Journal of pharmaceutical sciences最新文献_第9页

An integrated approach combining experimental, informatics and energetic methods for solid form derisking of PF-06282999. 结合实验、信息学和能量学方法的综合方法用于 PF-06282999 的固态脱脂。

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2024-10-16 DOI: 10.1016/j.xphs.2024.10.013

Ghazala Sadiq, Shubham Sharma, Joanna S Stevens, Pablo Martinez-Bulit, Lily M Hunnisett, Christopher Cameron, Brian Samas, Emma Hawking, Nicholas Francia, Jeff Lengyel, Elna Pidcock, Sadia Rahman, Matthew Nisbet, Kevin Back, Cheryl Doherty, Patricia Basford, Timothy G Cooper, Garry O'Connor, Rajni M Bhardwaj

引用次数: 0

Differentiation of puerarin chelate from salt by phase solubility test. 通过相溶性测试区分葛根素螯合物和盐类

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2024-10-16 DOI: 10.1016/j.xphs.2024.10.007

Yuanfeng Wei, Xin Chen, Runxue Ding, Jingwen Zhang, Hui Chen, Junxiao Zhu, Jianjun Zhang, Peiya Shen

{"title":"Differentiation of puerarin chelate from salt by phase solubility test.","authors":"Yuanfeng Wei, Xin Chen, Runxue Ding, Jingwen Zhang, Hui Chen, Junxiao Zhu, Jianjun Zhang, Peiya Shen","doi":"10.1016/j.xphs.2024.10.007","DOIUrl":"10.1016/j.xphs.2024.10.007","url":null,"abstract":"Different from salt, metal chelate is a novel state of drug constructed by more separate coordinate bonds to form a chelating circle. Due to their composition similarity, it is hard to distinguish them except identifying ionic bond (i.e., salt) or coordinate bond (i.e., chelate) in the single crystal structure. In this study, sodium chelate (CDCC No: 1865670) and lithium salt (CDCC No: 2161617) of puerarin (PUE) was prepared. In addition to difference in single crystal structure, it was found that they showed totally different phase solubility behaviors: lithium salt demonstrated a typical inverse proportion curve as other common salts, while sodium chelate exhibited disordered scatters. However, when incorporating the unit PUE-Na complex in solution state and complexation constant K11 in chemical equation, the scatters in phase solubility diagram of chelate could be well fitted and the value of K11 was dramatically higher with orders of magnitude than the dissociation constant Kc; while processing phase solubility curve of lithium salt by incorporating complex item, it could not well match the curve at all. PUE sodium chelate is more likely to be a weak electrolyte with partial dissociation, while PUE lithium salt acted as a strong electrolyte with complete dissociation. The phase solubility test would be served as a surrogate tool for differentiation of chelates from salts when single crystal was not available.","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dissolution, phase behavior and mass transport of amorphous solid dispersions in aspirated human intestinal fluids. 无定形固体分散体在吸入人体肠液中的溶解、相态行为和质量传输。

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2024-10-16 DOI: 10.1016/j.xphs.2024.10.005

Ahmed Elkhabaz, Dana E Moseson, Joachim Brouwers, Patrick Augustijns, Lynne S Taylor

{"title":"Dissolution, phase behavior and mass transport of amorphous solid dispersions in aspirated human intestinal fluids.","authors":"Ahmed Elkhabaz, Dana E Moseson, Joachim Brouwers, Patrick Augustijns, Lynne S Taylor","doi":"10.1016/j.xphs.2024.10.005","DOIUrl":"10.1016/j.xphs.2024.10.005","url":null,"abstract":"Amorphous solid dispersions (ASDs) typically show improved dissolution and generate supersaturated solutions, enhancing the oral bioavailability of poorly soluble drugs. To gain insights into intraluminal ASD behavior, we utilized two poorly soluble drugs with different crystallization tendencies, atazanavir and posaconazole, prepared as ASDs at a 10% drug loading with hydroxypropyl methylcellulose acetyl succinate (HPMCAS). We evaluated their release in aspirated fasted-state human intestinal fluid (FaHIF), and multi-component fasted-state simulated intestinal fluid (composite-FaSSIF), characterizing the supersaturation profiles and drug-rich nanodroplets that formed. Complete release was observed for atazanavir ASDs over a 90 min period. Flux for dissolved atazanavir ASDs remained high over the experimental time period of 3 h. In contrast, posaconazole solution concentrations were initially high and then decreased. Likewise, flux was initially high and then decreased where these changes are attributed to crystallization of the drug. Generation of spherical nano-sized amorphous droplets of ∼100-150 nm was found to occur in ex vivo FaHIF media for both ASDs, maximizing the diffusive flux during the supersaturation window. Moreover, buffer capacity differences were postulated to influence release rates of ASDs in simulated vs aspirated fluids. Importantly, the solution phase phenomena observed during ASD release in simulated fluids, namely amorphous nanodroplet formation and drug crystallization, were also found to occur in aspirated luminal fluids.","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Impact of Surface Tension, Viscosity, Pump Settings, and Nozzle Size on Filling Process Capability and Accuracy in High-Concentration Biopharmaceuticals. 表面张力、粘度、泵设置和喷嘴尺寸对高浓度生物制药灌装工艺能力和精度的影响

