The Journal of Practical Medicine >

2026 , Vol. 42 >Issue 11: 2083 - 2090

DOI: https://doi.org/10.3969/j.issn.1006-5725.2026.11.025

Treatise：Mechanism and Practice

Real-world study： Efficacy and safety analysis of butylphthalide combined with conventional therapy in the treatment of blast-induced deafness

  • Canfeng ZHAO ,
  • Jiaping REN ,
  • Chong OUYANG ,
  • Zijing ZHANG ,
  • Hua PENG
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  • 1.Graduate School，Guangzhou University of Chinese Medicine，Guangzhou 510006，Guangdong，China
    2.Department of Otolaryngology Head and Neck Surgery，General Hospital of Southern Theater Command，Guangzhou 510010，Guangdong，China
    3.The First School of Clinical Medicine，Southern Medical University，Guangzhou 510515，Guangdong，China
    4.Outpatient Department of Unit 75610，Shenzhen 518000，Guangdong，China

Received date: 2026-03-11

  Online published: 2026-06-15

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Abstract

Objective To investigate the effectiveness and safety of butylphthalide in treating sudden deafness under real-world clinical conditions. Methods A retrospective analysis was conducted on the clinical data of patients with blast-induced deafness admitted to the Department of Otorhinolaryngology Head and Neck Surgery， General Hospital of Southern Theater Command from January 2020 to April 2025. The patients were classified into a butylphthalide group （consisting of 51 patients with 66 affected ears） and a non-butylphthalide group （consisting of 54 patients with 70 affected ears） based on whether butylphthalide was administered during the treatment. All the patients included in the study received a therapeutic regimen centered on glucocorticoids， supplemented with drugs for improving microcirculation and nourishing nerves. On this basis， the patients in the butylphthalide group were additionally administered butylphthalide injection twice a day for 7 consecutive days. The hearing gain and treatment effective rate （defined as effective when the hearing gain was ≥ 15 dB） were assessed by comparing the results of pure-tone audiometry （PTA） before and after the treatment between the two groups. The safety of medication in both groups was also monitored. Results There were no statistically significant differences in baseline characteristics between the two groups. The butylphthalide group demonstrated significantly greater hearing gains in PTA thresholds at 250 Hz， 500 Hz， 1 000 Hz， 2 000 Hz， and 4 000 Hz when compared to the non-butylphthalide group （all P < 0.05）. The overall treatment effective rates in the butylphthalide group were 53.3%， 68.1%， 49.1%， 47.4%， and 52.5% at 250 Hz， 500 Hz， 1 000 Hz， 2 000 Hz， and 4 000 Hz， respectively. These rates were significantly higher than those in the non-butylphthalide group （15.4%， 14.9%， 17.1%， 22.0%， and 27.3%； all P < 0.05）. During treatment， mild pruritus was observed in 2 cases， and mild dizziness with nausea in 1 case. No serious adverse events associated with butylphthalide were reported during the treatment period. Conclusion In real-world clinical practice， the integration of butylphthalide into conventional therapy results in a substantial improvement in the hearing levels of patients with sudden deafness and demonstrates a favorable safety profile， which suggests significant clinical application value.

Key words： explosive deafness; butylphthalide; real-world study; therapeutic efficacy; safety

Cite this article

Canfeng ZHAO , Jiaping REN , Chong OUYANG , Zijing ZHANG , Hua PENG . Real-world study： Efficacy and safety analysis of butylphthalide combined with conventional therapy in the treatment of blast-induced deafness[J]. The Journal of Practical Medicine, 2026 , 42(11) : 2083 -2090 . DOI: 10.3969/j.issn.1006-5725.2026.11.025

