更新于：2024-11-01

Glyburide

格列本脲

更新于：2024-11-01

概要

概要

基本信息

药物类型

小分子化药

别名

1-((p-(2-(5-chloro-o-anisamido)ethyl)phenyl)sulfonyl)-3-cyclohexylurea、1-(p-(2-(5-chloro-2-methoxybenzamido)ethyl)benzenesulfonyl)-3-cyclohexylurea、5-chloro-N-(2-(4-((((cyclohexylamino)carbonyl)amino)sulfonyl)phenyl)ethyl)-2-methoxybenzamide

+ [22]

靶点

Kir6.2 x SUR1

作用机制

Kir6.2激动剂(potassium inwardly rectifying channel subfamily J member 11 agonists)、SUR1抑制剂(磺酰脲类受体1抑制剂)

治疗领域

内分泌与代谢疾病其他疾病

在研适应症

6q24暂时性新生儿糖尿病新生儿糖尿病2型糖尿病+ [1]

非在研适应症

原研机构

在研机构

+ [1]

非在研机构

Remedy Pharmaceuticals, Inc.

Biogen, Inc.

江苏奥赛康药业有限公司

+ [1]

最高研发阶段批准上市

首次获批日期

中国 (1981-01-01),

糖尿病

最高研发阶段(中国)批准上市

特殊审评孤儿药 (欧盟)、优先审评 (中国)

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结构

分子式C23H28ClN3O5S

InChIKeyZNNLBTZKUZBEKO-UHFFFAOYSA-N

CAS号10238-21-8

关联

项与格列本脲相关的临床试验

NCT06589141 / Not yet recruitingN/AIIT

Comparison Between Metformin and Glyburide in the Management of Gestational Diabetes: a Randomized Controlled Trial (GDM-MERGE Trial)

This study aims to compare the maternal, fetal, and neonatal outcomes associated with the use of metformin versus glyburide for managing gestational diabetes.
The objective is to assess the safety and effectiveness profiles of both medications as potential alternatives to initiating insulin therapy.

开始日期2025-01-01

申办/合作机构

Assiut University

CTRI/2023/12/060716 / RecruitingN/AIIT

Role of Sulphonylurea-receptor1(SUR1) inhibition in Traumatic Brain injury (TBI): A randomized controlled trial to assess efficacy and safety of Glibenclamide in moderate to severe TBI - STRATEGY

开始日期2024-01-01

申办/合作机构

Indian Council of Medical Research

NCT05687500 / Recruiting临床2期IIT

Oral Glibenclamide in Preterm Infants With Hyperglycaemia (GALOP)

The purpose of this study is to confirm hypothesis that Glibenclamide can be administered orally and is an alternative to insulin therapy in treating transient hyperglycemia of premature newborns.

开始日期2023-05-20

申办/合作机构

Assistance Publique des Hôpitaux de Paris SA

100 项与格列本脲相关的临床结果

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100 项与格列本脲相关的转化医学

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100 项与格列本脲相关的专利（医药）

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10,768

项与格列本脲相关的文献（医药）

2025-01-01·Journal of Ethnopharmacology

Bioactive phytocompounds profiling and the evaluation of analgesic, anti-inflammatory, and antihyperglycemic potential of Argyreia capitiformis (Poir.) Ooststr.: A combined n vitro, n vivo, and computational investigations

Article

作者: Islam, Md Naharul ; Biswas, Biswajit ; Islam, Md. Naharul ; Oisay, Debasree Sen ; Hasan, Md Nazmul ; Hasan, Md. Nazmul ; Biswas, Partha ; Medha, Maisha Maliha ; Devnath, Hiron Saraj ; Hossain, Arafat ; Sadhu, Samir Kumar ; Ahmed, Khondoker Shahin ; Hossain, Hemayet

