Frontiers in Pharmacology
·
2025
·
IF 4.8
Fengyichi Zhang,Fanxi Guo,Xinyu Zhao,Chongyang Li,Junli Wang,Mengyun Wang,Ruixia Ma,Baochang Chen,Qiangqiang Miao,Yimeng Wang,Zihan Wang,Di Cao,Zugong Yu
A rapid, sensitive and reliable ultra–performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) was developed and validated for the simultaneous quantitation of pyrantel (PYR), praziquantel (PRA), febantel (FBT) and its active metabolites, fenbendazole (FEN) and oxfendazole (OXF) in dog plasma. Fenbendazole–D3 (FEN–D3) was used as an internal standard (IS). The analytes and IS were prepared using simple protein precipitation (PP) combined with liquid–liquid extraction (LLE). Chromatographic analysis was performed on UPLC BEH C18 column using acetonitrile–0.1% formic acid in water for gradient elution. Detection was carried out in multiple reaction monitoring (MRM) mode under positive electrospray ionization. The standard curves were linear through the concentration range of 4–240 ng/mL for PYR and OXF, 15–900 ng/mL for PRA, 2–120 ng/mL for FBT and 10–600 ng/mL for FEN with all correlation coefficients >0.99. The intra–and inter–batch precision was 1.08%–14.26% and accuracy was from 90.66% to 110.28%. The mean extraction recoveries for the analytes and IS were >90%. The total run time was 9.0 min. The developed method was successfully applied to a bioequivalence study after oral administration of compound febantel tablets in 38 healthy dogs.
研究领域:
兽医学
·
分析化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CHEMICAL THERMODYNAMICS
·
2020
·
IF 2.888
Jiao Sha,Yi Gong,Zidan Cao,Zibo Huang,Xiaoran Hu,Yameng Wan,Renren Sun,Haixia He,Gaoliang Jiang,Yu Li,Tao Li,Baozeng Ren
The equilibrium solubility and thermodynamic properties of praziquantel (PZQ) in eleven organic mono-solvents were reported. Solubility determinations were performed through the laser monitoring method at T = (278.15–323.15) K and p = 101.3 kPa. It is found that the mole fraction solubility of PZQ increases apparently with the augmented experimental temperature. The solubility of PZQ in mono-solvents exhibits the following order from maximum to minimal at 298.15 K: DMA (0.04891) > DMF (0.04191) > 2-butoxyethanol (0.03351) > 2-propoxyethanol (0.03137) > 2-ethoxyethanol (0.02931) > n-butanol (0.02008) > n-propanol (0.01834) > ethanol (0.01735) > n-propyl acetate (0.01446) > n-butyl acetate (0.01183) > ethanediol (0.002505). The highest value in PZQ solubility profile is related to DMA at 323.15 K ( x 1 = 0.1026) and the lowest one is obtained for ethanediol (9.430e-4, T = 278.15 K). The results of using the KAT-LSER model to study the solvent effect of PZQ solubility show that the solute-solvent interactions are principally attributed to the hydrogen bonding basicity and solvent’s self-cohesiveness. Then, the analysis of solute-solvent interaction using MD simulation shows that the interaction between solute and solvent molecules has a great influence on the solubility of PZQ in selected solvents. In addition, all recorded solubility of PZQ was regressed by λh model, modified Apleblat model, Two-Suffix Margules model, NRTL model and UNIQUAC model. By calculating the deviation between the experimental data and the regression data, it shows that the modified Apelblat model and λh model can provide more accurate correlation results for the solubility of PZQ in all the solvents studied. Furthermore, apparent thermodynamic properties of PZQ in all mono-solvents studied were calculated and investigated according to Van’t Hoff equation, and it turns out that the dissolution process is an endothermic, non-spontaneous process driven by entropy.
