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更新于：2026-10-19

Donepezil Hydrochloride

盐酸多奈哌齐

更新于：2026-10-19

概要

基本信息

简介多奈哌齐是一种小分子药物，作为乙酰胆碱酯酶抑制剂，有助于提高认知功能。该药物用于治疗轻度、中度和重度阿尔茨海默病患者，最初由日本的制药公司Eisai于1996年11月获得批准。尽管多奈哌齐盐酸盐不能治愈阿尔茨海默病，但它可以帮助控制与该病有关的某些症状，如记忆丧失、混乱和其他认知障碍。

药物类型

小分子化药

别名

ARIPEZIL、BNAG、Domepezil

+ [47]

靶点

ACHE

作用方式

抑制剂

作用机制

AChE抑制剂(乙酰胆碱酯酶抑制剂)

治疗领域

神经系统疾病内分泌与代谢疾病其他疾病

在研适应症

路易体病阿尔茨海默症痴呆+ [1]

非在研适应症

晚期癌症注意缺陷障碍常染色体显性遗传病合并皮质下梗死和白质脑病+ [15]

原研机构

Eisai Co., Ltd.

在研机构

McGill University

MYUNGMOON Pharm Co., Ltd.

山西皇城相府药业股份有限公司

+ [11]

非在研机构

Pfizer Inc.

ICURE PHARM INC

Teikoku Pharma USA, Inc.

+ [8]

权益机构

Inventage Lab, Inc.

ICURE PHARM INC

Lotus Pharmaceutical Co., Ltd.

+ [9]

最高研发阶段批准上市

首次获批日期

美国 (1996-11-25),

阿尔茨海默症

最高研发阶段(中国)批准上市

特殊审评优先审评 (中国)

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结构/序列

分子式C24H30ClNO3

InChIKeyXWAIAVWHZJNZQQ-UHFFFAOYSA-N

CAS号120011-70-3

关联

456

项与盐酸多奈哌齐相关的临床试验

NCT07768592

/ Not yet recruiting临床1期

A Proof-of-Mechanism, Open-Label, Parallel Group Study With an Open-Label Extension Phase to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of E2511 in Participants With Early Alzheimer's Disease

The primary purpose of this study is to evaluate proof of mechanism (POM) and long-term safety and tolerability of E2511 in participants with Early AD. The study consists of 2 parts. In Part A, participants will be randomly assigned to receive either E2511 or donepezil. In Part B, participants will receive E2511 only. Once Part A and Part B participants complete the Core Trial (which includes Pretreatment and Treatment phases) they will have the option to enter the Extension Phase where they will receive E2511 for 18 months.

开始日期2026-10-15

申办/合作机构

Eisai, Inc.

NCT07680660

/ Not yet recruitingN/AIIT

A Multicenter Randomized Controlled Trial on the Efficacy and Safety of Cervical Lymph Vessel/Node-venous Anastomosis Combined With Donepezil Versus Donepezil Alone in the Treatment of Alzheimer's Disease

This study employed a multicenter, randomized controlled trial (RCT) design to evaluate the efficacy and safety of deep cervical lymphatic/lymph node-venous anastomosis combined with oral donepezil compared to donepezil monotherapy in patients with Alzheimer's disease and moderate dementia. Participants were randomized using a central randomization system with stratified block design, with the study center and age group (50-64 years, 65-80 years) as stratification factors. While study participants and surgical investigators could not be blinded due to the nature of the intervention, efficacy assessors and imaging specialists remained blinded to ensure the objectivity and reliability of the findings. The intervention group received deep cervical lymphatic/lymph node-venous anastomosis (detailed surgical procedure is specified in the protocol) in combination with oral donepezil (5-10 mg/day), while the control group received oral donepezil alone. The total treatment and follow-up period was 18 months, with assessments conducted at baseline, 1 week, 1, 3, 6, 12, and 18 months post-operation. These included neuropsychological evaluations (MMSE, MoCA, CDR, BADL, IADL, NPI, AES), neuroimaging (MRI, PET, ultrasound), fluid biomarker analyses (CSF and blood levels of Aβ, Tau, neuroinflammatory factors, etc.), and safety monitoring. The primary efficacy endpoint was the change in CDR-SB score at 12 months post-treatment. Secondary endpoints included changes in multiple cognitive scales, neuroimaging metrics, and biomarkers at 18 months. Safety indicators encompassed adverse event recording, vital signs, and laboratory tests.

开始日期2026-07-15

申办/合作机构

上海交通大学医学院附属第九人民医院

ChiCTR2600133844

/ SuspendedN/AIIT

Brain Connectivity Impairment Patterns and Prognosis of Neuropsychiatric Symptoms in Alzheimer’s Disease-Efficacy and Adverse Effects of Anti-Dementia Drugs Based on Brain Connectivity Impairment Patterns in Patients with Neuropsychiatric Symptoms among Alzheimer\'s Dementia: Rationale and Design of a Randomized, Blinded-Endpoint Trial

开始日期2026-07-01

申办/合作机构

首都医科大学附属北京天坛医院

100 项与盐酸多奈哌齐相关的临床结果

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100 项与盐酸多奈哌齐相关的转化医学

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100 项与盐酸多奈哌齐相关的专利（医药）

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6,436

项与盐酸多奈哌齐相关的文献（医药）

2027-03-01·Value in Health Regional Issues

Epidemiology, Patient Characteristics, Treatment Patterns, and Costs of Mild Cognitive Impairment and Alzheimer’s Disease in Taiwan

Article

作者: Cho, Sarah ; Hu, Chaur-Jong ; Shen, Shih-Pei ; Wang, Bruce C M ; Tang, Chao-Hsiun ; Newson, Rachel S ; Huang, Yao Hsien

OBJECTIVES:

Alzheimer's disease (AD) with mild cognitive impairment (MCI) and AD are stages along the cognitive decline continuum and represent growing public health concerns. This study aimed to assess the diagnosed prevalence, claims-identified incidence, treatment patterns, healthcare costs, comorbidities, and observed mortality outcomes of individuals with AD with MCI, and AD with dementia in Taiwan claims data over a 10-year period.

