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co-Condensation Synthesis of Salicylaldimine Calcium Complex Containing Mesoporous Silica Nanoparticles as Carriers for Drug Release

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Chemical Research in Chinese Universities 2014年第4期30卷 531-537页

作者： TANG Duihai ZHANG Weiran WANG yifan miao Jing QIAO Zhen'an HUO Qisheng ZHANG Lirong State Key Laboratory of Inorganic Synthesis and Preparative Chemistry College of Chemistry Jilin University Changchun 130012 P. R. China

A series of functional mesoporous silica nanoparticles（MSNs） was synthesized by a one-step simple synthesis approach involving co-condensation of tetraethoxysilane（TEOS） and salicylaldimine ligand（Sal-Si） in the presence of cetyltrimethylammonium chloride（CTAC） under basic *** target MSNs with different sizes （50,100 and 200 nm,respectively） were ***,the Ca^2＋ cations were also introduced into *** prepared nanoparticles were characterized by means of infrared（IR） spectra,thermogravimetric analysis（TGA）,inductively coupled plasma（ICP）,CHN elemental analysis,nitrogen adsorption-desorption,scanning electron microscope（SEM） and transmission electron microscope（TEM）.Ibuprofen（IBU） which contains carboxyl groups was selected as a model *** results of drug loading and release reveal that the loading capacities and release behaviors of the model drug are highly dependent on the Ca^2＋ cations in *** release of IBU from the MSNs functionalized by Ca^2＋ cations is found to be effectively controlled when compared to the release from the MSNs without the functionalization of Ca^2＋ cations,which is due to the ionic interaction between carboxyl groups in IBU and Ca^2＋ cations in MSNs.

关键词： Mesoporous silica nanoparticle co-Condensation method Release of ibuprofen Calcium ion

Boosting SN38-based oral chemotherapy to combine reductionbioactivated structured lipid-mimetic prodrug with ascorbic acid

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Nano Research 2022年第10期15卷 9092-9104页

作者： Helin Wang Qi Lu yifan miao Jiaxuan Song Mingyang Zhang Zixuan Wang Haotian Zhang Zhonggui He Chutong Tian Jin Sun Department of Pharmaceutics Wuya College of InnovationShenyang Pharmaceutical UniversityShenyang 110016China School of Life Science and Biopharmaceutics Shenyang Pharmaceutical UniversityShenyang 110016China

The reduction-responsive disulfide bonds have been widely used as bioactive linkages to facilitate a rapid release of anticancer drugs into tumor ***,the activation can be hindered by the kinetics of the thiol-disulfide exchange *** with an additional reductant is a promising strategy to further boost drug ***,inspired by the specific absorption mechanism of triglyceride fat,structured lipid-mimetic oral prodrugs of 7-ethyl-10-hydroxycamptothecin(SN38)were designed to improve intestinal permeability and bypass the first-pass ***38 prodrugs were prepared into lipid formulations that could self-emulsify into nano-sized particles after entering the gastrointestinal ***,we found that the oral bioavailability of the prodrug lipid formulation could be up to 2.69-fold higher than that of the parent SN38,indicating an effective oral *** addition,the reduction-responsive disulfide bond was used as a linker,and ascorbic acid(ASC)was coadministrated to further promote the efficient release of SN38 from the *** enhanced the oral antitumor effect of the reduction-responsive oral prodrug and exhibited good *** summary,the combination of a structured lipid-mimetic prodrug and ASC was firstly demonstrated to boost the oral chemotherapy effect of the difficult-for-oral chemotherapeutics.

关键词： oral chemotherapy structured lipid-mimetic prodrug 7-ethyl-10-hydroxycamptothecin(SN38) ascorbic acid

Fine-tuning the activation behaviors of ternary modular cabazitaxel prodrugs for efficient and on-target oral anti-cancer therapy

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Asian Journal of Pharmaceutical Sciences 2024年第2期19卷 188-203页

作者： Mingyang Zhang yifan miao Can Zhao Tong Liu Xiyan Wang Zixuan Wang Wenxin Zhong Zhonggui He Chutong Tian Jin Sun Department of Pharmaceutics Wuya College of InnovationShenyang Pharmaceutical UniversityShenyang 110016China Key Laboratory of Advanced Drug Delivery Systems of Zhejiang Province Hangzhou 310058China Joint International Research Laboratory of Intelligent Drug Delivery Systems Ministry of EducationShenyang 110016China Liaoning Provincial Institute of Drug Inspection and Testing Shenyang 110036China

