1.Study on Preparation and Stability of the Solid Dispersion of Radix Arnebiae seu Lithospermi
Xiujuan PANG ; Xiaohong LIU ; Fude CUI ; Changshan SUN ;
Chinese Traditional Patent Medicine 1992;0(01):-
Objective: To enhance the dissolution rate in vitro and bioavailability in vivo of the active components of extraction of Radix Arnebiae seu Lithospermi. Methods: Solid dispersion of extract of Radix Arnebiae seu Lithospermi were prepared with solid dispersion technology, X ray diffraction and stability experiments were also carried out. Results: The dissolution rates in vitro of the active components of extraction of Radix Arnebiae seu Lithospermi solid dispersion were obviously raised and stable, and the solid dispersion was not easy to age. Conclusion: The dissolution rate in vitro of the active components in Radix Arnebiae seu Lithospermi can be inproved greatly by the solid dispersion using PVP and HPMC as a carrier.
2.Preparation of two poor water soluble drugs - nanoporous ZnO solid dispersions and the mechanism of drug dissolution improvement.
Bei GAO ; Changshan SUN ; Zhuangzhi ZHI ; Yan WANG ; Di CHANG ; Siling WANG ; Tongying JIANG
Acta Pharmaceutica Sinica 2011;46(11):1399-407
Nanoporous ZnO was used as a carrier to prepare drug solid dispersion, the mechanism of which to improve the drug dissolution was also studied. Nanoporous ZnO, obtained through chemical deposition method, was used as a carrier to prepare indomethacin and cilostazol solid dispersions by melt-quenching method, separately. The results of scanning electron microscope, surface area analyzer, fourier transform infra-red spectroscopy, differential scanning calorimeter and X-ray diffraction showed that drugs were implanted into nanopores of ZnO by physical adsorption effect and highly dispersed into nanopores of ZnO in amorphous form, moreover, these nanopores strongly inhibited amorphous recrystallization in the condition of 45 degrees C and 75% RH. In addition, the results of the dissolution tested in vitro exhibited that the accumulated dissolutions of indomethacin and cilostazol solid dispersions achieved about 90% within 5 min and approximately 80% within 30 min. It was indicated in this study that the mechanism of drug dissolution improvement was associated with the effects of nanoporous ZnO carrier on increasing drug dispersion, controlling drug in nanopores as amorphous form and inhibiting amorphous recrystallization.
3.Expression of Brain-derived Neurotrophic Factor in Temporal Cortex of Autism Model Rats
Shujuan CHEN ; Zhimei JIANG ; Lanmin GUO ; Shiling ZHANG ; Qifeng SUN ; Li LI ; Changshan WANG
Chinese Journal of Rehabilitation Theory and Practice 2012;18(5):426-429
Objective To explore the role of brain-derived neurotrophic factor (BDNF) in pathogenesis of autism. Methods 12.5 d pregnantWistar rats were injected sodium valproate (VPA) 600 mg/kg or normal saline (NS). Their newborn rats were observed ethologically.The expression of BDNF was measured in their temporal cortex with immunohistochemical stain. Results Compared with NS group, VPAgroup expressed less body mass (P<0.05), eyes opening delay (P<0.05), poorer coordination response (P<0.05), slower taxis response (P<0.05). The number of social behavior decreased (P<0.05), latency increased (P<0.05), duration shortened (P<0.05), repetitive activities increased(P<0.05). Purkinje cells reduced in cerebellum. The expression of BDNF increased significantly in temporal cortex 1 d, 7 d and 14 dpostnatally (P<0.01), but decreased 35 d and 49 d postnatally (P<0.01). Conclusion BDNF plays a role in the pathogenesis of autism.
4.Simultaneous determination of trillin and desgalactotigonin contents in Solanum lyratum by HPLC-ELSD.
Yurong JIA ; Changshan SUN ; Yanxiu SUN ; Wenwen YANG ; Lixin SUN
China Journal of Chinese Materia Medica 2012;37(3):323-326
OBJECTIVETo establish a HPLC-ELSD method for simultaneous determination of trillin and desgalactotigonin contents in Solanum lyratum.
METHODA Diamonsil C18 column (4.6 mm x 250 mm, 5 microm) was adopted, with the mobile phase consisting of acetonitrile-10 mmol x L(-1) ammonium acetate (52: 48). The temperature was 25 degrees C, the flow rate was set at 0.6 mL x min(-1), and the sample size is 20 microL. The temperature of drift tubes and gas flow rate of the detector were set at 95 degrees C and 2.3 L x min(-1), respectively.
