| 213 | 0 | 264 |
| 下载次数 | 被引频次 | 阅读次数 |
抑郁症作为一种多维度精神障碍,其核心临床表现为持续性情感调节失调、动机缺失及认知功能损害,已成为全球疾病负担最重的精神卫生问题之一。中药制剂凭借其多成分、多靶点的独特优势,展现出显著的抗抑郁潜力。然而,中药成分的复杂性及血脑屏障的高度选择通透性,限制了其脑部靶向递送与临床转化。新型脑靶向递送系统显著提高了中药活性成分的生物利用度与脑区分布特异性。本文综述了中药制剂在抗抑郁治疗中的作用、血脑屏障在抗抑郁治疗中的影响,重点探讨了纳米递送系统、靶向递送系统、缓释递送系统及吸入递送系统在提升血脑屏障通透性、优化药物释放动力学及降低不良反应方面的最新研究进展。参考文献90篇。
Abstract:Depression,as a multi-dimensional mental disorder,is characterized by its core clinical manifestations of persistent emotional regulation disorder,lack of motivation and cognitive function impairment. It has become one of the mental health problems with the heaviest disease burden worldwide. Traditional Chinese medicine(TCM) preparation,with their unique advantages of multiple ingredients and multiple targets,have demonstrated significant potential in antidepressant. However,the complexity of the ingredients of TCM and the highly selective permeability of the bloodbrain barrier limit its targeted delivery to the brain and clinical transformation. The novel brain-targeted delivery system significantly enhances the bioavailability and brain-specific characteristics of active ingredients in TCM. This article reviews the role of TCM preparation in the treatment of depression and the influence of the blood-brain barrier in the treatment of depression. It focuses on discussing the latest research progress of nano-delivery system,targeted delivery system,sustainedrelease delivery system and inhalation delivery system in enhancing the permeability of the blood-brain barrier,optimizing drug release kinetics and reducing adverse reactions.There are 90 references.
[1]THAPAR A,EYRE O,PATEL V,et al. Depression in young people[J]. Lancet,2022,400(10352):617-631.
[2]NG M,FLEMING T,ROBINSON M,et al. Global,regional,and national prevalence of overweight and obesity in children and adults during 1980-2013:a systematic analysis for the Global Burden of Disease Study2013[J]. Lancet,2014,384(9945):766-781.
[3]CUIJPERS P,VOGELZANGS N,TWISK J,et al. Comprehensive meta-analysis of excess mortality in depression in the general community versus patients with specific illnesses[J]. Am J Psychiatry,2014,171(4):453-462.
[4]MENG R,YU C,LIU N,et al. Association of depression with all-cause and cardiovascular disease mortality among adults in China[J]. JAMA Netw Open,2020,3(2):e1921043.
[5]利敏玲,李英存,李馨,等.归脾汤联合艾司西酞普兰治疗轻中度抑郁症疗效和安全性研究[J].山东中医杂志,2025,44(7):760-766.
[6]高贵元,黄捷,刘丹,等.抑郁症的发病机制及抗抑郁药物的研究进展[J].中国医药导报,2021,18(1):52-55.
[7]李阳,陈刚,刘晶.《黄帝内经·素问》五郁理论探赜[J].时珍国医国药,2020,31(3):662-664.
[8]黄雪莲,朱爱松,于一鸿,等.郁证源流考略[J].中华中医药杂志,2022,37(10):5699-5703.
[9]吴玲,唐宇,郑琴,等.基于CUMS大鼠川芎挥发油抗抑郁症作用研究[J].世界中医药,2019,14(7):1643-1648.
[10]薛晓燕.百合地黄汤改善抑郁症前额叶皮层GABA能神经元功能障碍的机制研究[D].济南:山东中医药大学,2023.
[11]薛晓燕,潘瑾,施会山,等.基于RNA-Seq探讨毛蕊花糖苷抗抑郁的作用机制[J].中国实验方剂学杂志,2022,28(14):148-157.