研究领域:
药学
·
物理化学
✓ 已验证
DOI
高影响因子
Frontiers in Veterinary Science
·
2023
·
IF 3.2
Shiting Xie,Yixing Lu,Jun Wang,Changcheng Lin,Peiyu Ye,Xiaolin Liu,Wenguang Xiong,Zhenling Zeng,Dongping Zeng
Introduction Milbemycin oxime (MBO) and praziquantel (PZQ) have a broad spectrum of biological activity and are commonly used to treat the parasitic infection in the veterinary clinic. In this study, a fast and efficient LC-MS/MS method was established and validated for the simultaneous determination of MBO, PZQ, cis-4-hydroxylated-PZQ (C-4-OH-PZQ) and trans-4-hydroxylated-PZQ (T-4-OH-PZQ) and in cat plasma. Methods Extraction of analytes and internal standards from cat plasma by acetonitrile protein precipitation, allows rapid processing of large batches of samples. MBO, PZQ, C-4-OH-PZQ, T-4-OH-PZQ, and internal standard (IS) were eluted for 13.5 min on a C 18 column with a 0.1% formic acid water/acetonitrile mixture as the mobile phase. Results Results showed that the method had good precision, accuracy, recovery, and linearity. The linearity range was 2.5–250 ng/mL for MBO, and 10–1000 ng/mL for PZQ, C-4-OH-PZQ, and T-4-OH-PZQ. The intra-day and inter-day precision CV values of the tested components were within 15%. The extraction recoveries of the four components ranged from 98.09% to 107.46%. The analytes in plasma remained stable for 6 h at room temperature, 26 h in the autosampler (4 °C), after freeze–thaw (−20°C) cycles, and 60 days in a −20°C freezer. Method sensitivity sufficed for assessing pharmacokinetic parameters of MBO, PZQ, C-4-OH-PZQ, and T-4-OH-PZQ in plasma samples with LLOQ of 2.5 ng/mL for MBO and 10 ng/mL for PZQ, C-4-OH-PZQ, and T-4-OH-PZQ. Conclusion In this study, a selective and sensitive LC-MS/MS method for the simultaneous quantification of MBO, PZQ, C-4-OH-PZQ, and T-4-OH-PZQ in cat plasma was developed and validated.This method had been successfully applied to evaluate the pharmacokinetics of MBO, PZQ, C-4-OH-PZQ, and T-4-OH-PZQ after a single oral administration of 8 mg MBO and 20 mg PZQ in cats.
研究领域:
兽医学
·
分析化学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PARASITOLOGY
·
2024
·
IF 2.1
Weisi Wang,Jun Li,Wenjing Qi,Ying Chen,Mengxiao Tian,Chuanchuan Wu,Yao Zhang,Yingfang Yu,Shuai Han,Xiumin Han,Liping Duan,Wenbao Zhang
Human alveolar echinococcosis is a hard-to-treat and largely untreated parasitic disease with high associated health care costs. The current antiparasitic treatment for alveolar echinococcosis relies exclusively on albendazole, which does not act parasiticidally and can induce severe adverse effects. Alternative, and most importantly, improved treatment options are urgently required. A drug repurposing strategy identified the approved antimalarial pyronaridine as a promising candidate against Echinococcus multilocularis infections. Following a 30-day oral regimen (80 mg kg−1 day−1), pyronaridine achieved an excellent therapeutic outcome in a clinically relevant hepatic alveolar echinococcosis murine model, showing a significant reduction in both metacestode size (72.0%) and counts (85.2%) compared to unmedicated infected mice, which revealed significantly more potent anti-echinococcal potency than albendazole treatment at an equal dose (metacestode size: 42.3%; counts: 4.1%). The strong parasiticidal activity of pyronaridine was further confirmed by the destructive damage to metacestode tissues observed morphologically. In addition, a screening campaign combined with computational similarity searching against an approved drug library led to the identification of pirenzepine, a gastric acid-inhibiting drug, exhibiting potent parasiticidal activity against protoscoleces and in vitro cultured small cysts, which warranted further in vivo investigation as a promising anti-echinococcal lead compound. Pyronaridine has a known drug profile and a long track record of safety, and its repurposing could translate rapidly to clinical use for human patients with alveolar echinococcosis as an alternative or salvage treatment.
