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更新于：2026-04-09

Indomethacin

吲哚美辛

更新于：2026-04-09

概要

基本信息

简介吲哚美辛是一种小分子，属于非甾体类抗炎药 (NSAID)，通过抑制 COX 酶，可阻止炎症和疼痛。该药物可用于治疗多种疾病，包括动脉导管、关节炎、网球肘、急性臂神经炎、痛风性关节炎、强直性脊柱炎、滑囊炎、肌腱病、骨关节炎、类风湿性关节炎、肿胀、疼痛、肘部肌腱病、炎症和肌肉骨骼疼痛。由 iROKO Partners Ltd. 开发，于 1965 年 6 月获得批准。

药物类型

小分子化药

别名

IM-P、Indaflex、Indometacin

+ [32]

靶点

COXs

作用方式

抑制剂

作用机制

COX抑制剂(环氧化酶抑制剂)

治疗领域

在研适应症

非在研适应症

原研机构

在研机构

Hisamitsu Pharmaceutical Co., Inc.

Kowa Co., Ltd.

Teika Pharmaceutical Co., Ltd.

+ [8]

非在研机构

Rising Pharmaceuticals, Inc.

Novartis AGMerck Frosst Canada Ltd.

+ [5]

权益机构

Zyla Life Sciences LLC

Assertio Holdings, Inc.

Cosette Pharmaceuticals, Inc.

+ [1]

最高研发阶段批准上市

首次获批日期

美国 (1965-06-10),

强直性脊柱炎滑囊炎骨关节炎+ [4]

最高研发阶段(中国)批准上市

特殊审评-

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结构/序列

分子式C19H16ClNO4

InChIKeyCGIGDMFJXJATDK-UHFFFAOYSA-N

CAS号53-86-1

关联

226

项与吲哚美辛相关的临床试验

NCT07218653

/ Not yet recruiting早期临床1期IIT

Sex-Specific Cerebrovascular Dysfunction in Metabolic Syndrome-Role of COX

This study tests the hypothesis that Metabolic Syndrome (MetSyn) decreases cerebral blood flow (CBF) more in females than males due in part to the sex-specific loss of COX vasodilation. Male and female participants will be enrolled in two groups: Health Controls versus participants with MetSyn.

开始日期2026-07-01

申办/合作机构

University of Wisconsin-Madison

[+1]

CTR20255184

/ CompletedN/A

吲哚美辛凝胶贴膏在中国健康受试者外用条件下的单中心、随机、开放、两制剂、两周期、两序列、单次给药、交叉设计生物等效性研究

主要目的：以吲哚美辛的主要药代动力学参数（AUC和Cmax）为生物等效性的评价指标，在中国健康受试者外用条件下评估受试制剂【海南回元堂药业有限公司申报的吲哚美辛凝胶贴膏，规格：每贴（14cm×10cm）含膏体14g，含吲哚美辛70mg】和参比制剂【帝國製薬株式会社持证的吲哚美辛凝胶贴膏剂，规格：每贴（14cm×10cm）含膏体14g，含吲哚美辛70mg；商品名：Catlep®】的生物等效性。次要目的：观察外用条件下受试制剂和参比制剂的黏附性、皮肤刺激性和安全性。

开始日期2025-12-29

申办/合作机构

海南回元堂药业有限公司

NCT07202559

/ Not yet recruitingN/AIIT

Aggressive Intravenous Hydration With Lactated Ringer's Solution Plus Rectal Indometacin Versus Rectal Indometacin Alone to Prevent Pancreatitis After Pancreatic Extracorporeal Shock Wave Lithotripsy: A Multicentre, Superiority, Randomised, Controlled Trial

This study aims to determine whether combining aggressive intravenous hydration with indometacin is more effective at preventing pancreatitis after a Extracorporeal Shock Wave Lithotripsy (ESWL) than using indometacin alone.
The study will involve patients who are scheduled to undergo ESWL for pancreatic stones. Participants will be randomly assigned to one of two groups: one will receive both the intravenous hydration and the rectal indometacin, while the other will receive only the rectal indometacin.
The trial will be conducted at multiple centers, ensuring a broad and diverse patient population.
The primary outcome of the study will be the incidence of pancreatitis after the ESWL procedure.
This study is important because it could lead to a better understanding of how to prevent pancreatitis after ESWL, potentially improving patient outcomes and reducing the risk of serious complications.

开始日期2025-12-01

申办/合作机构

海军军医大学第一附属医院

[+7]

100 项与吲哚美辛相关的临床结果

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100 项与吲哚美辛相关的转化医学

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100 项与吲哚美辛相关的专利（医药）

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41,629

项与吲哚美辛相关的文献（医药）

2026-12-31·Journal of Maternal-Fetal & Neonatal Medicine

Long-term indomethacin therapy and cervical stabilization in dichorionic twin pregnancies

Article

作者: Goetzinger, Katherine ; Turan, Sifa ; Harman, Christopher ; Bucak, Mevlut ; Seif, Karl ; Turan, Ozhan

OBJECTIVE:

To evaluate the effect of long-term indomethacin therapy (LIT) in stabilizing cervical length in dichorionic-diamniotic (DCDA) twin pregnancies with a short cervix.