METHODS:

We conducted a retrospective cohort study using Taiwan's National Health Insurance Research Database. Individuals diagnosed with AD with MCI, or AD, between 2013 and 2022 were identified via ICD-9-CM and ICD-10-CM codes. Cross-sectional and longitudinal analyses examined epidemiology, treatment trends, costs, comorbidities, and mortality using descriptive statistics, survival analysis, and cost evaluations.

RESULTS:

The estimated prevalence of AD with MCI, and AD from the claims database, increased from 109 379 cases in 2018 to 131 053 in 2022. Among pharmaceutical interventions, donepezil usage was predominant and increased over time, whereas nonpharmacologic therapies remained minimal. Healthcare costs rose with disease severity, with nonpharmacological inpatient care being the highest expense. Cardiovascular and metabolic comorbidities were prevalent and increased with severity. Observed cumulative mortality proportions increased with advancing disease severity; patients with AD with severe dementia had the highest mortality burden (41.98% at year 3).

CONCLUSION:

AD with MCI and AD with dementia prevalence estimation is rising, demonstrating increasing costs and high comorbidity burdens. Disease severity is linked to higher mortality, reinforcing the need for integrated care and early cost-effective interventions to optimize outcomes in AD with MCI and AD with patients with dementia.

2027-02-01·JOURNAL OF ETHNOPHARMACOLOGY

Bushen-Yizhi formula promotes neurogenesis and ameliorates cognitive impairment by activating ST8Sia Ⅱ/Ⅳ-PSA-NCAM pathway in ibotenic acid induced mice

Article

作者: Liang, Yong ; Tan, Qiwen ; Wang, Qi ; Zheng, Jingjing ; Liu, Guoqing ; Xie, Ruiye

ETHNOPHARMACOLOGICAL RELEVANCE:

Bushen-Yizhi formula (BSYZ), a traditional Chinese herbal prescription, has been widely used to treat kidney deficiency syndrome and alleviate cognitive impairment associated with Alzheimer's disease (AD). Loss of polysialylation of the neural cell adhesion molecule (PSA-NCAM) is closely associated with cognitive dysfunction. However, whether BSYZ regulates PSA-NCAM polysialylation and the underlying mechanisms remain unclear.

AIM OF THE STUDY:

This study aimed to investigate whether BSYZ promotes hippocampal neurogenesis and ameliorates cognitive impairment through activation of the ST8Sia II/IV-PSA-NCAM pathway.

METHODS:

An AD-like mouse model was established by bilateral ibotenic acid (IBO) injections into the basal nuclei of C57BL/6 mice. Animals were randomly assigned to five groups: control, model, low- BSYZ (1.46 g/kg), high-dose BSYZ (5.84 g/kg), and donepezil (3 mg/kg). Cognitive function was evaluated using the open field test (OFT), novel object recognition test (NORT), and Morris water maze (MWM). Hippocampal PSA-NCAM expression was assessed by immunofluorescence staining and further investigated using proteomic analysis combined with network pharmacology. PSA-NCAM-associated polysialic acid levels were quantified by hydrochloric acid hydrolysis followed by 4,5-methylenedioxy-1,2-phenylenediamine dihydrochloride (DMB) derivatization coupled with mass spectrometry. The mRNA and protein expression levels of α-2,8-sialyltransferase II and IV (ST8Sia II/IV) were determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blotting. Hippocampal neurogenesis was evaluated by immunofluorescence double-labeling. The bioactive compounds targeting ST8Sia II/IV were identified using HPLC-Q-TOF MS/MS, followed by molecular docking and molecular dynamics simulations to predict their binding affinities.

RESULTS:

The IBO-induced mouse model exhibited significant cognitive deficits, confirming successful model establishment. Behavioral assessments demonstrated that both low- and high-dose BSYZ significantly improved learning and memory performance. Proteomic analysis and immunofluorescence staining revealed that BSYZ markedly increased hippocampal PSA-NCAM expression (**P < 0.01, n = 5). Quantitative analysis further showed that PSA-NCAM-associated polysialic acid levels increased by 78% (*P < 0.05, n = 5) and 102% (**P < 0.01, n = 5) following low- and high-dose BSYZ treatment. BSYZ significantly increased the number of PSA-NCAM⁺/DCX⁺ cells in the hippocampal dentate gyrus (*P < 0.05), accompanied by significant increases in Nestin⁺/BrdU⁺ (*P < 0.05), DCX⁺/BrdU⁺ (**P < 0.01), and NeuN⁺/BrdU⁺ (**P < 0.01) double-positive cells, indicating enhanced neurogenesis and neuronal maturation. Furthermore, BSYZ significantly upregulated both the mRNA and protein expression of ST8Sia II (**P < 0.01) and ST8Sia IV (**P < 0.01) in the hippocampus. HPLC-Q-TOF MS/MS, molecular docking, and molecular dynamics simulations identified isoimperatorin as a major active constituent of BSYZ with strong binding affinity toward both ST8Sia II/IV, exhibiting docking energies of -8.7 and -7.6 kcal/mol, respectively (n = 3, RSD < 2%).

CONCLUSIONS:

Our study demonstrates BSYZ promotes hippocampal neurogenesis to ameliorate cognitive impairment by activating ST8Sia II/IV-PSA-NCAM pathway. These findings provide mechanistic evidence supporting the therapeutic potential of BSYZ for AD treatment.