The disulfide bond plays a crucial role in the design of anti-tumor prodrugs due to its exceptional tumor-specific redox responsiveness. However, premature breaking of disulfide bonds is triggered by small amounts of reducing substances (e.g., ascorbic acid, glutathione, uric acid and tea polyphenols) in the systemic circulation. This may lead to toxicity, particularly in oral prodrugs that require more frequent and high-dose treatments. Fine-tuning the activation kinetics of these prodrugs is a promising prospect for more efficient on-target cancer therapies. In this study, disulfide, steric disulfide, and ester bonds were used to bridge cabazitaxel (CTX) to an intestinal lymph vessel-directed triglyceride (TG) module. Then, synthetic prodrugs were efficiently incorporated into self-nanoemulsifying drug delivery system (corn oil and Maisine CC were used as the oil phase and Cremophor EL as the surfactant). All three prodrugs had excellent gastric stability and intestinal permeability. The oral bioavailability of the disulfide bond-based prodrugs (CTX-(C)S-(C)S-TG and CTX-S-S-TG) was 11.5- and 19.1-fold higher than that of the CTX solution, respectively, demonstrating good oral delivery efficiency. However, the excessive reduction sensitivity of the disulfide bond resulted in lower plasma stability and safety of CTX-S-S-TG than that of CTX-(C)S-(C)S-TG. Moreover, introducing steric hindrance into disulfide bonds could also modulate drug release and cytotoxicity, significantly improving the anti-tumor activity even compared to that of intravenous CTX solution at half dosage while minimizing off-target adverse effects. Our findings provide insights into the design and fine-tuning of different disulfide bond-based linkers, which may help identify oral prodrugs with more potent therapeutic efficacy and safety for cancer therapy.

关键词： Steric disulfide bond Triglyceride-like pr odrugs Cabazitaxel Lymphatic transport Oral chemotherapy

Erratum to:Boosting SN38-based oral chemotherapy to combine reduction-bioactivated structured lipid-mimetic prodrug with ascorbic acid

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Nano Research 2023年第4期16卷 6010-6011页

作者： Helin Wang Qi Lu yifan miao Jiaxuan Song Mingyang Zhang Haotian Zhang Zhonggui He Zixuan Wang Chutong Tian Jin Sun Department of Pharmaceutics Wuya College of InnovationShenyang Pharmaceutical UniversityShenyang 110016China School of Life Science and Biopharmaceutics Shenyang Pharmaceutical UniversityShenyang 110016China

Erratum to Nano Research 2022,15(10):9092-9104 https://***/10.1007/s12274-022-4544-7 Figure 9 was unfortunately mistakenly *** error did not affect any of the conclusions from the published paper.

关键词： chemotherapy Figure combine

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行政裁决适用变更判决的法律空间之探讨

法律适用 2023年第8期 42-51页

作者：闫尔宝苗奕凡南开大学法学院

在现行行政裁决案件中,囿于撤销判决的局限性,法院无法深入裁处民事争议,行政附带民事诉讼途径也面临一定困境。行政裁决适用变更判决有其正当性基础。依据当事人之间发生的民事纠纷是否必须由行政机关先行裁决,可以将行政裁决区分为前... 详细信息

在现行行政裁决案件中,囿于撤销判决的局限性,法院无法深入裁处民事争议,行政附带民事诉讼途径也面临一定困境。行政裁决适用变更判决有其正当性基础。依据当事人之间发生的民事纠纷是否必须由行政机关先行裁决,可以将行政裁决区分为前置型与选择型两种类型。对前者而言,在不涉及判断余地的情况下,法院对不确定法律概念的解释要优于行政机关,在案件事实清楚、证据充分的情况下,可以行使变更权。在现阶段,选择型行政裁决的司法审查应保持充分的谦抑性,并无变更判决的适用空间。为了实质性解决行政争议,应当从保障当事人诉权、强化法官依职权调取证据的责任、禁止不利变更原则例外等三方面对行政裁决适用变更判决予以完善。

关键词：行政裁决变更判决不确定法律概念判断余地实质性解决行政争议

行政裁决在多元化纠纷解决机制中的定位与完善

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北京行政学院学报 2023年第4期 117-128页

作者：宋华琳苗奕凡南开大学法学院天津300350

作为多元化纠纷解决机制的重要组成部分,行政裁决不仅可以疏解法院办案压力,扮演化解民事纠纷“分流阀”的角色,还可以在行政性解纷机制里发挥“中坚力量”的作用。行政裁决在多元解纷机制中存在认可度低、制度设计缺失、救济途径成本... 详细信息