研究领域:
药理学
·
寄生虫学
·
传染病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2025
·
IF 6.5
Jing Yuan,Wenhao Su,Jingyang Gao,Xiaoqing Ma,Ronghuan Yin,Tong Jia
Purpose Praziquantel (PZQ) is currently the preferred medication for treating various parasites. However, its use is hindered by several issues, such as poor solubility, first-pass effect, and individual variability. A novel immediate release system was developed by loading PZQ onto Pluronic P123/L64 mixed micelles (PMMs). This approach aims to improve its bioavailability following oral administration.Methods PZQ-PMMs were prepared by thin film dispersion method. The encapsulation efficiency (EE), particle size, and polydispersity index (PDI) were utilized to identify the optimal formulation. Characterization techniques, including electron microscopy, infrared spectroscopy, thermal analysis, and X-ray diffraction were utilized to get an understanding of the molecular interactions between PZQ and micelles. This system was compared with commercially available preparations both in vitro and in vivo.Results The particle size of the prepared PZQ-PMMs (P123:L64 1:1, w/w) was 19.33 ± 0.22 nm, with a PDI value of 0.106 ± 0.044, an EE of 86.88 ± 4.60%, and a drug loading of 4.16 ± 0.21%. Structural characterization results indicated that the spherical micelles were uniformly dispersed, with the drug existing in an amorphous form within PMMs. In vitro, PZQ-PMMs exhibited a faster immediate release in both pH 1.2 and pH 6.8 buffers. In vivo, at the same dosage, the micelles rapidly produced higher blood drug concentrations. The relative bioavailability of PZQ-PMMs was comparable to that of the PZQ 30% ethanol solution and was 1.7 times greater than that of commercially available preparations, with the increase in bioavailability being highly significant (P < 0.01).Conclusion The findings of this study confirm that Pluronic P123/L64 PMMs represent a novel and promising approach for enhancing solubility and bioavailability of PZQ, both in vitro and in vivo. The development of immediate release formulations is anticipated to be an effective option for drugs exhibiting a notable first-pass effect.
研究领域:
药剂学
·
药物递送系统
·
药代动力学
·
纳米医学
·
生物药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Infectious Diseases of Poverty
·
2021
·Vol. 10
·期 1
·1-12
·
IF 4.388
Yang Shi-Jie,Xiao Ning,Li Jing-Zhong,Feng Yu,Ma Jun-Ying,Quzhen Gong-Sang,Yu Qing,Zhang Ting,Yi Shi-Cheng,Zhou Xiao-Nong
Background As a neglected cross-species parasitic disease transmitted between canines and livestock, echinococcosis remains a global public health concern with a heavy disease burden. In China, especially in the epidemic pastoral communities on the Qinghai-Tibet Plateau, the harsh climate, low socio-economic status, poor overall hygiene, and remote and insufficient access to all owned dogs exacerbate the difficulty in implementing the ambitious control programme for echinococcosis. We aimed to design and implement a remote management system (RMS) based on internet of things (IoT) for control and surveillance of echinococcosis by combining deworming devices to realise long-distance smart deworming control, smooth statistical analysis and result display. New methods and tools are urgently needed to increase the deworming coverage and frequency, promote real-time scientific surveillance, and prevent transmission of echinococcosis in remoted transmission areas. Methods From 2016 to 2019, we had cooperated and developed the smart collar and smart feeder with the Central Research Institute of Shanghai Electric Group Co., Ltd. (Shanghai, China) and Shenzhen Jizhi Future Technology Co., Ltd. (Shenzhen, China). From September 2019 to March 2020, We had proposed the RMS based on IoT as a novel tool to control smart deworming devices to deliver efficient praziquantel (PZQ) baits to dogs regularly and automatically and also as a smart digital management platform to monitor, analyse, and display the epidemic trends of