The Comparative Pilot Bioavailability Study of a Generic Test Formulation of Selegiline TDS 6 mg/24 Hours Against the Comparator EMSAM® 6 mg/24 Hours in Healthy Adult Subjects

The goal of this clinical study is to obtain the bioavailability of the test patch of a generic formulation of Selegiline TDS 6mg/24 hours by Corium Innovations against the comparator (EMSAM), and the systemic and local safety and tolerability will be also observed and evaluated.

开始日期2025-02-10

申办/合作机构

Corium Innovations, Inc.

DRKS00023352

/ Completed临床1期IIT

Pharmacokinetic profile of betahistine blood concentration with and without selegiline in healthy volunteers - a mono-center, open-labeled phase I trial - PK-BeST

开始日期2021-06-08

申办/合作机构-

IRCT20200719048136N1

/ Recruiting临床2/3期IIT

The effect of selegiline on functional and cognitive recovery in stroke patients

开始日期2020-08-22

申办/合作机构-

100 项与司来吉兰相关的临床结果

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100 项与司来吉兰相关的转化医学

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100 项与司来吉兰相关的专利（医药）

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2,757

项与司来吉兰相关的文献（医药）

2025-12-31·Annals of Medicine

Inhibition of 5-hydroxyindoleacetic acid to reduce neutrophil extracellular trap production improves lung condition in chronic obstructive pulmonary disease mice

Article

作者: Li, Wu ; Dai, Xiaotian ; Liang, Cheng ; Xiong, Wei ; Zeng, Qiang ; Zhou, Weijia ; Xue, Lei

BACKGROUNDNeutrophil extracellular trap (NET) correlate with chronic obstructive pulmonary disease (COPD) severity. Platelets can promote NET generation. However, serotonin alone or serotonin-deficient platelets do not adequately promote NET production. The metabolism of serotonin to 5-hydroxyindoleacetic acid (5-HIAA) in platelets may be the key to this difference.OBJECTIVEThe study aimed to determine whether 5-HIAA can influence NET production and thus play a role in COPD.METHODSAfter a 4-hour co-incubation with lipopolysaccharide (LPS) and 5-HIAA, NET and ROS levels in the culture medium were measured by ELISA, and NET production with aryl hydrocarbon receptor (AHR) expression in adherent cells were analyzed by immunofluorescence.A COPD model was established in C57BL/6 mice through smoke exposure combined with LPS tracheal administration, followed by selegiline or 5-HIAA treatment. Post-intervention, lung function tests and sample collection were performed. The levels of 5-HIAA, ROS‌, NET‌, IL-6‌, and AHR ‌in the samples were quantified by ELISA, pathological changes were assessed by HE staining, and NET/AHR expression was detected by immunofluorescence.RESULTS5-HIAA promoted NET production in vitro, and the nuclei of neutrophils secreting NET-like structures express AHR. In animal experiments, 5-HIAA levels were higher in both the plasma and lung tissues of COPD mice compared with normal mice. Inhibition of 5-HIAA in COPD mice down-regulated AHR expression, reduced reactive oxygen species and NET generation, elevated lung function indices (FEV0.1, FVC, PEF, and FEV0.1/FVC), decreased interleukin-6 levels, and improved lung tissue condition.CONCLUSIONInhibiting 5-HIAA reduces NET generation, thereby improving lung conditions in COPD mice, which is associated with the 5-HIAA/AHR pathway.

2025-12-01·Molecular Biology Reports

Molecular pathways: the quest for effective MAO-B inhibitors in neurodegenerative therapy

Review

作者: Udi, Onoriode Andrew ; Oyovwi, Mega Obukohwo ; Ogbutor, Udoji Godsday ; Atere, Adedeji David ; Joseph, Gregory Uchechukwu

Neurodegenerative diseases like Parkinson's and Alzheimer's are a global health challenge due to their progressive degeneration, leading to cognitive decline and motor dysfunction. Monoamine oxidase B (MAO-B) enzyme is implicated in neurodegeneration, and developing inhibitors could be a promising therapeutic strategy. This review explores MAO-B activity molecular pathways, evaluates MAO-B inhibitors in neurodegenerative therapy, identifies challenges, and suggests future research directions. This review synthesizes findings from a range of scientific literature, including experimental studies, clinical trials, and biochemical analyses that focus on the role of MAO-B in neurodegeneration. Information was gathered from databases such as PubMed, Scopus, and Web of Science, ensuring a comprehensive overview of recent advancements in MAO-B inhibition strategies. The review reveals several promising MAO-B inhibitors that have demonstrated efficacy in preclinical models, as well as some that have progressed to clinical trials. Compounds such as rasagiline and selegiline have shown neuroprotective effects and benefits in symptom management in patients with Parkinson's disease. Furthermore, the review discusses novel inhibitors that target specific molecular pathways, enhancing the potential for improved therapeutic outcomes. However, several inhibitors also present challenges regarding their selectivity, side effects, and long-term efficacy. Research on MAO-B inhibitors for neurodegenerative diseases is crucial, with ongoing studies aiming for selective, potent molecules with fewer side effects and multimodal therapies.

2025-05-01·Clinical Neurology and Neurosurgery

Clinical predictors of freezing of gait in patients with Parkinson's disease: A systematic review

Review

作者: Alhayssoni, Abdulrahman ; Alshimemeri, Sohaila ; Hazazi, Reema

BACKGROUNDFreezing of gait (FOG) is a debilitating motor symptom of Parkinson's disease (PD) that markedly impacts patients' quality of life. This review aims to identify clinical predictors of FOG to facilitate early prediction and future interventions.METHODSA systematic review adhering to PRISMA guidelines was conducted. Comprehensive searches in PubMed, EBSCO, and Web of Science yielded 1761 records. After removing duplicates, 1558 records were screened by title and abstract, and 92 full-text articles were assessed. Nine studies met the inclusion criteria and were qualitatively synthesized.RESULTSOur systematic review indicates that higher baseline MDS-UPDRS scores, which reflect greater disease severity, alongside elevated doses and early use of levodopa, are predictive of FOG in patients with PD. Additionally, higher Postural Instability and Gait Disorder (PIGD) scores, motor fluctuations, and lower limb disease onset further increase the risk of FOG. Other factors associated with an increased risk of FOG include older age, longer disease duration, anxiety, hyposmia, cognitive deficits, and sleep disorders. Furthermore, decreased step initiation duration when using visual cues serves as a predictor for the development of FOG. Early treatment with amantadine, selegiline, and dopamine agonists may help reduce the risk of developing FOG.CONCLUSIONA combination of motor and non-motor factors predicts the development of FOG. Understanding FOG predictors is crucial for developing future therapeutics and personalized management plans, enabling targeted interventions and improved outcomes.

