Journal of pharmaceutical sciences最新文献_第2页

Presenting the Lynne S. Taylor dedicated issue of JPharmSci®. 推出 Lynne S. Taylor 专刊《JPharmSci®》。

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2024-11-12 DOI: 10.1016/j.xphs.2024.11.001

Kenneth L Audus

引用次数: 0

Discovery of the Most Stable Form of an Adenosine Receptor Antagonist through Virtual Polymorph Screening and Targeted Crystallization. 通过虚拟多态性筛选和定向结晶发现腺苷受体拮抗剂的最稳定形式。

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2024-11-12 DOI: 10.1016/j.xphs.2024.10.027

Dedong Wu, Emma S E Eriksson, Sten O Nilsson Lill, James F McCabe, Christoph Bauer, Michelle L Lamb

{"title":"Discovery of the Most Stable Form of an Adenosine Receptor Antagonist through Virtual Polymorph Screening and Targeted Crystallization.","authors":"Dedong Wu, Emma S E Eriksson, Sten O Nilsson Lill, James F McCabe, Christoph Bauer, Michelle L Lamb","doi":"10.1016/j.xphs.2024.10.027","DOIUrl":"10.1016/j.xphs.2024.10.027","url":null,"abstract":"An innovative approach was developed to identify the optimal crystalline form, usually the thermodynamically most stable form. This method involves using virtual polymorph screening and targeted crystallization based on in silico solid-state modeling. By utilizing advanced crystal structure prediction (CSP) technology, the virtual polymorph screening method helps confirm whether the most stable crystalline form has been identified in actual crystallization experiments. If the predicted most stable form is not observed in experiments, predictions based on the method of COnductor like Screening MOdel for Real Solvents (COSMO-RS) are used to highlight solvent systems that can increase the likelihood of experimentally obtaining the desired form through a targeted crystallization process. In this work, such an approach has enabled the rapid discovery of the most stable polymorphic form and the development of a crystallization process of an adenosine receptor antagonist using minimal amounts of the sample within a shortened timeframe. Additionally, it provides a scientific rationale for ensuring the selection of the most stable form in the early stages of drug discovery, thereby reducing risks in future pharmaceutical development.","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142622884","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

Effect of material properties and extrusion process parameters on permeability of etonogestrel in ethylene vinyl acetate copolymer (EVA) films. 材料特性和挤压工艺参数对乙烯-醋酸乙烯共聚物（EVA）薄膜中依诺孕酮渗透性的影响。

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2024-11-11 DOI: 10.1016/j.xphs.2024.10.057

Ziyue Zhong, Angela Ren, Lance Arbilo, Qiangnan Zhang, William Smith, Bin Qin, Yan Wang, Feng Zhang

{"title":"Effect of material properties and extrusion process parameters on permeability of etonogestrel in ethylene vinyl acetate copolymer (EVA) films.","authors":"Ziyue Zhong, Angela Ren, Lance Arbilo, Qiangnan Zhang, William Smith, Bin Qin, Yan Wang, Feng Zhang","doi":"10.1016/j.xphs.2024.10.057","DOIUrl":"https://doi.org/10.1016/j.xphs.2024.10.057","url":null,"abstract":"Ethylene vinyl acetate copolymers (EVA) have been extensively used in controlled drug delivery systems due to its good biocompatibility and tunable applicability based on simple variations in vinyl acetate (VA) content. We investigated impacts of material properties of EVA, including VA content and molecular weight, as well as extrusion process parameters, including draw down ratio and cooling rate, on permeability of etonogestrel in EVA films. Among all factors studied, the VA content was the most dominant factor that controls drug permeability by affecting crystallinity of EVA. MW, DDR, and cooling rate exhibited less significant effects. The impacts of these factors on crystallinity, crystallite size, and degree of crystalline orientation of EVA were characterized using polarized light microscope, differential scanning calorimetry (DSC) and wide-angle X-ray scattering (WAXS). Based on the solution-diffusion model, the mechanisms by which the crystalline properties controlled drug solubility and diffusivity in EVA were discussed. These results can be applied to investigate the effects of material properties of EVA and manufacturing process conditions on drug release properties of reservoir-type EVA-based drug delivery systems with a rate-controlling membrane.","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142622885","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

Combating Pharmaceutical Folklore: No Alkyl-Sulfonate Impurities Formed During the Synthesis of Sulfonate Salts. 打击制药业的民间传说：磺酸盐合成过程中不会产生烷基磺酸盐杂质。

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2024-11-09 DOI: 10.1016/j.xphs.2024.11.002