ETHNOPHARMACOLOGICAL RELEVANCEArgyreia capitiformis (Poir.) Ooststr. (Convolvulaceae) is traditionally used by the Chakma community in the hilly region of Bangladesh to treat minor disorders such as pain.AIM OF THE STUDYThis study intended to determine the secondary metabolites to identify bioactive compounds and evaluate antioxidant potential, in vitro anti-inflammatory and in vivo analgesic, anti-inflammatory, and antihyperglycemic activities of A. capitiformis along with in silico investigations.MATERIALS AND METHODSChemical profiling was carried out using HPLC and GC-MS analysis. The analgesic effect was measured employing tail immersion and acetic acid-induced writhing methods. Following protein denaturation and formalin-induced paw edema, anti-inflammatory activity was studied. The antihyperglycemic potential was assessed using an oral glucose tolerance test (OGTT), while further mechanistic investigation was conducted using an alpha-glucosidase enzyme inhibitory assay. Simulations and molecular docking analyses were performed to ascertain the stability and binding affinities of the drug-protein complex.RESULTSA. capitiformis ethanolic extract confirmed the presence of phenolics, alkaloids, flavonoids, terpenoids, tannins, gums, steroids, and reducing sugars. HPLC analysis revealed the presence of eight polyphenolic compounds, the most abundant of which was myricetin (64.10 ± 0.14 mg per 100 g dry extract). Moreover, the GC-MS analysis revealed twenty-four molecules, the most important of which was 2,4-bis (dimethylbenzyl)-6-t-butylphenol (9.19%). The concentrations of total flavonoids, total terpenoids, total phenolics, and total tannins were ascertained to be 142.48 mg QE/g, 173.1 mg UAE/g, 19.35 mg GAE/g, and 13.05 mg GAE/g, respectively. Furthermore, the plant extract had a total antioxidant capacity of 388 mg AAE/g. In the writhing assay, the plant extract suppressed writhing by 59.73% and 76.99% at the doses of 250 and 500 mg/kg, respectively, compared to the standard diclofenac Na 87.17%, and in the tail immersion assay, the plant extract displayed a maximum average reaction time of 1.94 and 2.40 s at the doses of 250 and 500 mg/kg, respectively as compared to the control tramadol 2.84 s at 60 min. In an in vitro anti-inflammatory assay, the plant extract possessed an IC₅₀ of 95.51 μg/ml while diclofenac Na (standard drug) was found to be 69.50 μg/ml. Afterward, in vivo anti-inflammatory activity was observed in mice over a period, particularly after 3 h, the plant extract exerted maximum percent inflammation inhibitions of 36.36% and 45.45% at the doses of 250 and 500 mg/kg, respectively whereas ibuprofen the standard drug (100 mg/kg) exhibited 61.82%. The plant extract demonstrated antihyperglycemic activity, lowering blood sugar levels to 5.7 and 4.62 mM at doses of 250 and 500 mg/kg, respectively, as opposed to 8.58 mM in the control group. Meanwhile, the standard drug glibenclamide (5 mg/kg) dropped blood glucose levels to 2.38 mM in 60 min after glucose administration. Molecular docking (MD) and molecular dynamics simulation (MDS) studies support the stability of the protein complex responsible for exerting pharmacological activities.CONCLUSIONA. capitiformis extract exhibited strong medicinal values supporting its traditional uses.

2025-01-01·Journal of Ethnopharmacology

Assessing the potential fasting and postprandial mechanisms involved in the acute hypoglycemic and anti-hyperglycemic effects of four selected plants from Iran used in traditional Persian medicine

Article

作者: Espinoza-Hernández, Fernanda A ; Safavi, Fereshteh ; Andrade-Cetto, Adolfo ; Escandón-Rivera, Sonia M

ETHNOPHARMACOLOGICAL RELEVANCEIn traditional Persian medicine (TPM), people often use herbal infusions as a dosage form to treat diseases related to hyperglycemia, known as 'dam-kardeh'. Traditionally, herbal preparations of Eryngium bungei Boiss. (E. b), Tragopogon buphthalmoides (DC.) Boiss. (T. b), Salvia hydrangea DC. ex Benth. (S. h), and Juniperus polycarpos K. Koch. (J. p) are used to manage diabetes in Iran. However, there is no evidence of their effectiveness in controlling glucose levels and their mechanisms remain unclear.AIM OF THE STUDYThis study aimed to investigate whether traditional doses of plant infusions can have hypoglycemic and/or anti-hyperglycemic effects during fasting and/or postprandial states and establish the basis for future research on their potential mechanisms of action.MATERIALS AND METHODSThe effects of traditional doses of herbal extracts on blood glucose levels in STZ-NA-induced hyperglycemic rats were investigated in 2-h acute tests during fasting and postprandial states (with a glucose load). In addition, the potential inhibitory effect in vitro of enzymes involved in relevant pathways, such as gluconeogenesis (fructose-1,6-bisphosphatase, FBPase and glucose-6-phosphatase, G6Pase), carbohydrate breakdown (intestinal α-glucosidases), and insulin sensitivity (protein tyrosine phosphatase 1B, PTP-1B) was evaluated. Acute toxicity tests were carried out and HPLC-SQ-TOF was used to analyze the chemical profiles of the plant extracts.RESULTSIn the fasting state, T. b, S. h, and E. b were as effective as glibenclamide in lowering blood glucose levels in hyperglycemic rats. Moreover, all three suppressed G6Pase and FBPase enzymatic activity by 90-97% and 80-91%, respectively. On the other hand, significant postprandial hypoglycemic efficacy was observed for E. b, S. h, and T. b. Based on the AUC values, T. b caused a reduction comparable to the therapeutic efficacy of repaglinide. When investigating the possible mechanisms of action involved in this activity, E. b, S. h, and T. b showed significant inhibition of PTP-1B in vitro (>70%). Finally, all plant extracts showed no signs of acute toxicity. Several compounds that may contribute to biological activities were identified, including phenolic acids and flavonoid glycosides.CONCLUSIONSThe present study supports the traditional use of T. b, E. b and S. h for the control of diabetes in the fasting and postprandial state. Moreover, these plants were found to be rich in bioactive compounds with hypoglycemic and antihyperglycemic activities. On the other hand, J. p, showed a modest effect only in the fasting state and after 90 min. Further studies are needed to expand these results by analyzing the chemical composition and using complementary experimental models.