References

[1] CHADHA S， KAMENOV K， CIEZA A. The world report on hearing， 2021［J］. Bull World Health Organ， 2021， 99（4）： 242-242A. doi：10.2471/blt.21.285643 .
[2] 石勇兵， MARTIN W H， 隋音（译， 等. 中国的噪声性听力损害是一个潜在严重的公众健康问题［J］. 中华耳科学杂志， 2016， 14（6）： 713-718. doi：10.3969/j.issn.1672-2922.2016. 06.004 .
[3] LACHAUX J， GIéRé P A， VUILLEMIN Q， et al. Long-term hearing loss after acute acoustic trauma in the French military： A retrospective study［J］. Mil Med， 2024， 189（3/4）： e698-e704. doi：10.1093/milmed/usad337 .
[4] HELFER T M， CANHAM-CHERVAK M， CANADA S， et al. Epidemiology of hearing impairment and noise-induced hearing injury among U.S. military personnel， 2003-2005［J］. Am J Prev Med， 2010， 38（1 ）： S71-S77. doi：10.1016/j.amepre.2009. 10.025 .
[5] ALARAIFI A， ALSAAB F， ALHOMAYDAN W， et al. Hearing impairment in military personnel in Eastern Saudi Arabia［J］. J Fam Community Med， 2021， 28（2）： 110. doi：10.4103/jfcm.jfcm_501_20 .
[6] ZHOU J， SHI Z， ZHOU L， et al. Occupational noise-induced hearing loss in China： A systematic review and meta-analysis［J］. BMJ Open， 2020， 10（9）： e039576. doi：10.1136/bmjopen-2020-039576 .
[7] WANG Q， YANG L， QIAN M， et al. Acute recreational noise-induced cochlear synaptic dysfunction in humans with normal hearing： A prospective cohort study［J］. Front Neurosci， 2021， 15： 659011. doi：10.3389/fnins.2021.659011 .
[8] HAILE L M， ORJI A U， REAVIS K M， et al. Hearing loss prevalence， years lived with disability， and hearing aid use in the United States from 1990 to 2019： Findings from the global burden of disease study［J］. Ear Hear， 2024， 45（1）： 257-267. doi：10.1097/AUD.0000000000001420 .
[9] MOORE B C J. The Effect of Exposure to Noise during Military Service on the Subsequent Progression of Hearing Loss. Int J Environ Res Public Health， 2021， 18（5）： 2436. doi： 10.3390/ijerph18052436 .
[10] 肖海燕， 杨淑贤， 韩雯， 等. 丁苯酞及其衍生物药理学研究进展［J］. 中国中药杂志， 2022， 47（13）： 3425-3431. doi：10.19540/j.cnki.cjcmm.20220117.701 .
[11] 王敏， 刘建勋， 姚明江， 等. 抗脑缺血后神经损伤中药及其药理学研究进展［J］. 中国中药杂志， 2020， 45（3）： 513-517. doi：10.19540/j.cnki.cjcmm.20191022.403 .
[12] 中华耳鼻咽喉头颈外科杂志编辑委员会， 中华医学会耳鼻咽喉头颈外科学分会. 突发性聋诊断和治疗指南（2015）［J］. 中华耳鼻咽喉头颈外科杂志， 2015， 50（6）： 443-447. doi：10.3760/cma.j.issn.1673-0860.2015.06.002 .
[13] MIZUTARI K. Blast-induced hearing loss［J］. J Zhejiang Univ Sci B， 2019， 20（2）： 111-115. doi：10.1631/jzus.b1700051 .
[14] SU Z， CHEN Y， LIU Y， et al. Oxidative stress and inflammation combine to exacerbate cochlear damage and sensorineural hearing loss in C57BL/6 mice［J］. Front Neurosci， 2025， 19：1563428. doi： 10.3389/fnins.2025.1563428 .
[15] TERAOKA M， HATO N， INUFUSA H， et al. Role of oxidative stress in sensorineural hearing loss［J］. Int J Mol Sci， 2024， 25（8）： 4146. doi：10.3390/ijms25084146 .
[16] 唐凌媛， 熊敏， 刘雲. 活性氧在噪声性听力损伤发生中的作用研究进展［J］. 医学研究生学报， 2017， 30（7）： 770-774. doi： 10.16571/j.cnki.1008-8199.2017.07.019 .
[17] MOHRI H， NINOYU Y， SAKAGUCHI H， et al. Nox3-derived superoxide in cochleae induces sensorineural hearing loss［J］. J Neurosci， 2021， 41（21）： 4716-4731. doi：10.1523/JNEUROSCI.2672-20.2021 .
[18] BASKIN B M， LOGSDON A F， JANET L S， et al. Timing matters： Sex differences in inflammatory and behavioral outcomes following repetitive blast mild traumatic brain injury［J］. Brain Behav Immun， 2023， 110： 222-236. doi：10.1016/j.bbi.2023. 03.003 .
