舌下片剂型药物在心、脑梗死疾病急救治疗中的研究进展

徐剑培, 诸舜伟, 陈荣, 徐善森, 任健, 王岚, 王峰

中国新药杂志 ›› 2026, Vol. 35 ›› Issue (11) : 1175 -1182.

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中国新药杂志 ›› 2026, Vol. 35 ›› Issue (11) : 1175 -1182. DOI: 10.20251/j.cnki.1003-3734.2026.11.008
综述

舌下片剂型药物在心、脑梗死疾病急救治疗中的研究进展

    徐剑培1, 诸舜伟1, 陈荣2, 徐善森1, 任健2, 王岚1, 王峰1*
作者信息 +

Progress in researches for sublingual tablets in emergency treatment of cardiac and cerebral ischemic infarction

    XU Jian-pei1, ZHU Shun-wei1, CHEN Rong2, XU Shan-seng1, REN Jian2, WANG Lan1, WANG Feng1*
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摘要

心、脑梗死发病率逐年上升,疾病负担日趋加重,迫切需求有效治疗药物。心、脑缺血性梗死发病急、进展快,致死致残率高,黄金治疗时间窗内的快速救治和组织保护是改善预后和减轻疾病负担的关键。传统口服药物起效慢、首过效应显著,静脉溶栓与介入治疗受医疗条件限制难以普惠患者。舌下片吸收迅速,使用便捷,不受地域和医疗条件限制,已成为急救治疗的首选剂型。硝酸甘油舌下片革命性改变了心肌梗死急救格局,而脑梗死急救仍面临用药困难的窘境。依达拉奉右莰醇舌下片脑保护作用明确,透脑吸收迅速,可满足吞咽困难患者在院内外多场景中的用药需求。此外,在生产、运输、用药和存储等成本方面均优于注射液,具有经济性高、疗效好的特点,有望改变脑梗死急救现状。本文结合心、脑梗死疾病特征,综述舌下片剂型药物的研究进展,为心、脑梗死疾病治疗的新药研发提供新思路。

Abstract

The incidence and disease burden of myocardial and cerebral infarction is rising annually, creating an urgent need for effective therapeutic drugs. Cardiac and cerebral ischemic infarction has an acute onset and rapid progression, resulting in high mortality and disability rates. Rapid treatment and tissue protection within the golden therapeutic time window are the keys to improving prognosis and reducing disease burden. Traditional oral drugs have a slow onset and significant first-pass effect, while intravenous thrombolysis and interventional therapy are limited by medical conditions and cannot be widely accessible to patients. Sublingual tablets, with rapid absorption and convenient administration unrestricted by region or medical resources, have become the preferred dosage form for emergency treatment. Sublingual nitroglycerin tablets have revolutionized the emergency treatment landscape of myocardial infarction, whereas cerebral infarction emergency treatment still faces medication difficulties. Edaravone dexborneol sublingual tablets have demonstrated a clear cerebral protective effect with rapid brain penetration, meeting the medication needs of patients with dysphagia in various settings both inside and outside the hospital. Moreover, they are superior to injections in terms of production, transportation, administration, and storage costs, exhibiting high cost-effectiveness and good efficacy, and are expected to change the current emergency treatment situation of cerebral infarction. This article summarizes the research progress on sublingual tablets formulations based on the pathological features of cardiac and cerebral infarction, aiming to provide new ideas for drug development in the treatment for these diseases.    

关键词

依达拉奉右莰醇 / 舌下剂型药物 / 脑卒中 / 急救治疗 / 研究进展

Key words

edaravone dexborneol / sublingual dosage form / stroke / emergency medical treatment / research progress

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引用格式 ▾
徐剑培, 诸舜伟, 陈荣, 徐善森, 任健, 王岚, 王峰. 舌下片剂型药物在心、脑梗死疾病急救治疗中的研究进展[J]. 中国新药杂志, 2026, 35(11): 1175-1182 DOI:10.20251/j.cnki.1003-3734.2026.11.008