David J Snodin

{"title":"Combating Pharmaceutical Folklore: No Alkyl-Sulfonate Impurities Formed During the Synthesis of Sulfonate Salts.","authors":"David J Snodin","doi":"10.1016/j.xphs.2024.11.002","DOIUrl":"https://doi.org/10.1016/j.xphs.2024.11.002","url":null,"abstract":"Whilst an alcohol can be forced to react with a sulfonic acid, this reaction produces minimal ester conversion even under extreme conditions (anhydrous, very low pH) that bear no resemblance to the mild synthetic procedures typically used for the formation of sulfonate salts of basic drugs. The latter involve the addition of a molar equivalent of pharma-grade sulfonic acid to the base form of a drug substance (pKa ≥3.5), dissolved or suspended in an alcohol solvent, normally ethanol (pKa -2). All added acid is neutralized, and so there is no potential for ester formation. Many drug-substance base forms are polyamines, thus preventing the generation of acidic reaction conditions even in the presence of excess of sulfonic acid. Despite the experimental evidence, the perception that short-chain mutagenic alkyl sulfonates are \"potential impurities\" in sulfonate salts is widely held within regulatory bodies. This stance implies that a mechanistically-impossible reaction can occur: nucleophilic displacement by sulfonate anion of the hydroxyl group from a short-chain alcohol under non-acidic conditions. The European Pharmacopoeia (Ph.Eur.) and the British Pharmacopoeia (BP) include \"production statements\" in monographs for sulfonate-salt drug substances requiring a \"risk assessment\" of the production process. Neither body has provided supporting evidence. Information obtained from the BP via Freedom of Information requests showed that expert-group discussions were characterised by a range of ad-hoc opinions rather than an evidence-based evaluation of mechanism, kinetics and experimental data. Alternative sources of alkyl-sulfonate impurities such as methyl methanesulfonate (MMS) arising from the use of impure, reagent-grade methanesulfonic acid (MSA) were not considered. Both BP and Ph.Eur. production statements appear to be based on policy rather than scientific evidence and so should be discontinued.","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142622883","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

Counteracting the loss of release for indomethacin-copovidone ASDs. 抵消吲哚美辛-科波维酮 ASD 的释放损失。

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2024-11-06 DOI: 10.1016/j.xphs.2024.10.022

Dominik Borrmann, Pascal Friedrich, Justin Smuda, Gabriele Sadowski

{"title":"Counteracting the loss of release for indomethacin-copovidone ASDs.","authors":"Dominik Borrmann, Pascal Friedrich, Justin Smuda, Gabriele Sadowski","doi":"10.1016/j.xphs.2024.10.022","DOIUrl":"10.1016/j.xphs.2024.10.022","url":null,"abstract":"This work revisits the changing release behavior of indomethacin(IND)-copovidone amorphous solid dispersions (ASDs) when increasing their drug load (DL). While showing congruent release behavior at DL 0.1, ASDs with DLs of 0.3 and higher show incongruent release finally resulting in a complete loss of release. To study and explain this phenomenon, we modeled the release kinetics of these ASDs and looked into their phase behavior both experimentally and theoretically. We applied a diffusion model to accurately describe experimental release profiles for congruent release, incongruent release as well as for loss of release. Predicted concentration profiles for IND, copovidone, and water within the ASD revealed the formation of an ASD layer that almost exclusively contains amorphous IND. Our phase-diagram predictions and experimental data explain this phenomenon by water-induced phase separation in those parts of the ASD which did absorb water from the dissolution medium. Whereas the evolving copovidone-rich phase dissolved, the IND-rich phase remained undissolved and formed a super-hydrophobic cover of the remaining inner core of the ASD, thus finally completely preventing its dissolution. Higher DLs promote phase separation. This leads to the counterintuitive effect that the higher the DL, the lower the absolute amount of IND released. While the ASD containing 6 mg IND (DL 0.1) released 6 mg IND, the one containing 42 mg IND (DL 0.7) released only 1 mg IND. The theoretical approach applied in this work is for the first time able to quantitatively predict that reducing DL or tablet size could be used to overcome this problem.","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142605056","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

Understanding the effect of plasticizers in film coat materials on the physical stability of amorphous solid dispersions. 了解薄膜涂层材料中的增塑剂对无定形固体分散体物理稳定性的影响。

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2024-11-04 DOI: 10.1016/j.xphs.2024.10.024