2024-12-01·European Journal of Pharmacology

Glibenclamide reverses cardiac damage and NLRP3 inflammasome activation associated with a high refined sugar diet

Article

作者: Rodrigues, Yuri Blanc ; Tostes, Rita de Cassia ; de Assis Cau, Stefany Bruno ; Bello, Fernanda Luiza Menezes ; e Castor, Marina Gomes Miranda ; Cau, Stêfany ; Bernardes, Sara Santos ; Ferreira, Anderson Jose ; Miranda e Castor, Renata Gomes ; Bruno, Alexandre Santos ; Miranda E Castor, Renata Gomes ; Silva, Mychel Gonçalves ; E Castor, Marina Gomes Miranda ; Pereira, Camila André

Increased energy intake from carbohydrates has been associated with major cardiovascular outcomes. Mice fed a highly-refined carbohydrate (HC) diet develop cardiac hypertrophy and inflammation. During cardiac injury, NLRP3 inflammasome is activated which results in a local inflammatory response. In this study, we hypothesized that a nom-hypoglycemic dose of glibenclamide may reverses sugar diet-induced cardiac damage by NRLP3 inflammasome inhibition. Mice were fed the HC diet for eight weeks and divided into a group treated with glibenclamide (20 mg/kg, gavage) and another with vehicle for four weeks. Afterward, hearts were excised for morphometric analysis and ex vivo function determination. NLRP3 inflammasome activation was investigated by western blotting and in situ fluorescent detection of reactive oxygen species (ROS) and active caspase-1. The HC diet promotes heart hypertrophy and collagen deposition, which were reverted by glibenclamide without ameliorating HC diet-induced insulin resistance. Changes in cardiac performance were observed in vivo by invasive catheterization and in Langendorff-perfused hearts due to the HC diet, which were prevented by glibenclamide. Hearts from HC diet mice had increased levels of NLRP3 and cleaved IL-1β. Glibenclamide reversed ROS production and caspase-1 activity induced by HC diet. These findings suggest glibenclamide's cardioprotective effects on heart damage caused by the HC diet are related to its inhibitory action on the NLRP3 inflammasome.

项与格列本脲相关的新闻（医药）

2024-10-22

·PRNewswire

Remedy Pharmaceuticals Announces FDA Orphan Drug Designation Granted for the Treatment of Large Territory Acute Ischemic Stroke with CIRARA

NEW YORK, Oct. 22, 2024 /PRNewswire/ -- Remedy Pharmaceuticals, a pioneer in stroke drug development, today announced that the U.S. Food and Drug Administration (FDA) Office of Orphan Products Division (OOPD) has granted Orphan Drug Designation for CIRARA for the treatment of "large territory acute ischemic stroke," which includes large hemispheric infarctions (LHI). LHI is a particularly severe form of ischemic stroke caused by a blockage in the one of two large blood vessels in the brain: internal carotid artery or middle cerebral artery (MCA), which cuts off the blood supply to large areas of the brain, resulting in severe swelling, significant mortality, and high disability rates. "The Orphan Drug Designation for CIRARA underscores the uniqueness of large territory ischemic strokes in terms of mechanism and universally poor outcomes in contrast to smaller strokes," said Sven Jacobson, CEO of Remedy Pharmaceuticals. "This designation will accelerate our efforts to bring CIRARA to acute ischemic stroke patients at the highest risk of severe disability and death." The FDA's Orphan Drug Designation program provides orphan status to drugs or biologics intended to treat diseases or conditions that affect fewer than 200,000 people in the United States. Sponsors of medicines with Orphan Drug Designation may be eligible for various incentives, including tax credits for qualified clinical trials, prescription drug user fee exemptions, and seven years of marketing exclusivity upon FDA approval. About Large Hemispheric Infarction A large hemispheric infarction is a particularly severe type of ischemic stroke that affects a substantial portion of the brain. This occurs when there is a blockage in a major cerebral artery, such as the middle cerebral artery (MCA) or the internal carotid artery (ICA), both of which are responsible for supplying large regions of the brain with oxygen-rich blood. Treatment for LHI typically involves rapid revascularization strategies to restore blood flow, such as mechanical thrombectomy or intravenous thrombolysis (administering clot-dissolving drugs like tPA). However, the large scale of the infarction and the resultant edema leads to poorer outcomes compared to smaller strokes, with many patients suffering long-term disability or, in some cases, death. About Remedy Pharmaceuticals: New York-based Remedy Pharmaceuticals, Inc. is a privately held, clinical-stage pharmaceutical company focused on developing and bringing lifesaving treatments to people affected by acute central nervous system (CNS) diseases and injuries. Contact: Sven Jacobson CEO Remedy Pharmaceuticals 212.586.2226 [email protected] SOURCE Remedy Pharmaceuticals WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