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2024-10-16 DOI: 10.1016/j.xphs.2024.10.020

Qizhou Chen, Chenxi Wang, Tingting Wang, Bin Lei, Jing Wang, Jeremy Guo

{"title":"Impact of Surface Tension, Viscosity, Pump Settings, and Nozzle Size on Filling Process Capability and Accuracy in High-Concentration Biopharmaceuticals.","authors":"Qizhou Chen, Chenxi Wang, Tingting Wang, Bin Lei, Jing Wang, Jeremy Guo","doi":"10.1016/j.xphs.2024.10.020","DOIUrl":"https://doi.org/10.1016/j.xphs.2024.10.020","url":null,"abstract":"Filling is the final critical unit operation in the manufacturing process of liquid biological drug products. This paper thoroughly investigates the influence and mechanisms of peristaltic pump settings, nozzle size, product surface tension and viscosity on the biopharmaceutical filling processes based on the established filling process model of surrogates. Our study highlights the significant role of pump settings in influencing filling process capability indexes, in addition to their primary function of regulating flow rate. Surface tension minimally impacts flow behavior but significantly regulates the final drop's behavior, with lower surface tension increasing dripping tendencies. Viscosity proves crucial; higher viscosity intensifies friction and head loss of filling flow in tube/nozzle, causing pressure and flow rate losses, more pronounced dripping, and worse filling accuracy. Furthermore, nozzle size moderates the impact of pump settings, surface tension, and viscosity on filling performance. Larger nozzles help mitigate these effects, contributing to enhanced stability in filling performance under challenging conditions. For high-concentration biopharmaceuticals with elevated viscosity during filling, utilizing larger nozzles and reducing pump speed could achieve enhanced Cpk values and improved filling accuracy. Understanding the complex interactions among these factors is vital for optimizing the biopharmaceutical industry, promoting cost-effective practices, and enhancing production efficiency.","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Letter to Editor: Comments about "Structural studies of a non-stoichiometric channel hydrate using high resolution X-ray powder diffraction, solid-state nuclear magnetic resonance, and moisture sorption methods". 致编辑的信：关于 "利用高分辨率 X 射线粉末衍射、固态核磁共振和吸湿方法对非均匀通道水合物进行结构研究 "的评论。

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2024-10-16 DOI: 10.1016/j.xphs.2024.10.006

Jean René Authelin

引用次数: 0

A novel cocrystal approach celecoxib with piperine: Simultaneously enhance dissolution rate and compressibility. 塞来昔布与胡椒碱的新型共晶体方法：同时提高溶出率和可压缩性

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2024-10-15 DOI: 10.1016/j.xphs.2024.10.011

Lili Fitriani, Fauziyyah Dirfedli, Yori Yuliandra, Dwi Setyawan, Masaki Uchida, Hironaga Oyama, Hidehiro Uekusa, Erizal Zaini

{"title":"A novel cocrystal approach celecoxib with piperine: Simultaneously enhance dissolution rate and compressibility.","authors":"Lili Fitriani, Fauziyyah Dirfedli, Yori Yuliandra, Dwi Setyawan, Masaki Uchida, Hironaga Oyama, Hidehiro Uekusa, Erizal Zaini","doi":"10.1016/j.xphs.2024.10.011","DOIUrl":"10.1016/j.xphs.2024.10.011","url":null,"abstract":"Celecoxib, a selective COX-2 inhibitor non-steroidal anti-inflammatory drug (NSAID), exhibits analgesic and anti-inflammatory properties similar to piperine, the secondary metabolite of Piper nigrum L. Unfortunately, celecoxib has a low compressibility and low dissolution rate in aqueous medium. This study aimed to prepare a cocrystal of celecoxib and piperine to enhance the dissolution rate and compressibility properties of celecoxib. The cocrystal was synthesized using the seeding method and thoroughly characterized using Powder X-ray diffraction (XRD), differential scanning calorimetry (DSC), infrared spectrophotometry, and single-crystal X-ray diffraction techniques. The complete change in PXRD, decrease in melting point in DSC measurements, and shift in the NH stretching band in the FT-IR spectrum suggested the formation of cocrystals phase. Single-crystal XRD confirmed the formation of an equimolar ratio of cocrystals of celecoxib and piperine. The intrinsic dissolution test was conducted to confirm the impact on the cocrystal to dissolution, and it showed a slight increase compared to intact celecoxib. To assess the physico-mechanical properties, the cocrystal powders were compressed into tablets with varying forces. The results demonstrated a significant improvement in compressibility compared with intact celecoxib owing to the slip plane in the crystal lattice of the cocrystal. In conclusion, our novel celecoxib-piperine cocrystal exhibited distinct physicochemical characteristics compared to intact celecoxib, showing enhanced dissolution rate and compressibility.","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Bioequivalence requirements for orally inhaled and nasal drug products and use of novel physiologically based biopharmaceutics modeling approaches for assessing in vivo performance. 口服和鼻腔药物产品的生物等效性要求，以及使用基于生理学的新型生物药剂学建模方法评估体内性能。