RESULTWith in the linear ranges of 20-200 mg x L(-1) and 10-100 mg x L(-1), trillin and desgalactotigonin show a good linear relationship. The average recovery was 99.4% (RSD 0.90%) for trillin and 100.3% (RSD 1.1%) for desgalactotigonin.
CONCLUSIONThe method is so accurate and easily reproducible that it is suitable for the quality control of S. lyratum medicinal materials.
Chromatography, High Pressure Liquid ; Drug Stability ; Drugs, Chinese Herbal ; analysis ; chemistry ; Quality Control ; Reproducibility of Results ; Scattering, Radiation ; Solanum ; chemistry
5.Current situation and exploration of standardized asthma clinic for children in China
Xin SUN ; Huajie WU ; Yixiao BAO ; Baoping XU ; Aihuan CHEN ; Changshan LIU ; Chuangli HAO ; Enmei LIU ; Li SHA ; Kunling SHEN
Chinese Journal of Applied Clinical Pediatrics 2021;36(7):514-519
Objective:To understand the present situation of the construction of standardized asthma clinic for children in China, to explore the problems existing in the process of construction, and to promote the healthy development of standardized clinic construction.Methods:The process and current situation of the construction of standar-dized asthma clinics for children in China were reviewed and investigated, and the practical significance of the China Children′s Asthma Action Plan (CCAAP) in the construction of standardized asthma clinics for children was explored.Results:(1)By December 2020, 1 289 standardized asthma clinics for children and 135 regional demonstration centers had been built; 56 training sessions had been held, with a total of 2 560 doctors and 650 nurses trained, covering 2 560 hospitals across the country; and 4 518 patient education sessions were held.Online publicity covers a total of 1 million person-times, with an annual average of 1.33 million patients.(2)CCAAP improved the quality control level of standardized asthma clinic and promoted the standardized management of children.Conclusions:Through process optimization, professional evaluation, individual health education and real-time disease monitoring, standardized asthma clinic for children with asthma can effectively enhance asthma management awareness of children and their parents, improve disease awareness, and promote better control of asthma.It is an effective management model of asthma in children at present, and it is worthy of clinical promotion.CCAAP plays a good role in the construction of standardized outpatient clinic for asthma in children.The construction of standardized asthma clinic for children in China has achieved remarkable results, and the development trend is good in the future.
6.Progress on mechanisms and clinical application of allergen immunotherapy
Xinyu SUN ; Changshan LIU ; Xueyan WANG
International Journal of Pediatrics 2023;50(9):624-629
Allergen immunotherapy(AIT)is an effective treatment for allergic diseases that have been used for more than a century.At present, AIT is administered in two main ways: subcutaneous immunotherapy(SCIT)and sublingual immunotherapy(SLIT), which aims to induce immune tolerance to allergens and provide long-term clinical benefit to patients.The effectiveness of AIT has been confirmed and the research on its mechanism has been deepened, and AIT combined with biological agents has been widely used in clinical practice.