echinococcosis dynamically, in real time in Hezuo City, Gannan Tibetan Autonomous Prefecture, Gansu Province, China. Starting from January 2018, The RMS has been maintained and upgraded by Shanghai Yier Information Technology Co., Ltd (Shanghai, China). The database was based on MySQL tools and the Chi-square test was used to probe the difference and changes of variables in different groups. Results The smart collars are fully capable of anti-collision, waterproof, and cold-proof performance, and the battery’s energy is sufficient, the anti-collision rate, water-proof rate, cold-proof rate and voltage normal rate is 99.6% (521/523), 100.0% (523/523), 100.0% (523/523) and 100.0% (523/523), respectively. The RMS can accurately analyse the monitoring data and parameters including positive rates of canine faeces, and the prevalence of echinococcosis in the general population livestock, and children. The data of dogs deworming and surveillance for echinococcosis is able to be controlled using RMS and has expanded gradually in townships to the whole Hezuo region. The automatic delivering PZQ rate, collar positioning rate, deliver PZQ reminding rate, and fault report rate is 91.1% (1914/2102), 92.1% (13 580/14 745), 92.1% (1936/2102) and 84.7% (1287/1519), respectively. After using the RMS from 2019, the missing rate of monitoring data decreased from 32.1% (9/28) to 0 (0/16). A total of 48 administrators (3, 3, 8, 11, 23 at the provincial, municipal, county, township, village levels, respectively) participated in the questionnaire survey, with 93.8% of its overall satisfaction rate. Conclusions The existing difficulties and challenges in the way of prevention and control for echinococcosis can partially be resolved using the innovative, IoT-based technologies and tools. The proposed RMS advance the upgrade of existing manual prevention and control models for echinococcosis, especially in the current ongoing COVID-19 pandemic, as social distance and community blockade continue. Graphic abstract
研究领域:
公共卫生
·
兽医学
·
远程医疗
·
传染病学
·
科技与医疗
✓ 已验证
DOI
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2013
·
IF 2.947
Guangzhao He,Huixin Qi,Meiyu Wang,Jingjing Yang,Fengjiao Wen,Weipeng Wang,Chunhua Qiao,Hongjian Zhang
Schistosomiasis is an infectious disease that has been recognized as a severe health burden for some regions of the world. While praziquantel is the drug of choice, there is an unmet medical need for novel therapies with greater efficacy and resistant profile. DW-3-15 is a novel and promising prodrug possessing both adult and juvenile schistosomes killing capability. Its proposed hydrolytic products, artesunate (ARS), dihydroartemisinin (DHA) and 10-hydroxypraziquantel (10-OHPZQ), are all active in preventing schistosomal infection in relevant disease models. To support pharmacokinetic and PK-PD studies of DW-3-15, a simple, specific and rapid liquid chromatography–tandem mass spectrometry (LC–MS/MS) method was developed and validated for the simultaneous determination of the three active components in rat plasma. Using a short C 18 column (2.1 mm × 50 mm, 5 μm) with linear gradient, a baseline resolution of the three analytes and corresponding internal standards was achieved with a total run time of 6 min. Mass detection was carried out by electrospray ionization in positive MRM mode with ion transitions of m / z 402.2 → m / z 267.3 for ARS, m / z 302.2 → m / z 163.1 for DHA, and m / z 329.2 → m / z 219.4 for 10-OHPZQ. The method was linear over concentration ranges of 1.0–500 ng/mL for ARS, 5.0–2500 ng/mL for DHA, and 1.0–500 ng/mL for 10-OHPZQ. The accuracy was within ±10.0% for ARS, ±6.4% for DHA, and ±13.0% for 10-OHPZQ. The within-run and between-run precision of all three analytes at four concentrations tested were less than 15%, except at the LLOQ for DHA which was between 15 and 20%. The method was successfully applied to pharmacokinetic evaluation of DW-3-15 in rats following intravenous administration.
