hearing), without increasing adverse reactions.

Facile approaches for determination of Bromhexine Hydrochloride and its active metabolite Ambroxol Hydrochloride using Eosin Y.

New validated Spectroscopic methods were developed to assay Bromhexine Hydrochloride and its active metabolite Ambroxol Hydrochloride separately in pure form and pharmaceutical formulations. The spectrophotometric assay (method I) shows complex formation between each of the drugs and Eosin Y at 540nm at pH 3.6 and 3.4mL of 4×10-4M Eosin for Bromhexine and Ambroxol. The Spectrofluorimetric assay (method II) depends on quenching eosin native fluorescence by the studied drugs, which measured at 540nm after excitation at 302nm. The spectrophotometric absorbance-concentration plot is rectilinear over the ranges (1.0-5.0) and (1.0-10.0) µg/mL for bromhexine and ambroxol with LOD of 0.31 and 0.14µg/mL and LOQ of 0.94 and 0.42µg/mL for the two drugs respectively. The fluorometric-concentration plot is linear along the range (1.0-5.0) µg/mL and (1-10) µg/mL for the two drugs respectively with LOD of 0.13µg/mL and 0.22µg/mL and LOQ of 0.4µg/mL and 0.65µg/mL for the two drugs, respectively. Developed assays have been validated in agreement with ICH recommendations and they were used in the analysis of commercial drug formulations containing the two mucolytic drugs and the results were matching with those obtained by the comparison method.

Thermo-Analytical and Compatibility Study with Mechanistic Explanation of Degradation Kinetics of Ambroxol Hydrochloride Tablets under Non-Isothermal Conditions.

Ambroxol hydrochloride (AMB), used as a broncho secretolytic and an expectorant drug, is a semi-synthetic derivative of vasicine obtained from the Indian shrub Adhatoda vasica. It is a metabolic product of bromhexine. The paper provides comprehensive and detailed research on ambroxol hydrochloride, gives information on thermal stability, the mechanism of AMB degradation, and data of practical interest for optimization of formulation that contains AMB as an active compound. Investigation on pure AMB and in commercial formulation Flavamed® tablet (FT), which contains AMB as an active compound, was performed systematically using thermal and spectroscopic methods, along with a sophisticated and practical statistical approach. AMB proved to be a heat-stable and humidity-sensitive drug. For its successful formulation, special attention should be addressed to excipients since it was found that polyvinyl pyrrolidone and Mg stearate affect the thermal stability of AMB. At the same time, lactose monohydrate contributes to faster degradation of AMB and change in decomposition mechanism. It was found that the n-th order kinetic model mechanistically best describes the decomposition process of pure AMB and in Flavamed® tablets.

The effect of adjuvant therapy with ambroxol hydrochloride in elderly chronic obstructive pulmonary disease patients.

OBJECTIVE: To investigate the influence of adjuvant therapy with ambroxol hydrochloride (ABH) on the clinical symptoms and pulmonary function of elderly chronic obstructive pulmonary disease (COPD) patients. METHODS: From September 2018 to September 2019, 142 elderly COPD patients admitted to the Affiliated Hospital of Hebei University were recruited as the research cohort. Based on different treatment method each patient underwent, they were assigned to the control group (CG, n=69) or the research group (RG, n=73). In the CG, the patients were treated with routine symptomatic treatment, and the patients in the RG were treated with ABH in addition to the treatment administered in the control group. RESULTS: After the therapy, the clinical symptom scores in the RG were significantly lower than they were in the CG (P<0.05), and the total effective rate of the clinical treatment was significantly higher than it was in the CG (P<0.05). The 6MWT scores in the RG were higher than they were in the CG (P<0.001), and the CAT scores were significantly lower than they were in the CG (P<0.001). The inflammatory factor levels in the RG were markedly lower than they were in the CG (P<0.001), and the pulmonary function and immune function indexes were better than they were in the CG (P<0.05). There was no significant difference in the adverse effects between the two groups (P>0.05). CONCLUSION: ABH can effectively relieve the clinical symptoms and improve the pulmonary function of elderly COPD patients, with a significant clinical effectiveness and high drug safety, so it is worthy of promoting.

Aerosol inhalation of ambroxol hydrochloride combined with terbutaline can promote recovery of children with severe pneumonia.