METHODS:

This retrospective cohort study included 54 dichorionic-diamniotic twin pregnancies with a short cervix (≤25 mm), managed with LIT between 18 and 26 weeks of gestation age (GA) at a single quaternary medical center from 2014 to 2024. LIT was initiated with a 100 mg oral loading dose, followed by 50 mg every 6 h for 48 h, and continued at 25 mg every 6 h until 32 weeks or delivery. Weekly monitoring included transvaginal ultrasound, amniotic fluid assessment, and fetal Doppler studies. The expected cervical length (E_LCL) was modeled by applying an assumed physiologic cervical shortening rate of 0.9 mm per week to the observed first cervical length (O_FCL) in twin pregnancies without intervention. E_CL = O_FCL - [(GA at O_LCL - GA at O_FCL (weeks)) × 0.9 (mm/week)]. Cervical stabilization was defined as the observed last cervical length (O_LCL) exceeding the expected last cervical length (E_LCL) at the last examination. The primary outcome was cervical stabilization, while the secondary outcome was gestational age at delivery.

RESULTS:

LIT was successful in stabilizing the cervix in 81.5% (n = 44/54) of cases. The mean GA at LIT onset was 22.9 ± 1.9 weeks, with a median O_FCL of 14.5 mm (IQR: 10.0-18.0). The mean duration of LIT was 48 days (IQR: 25-61). Final O_LCL was significantly longer than E_LCL (15.9 ± 6.1 mm vs. 9.3 ± 5.9 mm, p < .001). Median gestational age at delivery was higher in stabilized vs. non-stabilized patients (34.6 weeks [IQR: 31.7-36.6] vs. 30.8 weeks [IQR: 26.1-32.3], p = .004). No difference was observed in initial cervical length between groups (p = .282). LIT was discontinued in 11.2% due to ductus arteriosus constriction or oligohydramnios; no adverse neonatal outcomes were reported.

CONCLUSION:

These findings suggest an association between LIT and cervical stabilization in DCDA twin pregnancies with a short cervix; this exploratory, hypothesis-generating analysis warrants confirmation in prospective studies.

2026-05-01·EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES

Microdialysis during in vitro lipolysis explains enhanced permeation of indomethacin from phospholipid-based amorphous solid dispersions

Article

作者: Brandl, Martin ; Tønning, Mikkel Højmark ; Jacobsen, Ann-Christin ; Paulus, Felix ; Bauer-Brandl, Annette

Many new drugs are poorly water-soluble requiring enabling formulations like amorphous solid dispersions or lipid-based formulations for oral administration. Phospholipid-based amorphous solid dispersions (PL-based ASDs) may combine the solubility advantages of ASDs and lipid-based formulations. Like lipid-based formulations, digestion may influence the biopharmaceutical performance of PL-based ASDs. Evaluating performance in the presence of solubilizing species as vesicles and micelles, forming during dissolution of PL-based ASDs, is difficult. To mitigate this, we used a novel biopharmaceutical approach based on microdialysis sampling to assess drug release from PL-based ASDs loaded with indomethacin under non-lipolytic and lipolytic conditions. Microdialysis sampling, unlike conventional sampling, can discern between molecularly dissolved drug and drug associated with colloidal species. The free drug is the main driving force for absorption. Therefore, we conducted dissolution/permeation experiments in non-lipolytic and lipolytic conditions for comparison. Microdialysis revealed that under lipolytic conditions the free drug concentration was increased as compared to non-lipolytic conditions for all PL-based ASDs agreeing with increased permeation under lipolytic conditions. PL-based ASDs with low to intermediate PL-to-drug ratios significantly improved biopharmaceutical performance. High phospholipid content impaired the performance due to colloidal entrapment. Correspondingly, the positive effect of lipolysis was most prominent at high phospholipid content. Microdialysis provided near real- time free drug concentrations and accurately ranked the formulations based on their ability to cross an absorptive barrier independent of lipolysis. Thereby, microdialysis resolves the limitations of coupled dissolution/permeation for PL-based ASDs. In conclusion, these findings provide a deeper understanding of the mechanisms of action of this formulation. The correlation between free drug concentration and permeability under simulated intestinal conditions may provide a framework for future design of PL-based ASDs presupposing that the observed correlation will be confirmed in an appropriate animal model.

2026-05-01·EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES

Glycyl-l-histidyl-l-lysine as a novel co-former in co-amorphous systems: Enhanced aqueous solubility and physical stability

Article

作者: Liang, Guang ; Yuan, Yinyin ; Huang, Qiang ; Zou, Zhiren ; Wu, Wencheng ; Cheng, Dian ; Zhou, Lin ; Gao, Ruyu ; Wu, Wenqi ; Huang, Yuye ; Chun, ChangJu

Co-amorphous systems have emerged as a promising strategy to enhance the aqueous solubility of poorly water-soluble drugs. Although amino acids have been widely studied as co-formers, some amino acid-based co-amorphous systems exhibit limited dissolution improvement and inadequate physical stability. In this study, glycyl-l-histidyl-l-lysine (GHK) was selected as a co-former due to its biocompatibility and multiple functional groups, which were expected to enhance the dissolution and the physical stability of pure amorphous drugs. Basic mebendazole, neutral tadalafil and acidic indomethacin were selected as the model drugs. Glycine, histidine and lysine were used as co-formers for comparison. All drug-co-former combinations were prepared by ball milling at a 1:1 molar ratio. GHK achieved complete amorphization with all three model drugs within 15 min of milling, whereas most amino acid-based mixtures remained partially crystalline even after 60 min of milling. The formation of homogeneous amorphous forms was confirmed by differential scanning calorimetry, indicated by a single glass transition temperature in the drug-GHK system. The drug-GHK systems exhibited significantly enhanced dissolution performance, including faster dissolution rates, higher drug concentration and sustained supersaturation (up to 1440 min) compared to both the pure crystalline and amorphous drugs. Furthermore, physical stability studies confirmed that GHK-based systems maintained amorphous forms for at least 6 months, outperforming both amino acid-based counterparts and pure amorphous drugs. Notably, salt formation and hydrogen bonding were associated with the observed improvements in dissolution performance and physical stability. In conclusion, GHK represents a promising co-former, expanding the design space for co-amorphous systems.

