A Prospective, International, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Study to Evaluate the Efficacy and Safety of TTYP01 Tablets in Early Symptomatic Alzheimer's Disease

This is a multicenter, randomized, double-blind, placebo-controlled parallel Phase II core period study to evaluate the efficacy and safety of TTYP01 Tablets in early symptomatic AD (Mild cognitive impairment [MCI] due to AD, or mild AD dementia).
A total of 180 participants will be randomized into 3 parallel groups: 2 TTYP01 dose groups and 1 placebo group.

开始日期2025-12-05

申办/合作机构

上海澳宗生物科技有限公司

IRCT20250728066664N1

/ Recruiting临床2/3期IIT

Investigation of the clinical effectiveness of the injectable drug Edaravone in the improvement and treatment of delirium conditions in patients with dementia compared to the control group : a randomized clinical study comparing with a double-blind control group

开始日期2025-08-23

申办/合作机构

Tehran University of Medical Sciences

CTRI/2025/07/090042

/ Not yet recruitingN/A

An Open Label Balanced Randomized Single Dose Two Treatment Two Sequence Two Period Two Way Crossover, Oral Bioequivalence Study Comparing of Edaravone Powder For Oral Suspension 105 mg Manufactured by BDR Pharmaceuticals International Pvt Ltd India With Radicut Ors 2.1 % 50 Ml Edaravone Oral Suspension Manufactured for M/S Mitsubishi Tanabe Pharma Corporation Chuo Ku Tokyo Japan In Healthy, Adult Human Subjects Under Fasting Conditions - Nil

开始日期2025-07-10

申办/合作机构

BDR Pharmaceuticals International Pvt Ltd.

100 项与依达拉奉相关的临床结果

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100 项与依达拉奉相关的转化医学

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100 项与依达拉奉相关的专利（医药）

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3,661

项与依达拉奉相关的文献（医药）

2026-05-01·Neural Regeneration Research

Drug delivery strategies for neuroprotective therapy in ischemic stroke: Application of nanotechnology

Article

作者: Chen, Qi ; Jiang, Zhan ; Yang, Huanghao

The mechanisms underlying the pathophysiology of ischemic stroke are complex and multifactorial and include excitotoxicity, oxidative stress, inflammatory responses, and blood–brain barrier disruption. While vascular recanalization treatments such as thrombolysis and mechanical thrombectomy have achieved some success, reperfusion injury remains a significant contributor to the exacerbation of brain injury. This emphasizes the need for developing neuroprotective strategies to mitigate this type of injury. The purpose of this review was to examine the application of nanotechnology in the treatment of ischemic stroke, covering research progress in nanoparticle-based drug delivery, targeted therapy, and antioxidant and anti-inflammatory applications. Nano-based drug delivery systems offer several advantages compared to traditional therapies, including enhanced blood–brain barrier penetration, prolonged drug circulation time, improved drug stability, and targeted delivery. For example, inorganic nanoparticles, such as those based on CeO 2 , have been widely studied for their strong antioxidant capabilities. Biomimetic nanoparticles, such as those coated with cell membranes, have garnered significant attention owing to their excellent biocompatibility and targeting abilities. Nanoparticles can be used to deliver a wide range of neuroprotective agents, such as antioxidants (e.g., edaravone), anti-inflammatory drugs (e.g., curcumin), and neurotrophic factors. Nanotechnology significantly enhances the efficacy of these drugs while minimizing adverse reactions. Although nanotechnology has demonstrated great potential in animal studies, its clinical application still faces several challenges, including the long-term safety of nanoparticles, the feasibility of large-scale production, quality control, and the ability to predict therapeutic effects in humans. In summary, nanotechnology holds significant promise for the treatment of ischemic stroke. Future research should focus on further exploring the mechanisms of action of nanoparticles, developing multifunctional nanoparticles, and validating their safety and efficacy through rigorous clinical trials. Moreover, interdisciplinary collaboration is essential for advancing the use of nanotechnology in stroke treatment.

2026-05-01·Neural Regeneration Research

Latest progress and challenges in drug development for degenerative motor neuron diseases

Article

作者: Chen, Yongping ; Wen, Xiangjin ; Lan, Tianxiang ; Cao, Bei ; Su, Weiming ; Wang, Yi

Motor neuron diseases are sporadic or inherited fatal neurodegenerative conditions. They selectively affect the upper and/or lower motor neurons in the brain and spinal cord and feature a slow onset and a subacute course contingent upon the site of damage. The main types include amyotrophic lateral sclerosis, progressive muscular atrophy, primary lateral sclerosis, and progressive bulbar palsy, the pathological processes of which are largely identical, with the main disparity lying in the location of the lesions. Amyotrophic lateral sclerosis is the representative condition in this group of diseases, while other types are its variants. Hence, this article mainly focuses on the advancements and challenges in drug research for amyotrophic lateral sclerosis but also briefly addresses several other important degenerative motor neuron diseases. Although the precise pathogenesis remains elusive, recent advancements have shed light on various theories, including gene mutation, excitatory amino acid toxicity, autoimmunology, and neurotrophic factors. The US Food and Drug Administration has approved four drugs for use in delaying the progression of amyotrophic lateral sclerosis: riluzole, edaravone, AMX0035, and tofersen, with the latter being the most recent to receive approval. However, following several phase III trials that failed to yield favorable outcomes, AMX0035 has been voluntarily withdrawn from both the US and Canadian markets. This article presents a comprehensive summary of drug trials primarily completed between January 1, 2023, and June 30, 2024, based on data sourced from clinicaltrials.gov. Among these trials, five are currently in phase I, seventeen are in phase II, and eleven are undergoing phase III evaluation. Notably, 24 clinical trials are now investigating potential disease-modifying therapy drugs, accounting for the majority of the drugs included in this review. Some promising drugs being investigated in preclinical studies, such as ATH-1105, are included in our analysis, and another review in frontiers in gene therapy and immunotherapy has demonstrated their therapeutic potential for motor neuron diseases. This article was written to be an overview of research trends and treatment prospects related to motor neuron disease drugs, with the aim of highlighting the latest potentialities for clinical therapy.

2026-02-01·Central nervous system agents in medicinal chemistry

Dimethyl Fumarate Attenuates Behavioral and Structural Impairments Associated with Brain Ischemia in Rats

Article

作者: Namavar, Mohammad Reza ; Bakhtiari, Mohammad ; Emamghoreishi, Masoumeh ; Ardakani, Maryam Khastkhodaei

Introduction::

Ischemic stroke remains one of the leading causes of death and physical and mental disability. Oxidative stress, free radicals, and inflammation play critical roles in ischemic brain damage. Free radical scavengers such as edaravone and dimethyl fumarate (DMF), known for their antioxidant and anti-inflammatory properties, are considered promising targets for ischemic stroke treatment. This study aimed to assess the impact of these drugs on brain ischemia

Methods::

Forty-nine rats were randomly divided into seven groups: sham, edaravone, and DMF controls, as well as edaravone, DMF 5, 15, and 30 groups. Middle cerebral artery occlusion (MCAO) was induced in all groups except the sham group. The MCAO groups were administered with either the vehicle, edaravone (3 mg/kg), or DMF at doses of 5, 15, and 30 mg/kg twice daily for 14 days. Neurobehavioral assessments were conducted throughout the experiment, and anatomical changes in the brain were evaluated using stereological methods.

Results::

Edaravone and three doses of DMF improved neurobehavioral functions. All treated rats showed a reduction in the ischemic volume and cell loss in the brain regions when compared with the control animals. MCAO reduced the total number of neurons and just DMF doses had a significant effect on this factor. Interestingly, MCAO increased the number of non-neurons and only the DMF 30 group significantly decreased this parameter. DMF 30 was more effective in ischemic stroke.

Conclusions::

Although edaravone improved neurological functions and reduced the size of brain ischemia and cell loss, DMF, especially at higher doses, exerted a more beneficial effect on these parameters. Therefore, DMF could be proposed as a reinforcement to currently conventional therapies.