孤儿药

2024-10-12

·蒲公英Ouryao

FDA溶出方法数据库的特点分析

本文作者：曾文亮博士，迪哲医药CMCRA副总监 FDA溶出数据库可使用以下标准进行评价：剂型、仪器、旋转速度、溶出介质、取样时间点和特殊剂型的趋势。2015年7月，数据库中有1084种药品，其中超过50%为片剂。桨法（设备2）是数据库中最常见的设备，推荐用于488种产品（45%）。数据库中列出的转速对于设备1是35-200rpm，对于设备2是25-200rpm。114种方法推荐脱气或脱气水。最常引用的溶出介质的pH值在1-7.5的范围内；然而，几种溶出方法的pH值超出了生理范围（塞来昔布胶囊pH 1.2，格列本脲片剂pH 9.5，雷贝拉唑钠片剂pH 8.0，格列美脲片剂pH 7.8）。溶出曲线测试是在药品生命周期的不同阶段使用的最有用的方法之一：药物开发、稳定性研究、替代性评估、常规质量控制以及放大和批准后变更。该测试适用于多种剂型，如片剂和胶囊、透皮剂、内部使用和注射用混悬剂、栓剂、口香糖、咀嚼片、散剂、阴道插入物、植入物等。 FDA溶出度数据库(1)是开放访问的，每季度更新一次。检索时（2015年7月），数据库中有1084种药品。该数据库提供了药品的国际非专利名称（INN）、剂型、USP仪器类型、速度（rpm）、溶出介质、体积、取样时间点和最新更新日期等信息。该数据库是关于溶出度最易访问、最合适、最完整和信息最丰富的资源之一。本文是从剂型、仪器、转度和溶出介质方面对数据库进行简要综述。剂型 FDA数据库中最常见的剂型是片剂和胶囊（图1）。超过65%的产品为片剂剂型。有缓释片、包衣片、肠溶片、口腔崩解片（ODT）和咀嚼片。约26%的产品为胶囊，其中包括软胶囊、液体胶囊和缓释胶囊。图1:FDA溶出数据库中剂型统计 FDA数据库包含内服和外用、注射用混悬液的溶出方法悬浮液以及眼用和耳用悬浮液。然而，用于此类剂型的方法相当罕见(约占数据库内容的2.5%)。约2.5%的数据库描述了透皮剂型如贴剂、薄膜等的溶出。它还包含栓剂、散剂、丸剂、阴道环、阴道插入物、植入物、凝胶和口香糖的方法。仪器所有USP溶出仪器（设备1-7）都列在溶出方法数据库中。桨（设备2）是数据库中最常见的设备。推荐用于大约70%的溶出方法（图2），并被认为是速释固体剂型溶出曲线测试的首选仪器。对于胶囊剂型，可以使用沉降子来防止漂浮。它们包括螺旋、分叉和篮子下沉物。然而，锥体是桨叶的一个重要缺点。剂型的崩解物质可能沉降在搅拌速率最小的USP容器的底部，并形成捕获的药物颗粒的锥体，这导致低溶解速率。图2:FDA溶出数据库中桨法的使用频率大约17%的溶出方法（122种方法）推荐使用篮（设备1）。该装置通常用于溶出漂浮剂型。然而，它有几个缺点：分解的颗粒会堵塞篮子，小的分解的颗粒会掉出来。数据库中的三种缓释片推荐使用设备3（往复式圆筒）：马来酸氯苯那敏、马来酸右溴苯那敏、硫酸伪麻黄碱。在溶出测试程序中需要一个或多个pH/缓冲液变化的情况下，或者当流体动力学可以通过改变浸渍速率直接影响时，设备3可以特别有用。设备4（流通池）仅推荐用于三种方法：醋酸倍他米松/倍他米松磷酸钠注射用混悬液、醋酸甲羟孕酮注射用混悬液、醋酸甲泼尼龙注射用混悬液。设备5(盘上桨)用于局部和透皮剂型(盐酸丁丙诺啡/盐酸纳洛酮舌下膜、双氯芬酸依泊拉明局部贴剂、雌二醇透皮膜等)的溶出。设备6（旋转圆筒）被推荐用于七种方法，以确保局部和透皮药物产品的质量和性能。设备7(往复保持器)也用于透皮递送系统和各种剂型(例如，地塞米松的玻璃体内植入物)。 FDA数据库还提到了许多非药典设备，例如用于溶解药典中未描述的阴道环的培养箱振荡器。还有用于尼古丁口香糖分析的咀嚼机，欧洲药典对此有描述。对于254种产品（约23%），数据库没有说明试验条件，而是参考了相关的USP专论。许多药品没有提到方法，在这些情况下，需要进行方法开发，这对于注射剂型尤其重要。转速设备2（桨）的转速为25-200 rpm，如数据库中所列。最低值（25 rpm）通常用于混悬液（例如，氨苄西林用于口服混悬液，美洛昔康用于混悬液）。在双羟萘酸曲普瑞林注射用混悬液（200 rpm）和枸橼酸芬太尼锭剂（175 rpm）的溶出方法中列出了设备2的最快转速。典型的桨式搅拌速率为50rpm。设备1(篮)的转速值在35-200RPM的范围内变化。最常见的篮子转速是100 rpm（122种方法中的87种）。在富马酸喹硫平缓释片的溶出方法中，篮以最大速度（200 rpm）旋转。用于匹伐他汀钙片的设备1的最低速度为35 rpm，而用于雌二醇阴道片的最低速度推荐为40 rpm。