项与司来吉兰相关的新闻（医药）

2025-04-22

·PRNewswire

XADAGO/EQUFINA Set to Revolutionize Parkinson's Disease Treatment Landscape | DelveInsight

As a selective monoamine oxidase B (MAO-B) inhibitor, XADAGO offers a unique mechanism of action that complements traditional therapies, potentially improving motor function and reducing "off" time in patients. The increasing prevalence of Parkinson's disease and the growing demand for effective therapies create a substantial market opportunity for XADAGO, particularly in regions with aging populations. LAS VEGAS, April 22, 2025 /PRNewswire/ -- DelveInsight's " XADAGO/EQUFINA Market Size, Forecast, and Market Insight Report" highlights the details around XADAGO/EQUFINA, an inhibitor of monoamine oxidase B (MAO-B) indicated as an adjunctive treatment to levodopa/carbidopa in patients with Parkinson's disease experiencing "off" episodes. The report provides product descriptions, patent details, and competitor products (marketed and emerging therapies) of XADAGO/EQUFINA. The report also highlights the historical and forecasted sales from 2020 to 2034 segmented into 7MM [the United States, the EU4 (Germany, France, Italy, and Spain), the United Kingdom, and Japan]. Newron Pharmaceuticals/Eisai/Meiji Seika Pharma's XADAGO/EQUFINA (safinamide) Overview XADAGO is a monoamine oxidase B (MAO-B) inhibitor used alongside levodopa/carbidopa to help manage "off" episodes in individuals with Parkinson's disease. While its exact mode of action in treating Parkinson's is not fully understood, it is thought to work by inhibiting MAO-B, thereby reducing dopamine breakdown. This leads to increased dopamine levels and enhanced dopaminergic activity in the brain. XADAGO contains the active ingredient safinamide in the form of a mesylate salt and is available in 50 mg and 100 mg film-coated oral tablets. Each tablet provides either 65.88 mg or 131.76 mg of safinamide mesylate, equivalent to 50 mg or 100 mg of the safinamide base. The medication is marketed as XADAGO in the United States and Europe and under the name EQUFINA in Japan. Learn more about XADAGO/EQUFINA projected market size for Parkinson's disease @ XADAGO/EQUFINA Market Potential Parkinson's disease is a progressive neurological disorder that mainly impairs movement control. It results from the slow degeneration of dopamine-producing neurons in the brain, especially in the substantia nigra, a region crucial for managing voluntary motor function. According to estimates by DelveInsight, there were 2.7 million diagnosed prevalent cases of Parkinson's disease in the 7MM in 2023, with the United States accounting for around 45% of these cases. While a cure for Parkinson's remains elusive, a combination of pharmacological and non-pharmacological therapies is used to manage symptoms. Physical, occupational, and speech therapies form key components of treatment, and surgical procedures may benefit select patients. Additionally, complementary therapies are sometimes employed to help address particular symptoms. Frequently prescribed medications for Parkinson's include levodopa, dopamine agonists, MAO-B inhibitors, COMT inhibitors, amantadine, anticholinergics, and adenosine A2A antagonists. These treatments primarily target motor symptoms, which are a major concern for those affected. DelveInsight reports that the Parkinson's disease market in the 7MM was valued at USD 3.2 billion in 2023. The market is expected to grow over the forecast period (2020–2034), fueled by the launch of new therapies, increasing prevalence, better access to healthcare, and rising demand for more advanced and effective treatment options. Discover more about the Parkinson's disease market in detail @ Parkinson's Disease Market Report Emerging Competitors of XADAGO/EQUFINA Some of the drugs in the pipeline include Solengepras (Cerevance), Minzasolmin (UCB Biopharma SRL/Novartis), Buntanetap (Annovis Bio), and others. Buntanetap has successfully completed Phase III trials for early-stage Parkinson's disease. Annovis Bio has scheduled a meeting with the FDA in Q1 2025 to determine the development path forward for Buntanetap in the treatment of Parkinson's disease. Buntanetap is also being developed for Alzheimer's disease, Lewy Body Dementia, and other neurodegenerative disorders. In November 2024, Cerevance announced the dosing of the first patient in its pivotal Phase III ARISE trial, evaluating solengepras as a potential adjunctive treatment for Parkinson's disease. Cerevance expects to report topline data in the first half of 2026. In December 2021, UCB partnered with Novartis to globally co-develop and co-commercialize UCB0599, a pioneering alpha-synuclein misfolding inhibitor currently in Phase II clinical trials for Parkinson's disease. To know more about the number of competing drugs in development, visit @ XADAGO/EQUFINA Market Positioning Compared to Other Drugs Key Milestones of XADAGO/EQUFINA In April 2020, Newron Pharmaceutical acknowledged that US WorldMeds, who held the US commercialization rights for the licensed drug, XADAGO, as a sub licensee of Zambon, had entered into a definitive agreement with Supernus Pharmaceuticals under which Supernus would acquire the CNS portfolio of US WorldMeds, including the US rights to XADAGO In November 2019, Eisai announced that it had launched the EQUFINA 50mg tablets for the indication of improvement of the wearing-off phenomenon in patients with Parkinson's disease under treatment with a drug containing levodopa in Japan. Manufacturing and marketing approval of EQUFINA was obtained in September 2019. In April 2017, Eisai Co., Ltd. and Meiji Seika Pharma announced entering into a license agreement for the commercialization of safinamide (development code: ME2125) to treat Parkinson's disease in Japan and Asia. In March 2017, Newron Pharmaceuticals announced the US FDA approval of XADAGO to treat Parkinson's disease as an add-on therapy to levodopa/carbidopa for patients experiencing "off" episodes. In March 2016, Zambon announced a strategic agreement with US WorldMeds to commercialize Newron's lead