167

项与吲哚美辛相关的新闻（医药）

2026-04-08

·科研猫猫猫

Nature子刊（NC）：通过表型筛选与结构优化从“东革阿里”发现多靶点抗痛风药物颠覆痛风治疗！

🔥颠覆痛风治疗！Nature子刊：从“东革阿里”发现多靶点抗痛风分子32——降尿酸&抗炎双效合一，安全性完胜现有药物 📅 2026-04-07 ｜来源：Nature Communications ｜编译：药靶新视野 ✨ 亮点展示 🌿 天然产物启发+药效团引导设计：从东革阿里（Eurycoma longifolia Jack）中鉴定β-卡波林-1-丙酸，经多轮优化获得先导化合物32； 🎯 独特性多靶点药理学：化合物32同时抑制尿酸重吸收转运蛋白（URAT1 / GLUT9 / OAT4）和NLRP3炎症小体，实现降尿酸+抗炎双重功效； 💊 药效卓越：急性高尿酸血症小鼠模型中降尿酸率93.4%（媲美非布司他），慢性模型改善肝肾损伤，疗效优于lesinurad和苯溴马隆； 🛡️ 安全性显著提升：无hERG心脏毒性，急性毒性1000 mg/kg无死亡，长期高剂量无器官病变，安全性优于非布司他和lesinurad； 🧬 机制清晰：SPR与分子动力学证实32直接结合URAT1/GLUT9/OAT4及NLRP3，抑制IL-1β释放，缓解痛风性关节炎肿胀； 📊 口服生物利用度高：大鼠口服生物利用度53.2%，成药性良好，为痛风及高尿酸血症提供全新治疗选择。📖 研究背景：痛风治疗困境与多靶点策略痛风是由持续高尿酸血症（HUA）导致单钠尿酸盐（MSU）晶体沉积，进而激活NLRP3炎症小体引发剧烈炎症的慢性疾病。目前临床药物主要分为两类：黄嘌呤氧化酶抑制剂（非布司他、别嘌醇）和URAT1抑制剂（lesinurad、苯溴马隆）。然而，现有药物存在明显局限性——非布司他/别嘌醇对急性痛风性关节炎效果有限，且伴有心血管风险；苯溴马隆有致命性肝毒性；lesinurad因严重肾毒性已撤市。此外，抗炎药物（秋水仙碱、吲哚美辛）仅对症处理且长期使用耐受性差。鉴于约90%原发性HUA由肾脏尿酸排泄障碍引起，而MSU晶体活化NLRP3是痛风关节炎核心环节，开发能同时促进尿酸排泄和抑制炎症的双功能分子成为痛风药物研发的破局关键。传统草药东革阿里（Eurycoma longifolia Jack）在东南亚被用于抗炎、抗痛风。本研究团队通过表型筛选发现其天然产物β-卡波林-1-丙酸具有降尿酸活性，降尿酸率41.7%优于lesinurad（32.5%），但不抑制XOD或URAT1。受此启发，研究者采用药效团模型指导的结构优化策略，设计合成了64个衍生物，最终获得化合物32 —— 首个同时靶向URAT1/GLUT9/OAT4和NLRP3的天然产物来源抗痛风候选分子。🔬 研究方法总览基于β-卡波林-1-丙酸和lesinurad的药效团模型，融合URAT1/NLRP3抑制剂的关键特征，采用分子杂交、骨架跃迁及酰基磺酰胺修饰策略，设计合成了8个β-卡波林类（系列I）、8个吲哚酰胺类（系列II）及48个吲哚酰基磺酰胺类（系列III）共64个化合物。通过体内急性高尿酸血症小鼠模型表型筛选降尿酸活性，结合体外URAT1/GLUT9/OAT4转运实验、NLRP3炎症小体IL-1β释放抑制、表面等离子体共振（SPR）、细胞热转移分析（CETSA）、分子对接及100 ns分子动力学模拟，深入验证靶点结合及机制。并利用大鼠急性痛风性关节炎模型、慢性高尿酸血症小鼠模型、急性及亚急性毒性、hERG心脏毒性及药代动力学全面评价候选分子32的药效与安全性。📊 研究结果：从天然产物到多靶点候选药物32的诞生 🧬 图1 | 化合物设计策略与药效团模型（a）抗痛风及NLRP3抑制剂代表结构；（b）β-卡波林-1-丙酸与lesinurad药效团叠合；（c）URAT1抑制剂药效团；（d）NLRP3抑制剂药效团；（e）URAT1/NLRP3双靶点药效团模型；（f）药效团引导的目标化合物设计。 ▲ 基于双靶点药效团模型，从天然β-卡波林骨架出发，引入疏水区B及磺酰胺阴离子中心，最终获得系列III吲哚酰基磺酰胺衍生物。1. 结构优化与降尿酸活性筛选在急性HUA小鼠模型（口服2 mg/kg）中，系列I和II多数衍生物降尿酸活性显著提升，系列III中化合物25、27、32、41、47降尿酸率(DR) >80%。二次复筛结果显示（见下表），化合物27 (DR 94.68%)、32 (93.42%) 和 41 (95.89%) 降尿酸功效媲美非布司他(96.16%)，远高于lesinurad (41.12%)和苯溴马隆(80.60%)。表1 代表性化合物的降尿酸活性及URAT1抑制作用化合物 SUA (μM) DR (%) URAT1 IC₅₀ (μM) 1 241.33 78.82 3.02 ± 0.82 17 270.00 82.53 12.01 ± 2.39 27 188.20 94.68 5.85 ± 2.8632196.6793.423.81 ± 0.99 41 180.00 95.89 4.09 ± 0.79 lesinurad 549.00 41.12 6.88 ± 0.81 febuxostat 178.00 96.16 —2. 多靶点机制：抑制尿酸重吸收转运蛋白URAT1/GLUT9/OAT4 体外功能实验表明，32对URAT1的抑制作用(IC₅₀ = 3.81 μM)是lesinurad的1.8倍；同时，32对OAT4的IC₅₀为6.08 μM（与lesinurad相当），对GLUT9电流抑制IC₅₀为11.0 μM。SPR结合实验进一步证实32与URAT1（KD=2.84 μM）、OAT4（KD=0.71 μM）及GLUT9（KD=6.37 μM）具有直接结合亲和力。分子对接和动力学模拟揭示32通过氢键、π-π堆积及疏水作用稳定结合于这些转运蛋白的活性口袋，且复合物RMSD波动较小，动力学稳定。 🧪 图3 & 图5 | 化合物32与URAT1、OAT4、GLUT9的结合模式及分子动力学左：32与URAT1关键残基PHE364/ARG477形成氢键和π-π堆积；右：32嵌入OAT4/GLUT9疏水腔，磺酰胺基与极性残基相互作用。RMSD轨迹显示复合物在100 ns内构象稳定。3. 抗炎活性：靶向NLRP3炎症小体，缓解痛风性关节炎在LPS+ATP诱导的小鼠骨髓源性巨噬细胞（BMDMs）中，32浓度依赖性抑制IL-1β释放，IC₅₀ = 2.61 μM，而对TNF-α和IL-6无影响，提示其特异性抑制NLRP3炎症小体活化而不干扰初始启动信号。