设备5和6（分别为桨盘和旋转圆筒）最常见的速度是50rpm。用于装置4(流通池)的溶解介质的流速在8-17mL/min的范围内。溶出介质 FDA溶出数据库描述了大量不同的介质，从水或不同pH值的简单缓冲溶液到添加了表面活性剂、有机溶剂和酶的溶液。溶解介质的最简单选择是水。有114种方法推荐脱气或脱气水。水作为溶解介质的主要缺点是缓冲能力低。也不鼓励使用水作为溶出介质，因为pH和表面张力等测试条件可能因水源而异，并且在溶出测试本身期间可能由于活性和非活性成分的影响而发生变化。因此，当使用水作为介质时，在测试期间监测pH值是很重要的。然而，水仍然广泛用于溶出曲线测试（约10%的方法）。数据库中最常见的溶出介质的pH值范围为1-7.5（即1.2、2、4、4.5、5、6、6.8、7.2和7.5）。这些pH值存在于胃肠道中，被认为是生理相关的。值得注意的是，FDA数据库方法主要是为了确定药品的体外溶出曲线而开发的；因此，这些介质在某些情况下可能不反映体内生理状况。如今，该机构正在强调这种方法的区分力。它不必模拟体内发生的情况，但它必须对关键质量属性具有区分力。因此，FDA数据库描述了8种pH值超出生理参数范围的培养基（例如，塞来昔布胶囊的pH值为12，格列本脲片的pH值为9.5，雷贝拉唑钠片和盐酸氯胍片的pH值为8.0；格列美脲片、阿齐沙坦酯片、维a酸和异维a酸胶囊的pH值为7.8）。根据数据库，几种酸的水溶液可以用作溶出介质。最常用的酸性介质是以盐酸为基础的：0.1 М、0.01 М和0.001 М HCl。也可以使用磷酸(0.01 М)和其它酸性溶液。建议使用各种缓冲溶液（乙酸盐、柠檬酸盐和磷酸盐）在轻度低pH下进行溶出度测试。通过添加氢氧化钠溶液、硼酸盐缓冲液和Tris缓冲液来制备具有高pH值的溶出介质。对于水不溶性或微溶性药品（BCS II类或IV类），建议使用表面活性剂（数据床中有18.5%的方法），如十二烷基硫酸钠、吐温（聚山梨酯20和80）、十二烷基二甲胺氧化物（LDAO）、Triton X、Brij 35（聚氧乙烯月桂基醚）、十六烷基三甲基溴化铵（CTAB）等（图3）。最常用的表面活性剂是十二烷基硫酸钠（SLS，SDS）；据报道，其浓度范围为0.01-3%（图4）。溶出度是难溶性药物产品的吸收限制因素；因此，溶出度测试对于此类制剂特别有用。图3:FDA溶出数据库中常用的表面活性剂统计图4:FDA溶出数据库中常用的十二烷基硫酸钠浓度在某些特定情况下，建议使用有机化合物。例如，在阿托伐醌片剂的方法中使用含有40%异丙醇的介质。双羟萘酸曲普瑞林注射混悬液推荐使用含有5%甲醇的培养基。这些制剂中溶出度测试需要有机溶剂，这与阿托伐醌（<0.2 μ g/mL）和双羟萘酸曲普瑞林极低的水溶性有关。数据库中的溶出介质可能含有酶。例如，对于外层含有明胶的制剂(例如硬明胶和软明胶胶囊)，可以考虑添加酶。盐酸胃蛋白酶溶液用于度他雄胺、氯雷他定、双羟萘酸丙咪嗪、恩杂鲁胺和恩曲他滨胶囊的溶出。在溶出布洛芬、贝沙罗汀和盐酸伪麻黄碱胶囊的情况下，建议在溶出介质中加入胰酶。以模拟胃液（SGF）或模拟肠液（SIF）为溶出介质的方法有32种。在一些情况下，这些培养基可以含有酶。在FDA数据库的35个质量标准中，试验期间溶出介质pH值发生变化。对于溶出度测试必须模拟剂型在具有不同pH水平的GI部分之间的通过的产品和制剂（例如肠溶包衣片剂）是重要的。溶出介质的体积通常在500-1000 mL的范围内（图5）。最常用的体积是900 mL（56%的方法）、500 mL（12%的方法）和1000 mL（10%的方法）。在需要改变溶出介质pH的方法中，通常会出现750 mL和600 mL的体积。图5:FDA溶出数据库中常见的介质体积在特定情况下，FDA数据库建议体积小于500 mL（例如，双氯芬酸钾混悬液为400 mL）。溶出体积的降低通常是由增加定量测定方法的灵敏度和获得低剂量药物产品的溶出曲线的需要决定的。例如，数据库推荐设备1和设备2，其特别适用于剂量为0.1-1.2 mg的芬太尼口腔片剂和薄膜的小体积溶出介质(60-200mL)。 FDA数据库中的大多数溶出度测试应该在37±0.5℃下进行。如果溶出介质的温度不同于37℃，则规定溶出介质的温度。一般介质的温度应与产品应用部位的温度相同。局部剂型最常用的温度是32℃。在某些缓释剂型的情况下，产品将在施用部位停留很长时间，通常是几个月，如果测试温度大于37°C，则可以缩短溶出度测试的持续时间(7)。地塞米松植入物（玻璃体内）的试验温度为45°С，美沙拉秦栓剂为40°С，丙氯拉嗪直肠栓剂为38°С。