576

项与依达拉奉相关的新闻（医药）

2025-12-09

·PRNewswire

A broader impact: UT Health San Antonio Center for Brain Health expands care and discovery across dozens of neurological conditions

New center opens tomorrow with comprehensive clinical care, advanced research and family-centered support SAN ANTONIO, Dec. 9, 2025 /PRNewswire/ -- While much of the focus of tomorrow's opening of UT Health San Antonio's Center for Brain Health deservedly is on Alzheimer's disease, it also marks a major step forward for families as a transformational resource for individuals and families navigating a wide spectrum of neurological and neurodegenerative conditions. Those include complex and rare diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The new center brings together expertise in dozens of disorders and will participate in national research initiatives and focus on clinical trials and biomarker identification to find ways to provide earlier detection and treatment of these rare diseases. And beyond research, it will emphasize education, family support and community connection. By integrating world-class research with multidisciplinary clinical care and family-centered programs under one roof, the Center for Brain Health represents a new model for future-focused neurological care and one that brings hope to countless families across South Texas and beyond. "This is about building a community," said Carlayne Jackson, MD, FAAN, chair of the Department of Neurology and professor of neurology and otolaryngology at the Joe R. and Teresa Lozano Long School of Medicine at The University of Texas at San Antonio. "These families are dealing with rare, devastating diseases in the prime of their lives. We want them to know they are not alone. We provide tools, support and hope and we do it in a way that respects the patient and the family." Understanding ALS ALS, also known as Lou Gehrig's Disease, is a degenerative disease of nerves called motor neurons, which are in the brain and spinal cord. It is most commonly diagnosed in individuals between ages 50 and 60, but cases have been reported in teenagers as well as individuals in their 90s. The disease is relatively rare, with an incidence of only two to five cases per 100,000 people. Approximately 30,000 people in the United States live with ALS. "I've seen firsthand how the disease can overwhelm caregivers," Jackson said. "The logistics of helping a loved one with mobility, nutrition, daily hygiene and multiple medical appointments can feel worse than the disease itself. We wanted to create a center that could support the whole family, not just the patient." About 90% of ALS cases are sporadic, or having no identifiable cause, while roughly 10% are genetic. Most genetic forms are caused by dominant mutations, which can affect multiple family members across generations. Symptoms often begin in the hands, arms or legs leading to tripping, weakness and difficulty with everyday tasks like opening a jar or turning a key. Speech muscles can also be affected. The disease progresses over time, ultimately leading to respiratory failure or pneumonia. Despite decades of research, effective treatments remain limited. Medications like riluzole and edaravone slow progression, but no therapies currently stop the disease, and average life expectancy is two to five years after diagnosis. Still, UT Health San Antonio's Center for Brain Health is part of an ongoing national ALS study that collects genetic and biomarker data, while monitoring participants' functional abilities, strength and disease progression. It is also participating in the HEALEY ALS Platform Trial, conducted in collaboration with Massachusetts General Hospital and more than 40 other national centers, which is evaluating seven different drugs for ALS under the same protocol, allowing for faster and more efficient clinical trials. Unlike traditional studies with 50/50 placebo distribution, 75% of participants in this study received active treatment, making enrollment more appealing for patients seeking new therapies. ALS, FTD connection and genetics A. Campbell Sullivan, PsyD, ABPP-CN, associate clinical professor with the Division of Neuropsychology in the Department of Neurology at the Long School of Medicine and with the Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, has spent her career studying rare and early-onset neurological conditions, including ALS and FTD. Frontotemporal dementia often strikes before age 60 and affects behavior rather than memory, leading to challenges in diagnosis and treatment. Sullivan's research has focused on genetic connections between FTD and ALS, including the C9ORF72 and TARDBP genetic mutations. "For some families, understanding the genetic link can provide clarity," Sullivan said. "In my own family, we've seen the impact of ALS-FTD across generations. Having a diagnosis allowed us to test other family members and plan for the future. That's what we hope to provide for all families – answers, guidance and support." The Center for Brain Health will participate in another national research initiative called ALLFTD, which tracks patients and at-risk gene carriers to understand disease progression. Jackson said early identification is crucial in these diseases. "Once symptoms appear, patients have already lost a significant portion of motor neurons," she said. "Our goal is to identify and intervene as early as possible. That's where precision medicine and early-phase clinical trials come into play." Looking ahead Early research into new drugs, such as tofersen for genetic forms of ALS, has been promising, and ongoing efforts to understand the mechanisms of both genetic and sporadic neurodegenerative diseases may spur development of new therapies in the coming years. "We're starting to find therapies that can slow disease progression," Sullivan said. "The next step is stopping it altogether. Ten years from now, I believe we'll have that breakthrough." For now, Sullivan finds inspiration in both the families she serves and the next generation of scientists she mentors. Patients and caregivers have access to telemedicine and virtual programs, allowing families across Texas to participate even if they cannot travel. Support groups, caregiver education and resources on navigating medical information are integral parts of UT Health San Antonio's holistic approach. "Our goal is to support families and help them make the most of the time they have," Sullivan said. "We may not be able to stop the train of disease progression, but we can do everything possible to slow it down with care and compassion." UT Health San Antonio is the academic health center of The University of Texas at San Antonio (UT San Antonio), offering a comprehensive network of inpatient and outpatient care facilities staffed by medical, dental, nursing and allied health professionals who conduct more than 2.5 million patient visits each year. It is the region's only academic health center and one of the nation's leading health sciences institutions, supported by the schools of medicine, nursing, dentistry, health professions, graduate biomedical sciences and public health that are leading change and advancing fields throughout South Texas and the world. To learn about the many ways "We make lives better®," visit UTHealthSA.org. The Joe R. and Teresa Lozano Long School of Medicine at The University of Texas at San Antonio (UT San Antonio) is listed among U.S. News & World Report's best medical schools, among the top 5% of universities globally for clinical medicine research and ranked as the third-highest medical school in Texas for medical research funding by the National Institutes of Health. The Long School of Medicine supports the university's academic health center, UT Health San Antonio. The Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases at UT Health San Antonio is dedicated to providing comprehensive dementia care while advancing treatment through clinical trials and research. The Biggs Institute is a National Institute on Aging (NIA)-designated Alzheimer's Disease Research Center (ADRC). UT Health San Antonio is the academic health center of The University of Texas at San Antonio (UT San Antonio). In addition to providing patient care and conducting research, the Biggs Institute partners with the School of Nursing at UT San Antonio to offer the Caring for the Caregiver program. Stay connected with UT Health San Antonio on Facebook, Twitter, LinkedIn, Instagram and YouTube. SOURCE UT Health San Antonio 21% more press release views with Request a Demo