[19] MURILLO-CUESTA S， SEOANE E， CERVANTES B， et al. NLRP3 inflammasome and hearing loss： From mechanisms to therapies［J］. J Neuroinflammation， 2025， 22（1）： 225. doi：10.1186/s12974-025-03561-w .
[20] PACIELLO F， DI PINO A， ROLESI R， et al. Anti-oxidant and anti-inflammatory effects of caffeic acid： In vivo evidences in a model of noise-induced hearing loss［J］. Food Chem Toxicol， 2020， 143： 111555. doi：10.1016/j.fct.2020.111555 .
[21] LI M， ZHANG Y， QIU S， et al. Oridonin ameliorates noise-induced hearing loss by blocking NLRP3-NEK7 mediated inflammasome activation［J］. Int Immunopharmacol， 2021， 95： 107576. doi：10.1016/j.intimp.2021.107576 .
[22] WAKE N， SHIRAMATSU T I， TAKAHASHI H. Map plasticity following noise exposure in auditory cortex of rats： Implications for disentangling neural correlates of tinnitus and hyperacusis［J］. Front Neurosci， 2024， 18： 1385942. doi：10.3389/fnins.2024. 1385942 .
[23] LU J， WEST M B， DU X， et al. Electrophysiological assessment and pharmacological treatment of blast-induced tinnitus［J］. PLoS One， 2021， 16（1）： e0243903. doi：10.1371/journal.pone.0243903 .
[24] XU X M， WANG J， SALVI R， et al. Altered resting-state functional connectivity of the anterior cingulate cortex in rats post noise exposure［J］. CNS Neurosci Ther， 2022， 28（10）： 1547-1556. doi：10.1111/cns.13896 .
[25] LI Q， LI H， YAO X， et al. Stress response and hearing loss differentially contribute to dynamic alterations in hippocampal neurogenesis and microglial reactivity in mice exposed to acute noise exposure［J］. Front Neurosci， 2021， 15： 749925. doi：10.3389/fnins.2021.749925 .
[26] WU P Z， LIBERMAN L D， LIBERMAN M C. Noise-induced synaptic loss and its post-exposure recovery in CBA/CaJ vs. C57BL/6J mice［J］. Hear Res， 2024， 445： 108996. doi：10.1016/j.heares. 2024.108996 .
[27] KUJAWA S G， LIBERMAN M C. Adding insult to injury： Cochlear nerve degeneration after “temporary” noise-induced hearing loss［J］. J Neurosci， 2009， 29（45）： 14077-14085. doi：10.1523/jneurosci.2845-09.2009 .
[28] KUJAWA S G， LIBERMAN M C. Synaptopathy in the noise-exposed and aging cochlea： Primary neural degeneration in acquired sensorineural hearing loss［J］. Hear Res， 2015， 330： 191-199. doi：10.1016/j.heares.2015.02.009 .
[29] LIU H， LU J， WANG Z， et al. Functional alteration of ribbon synapses in inner hair cells by noise exposure causing hidden hearing loss［J］. Neurosci Lett， 2019， 707： 134268. doi：10.1016/j.neulet.2019.05.022 .
[30] TEPE V， SMALT C， NELSON J， et al. Hidden hearing injury： The emerging science and military relevance of cochlear synaptopathy［J］. Mil Med， 2017， 182（9）： e1785-e1795. doi：10.7205/milmed-d-17-00025 .
[31] BAEK J I， KIM Y R， LEE K Y， et al. Mitochondrial redox system： A key target of antioxidant therapy to prevent acquired sensorineural hearing loss［J］. Front Pharmacol， 2023， 14： 1176881. doi：10.3389/fphar.2023.1176881 .
[32] YU Q， LUO B， LUO Z， et al. Synthesis of novel 3-butylphthalide derivatives containing isopentenylphenol moiety as potential antiplatelet agents for the treatment of ischemic stroke［J］. Chem Biodivers， 2023， 20（1）： e202201002. doi：10.1002/cbdv. 202201002 .
[33] YE J， ZHAI L， ZHANG S， et al. Dl-3-n-butylphthalide inhibits platelet activation via inhibition of cPLA2-mediated TXA2 synthesis and phosphodiesterase［J］. Platelets， 2015， 26（8）： 736-744. doi：10.3109/09537104.2014.989826 .