IF 4.3 3区医学

Journal of pharmaceutical sciences Pub Date : 2024-10-15 DOI: 10.1016/j.xphs.2024.10.009

Aravind Rachapally, Rajkumar Boddu, Sivacharan Kollipara, Tausif Ahmed

{"title":"Bioequivalence requirements for orally inhaled and nasal drug products and use of novel physiologically based biopharmaceutics modeling approaches for assessing in vivo performance.","authors":"Aravind Rachapally, Rajkumar Boddu, Sivacharan Kollipara, Tausif Ahmed","doi":"10.1016/j.xphs.2024.10.009","DOIUrl":"10.1016/j.xphs.2024.10.009","url":null,"abstract":"Orally inhaled and nasal drug products (OINDPs) are complex due to the interplay between the device, formulation, and patient characteristics. Establishing bioequivalence (BE) of OINDPs with reference is highly complex and require in vitro, in vivo pharmacokinetic and comparative clinical endpoint studies that are challenging to conduct. In order to increase the rate of submission and approval of generics, regulatory agencies are encouraging the use of alternative in vitro and in silico methodologies to replace complex in vivo studies. The present review attempts to summarize current understanding of alternative BE approaches for OINDPs. In vitro characterization studies required for establishing BE for OINDPs considering USFDA and EMA guidance's are detailed. In silico models such as pulmonary compartmental absorption and transit (PCAT) with emphasis on model input parameters are portrayed. Further, two detailed case studies of inhalation nebulizer and nasal spray formulations are described where PCAT models are developed for predicting BE and local concentrations. Lastly, current understanding of such BE approaches from regulatory perspectives are discussed summarizing recent regulatory workshops and through collation of USFDA product specific guidance's for almost 70 drug products. Overall, this manuscript can act as ready-to-use guide to understand alternative approaches for establishing BE for OINDPs.","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Changes in drug crystallinity in a commercial tacrolimus amorphous formulation result in variable pharmacokinetics. 商用他克莫司无定形制剂中药物结晶度的变化导致不同的药代动力学。

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2024-10-15 DOI: 10.1016/j.xphs.2024.09.025

Lynne S Taylor, Niraj S Trasi, Hitesh S Purohit, Dajun Sun, Minori Kinjo, Zhanglin Ni, Sanjida Mahjabeen, Kairui Kevin Feng, Wei-Jhe Sun, Murali K Matta, Brian Decker, Raymond E Galinsky

{"title":"Changes in drug crystallinity in a commercial tacrolimus amorphous formulation result in variable pharmacokinetics.","authors":"Lynne S Taylor, Niraj S Trasi, Hitesh S Purohit, Dajun Sun, Minori Kinjo, Zhanglin Ni, Sanjida Mahjabeen, Kairui Kevin Feng, Wei-Jhe Sun, Murali K Matta, Brian Decker, Raymond E Galinsky","doi":"10.1016/j.xphs.2024.09.025","DOIUrl":"10.1016/j.xphs.2024.09.025","url":null,"abstract":"Tacrolimus capsules contain the drug as the amorphous form. It is well known that drug crystallinity is a risk factor for the performance of amorphous formulations. This study investigated the impact of varying levels of crystalline drug on the pharmacokinetics of tacrolimus following oral dosing of a 5 mg capsule under fasting conditions. Two treatments with percent crystallinity of 20% and 50% were achieved by exposing a marketed generic tacrolimus product to open dish storage conditions of 35 °C and 75% relative humidity (RH) for up to 20 days. Crystallinity was monitored with X-ray powder diffraction. Prograf®, the reference listed drug (RLD), an amorphous generic drug product, and generic drug products containing 20% and 50% crystalline tacrolimus were evaluated. All four treatments were administered to healthy participants in a randomized, single-dose, four-treatment, four-period, four-way crossover study. Blood sampling occurred over 24 h. The amorphous generic tacrolimus product was determined not to be bioequivalent to the RLD. The capsules containing both 20% and 50% crystalline tacrolimus also failed the bioequivalence recommendations when compared to the amorphous generic or to the RLD. Both levels of crystalline tacrolimus resulted in BE failure for both Cmax and AUC parameters. The impact of tacrolimus crystallization was greater for maximum blood concentration (Cmax) values relative to the area-under-the-curve (AUC) values. This study demonstrates that crystalline tacrolimus formed in a marketed generic product and these changes resulted in variable pharmacokinetics which could be of significant clinical concern.","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correlation of surface properties with dissolution behavior of amorphous solid dispersion of Riluzole and its pharmacodynamic evaluation. 利鲁唑无定形固体分散体表面特性与溶解行为的相关性及其药效学评价