作为多元化纠纷解决机制的重要组成部分,行政裁决不仅可以疏解法院办案压力,扮演化解民事纠纷“分流阀”的角色,还可以在行政性解纷机制里发挥“中坚力量”的作用。行政裁决在多元解纷机制中存在认可度低、制度设计缺失、救济途径成本高等诸多困境。为此,有必要从规范适用范围、强化主体独立与提升程序公正三方面对行政裁决进行制度重构。为优化行政裁决与其他非诉机制的协调,需要推动行政裁决与民间性解纷机制的互动,并强化行政调解与行政裁决的配合。为促进行政裁决与诉讼机制的衔接,需要充分发掘不同种类行政裁决的独特属性,重新构建差异化的诉讼救济途径。

关键词：多元化纠纷解决机制行政裁决非诉纠纷解决机制民事争议

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注册商标无效宣告案件救济模式之完善

行政与法 2022年第6期 119-128,F0003页

作者：苗奕凡南开大学法学院天津300350

以行政诉讼案件审理模式作为注册商标无效宣告的救济程序,不仅无法有效回应当事人诉求,还会浪费有限的行政与司法资源。此外,民事侵权程序与无效宣告二元分立体制易造成当事人乃至公共利益的损失。从行为本质来看,商标评审机构复审决定... 详细信息

以行政诉讼案件审理模式作为注册商标无效宣告的救济程序,不仅无法有效回应当事人诉求,还会浪费有限的行政与司法资源。此外,民事侵权程序与无效宣告二元分立体制易造成当事人乃至公共利益的损失。从行为本质来看,商标评审机构复审决定符合行政复议的特征,可以继续适用行政诉讼,但需扩展司法变更权的行使范围。商标评审机构裁定属于行政裁决,应当改采民事诉讼救济途径。在商标民事侵权诉讼中,法院可以在个案中直接认定商标有效性,达到一次性化解纠纷的目的。

关键词：商标无效宣告行政诉讼行政复议行政裁决民事诉讼

运动疗法联合心理护理在妊娠期糖尿病患者护理中的应用效果

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中国医药指南 2021年第9期19卷 1-3页

作者：苗艺凡沈阳市妇婴医院辽宁沈阳110015

目的针对患有妊娠期糖尿病的孕产妇采用运动疗法联合心理护理后的临床效果进行分析。方法在本院2018年6月至2019年5月,随机选取患有妊娠期糖尿病的孕产妇80例,观察组(n=40)采用运动疗法联合心理护理干预,对比组(n=40)采用常规护理法,对... 详细信息

目的针对患有妊娠期糖尿病的孕产妇采用运动疗法联合心理护理后的临床效果进行分析。方法在本院2018年6月至2019年5月,随机选取患有妊娠期糖尿病的孕产妇80例,观察组(n=40)采用运动疗法联合心理护理干预,对比组(n=40)采用常规护理法,对比两组孕产妇的焦虑/抑郁情绪改善情况、护理效果、血糖控制情况以及分娩结局。结果观察组孕产妇的焦虑/抑郁情绪改善情况、护理效果、血糖控制情况以及分娩结局均要优于对比组(P<0.05)。结论通过对患有妊娠期糖尿病的孕产妇进行运动疗法联合心理护理后,能够有效提高孕产妇的护理效率,使孕产妇的心理情绪和血糖指标得到有效控制,并有效改善其分娩结局。

关键词：妊娠期糖尿病运动疗法心理护理护理效果分娩结局联合护理

“三位一体”无缝隙护理服务模式在妊娠期高血压患者中的应用效果

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中国医药指南 2021年第10期19卷 158-160页

作者：苗艺凡沈阳市妇婴医院辽宁沈阳110015

目的探讨妊娠期高血压患者实施“三位一体”无缝隙护理服务模式的效果。方法选择96例妊娠期高血压患者为研究对象,均为2017年5月至2019年5月在我院接受治疗,按照护理模式的不同分为对照组(n=48)和研究组(n=48)。对照组实施常规护理服务... 详细信息

目的探讨妊娠期高血压患者实施“三位一体”无缝隙护理服务模式的效果。方法选择96例妊娠期高血压患者为研究对象,均为2017年5月至2019年5月在我院接受治疗,按照护理模式的不同分为对照组(n=48)和研究组(n=48)。对照组实施常规护理服务模式,研究组实施“三位一体”无缝隙护理服务模式。比较两组的护理效果。结果研究组收缩压与舒张压低于对照组(P<0.05)。研究组焦虑、敌对、抑郁、强迫、精神病性症状评分明显低于对照组(P<0.05)。研究组心理功能、生理功能、社会功能、总体健康评分明显优于对照组(P<0.05)。研究组护理满意度明显高于对照组(P<0.05。结论对妊娠期高血压患者实施“三位一体”无缝隙护理服务模式,可有效控制其血压水平,疏导消极情绪,提高生活质量以及护理满意度。

关键词：妊娠期高血压三位一体无缝隙护理服务模式生活质量护理满意度