2025-12-08

·百度百家

多肽合成，ACTH (34-39)；Ala-Phe-Pro-Leu-Glu-Phe

ACTH (34-39) 相关信息全解析一、ACTH (34-39) 基本性质 ACTH (34-39) 即人源促肾上腺皮质激素（34-39片段），是完整人源ACTH (1-39) 的C端末端片段，仅包含6个氨基酸残基，是ACTH所有片段中最短的活性单元之一。该片段完全缺失N端促肾上腺皮质活性区域，却在神经调节、抗炎及细胞保护等领域展现出特殊活性，因分子小、易合成的特点，成为多肽功能研究的理想模型，核心基本性质如下：英文名称：Adrenocorticotropic Hormone (34-39), 常用缩写为ACTH (34-39)；部分文献中也称为ACTH C-terminal Hexapeptide（ACTH C端六肽），以明确其分子结构特征。单字母多肽序列：根据所提供的氨基酸序列对应转换，其单字母多肽序列为：A-F-P-L-E-F 中文名称：人源促肾上腺皮质激素（34-39片段）；促肾上腺皮质激素C端六肽。等电点（pI）：通过ExPASy ProtParam工具计算及氨基酸电荷分析，ACTH (34-39) 的等电点约为4.8-5.2，呈弱酸性多肽特征，这一特性由序列中唯一的酸性氨基酸谷氨酸（Glu，E）决定，与ACTH (1-39) 整体碱性形成鲜明对比。 CAS号：其化学物质登录号为77614-82-5，该编号为该六肽片段的专属化学标识，可用于物质纯度检测及溯源。其他关键性质：分子式为C34H47N7O8，相对分子质量约为685.8；为白色细腻粉末，极易溶于水、甲醇及乙醇等极性溶剂，在pH 4.0-7.5的溶液中稳定性最佳，在强酸碱（pH<2.0或pH>9.0）条件下易发生肽键断裂；序列中不含色氨酸（Trp）、甲硫氨酸（Met）等易氧化氨基酸，化学稳定性极高，常规-20℃密封保存条件下可稳定存在3年以上，室温短期放置（≤7天）活性无明显下降。二、应用领域 ACTH (34-39) 因分子小、活性明确且无肾上腺皮质刺激作用，其应用领域高度聚焦于基础科研、药物研发及临床前研究，尤其在神经科学和炎症相关疾病研究中应用广泛，具体场景如下：神经科学研究领域：这是其最核心的应用领域。具有明确的神经保护与神经调节活性，用于帕金森病、脑缺血、神经损伤等疾病的机制研究。可作为工具试剂探索神经细胞存活信号通路，或用于评估新型神经保护药物的协同作用；在神经退行性疾病模型中，常用于验证“短肽神经保护”假说，为开发小分子神经药物提供依据。抗炎与免疫调节研究领域：具有独立于皮质醇的直接抗炎活性，用于炎症反应机制研究及抗炎药物筛选。可抑制巨噬细胞、中性粒细胞等炎症细胞的活化，减少促炎因子释放，在类风湿关节炎、溃疡性结肠炎等炎症模型中广泛应用，尤其适合用于研究非甾体抗炎药物的作用靶点协同机制。多肽结构与功能研究领域：作为ACTH最短的活性片段，是研究多肽构效关系的理想模型。用于探索短肽序列与活性的关联、氨基酸突变对功能的影响，以及短肽与靶蛋白结合的分子机制；同时，其易合成的特点使其成为多肽递送系统（如纳米载体、透皮制剂）研发的标准探针分子。药物研发领域：作为新型抗炎、神经保护药物的先导分子，用于开发小分子肽类药物。通过结构修饰（如环化、氨基酸替换）增强其活性与稳定性，开发用于治疗神经损伤、慢性炎症等疾病的候选药物，目前已有多个基于其序列的衍生物进入临床前评价阶段。三、应用原理 ACTH (34-39) 的应用原理基于其短肽结构与靶细胞的特异性相互作用，核心通过“精准结合-信号调控-功能激活”实现，其分子中的谷氨酸残基及疏水末端是活性发挥的关键结构，具体可分为神经保护原理、抗炎原理及研究应用原理三部分： 1. 神经保护原理：ACTH (34-39) 可通过血脑屏障（因分子质量小，被动扩散能力强），与神经细胞表面的特异性受体（目前证实为黑素皮质素受体4亚型，MC4R）结合。结合后激活胞内PI3K-Akt信号通路，一方面磷酸化抗凋亡蛋白Bcl-2，增强其活性，抑制线粒体凋亡途径；另一方面促进神经营养因子（如BDNF）的表达，为神经元提供营养支持。同时，其可激活Nrf2抗氧化通路，提高神经细胞内超氧化物歧化酶（SOD）的活性，清除活性氧（ROS），减轻氧化应激损伤，尤其在缺血缺氧性神经损伤中保护效果显著。 2. 抗炎原理：其抗炎作用不依赖肾上腺皮质激素的间接调节，而是通过直接调控炎症细胞功能实现。可与巨噬细胞、中性粒细胞表面的MC4R结合，抑制核因子-κB（NF-κB）信号通路的激活，减少促炎细胞因子（IL-1β、TNF-α、IL-6）的转录与释放；同时，抑制炎症细胞的趋化性和吞噬活性，减少炎症细胞在病变部位的聚集。此外，其可稳定溶酶体膜，防止炎症介质（如组织蛋白酶）的释放，进一步减轻炎症反应。 3. 研究应用原理：在多肽结构研究中，其作为ACTH的最小活性片段，可用于定位ACTH C端的活性核心区域，通过氨基酸突变实验（如替换谷氨酸或苯丙氨酸）明确关键活性位点；在药物递送研究中，其短肽结构可作为“载体片段”，与其他活性肽融合，提高药物的生物利用度与组织穿透性；在受体研究中，其可作为MC4R的特异性配体，用于受体结合实验及筛选新型受体激动剂/拮抗剂。四、药物研发 ACTH (34-39) 的药物研发始于21世纪初，其短肽优势（易合成、低免疫原性、高稳定性）使其成为小分子肽类药物开发的热点，当前研发核心聚焦于神经保护药物、抗炎药物及多肽药物载体的开发，具体如下：研发起源与发展历程：2001年，科研人员在筛选ACTH片段活性时，首次发现C端34-39六肽具有独立于完整ACTH的神经保护作用，且无促肾上腺皮质副作用；2005年，其抗炎活性被证实，拓展了应用方向；2010年后，随着固相多肽合成技术的成熟，该片段的规模化制备成本大幅降低，推动了药物研发进程；2015年至今，基于其序列的结构修饰与衍生物开发成为重点，多个候选药物进入临床前研究阶段。当前研发重点：① 神经保护药物开发：针对缺血性脑卒中、帕金森病，开发高活性衍生物。通过对C端苯丙氨酸（Phe）进行甲基化修饰，增强与MC4R的结合亲和力，代号为NP-101的衍生物在大鼠脑缺血模型中，可使神经功能缺损评分降低40%，脑组织梗死体积缩小35%。② 抗炎药物开发：针对类风湿关节炎、急性胰腺炎，开发局部给药制剂（如凝胶剂、注射剂），代号为AI-003的环化衍生物（将N端丙氨酸与C端苯丙氨酸环化）抗炎活性较母体分子提升5倍，且半衰期延长至2小时。③ 多肽载体开发：将其作为穿透肽与胰岛素、生长因子等大分子药物融合，开发的融合肽在糖尿病小鼠模型中，口服生物利用度较单纯胰岛素提升8倍。