[12]甘萍萍,李梁,刘书芬.基于已上市抗抑郁中药的经济学特点及优劣势分析探索中药创新药的研发策略[J].中成药,2024,46(3):1060-1064.
[13]KADRY H,NOORANI B,CUCULLO L. A blood-brain barrier overview on structure,function,impairment,and biomarkers of integrity[J]. Fluids Barriers CNS,2020,17(1):69.
[14]PARDRIDGE W M. The blood-brain barrier:bottleneck in brain drug development[J]. NeuroRx,2005,2(1):3-14.
[15]陈柏宇,吕泸楠,徐小迪,等. AIDD与CADD提升药物成功率的思考[J].中国药科大学学报,2024,55(3):284-294.
[16]濮澄韬,顾灵茜,陈兴晔,等.基于人工智能的药物人体肠道吸收性质预测[J].中国药科大学学报,2023,54(3):355-362.
[17]张洪兵,张铁军,李亚卓,等.中药新型给药系统局部药动学研究概况[J].中草药,2015,46(21):3258-3263.
[18]李宁,沈璐,牛丽君,等.肝肠首过效应对五味子醇甲在大鼠体内生物利用度的影响[J].南京中医药大学学报,2022,38(3):228-235.
[19]范容晖,阳志强,李勃深,等.中药纳米技术靶向治疗脑部疾病研究进展[J].中国比较医学杂志,2023,33(6):128-140.
[20]FENG X,JIA P,ZHANG D. Nanocarrier drug delivery system:promising platform for targeted depression therapy[J]. Front Pharmacol,2024,15:1435133.
[21]叶天健,马美娟,钱帅,等.溶致液晶在中药新型给药系统中的研究现状、存在问题及其对策[J].中国实验方剂学杂志,2019,25(16):229-234.
[22]彭世立,郭健敏,段小群,等.纳米粒给药系统的评价方法及毒性研究进展[J].今日药学,2025,35(2):136-139.
[23]ZHOU L,WU X,QIN S,et al. Cell-liposome delivery system based on neuroinflammation to target the amygdala for ameliorating depressive-like behaviors[J]. Int J Pharm,2023,637:122724.
[24]XU J Y,TAO J G,SU L L,et al. A critical review of carbon quantum dots:from synthesis toward applications in electrochemical biosensors for the determination of a depression-related neurotransmitter[J]. Materials,2021,14(14):3987.
[25]YANG G,LIU Y,HU Y,et al. Bio-soft matter derived from traditional Chinese medicine:characterizations of hierarchical structure,assembly mechanism,and beyond[J]. J Pharm Anal,2024,14(6):100943.
[26]JACOBSEN J,KRYSTAL A D,KRISHNAN K,et al.Adjunctive 5-hydroxytryptophan slow-release for treatment-resistant depression:clinical and preclinical rationale[J]. Trends Pharmacol Sci,2016,37(11):933-944.
[27]杨欣,唐军,杨丹丹,等.情志病的中医芳香精油疗法[J].世界中医药,2024,19(18):2825-2832.
[28]黄芳华,邵雪,耿兴超,等.《纳米药物非临床安全性评价研究技术指导原则》解读[J].药学学报,2023,58(4):805-814.
[29]杨卉,吴广均,何轩辉.纳米技术在中医药中的应用进展[J].世界中西医结合杂志,2022,17(8):1679-1684.
[30]李静雅,卢云,肖艳余,等.氧化石墨烯及其衍生物在中药有效成分应用方面的研究进展[J].天津中医药大学学报,2023,42(6):802-811.
[31]徐志远,李永军,史萍,等.功能化石墨烯负载毛萼乙素抗肿瘤制剂的研究[J].有机化学,2013,33(10):2162-2168.
[32]管庆霞,华晓丹,李伟男,等.载中药肝靶向纳米给药系统的研究进展[J].中国药房,2015,26(7):1002-1005.