OBJECTIVE: This research aimed to investigate the clinical efficacy of aerosol inhalation of ambroxol hydrochloride combined with terbutaline on children with severe pneumonia, and to evaluate its influence on their immune function and inflammatory level. METHODS: Totally 113 severe pneumonia children were included. Thereinto, 55 children in the control group (CG) were treated with terbutaline aerosol inhalation, while 58 in the research group (RG) were given ambroxol hydrochloride on the basis of the CG. Their symptom alleviating time, blood gas parameters, adverse reactions during treatment, clinical efficacy, immune function and inflammatory factors were compared. RESULTS: The time of fever clearance time, disappearance of cough and pulmonary rates, chest shadow absorption and hospitalization of children in the RG were shorter than those in the CG. The combined treatment did not increase additional adverse reactions; instead, its effective rate was markedly higher than that in the CG. Further research found that after treatment, the arterial partial pressure of oxygen (PaO2), oxygenation index (OI), CD4+ and CD4+/CD8+, and interleukin-10 (IL-10) levels were dramatically increased, while the arterial partial pressure of carbon dioxide (PaCO2), C-reactive protein (CRP), interleukin-6 (IL-6), interleukin-17 (IL-17) and CD8+ levels were obviously increased. In addition, these indexes of children in the RG were obviously better than those in the CG. CONCLUSION: Aerosol inhalation of ambroxol hydrochloride combined with terbutaline has a remarkable clinical efficacy on children with severe pneumonia, which can improve their immune function and reduce inflammatory reaction.

Comparison of the efficacy of ambroxol hydrochloride and N -acetylcysteine in the treatment of children with bronchopneumonia and their influence on prognosis.

The aim of the present study was to compare the efficacy of ambroxol hydrochloride and N-acetylcysteine in the treatment of children with bronchial pneumonia and their influence on prognosis. A total of 120 children with bronchial pneumonia, admitted to The Affiliated Yantai Yuhuangding Hospital of Qingdao University from July 2015 to August 2018, were enrolled in the study. Among them, 58 children were treated with N-acetylcysteine and comprised the experimental group, and 62 children were treated with ambroxol hydrochloride and comprised the control group. Children's physical signs (such as fever, short breath, cough and pulmonary rales) and the adverse reactions to treatment were observed, and the disappearance time of the signs was recorded. In addition, the cellular immune function indicators and the quality of life after treatment were investigated. There was no significant difference in clinical data between the two groups (P>0.05). The effective rate in the experimental group was significantly higher than that in the control group (P<0.05). The disappearance time of symptoms, such as fever, cough, asthma and rales in the lung, was significantly shorter in the experimental group than that in the control group (P<0.05). The hospitalization time of patients in the experimental group was shorter than that in the control group (P<0.05). After treatment, immunoglobulin A (IgA), immunoglobulin G (IgG), immunoglobulin M (IgM) and complement C3 were significantly increased in the experimental group (P<0.01), and the IgA and IgG in the experimental group were significantly higher than those in the control group (P<0.01). The incidence of adverse reactions in the experimental group was significantly lower than that in the control group (P<0.05). In conclusion, N-acetylcysteine has a significant effect on the treatment of bronchopneumonia in children providing a quick relief from symptoms, such as lung rales, and therefore is worthy of use in clinic.

Microsphere formulations of ambroxol hydrochloride: influence of Okra (Abelmoschus esculentus) mucilage as a sustained release polymer.

Ambroxol hydrochloride (AH), a secretion-releasing expectorant, is a good candidate for sustained delivery. Mucilages are biodegradable, inexpensive carriers in microsphere formulations. The study aimed to prepare microspheres of AH using Okra mucilage obtained from pods of Abelmoschus esculentus combined with sodium alginate at various polymer/drug ratios. Okra mucilage was characterized for morphology, swelling, viscosity and flow properties. AH microspheres were prepared by ionic emulsification method and characterized using size, entrapment efficiency, swelling index and dissolution time (t50). A full 2 by 3 factorial experimental design using three factors (Okra mucilage/alginate ratio X1; drug/polymer ratio X2; and polymer concentration X3), each at two levels, was used to determine the effects of formulation variables on the responses. Optimized formulations of AH microspheres had sizes ranging from 250.91 ± 16.22 to 462.10 ± 23.85 µm; swelling index 1.35 ± 0.05 and 3.20 ± 0.03 and entrapment 55.70 ± 3.55-94.11 ± 4.50%. The microspheres exhibited sustained release of AH over a prolonged period as revealed by the dissolution time (t50) 2.85 ± 1.03-7.50 ± 0.96 h. Drug release kinetics generally followed zero order, implying that the process is constant and independent of the initial concentration of drug. Polymer concentration had the highest influence on microsphere size, entrapment efficiency and dissolution time while Okra/alginate ratio had the highest influence on swelling. Okra mucilage was a suitable polymer that could serve as an alternative to synthetic polymers in sustaining the release of ambroxol hydrochloride.