[34] SUN M， CHEN J， LIU F， et al. Butylphthalide inhibits ferroptosis and ameliorates cerebral Ischaemia-Reperfusion injury in rats by activating the Nrf2/HO-1 signalling pathway［J］. Neurotherapeutics， 2024， 21（5）： e00444. doi：10.1016/j.neurot.2024.e00444 .
[35] TU E， CHEN Q， TAN L， et al. Dl-3-n-Butylphthalide promotes neovascularization and neurological recovery in a rat model of intracerebral hemorrhage［J］. BMC Neurosci， 2020， 21（1）： 24. doi：10.1186/s12868-020-00575-3 .
[36] LIU Y， GONG Z， ZHAI D， et al. Unveiling the therapeutic potential of Dl-3-n-butylphthalide in NTG-induced migraine mouse： Activating the Nrf2 pathway to alleviate oxidative stress and neuroinflammation［J］. J Headache Pain， 2024， 25（1）： 50. doi：10.1186/s10194-024-01750-1 .
[37] ZHANG P， GUO Z F， XU Y M， et al. N-Butylphthalide （NBP） ameliorated cerebral ischemia reperfusion-induced brain injury via HGF-regulated TLR4/NF-κB signaling pathway［J］. Biomed Pharmacother， 2016， 83： 658-666. doi：10.1016/j.biopha.2016. 07.040 .
[38] QUE R， ZHENG J， CHANG Z， et al. Dl-3-n-butylphthalide rescues dopaminergic neurons in Parkinson′s disease models by inhibiting the NLRP3 inflammasome and ameliorating mitochondrial impairment［J］. Front Immunol， 2021， 12： 794770. doi：10.3389/fimmu.2021.794770 .
[39] LI J， ZHU X. 3-n-butylphthalide improves cerebral ischemia/reperfusion injury by regulating neuronal mitochondrial biogenesis via AMPK/PGC-1α signaling pathway［J］. Int Immunopharmacol， 2025， 164： 115343. doi：10.1016/j.intimp.2025.115343 .
[40] LI W， WEI D， LIN J， et al. Dl-3-n-butylphthalide reduces cognitive impairment induced by chronic cerebral hypoperfusion through GDNF/GFRα1/ret signaling preventing hippocampal neuron apoptosis［J］. Front Cell Neurosci， 2019， 13： 351. doi：10.3389/fncel.2019.00351 .
[41] WU F， XU K， XU K， et al. Dl-3n-butylphthalide improves traumatic brain injury recovery via inhibiting autophagy-induced blood-brain barrier disruption and cell apoptosis［J］. J Cellular Molecular Medi， 2020， 24（2）： 1220-1232. doi：10.1111/jcmm.14691 .
[42] LIAO W， ZHONG Y， CHENG W， et al. 3-N-butylphthalide inhibits neuronal apoptosis in rats with cerebral infarction via targeting P38/MAPK［J］. Eur Rev Med Pharmacol Sci， 2019， 23（3 ）： 144-152. doi：10.26355/eurrev_201908_18641 .
[43] CHEN J， XIAO L， CHEN Y， et al. Butylphthalide alleviates sleep deprivation-induced cognitive deficit by regulating Nrf2/HO-1 pathway［J］. Sleep Med， 2022， 100： 427-433. doi：10.1016/j.sleep.2022.09.016 .
[44] YANG L C， LI J， XU S F， et al. L-3-n-butylphthalide promotes neurogenesis and neuroplasticity in cerebral ischemic rats［J］. CNS Neurosci Ther， 2015， 21（9）： 733-741. doi：10.1111/cns.12438 .
[45] XIONG M， FENG X， TANG L， et al. Butylphthalide enhances recovery from sudden deafness［J］. Am J Otolaryngol， 2021， 42（2）： 102891. doi：10.1016/j.amjoto.2020.102891 .
[46] BERGER M L， SOX H， WILLKE R J， et al. Good practices for real‐world data studies of treatment and/or comparative effectiveness： Recommendations from the joint ISPOR‐ISPE special task force on real-world evidence in health care decision making［J］. Value Health， 2017， 20（8）： 1003-1008. doi：10.1016/j.jval. 2017.08.3019 .
[47] WANG A， JIA B， ZHANG X， et al. Efficacy and safety of butylphthalide in patients with acute ischemic stroke： A randomized clinical trial［J］. JAMA Neurol， 2023， 80（8）： 851. doi：10.1001/jamaneurol.2023.1871 .
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