SPR测得32与NLRP3蛋白直接结合(KD=27.8 μM)，CETSA实验也证实32增强NLRP3热稳定性。在MSU晶体诱导的大鼠急性痛风性关节炎模型（2 mg/kg灌胃）中，32显著减轻踝关节肿胀，效果与MCC950相当，且关节局部药物浓度（83733 ng/g）远高于MCC950（9709 ng/g），凸显组织蓄积优势。 🔥 图4 | 32抑制NLRP3炎症小体及缓解痛风性关节炎（a）32对IL-1β抑制IC₅₀为2.61 μM；（b-c）不影响TNF-α/IL-6；（d）大鼠踝关节肿胀曲线；（e）踝关节照片；（f）SPR结合曲线KD=27.8 μM；（g）CETSA热稳定性；（h）分子对接显示32锚定于NLRP3中央电正性通道，与PHE575/TYR632形成π-π作用。4. 体内药效：急慢性高尿酸血症模型均显优势在急性HUA模型中，32在1 mg/kg低剂量下降尿酸率即达90.6%，优于lesinurad（10.8%）和苯溴马隆（17.3%）。在持续30天的慢性HUA小鼠模型中，32能显著降低SUA、血清肌酐(SCr)、尿素氮(BUN)及转氨酶(ALT/AST)水平，HE染色显示32组肝、肾病理损伤明显轻于模型组，而lesinurad组甚至加重肾小球损伤和肝细胞气球样变，提示32在长期用药中具有肝肾保护潜力。 📈 图6 | 慢性HUA模型及体内安全性评估（a）慢性模型流程；（b）体重变化；（c-g）SUA、SCr、BUN、ALT、AST显著改善；（h）hERG实验IC₅₀>10 μM，无心脏毒性风险；（i-l）急性毒性1000 mg/kg未见死亡，亚急性毒性50 mg/kg 30天脏器指数及血常规正常，组织病理无异常；（o）PK显示口服生物利用度53.2%。5. 成药性评价与安全性优势化合物32对人CYP450酶（除2C9/2C19中等抑制外）无明显抑制作用，DDI风险可控。在KM小鼠急性毒性实验中，1000 mg/kg单次灌胃未引起死亡或体重下降，而非布司他组死亡率50%，lesinurad组死亡率100%。30天亚急性毒性（50 mg/kg bid）中，32组动物行为、体重、血常规、主要脏器（心肝脾肺肾）系数及HE染色均未见异常，而非布司他组可见心肌细胞水肿，lesinurad组肝/肾损伤明显。上述结果证明32具有远超现有上市药物的安全窗口。💡 讨论与意义：开创多靶点抗痛风新纪元痛风和高尿酸血症的复杂病理机制决定单靶点药物难以兼顾降尿酸与抗炎需求，联合用药则带来药代/药效相互作用及累积毒性风险。本研究从天然产物β-卡波林-1-丙酸出发，基于药效团模型精准设计，发现化合物32同时抑制三大尿酸重吸收转运体（URAT1、GLUT9、OAT4）和NLRP3炎症小体，首次实现“促尿酸排泄+抗炎”双重机制于同一分子内。尤其值得注意的是，32对GLUT9的抑制填补了该靶点无临床可用抑制剂的空白，且对OAT4的抑制作用增强了尿酸盐排泄协同效应。32在远低于URAT1 IC₅₀的血浆暴露下仍表现出强大的降尿酸活性，提示多靶点协同贡献，这种作用模式可避免过度抑制单一转运体带来的毒性风险。同时，32直接结合NLRP3缓解痛风性关节炎，在慢性模型中改善肝肾损伤，而现有药物常引起肝肾毒性。安全性方面，32无hERG毒性、急性毒性极低、长期给药耐受性好，相较非布司他/lesinurad具有革命性提升。综上，32作为天然产物来源的first-in-class多靶点抗痛风候选药物，为痛风及高尿酸血症治疗提供了全新的“一石多鸟”策略，且其设计理念——天然产物骨架+药效团指导的多靶点药理学——为复杂慢性病药物研发提供了极具价值的范式。📌 结论本研究通过表型筛选、药效团模型引导的多轮结构优化，成功获得化合物32，一个兼具强效降尿酸（抑制URAT1/GLUT9/OAT4）与抗炎（抑制NLRP3炎症小体）双重功能的抗痛风候选分子。在多种动物模型中，32降尿酸疗效媲美非布司他，抗关节炎活性与MCC950相当，且急慢性安全性显著优于临床现有药物。化合物32不仅揭示了东革阿里来源天然产物作为多靶点药物先导的巨大潜力，更为未来痛风治疗提供了安全、高效、可长期服用的创新疗法，目前正推进临床前开发。该工作也示范了基于天然产物的理性多靶点药物设计策略在复杂代谢及炎症性疾病中的广阔应用前景。 📌 编者按：尽管化合物32展现出令人振奋的临床前数据，仍需进一步临床研究验证其人体安全性及有效性。此外，其对CYP2C9/2C19中等抑制需关注潜在的药物相互作用，但整体风险可控。本研究的最大价值在于验证了“天然产物启发的多靶点药物设计”策略可行，并提供了一个极具转化潜力的候选分子。参考文献：Zhang ZJ, Shi XY, Wu T, et al. Discovery of multi-target anti-gout agents from Eurycoma longifolia Jack through phenotypic screening and structural optimization. Nature Communications, 2025, 16: 62645. DOI: 10.1038/s41467-025-62645-6 数据来源：本文数据源自原文主图及补充材料，包括表型筛选、分子动力学模拟、SPR结合分析、体内药效及毒理学实验。资助项目：国家自然科学基金（中国）等项目资助。📎 附：更多关键实验数据展示 🧬 图2 | 系列III化合物的构效关系(SAR)热图不同颜色代表降尿酸活性强弱（红色 DR>70%，蓝色 DR>50%，橙色 DR>30%），表明环丙基取代萘环和特定磺酰胺基团对活性贡献最大。 🧫 补充图1 | 32对大鼠踝关节IL-1β水平及组织暴露量32在关节腔蓄积水平远高于MCC950，2h关节浓度达83.7 μg/g，显著抑制局部炎症因子。 🧪 补充图2 | 慢性HUA小鼠肝肾HE染色模型组可见肾小管扩张、肝细胞水肿；32组病变轻微；lesinurad组肾小球囊扩张、肝细胞气球样变明显。 📊 补充表5-9 | 32的剂量依赖性、PK参数及CYP抑制谱32口服生物利用度53.2%，T1/2适宜，对CYP1A2/2D6/3A4抑制作用弱，安全窗口高。 🌟 从传统草药到精准多靶点药物——化合物32的问世，为全球数亿痛风患者带来更安全、更高效的治疗曙光！ ⚡ 原创编译 · 欢迎分享 · 关注抗痛风新药前沿点击蓝字关注我们科研猫猫猫微信号丨x17585577064 可私信合作扫码私信我进学术交流讨论群关注我，分子网络/代谢组学不迷路！更多精彩内容，扫码加入社群查看！