2027-02-01·JOURNAL OF ETHNOPHARMACOLOGY

Neuroprotective effects of Isodon ramosissimus (Hook.f.) Codd (Lamiaceae) aqueous extract against scopolamine-induced Alzheimer-like phenotype

Article

作者: Owona, Pascal Emmanuel ; Kengne, Ségolène Flore ; Follesa, Paolo ; Bidinga A Goufani, Cédrick Ronald ; Akamba Ambamba, Bruno Dupon ; Kamtchouing, Pierre ; Kahou Tadah, Rivaldo Bernes ; Bilanda, Danielle Claude ; Tcheutchoua, Yannick Carlos ; Ngapout Fifen, Joseph Rodrigue ; Dzeufiet Djomeni, Paul Désiré

ETHNOPHARMACOLOGICAL RELEVANCE:

Isodon ramosissimus is traditionally used in folk medicine for the management of neurological disorders. However, its neuroprotective properties against scopolamine-induced cognitive impairments have not yet been scientifically investigated.

AIM OF THE STUDY:

This study investigated the anti-amnesic and neuroprotective effects of the aqueous extract of Isodon ramosissimus (IrAE) in a scopolamine-induced Alzheimer's-like phenotype in rats.

MATERIALS AND METHODS:

Liquid chromatography-mass spectrometry (LC-MS) and quantitative phytochemical analyses were performed to tentatively identify IrAE bioactive compounds. Forty-eight male Wistar rats were randomly assigned to six groups receiving saline, scopolamine (1 mg/kg), scopolamine plus donepezil (5 mg/kg), or scopolamine plus IrAE (75, 150, or 300 mg/kg) for 14 consecutive days. Learning and memory were evaluated using the novel object recognition and Morris water maze tests. Cholinesterase activity, oxidative stress biomarkers, and histopathological changes in the prefrontal cortex and hippocampus were also assessed.

RESULTS:

Scopolamine induced significant cognitive deficits (p < 0.01), increased Acetylcholinesterase activity and oxidative stress (p < 0.01), and caused substantial neuronal damage. IrAE treatment significantly reversed learning and memory deficits (p < 0.01), attenuated acetylcholinesterase activity and oxidative stress (p < 0.01), and preserved cortical and hippocampal neurons from scopolamine's neurotoxic effects. LC-MS analysis tentatively identified oridonin, stigmasterol, chrysoeriol, ferruginol, and corosolic acid, compounds with reported cognitive-enhancing, antioxidant, anti-inflammatory, anticholinesterase, and neuroprotective activities.

CONCLUSION:

IrAE exerts marked anti-amnesic and neuroprotective effects, associated with cholinergic and antioxidant modulation. These findings provide preliminary pharmacological support for the traditional use of IrAE, warranting further preclinical investigation of its potential in the management of cognitive disorders.