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参考文献

[1] SALARI N, MORDDARVANJOGHI F, ABDOLMALEKI A, et al. The global prevalence of myocardial infarction: a systematic review and meta-analysis[J]. BMC Cardiovasc Disord, 2023, 23(1): 206.
[2] GAO WW, YU LF, SHE JJ, et al. Cardio-cerebral infarction: a narrative review of pathophysiology, treatment challenges, and prognostic implications[J]. Front Cardiovasc Med, 2025, 12: 1507665.
[3] FESKE SK. Ischemic stroke[J]. Am J Med, 2021, 134(12): 1457-1464.
[4] 中华预防医学会, 中华预防医学会心脏病预防与控制专业委员会, 中华医学会糖尿病学分会, 等. 中国健康生活方式预防心血管代谢疾病指南[J]. 中华预防医学杂志, 2020, 54(3): 256-277.
[5] MARTIN SS, ADAY AW, ALLEN NB, et al. 2025 Heart Disease and Stroke Statistics: A Report of US and Global Data From the American Heart Association[J]. Circulation, 2025, 151(8): e41-e660.
[6] ROTH GA, MENSAH GA, JOHNSON CO, et al. Global burden of cardiovascular diseases and risk factors, 1990-2019 update from the GBD 2019 study[J]. J Am Coll Cardiol, 2020, 76(25): 2982-3021.
[7] GBD 2021 Stroke Risk Factor Collaborators. Global, regional, and national burden of stroke and its risk factors, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021[J]. Lancet Neurol, 2024, 23(10): 973-1003.
[8] LIBBY P. The changing landscape of atherosclerosis[J]. Nature, 2021, 592(7855): 524-533.
[9] LIBBY P, BURING JE, BADIMON L, et al. Atherosclerosis[J]. Nat Rev Dis Primers, 2019, 5: 56.
[10] PAGLIARO BR, CANNATA F, STEFANINI GG, et al. Myocardial ischemia and coronary disease in heart failure[J]. Heart Fail Rev, 2020, 25(1): 53-65.
[11] BEARD E, LENGACHER S, DIAS S, et al. Astrocytes as key regulators of brain energy metabolism: new therapeutic perspectives[J]. Front Physiol, 2022, 12: 825816.
[12] WELT FGP, BATCHELOR W, SPEARS JR, et al. Reperfusion injury in patients with acute myocardial infarction JACC scientific statement[J]. J Am Coll Cardiol, 2024, 83(22): 2196-2213.
[13] JURCAU A, ARDELEAN IA. Molecular pathophysiological mechanisms of ischemia/reperfusion injuries after recanalization therapy for acute ischemic stroke[J]. J Integr Neurosci, 2021, 20(3): 727-744.
[14] PRZYKAZA Ł. Understanding the connection between common stroke comorbidities, their associated inflammation, and the course of the cerebral ischemia/reperfusion cascade[J]. Front Immunol, 2021, 12: 782569.
[15] XU JP, SUN YZ, YOU Y, et al. Bioorthogonal microglia-inspired mesenchymal stem cell bioengineering system creates livable niches for enhancing ischemic stroke recovery via the hormesis[J]. Acta Pharm Sin B, 2024, 14(3): 1412-1427.
[16] LIU SS, XU JP, LIU YP, et al. Neutrophil-biomimetic “nanobuffer” for remodeling the microenvironment in the infarct core and protecting neurons in the penumbra via neutralization of detrimental factors to treat ischemic stroke[J]. ACS Appl Mater Interfaces, 2022, 14(24): 27743-27761.
[17] ZHANG S, YAN F, LUAN F, et al. The pathological mechanisms and potential therapeutic drugs for myocardial ischemia reperfusion injury[J]. Phytomedicine, 2024, 129: 155649.
[18] ZHAO YF, ZHANG XJ, CHEN XY, et al. Neuronal injuries in cerebral infarction and ischemic stroke: From mechanisms to treatment (Review)[J]. Int J Mol Med, 2021, 49(2): 15.
[19] FRANK D, GRUENBAUM BF, ZLOTNIK A, et al. Pathophysiology and current drug treatments for post-stroke depression: a review[J]. Int J Mol Sci, 2022, 23(23): 15114.
[20] LI XY, KONG XM, YANG CH, et al. Global, regional, and national burden of ischemic stroke, 1990-2021: an analysis of data from the global burden of disease study 2021[J]. eClinicalMedicine, 2024, 75: 102758.
[21] MÖLLER L, TIMMERMANN L, GERSTNER A. Time is Brain-Preclinical Emergency Care for Acute Ischemic Stroke[J]. Anasthesiol Intensivmed Notfallmed Schmerzther, 2021, 56(11-12): 745-759.