Kaustav Chatterjee, Ashish Punia, Alex M Confer, Matthew S Lamm

{"title":"Understanding the effect of plasticizers in film coat materials on the physical stability of amorphous solid dispersions.","authors":"Kaustav Chatterjee, Ashish Punia, Alex M Confer, Matthew S Lamm","doi":"10.1016/j.xphs.2024.10.024","DOIUrl":"10.1016/j.xphs.2024.10.024","url":null,"abstract":"Amorphous solid dispersions (ASDs) have been extensively utilized to improve the bioavailability of drugs that have low aqueous solubility. The influence of different excipients on the conversion of amorphous drugs into their crystalline forms in ASDs has been extensively researched. However, there is limited knowledge examining the impact of film coating materials on the physical stability of oral tablet formulations containing ASDs. In this study, we demonstrate that plasticizers present in film coats can have a detrimental impact on the physical stability of ASDs. We systematically compared two frequently used plasticizers in film coats: triacetin and polyethylene glycol 3350 (PEG 3350). To gain mechanistic insights into the detrimental effects of plasticizers on the physical stability of ASDs, plasticizer leaching studies and physical stability studies of solvent-evaporated and spray-dried intermediates (SDI) using two BCS class II drugs were conducted. Triacetin was found to leach into the tablet core within one week when stressed at 40 °C/75 % RH, whereas no leaching was observed for PEG 3350, as discerned from spectroscopic studies. We also found that triacetin-containing ASDs exhibited greater amorphous to crystalline form conversion of the drug compared to PEG 3350-containing ASDs after stability testing. Moreover, the incorporation of triacetin into polymers was found to cause a significant depression of glass transition temperature and upon equilibration with moisture, a drop below room temperature. Overall, these observations underscore the importance of carefully selecting plasticizers to be present in film coatings when developing ASD pharmaceutical products.","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590684","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

Insights into pharmaceutical co-crystallization using coherent Raman microscopy. 利用相干拉曼显微镜深入了解药物共结晶。

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2024-11-02 DOI: 10.1016/j.xphs.2024.10.054

Alba M Arbiol Enguita, Elina Harju, Lea Wurr, Teemu Tomberg, Oona Auvinen, Leena Peltonen, Clare Strachan, Jukka Saarinen

{"title":"Insights into pharmaceutical co-crystallization using coherent Raman microscopy.","authors":"Alba M Arbiol Enguita, Elina Harju, Lea Wurr, Teemu Tomberg, Oona Auvinen, Leena Peltonen, Clare Strachan, Jukka Saarinen","doi":"10.1016/j.xphs.2024.10.054","DOIUrl":"https://doi.org/10.1016/j.xphs.2024.10.054","url":null,"abstract":"Formulating active pharmaceutical ingredients (APIs) as co-crystals requires a thorough understanding of co-crystallization behavior under different process conditions. This study employs two forms of coherent Raman microscopy, narrowband coherent anti-Stokes Raman scattering (CARS) and stimulated Raman scattering (SRS) with spectral focusing, to study co-crystallization via liquid-assisted ball milling. Indomethacin and nicotinamide served as the model API and co-former, and the results were compared with established analytical methods. Narrowband CARS, with univariate peak position analysis, was useful to visualize co-crystal formation, but suffered some degree of signal mixing that affected component identification. Hyperspectral SRS imaging, combined with classical least squares multivariate analysis, separated the different components with high confidence and proved to be a robust and rapid tool to qualitatively and quantitatively image co-crystallization. The coherent Raman imaging results explained divergent co-crystallization endpoints obtained with the conventional solid-state analysis methods. CARS and SRS microscopies also revealed the presence of otherwise undetected trace forms. Finally, we also demonstrated the dramatic reversal of partial co-crystal formation during milling, depending on ethanol content. Overall, the study demonstrates the added value coherent Raman microscopy can provide for analysis of co-crystallization processes.","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569093","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

A survey of solid form landscape: Trends in occurrence and distribution of various solid forms and challenges in solid form selection. 固体形式现状调查：各种固体形态的出现和分布趋势以及固体形态选择方面的挑战。

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2024-11-02 DOI: 10.1016/j.xphs.2024.10.045

Z Jane Li, Yue Lu, Ruiping Wang, Xiaomei Dong, Pengyuan Chen, Jie Duan, Meiting Shi, Liyu Wang, Yuan Liu

{"title":"A survey of solid form landscape: Trends in occurrence and distribution of various solid forms and challenges in solid form selection.","authors":"Z Jane Li, Yue Lu, Ruiping Wang, Xiaomei Dong, Pengyuan Chen, Jie Duan, Meiting Shi, Liyu Wang, Yuan Liu","doi":"10.1016/j.xphs.2024.10.045","DOIUrl":"10.1016/j.xphs.2024.10.045","url":null,"abstract":"This survey provides a comprehensive analysis of solid form screens for 476 new chemical entities (NCEs) conducted at Pharmaron from 2016 to 2023. The findings from this survey reveal notable trends in polymorphism, salt formation, crystallization behavior and molecular weight (MW) distribution of the NCEs evaluated. Most solid form screens were conducted to select the preferred solid form for Investigational New Drug (IND) enabling projects, others were for candidate selection or late-stage development. Comparison to published historical data was made to show changes in occurrence of counterions/co-formers for salts/co-crystals, polymorphs, and the distribution of MWs over time. Increased complexity in the solid-form landscape and selection of the development form are discussed, including challenges in crystallization and selection of lead forms. The distribution of types of crystal forms and the observation of emerging and disappearing polymorphs are presented. These results highlight the evolving challenges and considerations in solid form screening and form selection and offer insights for future pharmaceutical development and crystallization strategies.","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569046","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