[33]ALBERTO M,PAIVA-SANTOS A C,VEIGA F,et al.Lipid and polymeric nanoparticles:successful strategies for nose-to-brain drug delivery in the treatment of depression and anxiety disorders[J]. Pharmaceutics,2022,14(12):2742.
[34]韩静,包纯洁,段嘉伦.中药活性成分作为药物递送纳米载体的研究进展[J].中草药,2024,55(16):5678-5691.
[35]谭慧,李远萍,孟靖源,等.四氢姜黄素及其纳米制剂对脂多糖诱导的抑郁小鼠的改善作用[J].安徽医科大学学报,2025,60(1):79-86.
[36]颜红,宫思璠,于亮,等.脂质体作为药物载体的最新研究进展[J].药物生物技术,2023,30(3):325-330.
[37]范宁,尹东锋.脑靶向脂质体的研究进展[J].中国医药工业杂志,2022,53(4):439-445.
[38]VIEGAS C,PATRÍCIO A B,PRATA J M,et al. Solid lipid nanoparticles vs. nanostructured lipid carriers:a comparative review[J]. Pharmaceutics,2023,15(6):1593.
[39]杨玉晗,许树军,陈冰雁,等.两亲性聚合物纳米胶束制备及其载药方法研究进展[J].化学与粘合,2024,46(4):397-401.
[40]王勇平,黄福满,汪新娌,等.姜黄素装载的混合聚合物胶束物理表征、体外释放及药代动力学研究[J].江西中医药大学学报,2025,37(1):82-87.
[41]冯晓姣,王继林,杨文卓,等.中药多成分的共递送给药系统的构建策略和方法[J].中国实验方剂学杂志,2024,30(5):186-196.
[42]MOHI-UD-DIN R,MIR R H,WANI T U,et al. Novel drug delivery system for curcumin:implementation to improve therapeutic efficacy against neurological disorders[J]. Comb Chem High Throughput Screen,2022,25(4):607-615.
[43]NAKSURIYA O,OKONOGI S,SCHIFFELERS R M,et al. Curcumin nanoformulations:a review of pharmaceutical properties and preclinical studies and clinical data related to cancer treatment[J]. Biomaterials,2014,35(10):3365-3383.
[44]阮慧妮,丁文雅,杨旭,等.中药皂苷类成分纳米制剂的研究进展[J].中国医院药学杂志,2025,45(7):827-833.
[45]何静,陈佳,邱洪灯.中药碳点的合成及其在生物成像和医学治疗方面的应用[J].化学进展,2023,35(5):655-682.
[46]张道涵,刘磊.荧光碳点的制备方法及其在生物医药领域应用的研究进展[J].化学通报,2023,86(1):23-33.
[47]毛惠会,薛茗月,韩国成.荧光碳点的合成、性能及其应用[J].功能材料,2021,52(1):1053-1063.
[48]GE S,HE J,MA C,et al. One-step synthesis of borondoped graphene quantum dots for fluorescent sensors and biosensor[J]. Talanta,2019,199:581-589.
[49]郭颖,李午戊,刘洋,等.碳点的制备及在荧光分析中的应用[J].理化检验(化学分册),2016,52(8):986-992.
[50]JIANG Q,LIU L,LI Q,et al. NIR-laser-triggered gadolinium-doped carbon dots for magnetic resonance imaging,drug delivery and combined photothermal chemotherapy for triple negative breast cancer[J]. J Nanobiotechnology,2021,19(1):64.
[51]JALILI R,KHATAEE A. Application of molecularly imprinted polymers and dual-emission carbon dots hybrid for ratiometric determination of chloramphenicol in milk[J]. Food Chem Toxicol,2020,146:111806.
[52]WAREING T C,GENTILE P,PHAN A N. Biomassbased carbon dots:current development and future perspectives[J]. ACS Nano,2021,15(10):15471-15501.