555

项与盐酸多奈哌齐相关的新闻（医药）

2026-10-17

·智科院

分子里的"换人"手术：在复杂分子的骨架上直接替换原子，而且用上了氧气

副标题：芝加哥大学团队让一个"出了岔子就彻底失败"的中间体变成了捷径——C到 N 原子替换的反应条件温和到能用在天然产物上在化学里，有一种改分子的手法叫"骨架编辑"（skeletal editing）。它的意思是：不改动分子表面的官能团，而是直接动分子"骨架"上的原子——把一个碳换成氮，或者把一个氮换成碳。听起来像科幻。但药物化学家想要这个能力，已经想要了至少二十年。01为什么药物化学家想要"换原子" 先说清楚这项技术的需求方到底是谁，以及它到底解决什么问题。现代药物研发的主流方法是"先搭骨架、后加装饰"：先用一个现成、易得的分子骨架（scaffold），再往上挂各种官能团来调整活性。这有点像盖房子——先有房型，再装修。但骨架编辑提供的是另一种能力：直接改造房型本身。为什么这很重要？因为药物分子的性质（活性、毒性、溶解度、代谢稳定性）在很大程度上是由骨架决定的。一个碳换成氮，会改变：分子的电子分布 → 影响它和靶点的结合强度；分子的极性和溶解度 → 影响它能不能被吸收、能不能进血脑屏障；分子的代谢稳定性 → 影响它在体内被分解的速度。而"只换掉一个原子，其他一切不变"——这正是理解"这个碳换成氮会怎样"的最干净的方法。药物化学家管这类系统探索叫"氮扫描"（nitrogen scanning）——在一个芳香环的各个位置上，迭代地把碳原子替换成氮，看结果如何变化。问题在于：从头合成这些替换后的分子，非常耗时耗力。由于含氮杂环（吡啶、咪唑、哒嗪之类）在药物里极其常见，化学家们真正想要的是——能不能从一个现成的分子出发，直接把某个位置换成氮？这项由芝加哥大学马克·莱文（Mark D. Levin）教授团队完成、发表在《科学》（Science）上的工作，就是这个问题的答案。02之前为什么做不到在此之前，做"芳香环碳换氮"最主流的路线是这样的：把芳香环上的一个碳先变成叠氮（azide）；用紫外光照射，生成一个单重氮宾（singlet nitrene）中间体；单重氮宾发生扩环反应，把氮原子并入环里——环变大了一圈；再用氧化剂把环缩回原来的大小，但此时多出来的那个位置已经是氮了。这个设计的巧妙之处在于：先用扩环"腾出位置"，再缩环"锁定位置"。而它的死穴在第2 步和第 3 步之间。单重氮宾有一个致命弱点：在电子丰富或者高度共轭的体系里，它极易"跳"到三重态（三重氮宾，triplet nitrene）。而问题在于——药物候选分子，恰恰绝大多数都是高度共轭的芳香环系统。一旦跳到三重态，它就无法完成扩环反应。这条路就到此为止了。莱文教授在2023 年就报道过第一代的碳转氮反应，但他在接受《化学与工程新闻》采访时说得很直接：那是一个令人兴奋的概念验证，但它受限——基本是一条死胡同。三代之间的差距，是全世界的药物化学家都卡着的一道墙。03转折点：把"缺点"当成"优点"用这个故事的精彩之处，在于莱文是怎么解决它的。他没有试图阻止三重态的出现——他反过来，利用它。故事的开始是一条线索。莱文提到，他在读文献时看到俄罗斯乌法化学研究所（Ufa Institute of Chemistry）Ekaterina Chainikova 课题组的一些工作——那些工作发现，三重氮宾可以与分子氧反应，生成腈氧化物（nitrile oxide）。紧接着，他又读到隔壁办公室的同事 Viresh Rawal 做的一份合成工作——用腈氧化物来合成异硫氰酸酯（isothiocyanate）。莱文把这两件事拼在了一起。他的推理是：如果三重氮宾能和氧反应生成腈氧化物，而腈氧化物又能转化成异硫氰酸酯——那把这两步接起来，就能让三重氮宾继续往前走完这条反应链，而不是卡在原地。莱文这样评价自己的新反应："本次工作最关键的一个进展是，最'难处理'的那个试剂是分子氧——而这恰恰使反应比以往任何策略都温和得多。" 这个"思路转弯"是整项工作的核心。第一代反应里，三重氮宾是失败的原因（它无法完成扩环）。而在第二代里，三重氮宾成了起点——它是唯一能进入后续反应链的中间体。换句话说：卡死的地方，成了这条新路线的起点。这种"把缺陷转化为特性"的解题思路，在化学里并不常见，但一旦成功，效率极高。04反应是怎么走的新的反应路径具体是这样的：含叠氮的化合物先经蓝光光化学活化，生成三重氮宾（也就是上一代失败的那个中间体）；三重氮宾与氧气（O₂）反应，生成亚硝基氧化物阴离子（nitroso oxide anion）；该中间体发生分子内反应，形成一个不稳定的腈氧化物（nitrile oxide）；加入硫脲（thiourea）类化合物后，发生环加成反应，生成异硫氰酸酯（isothiocyanate）；最后，异硫氰酸酯在酸或碱作用下反应，重新闭合形成原来的环——但那个位置上已经是氮了。整条链的起点是氧气，而氧是世界上最便宜、最不稀缺的试剂之一。莱文对整体反应的形容非常直白："整体转化简直疯狂（bonkers）。" 而他在被问到相比上一代的改进时，强调了两个变化：其一，"问题"被解决了——现在它对以前最成问题的三重氮宾也能正常反应。其二，反应"温和"了。这句"温和"是有具体来源的：温和性恰恰来自用氧气取代了传统的化学氧化剂——氧是全世界最不稀缺、最便宜的试剂之一。温和意味着什么？意味着它能用在更脆弱的分子上。05用在天然产物上：最有说服力的证明一个反应方法好不好，最硬的检验标准从来不是"在简单底物上多高的收率"，而是：它能不能在那些又复杂、又脆弱的天然产物分子上工作？而这项研究做到了。团队把它用在了长春西汀（vinpocetine）上——这是一种从长春花中提取的生物碱类化合物，被用作改善认知功能的药物。结果是实打实的：研究显示，把氮原子引入长春西汀的芳香环后，该化合物的溶解度大幅提升，代谢清除率降低（即代谢稳定性提高）。 "改善"是褒义词——溶解度太低、代谢太快，是药物开发中非常常见、也非常头疼的问题。很多候选药物就卡在这里：体外活性很好，但进不去身体，或者进去之后马上被代谢掉。长春西汀的这条合成路线，步骤也比过去合成同一个分子的方法更少。这意味着两件事：第一，这个改造不是纯粹的学术游戏——它产出了一个可能更有用的分子。第二，路线更短意味着更便宜、更适合放大生产。