compound, XADAGO, to treat Parkinson's disease in the US. In February 2015, XADAGO was approved in the European Union as an add-on therapy to levodopa, alone or in combination with other Parkinson's medications, in mid-late stage PD patients with motor fluctuations. XADAGO/EQUFINA Patent Details XADAGO tablets are currently protected by three XADAGO patents with US patent numbers 8,076,515, 8,278,485, and 8,283,380, which expire between June 2027 and December 2028 and are listed in the FDA's publication, Approved Drug Products with Therapeutic Equivalence Evaluations, commonly referred to as the Orange Book. The company has a license agreement with Zambon S.p.A., Newron's partner, related to the XADAGO Patents, and as a new chemical entity, XADAGO is under the 5-year FDA exclusivity period that expires on March 21, 2022. In May 2017, Zambon filed a worldwide patent under the patent number WO2017207587A1. The invention relates to pharmaceutical compositions comprising safinamide and, more particularly, to taste-masked particles comprising said active ingredient or pharmaceutically acceptable salts thereof, oral dosage forms that include said particles, and a process for preparing them. Discover how XADAGO/EQUFINA is shaping the Parkinson's disease treatment landscape @ XADAGO 50mg XADAGO/EQUFINA Market Dynamics XADAGO, marketed as EQUFINA in some regions (notably in South Korea and Japan), is a once-daily oral selective MAO-B inhibitor used as an add-on treatment for Parkinson's disease patients experiencing "off" episodes while on a stable dose of levodopa. The drug's unique dual mechanism of action—MAO-B inhibition and modulation of glutamate release—offers both dopaminergic and non-dopaminergic effects, positioning it as a differentiated product in the PD adjunctive therapy landscape. This has helped it carve a niche in markets where patients are inadequately controlled by levodopa alone, particularly those in mid-to-late-stage PD. The global market dynamics for XADAGO/EQUFINA are shaped by a mix of competitive intensity, regional adoption trends, and payer dynamics. In the U.S. and Europe, the drug has faced stiff competition from generic MAO-B inhibitors (like selegiline and rasagiline) and newer Parkinson's disease therapies, including COMT inhibitors, dopamine agonists, and extended-release levodopa formulations. Despite this, its favorable safety profile and once-daily dosing have supported its uptake in certain patient segments, especially in Europe. Market penetration has been slower in the U.S. due to both reimbursement hurdles and physician preference for more established adjunctive treatments. In Asia, particularly Japan and South Korea, EQUFINA has demonstrated stronger market performance thanks to focused commercial strategies and a high unmet need for effective "off time" management. Meiji Seika Pharma and Eisai, the regional marketing partners, have successfully leveraged the drug's differentiated profile in clinician education, which has led to growing adoption among neurologists. In Japan, where the aging population is rapidly expanding and Parkinson's prevalence is rising, EQUFINA has benefited from both demographic tailwinds and formulary access. Looking ahead, the market outlook for XADAGO/EQUFINA depends on several strategic levers, including lifecycle management, regional partnerships, and real-world evidence generation. The manufacturer's ability to expand into new geographies, secure favorable reimbursement, and differentiate against both generics and newer entrants will be critical. Moreover, as Parkinson's disease treatment moves toward more personalized approaches, XADAGO/EQUFINA may find sustained relevance in specific subpopulations, particularly those requiring a balance of efficacy and tolerability. Dive deeper to get more insight into XADAGO/EQUFINA's strengths & weaknesses relative to competitors @ XADAGO/EQUFINA Market Drug Report Table of Contents Related Reports Parkinson's Disease Market Parkinson's Disease Market Insights, Epidemiology, and Market Forecast – 2034 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key Parkinson's disease companies, including UCB Biopharma SRL, Novartis, Annovis Bio, Supernus Pharmaceuticals, Inc., Britannia Pharmaceutical, Pharma Two B, Mitsubishi Tanabe Pharma (NeuroDerm), AbbVie, Cerevel Therapeutics, Cerevance, among others. Parkinson's Disease Pipeline Parkinson's Disease Pipeline Insight – 2025 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key Parkinson's disease companies, including Cerevel Therapeutics, Inhibikase Therapeutics, Neuraly, Peptron, Biogen, Roche, Brain Neurotherapy Bio, Inc., Modag, Annovis Bio Inc., BioVie Inc., United Neuroscience Ltd., Luye Pharma Group, AbbVie, UCB Biopharma SRL, InnoMedica Schweiz AG, Integrative Research Laboratories AB, H. Lundbeck A/S, Shanghai WD Pharmaceutical Co., Ltd., Cerevance Beta, Inc., Nobilis Therapeutics Inc., BlueRock Therapeutics, Taiwan Mitochondrion Applied Technology Co., Ltd., among others. Cell and Gene Therapy in Parkinson's Disease Market Cell and Gene Therapy in Parkinson's Disease Market Insights, Epidemiology, and Market Forecast – 2034 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key cell and gene therapy in Parkinson's disease companies including MeiraGTx, Hope Biosciences, Sumitomo Pharma, Prevail Therapeutics, BlueRock Therapeutics, Voyager Therapeutics, among others. Parkinson's Disease Psychosis Market Parkinson's Disease Psychosis Market Insights, Epidemiology, and Market Forecast – 2034 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key Parkinson's disease psychosis companies, including Sumitomo Pharma America Inc., Vanda Pharmaceuticals, Acadia Pharmaceuticals Inc., Otsuka America Pharmaceutical, Lundbeck LLC, Jazz Pharmaceuticals, Alkahest Inc., Sandoz, Sio Gene Therapies, Axovant Sciences Ltd, among others. About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . Contact Us Shruti Thakur [email protected] +14699457679 Logo: SOURCE DelveInsight Business Research, LLP WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