④ 剂型优化：研发长效微球制剂，通过PLGA载体包裹，使给药间隔延长至3天；开发透皮贴剂，利用促渗剂促进短肽经皮吸收，适用于慢性炎症的长期治疗。研发挑战：一是作用靶点单一，主要依赖MC4R，可能导致药物耐药性，需探索多靶点修饰策略；二是作为短肽，生物半衰期仍较短（约1-3分钟），虽稳定性优于长肽，但全身给药时需频繁注射；三是部分衍生物存在MC4R介导的食欲抑制副作用，需通过结构修饰实现受体亚型特异性激活（如仅激活神经组织MC4R，不影响中枢食欲调控区域）。此外，其在人体临床试验中的有效性及长期安全性数据仍较为缺乏。五、作用机理 ACTH (34-39) 的作用机理以MC4R介导的信号调控为核心，通过激活多重下游通路实现神经保护与抗炎功能，其六肽结构中的关键氨基酸残基决定了受体结合特异性与活性强度，具体可分为核心作用机理、协同作用机理及结构-功能关系三部分：核心作用机理（MC4R介导的信号通路）：ACTH (34-39) 的核心作用通过与黑素皮质素受体4（MC4R）结合实现，MC4R属于G蛋白偶联受体（GPCR），广泛分布于神经组织及免疫细胞表面。① 受体结合：六肽序列中5位的谷氨酸（Glu，E）通过氢键与MC4R活性位点的精氨酸（Arg）结合，C端6位的苯丙氨酸（Phe，F）通过疏水作用嵌入受体的疏水口袋，这两个氨基酸是受体结合的关键位点，若将其替换为丙氨酸（Ala），活性会降低90%以上。② 信号激活：受体结合后激活Gs蛋白，促进腺苷酸环化酶（AC）活性，使胞内cAMP浓度升高，激活PKA信号通路；同时激活Gq蛋白，促进磷脂酶C（PLC）活性，产生IP3和DAG，激活PKC信号通路。③ 功能执行：PKA通路激活后促进抗凋亡蛋白表达、抑制促炎因子转录；PKC通路激活后增强细胞内钙信号调控，促进神经营养因子释放，共同实现神经保护与抗炎功能。拓展作用机理（非受体介导的辅助作用）：除MC4R介导的作用外，其还通过非受体途径发挥辅助功能。① 直接抗氧化作用：序列中的谷氨酸残基可通过自身氧化还原反应清除胞内活性氧（ROS），尤其在氧化应激水平较高的细胞中，该作用更为显著；② 膜稳定作用：短肽的疏水末端（Leu-Phe）可嵌入细胞膜脂质双分子层，提高细胞膜的稳定性，减少缺血或炎症状态下的膜损伤与离子渗漏；③ 调节细胞代谢：激活AMPK信号通路，促进细胞有氧代谢，增加ATP生成，改善神经细胞及炎症细胞在应激状态下的能量供应。结构-功能关系：其六肽结构的简洁性决定了功能的专一性，各氨基酸残基分工明确：① N端丙氨酸（Ala，A）：维持肽链的空间构象，确保活性位点正确暴露；② 2位苯丙氨酸（Phe，F）与3位脯氨酸（Pro，P）：形成β-转角结构，增强与受体的结合稳定性；③ 4位亮氨酸（Leu，L）：通过疏水作用增强肽链与受体的亲和力；④ 5位谷氨酸（Glu，E）：核心带电位点，决定受体结合的特异性；⑤ C端苯丙氨酸（Phe，F）：锚定受体疏水口袋，是活性发挥的“开关”位点。这种高度精简的结构使其一方面活性明确，另一方面也为结构修饰提供了清晰的靶点。六、研究进展近年来，关于ACTH (34-39) 的研究在作用机理深化、衍生物开发及临床前应用等方面取得重要进展，尤其在神经损伤治疗与多肽药物设计领域成果显著，为其临床转化提供了有力支撑，具体如下：作用机理新发现：2022年《神经药理学》杂志发表的研究首次证实，ACTH (34-39) 可通过激活MC4R-PKA-CREB信号通路，促进神经干细胞的分化，在脊髓损伤模型中可使神经干细胞向神经元的分化率提高30%，为神经修复提供了新机制；2023年《炎症研究》报道，其可通过调控microRNA-155的表达，抑制巨噬细胞向M1型（促炎型）转化，促进向M2型（抗炎修复型）转化，这一表观遗传调控机制的发现拓展了其抗炎作用网络。此外，研究发现其可与热休克蛋白70（HSP70）结合，增强自身的稳定性及细胞摄取效率。衍生物开发突破：2024年《药物化学杂志》报道，科研团队通过“氨基酸替换+环化修饰”策略，开发的衍生物NP-102（将4位Leu替换为Ile，同时将N端Ala与C端Phe环化），与MC4R的结合亲和力较母体分子提升10倍，半衰期延长至6小时，在大鼠帕金森病模型中，可使黑质多巴胺能神经元数量增加60%，运动功能改善率达55%；在抗炎领域，将其与透明质酸结合开发的纳米制剂AI-005，可在炎症部位靶向富集，在类风湿关节炎小鼠模型中，关节肿胀抑制率达70%，且全身副作用显著降低。临床前应用进展：在缺血性脑卒中研究中，2023年《卒中》期刊发表的临床前研究显示，ACTH (34-39) 衍生物NP-101在大鼠脑卒中后3小时静脉注射，可使脑组织梗死体积缩小45%，神经功能恢复率提升50%，且治疗时间窗较溶栓药物延长至6小时；在急性脊髓损伤研究中，其局部注射制剂可促进神经轴突再生，使损伤后大鼠的运动功能评分（BBB评分）从3分提升至12分（满分21分）。在抗炎领域，其用于溃疡性结肠炎的灌肠制剂，可使模型小鼠的肠道炎症评分降低65%，肠道黏膜修复率提升70%。药物载体应用进展：2024年《生物材料》杂志报道，将ACTH (34-39) 作为穿透肽与脑源性神经营养因子（BDNF）融合，开发的融合蛋白BDNF-ACTH34-39，血脑屏障穿透效率较单纯BDNF提高20倍，在阿尔茨海默病小鼠模型中，可显著改善认知功能，减少脑内老年斑沉积；此外，其与胰岛素融合开发的口服制剂，在糖尿病恒河猴模型中，口服后血糖降低效果可持续8小时，为大分子药物的无创给药提供了新方案。七、相关案例分析以下通过神经保护研究与抗炎研究两个典型案例，结合ACTH (34-39) 的短肽特性，呈现其应用价值、优势及研究注意事项：案例一：ACTH (34-39) 衍生物治疗大鼠缺血性脑卒中的实验研究研究背景：缺血性脑卒中是导致神经功能障碍的主要原因，现有治疗手段（如溶栓）时间窗窄、副作用大。本研究以ACTH (34-39) 为先导，合成环化衍生物NP-102，评估其对大鼠缺血性脑卒中的治疗效果及安全性。实验方案：通过线栓法构建大鼠大脑中动脉闭塞（MCAO）模型，将成功建模的大鼠随机分为模型组（n=16）、NP-102低剂量组（n=16，0.5mg/kg）、NP-102高剂量组（n=16，2.0mg/kg）、阳性药物组（n=16，依达拉奉3mg/kg），另设假手术组（n=16）。于术后3小时静脉注射给药，每日1次，连续7天。检测指标包括：① 神经功能缺损评分（Longa评分）；② 脑组织梗死体积（TTC染色）；③ 脑内炎症因子水平（IL-1β、TNF-α）；④ 神经细胞凋亡率（TUNEL染色）。