2026-04-08

·化学经纬

DMSO再次成为主角，这个溶剂真的是越来越妖！

环外烯烃氮杂环骨架广泛存在于聚氧菌素 A、氯雷他定等药物和天然产物中，是构建复杂含氮化合物的重要合成砌块，其高效合成一直是有机化学的研究热点。传统合成方法存在试剂不环保、步骤繁琐等问题，过渡金属催化策略又依赖贵金属催化剂，开发无过渡金属、原料简单的合成方法成为亟待解决的问题。近期，贵州医科大学杨小生研究员团队在《The Journal of Organic Chemistry》发表最新研究，开发了一种 KF 催化的自由基介导氮杂环羧酸与 DMSO 的甲基化反应，为环外烯烃氮杂环的合成提供了全新策略，相关成果值得关注！巧选催化体系，优化反应条件团队瞄准无过渡金属催化方向，选择廉价、空气稳定的 KF 作为催化剂，同时将成本低、毒性小的 DMSO 作为亚甲基源，以 1-Cbz-哌啶-4- 羧酸为模型底物开展反应探索。初始实验在 160℃、4h 条件下仅获得 25% 的目标产物收率，团队随后进行了系统的条件优化：筛选 NaF、LiF 等多种氟化物及 KCl，证实 KF 是该自由基级联反应的最优催化剂；尝试 DMF、DCE 等溶剂后，发现无溶剂体系更利于反应进行；提升温度至 180℃并延长反应时间至 6h 后，产物收率显著提升至 78%；进一步优化 KF 当量、DMSO 体积及添加剂，未发现更优条件。最终确定最优反应条件：20 mol% KF 为催化剂，无溶剂、180℃反应 6h。拓展底物范围，验证反应普适性在最优条件下，团队对氮杂环羧酸底物的普适性进行了全面考察。哌啶羧酸类底物均能以 53%-78% 的收率得到相应环外烯烃氮杂环；氮杂庚烷羧酸底物反应效果更佳，收率达 80%；吡咯烷和氮杂环丁烷羧酸类底物也能顺利转化，收率 69%-74%，且发现底物环张力越大，产物收率越低，符合环张力原理。同时，团队利用氘代 DMSO 实现了氘代环外烯烃氮杂环的合成，虽收率较普通 DMSO 有所降低，但为同位素标记衍生物的制备提供了方法。此外，放大实验中目标产物仍能获得 51% 的分离收率，证明该方法具备一定的工业化应用潜力。而其他环状、线性羧酸及二乙基亚砜、二丁基亚砜等底物则无法得到目标产物，体现了反应的底物特异性。开展机理研究，揭示反应本质为明确反应机理，团队设计了一系列控制实验和动力学同位素效应（KIE）研究。向反应体系中加入 BHT、TEMPO 等自由基抑制剂后，目标产物无法生成，且 TEMPO 与底物形成的加合物被 HRMS 表征，证实反应为自由基机理；甲酯化的底物无法发生反应，说明自由基脱羧是反应的关键步骤；1-Boc、1-Fmoc 取代的哌啶羧酸未得到目标产物，表明反应对 Cbz 保护基存在特异性要求。 KIE 实验测得数值为 1.5，提示 DMSO 的 C-H 键断裂参与反应决速步。结合文献报道和实验结果，团队提出反应机理：K+与羧酸形成复合物促进脱羧生成哌啶自由基，F-通过 Pummerer 型反应活化 DMSO 形成中间体，二者结合后释放甲硫醇，最终得到目标产物，反应体系中检测到的硫味也为甲硫醇的生成提供了间接证据。拓展应用场景，彰显实用价值为验证方法的实际应用价值，团队将该策略应用于商业药物和天然产物的结构修饰。布洛芬、萘普生、吲哚美辛三种常用非甾体抗炎药，以及具有生物活性的天然产物松香酸，均能顺利转化为对应的环外烯烃氮杂环衍生物，收率 61%-75%。这一成果为药物分子和天然产物的结构改造与活性优化提供了新的思路，具有重要的应用前景。研究总结该研究开发了首例 KF 催化的氮杂环羧酸与 DMSO 的自由基脱羧甲基化反应，以无过渡金属、DMSO 直接作为亚甲基源、自由基级联过程为显著特征，高效合成了一系列环外烯烃氮杂环及其氘代衍生物。该方法具有催化剂廉价易得、反应条件温和、底物普适性较好、可放大制备等优点，同时成功应用于药物和天然产物的结构修饰，为环外烯烃氮杂环的合成提供了绿色、高效的新途径，也为 DMSO 在有机合成中的新应用及无过渡金属氟催化研究提供了新的参考。文献：Radical-Mediated Methylenation of N‑Heterocyclic Carboxylic Acids with DMSO to Access Exocyclic Olefinic Azacycles；https://doi.org/10.1021/acs.joc.5c03092.