临床3期上市批准引进/卖出临床2期

2025-04-14

·微信

2025 MDS 运动波动循证建议更新解读

帕金森病（PD）患者在长期使用左旋多巴治疗后，超过80%的患者最终会出现症状波动（如 “关期” 延长、“开期” 缩短、剂末现象等）1。在另一项国内的研究中，接受左旋多巴治疗的中国患者在近1年内有29.0%出现症状波动，而10年以上人群中症状波动的发生率则高达68.3%2。在一项针对帕金森患者的问卷调查中，高达66.3%的患者认为改善症状波动非常重要3。因此，对帕金森患者的症状波动现象进行更好的管理对改善患者的生活质量有很重要的意义。为了更好地协助医生们针对患者个体选择合适的治疗方案，MDS（International Parkinson and Movement Disorder Society，国际帕金森和运动障碍学会）在2002年第一次基于循证医学证据发表了选择治疗方法的建议，而且之后也在定期更新，最近一次的更新是在2018年。截至目前，针对帕金森病运动症状的治疗方案仍然在不断增加，多项临床试验结果也在陆续发表。因此在2025年，MDS基于102项随机对照试验（RCT，randomized controlled trial），采用了新的评估方法，系统评估了现有治疗手段（包括药物和手术）的有效性与安全性，为临床决策提供了重要参考（图1）4。图1在文章中，针对每一项干预措施的疗效评价都采用了两个维度：（1）结局的临床相关性（the clinical relevance of the outcome）；（2）证据质量（the quality of the evidence）。为了确定临床结局的相关性，如果有临床数据，就会使用相应量表上的最小临床重要差异（MCID，minimal clinically important differences）。对于 “开期” 时长、“关期” 时长以及无异动症的时间长度，最小临床重要差异为每天1小时5。而对于PDQ-39（帕金森病问卷 - 39 项，Parkinson's Disease Questionnaire - 39），最小临床重要差异为5分6。在证据质量方面，采用改良的GRADE方法（modified version of Grading of Recommendations, Assessment, Development, and Evaluations)，基于偏倚风险、不精确性、不一致性、间接性以及发表偏倚的可能性，对每一项干预措施有效性的证据质量进行评估（图2）。图2沙非胺（既往称沙芬酰胺，safinamide）是新一代的MAO-B（ B型单胺氧化酶，monoamine oxidase B）抑制剂，并且是所有药物中唯一的具有双重作用机制抗帕金森的药物。沙非胺除了通过抑制MAO-B对多巴胺递质的分解代谢外，还可以通过阻滞离子通道的途径来抑制过量谷氨酸的释放来改善帕金森患者的症状7。该篇文献经过筛查最终纳入了4项与沙非胺相关的RCT8-11。在4项RCT中，对比评估了沙非胺和安慰剂之间对于改善“开期”和“关期”时间的疗效。全部试验都观察到了具有临床意义的“关期”时间减少（相比安慰剂组减少约1h），并且增加了不伴有令人困扰的运动障碍的“开期”时间（相比安慰剂组增加约1h），显示了沙非胺对于症状波动者的优越疗效。在PDQ-39评分表方面，其中1项研究8显示沙非胺达到了改善日常生活质量的阈值，另一项研究9提示在沙非胺100mg组中，对于安慰剂，PDQ-39评分的改善也超过了5分的阈值均提示了其在改善帕金森病患者日常生活质量的作用。另一方面，值得注意的是MDS目前基于现有研究认为，沙非胺是唯一具有双重作用机制（MAO-B抑制和通道阻滞）的抗帕金森药物。而且在药物有效性方面，相比于前两代MAO-B阻滞剂司来吉兰和雷沙吉兰，其对于症状波动的改善有更高程度的证据支持（沙非胺为有效，司来吉兰为证据不足，雷沙吉兰为可能有效）。并且唑尼沙胺（zonisamide）不再被认为是双机制治疗药物，其对症状波动的有效性方面，MDS也基于最新证据也将其从有效调整为可能有效（图3）。图3此外，IPX 066, ER（卡比多巴 / 左旋多巴缓释剂，Levodopa Carbidopa Extended – Release，IPX 066为其研究代码）在治疗症状波动上也有令人满意的效果，而且是唯一被MDS认为有效的Levodopa/PDI（左旋多巴 / 外周脱羧酶抑制剂）类药物。文中参考了1篇发表于2013年的RCT12。该研究发现IPX 066相比对照组在减少“关期”时间上有明显优势（约1.2 h ，P < 0.0001），并且在“开期”时间上也有明确改善（不伴令人困扰的运动障碍的“开期”时间为0.9 h, P < 0.001；不伴任何运动障碍的“开期”时间为0.7 h, P < 0.05）（图4）。图4在外科治疗方面，MDS也对各种治疗方式的临床有效性做了较大的调整。当前，Bilateral STN DBS（Bilateral Subthalamic Nucleus Deep Brain Stimulation，双侧丘脑底核脑深部电刺激术）是唯一被MDS认为有效的术式。而在上一版推荐中同样被认为有效的Bilateral GPi DBS（Bilateral Globus Pallidus Internus Deep Brain Stimulation，双侧苍白球内侧部脑深部电刺激术）和Unilateral pallidotomy（单侧苍白球切开术）现已被调整为可能有效（图5）。图5时隔7年 MDS 从数据库中15485篇相关文章最终筛选了102项高质量 RCT，并且采用了新的方法来对所有纳入的文章进行治疗有效性分析和证据质量分级。随着时间推移、新药的开发和更多临床试验结果的发表，人们对于帕金森运动波动的理解和治疗观念也随之发生改变：IPX 066成为唯一达到有效级别的 Levodopa/PDI 类药物、普拉克索和罗替高汀的治疗地位仍然稳固、恩他卡朋和雷沙吉兰的有效性级别下降、沙非胺成为唯一有效的双机制药物、唑尼沙胺在有效性级别下降的同时也不再被认为具有通道阻滞的作用、 Bilateral STN DBS是当前证据最充分的针对运动波动症状的手术方案。未来随着更多新药的开发和临床试验的进行，治疗的选择仍然可能会出现变化。 MDS最新的循证医学建议确认了沙非胺对于帕金森病症状波动治疗的有效性。作为新一代的MAO-B抑制剂，沙非胺可以抑制MAO-B对于多巴胺递质的代谢，同时调节钠离子和钙离子通道抑制过量谷氨酸的释放，通过目前唯一的双重抗帕金森机制，可以明显减少“关期”时间并且增加不伴有令人困扰的运动障碍的“开期”时间，其在改善PDQ-39评分方面也有一定的优势，并且对于非运动症状也有明显的改善作用13-15。在帕金森病的治疗中，尤其是出现运动并发症的患者，沙非胺将会是很有优势的选择。参考文献1. Stocchi F, Antonini A, Barone P,et al. Early DEtection of wEaring off in Parkinson disease: the DEEP study. Parkinsonism Relat Disord. 2014 Feb;20(2):204-11. 2. Wan Y, Yuan C. Hou X, et al. Wearing-off Identification in Parkinson's Disease: The shapd-woq Study. Front Neurol. 