In vitro interactions of ambroxol hydrochloride or amlodipine in combination with antibacterial agents against carbapenem-resistant Acinetobacter baumannii.

The aim of this study was to investigate the in vitro interactions of ambroxol hydrochloride (ABH) or amlodipine (AML) with commonly used antibacterial agents, including meropenem, imipenem-cilastatin sodium, biapenem, cefoperazone-sulbactam, polymyxin B, and tigecycline, against six carbapenem-resistant Acinetobacter baumannii (CRAB) clinical isolates. Drug interactions were interpreted using two models, that is, the fractional inhibitory concentration index (FICI) model and the percentage of growth difference (ΔE) model. The results show that a majority of the combination groups exhibited partial synergy and additive interactions, such as the combinations of carbapenems and cefoperazone-sulbactam (SCF) with ABH or AML. While the combination of PB/AML exhibited synergistic interactions against all tested isolates, and PB/ABH exhibited synergistic interactions against two isolates. The FICI and ΔE model correlated very well for the combinations of PBABH and PB/AML against AB2. The combinations of TGC with ABH or AML mainly exhibited additive and indifferent interactions. There were no antagonistic interactions observed in any of the combinations. In conclusion, this study revealed that the non-antibacterial agents ABH or AML can work synergistically or partial synergistically with antibacterial agents against CRAB. This finding is crucial for overcoming the carbapenem resistance of A. baumannii. SIGNIFICANCE AND IMPACT OF THE STUDY: Drug combination is an effective approach for the treatment of resistant bacterial infection. The significance of using drug combination is that it can reduce drug dosage requirements, reduce the toxic effects of agents and prevent or delay the emergence of drug resistance. This study measured the in vitro interactions between non-antimicrobial agents and antibacterial agents against carbapenem-resistant Acinetobacter baumannii and the results of this study provide new insight to find strategies to overcome the carbapenem resistance in A. baumannii.

Efficacy of pulmonary surfactant combined with high-dose ambroxol hydrochloride in the treatment of neonatal respiratory distress syndrome.

Clinical efficacy of pulmonary surfactant combined with high-dose ambroxol hydrochloride in the treatment of neonatal respiratory distress syndrome (NRDS) was investigated. One hundred child patients with NRDS in Linyi Central Hospital were collected according to the diagnostic criteria for RDS in the Pediatrics, and randomly divided into the treatment group (n=50) and the control group (n=50) based on different therapeutic methods. Patients in the control group were treated with basic treatment and high-dose ambroxol hydrochloride injection, while those in the treatment group were additionally administered with pulmonary surfactant Curosurf based on conventional therapy in the control group. The chest X-rays were collected before the treatment and at 12 h after the drug administration, the degree of respiratory distress in child patients was observed and evaluated via Silverman grading, and changes in blood gas indexes were recorded before treatment and at 2, 6 and 12 h after the drug administration. The chest X-ray grade, Silverman grade and blood gas analysis results had no differences between the two groups before the treatment (P>0.05). In the treatment group, partial pressure of oxygen (PaO2) and PH were increased and partial pressure of carbon dioxide (PaCO2) was decreased compared with those in the control group at 2, 6 and 12 h after the drug administration (P<0.05). At 12 h after the drug administration, chest X-ray grade and Silverman grade in both groups were improved, which were significantly superior in the treatment group to those in the control group (P<0.01). Moreover, the efficacy in the treatment group was remarkably better than that in the control group at 12 h after drug administration (P<0.01). Pulmonary surfactant combined with high-dose ambroxol hydrochloride has definite efficacy in the treatment of NRDS, which can significantly improve the pulmonary infection, respiratory distress and blood gas indexes of child patients.

Design and evaluation of anti-fibrosis drug engineered resealed erythrocytes for targeted delivery.