7.Mechanism of infliximab in preventing autoimmune hepatitis in mice model
Mengyu SUN ; Changshan WAN ; Mengnan LYU ; Yan SONG ; Runzhi MA ; Wentian LIU
Chinese Journal of Digestion 2020;40(3):192-198
Objective:To observe the preventive effects of infliximab in autoimmune hepatitis (AIH) and to explore its mechanism.Methods:The mice AIH model was established by injecting concanavalin A (Con-A) into the caudal vein. Forty mice were divided into prevention group and control group, with 20 mice in each group. The mice of prevention group were injected intravenously with infliximab (20 mg/kg) one hour before Con-A injection and the mice of control group were administrated with 200 μL phosphate buffered saline (PBS). Serum was collected 3, 8, 12 and 24 h after Con-A/PBS injection. The serum level of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) was detected by colorimetry. The level of cytokine interleukin (IL)-6, IL-1β, interferon gamma (IFN-γ), IL-4, IL-17A, IL-10 and chemokine C-X-C motif ligand 10 (CXCL10) was measured by enzyme-linked immunosorbent assay (ELISA). Liver samples were taken 12 h after Con-A/PBS injection for hematoxylin-eosin staining. Liver infiltrated lymphocytes were assessed by flow cytometry. The expression of T-box transcription factor 21 ( TBX21), GATA binding protein 3 ( GATA3), RAR related orphan receptor C ( RORC) and CXCL10 at mRNA level was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). The expression of CXCL10 in liver was detected by Western blotting. Paired t test and one-way analysis of variance were used for statistic analysis. Results:At 8, 12, and 24 h after Con-A injection, the serum ALT level, AST level, IL-1β and IFN-γ of prevention group were all lower than those of control group ((545.8±190.3) U/L vs. (865.8±237.7) U/L, (947.6±267.9) U/L vs. (1 448.0±403.5) U/L, (508.6±131.1) U/L vs. (976.6±207.6) U/L; (620.7±132.0) U/L vs. (952.9±106.8) U/L, (801.6±212.0) U/L vs. (1 424.8±236.0) U/L, (632.1±117.8) U/L vs. (1 008.3±187.5) U/L; (31.38±10.12) ng/L vs. (48.12±11.53) ng/L, (39.34±11.40) ng/L vs. (60.00±14.17) ng/L, (29.49±8.22) ng/L vs. (46.89±5.50) ng/L; and (432.93±66.82) ng/L vs. (674.66±97.88) ng/L, (655.09±169.17) ng/L vs. (937.90±166.36) ng/L, (263.40±54.97) ng/L vs. (410.74±86.64) ng/L), and the differences were statistically significant ( t = 2.350, 2.308, 4.263, 4.374, 4.860, 3.806, 2.440, 2.541, 3.939, 4.560, 2.660 and 3.210; all P<0.05). The serum IL-6 levels 3, 8, 12 and 24 h after Con-A injection of prevention group were all lower than those of control group ((1 075.79±303.77) ng/L vs. (1 914.48±317.80) ng/L, (1 945.97±271.85) ng/L vs. (2 100.80±378.42) ng/L, (1 578.60±504.54) ng/L vs. (2 525.40±406.55) ng/L, (1 020.64±280.03) ng/L vs. (1 582.00±311.96) ng/L), and the differences were statistically significant ( t=4.266, 2.903, 3.267 and 2.994; all P < 0.05). At 3 h after Con-A injection, serum CXCL10 level and CXCL10 mRNA expression in liver tissues of prevention group were both lower than those of control group ((1 755.8±148.1) ng/L vs. (2 102.0±334.0) ng/L and 7.20±3.00 vs. 27.60±1.90), and the differences were statistically significant ( t=2.356 and 2.623, both P<0.05). At 3 and 8 h after Con-A injection, T- bet expression at mRNA level in liver tissues of prevention group was lower than that of control group (6.94±2.29 vs. 15.20±3.48 and 9.38±3.48 vs. 18.17±4.48), and the differences were both statistically significant ( t = 4.427 and 3.673, both P<0.05). However, 3, 8, 12 and 24 h after Con-A injection, there were no statistically significant differences in serum IL-4, IL-17A, IL-10, or GATA3 or RORC expression at mRNA level between prevention group and control group (all P > 0.05). Conclusions:Infliximab has certain preventive effects in mice AIH model, which may be achieved by antagonizing TNF-α and decreasing the expression of CXCL10 in liver, reducing the infiltration of T-helper 1 cells and CD8 + T cells into liver, and by reducing T lymphocyte activation induced by inflammatory cytokines thus alleviating the damage of T lymphocytes to hepatocytes.