2020 Mar 13:11:116.3. Wüllner U, Fuchs G, Reketat N, et al. Requirements for Parkinson's disease pharmacotherapy from the patients' perspective: a questionnaire-based survey. Curr Med Res Opin. 2012 Jul;28(7):1239-46. study. Parkinsonism Relat Disord. 2014 Feb;20(2):204-11. 4. de Bie RMA, Katzenschlager R, Swinnen BEKS, Peball M, Lim SY, Mestre TA, Perez Lloret S, Coelho M, Aquino C, Tan AH, Bruno V, Dijk JM, Heim B, Lin CH, Kauppila LA, Litvan I, Spijker R, Seppi K, Costa J, Sampaio C, Fox SH, Silverdale MA. Update on Treatments for Parkinson's Disease Motor Fluctuations - An International Parkinson and Movement Disorder Society Evidence-Based Medicine Review. Mov Disord. 2025 Mar 8. doi: 10.1002/mds.30162. Epub ahead of print. PMID: 40055961. 5. Hauser RA, Gordon MF, Mizuno Y, et al. Minimal clinically important difference in Parkinson’s disease as assessed in pivotal trials of pramipexole extended release. Parkinsons Dis 2014;2014: 467131. 6. Horvath K, Aschermann Z, Kovacs M, et al. Changes in quality of life in Parkinson’s disease: how large must they be to be relevant Neuroepidemiology 2017;48(1–2):1–8. 7. Calabresi p, Kulisevsky J. Safinamide as Add-on Therapy - Moving Beyond Dopamine for a Multifaceted Approach in Parkinson's Disease.European Neurological Review,2017:12(Suppl. 5):2-6. 8. Borgohain R, Szasz J, Stanzione P, et al. Randomized trial of safinamide add-on to levodopa in Parkinson’s disease with motor fluctuations. Mov Disord 2014;29(2):229–237. 9. Hattori N, Tsuboi Y, Yamamoto A, Sasagawa Y, Nomoto M. Efficacy and safety of safinamide as an add-on therapy to L-DOPA for patients with Parkinson’s disease: a randomized, double-blind, placebo- controlled, phase II/III study. Parkinsonism Relat Disord 2020;75:17–23. 10. Schapira AHV, Fox SH, Hauser RA, et al. Assessment of safety and efficacy of safinamide as a levodopa adjunct in patients with Parkinson disease and motor fluctuations: a randomized clinical trial. JAMA Neurol 2017;74(2):216–224. 11. Wei Q, Tan Y, Xu P, et al. The XINDI study: a randomized phase III clinical trial evaluating the efficacy and safety of safinamide as add-on therapy to levodopa in Chinese patients with Parkinson’s disease with motor fluctuations. CNS Drugs 2022;36:1217–1227. 12. Hauser RA, Hsu A, Kell S, et al. Extended-release carbidopa-levodopa (IPX066) compared with immediate-release carbidopa-levodopa in patients with Parkinson’s disease and motor fluctuations: a phase 3 randomised, double-blind trial. Lancet Neurol 2013;12(4): 346–356. 13. Cattaneo C, M¨uller T, Bonizzoni E, et al. Long-Term Effects of Safinamide on Mood Fluctuations in Parkinson's Disease. J Parkinsons Dis. 2017;7(4):629-634. 14. Cattaneo C, Barone P, Bonizzoni E, et al. Effects of Safinamide on Pain in Fluctuating Parkinson's Disease Patients: A Post-Hoc Analysis. J Parkinsons Dis. 2017;7(1):95-101. 15. García DS, López IC, Guerra CL,et al. Safinamide improves sleep and daytime sleepiness in Parkinson's disease: results from the SAFINONMOTOR study. Neurol Sci. 2022 Apr;43(4):2537-2544. 提示：本材料仅供医疗卫生专业人士进行医学科学交流，不用于推广目的。