而且这项技术还能在多个复杂分子上做"骨架编辑"——除了长春西汀等天然产物（包括育亨宾、长春花碱），测试范围还包括一个已上市的合成药物（盐酸多奈哌齐类的抗心律失常药 dronedarone），以及吲哚、哒唑、萘、蒽、苯并呋喃、苯并噻吩等多种骨架。06这个技术真正的价值：氮扫描资深药物化学家尼克·梅恩威尔（Nick Meanwell）——他经营一家药物化学咨询公司——对这个方法的评价最为直接：这是那种我会很乐意采用的优雅工作。而他特别指出的一点，才是这项技术最核心的价值：它让化学家可以做"氮扫描"（nitrogen scans）——在一个芳香环的每个位置上，迭代地把碳原子替换成氮。 "通常，我们不得不回到起点，把它们全部从头合成一遍。" 这句话解释了为什么这项技术对制药业如此重要。在传统流程下，做一次氮扫描意味着：你有一个化合物分子，为了研究氮替换的效果，你得把整个合成路线重做一遍。而一个含氮杂环药物的完整合成，可能需要十几步甚至几十步，其中还包括多次色谱分离和纯化。而这个新反应让你"在合成序列的后段把已有的分子改一下"——这就意味着你可以在一条已经建好的合成路线上，迭代地探索多个变体。莱文自己也给出了同一个判断：这项技术最大的用处，是让研究者能研究"位置异构体"的影响，而不必为每一个化合物从头合成。换句话说：它把"探索空间"的成本，从"每试一个变体付一次完整合成的代价"，降到了"付一次反应的低成本代价"。这个改进对药物研发效率的提升，可能是数量级的。07局限：必须说清楚的三件事这类反应技术报道最容易出现的问题是"只报突破不报瓶颈"。莱文的团队其实相当坦诚。第一，起始原料的叠氮有安全和毒性问题。叠氮化合物是很多药物合成的常用中间体，但它们有爆炸性。莱文明确提醒了这一点。第二，需要在有机溶剂中使用氧气，这意味着可燃性风险。有机溶剂 + 氧气，这个组合在工业安全上是需要严格管理的。这不是一个小问题，而是决定这个方法能否走向规模化的实际障碍。第三，也是最关键的：反应需要极度稀释的条件。 "这个反应最大的局限是——出于莱文和他的团队还没有完全理解的原因——它需要极度的稀释条件。" 这句话的分量要说清楚：它意味着溶剂用量会非常大。莱文的解释是：对于合成 100 毫克或更少量的化合物，溶剂用量是合理的——而这正是药物化学家日常工作的量级。 "但当规模放大时，溶剂的用量就变得难以处理了。" 所以这项技术目前最合适的场景是：药物化学家在小试阶段探索分子结构，而不是工业化的量产。不过莱文自己也给出了一个可能是最重要的进展：团队已经在探索用sulfilimine（亚磺酰亚胺，RNSR₂）替换叠氮基团——这可以降低含叠氮化合物的安全顾虑。而这一方向的配套论文已经发表（Purinš、Hwang 与 Levin，J. Am. Chem. Soc., 2026, 148, 31668）——注意这是莱文自己团队的配套工作，而不是第三方验证。莱文认为，这可能有助于这类反应的规模化。08怎么评价这项工作第一，它是一个教科书级别的"问题重新定义"的案例。第一代反应的失败原因（三重氮宾）和第二代反应的成功起点（同一个三重氮宾）是同一个东西。这在化学里是很高的境界——不回避缺陷，而是找到缺陷背后被浪费的价值。第二，它是基础研究转化为实用工具的典型速度。从2023 年的第一代（作者自己说是"死胡同"），到 2026 年的第二代并且已经用在真实药物分子上——三年时间，从概念验证走到天然产物改造。这个迭代速度在化学里相当可观。第三，但它离制药业还需要几步。极度稀释的溶剂用量、叠氮的安全问题、氧气与有机溶剂的兼容性——这三条都是真实的工程障碍，不是靠"再想想办法"就能绕过的，需要工艺上的实质性改进。第四，也是我觉得最值得记住的一点：它体现了一种研究风格。莱文做这件事的历史很有意思：他是在读别人的论文时发现了零件，然后在办公室里把它们拼了起来。 Chainikova 的工作是俄罗斯一个研究所做的；Rawal 的工作是他隔壁办公室的同事做的。莱文把这两块别人做的零件拼成了一条新的反应路线。科学的进步，很多时候就是这样发生的——不是一个人发明了一切，而是有人看到了别人已经造好的零件，并且知道它们能拼在一起。09最后：一个更长远的问题这项技术最终指向一个药物化学家长期的目标：可编程的分子编辑。理想的形态是这样的：在分子的任意位置，可以精确地插入、删除或替换任意原子——而且不管那个位置有多复杂。要实现这个目标，还需要解决几个方向的问题：不依赖叠氮作为入口（目前叠氮的安装本身在后期合成中就"不那么简单"）；突破极度稀释的限制（这是工业化的硬门槛）；实现催化量级（这项反应目前使用的是化学计量的试剂，而非催化循环）；扩展到饱和杂环与糖分子（这是骨架编辑领域公认的下一批难点，目前进展有限）。德国明斯特大学的化学家 Armido Studer（未参与这项工作）也提出了一个很中肯的观察：这项技术的用处可能主要在于研究异构体的影响，而不是从零合成化合物。而 Studer 提到的那个技术难点也值得记住：这项方法可能需要化学家先引入一个叠氮基团——如果原本没有的话——而在合成的后期阶段，这"并不是那么简单"。换句话说：入口本身就是一道门槛。这一步如果很难跨过，后面那套精妙的反应机制就用不上。所以这项技术现在最大的价值，是"让已有的分子可以改一改"；而它最终要达到的，是"让任意的分子都能随意改"。从 2023 年的"死胡同"到 2026 年的天然产物改造，它走了三年。而从一个药物化学家的辅助工具，走到制药业的主力工具，可能还需要同样长的时间。 📌 关注我们每天一篇硬核科技深度解读，带你看见科学前沿的真实进展。如果这篇文章让你对"化学"或者"制药"多了一点兴趣，请长按关注，我们会把最值得读的科技内容第一时间送到你面前。转发给那个关心新药研发、或者只是想弄明白"为什么新药总是研发得那么慢"的朋友。你也可以留言告诉我：你最想看哪一类科技话题的深度拆解？留言区我会逐条看，并优先安排呼声最高的那一个。（本文信息来源于芝加哥大学 Mark D. Levin 团队的研究，论文 Park, D.-I. et al. Science (2026)，DOI: 10.1126/science.aef3511；以及该团队 Purinš, Hwang, Levin, J. Am. Chem. Soc. (2026) 148, 31668）