8.Application of Omalizumab combined with allergen immunotherapy in the treatment of allergic asthma in children
Xinyu SUN ; Xueyan WANG ; Changshan LIU
Chinese Journal of Applied Clinical Pediatrics 2023;38(12):914-920
Objective:To analyze the efficacy and safety of Omalizumab (OMA) combined with allergen immunotherapy (AIT) on children with allergic asthma.Methods:Clinical data of 43 children with allergic asthma from the Second Hospital of Tianjin Medical University between August 2018 and October 2022, who were managed by OMA combined with double mite subcutaneous immunotherapy (SCIT) were retrospectively analyzed, including 30 males and 13 females with the age of 5-15 years.Twenty children with allergic asthma who were managed by the monotherapy for SCIT during the same period, including 16 males and 4 females with the age of 4-13 years were included in the control group(group1: conventional immunotherapy; group2: cluster immunotherapy). Among the 43 cases managed by OMA combined with SCIT, 20 were treated with OMA, followed by AIT (OMA-AIT group), and 23 were treated with AIT, followed by OMA (AIT-OMA group). Notably, 6 cases in AIT-OMA group who were additionally given OMA due to the difficulty in increasing doses were subgrouped in AO1 group, and 17 who were additionally given OMA due to poor control of asthma or comorbidities during the course of AIT and frequent adverse events were subgrouped in AO2 group.The number of asthma exacerbations within 1 year and during the combination therapy, the Childhood Asthma Control Test/Asthma Control Test (C-ACT/ACT) findings, the Visual Analogue Scale (VAS) for grading rhinitis, inhaled corticosteroid (ICS) dosage converted to budesonide equivalent, the Total Medication Score (TMS), comorbidities, lung function [percent-predicted forced expiratory volume in 1 second(FEV 1% pred), percent-predicted peak expiratory flow(PEF%pred), percent-predicted maximal mild-expiratory flow(MMEF%pred)], exhaled nitric oxide (FeNO), completion of the initial SCIT and adverse effects [local adverse reactions (LRs) and systemic adverse reactions (SRs)] were analyzed for assessing the efficacy and safety of OMA combined with AIT on children with allergic asthma.The t-test of two independent samples was used for comparison of measurement data that followed normal distribution.Wilcoxon′s test was used for non-normally distributed between-group comparisons.The χ2 test was used for the between-group comparison of counting data. Results:(1)Baseline comparison showed that the male ratio (17/20 cases vs.13/23 cases) and the proportion of moderate-to-severe persistent asthma (18/20 cases vs.18/23 cases) in the OMA-AIT group were significantly higher than those of the AIT-OMA group (all P<0.05). (2)Efficacy: ①In OMA-AIT group, all children reached the AIT maintenance treatment stage successfully after combination therapy.At the maintenance treatment stage, the C-ACT/ACT, VAS and TMS scores(26.0±1.25 vs.24.55±2.28, 1.50±1.24 vs.2.55±1.70, 3.60±1.47 vs.5.45±1.19)were significantly improved from baseline(all P<0.05). There were no significant differences in lung function indexes FEV 1%pred, PEF%pred, and MMEF%pred ( P>0.05), and FeNO level did not change significantly than baseline.After the combination treatment, ICS dosage significantly decreased from 240.00 (160.00, 380.00) μg/d at baseline to 140.00 (80.00, 300.00) μg/d ( P<0.05). Comorbidities, including allergic rhinitis, food allergy, atopic dermatitis and angioedema were improved.Five cases (25.00%) had once asthma exacerbation during the treatment.The duration of maintenance dose of conventional (22.70±7.10 vs.15.20±1.32) and cluster immunotherapy (13.00±4.97 vs.7.30±1.06) were longer than those of the corresponding control group(all P<0.05). ②AIT-OMA group: In AO1 group, the C-ACT/ACT score were improved from baseline( P<0.05), and VAS score, TMS score decreased from 3.00(1.75, 3.00), (4.67±1.97) points at baseline to 1.00(0, 1.00), (2.83±1.60) points by the maintenance dose in AO1 group (all P<0.05). There were no significant differences in the FEV 1%pred, PEF%pred, MMEF%pred and FeNO compared with baseline in AO1 group.ICS dosage in AO1 group significantly decreased from (180.00±78.99) μg/d at baseline to (88.88±26.23) μg/d ( P<0.05). In AO2 group, the C-ACT/ACT, VAS and TMS scores at the completion of OMA treatment[26.53±0.94 vs.25.06±2.05, 1.00 (0, 2.00) vs.2.00(2.00, 3.50), 3.41±0.94 vs.5.53±1.23]were significantly improved from baseline (all P<0.05). PEF%pred[(106.47±22.37)% vs.(94.47±26.39)%] significantly increased than baseline ( P<0.05), and the remaining lung function indexes and FeNO were not significantly improved.ICS dosage significantly decreased from 240.00(160.00, 400.00) μg/d at baseline to 80.00 (20.00, 160.00) μg/d ( P<0.05). During the combination treatment, 1 case (5.88%) had once asthma exacerbation, and all 8 cases with food allergy or atopic dermatitis or conjunctivitis had improved comorbidities.(3)Safety: adverse events during OMA injection were not reported.①In OMA-AIT group, a total of 165 OMA injections were performed in the initial treatment stage of the conventional immunotherapy group, with 13 (7.88%) reported LRs and 2 (1.21%) grade-1 SRs.A total of 143 OMA injections were performed in the initial treatment stage of the cluster immunotherapy group, with 19(13.29%) reported LRs and none of SRs.②In AIT-OMA group, there were 6 cases of adverse events in the initial treatment stage of AIT who were successfully reached the maintenance treatment stage after the addition of OMA in AO1 group.In AO2 group, children who were additionally given OMA due to adverse events in the maintenance treatment phase did not report adverse events during the combination therapy. Conclusions:OMA combined with AIT not only expands the scope of AIT, improves allergic and asthma symptoms in children, reduces the use of drugs, but also enhance the safety of AIT and compliance, reduces adverse events during AIT treatment, and even shortens the time of initial treatment.