临床研究临床结果

2025-02-22

·药时空

纳米药物研究现状

摘要目的：为保障纳米药物的有效性和安全性提供参考。方法：参考国家药品监督管理局药品审评中心《纳米药物质量控制研究技术指导原则（试行）》，并检索药智网及美国食品和药物管理局、国家药品监督管理局官方网站，总结纳米药物的分类、上市情况和质量控制指标，并提出针对性建议。结果：纳米药物分为药物纳米粒、载体类纳米药物（脂质体、纳米乳、聚合物胶束等）及其他类别。全球上市纳米药物主要集中于肿瘤和感染的治疗，脂质体或脂质基纳米颗粒较普遍，其次为抗体-药物偶联物、聚合物-药物偶联物和聚合物纳米粒；中国纳米药物市场发展起步晚，但发展迅速。纳米药物特性相关的质量控制指标主要包括粒径大小及分布、结构及形态、Zeta电位、药物载体的载药量和包封率、药物体外溶出与释放等。结论：随着越来越多纳米药物的上市，其安全性、质量研究相关问题应得到重视。研发企业应结合纳米药物的载药量和包封率及药物体外溶出与释放行为，合理设计粒径大小与分布、结构及形态、Zata电位等关键性能；监管部门应建立纳米药物质量控制体系，进一步完善纳米药物监管机制。 _ 正文 _ 纳米药物，是指使用纳米技术生产纳米级颗粒形式的活性药物成分，或将活性药物成分与合适的纳米材料相结合以进一步配制成多功能剂型的纳米级颗粒。其发展过程分为3个阶段：初级研究阶段（第1阶段，1964—1995年），始于1964年发现脂质体结构，1995年美国食品和药物管理局（FDA）批准了首个基于脂质体阿霉素（DOX）递送系统的纳米药物Doxil®[1]；第2阶段（1995—2007年），相关研究开始迈向临床验证和商业化；第3阶段（2007年至今），纳米医学迅速发展，出现多种创新的纳米药物[2]。纳米药物的优点有：易进入细胞，更高效；比表面积大，可承载的功能基团或活性中心多；性能优越，便于生物降解或吸收，因有多孔、多层、中空等结构特性，易于实现药物的缓释、控释等功能。2021年8月国家药品监督管理局药品审评中心（CDE）发布的《纳米药物质量控制研究技术指导原则（试行）》[3]指出，与普通药物相比，纳米药物具有基于纳米结构的尺度效应。纳米药物特殊的纳米尺寸、纳米结构和表面性质等可能导致药物体内外行为的明显变化，从而实现临床获益；但纳米尺度效应带来的安全性风险可能会相应增加。本研究中参考《纳米药物质量控制研究技术指导原则（试行）》，并检索药智网及FDA、国家药品监督管理局（NMPA）官方网站，总结了纳米药物的分类、上市情况、质量控制指导，并提出针对性建议，为保障纳米药物的有效性和安全性提供参考。现报道如下。 1 分类 1.1 药物纳米粒无需载体材料，利用纳米制备技术可将活性成分通过高强度机械力直接粉碎成纳米级的纳米晶体药物。通常以结晶态分散粒子存在，当以液体形式存在时，又常被称为纳米混悬剂。具有粒径小、比表面积大的特点，可显著提高药物溶解性和生物利用度。与其他纳米给药系统相比载药量大，适合大剂量给药，同时高载药量可减少给药体积，多为口服制剂，是发展最早的纳米药物类型，如1996年获批于美国上市的盐酸替扎尼定片。 1.2 载体类纳米药物是利用各种材料（包括脂质、聚合物、蛋白质、金属和无机材料）制备的纳米载体负载药物，借助适当的载体材料与药物结合，对疾病进行靶向治疗。可利用各种纳米载体进行体内药物递送，通过主动靶向或被动靶向等多种机制实现跨生物屏障运输，将药物递送至肿瘤等病变部位，实现靶向治疗。目前研究较多的纳米载体主要有脂质体、纳米乳、聚合物胶束、聚合物纳米粒、无机纳米粒等。脂质体：是由磷脂双分子层包裹形成的封闭囊状体系，其水性内腔可用于水溶性肽类药物的运载，磷脂双分子层则起到阻滞药物泄漏的作用，同时可在表面进行功能化修饰以提高吸收效率。脂质体具有细胞膜样脂质双层结构，可同时负载疏水和亲水药物，具有稳定性好、生物相容性高、无毒性等优点[4]。但由于其复杂和异质的结构，需克服囊泡系统的物理和化学不稳定性相关的特定问题。目前已批准上市的脂质体药物主要集中于肿瘤治疗，同时也涉及感染、麻醉、疫苗、肺部疾病等领域。剂型主要为无菌混悬液和冻干粉，多用于静脉输注、肌内注射和鞘内注射。Doxil®脂质体的治疗范围已扩展到各种疾病，可有效负载一系列小分子和生物大分子药物（如肽、单克隆抗体等）[5-6]。纳米乳：是一种由2种不混溶液体组成的各向同性、透明/半透明、异质系统，由药物在纳米液滴中的精细分散组成[7]，是热力学和动力学稳定的系统（长期储存期间无任何明显的絮凝或聚结），具有极小的液滴尺寸（20~400nm）、均匀的尺寸分布及与其他乳液（>500nm）不同的物理、化学和生物学特性[8]。且对亲水性和亲脂性物质的溶解度较高，载药量百分比高，以及作用于赋形剂（与特定组织相互作用中起重要作用）的能力。纳米乳作为药物递送载体已被广泛用于注射、口服、经皮渗透等多种给药途径，由于透皮吸收效率较高，其已被证明是用于各种药物的皮肤和透皮递送的多功能载体[9]，如负载司来吉兰的纳米乳液，可用于鼻内递送司来吉兰治疗帕金森病。聚合物胶束：是在液体基质中形成的自组装聚合物，其特征在于核壳结构是由两亲性嵌段共聚物形成的纳米尺寸的球状胶束，具有疏水性核心和亲水性外壳，疏水性核心可包封水溶性差的药物，亲水性外壳可负载亲水性药物并使其维持稳定状态。在与高于其临界胶束浓度的水性介质接触时，通过共聚物的自组装形成载药聚合物胶束[9]。胶束分子特征灵活，可用于封装复杂、水溶性差的药物，将不同的两亲体组合在一个单一的聚集体中并产生能利用不同组分特征的混合胶束，从而大幅扩展了纳米载体的治疗潜力。聚合物胶束药物已达到癌症治疗评估和监管批准的临床阶段，如Genexol-PM®是由甲氧基聚乙二醇聚DL-丙交酯组成的共聚胶束，用于增加紫杉醇的水溶性和治疗效果[10]；其已获批应用于临床，作为癌症治疗药物。聚合物纳米粒：是一种基于聚合物的控释技术，核心包封活性药物组成的纳米级别的球形聚合物颗粒[11]。聚合物外壳可增加所负载蛋白质和核酸的稳定性，使其免受蛋白酶和核酸酶的降解，可通过筛选不同功能单体或交联剂来调控纳米粒的性质。与其他递送系统相比，聚合物纳米颗粒在储存期间具有更高的保质期稳定性、结构完整性；且其可使治疗剂持续释放，具有改进的特异性生物分布及易于通过静脉内途径给药[12]。常用的聚合物包括天然聚合物（白蛋白和壳聚糖等）及合成聚合物（聚乙二醇等），目前，已获批上市的有用于治疗胰腺癌、转移性乳腺癌的白蛋白-紫杉醇纳米颗粒Abraxnae®和用于治疗肝细胞性肝癌的阿霉素纳米颗粒Transdrug®[13]。