Resealed erythrocytes (RSE) are potential, site-specific carrier system for drug delivery with prolonged drug release activity. In this study, erythrocytes obtained from Wistar albino rats were loaded with ambroxol hydrochloride (AH) with the focus to convenience the lung targeting possibility of the carrier erythrocytes. AH loading in erythrocytes using preswell dilution technique with glutaraldehyde (GA) as a cross-linking agent was evaluated and validated. Drug-loaded erythrocyte was characterized in terms of in vitro drug release followed by osmotic fragility study which showed amplified drug entrapment efficiency (DEE) and hemoglobin content values as well. In vivo lung fibrosis study, rats were sensitized to egg albumin by intraperitoneal (i.p.) injection and then inhalation in a whole body inhalation chamber. A sign of inflammation, airway sub-mucosal fibrosis, hypertrophy, and hyperplasia was observed. A series of in vivo studies were carried out to describe the effect of AH-loaded RSE including measurement of cytokines in Bronchoalveolar Lavage (BAL) fluid and histopathology study. AH showed a stepwise reduced level of cytokines in BAL at a different time interval after being injected of AH-loaded RSE. Furthermore, in vivo lung distribution experiments were performed for optimized formulation, and degree of distribution of the drugs inside the targeted organ was found to be satisfactory.

Effects of Xingnaojing injection on PCT, CRP and WBC in elderly patients with severe pneumonia / 中国基层医药

Objective To investigate the effect of Xingnaojing injection combined with ambroxol hydrochloride on precalcitonin (PCT),C-reactive protein (CRP) and white blood cell count (WBC) in the elderly patients with severe pneumonia,and to observe the clinical effect.Methods From December 2013 to March 2015,94 cases of severe pneumonia in Zhejiang Quhua Hospital were selected and divided into treatment group and control group according to the random digital table method,with 47 cases in each group.The control group was treated with ambroxol hydrochloride,while the treatment group was treated with Xingnaojing injection on the basis of the control group.The main symptom scores,blood gas analysis indicators,PCT,CRP and WBC changes and therapeutic effects were compared between the two groups before and after treatment.Results After treatment,the fever score and cough score in the treatment group [(1.03 ± 0.25) points,(1.12 ± 0.29) points] were significanly lower than those in the control group [(2.17 ± 0.42) points,(2.34 ± 0.71) points] (t =15.989,10.905,all P ＜ 0.05).After treatment,the PaO2 of the treatment group [(89.47 ± 8.41) mmHg] was higher than that of the control group [(76.39 ± 5.63) mmHg],while PaCO2 [(48.37 ± 7.19) mmHg] was lower than that in the control group [(63.27 ± 3.48) mmHg],the differences were statistically significant (t =8.860,12.780,all P ＜ 0.05).After treatment,the serum levels of PCT,CRP and WBC in the treatment group were (5.41 ± 0.97) ng/L,(48.98 ± 8.97) mg/L,(7.82 ± 1.23) × 109/L,respectively,which were significanly lower than those in the control group [(7.98 ± 1.47) ng/L,(76.45 ± 12.54) mg/L and (12.56 ± 1.89) × 109/L] (t =10.004,12.214,14.410,all P ＜ 0.05).The total effective rate in the treatment group(91.49％) was higher than that in the control group (72.34％),and there was statistically significant difference (x2 =5.817,P ＜ 0.05).Conclusion Xingnaojing injection combined with ambroxol can reduce the changes of serum PCT,CRP and WBC in the elderly patients with severe pneumonia,and the curative effect is significant.It is worthy of clinical study.

[Determination of ambroxol hydrochloride in human plasma by ultra high performance liquid chromatography-tandem mass spectrometry and bioequivalence evaluation of its preparation].

A rapid, simple and sensitive ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed for the determination of ambroxol hydrochloride in human plasma, and bioequivalence of its preparation was evaluated. The 50 µL-plasma sample was treated with methanol for protein precipitation, while ambroxol-d5 was used as an internal standard (IS). The separation was carried out on a Waters XBridge BEH C18 column (50 mm×2.1 mm, 2.5 µm) by gradient elution at a flow rate of 0.4 mL/min, with 0.1% (v/v) formic acid aqueous solution and methanol containing 0.1% (v/v) formic acid as the mobile phases. The analyte was detected using an electrospray ionization source in positive ion multiple reaction monitoring (MRM) mode. The calibration curves were linear in the range of 2-400 ng/mL (r=0.998). The intra- and inter-run accuracies were 97.1%-108.7%, the intra- and inter-run precisions were 1.0%-5.6%. The method was applied to the determination of the plasma concentration of the six healthy subjects after the oral administration of 30 mg of test and reference preparations. The bioavailability was (102.3±14.8)%. The 90% confidence intervals of the test preparation's pharmacokinetic parameters were 80.0%-125.0% of the reference preparation's corresponding parameters. Thus, it is proved that the test preparation and reference preparation are bioequivalent.