研究领域:
药理学
·
分析化学
·
传染病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
AQUACULTURE
·
2021
·
IF 4.242
Xiao Tu,Chenxi Duan,Siwei Wu,Shengli Fu,Jianmin Ye
Monogenean parasites are responsible for severe economic losses of both freshwater and marine aquaculture industries. Current chemotherapeutic treatments are consuming, expensive, and harmful to water quality and human health. Medicinal plants are a reliable source of alternative anthelmintic agents. In the pursuit of novel anti-monogenean drugs, in vivo anthelminthic efficacy of 26 selected phytochemical compounds was studied, by choosing Gyrodactylus kobayashi infecting goldfish ( Carassius auratus ) as a model. The screening results showed that four compounds (plumbagin (PLB), thymoquinone, osthole and psoralen) had the highest activity against G. kobayashii with EC 99 value ranging from 0.4 to 4.0 mg/L after 48-h exposure. Among these active compounds, PLB was the most efficacious one and selected for the next study. In vitro trials revealed the clear anti-parasitic effects of PLB, with complete death at 45 min of exposure at a concentration of 2.0 mg/L, withdrawal of PLB afterward did not lead to the recovery of the exposed parasites. Bathing G. kobayashii infected goldfish in PLB also significantly reduced the worm burden, with an extremely low EC 50 value of 0.09 mg/L after 48-h immersion. The results also showed that one short bath using very low concentrations of 0.4–0.7 mg/L for 30–60 min was effective in eliminating G. kobayashii infection with no visible fish toxicity. Acute toxicity assay indicated the 48-h LC 50 of PLB against goldfish was 0.657 mg/L. Furthermore, SEM analysis displayed that PLB-mediated worm killing was associated with the tegumental damages. As seen by TEM , in vivo treatment against G. kobayashii with PLB also caused vacuolization and lysis of parasite's tegument, besides, differing degrees of damage to vitelline cells were observed in treated worms. Collectively, simple chemical structure along with the potent efficacy demonstrated that PLB could serve as an ideal leading compound in the development of a commercial drug to control Gyrodactylus infections in aquaculture
研究领域:
水产养殖学
·
药理学
·
寄生虫学
✓ 已验证
产品关联
DOI
高影响因子
CHINESE JOURNAL OF ANALYTICAL CHEMISTRY
·
2018
·
IF 0.824
Qiang LI,Yuan-Yuan LI,Nan ZHU,Zhu-Xian GAO,Tian-Jun LI,Tong ZHOU,Yu-Long MA
Graphene oxide (GO) was covalently coupled to the surface of amino silica gel by amide bond. β -cyclodextrin ( β -CD) was further chemically bonded with GO to prepare a novel chiral stationary phase. The resulting material was characterized by Fourier transform-infrared (FT-IR) spectra, scanning electron microscopy (SEM), transmission electron microscopy (TEM), elemental analysis and thermogravimetric analysis (TGA). The separation of seven enantiomers was improved in varying degrees. Meanwhile, the stationary phase showed typical characteristics of hydrophilic interaction chromatography (HILIC), and four small nucleoside molecules were separated with the mobile phase of methanol-acetonitrile-water (45:45:10, V/V ) in the HILIC mode. In addition, the separation mechanism of the stationary phase was further explored by studying the effects of mobile phase composition, temperature and pH value on the analyte retention. The low temperature was conducive to the separation of analytes at 20–60 °C. The addition of protonated solvent methanol significantly decreased the retention time of the four analytes. The change of pH affected the degree of protonation of the analyte, the interaction between analytes and the stationary phase, and retention time of analytes. The results showed that GO and β -CD played a synergistic effect in the chiral resolution of the chromatographic stationary phase. The retention of analytes in HILIC was attributed to their mixed-mode retention mechanisms including hydrophilic interaction, electrostatic interaction, hydrogen bonding, π-π stacking and so on.