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2024-10-15 DOI: 10.1016/j.xphs.2024.10.010

Kanchan Bharti, Abhishek Jha, Manish Kumar, Manjit, Amol Parasram Satpute, Akhilesh, Vinod Tiwari, Brahmeshwar Mishra

{"title":"Correlation of surface properties with dissolution behavior of amorphous solid dispersion of Riluzole and its pharmacodynamic evaluation.","authors":"Kanchan Bharti, Abhishek Jha, Manish Kumar, Manjit, Amol Parasram Satpute, Akhilesh, Vinod Tiwari, Brahmeshwar Mishra","doi":"10.1016/j.xphs.2024.10.010","DOIUrl":"10.1016/j.xphs.2024.10.010","url":null,"abstract":"Formulation of amorphous solid dispersion (ASD) of any poorly water-soluble drug is among the most promising techniques to increase the dissolution profile of drug and hence its bioavailability. Various literatures give evidences of the role of drug-polymer interactions in the ASD systems, very little information is available about the surface properties of the drug molecule and their ASDs which contributes to a higher dissolution profile. Current work focuses on exploring the surface behavior of a poorly water-soluble drug Riluzole (RLZ) and its ASDs prepared with two highly hydrophilic polymers, polyacrylic acid (PAA), and polyvinylpyrrolidone vinyl acetate (PVP VA). Initial characterization using X-ray diffraction (XRD) revealed about the weight fraction of drug required to prepare a single-phase homogenous system with both the polymers. The saturation solubility and the dissolution studies showed an increase in RLZ solubility as well as the dissolution profile due to the presence of polymers. The role of polymers in changing the surface properties in terms of wettability and polarity were explored using contact angle method and X-ray photon spectroscopy (XPS). Additionally, the neuroprotective efficacy and dose dependent hepatotoxicity were also evaluated in male wistar rats. These studies confirmed the increase in the surface polarity and hence the enhanced ability of ASD formulations to interact with water. The in vivo studies indicated that at the current recommended dose the efficacy as well as toxicity is increased for the ASD formulation. Hence, this formulation can be given at a lower dose to achieve same therapeutic effect with lower toxicity.","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Importance of RNase monitoring during large-scale manufacturing and analysis of mRNA-LNP based vaccines. 在大规模生产和分析基于 mRNA-LNP 的疫苗过程中监测 RNase 的重要性。

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2024-10-14 DOI: 10.1016/j.xphs.2024.10.012

Robbe Van Pottelberge, Roman Matthessen, Shauna Salem, Ben Goffin, Nancee Oien, Pratima Bharti, David Ripley

{"title":"Importance of RNase monitoring during large-scale manufacturing and analysis of mRNA-LNP based vaccines.","authors":"Robbe Van Pottelberge, Roman Matthessen, Shauna Salem, Ben Goffin, Nancee Oien, Pratima Bharti, David Ripley","doi":"10.1016/j.xphs.2024.10.012","DOIUrl":"10.1016/j.xphs.2024.10.012","url":null,"abstract":"Ribonucleases (RNases) are ubiquitous in nature, being able to cleave a wide range of polyribonucleotides. While the presence of microbial and viral contamination in sterile manufacturing is highly studied and controlled, there are no standardized practices for evaluating RNase in the production facility. Since the COVID-19 pandemic, mRNA-LNP based vaccines have become part of routine large-scale manufacturing. The unstable nature of mRNA poses new challenges to safeguard the working efficacy of mRNA - Lipid nanoparticle (LNP) based vaccines or therapeutics, where the presence of RNase in the formulation process could have a profound impact on the mRNA integrity. In this article, lessons learned are presented with respect to the evaluation of RNase contamination during LNP drug product formulation and analysis. Using sensitive detection methods, the potential presence of RNase in the manufacturing of mRNA-LNPs was investigated. Additionally, capillary gel electrophoresis (CGE) data, used to measure mRNA integrity, demonstrate the quality of the active mRNA substance and importance of suitable RNase control strategies. The results and cases presented in this paper should pave the way forward for evaluation and control strategies dedicated to mRNA-LNP based vaccines and therapeutics.","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0