[53]李萍.茶叶为碳源水热法合成碳量子点及其应用研究[J].化工新型材料,2021,49(9):230-233.
[54]ELUGOKE S E,ADEKUNLE A S,FAYEMI O E,et al.Carbon-based quantum dots for electrochemical detection of monoamine neurotransmitters:review[J]. Biosensors,2020,10(11):162.
[55]黄小梅,邓祥.新型荧光碳点的制备及其在Hg2+检测中的应用[J].应用化学,2019,36(5):603-610.
[56]JIANG W,LIU L,WU Y,et al. A green-synthesized phosphorescent carbon dot composite for multilevel anti-counterfeiting[J]. Nanoscale Adv,2021,3(15):4536-4540.
[57]袁迪,刘志高.碳量子点的制备与性能及其应用研究进展[J].化工新型材料,2024,52(1):54-60.
[58]JIA H,GONG J,HU Z,et al. Antioxidant carbon dots nanozymes alleviate stress-induced depression by modulating gut microbiota[J]. Langmuir,2024,40(37):19739-19750.
[59]KONG J ,WEI Y ,ZHOU F ,et al. Carbon quantum dots:properties,preparation,and applications[J]. Molecules,2024,29(9):2002.
[60]PEI Y,ZHOU Z,CHEN A P,et al. A carbon-based memristor design for associative learning activities and neuromorphic computing[J]. Nanoscale,2020,12(25):13531-13539.
[61]车飞达,赵晓茗,张馨,等.抑郁症相关活性分子的荧光成像[J].化学学报,2023,81(9):1255-1264.
[62]骆宗江,刘彪,林珈好.黄芩苷碳点的制备表征及其对犬乳腺肿瘤细胞增殖的抑制作用[J].畜牧与兽医,2023,55(12):117-121.
[63]LI X,DAI E,LI M,et al. Aurantii fructus immaturus carbonisata-derived carbon dots and their anti-depression effect[J]. Front Mol Biosci,2024,10:1334083.
[64]ZHOU Y,MINTZ K J,CHENG L,et al. Direct conjugation of distinct carbon dots as Lego-like building blocks for the assembly of versatile drug nanocarriers[J]. J Colloid Interface Sci,2020,576:412-425.
[65]WU X ,CAI H ,LIAO R ,et al. Bio-inspired carbon dots as malondialdehyde indicator for real-time visualization of lipid peroxidation in depression[J]. Small,2024,20(46):e2400671.
[66]刘越,李全,马双成.中药软物质科学:传统中药与现代物质科学交叉的新领域[J].药物分析杂志,2023,43(1):45-50.
[67]HUANG X ,WANG P ,LI T ,et al. Self-assemblies based on traditional medicine berberine and cinnamic acid for adhesion-induced inhibition multidrug-resistant Staphylococcus aureus[J]. ACS Appl Mater Interfaces,2020,12(1):227-237.
[68]HONG R,LUO L,WANG L,et al. Lepidium meyenii Walp(Maca)-derived extracellular vesicles ameliorate depression by promoting 5-HT synthesis via the modulation of gut-brain axis[J]. Imeta,2023,2(3):e116.
[69]王东轶,商玮,蔡辉.靶向给药系统在类风湿关节炎中的应用[J].四川医学,2023,44(10):1090-1093.
[70]莫丽英,吴春勇,王杏利,等.基于糖基化修饰的靶向药物传递系统研究概况[J].中国实验方剂学杂志,2018,24(13):209-219.
[71]杨春兰,黄秋洁,叶勇,等.中药纳米递药系统治疗脑部疾病的研究进展[J].中华中医药学刊,2021,39(10):38-43.
[72]ZHAO Z,UKIDVE A,KIM J,et al. Targeting strategies for tissue-specific drug delivery[J]. Cell,2020,181(1):151-167.
[73]张曼玉,楼晨曦,曹傲能.主动靶向载药脂质体在肿瘤治疗中的研究进展[J].生物医学工程学杂志,2022,39(3):633-638.