研究领域:
分析化学
·
材料科学
·
色谱技术
✓ 已验证
产品关联
DOI
高影响因子
VETERINARY PARASITOLOGY
·
2025
·
IF 2.2
Xiao Tu,Jiaxin Hu,Jinghao Peng,Qihan Chen,Yangle Zhao,Zemao Gu
Monogenean parasites are harmful pathogens in aquaculture systems. Current treatment strategies for monogenean infections are unsatisfactory, making the discovery of new drugs urgent. Thymoquinone (TQ), a natural monoterpene isolated from Nigella sativa L., has demonstrated its potential as lead structure against the monogenean parasites. In the present study, the anthelmintic activity of 26 selected TQ analogues was investigated against the monogenean parasite Gyrodactylus kobayashii in the goldfish ( Carassius auratus ). The results indicated that 18 TQ analogues displayed the EC 50 value below 1.0 mg/L, 14 of them showed more potent anthelmintic activity than TQ (EC 50 =0.303 mg/L). Particularly, compounds 9 and 23 exhibited the best efficacies with the EC 50 values of 0.058 and 0.034 mg/L, outperforming the standard drug praziquantel as well. Structure-activity relationship analysis revealed that large electron-donating substituents at the 2-position of the quinone ring contribute to enhanced in vivo anthelmintic activity. Additionally, four analogues ( 9 , 12 , 23 and 25 ) displayed low fish toxicity, with the therapeutic index (TI, LC 50 /EC 50 ) above 9.23, and were selected for further in silico drug‑likeness assessment. The results demonstrated an excellent drug-likeness profile and an adherence to major pharmaceutical companies’ filters for compounds 9 and 23 . Besides, TQ analogue 9 was chosen for an in vivo study in large-scale trial based on its potency, low fish toxicity, and excellent drug-likeness profiles. Treatment of G. kobayashii infected goldfish for 24 h at 0.1 and 0.2 mg/L was effective, reducing the infection prevalence from 100 % to 0 % post-treatment. The experimental fish exhibited normal behavior, despite minor modifications were displayed in the gills and liver according to histopathological results. Collectively, this study suggested that TQ analogues are excellent scaffolds in the discovery of novel anthelmintic agents against monogenean infections.
研究领域:
水产养殖学
·
药理学
·
寄生虫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2018
·
IF 2.831
Renjie Hui,Yueying Gao,Jingyi Liu,Haili Liu,Chunlei Tang,Bainian Feng
Heart failure (HF) is one of the most serious health problems worldwide. A new positive inotropic compound, an isonicotinylhydrazide derivative (AF-HF001) was designed recently. A liquid chromatography-tandem mass spectrometry (LC–MS/MS) method was developed for the determination of the target analyte in mouse plasma. Samples were prepared by one step precipitation with ethyl acetate and stored in acetonitrile. Chromatographic analysis was carried out on a Hypersil Gold C 18 column (2.1 mm × 50 mm, 3 μm) with a gradient mobile phase consisting of acetonitrile and 0.1% aqueous formic acid. The analyte was detected by selective reaction monitoring (SRM) mode with target quantitative ion pair of m/z 292.1 → 148.2, using praziquantel as the internal standard (IS) m/z 313.1 → 203.2. Good linearity ( r = 0.995) was observed over a wide concentration range. The validation of method showed acceptable recovery and precision. The method has been then applied to a very first pharmacokinetic assay of AF-HF001 in mice.
研究领域:
药物分析
·
心血管药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2022
·
IF 8.008
Jieqing Feng,Qisheng Zhong,Ting Zhou
The online coupling technique of sample preparation with chromatography is a frontier topic in analytical chemistry since it minimizes errors caused by sample loss, shortens analysis time, and reduces solvent consumption. An online pressure change focusing-supercritical fluid selective extraction chromatography (PCF-SFSEC) technique was developed in this study, realizing extraction, purification, separation, and detection in a single run with only microliter-scale samples. The pressure change focusing strategy achieved column-head stacking by decreasing the dissolving capacity of the supercritical fluid, enabling the large volume introduction of extractants into supercritical fluid chromatography without causing peak broadening or distortion. All the extracts could be directly loaded into the chromatography system without split flow. Based on the supercritical fluid selective extraction (SFSE) strategy, the sorbents removed interferences and water from samples, effectively alleviating matrix effects and realizing the direct aqueous sample analysis. The efficiency of online PCF-SFSEC was demonstrated by the enantioselective analysis of 22 chiral drugs in rat plasma, covering eight categories with different pharmacological effects. The entire analysis took 25 min, consuming only 5 μL samples. All analytes in PCF-SFSEC obtained sharp and symmetrical peaks with resolutions higher than 1.0, and 86% had resolutions higher than 1.5. Limits of quantification (LOQs) ranged from 0.0600 to 32.1 μg/L. Recoveries were in the range of 75.8–117.2%. In addition, the developed approach obtained more satisfactory repeatability and significantly reduced matrix effects than conventional methods. The newly established online PCF-SFSEC technique is believed to be a green and powerful tool for the chiral analysis of complex samples.
研究领域:
分析化学
·
色谱技术
·
药物分析
·
样品制备技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）