2026-10-13

·BioSpace

Alpha Cognition Announces Publication of U.S. Patent Application Relating to Proprietary Manufacturing Process for ZUNVEYL®

VANCOUVER, British Columbia & GRAPEVINE, Texas--(BUSINESS WIRE)-- Alpha Cognition Inc. (NASDAQ: ACOG) ("Alpha Cognition" or the "Company"), a biopharmaceutical company developing and commercializing novel therapeutics for debilitating neurodegenerative disorders, today announced that the United States Patent and Trademark Office (USPTO) published U.S. Patent Application No. 19/090,242, titled “Process for Preparing Benzgalantamine and Salts Thereof,” on October 1, 2026, as U.S. Patent Application Publication No. US 2026/0297103 A1. The published patent application covers Alpha Cognition's proprietary manufacturing technology for benzgalantamine, the active ingredient in ZUNVEYL®. The application includes innovations designed to improve manufacturing efficiency, product quality, impurity control and production scalability, while also covering the preparation of benzgalantamine salts and related pharmaceutical compositions. The disclosed technology is intended to support the consistent production of high-purity benzgalantamine at commercial scale. The application further describes methods for controlling critical product characteristics, which are important for manufacturing reliability and product stability of the ZUNVEYL® franchise. “The publication of this U.S. patent application represents another step in our strategy to build broad intellectual property protection around benzgalantamine and ZUNVEYL®,” said Michael McFadden, Chief Executive Officer of Alpha Cognition. “The application is focused on manufacturing innovations designed to support consistent product quality, impurity control and scalable production. We believe these capabilities are important to the long-term commercial potential of ZUNVEYL® and our broader benzgalantamine development programs.” About Alpha Cognition Inc. Alpha Cognition Inc. is a commercial stage, biopharmaceutical company dedicated to developing treatments for patients with neurodegenerative diseases, such as Alzheimer’s disease and Cognitive Impairment with mild Traumatic Brain Injury (“mTBI”), for which there are limited or no approved treatment options. ZUNVEYL is a patented drug approved as a new generation acetylcholinesterase inhibitor for the treatment of Alzheimer’s disease, with expected minimal gastrointestinal side effects. ZUNVEYL’s active metabolite is differentiated from donepezil and rivastigmine in that it binds neuronal nicotinic receptors, most notably the alpha-7 subtype, which is known to have a positive effect on cognition. ALPHA-1062 is also being developed in combination with memantine to treat moderate to severe Alzheimer’s dementia, and as an intranasal formulation for Cognitive Impairment with mTBI. Forward-Looking Statements This news release contains forward-looking statements within the meaning of applicable securities laws. Forward-looking statements are neither historical facts nor assurances of future performance and are based on the Company's current expectations, estimates, assumptions and projections. Forward-looking statements in this news release include, but are not limited to, statements regarding the prosecution and potential issuance of patents arising from U.S. Patent Application No. 19/090,242; the potential scope, validity, enforceability and commercial value of any resulting patent rights; the ability of the disclosed manufacturing processes to support product quality, reproducibility, impurity control, scalability and commercial manufacturing; and the Company's ability to protect and expand its intellectual property portfolio relating to benzgalantamine and ZUNVEYL®. In some cases, forward-looking statements can be identified by words such as "may," "might," "will," "could," "would," "should," "expect," "intend," "plan," "anticipate," "believe," "estimate," "predict," "project," "potential," "target," "seek," "continue," or similar expressions. Although the Company believes it has a reasonable basis for these forward-looking statements, they are subject to significant risks and uncertainties that could cause actual results to differ materially, including risks that patent applications may not result in issued patents; that any issued claims may be narrower than claims currently pending; that issued patents may be challenged, invalidated, narrowed, circumvented or held unenforceable; that the disclosed manufacturing processes may not achieve the anticipated benefits; and other risks described in the Company's filings with the U.S. Securities and Exchange Commission and Canadian securities regulatory authorities. No assurance can be given that U.S. Patent Application No. 19/090,242 or any related application will result in an issued patent, that any patent granted will provide commercially meaningful protection, or that any resulting patent will remain valid or enforceable for its full term. Further information regarding these and other risks can be found under "Risk Factors" in the Company's most recent Annual Report on Form 10-K and subsequent filings with the SEC and Canadian securities regulatory authorities. The forward-looking statements contained in this news release speak only as of the date hereof. Except as required by applicable law, the Company undertakes no obligation to update or revise any forward-looking statements to reflect subsequent events or circumstances. Contacts For further Information: LifeSci Advisors, PJ Kelleher pkelleher@lifesciadvisors.com

上市批准专利到期

2026-10-11

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山东药企大爆发！18个重磅新品收入囊中，潜力产品猛涨276%，4款1类新药超亮眼

精彩内容山东明星药企新华制药正从“解热镇痛原料药龙头”向“创新药企”快速切换：2026年至今公司的产品线新增了18个产品，并成功开拓了两个新亚类市场；上半年在中国三大终端六大市场，公司12个爆款产品涨势喜人；4款1类新药正加速推进临床，过评产品数量已突破100个大关。内外协同拿下18个新品，12个爆款涨势喜人 10月8日，国家药监局官网发布药品获批信息，新华制药的沙库巴曲缬沙坦钠片成功获批，截至目前新华制药及子公司在2026年按上市申请获批的新产品有15个，并通过上市许可持有人变更再把3个产品收入囊中。值得注意的是，新华制药在今年已成功进军了两个火热亚类市场。新华制药2026年至今收获的新产品来源：米内网中国申报进度（MED）数据库、公司公告米内网数据显示，恩他卡朋片是新华制药首个上市的抗帕金森氏病药，从中晟制药转让获得的人工牛黄甲硝唑胶囊则为公司开拓了口腔科用药市场。2025年在中国三大终端六大市场（统计范围见文末），抗帕金森氏病药和口腔科用药的市场规模分别达到了40亿元、20亿元。截至目前，新华制药及子公司合计拥有化学药超过200个（按现有批文统计，含上市许可持有人变更获得的批文，不含原料药），2026上半年在中国三大终端六大市场，集团的热销产品集中在全身用抗感染药物、消化系统及代谢药、心脑血管系统药物、血液和造血系统药物4个大类，合计为集团贡献超过75%的业绩。 2026上半年中国三大终端六大市场新华制药TOP20产品中正增长的产品情况来源：米内网格局数据库 2026上半年在中国三大终端六大市场，新华制药TOP20产品中有12个销售额保持正增长，其中公司在2021年获批的新产品阿托伐他汀钙片在2026上半年暴涨275.77%，公司的新品获得了市场的高度认可，潜力可期。 4款1类新药全力推进，12个新品在路上新华制药始终致力于科技创新引领战略落地，近几年公司加快由仿制药向创新药战略转型，加速形成“创新为主+仿制为辅”的双线研发体系。今年6月，公司再有1类新药获批临床，LXH-2103注射液是新一种新型镇痛药，旨在解决传统阿片类药物因CYP2D6基因多态性导致的个体间疗效和安全性差异问题。研究显示，LXH-2103具有偏向性μ阿片受体（MOR）激动剂的特性，这使其在规避CYP2D6基因多态性影响的同时，具备显著的镇痛潜力和安全性优势。新华制药在研新药情况来源：米内网中国临床试验数据库 LXH-2301片目前临床进度最快，最新消息指该新药正准备启动III期临床，有望成为新华制药首个报产的化药1类新药。公司在2024年获批了非布司他片，成功打开了抗痛风制剂市场大门，LXH-2301片拟用于治疗尿酸排泄不良型痛风伴高尿酸血症。 OAB-14干混悬剂是全球首个靶向Aβ清除的多靶点小分子抗AD候选药物，目前用于治疗阿尔茨海默病的IIa期临床正在进行中。截至目前，新华制药在治疗阿尔茨海默病领域已拥有多奈哌齐（胶囊及口崩片）和美金刚（片及口服溶液）两大品种。 LXH-1211片在今年7月完成了肺动脉高压I期临床首例受试者入组，目前进展顺利，该新药具备双重作用机制，一方面通过激活可溶性鸟苷酸环化酶（sGC）促进血管舒张，降低肺动脉压力，另一方面通过抑制AMP-激活蛋白激酶（AMPK）减缓血管重构和纤维化进程。截至目前，新华制药暂无专用于肺动脉高压药获批。新华制药报产在审的仿制药新品来源：米内网中国申报进度（MED）数据库 2025年至今，新华制药及子公司还有12个仿制药新品报产在审，涉及5个大类（8个亚类）。值得注意的是，抗炎药和抗风湿药占了3个，均为注射剂，目前新华制药已获批的抗炎药和抗风湿药均为口服制剂，公司在该药物市场有望迎来新突破。上百个产品已过评，6个亿级产品备战新集采随着新品陆续获批，新华制药已过评/视同过评的产品数量已达到了107个，分布在11个大类市场，可谓多点开花、全面布局。今年8月，第12批集采中选结果官宣，新华制药在2025年获批的新品注射用硫酸艾沙康唑成功中标，据米内网统计前12批集采新华制药及子公司已累计有23个产品中标。新华制药已过评产品注：统计含上市许可持有人变更后获得的过评产品，*表示集采中标来源：米内网中国上市药品（MID）数据库 2026年还剩不到3个月，第13批集采会否在今年进行备受市场瞩目，目前新华制药过评且暂未纳入集采的产品中竞争企业（原研+过评）数量在7家及以上的产品有13个。新华制药备战第13批集采的产品情况注：销售额低于1亿元用*表示来源：米内网综合数据库新华制药备战第13批集采的产品中有6个2025年在公立医疗机构终端的销售额超过了1亿元，其中乳果糖口服溶液大卖超过19亿元，目前竞争企业数据超过60家，最终新一轮集采会否盯上这个火热产品，我们将继续跟踪报道。集采已进入常态化阶段，重磅产品被盯上是大势所趋，药企要以主动求变替代被动承压，以差异化创新打开第二增长曲线，谋求新的发展方向。资料来源：米内网数据库、公司公告等注：米内网《中国三大终端六大市场药品竞争格局》，统计范围：城市公立医院和县级公立医院、城市社区中心和乡镇卫生院、城市实体药店和网上药店，不含民营医院、私人诊所、村卫生室，不含县乡村药店；上述销售额以产品在终端的平均零售价计算。数据统计截至10月9日。信息来源：米内网往期推荐 ! 免责声明 “汇聚南药”公众号所转载文章来源于其他公众号平台，主要目的在于分享行业相关知识，传递当前最新资讯。图片、文章版权均属于原作者所有，如有侵权，请在留言栏及时告知，我们会在24小时内删除相关信息。本平台不对转载文章的观点负责，文章所包含内容的准确性、可靠性或完整性提供任何明示暗示的保证。喜欢的点个“看一看”和"喜欢"吧不然微信推送规则改变，有可能每天都会错过我们哦~