临床研究诊断试剂

2026-04-08

·BioSpace

Cosette Pharmaceuticals Expands Branded Portfolio through Acquisition of SYMPAZAN® and Additional Products from Assertio

-- Adds Portfolio of Branded Products with $48.9 million in 2025 Net Sales and an Established Commercial Presence -- -- SYMPAZAN ® Establishes a Neurology Rare Disease Footprint within Cosette -- -- Additional Brands include INDOCIN ® , SPRIX ® , ZIPSOR ® , CAMBIA ® , and OTREXUP ® -- BRIDGEWATER, N.J.--(BUSINESS WIRE)--Cosette Pharmaceuticals, Inc., a U.S.-based, branded specialty pharmaceutical company, announced today the closing of a definitive agreement to acquire the U.S. sales and distribution rights for a portfolio of seven branded products from Assertio Holdings, Inc. (Nasdaq: ASRT). The acquisition expands Cosette’s branded portfolio and adds the U.S. rights to SYMPAZAN ® , a growing, patent-protected asset, further advancing Cosette’s disciplined growth strategy. SYMPAZAN ® (clobazam) oral film is an FDA-approved medicine for the adjunctive treatment of seizures associated with Lennox‐Gastaut Syndrome (LGS), a rare and severe form of epilepsy, in patients 2 years of age or older. SYMPAZAN ® is a growing product with patent protection extending until 2040. As the first and only FDA-approved oral film formulation of clobazam, SYMPAZAN ® addresses an important unmet need for LGS patients and establishes a Neurology rare disease footprint within Cosette’s branded portfolio. “This acquisition reflects Cosette’s strategic approach to expanding our branded portfolio,” said Apurva Saraf, President and CEO of Cosette Pharmaceuticals. “It adds immediate scale through branded, on-market products and includes SYMPAZAN ® , a growing, patent-protected asset in an orphan indication. Just as important, it reinforces our ability to execute strategic transactions propelling our growth. We look forward to successfully integrating these important medicines into Cosette and continuing to make them available for patients and prescribers.” In addition to SYMPAZAN ® , Cosette has acquired the rights to a portfolio that includes Assertio’s branded non-steroidal anti-inflammatory drugs (NSAIDs) treating indications in inflammation, pain management, and migraine: INDOCIN ® (indomethacin), oral suspension INDOCIN ® (indomethacin), suppositories SPRIX ® (ketorolac tromethamine), nasal spray ZIPSOR ® (diclofenac potassium), liquid-filled capsules CAMBIA ® (diclofenac potassium), for oral solution OTREXUP ® (methotrexate), injection for subcutaneous use The agreement includes a transition period during which Assertio and Cosette will transfer responsibilities for the manufacture, supply, and commercialization of these products, including quality assurance, pharmacovigilance, and regulatory matters. Products: Please see Package Insert (PI) for full prescribing information including complete safety information: SYMPAZAN ® (clobazam) oral film: See full prescribing information for important safety information, including Boxed Warning. INDOCIN ® (indomethacin) oral suspension: See full prescribing information for important safety information, including Boxed Warning. INDOCIN ® (indomethacin) suppositories: See full prescribing information for important safety information, including Boxed Warning. SPRIX ® (ketorolac tromethamine) nasal spray: See full prescribing information for important safety information, including Boxed Warning. ZIPSOR ® (diclofenac potassium) liquid-filled capsules: See full prescribing information for important safety information, including Boxed Warning. CAMBIA ® (diclofenac potassium), for oral solution: See full prescribing information for important safety information, including Boxed Warning. OTREXUP ® (methotrexate) injection for subcutaneous use: OTREXUP ® was discontinued by Assertio in August 2025. About Cosette Pharmaceuticals Cosette Pharmaceuticals, Inc. is a U.S.-based, leading specialty pharmaceutical company providing some of the most trusted and well-known brands in medicine — acquiring, developing, and delivering products that make a difference in patients’ lives. Cosette’s strong growth has been driven by its proven ability to maximize the value of its portfolio through best‑in‑class marketing, promotion, and strategic distribution capabilities, enabling the company to scale efficiently while continuing to invest in high-quality, patient-centered therapies. Cosette has corporate headquarters in Bridgewater, New Jersey and is supported by 350+ dedicated team members across all functional areas. Cosette is backed by Avista Healthcare Partners, a healthcare focused private equity firm, and funds managed by Hamilton Lane, a private markets investment management firm (Nasdaq: HLNE). For more information, please visit or follow Cosette on LinkedIn . Contacts Cosette Pharmaceuticals Contacts: Cosette Pharmaceuticals media@cosettepharma.com