[22] ZUBAIR AS, SHETH KN. Emergency care of patients with acute ischemic stroke[J]. Neurol Clin, 2021, 39(2): 391-404.
[23] HAN YJ, XIANG ML, WANG LL, et al. Enhancing the efficacy of emergency care pathways in the management of stroke patients[J]. Altern Ther Health Med, 2024, 30(12): 159-163.
[24] BOSSON N, ISAKSON B, MORGAN JA, et al. Safety and effectiveness of field nitroglycerin in patients with suspected ST elevation myocardial infarction[J]. Prehospital Emerg Care, 2019, 23(5): 603-611.
[25] FERREIRA JCB, MOCHLY-ROSEN D. Nitroglycerin use in myocardial infarction patients-risks and benefits-: -risks and benefits-[J]. Circ J, 2012, 76(1): 15-21.
[26] TSIVGOULIS G, KATSANOS AH, SANDSET EC, et al. Thrombolysis for acute ischaemic stroke: current status and future perspectives[J]. Lancet Neurol, 2023, 22(5): 418-429.
[27] LIU YM, LUO XC, XIANG HN, et al. Nationwide analysis of routine clinical practices in the management of acute ischemic stroke patients in China[J]. Int J Stroke, 2025, 20(9): 1102-1113.
[28] FLADT J, OSPEL JM, SINGH N, et al. Optimizing patient-centered stroke care and research in the prehospital setting[J]. Stroke, 2023, 54(9): 2453-2460.
[29] XU J, WANG AX, MENG X, et al. Edaravone dexborneol versus edaravone alone for the treatment of acute ischemic stroke: a phase III, randomized, double-blind, comparative trial[J]. Stroke, 2021, 52(3): 772-780.
[30] FU Y, WANG AX, TANG RH, et al. Sublingual edaravone dexborneol for the treatment of acute ischemic stroke: the TASTE-SL randomized clinical trial[J]. JAMA Neurol, 2024, 81(4): 319.
[31] RAWAS-QALAJI M, THU HE, HUSSAIN Z. Oromucosal delivery of macromolecules: Challenges and recent developments to improve bioavailability[J]. J Control Release, 2022, 352: 726-746.
[32] JOSHI D, CHOUDHARY NK. A review on sublingual drug delivery: enhancing bioavailability and therapeutic outcomes[J]. Ijnrph, 2024: 243-250.
[33] AHMAD A, AKHTAR J, AHMAD M, et al. Drug delivery approaches for buccal and sublingual administration[J]. Drug Res, 2025, 75(7): 239-250.
[34] BASTOS F, PINTO AC, NUNES A, et al. Oromucosal products-Market landscape and innovative technologies: a review[J]. J Control Release, 2022, 348: 305-320.
[35] SHARMA N, KUMAR SHARMA T, CHAUDHARY A, et al. A detailed review on fast dissolving niosomal films for sublingual drug delivery[J]. Res J Pharm Dosage Forms Technol, 2022: 163-170.
[36] HUA SS. Advances in nanoparticulate drug delivery approaches for sublingual and buccal administration[J]. Front Pharmacol, 2019, 10: 1328.
[37] SAJATOVIC M, SCHEIDEMANTEL T, KOROBKOVA I, et al. Asenapine for bipolar disorder[J]. Neuropsychiatr Dis Treat, 2015: 3007.
[38] REN J, HU CL, ZHANG ZP, et al. Development and validation an LC-MS/MS method to quantify (+)-borneol in rat plasma: Application to a pharmacokinetic study[J]. J Chromatogr B, 2019, 1109: 121-127.
[39] MURRELL W. Nitro-glycerine as a remedy for angina pectoris[J]. Lancet, 1879, 113(2891): 113-115.
[40] SILBER S. Nitrates: Why and how should they be used today?: Current status of the clinical usefulness of nitroglycerin, isosorbide dinitrate and isosorbide-5-mononitrate[J]. Eur J Clin Pharmacol, 1990, 38(S1): S35-S51.
[41] FU QJ, HUANG CQ, YUAN Y, et al. Assessment of pharmacokinetics and safety with bioequivalence of the nitroglycerin sublingual tablets of two formulations in Chinese healthy subjects: a bioequivalence study[J]. Drugs R&D, 2025, 25(3): 263-274.
[42] DIVAKARAN S, LOSCALZO J. The role of nitroglycerin and other nitrogen oxides in cardiovascular therapeutics[J]. J Am Coll Cardiol, 2017, 70(19): 2393-2410.
[43] ROSS AM, HURN P, PERRIN N, et al. Evidence of the peripheral inflammatory response in patients with transient ischemic attack[J]. J Stroke Cerebrovasc Dis, 2007, 16(5): 203-207.