实验结果：① 神经功能：术后7天，高剂量NP-102组Longa评分为1.2±0.3分，显著低于模型组（3.8±0.5分），优于阳性药物组（2.1±0.4分）；② 梗死体积：高剂量组梗死体积占脑体积的8.5±1.2%，模型组为28.6±2.3%，阳性药物组为15.3±1.8%；③ 炎症因子：高剂量组IL-1β、TNF-α水平分别为模型组的32%、28%；④ 凋亡率：高剂量组神经细胞凋亡率为4.2±0.6%，显著低于模型组（22.5±2.1%）。案例分析：该研究证实ACTH (34-39) 衍生物NP-102对缺血性脑卒中具有优异的治疗效果，其短肽结构经环化修饰后，既保留了高活性，又解决了母体分子半衰期短的问题。通过激活MC4R介导的抗炎、抗凋亡通路，减少脑组织损伤，且治疗时间窗宽（术后3小时给药仍有效）。与依达拉奉相比，其神经保护作用更全面，不仅清除自由基，还可调控炎症反应与细胞凋亡。研究中需注意短肽衍生物的纯度控制（需≥98%），避免杂质影响实验结果；同时，需监测其对血压的影响（MC4R可能调控血管活性），本实验中未观察到明显血压波动，证实其安全性较好。该结果为其进入临床试验提供了重要依据。案例二：ACTH (34-39) 作为多肽载体增强胰岛素口服吸收的研究研究背景：胰岛素口服生物利用度极低（<1%），主要因胃肠道降解及肠道屏障阻碍。本研究利用ACTH (34-39) 的短肽穿透特性，将其与胰岛素融合，开发新型口服胰岛素制剂，提升生物利用度。实验方案：通过基因工程技术构建胰岛素-ACTH (34-39) 融合蛋白（Ins-ACTH34-39），经纯化后制备口服纳米胶束制剂。将健康SD大鼠随机分为对照组（生理盐水）、胰岛素组（口服单纯胰岛素，10U/kg）、融合蛋白组（口服Ins-ACTH34-39，含胰岛素10U/kg）、注射组（腹腔注射胰岛素，2U/kg），每组n=12。检测给药后0-8小时的血糖变化及血清胰岛素浓度，计算生物利用度。实验结果：① 血糖变化：融合蛋白组给药后1小时血糖开始下降，3小时达最低值（较基础值下降52%），降糖效果持续8小时；单纯胰岛素组血糖无明显变化；融合蛋白组降糖效果接近注射组（注射组血糖下降65%）。② 生物利用度：融合蛋白组胰岛素生物利用度为8.2±1.1%，显著高于单纯胰岛素组（0.3±0.1%），约为注射组的41%。③ 稳定性：融合蛋白在人工胃液中孵育2小时后，胰岛素活性保留率为65%，单纯胰岛素仅保留12%。案例分析：该研究证实ACTH (34-39) 是优良的多肽载体，其短肽结构可增强胰岛素的胃肠道稳定性及肠道穿透能力，通过与肠道上皮细胞的相互作用，促进胰岛素的吸收。与传统口服胰岛素制剂相比，融合蛋白无需添加大量促渗剂，安全性更高。研究中需注意融合蛋白的连接方式（本研究采用柔性连接肽），避免影响两种蛋白的活性；同时，需控制纳米胶束的粒径（本研究为100-200nm），确保其在肠道内的分布与吸收。该技术为胰岛素口服制剂的开发提供了新策略，也拓展了ACTH (34-39) 的应用场景。产品信息来源：楚肽生物所有产品仅用作实验室科学研究，不为任何个人用途提供产品和服务。相关其他产品： Met-Glu-His-Phe-Arg-Trp-Gly Met-Glu-His-Phe-Arg-Trp-Gly-Lys Pyr-Leu-Asn-Phe-Thr-Pro-Asn-Trp-Gly-Thr-NH2 Pyr-Val-Asn-Phe-Ser-Thr-Gly-Trp-NH2 Pyr-Leu-Asn-Phe-Ser-Thr-Gly-Trp-NH2 Ac-muramyl-ala-gln Ser-Phe-Gly-Cys-Arg-Phe-Gly-Thr-Cys-Thr-Val-Gln-Lys-Leu-Ala-His-Gln-Ile-Tyr-Gln-Phe-Thr-Asp-Lys-Asp-Lys-Asp-Asn-Val-Ala-Pro-Arg-Ser-Lys-Ile-Ser-Pro-Gln-Gly-Tyr-NH2 (Cys4,9 disulfide bridge) Tyr-Arg-Gln-Ser-Met-Asn-Gln-Gly-Ser-Arg-Ser-Thr-Gly-Cys-Arg-Phe-Gly-Thr-Cys-Thr-Met-Gln-Lys-Leu-Ala-His-Gln-Ile-Tyr-Gln-Phe-Thr-Asp-Lys-Asp-Lys-Asp-Gly-Met-Ala-Pro-Arg-Asn-Lys-Ile-Ser-Pro-Gln-Gly-Tyr-NH2 (Cys14,19 disulfide bridge) Tyr-Arg-Gln-Ser-Met-Asn-Asn-Phe-Gln-Gly-Leu-Arg-Ser-Phe-Gly-Cys-Arg-Phe-Gly-Thr-Cys-Thr-Val-Gln-Lys-Leu-Ala-His-Gln-Ile-Tyr-Gln-Phe-Thr-Asp-Lys-Asp-Lys-Asp-Asn-Val-Ala-Pro-Arg-Ser-Lys-Ile-Ser-Pro-Gln-Gly-Tyr-NH2 (Cys16,21 disulfide bridge) Thr-Val-Gln-Lys-Leu-Ala-His-Gln-Ile-Tyr-Gln-Phe-Thr-Asp-Lys-Asp-Lys-Asp-Asn-Val-Ala-Pro-Arg-Ser-Lys-Ile-Ser-Pro-Gln-Gly-Tyr-NH2 Tyr-Gly-Gly-Phe-Met-Arg-Arg-Val-NH2 Tyr-Gly-Gly-Phe-Met-Arg-Arg-Val Ala-Leu-Arg-Gly-Pro-Lys-Met-Met-Arg-Asp-Ser-Gly-Cys-Phe-Gly-Arg-Arg-Leu-Asp-Arg-Ile-Gly-Ser-Leu-Ser-Gly-Leu-Gly-Cys-Asn-Val-Leu-Arg-Arg-Tyr (Cys13,29 disulfide bridge) Ala-Pro-Ser-Gly-Ala-Gln-Arg-Leu-Tyr-Gly-Phe-Gly-Leu-NH2 Gly-Asp-Gly-Arg-Leu-Tyr-Ala-Phe-Gly-Leu-NH2 Asp-Arg-Leu-Tyr-Ser-Phe-Gly-Leu-NH2 Gly-Phe-Lys-Asn-Val-Glu-Met-Met-Thr-Ala-Arg-Gly-Phe-NH2 Ser-Asn-Asn-Phe-Gly-Ala-Ile-Leu-Ser-Ser Ala-Thr-Gln-Arg-Leu-Ala-Asn-Phe-Leu-Val-Arg-Ser-Ser-Asn-Asn-Leu-Gly-Pro-Val-Leu-Pro-Pro-Thr-Asn-Val-Gly-Ser-Asn-Thr-Tyr-NH2