上市批准并购引进/卖出

100 项与吲哚美辛相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D00141	吲哚美辛	C01EB03 S01BC01 M01AB01	DB00328

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
急性疼痛	美国	Genus Lifesciences, Inc.	2014-02-24
动脉导管未闭	美国	Fresenius Kabi USA LLC	2010-03-17
炎症	日本	Hisamitsu Pharmaceutical Co., Inc.	1989-10-06
肌痛	日本	Teikoku Seiyaku Co. Ltd.	1989-10-06
网球肘	日本	Teikoku Seiyaku Co. Ltd.	1989-10-06
痛风性关节炎	美国	Rising Pharmaceuticals, Inc.	1984-04-20
肩周炎	日本	Kowa Co., Ltd.	1980-03-18
腱鞘炎	日本	Kowa Co., Ltd.	1980-03-18
肿胀	日本	Kowa Co., Ltd.	1980-03-18
疼痛	日本	Kowa Co., Ltd.	1980-03-18
强直性脊柱炎	美国	Zyla Life Sciences US LLC	1965-06-10
滑囊炎	美国	Zyla Life Sciences US LLC	1965-06-10
骨关节炎	美国	Zyla Life Sciences US LLC	1965-06-10
原发性痛风	美国	Zyla Life Sciences US LLC	1965-06-10
类风湿关节炎	美国	Zyla Life Sciences US LLC	1965-06-10
肩痛	美国	Zyla Life Sciences US LLC	1965-06-10
肌腱病	美国	Zyla Life Sciences US LLC	1965-06-10

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
腰痛	临床3期	中国	Teikoku Seiyaku Co. Ltd.	2013-10-10
腰痛	临床3期	中国	北京世纪利伟医药科技发展有限公司	2013-10-10
软组织损伤	临床3期	中国	北京世纪利伟医药科技发展有限公司	2013-10-10
软组织损伤	临床3期	中国	Teikoku Seiyaku Co. Ltd.	2013-10-10
软组织疼痛	临床3期	中国	北京世纪利伟医药科技发展有限公司	2013-10-10
软组织疼痛	临床3期	中国	Teikoku Seiyaku Co. Ltd.	2013-10-10
急性偏头痛	临床3期	美国	Novartis AG	2013-10-01
膝关节炎	临床3期	中国	Teikoku Seiyaku Co. Ltd.	2013-09-27
膝关节炎	临床3期	中国	北京世纪利伟医药科技发展有限公司	2013-09-27
术后疼痛	临床3期	美国	Iroko Pharmaceuticals LLC	2012-02-01

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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