9.Expert consensus on the rational application of interferon alpha in pediatrics
Kunling SHEN ; Yunxiao SHANG ; Guocheng ZHANG ; Baoping XU ; Zhou FU ; Ling CAO ; Jiahua PAN ; Guangmin NONG ; Changshan LIU ; Xin SUN ; Shuhua AN ; Hanmin LIU ; Xingwang LI ; Rongmeng JIANG ; Chuangli HAO ; Ying WANG
Chinese Journal of Applied Clinical Pediatrics 2018;33(17):1301-1308
10.Huai qi huang granules for the treatment of children with mycoplasma pneumoniae pneumonia: a multicenter clinical study
Lishen SHAN ; Yunxiao SHANG ; Miao LI ; Xiaohua HAN ; Huanji CHENG ; Yan HUANG ; Jicheng DAI ; Shuqiang QU ; Jun SUN ; Yan BAI ; Changshan LIU ; Shaomin REN ; Yingchun LI ; Liping SUN ; Yingxue ZOU ; Hao XU ; Xiuqing WU ; Hong YAN ; Jing CHEN ; Li YAO ; Yanqi SU ; Chunmei JIA ; Chenghua SHI ; Jianhua LIU ; Zhongping ZHANG ; Jun WANG ; Yuling HAN ; Yanfen WANG ; Yushui WANG ; Guang YANG
International Journal of Pediatrics 2018;45(1):53-57,72
Objective To analyze the effects of Hual qi huang granules on children with mycoplasma pneumoniae pneumonia.Methods A randomized,multicenter parallel controlled clinical trial was carried out.A total of 3 000 cases of hospitalized children with mycoplasma pneumoniae pneumonia were selected.All of them were given treatment for mycoplasma pneumoniae pneumonia with macrolide antibiotics and symptomatic treatment.They were randomly divided into 2 groups:research group and control group.The children of research group were give oral Huai qi huang granules for three months.According to the classification of pneumonia,these two groups were divided into:lobar pneumonia research group,lobar pneumonia control group,lobular pneumonia research group,lobular pneumonia control group.The hospitalization duration of fever,length of hospital stay,the absorption area of lung inflammation and pneumonia severity sores were observed.The frequency of upper respiratory infections,bronchitis,pneumonia were observed in 3 months after discharge.Results 2 378 cases were investigated.The hospitalization duration of fever,length of hospital stay of research group were significantly shorter than that of in control group (P < 0.001).The children with lobar pneumonia,2 weeks after treatment,the absorption of consolidation of the lobar pneumonia research group is significantly better than lobar pneumonia control group (P <0.001).After two weeks treatment,the pneumonia scores of lobar pneumonia research group is lower than lobar pneumonia control group (P < 0.05).Followup of 3 months after hospital discharge,frequency of upper respiratory infection and bronchitis of research group,were significantly lower than that of control.In addition,appetite increased significantly in research group than control (P < 0.001).There are 21 cases with drug associated adverse reactions (mild diarrhea),including 12 cases of research group,9 cases of control group,and there was no statistical significance (P >0.05).Conclusion Standard treatment combined with oral Huai qi huang granules in the treatment of mycoplasma pneumoniae pneumonia,can significantly shorten hospitalization duration of fever,length of hospital stay and reduce the severity score of pneumonia.Three months oral Huai qi huang granules can significant reduce the frequency of respiratory infections and bronchitis,also can increase patients appetite,and be safe.