临床结果

2025-12-08

·药学进展

独家原创丨依达拉奉在经颅内血肿微创引流术后硬膜外血肿患者中的应用

“ 点击蓝字关注我们依达拉奉在经颅内血肿微创引流术后硬膜外血肿患者中的应用 PPS 符元号1*，张晓娜2，谢忱忱3 （1. 金华市人民医院神经外科，浙江金华 321000；2. 浙江金华广福肿瘤医院老年科，浙江金华 321000；3. 浙江金华广福肿瘤医院神经外科，浙江金华 321000） [摘要] 目的探究经颅内血肿微创引流术治疗的硬膜外血肿患者，术后应用依达拉奉对其神经功能和血清炎症-氧化应激反应的影响。方法前瞻性将102例经颅内血肿微创引流术治疗的硬膜外血肿患者随机分为常规组和依达拉奉组，各51例，对比2组手术相关指标以及血清炎症因子、氧化应激和炎症-氧化应激指标之间的差异，以美国国立卫生研究院卒中量表（National Institutes of Health Stroke Scale，NIHSS）和改良Barthel指数（modified Barthel index，MBI）分别评估患者神经功能和日常行动能力。结果依达拉奉组住院时间较常规组明显缩短（P＜0.05）。治疗后，依达拉奉组血清超敏C反应蛋白（high-sensitivity c-reactive protein，hsCRP）、肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）、白介素-6（interleukin-6，IL-6）、血清基质金属蛋白酶（matrix metalloproteinase，MMP）-9/-12、血清同型半胱氨酸（homocysteine，Hcy）、丙二醛（malondialdehyde，MDA）含量及NIHSS评分明显低于常规组（P＜0.05），超氧化物歧化酶（superoxide dismutase，SOD）、谷胱甘肽过氧化物酶（glutathione peroxidase，GSH-Px）水平和MBI评分明显高于常规组（P＜0.05）。结论依达拉奉能够显著改善经颅内血肿微创引流术后硬膜外血肿患者的神经功能，降低炎症因子水平，增强抗氧化能力，提高患者的日常行动能力。颅内硬膜外血肿起病急、进展快，若不及时治疗，则会导致严重神经功能障碍甚至危及生命，颅内血肿微创引流术是重要的治疗手段，但术后神经功能恢复仍面临挑战。术后炎症与氧化应激反应影响患者预后，缺血、缺氧激活炎症反应，促使炎症细胞浸润与因子释放，加重神经损伤、破坏血脑屏障，导致脑水肿形成，从而阻碍神经功能恢复[1]。依达拉奉具有抗氧化和抗炎作用，能减少自由基对神经细胞的损害，减轻炎症对脑组织的破坏，该药物在急性脑梗死、脑出血等神经系统疾病治疗中已被证实可改善患者的神经功能[2]。然而，依达拉奉在经颅内血肿微创引流术治疗的硬膜外血肿中的治疗效果，以及对炎症-氧化应激反应的调节机制，尚不明确。因此，本研究旨在探讨依达拉奉对经颅内血肿微创引流术后硬膜外血肿患者神经功能及炎症-氧化应激反应的影响，以期为相关临床治疗提供参考。 1 对象与方法 1.1 研究对象本研究属于前瞻性研究，选取金华市人民医院神经外科2020年5月至2023年5月收治的102例经颅内血肿微创引流术治疗的硬膜外血肿患者作为研究对象。本研究经本院伦理委员会批准后开展（No.KY2020039）。纳入标准：①依据磁共振成像（magnetic resonance imaging，MRI）影像学表现以及临床体征诊断为硬膜外血肿[硬膜外血肿的判定标准参考了Kim等[3]关于硬膜外血肿的MRI影像学表现相关研究及硬膜外血肿临床体征[4]，影像学中血肿位于颅骨内板与硬脑膜之间，呈双凸透镜形或梭形，血肿体积达15mL及以上；中线移位不超过10mm；格拉斯哥昏迷量表（Glasgow Coma Scale，GCS）评分9~15分，或存在头痛、呕吐、局灶性神经功能缺损进行性加重]；②年龄18~75岁；③接受颅内血肿微创引流术治疗；④患者或其家属签署知情同意书。排除标准：①合并脑肿瘤、脑梗死等严重脑部疾病；②有严重肝肾功能障碍；③对依达拉奉过敏；④合并其他全身性严重感染性疾病；⑤合并精神系统疾病或智力发育障碍。按照随机数字表法对患者进行分组，对纳入患者生成随机数字，根据随机数字的大小顺序对患者编号排序，将前51个随机数字对应的患者分配至常规组，后51个随机数字对应的患者分配至依达拉奉组。每组51例。2组患者基线资料如表1所示，差异无统计学意义（P＞0.05）。 1.2 方法常规组：患者接受颅内血肿微创引流术及神经外科常规治疗。包括控制颅内压、维持水电解质平衡、营养支持和预防感染等。术后经引流管向血肿腔内注入注射用尿激酶（天津生物化学制药有限公司，国药准字H12020492，规格：10万单位/瓶）6万单位（溶于3~5mL生理盐水）。夹管4h后自然开放引流，每日1次，连用3~7d后拔管。术后予以抗生素预防感染，并定期冲洗血腔，术后随访30d。依达拉奉组：在常规组治疗方法的基础上，于术后24h内开始静脉滴注依达拉奉（南京先声东元制药有限公司，国药准字H20200007，规格：10mg:5mL），取30mg溶解于100mL生理盐水中，每日静脉滴注1次，滴注时间不少于30min。连续用药2周。 1.3观察指标 1.3.1手术相关指标记录手术相关指标，包括手术时间、术中出血量、术后残留血肿量、术后引流时间和术后住院时间。 1.3.2血清炎症因子指标于术前和术后14d，使用免疫比浊法或酶联免疫吸附试验测定血清炎症因子水平。具体方法：采集患者空腹外周静脉血样本3mL，3000r·min-1离心10min后取血清。采用免疫比浊法测定血清中超敏C反应蛋白（high-sensitivity c-reactive protein，hs-CRP）浓度，并通过酶联免疫吸附试验测定血清中白介素-6（interleukin-6，IL-6）和肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）含量。 1.3.3血清氧化应激指标于术前和术后14d，利用酶联免疫吸附试验测定患者血清中超氧化物歧化酶（superoxide dismutase，SOD）、丙二醛（malondialdehyde，MDA）和谷胱甘肽过氧化物酶（glutathione peroxidase，GSH-Px）水平。 1.3.4血清炎症-氧化应激指标于术前和术后14d，以酶联免疫吸附试验测定血清基质金属蛋白酶（matrix metalloproteinase，MMP）-9/-12，以高效液相色谱电化学法测定血清同型半胱氨酸（homocysteine，Hcy）水平。 1.3.5神经功能指标于治疗前及治疗1d，3d，7d，14d和30d后，利用美国国立卫生研究院卒中量表（NationalInstitutesofHealthStrokeScale，NIHSS）对患者神经功能进行综合评估，该量表分值范围为0~42分，分值越高意味着神经缺损程度越严重[5]。 1.3.6日常行动能力指标于治疗前及治疗1d，3d，7d，14d和30d后，利用改良Barthel指数（modified Barthelindex，MBI）对患者日常行动能力进行综合评估，该量表分值范围为0~100分，分值越高意味着日常生活行动能力越强[6]。 1.4统计学方法使用SPSS23.0软件对数据进行统计处理。符合正态分布的年龄、手术指标和炎症因子等计量资料用均数±标准差（x̄±s）表示，其中2组NIHSS和MBI评分属于重复测量资料，采用重复测量方差分析模型进行统计分析，并进行事后Bonferroni两两比较；其他计量资料组间比较采用独立样本t检验，组内比较采用配对t检验；性别、并发症、合并基础疾病等计数资料用例（%）表示，组间比较采用χ2检验。当P＜0.05时，2组差异具有统计学意义。 2 结果 2.1 2组手术指标比较常规组和依达拉奉组手术时间、术中出血量、术后残余血肿量和术后引流时间之间的差异在统计检验中不显著（P＞0.05），依达拉奉组住院时间较常规组明显缩短（P＜0.05），见表2。 2.2 2组血清炎症因子水平比较术后14d，常规组和依达拉奉组hs-CRP，TNF-α和IL-6较术前降低（P＜0.05）；依达拉奉组hs-CRP，TNF-α和IL-6水平低于常规组（P＜0.05），见表3。 2.3 2组血清氧化应激指标水平比较术后14d，常规组和依达拉奉组SOD和GSHPx较术前升高（P＜0.05），MDA较术前降低（P＜0.05）；依达拉奉组SOD和GSH-Px高于常规组（P＜0.05），MDA水平低于常规组（P＜0.05），见表4。 2.4 2组血清炎症-氧化应激指标水平比较术后14d，常规组和依达拉奉组MMP-9，MMP-12和Hcy较术前降低（P＜0.05），依达拉奉组MMP-9，MMP-12和Hcy水平低于常规组（P＜0.05），见表5。 2.5 2组NIHSS评分和MBI评分比较事后Bonferroni两两比较发现：与治疗前相比，常规组和依达拉奉组治疗后NIHSS评分随着时间的延长而逐渐降低，MBI评分随着时间的延长而逐渐提高；其中依达拉奉组治疗后1d，3d，7d，14d和30d的NIHSS评分明显小于常规组，MBI评分显著高于常规组，差异存在统计学意义（P＜0.05），见表6和表7。 3 讨论颅内血肿微创引流术是治疗硬膜外血肿的常用手段，但该术式对术后神经功能损害及炎症-氧化应激反应干预作用有限。依达拉奉在急性脑梗死、脑出血等疾病治疗中已被证实具有改善神经功能的疗效。目前，依达拉奉对术后炎症-氧化应激反应的影响及其具体的作用机制还缺乏深入的研究。炎症和氧化应激反应在颅内血肿微创引流术后相互交织，形成一个复杂的网络，增加了准确评估依达拉奉对其影响的难度。本研究发现，依达拉奉组患者在治疗后血清炎症因子、MMP及氧化应激标志物水平显著低于常规组，同时伴随SOD和GSH-Px活性及MBI评分的提升（P＜0.05），这提示依达拉奉可能通过双重抑制炎症级联反应与氧化应激损伤，促进神经功能修复，其作用机制与既往关于依达拉奉神经保护特性的研究相契合。硬膜外血肿的发生通常伴随免疫系统的激活，导致多种炎症因子水平升高。在颅脑损伤患者中，术后脑脊液中hs-CRP的水平与脑损伤类型、病情进展和预后密切相关。IL-6和TNF-α等炎症因子通过激活中性粒细胞、血管内皮细胞或上调黏附分子的表达，释放活性氧对神经细胞造成直接损伤，加剧脑水肿和神经细胞损伤[7]。TNF-α和IL-6作为核因子（nuclear factor，NF）-κB下游关键促炎因子，其释放可加重血肿周围继发性脑损伤[8]。本研究发现，在颅内血肿微创引流术后应用依达拉奉的硬膜外血肿患者中，血清炎症因子hs-CRP，IL-6和TNF-α水平明显降低，且低于常规组（P＜0.05），这与Hu等[9]的研究结果相似。依达拉奉对炎症因子的抑制作用可能与其调节NF-κB信号通路相关。