NCT05664074 (CTgov)	临床4期	ERCP术后急性胰腺炎	192	Rectal indomethacin (Rectal Indomethacin)	醖遞願淵範憲窪築鏇獵 = 窪餘齋選膚顧構範範觸構鹹獵製遞獵築顧廠膚 (繭膚遞鑰獵簾網鑰襯顧, 獵範願醖顧膚獵鹹鹽獵 ~ 簾憲鏇餘築選繭製繭艱) 更多	-	2026-03-12
				IV ketorolac (IV Ketorolac)	醖遞願淵範憲窪築鏇獵 = 醖齋選鬱鹹襯築製鏇獵構鹹獵製遞獵築顧廠膚 (繭膚遞鑰獵簾網鑰襯顧, 鏇壓鏇遞醖艱願餘網選 ~ 鏇襯網鑰衊餘襯選鏇夢) 更多
NCT04207060 (PAIR, Pubmed \| Clin Transl Gastroenterol)	临床1/2期	慢性胰腺炎	27	Indomethacin 50 mg	衊鬱醖憲糧觸製獵餘遞(鬱觸艱鏇糧壓壓襯繭顧): P-Value = 0.25 更多	不佳	2025-09-01
				Placebo
NCT04207060 (PAIR, CTgov)	临床1/2期	慢性胰腺炎	27	Endoscopy for Pancreatic Function Testing+Indomethacin (Indomethacin)	鬱鹽繭襯鹹艱襯顧範簾(鑰襯遞鹹製鏇遞鬱衊構) = 觸鬱鹽鏇窪衊淵築鑰網窪鬱夢鹹糧憲蓋構艱願 (窪選範範範艱選網齋壓, 489.8) 更多	-	2024-09-04
				Placebo (Placebo)	鬱鹽繭襯鹹艱襯顧範簾(鑰襯遞鹹製鏇遞鬱衊構) = 願憲繭鏇膚廠艱構窪艱窪鬱夢鹹糧憲蓋構艱願 (窪選範範範艱選網齋壓, 865.6) 更多
DDW2024	N/A	可见病灶 \| 胰腺炎	-	RECTAL INDOMETHACIN (No Prophylaxis)	鑰願壓壓餘窪衊壓範繭(願獵醖顧積鬱窪願艱鹽) = 1 case of acute renal failure was noted in the no prophylaxis group 築獵鏇鹽廠壓艱範鏇鬱 (觸積願獵壓壓衊獵鏇衊 ) 更多	-	2024-05-20
NCT02950259 (P212, CTgov)	临床1期	男性乳腺肿瘤 \| 三阴性乳腺癌 \| 早期乳腺癌	16	Multivitamin+Indomethacin+Omeprazole+Cyclophosphamide (IRX-2 Regimen -Early Stage Breast Cancer)	積獵醖壓獵遞糧遞廠製 = 壓獵壓製夢壓願憲齋願願網鑰廠築範網願餘壓 (製鏇鏇鏇憲鹽醖構獵淵, 窪糧獵餘蓋繭鏇艱蓋築 ~ 範遞艱鹹衊齋淵餘鹹齋) 更多	-	2024-01-30
				Multivitamin+Indomethacin+Omeprazole+Cyclophosphamide (IRX-2 Regimen -Triple Negative Breast Cancer)	積獵醖壓獵遞糧遞廠製 = 廠廠顧觸憲壓鬱鑰構廠願網鑰廠築範網願餘壓 (製鏇鏇鏇憲鹽醖構獵淵, 構壓選鹽醖製糧鹽醖廠 ~ 膚鹽鹹願夢廠衊憲壓製) 更多
NCT02797067 (RIPEP, CTgov)	临床4期	ERCP术后胰腺炎	1,370	indomethacin suppository (Indomethacin)	憲廠衊鏇構窪範齋淵衊 = 夢糧醖憲齋齋衊築膚構獵觸齋獵鏇醖選鑰鏇選 (壓範淵鏇壓範獵積觸憲, 廠鑰鹹簾鏇齋積築壓齋 ~ 鬱艱願糧選築齋積餘積) 更多	-	2022-05-26
				Glycerin Suppository (Glycerin)	憲廠衊鏇構窪範齋淵衊 = 簾餘夢選壓憲憲鹽鏇鹽獵觸齋獵鏇醖選鑰鏇選 (壓範淵鏇壓範獵積觸憲, 範廠製顧膚鏇獵築積夢 ~ 淵築鹽齋網齋夢餘鹹鹹) 更多
NCT02797067 (RIPEP, Pubmed \| Lancet Gastroenterol Hepatol) 人工标引	临床4期	胰腺炎	1,370	indometacin	糧鑰蓋築範壓糧糧餘鏇(鬱構壓壓積憲艱觸齋鏇) = 鏇廠鏇築窪鑰廠憲顧艱網範鏇獵糧廠憲遞壓鏇 (糧遞膚顧憲遞壓獵鑰壓 ) 更多	积极	2022-03-01
				Placebo	糧鑰蓋築範壓糧糧餘鏇(鬱構壓壓積憲艱觸齋鏇) = 鏇顧壓鏇窪願膚蓋遞選網範鏇獵糧廠憲遞壓鏇 (糧遞膚顧憲遞壓獵鑰壓 ) 更多
NCT02438371 (CTgov)	临床4期	早产	49	Nifedipine (Nifedipine)	範淵繭糧夢鏇衊壓觸憲 = 選鬱製醖廠鏇網窪餘積襯鹹簾簾鹽鹽積選醖蓋 (襯淵願壓襯淵鬱顧鹽構, 繭鹽築鹹齋廠觸醖艱壓 ~ 選鏇願鏇築遞艱築獵簾) 更多	-	2021-11-24
				Indomethacin+Nifedipine (Nifedipine Plus Indomethacin)	範淵繭糧夢鏇衊壓觸憲 = 獵醖糧選遞艱願廠構製襯鹹簾簾鹽鹽積選醖蓋 (襯淵願壓襯淵鬱顧鹽構, 鏇膚構選夢淵製淵繭鏇 ~ 網廠憲繭襯鹹鬱憲遞窪) 更多
NCT03129945 (CTgov)	N/A	早产	36	Nifedipine (Nifedipine)	糧積鏇製築餘窪壓廠齋 = 鑰齋積鬱構鹹艱觸遞壓簾範鹽獵鹹夢廠觸積範 (積遞獵夢鑰廠艱鑰餘醖, 糧齋壓鑰鏇積齋餘醖膚 ~ 壓蓋鏇繭觸鬱襯鬱膚襯) 更多	-	2021-11-05
				Indomethacin (Indomethacin)	糧積鏇製築餘窪壓廠齋 = 廠顧餘簾艱構顧衊選鏇簾範鹽獵鹹夢廠觸積範 (積遞獵夢鑰廠艱鑰餘醖, 範鑰製選構構壓廠糧選 ~ 鬱鏇獵構餘構構網遞繭) 更多
IRCT20080921001264N11 (Pubmed \| J Clin Gastroenterol)	临床4期	ERCP术后胰腺炎	530	Intravenous Somatostatin + Rectal Indomethacin	齋顧範顧觸壓願齋艱觸(衊艱遞餘廠獵遞膚顧壓) = PEP was the most common adverse event with 50 (13.2%) episodes, including 21 (5.5%) mild, 23 (6.1%) moderate, and 6 (1.2%) severe 積願膚顧鑰蓋鬱蓋夢餘 (簾膚築願鬱願遞夢顧鹽 )	不佳	2021-05-28
				Placebo + Rectal Indomethacin