溶解介质的温度也可以低于32℃。例如，硝唑尼特的口服混悬液和片剂以及棕榈酸帕利哌酮的注射混悬液为25°C。取样时间点应进行取样以获得完整的溶出曲线。对于速释产品，FDA数据库中的最小采样时间点数为3个（例如，利培酮口腔崩解片为5、10、15分钟）。然而，通常使用五个或更多个点（例如，59种方法中的10、20、30、45和60分钟；43种方法中的5、10、15、20和30分钟；25种方法中的10、15、20、30和45分钟；12种方法中的15、30、45、60和90分钟）。速释剂型最常用的采样时间点为10分钟（69%的方法）、20分钟（60%的方法）、30分钟（69%的方法）和45分钟（53%的方法）。较少使用的时间点是15分钟（37%的方法）、60分钟（25%的方法）等。 FDA数据库中的大多数方法要求在10分钟（319种方法）、5分钟（210种方法）或15分钟（48种方法）内开始取样。对于口腔崩解片剂，通常提前开始取样（2或3分钟）。数据库要求舌下剂型在1或2分钟开始取样。整个采样过程通常需要30至60分钟，但有时可能需要15分钟或180分钟或更长时间。缓释产品的取样时间应单独考虑，通常从0.5或1小时开始，从4至24小时开始，包括5-12个时间点。在最困难的情况下，溶出可持续96小时（盐酸纳曲酮胶囊、格拉司琼透皮膜）、240小时（地塞米松植入物）、使用眼眶振荡器（醋酸戈舍瑞林植入物，10.8 mg规格）的84天，使用培养箱振荡器（雌二醇阴道环）的45天。特殊剂型溶出曲线测试适用于各种新型或特殊剂型。这样的剂型在FDA溶出度数据库中通过口腔崩解片剂(ODT)、混悬剂以及局部和透皮递送系统来表示。可以注意到特殊剂型溶出曲线测试的一些重要特征。旋转桨法是ODT最常用的方法。有19种使用桨的ODT溶出方法和3种使用篮法。这些方法的一个显著特征是早期的第一采样点；它通常小于10分钟（通常为2-5分钟）。 25%的悬浮液药物释放试验方法推荐使用低搅拌速率（25-30 rpm）的旋转桨。此外，使用脱气水作为溶解介质相对频繁（16%的悬浮方法）。推荐使用盘上桨和旋转圆筒测试透皮剂型（约50/50）。这些方法的一个重要特征是介质pH值范围为4.5至6.8，反映了生理皮肤状况。出于同样的原因，测试温度通常设置为32℃(8)。结论 FDA溶出方法数据库可以作为溶出度测试各个方面的最新信息来源：仪器、溶出介质、旋转速度、测试条件和采样时间点。该数据库对于仿制药产品的溶出曲线测试特别有用。该数据库的一些最重要的优势是每季度更新、开放访问、数据系统化和易于使用。应该强调的是，数据库是溶出曲线测试的起点，如果有适当的理由，也可以使用其他条件。参考文献：略作者精彩原创集锦 1、创新药研发中原料药工艺与沟通交流常见难点 2、创新药研发中「制剂工」常见难点 3、创新药研发中「变更」相关难点 4、创新药研发中「质量分析控制」相关难点（1） 5、创新药研发中「质量分析控制」相关难点（2） 6、创新药研发难点分析与CMC研究策略探讨 7、《已上市化学药品药学变更研究技术指导原则（试行）原料药变更的问答》浅析 8、FDA：原料药中亚硝胺风险评估的最新观点 9、亚硝胺「传奇」：5年来监管和制药界的反思 10、【学习笔记】2023年度CDE审评报告 11、FDA审评：吡托布鲁替尼的药学变更桥接(完) 12、CDE：ICH指南在国内的实施概况 13、「解读」FDA审评：repotrectinib胶囊5次CMC会议内容 14、FDA：IND阶段CMC关注点 15、药品注册检验难点与建议曾文亮博士迪哲医药CMCRA副总监，公众号“文亮频道”主理人。山东大学本科与硕士，上海中医药大学博士。近20年药物研发经验，擅长新药研发与注册申报，近5年积累了近十个小分子新药中美IND申报成功和两个1类抗肿瘤新药上市申报成功经验。先后任职于某大型CRO医药研发公司、USP大中华区研发中心和港资原料药厂等，主导过MNC质量研究项目、USP各论更新和药厂QC实验室通过国家GMP检查和WHO审计。受中国医药保健品进出口商会邀请在二十二届世界制药原料药中国展（CPHI）主导策划了“小分子创新药质量研究和注册策略”沙龙并发表主题演讲；同时受专业药学论坛邀请发表了《创新药质量研究要点和案例分析》、《中美新药申报沟通交流常见问题和案例分析》、《亚硝胺杂质的FDA和EMA控制策略》、《分析方法开发，验证和转移的统计学评价》和《FDA483中清洁验证的典型案例分析》等十余次主题演讲。更多精彩内容可关注： ▲ 关注文亮频道，探索未知世界