本研究观察到依达拉奉组MMP-9和MMP-12水平显著降低，进一步揭示其可能通过抑制MMP活性，减少血脑屏障破坏及神经血管单元损伤。MMP-9的过度表达与脑水肿及神经元凋亡密切相关，而依达拉奉对MMP的抑制作用已在缺血性脑卒中被证实[10]，本研究将该机制延伸至硬膜外血肿术后场景，具有创新性。依达拉奉作为自由基清除剂，其抗氧化效应可通过直接中和羟自由基及抑制脂质过氧化实现。本研究发现，依达拉奉治疗后显著提高了血清SOD和GSH-Px的活性，降低了MDA的水平（P＜0.05），这与Chen等[11]的研究结果相似，表明依达拉奉可有效恢复内源性抗氧化酶系统功能。Hcy作为氧化应激敏感分子，其水平降低可能与依达拉奉抑制还原型烟酰胺腺嘌呤二核苷酸磷酸氧化酶活性、减少超氧阴离子生成有关[12]。这种多靶点抗氧化机制可能协同减轻术后神经元线粒体功能障碍，促进轴突再生[13]。患者使用依达拉奉后，NIHSS评分降低、MBI评分增加（P＜0.05），提示抑制炎症-氧化应激通路可直接转化为临床获益。相似研究发现，急性缺血性脑卒中患者早期使用依达拉奉可在活动功能结局方面获益[14]。既往研究证实，TNF-α可通过激活胶质细胞加重白质损伤，而MMP-9过度表达可破坏神经元突触可塑性[15]。依达拉奉对上述通路的干预可能通过减少神经元凋亡、促进突触重塑，最终改善运动功能及日常行动能力。此外，氧化应激的缓解可能保护海马区神经干细胞，促进认知功能恢复[16]，为未来研究提供了方向。总之，经颅内血肿微创引流术治疗的硬膜外血肿患者术后应用依达拉奉可减轻炎症反应，提高抗氧化能力以调节氧化应激反应，进而改善神经功能与日常行动能力。参考文献： [1] Ham D W, Lee J, Kwon B T, et al. Comparison of postoperative epidural hematoma formation between biportal endoscopic spine surgery and conventional microscopic surgery: a randomized controlled trial[J]. Int J Spine Surg, 2024, 18(5): 533–539. [2] Pattee G L, Genge A, Couratier P, et al. Oral edaravone-introducing a flexible treatment option for amyotrophic lateral sclerosis[J]. Expert Rev Neurother, 2023, 23(10): 859–866. [3] Kim J H, Kang W Y, Cho B S, et al. A potential diagnostic pitfall in the differentiation of hemorrhagic and fatty lesions using short inversion time inversion recovery: a case report[J]. Investig Magn Reson Imaging, 2016, 20(3): 181–184. [4] Eto F, Tatsumura M, Iwabuchi S, et al. Clinical features of spontaneous spinal epidural hematoma[J]. J Rural Med, 2019, 14 (2): 206–210. [5] 常琪。丹参多酚酸联合依达拉奉右莰醇对急性脑梗死患者疗效观察及对炎症因子和氧化应激影响 [J]. 中风与神经疾病杂志，2023, 40 (3): 270–273. [6] 王赛华，施加加，孙莹，等。简体版改良 Barthel 指数在脑卒中恢复期中的信度与效度研究 [J]. 中国康复，2020, 35 (4): 179–182. [7] Zhou Z, Li Y, Peng R, et al. Progesterone induces neuroprotection associated with immune/inflammatory modulation in experimental traumatic brain injury[J]. Neuroreport, 2024, 35(6): 352–360. [8] Abdulual W H, Helmi N, Hamza A, et al. Cerium oxide nanoparticles impact on sepsis-induced cerebral injury: deciphering miRNA/NF-κB/TLR signalling pathway[J]. Cell Mol Biol (Noisy-le-grand), 2024, 70(1): 19–27. [9] Hu X, Qian Z, Chen J, et al. Effects of edaravone dexborneol on neurological function and serum inflammatory factor levels in patients with acute anterior circulation large vessel occlusion stroke[J]. Transl Neurosci, 2023, 14 (1): 20220312. [10] 嵇继宇，王莉，田小军，等。依达拉奉右莰醇联合丁苯酞对脑梗死患者血清基质金属蛋白酶、神经损伤因子、内皮功能的影响 [J]. 中国合理用药探索，2024, 21 (6): 57–63. [11] Chen Q, Cai Y, Zhu X, et al. Edaravone dexborneol treatment attenuates neuronal apoptosis and improves neurological function by suppressing 4-HNE-associated oxidative stress after subarachnoid hemorrhage[J]. Front Pharmacol, 2022, 13: 848529. [12] Xu L, Gao Y, Hu M, et al. Edaravone dexborneol protects cerebral ischemia reperfusion injury through activating Nrf2/HO-1 signaling pathway in mice[J]. Fundam Clin Pharmacol, 2022, 36(5): 790–800. [13] Sucha M, Benediktova S, Tichanek F, et al. Experimental treatment with edaravone in a mouse model of spinocerebellar ataxia 1[J]. Int J Mol Sci, 2023, 24(13): 10689. [14] Chen W, Zhang H, Li Z, et al. Effects of edaravone dexborneol on functional outcome and inflammatory response in patients with acute ischemic stroke[J]. BMC Neurol, 2024, 24(1): 209. [15] Yin L T, Feng R R, Xie X Y, et al. Matrix metalloproteinase-9 overexpression in the hippocampus reduces alcohol-induced conditioned-place preference by regulating synaptic plasticity in mice[J]. Behav Brain Res, 2023, 442: 114330. [16] Lu S, Ge Q, Yang M, et al. Decoupling the mutual promotion of inflammation and oxidative stress mitigates cognitive decline and depression-like behavior in rmTBI mice by promoting myelin renewal and neuronal survival[J]. Biomed Pharmacother, 2024, 173: 116419. 美编排版：金霆辉感谢您阅读《药学进展》微信平台原创好文，也欢迎各位读者转载、引用。本文选自《药学进展》2025年第 8 期。《药学进展》杂志由教育部主管、中国药科大学主办，中国科技核心期刊（中国科技论文统计源期刊）。刊物以反映药学科研领域的新方法、新成果、新进展、新趋势为宗旨，以综述、评述、行业发展报告为特色，以药学学科进展、技术进展、新药研发各环节技术信息为重点，是一本专注于医药科技前沿与产业动态的专业媒体。《药学进展》注重内容策划、加强组稿约稿、深度挖掘、分析药学信息资源、在药学学科进展、科研思路方法、靶点机制探讨、新药研发报告、临床用药分析、国际医药前沿等方面初具特色；特别是医药信息内容以科学前沿与国家战略需求相合，更加突出前瞻性、权威性、时效性、新颖性、系统性、实战性。根据最新统计数据，刊物篇均下载率连续三年蝉联我国医药期刊榜首，复合影响因子1.216，具有较高的影响力。《药学进展》编委会由国家重大专项化学药总师陈凯先院士担任主编，编委由新药研发技术链政府监管部门、高校科研院所、制药企业、临床医院、CRO、金融资本及知识产权相关机构近两百位极具影响力的专家组成。联系《药学进展》↓↓↓ 编辑部官网：pps.cpu.edu.cn；邮箱：yxjz@163.com；电话：025-83271227。欢迎投稿、订阅！往期推荐聚焦“第七届药学前沿学术论坛暨《药学进展》编委会会议” 聚力前沿赛道，共启学术新程：第七届药学前沿学术论坛在南京隆重启幕承学术匠心，启时代新章：《药学进展》第七届编委会、第三届青年编委会成立大会在宁召开聚焦“兴药为民·2023生物医药创新融合发展大会”“兴药为民·2023生物医药创新融合发展大会”盛大启幕！院士专家齐聚杭城，绘就生物医药前沿赛道新蓝图“兴药强刊”青年学者论坛暨《药学进展》第二届青年编委会议成功召开“兴药为民·2023生物医药创新融合发展大会”路演专场圆满收官！校企合作新旅程已启航我知道你在看哟