[44] SHICHITA T, SAKAGUCHI R, SUZUKI M, et al. Post-ischemic inflammation in the brain[J]. Front Immun, 2012, 3: 132.
[45] XIONG YY, CAMPBELL BCV, SCHWAMM LH, et al. Tenecteplase for ischemic stroke at 4.5 to 24 hours without thrombectomy[J]. N Engl J Med, 2024, 391(3): 203-212.
[46] HUA Y, ZHOU LM, YANG WD, et al. Y-2 reduces oxidative stress and inflammation and improves neurological function of collagenase-induced intracerebral hemorrhage rats[J]. Eur J Pharmacol, 2021, 910: 174507.
[47] 马利萍, 孙建国, 彭英, 等. 依达拉奉清除自由基机制及临床应用[J]. 中国临床药理学与治疗学, 2011, 16(3): 341-348.
[48] WATANABE K, TANAKA M, YUKI S, et al. How is edaravone effective against acute ischemic stroke and amyotrophic lateral sclerosis?[J]. J Clin Biochem Nutr, 2018, 62(1): 20-38.
[49] ZHANG JB, SHI X, CHEN Z, et al. Edaravone reduces iron-mediated Hydrocephalus and behavioral disorder in rat by activating the Nrf2/HO-1 pathway[J]. J Stroke Cerebrovasc Dis, 2018, 27(12): 3511-3520.
[50] CHANG L, YIN CY, WU HY, et al. (+)-Borneol is neuroprotective against permanent cerebral ischemia in rats by suppressing production of proinflammatory cytokines[J]. J Biomed Res, 2017, 31(4): 306.
[51] DONG TW, CHEN N, MA X, et al. The protective roles of L-borneolum, D-borneolum and synthetic borneol in cerebral ischaemia via modulation of the neurovascular unit[J]. Biomed Pharmacother, 2018, 102: 874-883.
[52] ZHENG Q, CHEN ZX, XU MB, et al. Borneol, a messenger agent, improves central nervous system drug delivery through enhancing blood-brain barrier permeability: a preclinical systematic review and meta-analysis[J]. Drug Deliv, 2018, 25(1): 1617-1633.
[53] LI J, ZHANG L, XU C, et al. A pain killer without analgesic tolerance designed by co-targeting PSD-95-nNOS interaction and α2-containning GABAARs[J]. Theranostics, 2021, 11: 5970-5985.
[54] WU HY, TANG Y, GAO LY, et al. The synergetic effect of edaravone and borneol in the rat model of ischemic stroke[J]. Eur J Pharmacol, 2014, 740: 522-531.
[55] DONG Y, CHEN HW, GAO JL, et al. Molecular machinery and interplay of apoptosis and autophagy in coronary heart disease[J]. J Mol Cell Cardiol, 2019, 136: 27-41.
[56] VAN HORN N, KNIEP H, LEISCHNER H, et al. Predictors of poor clinical outcome despite complete reperfusion in acute ischemic stroke patients[J]. J Neurointerv Surg, 2021, 13(1): 14-18.
[57] LEE SH, KIM BJ, HAN MK, et al. Futile reperfusion and predicted therapeutic benefits after successful endovascular treatment according to initial stroke severity[J]. BMC Neurol, 2019, 19(1): 11.
[58] MEYER L, ALEXANDROU M, LEISCHNER H, et al. Mechanical thrombectomy in nonagenarians with acute ischemic stroke[J]. J Neurointerv Surg, 2019, 11(11): 1091-1094.
[59] WANG YC, QIU BS, GUAN L, et al. EFfects of Y-6 SUblingual Tablets for PaTients with AcUte Ischemic StRokE(FUTURE): a phase II, randomised, double-blind, double-dummy, placebo-controlled, parallel trial[J]. Stroke Vasc Neurol, 2025, 10(6): 793-799.
[60] YUAN J, LU ZK, XIONG XM, et al. Age and geographic disparities in acute ischaemic stroke prehospital delays in China: a cross-sectional study using national stroke registry data[J]. Lancet Reg Health West Pac, 2023, 33: 100693.
[61] WANG Y, ZHANG YY, YAN J, et al. The impact of diagnosis-related group-based medical insurance payment model on the prognosis and nursing care of patients undergoing composite trabeculectomy: a retrospective cohort study[J]. Front Public Health, 2025, 13: 1518546.
[62] XIE F, LU YQ, YANG Z, et al. Cost-effectiveness of edaravone dexborneol sublingual tablet versus concentrated solution for injection for the treatment of acute ischemic stroke in China[J]. Front Pharmacol, 2025, 16: 1661581.
[63] SAYEED VA, ASHRAF M. Considerations in Developing Sublingual Tablets-An Overview[J]. Pharm Technol, 2014, 38(11): 34-72.

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