医药出海一致性评价

2024-10-01

·PRNewswire

Remedy Pharmaceuticals' Phase 3 Trial in Large Lesion Stroke Patients Demonstrates Statistically Significant Effect at One Year

NEW YORK, Oct. 1, 2024 /PRNewswire/ -- Remedy Pharmaceuticals today announced additional promising data from the Phase 3 CHARM clinical trial of CIRARA (IV glyburide) in patients with Large Hemispheric Infarction (LHI), the most serious form of ischemic stroke, characterized by large-volume lesions that lead to malignant brain swelling, severe disability, and death. This latest analysis revealed that CIRARA demonstrated a significant, sustained effect at 12 months on the modified Rankin Scale (mRS) in patients with lesion volumes <125 mL. The odds ratio for CIRARA's effect across all <125 mL lesion volume patients was 2.22 (p=0.03), and in patients who also received endovascular thrombectomy (EVT), the odds ratio was even higher at 6.92 (p=0.02). The sustained effect of CIRARA over time is further exemplified by the fact that 78% of EVT patients treated with CIRARA were able to walk independently at 12 months, compared to only 51% in the placebo group—representing a 55% relative increase in this important outcome. In May 2024, Remedy announced that in the prespecified modified intent-to-treat (mITT) population with NIH Stroke Scale (NIHSS) ≤ 20 (n=274), CIRARA improved outcomes with an odds ratio of 1.8 (p=0.01) at Day 90. A post hoc analysis of patients with a lesion volume <125 mL (n=118) found an odds ratio of 2.2 in favor of CIRARA (p=0.04), while in the EVT population with lesion volumes <125 mL (n=34), the odds ratio was 7.1 (p=0.01). Further post hoc analysis showed that CIRARA significantly increased the likelihood of achieving an mRS score of 0-3 (indicating moderate disability or better) in patients with a lesion volume <125 mL (n=118), with an odds ratio of 4.1 (p<0.01). An mRS score of 0-3 includes the ability to ambulate independently—a highly desirable outcome. Among EVT patients with lesion volumes <125 mL (n=34), CIRARA's odds ratio for achieving an mRS score of 0-3 was an impressive 18.5 (p=0.03). "These latest findings are incredibly encouraging," said Sven Jacobson, CEO of Remedy Pharmaceuticals. "CIRARA continues to demonstrate its potential to dramatically improve outcomes for patients suffering from severe ischemic stroke. The ability to show sustained effects through one year and the profound impact on patients' ability to walk independently certainly strengthens our resolve as we move forward with a confirmatory Phase 3 study." About the CHARM Study The CHARM clinical trial was a multicenter, multinational, double-blind, randomized, placebo-controlled Phase 3 study involving patients aged 18-85 with LHI. Patients were eligible if the study drug was expected to start within 10 hours after they were last known well. A total of 535 patients were enrolled, including 431 patients aged 18-70 (the efficacy analysis population) and 81 patients aged 71-85. The study, which was sponsored by Cambridge-based Biogen, was terminated early after a strategic realignment of resources, leading to the return of the program to Remedy. About Remedy Pharmaceuticals: New York-based Remedy Pharmaceuticals, Inc. is a privately held, clinical-stage pharmaceutical company focused on developing and bringing lifesaving treatments to people affected by acute central nervous system (CNS) diseases and injuries. Remedy is planning a confirmatory Phase 3 study of CIRARA in LHI. Contact: Sven Jacobson CEO Remedy Pharmaceuticals 212.586.2226 [email protected] SOURCE Remedy Pharmaceuticals 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期临床结果

100 项与格列本脲相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D00336	格列本脲	A10BB01	DB01016

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
6q24暂时性新生儿糖尿病	冰岛	Ammtek Ltd.	2018-05-24
6q24暂时性新生儿糖尿病	列支敦士登	Ammtek Ltd.	2018-05-24
6q24暂时性新生儿糖尿病	挪威	Ammtek Ltd.	2018-05-24
6q24暂时性新生儿糖尿病	欧盟	Ammtek Ltd.	2018-05-24
新生儿糖尿病	欧盟	Ammtek Ltd.	2018-05-24
新生儿糖尿病	冰岛	Ammtek Ltd.	2018-05-24
新生儿糖尿病	挪威	Ammtek Ltd.	2018-05-24
新生儿糖尿病	列支敦士登	Ammtek Ltd.	2018-05-24
2型糖尿病	美国	Pfizer Inc.	1984-05-01
2型糖尿病	美国	Sanofi-Aventis U.S. LLC	1984-05-01
糖尿病	中国	天津力生制药股份有限公司	1981-01-01

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适应症	最高研发状态	国家/地区	公司	日期
梗塞	临床1期	瑞士	Remedy Pharmaceuticals, Inc.	2018-08-29
梗塞	临床1期	以色列	Remedy Pharmaceuticals, Inc.	2018-08-29
梗塞	临床1期	克罗地亚	Remedy Pharmaceuticals, Inc.	2018-08-29
梗塞	临床1期	德国	Remedy Pharmaceuticals, Inc.	2018-08-29
梗塞	临床1期	加拿大	Remedy Pharmaceuticals, Inc.	2018-08-29
梗塞	临床1期	巴西	Remedy Pharmaceuticals, Inc.	2018-08-29
梗塞	临床1期	中国台湾	Remedy Pharmaceuticals, Inc.	2018-08-29
梗塞	临床1期	意大利	Remedy Pharmaceuticals, Inc.	2018-08-29
梗塞	临床1期	俄罗斯	Remedy Pharmaceuticals, Inc.	2018-08-29
梗塞	临床1期	匈牙利	Remedy Pharmaceuticals, Inc.	2018-08-29

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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