申请上市临床3期

100 项与盐酸多奈哌齐相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D00670	盐酸多奈哌齐	N06DA02	DB00843

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
痴呆	美国	Corium LLC	2022-03-11
路易体病	日本	Eisai Co., Ltd.	2014-09-19
阿尔茨海默症	美国	Eisai, Inc.	1996-11-25

未上市

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
阿尔茨海默病引起的痴呆症	临床3期	日本	Teikoku Seiyaku Co. Ltd.	2019-01-18
神经认知障碍	临床3期	日本	Teikoku Seiyaku Co. Ltd.	2019-01-18
认知功能障碍	临床3期	美国	Pfizer Inc.	2008-09-01
认知功能障碍	临床3期	美国	Eisai, Inc.	2008-09-01
唐氏综合征	临床3期	美国	Pfizer Inc.	2008-09-01
唐氏综合征	临床3期	美国	Eisai, Inc.	2008-09-01
注意缺陷障碍	临床3期	美国	Eisai Co., Ltd.	2008-07-02
注意缺陷障碍	临床3期	阿根廷	Eisai Co., Ltd.	2008-07-02
注意缺陷障碍	临床3期	澳大利亚	Eisai Co., Ltd.	2008-07-02
注意缺陷障碍	临床3期	加拿大	Eisai Co., Ltd.	2008-07-02

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临床结果

适应症

分期

评价

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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