聚合物-药物偶联物（PDC）：是指一个或多个药物分子的药理活性部分（小分子蛋白质、肽等）与聚合物通过共价偶联形成的纳米药物[14]。由聚合物骨架、头、靶向配体、药物等模块组成，具有改善药物溶解度、增强药物生物利用度、延长半衰期、提高治疗效果、控制药物递送的优点[15]，但其聚合物异质性、偶联物变异性、聚合物的免疫原性、安全性、稳定性是其应用于临床的主要障碍。合成聚合物、多糖等各种大分子被用于PDC充当着药物递送和靶向的载体。无机纳米粒：是一类具有多种形态、粒径1~100nm的纳米粒，不仅可进行表面修饰，还可通过不同方式（如疏水相互作用、静电相互作用等）与药物分子结合。主要以碳纳米材料、磁性纳米粒、二氧化硅纳米粒、钙纳米材料等形式存在。其具有良好的生物相容性及光热和光动力效应，与各种配体和生物分子可较好兼容，但体内消除率低，可能存在长期的潜在毒性。 1.3 其他随着纳米医学技术的不断发展，越来越多先进的天然材料（蛋白质、多糖等）和合成材料（聚乳酸-羟基乙酸共聚物、聚乙二醇等）作为纳米药物载体，还有一些新型纳米载体，如细胞外囊泡[16]、仿生和仿生纳米载体[17]、金属有机骨架[18]等也不断涌现。 2 上市情况目前，全球范围内已有100余种纳米药物获批上市，主要集中于肿瘤和感染的治疗，美国占据主要市场。在市场或临床转换的各个阶段可获得的纳米药物中，脂质体或脂质基纳米颗粒较普遍，其次为抗体-药物偶联物、聚合物-药物偶联物和聚合物纳米粒。其他类型的纳米药物包括病毒载体、细胞衍生载体、无机纳米粒、纳米乳、蛋白质纳米粒、聚合物胶束、纳米晶体、树枝状聚合物、胶体铁等[19]。国外已上市部分纳米药物见表1。相较于国外，我国纳米药物市场发展起步晚，但发展迅速，我国已上市纳米药物（部分）见表2。可知，注射用紫杉醇（白蛋白结合型）已有7家生产企业，截至2024年12月26日，取得批准文号的脂质体注射液有16个。2020年上市的注射用紫杉醇脂质体为南京绿叶制药有限公司自主研发的创新制剂，是全球首个获批上市的紫杉醇脂质体产品；2021年，上海谊众药业股份有限公司研制的首个紫杉醇胶束获批国家2.2类新药上市；2022年批准的国家2.2类新药盐酸米托蒽醌脂质体注射液是石药集团自主研发的抗肿瘤纳米药物，也是全球首个上市的米托蒽醌纳米药物。 3 质量控制方法纳米药物的性质有别于传统药物，其相关性能分为制剂基本特性和纳米相关特性两大类。前者相关的质量控制指标包括鉴别、含量测定、有关物质、残留溶剂等；后者主要包括粒径大小及分布、结构及形态、Zeta电位、药物载体的包封率与载药量、药物体外溶出和释放等。不同纳米药物的质量研究重点和内容可能不同，应设置具有针对性、科学合理的评价指标。粒径大小及分布：纳米药物的粒径大小及分布影响活性成分的载药量和释放行为，并影响其质量和药效作用。通常采用动态光散射法、显微成像技术、纳米颗粒跟踪分析系统等进行分析。朱晓亮等[20]通过马尔文激光粒度仪对利多卡因纳米乳的粒径大小及分布进行测定；LU等[21]采用马尔文激光粒度仪、粒度电位仪和显微镜对布比卡因脂质体的粒度进行分析。结构及形态：纳米药物的结构和形态可能影响其在体内与蛋白质和细胞膜的相互作用、药物的释放、纳米颗粒的降解和转运等。NMPA发布的《盐酸多柔比星脂质体注射液仿制药研究技术指导原则（试行）》和《注射用紫杉醇（白蛋白结合型）仿制药研究技术指导原则（试行）》均将药物形态作为关键质量属性进行要求，可采用电镜法、X射线衍射法和偏振光显微镜法进行分析。 Zeta电位：纳米药物的表面电荷可维持纳米粒子的稳定性，其取决于纳米药物的粒径大小、组成及分散介质。纳米药物的表面电荷一般基于Zeta电位进行评估，应选择适当的方法和介质进行研究。张淼等[22]采用动态光散射仪对卡巴他赛纳米混悬剂进行Zeta电位测定以筛选稳定剂浓度，同时Zeta电位测定还可用于表征卡巴他赛纳米混悬剂。药物载体的包封率和载药量：包封率是指包封的药量与纳米药物中总药量的比值，是纳米药物实现高效、低毒的关键。分离方法包括葡聚糖凝胶柱法、超速离心法和超滤法；载药量是指装载的药量与载体类纳米药物量的比值，是纳米粒作为药物载体可行性的一个重要指标。二者一般经样品前处理后根据药物性质采用适宜的测定方法进行测定。马福旺等[23]采用葡聚糖凝胶柱分离固脂纳米粒与游离马钱子碱，并采用高效液相色谱法测定载药量和包封率；李亚男等[24]采用薄膜分散法制备多西他赛他莫昔芬复方脂质体，采用葡聚糖凝胶柱层析法分离脂质体和游离药物，采用高效液相色谱法测定脂质体中多西他赛和他莫昔芬包封率。药物体外溶出与释放：纳米药物的体外溶出与释放是其重要质量属性，也在一定程度上反映纳米药物的体内行为，从而确保药物临床使用的有效性和安全性。纳米药物的尺度效应导致影响药物释放的因素更复杂，纳米给药系统粒径的多样性和不均匀性、体内释放过程的多样性、纳米载体材料的自身降解、纳米载体孔径大小、外部环境刺激、内部构象、渗透性等均可影响药物释放[25]。测定纳米药物体外释放度的方法主要有透析法、离心法、流通池法等。前2种方法报道较多，但不具有代表性的流体动力学特性且各有其局限性；流通池法能更好地模拟体内流体力学且维持漏槽条件，SIEVENS-FIGUEROA等[26]分别采用转篮法和流通池法测定灰黄霉素纳米混悬液体外释放度，结果显示，流通池法具有更好的粒径区分能力。 4 结语纳米药物能改善药物递送、提升药物稳定性、延长体内循环时间、增加药物安全性，目前已被用于递送难溶性药物、抗肿瘤药物、基因药物及需要突破血脑屏障的药物等。随着越来越多纳米药物的上市，其安全性问题和质量研究的相关问题也应得到更多的重视。研发企业应结合纳米药物的载药量和包封率及药物体外溶出与释放行为，设计合理的粒径大小与分布、结构及形态、Zata电位等关键性能，降低纳米尺寸效应带来的安全性风险，提升纳米药物有效性和安全性。CDE发布了《纳米药物质量控制研究技术指导原则（试行）》《纳米药物非临床药代动力学研究技术指导原则（试行）》《纳米药物非临床安全性研究技术指导原则（试行）》，为纳米药物关键质量属性的探索提供了指导意见，标志着国内纳米药物的监管迈出重要一步；但由于纳米药物传递体系的多样性，提高其靶向性、有效性和安全性应引起重点关注，监管部门应建立纳米药物质量控制体系，进一步完善纳米药物监管机制。参考文献详见《中国药业》 2025年1月第34卷第2期识别微信二维码，可添加药时空小编请注明：姓名+研究方向！