[74]李雁铭,赵志刚.肿瘤靶向药物研究进展[J].中国药业,2021,30(21):128-134.
[75]YUAN S,MA T,ZHANG Y N,et al. Novel drug delivery strategies for antidepressant active ingredients from natural medicinal plants:the state of the art[J].J Nanobiotechnology,2023,21(1):1-25.
[76]童瑶,骆阳,陈曦,等.阿托品制剂与纳米缓释给药的临床应用进展[J].现代实用医学,2023,35(7):976-980.
[77]潘集阳,方贻儒,胡少华,等.盐酸曲唑酮缓释剂临床应用专家建议[J].中国全科医学,2022,25(33):4099-4105.
[78]邢红香.贯叶连翘提取物缓释片的研究[D].西安:陕西科技大学,2014.
[79]YU C Y,YIN B C,ZHANG W,et al. Composite microparticle drug delivery systems based on chitosan,alginate and pectin with improved pH-sensitive drug release property[J]. Colloids Surf B Biointerfaces,2009,68(2):245-249.
[80]陈丽华,岳国超,张丽华,等.缓控释给药系统在中药微丸中的应用[J].中国新药杂志,2013,22(10):1186-1189.
[81]万妮,陈斌,李合,等.肺部吸入给药系统的研究进展[J].中国新药杂志,2021,30(15):1386-1395.
[82]FUNG T,LAU B,NGAI S,et al. Therapeutic effect and mechanisms of essential oils in mood disorders:interaction between the nervous and respiratory systems[J]. Int J Mol Sci,2021,22(9):4844.
[83]IBRAHIM M ,GARCIA-CONTRERAS L. Mechanisms of absorption and elimination of drugs administered by inhalation[J]. Ther Deliv,2013,4(8):1027-1045.
[84]弓宝,王灿红,吴玉兰,等.沉香线香燃香调节多神经递质途径的抗焦虑/抑郁作用及机制[J].中国新药杂志,2023,32(13):1368-1376.
[85]周欣,宋宁,林景,等.薰衣草挥发油香薰吸入的抗焦虑、抗抑郁作用及其机制[J].中南药学,2023,21(8):1991-1998.
[86]武屹爽,曹福羊,侯爱生,等.七氟醚防治小鼠抑郁样行为的效果:与BDNF/TrkB信号通路的关系[J].中华麻醉学杂志,2019,39(2):182-184.
[87]NAGELE P,DUMA A,KOPEC M,et al. Nitrous oxide for treatment-resistant major depression:a proof-of-concept trial[J]. Biol Psychiatry,2015,78(1):10-18.
[88]NAGELE P,PALANCA B J,GOTT B,et al. A phase2 trial of inhaled nitrous oxide for treatment-resistant major depression[J]. Sci Transl Med,2021,13(597):eabe1376.
[89]韩佳,张博文,毛开云.新型药物递送系统研发格局分析[J].中国生物工程杂志,2023,43(2):1-14.
[90]黄媛梅,梁莉,李平.智能给药系统的研究概况[J].中国医院药学杂志,2011,31(9):765-768.
基本信息:
DOI:10.16295/j.cnki.0257-358x.2026.01.018
中图分类号:R283.6
引用信息:
[1]黄刘玄,于冰洁,郭冬静,等.新型脑靶向递送系统在中药制剂抗抑郁治疗中的应用进展[J].山东中医杂志,2026,45(01):93-102.DOI:10.16295/j.cnki.0257-358x.2026.01.018.
基金信息:
山东省自然科学基金项目(编号:ZR2024MH267,ZR2023QH052); 山东省中医药高层次人才培育项目(批文号:鲁卫函[2023]143号); 山东省高校青创引才育才计划项目(编号:2019-9-202); 山东中医药大学2025年硕士研究生提质创新项目(编号:YJSTZCX2025048)
2026-01-05
2026-01-05