NCT05078944 (CTgov)	N/A	家族性阿尔茨海默病1	160	Active acupuncture+Donepezil Hydrochloride (Active Acupuncture + Donepezil)	夢夢齋願繭簾廠遞憲觸(壓膚築鬱網醖鑰壓積壓) = 顧壓簾網觸製襯壓遞鑰觸觸餘壓製簾繭遞餘憲 (顧願顧窪餘範獵窪蓋糧, 0.31) 更多	-	2026-05-22
				Sham acupuncture+Donepezil Hydrochloride (Sham Acupuncture + Donepezil)	夢夢齋願繭簾廠遞憲觸(壓膚築鬱網醖鑰壓積壓) = 衊淵淵築壓網淵齋膚願觸觸餘壓製簾繭遞餘憲 (顧願顧窪餘範獵窪蓋糧, 0.32) 更多
NCT05801380 (PHRR230220-0054116, Pubmed \| J Alzheimers Dis Rep)	N/A	阿尔茨海默症	2	MemantineDonepezil + MemantineDonepezil	鑰選鹽繭顧壓窪遞窪醖(遞鑰淵憲網築糧鹹壓餘) = 廠網構襯積顧鏇網積鬱鹽膚窪餘願繭觸糧獵鹹 (遞蓋夢繭糧繭窪範製餘 ) 更多	不佳	2026-03-01
NCT04117178 (MONANTI, CTgov)	临床4期	阿尔茨海默症 \| 帕金森病所致痴呆 \| 路易体病	132	Measurement of serum level of anti-dementia drug (Standard of Care)	簾淵鹽窪餘願衊憲築製(醖鹽鏇憲築餘鬱衊簾鬱) = 遞觸簾淵鏇淵鏇艱壓顧築鹽鹽醖獵簾網淵範繭 (壓獵壓鹹襯艱壓顧醖製, 3.19) 更多	-	2025-02-10
				Measurement of serum level of anti-dementia drug+Memantine+Donepezil (Intervention Arm)	簾淵鹽窪餘願衊憲築製(醖鹽鏇憲築餘鬱衊簾鬱) = 壓膚蓋醖積鹽鹹糧鹽築築鹽鹽醖獵簾網淵範繭 (壓獵壓鹹襯艱壓顧醖製, 3.56) 更多
NCT04730635 (MK-0000-413, CTgov)	临床1期	阿尔茨海默症 \| 轻度认知障碍	44	Donepezil (Donepezil)	構鹽遞廠製繭窪蓋壓簾(鑰築繭淵繭網艱觸觸蓋) = 觸獵鬱襯鏇製壓繭遞獵顧遞糧製鬱醖鑰窪淵鬱 (顧衊壓築範鏇積膚築構, 0.078) 更多	-	2024-10-28
				Placebo (Placebo)	構鹽遞廠製繭窪蓋壓簾(鑰築繭淵繭網艱觸觸蓋) = 醖選鏇艱壓餘鬱鬱鬱衊顧遞糧製鬱醖鑰窪淵鬱 (顧衊壓築範鏇積膚築構, 0.091) 更多
NCT04617782 (CTgov)	临床1期	-	60	Donepezil (Treatment A 5 mg TDS)	構製壓夢鹽構鹹構齋範(選鏇鬱餘襯鑰餘膚壓積) = 網餘齋製製襯餘構獵衊齋製醖觸壓顧鬱壓鑰鹹 (鏇積鬱範鹹襯醖壓糧鏇, 9.1) 更多	-	2024-09-19
				Donepezil (Treatment B 10 mg TDS)	構製壓夢鹽構鹹構齋範(選鏇鬱餘襯鑰餘膚壓積) = 膚獵網製顧積淵鏇夢艱齋製醖觸壓顧鬱壓鑰鹹 (鏇積鬱範鹹襯醖壓糧鏇, 19.9) 更多
NCT02487082 (CTgov)	临床2期	自闭症谱系障碍	12	Placebo+Melatonin+Donepezil (Group A)	壓鏇網鹹顧鬱獵繭憲廠(網憲襯壓構鹽範壓範顧) = 鹽夢顧鑰築製構繭築選構鹹構鑰廠艱簾構簾繭 (夢憲窪餘糧鹹繭遞願簾, 壓蓋醖襯夢顧鹽艱糧鑰 ~ 鏇醖繭淵淵鏇艱網窪窪) 更多	-	2024-06-06
				Placebo+Melatonin+Donepezil (Group B)	壓鏇網鹹顧鬱獵繭憲廠(網憲襯壓構鹽範壓範顧) = 窪糧構襯鏇繭顧襯壓繭構鹹構鑰廠艱簾構簾繭 (夢憲窪餘糧鹹繭遞願簾, 簾鏇膚夢遞製觸顧願築 ~ 網齋願襯艱憲膚鑰襯獵) 更多
NCT02345213 (Pubmed)	临床4期	路易体病	160	多奈哌齐	製齋構鬱築構網簾網鑰(衊憲淵鏇選鑰觸壓夢選): difference = 1.4 (95% CI, 0.42 ~ 2.30), P-Value = 0.004 更多	积极	2024-03-04
				安慰剂
NCT02822573 (Remember, CTgov)	临床3期	认知功能障碍 \| 乳腺癌 \| 浸润性乳腺癌	276	Donepezil 5 mg (Donepezil)	簾廠鹽選鹹遞窪繭選製(範遞繭顧築製顧遞襯夢) = 夢淵鑰壓繭廠糧築醖艱繭窪積遞醖鹽艱憲襯夢 (製構艱積獵夢製淵齋範, 願顧鏇襯願醖鑰窪獵築 ~ 壓憲鬱積鏇憲簾簾構淵) 更多	-	2023-09-13
				Placebo (Placebo)	簾廠鹽選鹹遞窪繭選製(範遞繭顧築製顧遞襯夢) = 蓋鏇構窪醖壓窪積獵製繭窪積遞醖鹽艱憲襯夢 (製構艱積獵夢製淵齋範, 襯築顧醖鹽夢鬱鹽築餘 ~ 糧鏇餘壓鏇繭艱壓鹹膚) 更多
NCT04617782 (Pubmed \| J Alzheimers Dis)	临床1期	-	60	10-mg/d Corplex™ donepezil transdermal delivery system	淵蓋蓋膚範糧鏇繭鹽遞(餘觸選積繭製鏇淵獵繭) = oral donepezil was associated with higher incidence of gastrointestinal AEs (14.5% versus 53.6%) 衊艱廠鹽膚鬱遞積窪淵 (製觸憲艱簾廠選積窪積 ) 更多	-	2022-10-25
				5-mg/d Corplex™ donepezil transdermal delivery system
NCT04617782 (ANA2022)	临床1期	-	60	Donepezil TDS 10mg/d	鑰壓夢艱築蓋鏇鏇衊餘(鹽繭網窪齋淵淵選餘淵) = 鑰餘憲遞壓簾鬱窪觸夢簾範鹹鬱願遞衊鬱憲廠 (艱艱簾蓋遞鹽選齋廠顧, 100.5 ~ 117.4) 更多	积极	2022-09-14
				Donepezil TDS 5mg/d	鑰壓夢艱築蓋鏇鏇衊餘(鹽繭網窪齋淵淵選餘淵) = 觸鏇鏇襯構鏇齋範衊夢簾範鹹鬱願遞衊鬱憲廠 (艱艱簾蓋遞鹽選齋廠顧, 97.6 ~ 113.6) 更多