NCT02864953 (CHARM, PRNewswire) 人工标引	临床3期	脑梗塞	535	CIRARA	(製醖廠膚鏇獵廠積選衊): OR = 1.8, P-Value = 0.01 更多	积极	2024-09-03
				Placebo
NCT05137678 (Pubmed \| Neurocrit Care)	临床4期	颅内动脉瘤1 serum neuron-specific enolase (NSE) \| soluble protein 100B (S100B)	111	Glibenclamide tablet 3.75 mg/day	獵築壓選窪鹹糧願廠艱(夢夢遞夢範鑰繭選鏇製) = 顧獵構遞獵蓋醖網範簾餘襯獵糧糧鏇獵鏇範齋 (構鹽鹽願糧膚淵觸選鹹 )	不佳	2024-08-08
				Glibenclamide (Control group)	獵築壓選窪鹹糧願廠艱(夢夢遞夢範鑰繭選鏇製) = 顧遞艱壓襯襯餘鑰餘鬱餘襯獵糧糧鏇獵鏇範齋 (構鹽鹽願糧膚淵觸選鹹 )
CHARM (PRNewswire) 人工标引	临床3期	脑梗塞	535	BIIB093	(鏇積齋遞窪網鏇獵顧繭) = statistically significant improvements in functional outcomes (Odds Ratio 1.66, p=0.03). 壓糧憲鑰衊糧觸製壓願 (蓋夢廠鏇鏇膚襯獵選鏇 )	积极	2024-05-29
				Placebo
NCT02864953 (CHARM, CTgov)	临床3期	脑水肿 \| 脑梗塞 \| 梗塞	535	Placebo (Placebo)	醖製觸鏇壓夢餘蓋壓糧(糧築壓繭簾鏇鬱簾範夢) = 獵鏇鹹繭鑰壓鑰簾衊鑰鏇醖壓鹽繭鏇鏇觸遞壓 (艱糧鬱鏇顧築衊醖壓襯, 簾積糧廠廠範積鹹壓齋 ~ 範鏇淵膚憲廠築觸齋遞) 更多	-	2024-01-09
				BIIB093 (BIIB093)	醖製觸鏇壓夢餘蓋壓糧(糧築壓繭簾鏇鬱簾範夢) = 糧艱願遞積齋醖鹹鬱艱鏇醖壓鹽繭鏇鏇觸遞壓 (艱糧鬱鏇顧築衊醖壓襯, 顧鹹選鹹範鏇窪鹽糧艱 ~ 齋醖鬱範製鬱壓窪積遞) 更多
NCT00965991 (CTgov)	N/A	妊娠期糖尿病	149	Metformin (Metformin)	廠願鑰夢繭憲範衊襯淵(窪鑰壓淵衊齋鏇壓觸餘) = 淵鏇鏇顧廠網製衊糧製艱壓窪糧鹹選鹽遞壓廠 (積膚鹽齋淵鹹膚獵鬱獵, 選築鹹憲醖壓糧衊願製 ~ 壓選膚遞齋製獵鬱蓋鏇)	-	2023-12-21
				Glyburide (Glyburide)	廠願鑰夢繭憲範衊襯淵(窪鑰壓淵衊齋鏇壓觸餘) = 構獵範願遞鹹夢襯廠鹹艱壓窪糧鹹選鹽遞壓廠 (積膚鹽齋淵鹹膚獵鬱獵, 鑰範襯鬱餘淵選醖獵築 ~ 襯選夢鬱衊鬱選膚範願)
NCT03954041 (ASTRAL, CTgov)	临床2期	脑挫伤	92	Placebo	獵繭襯齋製鑰簾廠衊鏇(獵鹽繭蓋壓齋構製憲醖) = 製餘簾醖鏇選廠觸鏇範廠醖艱願衊顧選獵製鬱 (憲蓋醖選繭鹹鹽襯鬱襯, 構選鏇鑰構獵餘壓餘餘 ~ 鑰廠觸簾鹹製鏇選選齋) 更多	-	2023-12-20
ESPE2023	N/A	新生儿糖尿病 KCNJ11 gene mutation	-	Insulin therapy	(廠製鬱蓋夢蓋鑰網壓廠) = 壓淵鹽襯選鏇製襯範鏇築鹹獵夢淵獵願鹽範蓋 (衊鏇鏇網製繭鹽遞衊選, N ~ 0.92 to 3.73)	-	2023-09-21
				Glibenclamide	(廠製鬱蓋夢蓋鑰網壓廠) = 窪夢願艱艱顧衊築鬱鬱築鹹獵夢淵獵願鹽範蓋 (衊鏇鏇網製繭鹽遞衊選 )
NCT02460874 (CTgov)	临床1/2期	脑水肿 \| 脑转移瘤	1	Glyburide (Pilot Portion)	艱廠繭範鹽製遞淵廠構(餘網鑰願膚襯憲窪鹹觸) = 簾衊襯窪網廠餘鑰顧艱艱衊壓憲願齋遞簾蓋遞 (觸構餘糧鏇衊範範願築, 觸糧鹹獵積築憲範鏇廠 ~ 鏇蓋積齋繭鬱膚鏇鏇繭) 更多	-	2022-09-21
				Placebo+Glyburide (Randomized Portion)	艱廠繭範鹽製遞淵廠構(餘網鑰願膚襯憲窪鹹觸) = 網窪構餘網鑰獵夢艱選艱衊壓憲願齋遞簾蓋遞 (觸構餘糧鏇衊範範願築, 繭範壓襯壓餘醖膚鬱淵 ~ 廠遞窪廠獵鬱鹽襯餘鏇) 更多
NCT02524379 (SCING, CTgov)	临床1/2期	创伤性脊髓损伤 \| 急性脊髓损伤	3	Glyburide	艱繭糧鹽鏇獵簾醖鹹艱(窪範憲醖鹹積鑰醖遞製) = 憲製鏇醖膚範獵夢鑰繭糧糧淵膚選網齋蓋願衊 (蓋憲積齋網餘觸範鬱鏇, 範壓網遞鹽積蓋夢鏇壓 ~ 選醖窪窪壓積遞膚鹽範) 更多	-	2022-06-07
ADA2022	N/A	妊娠期糖尿病	786	Glyburide	製鹽選構願鹽廠簾膚膚(遞鑰糧繭蓋選膚繭構窪): OR = 0.83 (95% CI, 0.75 ~ 0.93) 更多	-	2022-06-01
				Glyburide (Diet)