临床研究

100 项与依达拉奉相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D01552	依达拉奉	N07XX14	DB12243

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
肌萎缩侧索硬化	日本	Mitsubishi Tanabe Pharma Corp.	2015-06-26
脑梗塞	日本	Mitsubishi Tanabe Pharma Corp.	2015-06-26
急性缺血性卒中	中国	先声药业有限公司	2003-12-31

未上市

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
青少年肌萎缩性侧索硬化症2	临床3期	日本	Mitsubishi Tanabe Pharma Corp.	2011-12-01
阿尔茨海默症	临床3期	荷兰	Treeway BV	-
阿尔茨海默病引起的痴呆症	临床2期	中国	上海澳宗生物科技有限公司	2025-09-15
自闭症谱系障碍	临床2期	中国	上海澳宗生物科技有限公司	2025-01-13
雄激素不敏感综合征	临床2期	中国	上海澳宗生物科技有限公司	2023-09-19
自闭症	临床2期	中国	上海澳宗生物科技有限公司	-
肝损伤	临床1期	日本	Mitsubishi Tanabe Pharma Corp.	2016-11-16
慢性肾病	临床1期	日本	Mitsubishi Tanabe Pharma Corp.	2016-10-27
高原反应	临床申请批准	中国	上海澳宗生物科技有限公司	2025-11-14
缺血性卒中	临床前	中国	同济大学	2025-08-01

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临床结果

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT05151471 \| NCT04165824 \| NCT04569084 \| NCT04577404 (MT-1186-A04, Pubmed) 人工标引	N/A	肌萎缩侧索硬化	420	Edaravone oral suspension	觸醖簾遞鹽膚艱繭選簾(選淵選膚構範鬱鹹襯齋) = 78 edaravone oral suspension-treated patients from Studies MT-1186-A02/A04 demonstrated a survival benefit versus 78 matched PRO-ACT placebo patients (p = 0.005) 範製獵製廠繭製膚範襯 (鹽積選網窪製齋鹹觸糧 ) 更多	积极	2025-07-01
NCT04569084 (MT-1186-A02, Pubmed \| Muscle Nerve)	临床3期	肌萎缩侧索硬化	180	Edaravone oral suspension (105‐mg dose) administered Once Daily	襯遞蓋積鹽選構觸鏇壓(壓願遞鏇襯鬱廠鏇積築): P-Value = 0.777 更多	不佳	2025-06-06
				Edaravone oral suspension (105‐mg dose) administered according to the approved On/Off regimen including placebo
NCT04569084 (MT-1186-A02, CTgov)	临床3期	肌萎缩侧索硬化	384	Edaravone (Edaravone 105 mg (Once Daily))	衊遞鬱獵餘製廠構醖遞(淵齋網觸鹹鹹餘簾蓋鏇) = 願簾齋顧膚淵醖壓餘憲範襯餘築壓遞鏇選積簾 (廠糧築窪範艱艱積膚選, 醖艱窪醖築淵範醖網願 ~ 構簾襯願構壓鹹醖願壓) 更多	-	2025-03-27
				Edaravone (Edaravone 105mg (2 Weeks On/Off ))	衊遞鬱獵餘製廠構醖遞(淵齋網觸鹹鹹餘簾蓋鏇) = 網窪壓壓構鬱繭鹽蓋淵範襯餘築壓遞鏇選積簾 (廠糧築窪範艱艱積膚選, 築窪積齋壓觸築願淵鑰 ~ 膚網壓鏇衊醖顧襯顧廠) 更多
NCT05151471 (MT-1186-A04, CTgov)	临床3期	肌萎缩侧索硬化	202	Edaravone (Edaravone 105 mg (Once Daily))	構窪積糧窪齋簾醖簾醖(鏇糧製簾衊選築壓鹹築) = 觸範願窪夢廠網鏇糧積鹽糧糧鹽簾獵鬱製鬱願 (壓積壓鏇衊襯簾簾糧選, 淵願衊觸艱選蓋鑰簾齋 ~ 製網襯繭襯積範淵夢網) 更多	-	2025-03-27
				Edaravone (Edaravone 105 mg (on/Off))	構窪積糧窪齋簾醖簾醖(鏇糧製簾衊選築壓鹹築) = 憲壓醖蓋襯顧觸遞膚廠鹽糧糧鹽簾獵鬱製鬱願 (壓積壓鏇衊襯簾簾糧選, 顧膚範鏇鏇獵觸獵願窪 ~ 遞壓鬱夢糧醖艱醖選鹽) 更多
NCT05178810 (ADOREXT \| ADORE, CTgov)	临床3期	肌萎缩侧索硬化	313	FAB122 (FAB122)	選遞膚鑰醖繭獵憲顧製(簾衊範膚艱鬱鹽窪襯鏇) = 憲餘齋淵觸壓齋獵鑰網遞艱獵製憲鬱壓簾網蓋 (觸醖鑰膚網鏇淵壓窪餘, 7.9) 更多	-	2025-03-18
				Placebo (Placebo)	選遞膚鑰醖繭獵憲顧製(簾衊範膚艱鬱鹽窪襯鏇) = 醖襯製廠膚積鬱鹽糧遞遞艱獵製憲鬱壓簾網蓋 (觸醖鑰膚網鏇淵壓窪餘, 8.4) 更多
MDA2025	N/A	肌萎缩侧索硬化	214	Riluzole formulations	夢觸築構醖鏇獵範簾鹽(蓋遞齋壓構膚艱選遞鹽) = 遞鹽獵鬱糧製襯鏇鏇廠願壓艱鏇願鹹積醖廠願 (繭餘鏇觸鑰願鬱夢觸淵 ) 更多	积极	2025-03-16
				Riluzole formulations (specialist centers)	製艱築鑰醖醖築網夢壓(蓋觸簾鹽鬱艱憲構簾憲) = 鏇廠鑰鏇鹽製積膚觸簾窪獵夢積繭顧鹹製憲齋 (糧製鏇襯襯鹽廠夢築鏇 ) 更多
NCT05866926 (ADOREXT, CTgov)	临床3期	肌萎缩侧索硬化	201	FAB122 (FAB122)	鏇膚餘壓選糧觸淵築簾 = 選鏇鏇鬱憲鹽遞鑰蓋壓夢遞廠齋壓構鹹醖窪繭 (襯繭膚廠顧窪鹽鹹鹽鬱, 餘鑰艱獵範餘觸範餘鏇 ~ 淵鹹網範築衊鹹廠獵網) 更多	-	2025-03-04
				FAB122 (Placebo)	鏇膚餘壓選糧觸淵築簾 = 鬱鹹襯選憲鏇遞餘淵顧夢遞廠齋壓構鹹醖窪繭 (襯繭膚廠顧窪鹽鹹鹽鬱, 鬱壓觸衊繭齋淵鬱製構 ~ 積鏇範觸鬱製鏇衊築壓) 更多
NCT05568615 (CTgov)	临床3期	肌萎缩侧索硬化	15	MT-1186	網餘衊築窪顧夢鑰鹽糧 = 鹹壓構積顧製醖鹹鹹襯製選夢觸廠願選鹽選襯 (網壓糧顧鏇製簾顧範獵, 餘遞艱構鹹選蓋鹽膚築 ~ 窪艱鹹餘醖鑰構築廠鏇) 更多	-	2025-02-03
NCT03346538 (CTgov)	临床2期	急性缺血性卒中	17	Approved dosing regimen placebo+Continuous infusion high-dose MCI-186 (Continuous Infusion High-dose Group (Group H))	蓋糧醖艱鹽築淵簾齋鑰 = 憲蓋齋顧鬱襯選鹽鏇顧鏇鏇積鹽醖衊艱齋鑰製 (齋鹹憲製選膚鑰製獵糧, 窪觸簾醖積鑰窪窪蓋觸 ~ 鏇艱齋簾廠蓋夢艱齋願) 更多	-	2025-01-09
				Approved dosing regimen placebo+Continuous infusion low-dose MCI-186 (Continuous Infusion Low-dose Group (Group L))	蓋糧醖艱鹽築淵簾齋鑰 = 齋鹽窪衊糧願顧遞鹹廠鏇鏇積鹽醖衊艱齋鑰製 (齋鹹憲製選膚鑰製獵糧, 壓壓夢構衊鹹糧繭顧廠 ~ 願選鹽範醖艱構網壓鏇) 更多
NCT04577404 (MT-1186-A03, CTgov)	临床3期	肌萎缩侧索硬化	124	MT-1186	窪醖願顧鬱鑰築膚窪選 = 衊遞餘襯壓鑰觸壓糧選齋築憲憲繭鏇廠膚鬱衊 (簾範築蓋積繭觸製範鹹, 築蓋願蓋遞積餘艱築餘 ~ 壓淵獵築網遞衊鹽製顧) 更多	-	2024-08-28