医药出海

100 项与司来吉兰相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D03731	司来吉兰	N04BD01	DB01037

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
重度抑郁症	美国	Somerset Pharmaceuticals, Inc.	2006-02-27

未上市

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适应症	最高研发状态	国家/地区	公司	日期
可卡因相关疾病	临床2期	美国	Somerset Pharmaceuticals, Inc.	2001-03-01

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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


NCT01330030 (CTgov)	临床2期	尼古丁依赖	243	Selegiline (Drug Selegiline)	鑰糧鏇夢積選糧夢壓糧(壓襯鹹襯顧窪繭顧簾蓋) = 窪鏇選願齋構餘構衊憲鬱鏇齋鏇願齋繭醖範鹹 (襯獵獵構窪餘簾鹽製衊, 夢夢鏇獵鏇遞壓夢淵鹹 ~ 獵壓窪築糧衊鑰簾築網) 更多	-	2016-04-04
				matching placebo (Matching Placebo)	鑰糧鏇夢積選糧夢壓糧(壓襯鹹襯顧窪繭顧簾蓋) = 鹽廠衊構顧憲淵遞鑰餘鬱鏇齋鏇願齋繭醖範鹹 (襯獵獵構窪餘簾鹽製衊, 鏇遞蓋顧窪膚築醖鹹餘 ~ 繭餘獵範衊窪範網糧鬱) 更多
AAN2015	临床3期	帕金森病	603	Rotigotine+Selegiline	廠遞積網壓鏇艱鬱構艱(鏇蓋蓋鑰鑰鏇鏇鏇製廠) = rotigotine+selegiline: 42%, placebo+selegiline: 15% 鬱製選選淵醖鹽齋廠鹽 (窪願鬱鹹淵鏇窪衊製齋 ) 更多	-	2015-04-06
				Placebo+Selegiline
NCT00535262 (CTgov)	临床4期	躁郁症	3	EmSam	鬱積繭範蓋膚鏇壓範鬱(窪製醖廠窪襯構築醖膚) = 淵齋憲糧廠齋夢繭選鹹簾艱鹽構繭選鏇獵簾醖 (衊衊衊鬱築鹹鏇積醖顧, 膚繭壓膚鑰蓋繭蓋窪夢 ~ 夢顧艱餘遞獵壓糧築製) 更多	-	2014-10-28
NCT00129311 (CTgov)	临床2期	尼古丁成瘾	101	Selegiline (Selegiline)	糧淵簾繭壓構鏇廠網窪(淵網憲顧窪糧衊襯簾窪) = 願簾網夢獵衊遞築製獵觸淵願壓襯夢淵鬱醖繭 (齋獵簾構積構繭獵範構, 構鹽遞遞壓顧觸繭蓋積 ~ 壓觸簾積糧襯鹹製蓋壓) 更多	-	2014-07-16
				placebo+Selegiline (Placebo)	糧淵簾繭壓構鏇廠網窪(淵網憲顧窪糧衊襯簾窪) = 鏇製願鹹鹹鬱積積築繭觸淵願壓襯夢淵鬱醖繭 (齋獵簾構積構繭獵範構, 衊獵醖遞積膚範築夢選 ~ 鏇願鬱淵艱鏇襯襯淵鑰) 更多
NCT00531947 (CTgov)	临床4期	重度抑郁症	308	Placebo (Placebo)	構壓膚艱鏇願鹹獵夢壓(網獵窪衊製憲壓衊顧遞) = 簾鏇鹹積顧鹽繭範鑰選製糧醖遞窪繭簾願繭壓 (選鏇衊鑰顧餘鑰鹽鹽淵, 衊餘憲願廠鬱廠鹹憲壓 ~ 簾齋積憲壓製醖構鑰糧) 更多	-	2013-06-26
				Selegiline Transdermal System (EMSAM)	構壓膚艱鏇願鹹獵夢壓(網獵窪衊製憲壓衊顧遞) = 鏇簾築鹽襯遞壓願壓鑰製糧醖遞窪繭簾願繭壓 (選鏇衊鑰顧餘鑰鹽鹽淵, 鹹築簾蓋築壓襯蓋廠廠 ~ 積鏇窪鑰遞蓋廠醖壓鹽) 更多
P06.087 (AAN2012)	N/A	帕金森病	-	Rasagiline	蓋製簾鹹壓遞遞獵築衊(廠獵顧範夢鬱顧選製衊) = 夢鑰鏇衊艱簾顧淵鑰鏇觸鏇繭獵積網鬱壓鑰網 (築夢鹽鑰鏇範夢衊鬱淵 )	积极	2012-04-23
				Selegiline	蓋製簾鹹壓遞遞獵築衊(廠獵顧範夢鬱顧選製衊) = 餘築鹹遞獵顧構觸窪鬱觸鏇繭獵積網鬱壓鑰網 (築夢鹽鑰鏇範夢衊鬱淵 )