Characteristics of surfactant proteins in tumorigenic and inflammatory lung lesions in rodents.

Surfactant proteins (SPs) are essential for the proper structure and respiratory function of the lungs. There are four subtypes of SPs: SP-A, SP-B, SP-C, and SP-D. The expectorant drug ambroxol hydrochloride is clinically used to stimulate pulmonary surfactant and airway serous secretion. In addition, previous studies showed that ambroxol regulated SP production and attenuated pulmonary inflammation, with ambroxol hydrochloride being found to suppress quartz-induced lung inflammation via stimulation of pulmonary surfactant and airway serous secretion. In this study, we investigated the expression of SP-A, SP-B, SP-C, and SP-D in neoplastic and inflammatory lung lesions in rodents, as well as their possible application as potential markers for diagnostic purposes. SP-B and SP-C showed strong expression in lung hyperplasia and adenoma, whereas SP-A and SP-D were expressed in the mucus or exudates of inflammatory alveoli. Rodent tumorigenic hyperplasic tissues induced by various carcinogens were positive for napsin A, an aspartic proteinase involved in the maturation of SP-B; this indicated a focal increase in type II pneumocytes in the lungs. Therefore, high expression of napsin A in the alveolar walls may serve as a useful marker for prediction of the tumorigenic potential of lung hyperplasia in rodents.

Effects of the expectorant drug ambroxol hydrochloride on chemically induced lung inflammatory and neoplastic lesions in rodents.

Ambroxol hydrochloride (AH) is an expectorant drug used to stimulate pulmonary surfactant and serous airway secretion. Surfactant proteins (SPs) are essential for maintaining respiratory structure and function, although SP expression has also been reported in lung inflammatory and proliferative lesions. To determine whether AH exerts modulatory effects on these lung lesions, we examined its effects on pleural thickening induced by intrathoracic administration of dipotassium titanate (TISMO) in A/JJmsSlc (A/J) mice. We also analyzed the modulatory effects of AH on neoplastic lung lesions induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in A/J mice and by N-nitrosobis (2-hydroxypropyl) amine (DHPN) in F344/DuCrlCrj (F344) rats. A/J mice treated with TISMO showed decreased body weight, increased white blood cell (WBC) counts, and pleural thickening caused by pleuritis and poor general condition. However, A/J mice treated with TISMO + 120 ppm showed significant recovery of body weight and WBC counts to the same levels as those of A/J mice not treated with TISMO, although no significant differences were observed in histopathological changes including the immunohistopathological expression of IL-1ß in the lung and maximum pleural thickness regardless of AH treatment. In the NNK and DHPN experiments, no significant differences in body weight, hematology, plasma biochemistry, and histopathological changes were associated with AH concentration. These results suggest that AH potentially exerts anti-inflammatory effects but does not have a direct suppressive effect on lung tumorigenesis in rodents.

Optimization of the Critical Parameters of the Spherical Agglomeration Crystallization Method by the Application of the Quality by Design Approach.

This research work presents the use of the Quality by Design (QbD) concept for optimization of the spherical agglomeration crystallization method in the case of the active agent, ambroxol hydrochloride (AMB HCl). AMB HCl spherical crystals were formulated by the spherical agglomeration method, which was applied as an antisolvent technique. Spherical crystals have good flowing properties, which makes the direct compression tableting method applicable. This means that the amount of additives used can be reduced and smaller tablets can be formed. For the risk assessment, LeanQbD Software was used. According to its results, four independent variables (mixing type and time, dT (temperature difference between solvent and antisolvent), and composition (solvent/antisolvent volume ratio)) and three dependent variables (mean particle size, aspect ratio, and roundness) were selected. Based on these, a 2⁻3 mixed-level factorial design was constructed, crystallization was accomplished, and the results were evaluated using Statistica for Windows 13 program. Product assay was performed and it was revealed that improvements in the mean particle size (from ~13 to ~200 µm), roundness (from ~2.4 to ~1.5), aspect ratio (from ~1.7 to ~1.4), and flow properties were observed while polymorphic transitions were avoided.