β-Cyclodextrin derivatives bind aromatic side chains of the cyclic peptide lanreotide. β-环糊精衍生物结合环肽兰瑞奥肽的芳香族侧链

IF 4.3 3区医学

Journal of pharmaceutical sciences Pub Date : 2024-11-02 DOI: 10.1016/j.xphs.2024.10.042

Negar Jafari, Justin T Douglas, Sarah A Neuenswander, Payam Kelich, Michael J Hageman

{"title":"β-Cyclodextrin derivatives bind aromatic side chains of the cyclic peptide lanreotide.","authors":"Negar Jafari, Justin T Douglas, Sarah A Neuenswander, Payam Kelich, Michael J Hageman","doi":"10.1016/j.xphs.2024.10.042","DOIUrl":"10.1016/j.xphs.2024.10.042","url":null,"abstract":"Cyclodextrin complexation has a potential to modulate the physicochemical properties of peptide drugs. The ability of peptides to form an inclusion complex can be influenced by factors such as size, amino acid sequence of peptide, and the size and charge of the cyclodextrin cavity. In this study, the inclusion complexes of the cyclic peptide drug lanreotide acetate with two common β-cyclodextrin derivatives, Sulfobutyl ether β-CD (SBEβ-CD) and hydroxypropyl β-CD (HPβ-CD) were investigated. NMR spectroscopy was used to examine the interaction between β-cyclodextrin derivatives and specific residues of lanreotide. It was observed that the hydrophobic side chain of aromatic residues in the lanreotide sequence can fit into the cavities of both β-cyclodextrin derivatives. Additionally, NMR revealed a lower diffusion coefficient and higher hydrodynamic radius of complex, indicative of binding to the cavities. Each aromatic residue was individually studied by substituting alanine in lanreotide to measure its association binding with both β-cyclodextrin derivatives. The alanine-substitute study indicated a stronger binding of SBEβ-CD to Lanreotide compared to HPβ-CD. Docking studies suggested that the 1:1 inclusion complex is more favorable than higher-order complexes due to the steric hindrance and size considerations. Docking analysis indicated the stable conformation of all three aromatic side chains with both β-cyclodextrin derivatives, SBEβ-CD and HPβ-CD.","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569096","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 surfactants on solution behavior and membrane transport of amorphous solid dispersions. 表面活性剂对无定形固体分散体的溶液行为和膜传输的影响

IF 4.3 3区医学

Journal of pharmaceutical sciences Pub Date : 2024-11-02 DOI: 10.1016/j.xphs.2024.10.023

Amjad Alhalaweh, Mira El Sayed, Lucia Kovac, Christel A S Bergström

{"title":"Impact of surfactants on solution behavior and membrane transport of amorphous solid dispersions.","authors":"Amjad Alhalaweh, Mira El Sayed, Lucia Kovac, Christel A S Bergström","doi":"10.1016/j.xphs.2024.10.023","DOIUrl":"10.1016/j.xphs.2024.10.023","url":null,"abstract":"The purpose of the study was to develop an amorphous solid dispersion (ASD) of a poorly soluble compound (AK100) and investigate the impact of different surfactants on its dissolution, supersaturation and membrane transport. The solubility of the AK100 was determined in crystalline and amorphous form in the absence and presence of three surfactants at different concentrations: sodium dodecyl sulphate (SDS), polysorbate 80 (PS80) and D-α-tocopherol polyethylene glycol succinate (TPGS). The relation between solubility and surfactant solubilization was evaluated using a computational model. The ASD powder was prepared by solvent evaporation for non-sink dissolution experiments with and without the pre-dissolved surfactants. A transport study with Caco-2 cells was conducted to evaluate the impact of surfactants-based formulation on membrane transport. Both the corresponding crystalline and amorphous solubility of AK100 increased linearly as a function of the surfactant concentrations. The supersaturation was maintained for at least three hours in absence of surfactant and in presence of TPGS, whereas supersaturation declined with SDS and PS80. As expected, the membrane flux of the AK100 was higher for the ASD than for the crystalline powder, and further increased with increased concentration of TPGS. The supersaturation ratio based on the activity-based calculation from Caco-2 cells study was always higher than that of the concentration-based one for the amorphous and crystalline forms of AK100. This study shows how additional solubilizing excipients during formulation development can improve the resulting dissolution and phase behavior of supersaturated drug solution.","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569089","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