A Phase 3 Placebo-controlled, Double-blind, Randomized, Parallel-group Study to Evaluate the Efficacy in Primary and Secondary Dysmenorrhea and the Long-term Safety of DSG/EE 150/20 using a Flexible Extended Regimen of Administration - DSG/EE 150/20

开始日期2023-07-21

申办/合作机构-

NCT03354494

/ CompletedN/AIIT

Desogestrel (DSG) and Corifolitropin (FSH-CTP) Alfa for Ovarian Stimulation in Donors

Currently, controlled ovarian stimulation (COS) in oocyte donors is performed by daily injections of gonadotropins( recombinant FSH) plus a GnRH Antagonist usually form 5th-6th stimulation day until ovulation induction with a bolus of another injection of a gonadotropin-releasing hormone (GnRH) Agonist. Injections of the GnRH Antagonist avoid untimely luteinizing hormone (LH) surge and spontaneous ovulation prior to follicular aspiration. There is a preparation of long-acting recombinant follicle stimulating hormone (rFSH= (corifollitropin alfa (FSH-CTP), Elonva®, MSD), that allows that a single subcutaneous injection substitutes the first 7 days of daily gonadotropin injections. On the other hand, a contraceptive oral progesterone only( Desogestrel, DSG) is available for contraception, avoiding the LH surge.
In donors, by administering a single injection of FSH-CTP and oral desogestrel since the first menstruation day, the total number of injections administered is reduced and less discomfort is experienced without adverse impact on ovarian response.
Other authors have reported good results using similar synthetic progestins (Medroxyprogesterone, dihydrogesterone, and natural progesterone).
No description of the hormonal and ovarian response under this protocol has been published. Direct comparison between this novel protocol and the classical GnRH- antagonist plus daily gonadotropins has not been reported.

开始日期2016-01-01

申办/合作机构

USP Institut Universitari Dexeus

NCT01446211

/ Terminated临床3期

Randomised, Evaluator-Blinded, Multicentre, International, Parallel-Group, Active-Controlled Clinical Trial of Gusperimus Versus Conventional Therapy in Relapse of Granulomatosis With Polyangiitis (Wegener's Granulomatosis) SPARROW Study - SPAnidin in Relapsing GRanulomatosis With POlyangiitis Wegener's Granulomatosis)

The aim of the study is to assess the efficacy (superiority testing) of gusperimus compared to conventional treatment in patients with a relapse of Wegener Granulomatosis with or without ongoing steroids, and/or immunosuppressive therapy. Further, to evaluate the safety and quality of life of gusperimus treatment compared to standard treatment in patients with relapse of Wegener Granulomatosis receiving glucocorticoids.

开始日期2011-11-01

申办/合作机构

Nordic Pharma SAS

100 项与盐酸胍立莫司相关的临床结果

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100 项与盐酸胍立莫司相关的转化医学

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100 项与盐酸胍立莫司相关的专利（医药）

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1,084

项与盐酸胍立莫司相关的文献（医药）

2025-02-01·Food and Bioprocess Technology

Effect of Cold Plasma and Microwave Pretreatments Combined with Hot-Air Drying on Physical Properties, Chemical Composition, and Volatile Profile of Pomegranate Peels

作者: Ozcan, Fahriye Seyma ; Özcan, Fahriye Şeyma

The use of non-thermal drying techniques for preserving fruits and vegetables has gained popularity due to their ability to enhance dried products quality, reduce drying time and energy consumption, and increase efficiency.In this study, the effects of cold plasma (CP) and microwave (MW) pretreatments combined with hot air drying (HAD) on the chem. composition (amino acid, sugar, organic acid, mineral, and volatile) and physicochem. properties of dried pomegranate peels were investigated.For this purpose, dry samples were compared with fresh ones.The results showed that CP pretreatment is the best technique for preserving the chem., phys., and nutritional quality of pomegranate peels.SEM (SEM) images showed that CP pretreatment significantly changed the surface morphol. of pomegranate peels, leading to faster drying rates.This study also found no significant changes in color parameters in CP-HAD peels.Consequently, this study showed that cold plasma is a promising, environmentally friendly, and innovative technol. that provides a great advantage in preserving food quality.

2025-02-01·CHEMOSPHERE

A biomarkers study of human skin fibroblasts exposition to glyphosate-based herbicide using an untargeted and targeted metabolomics approach

Article

作者: Gomes, Dawidson A ; Rodrigues, Michele A ; Menezes, Helvécio C ; Cardeal, Zenilda L ; Batista, Josimar M ; Armijos, María J G

Metabolomics is a valuable tool to assess glyphosate exposure and its potential impact on human health. However, few studies have used metabolomics to evaluate human exposure to glyphosate or glyphosate-based herbicides (GBHs). In this study, an untargeted and targeted metabolomics approach was applied to human skin fibroblasts exposed to the GBH Roundup (GLYP-R). Cytotoxicity, cell death, and oxidative stress assays were performed to evaluate potential damage caused by GLYP-R in fibroblasts. The herbicide showed a cytotoxic effect at concentrations above 100.0 mg L^-1, with IC₅₀ = 164.2 ± 8.7 mg L^-1, inducing significant reactive oxygen species (ROS) production and necrosis. A GC×GC/Q-TOFMS method using derivatization with propyl chloroformate/propanol was developed for untargeted analysis, allowing the identification of 400 metabolites of different classes in the samples. The most significant compounds in the discrimination and classification of the samples were fatty acids and amino acids (AA). Based on the relevance of AA in untargeted analysis, a targeted analysis of 21 AA was performed using the same validated GC×GC method. Metabolomic analyses allowed the construction of two biomarker models with performance evaluated by receiver operating characteristic (ROC) curves: an untargeted model formed by four metabolites (methylcysteine, N-acetyl-l-methionine, methyl stearate, and linoleic acid) and a targeted model formed by three AA (l-glutamic acid, l-cysteine, and γ-aminobutyric acid). This study is the first to report the use of metabolomics to evaluate human skin cells exposed to GLYP-R, contributing to the toxicological research on glyphosate.

2025-02-01·Clinical and Experimental Dental Research

Impact of Autoclaving on the Dimensional Stability of 3D‐Printed Guides for Orthodontic Mini‐Implant Insertion – An In Vitro Study

Article

作者: Brunello, Giulia ; Hüfner, Mira ; Becker, Kathrin ; David, Samuel ; Kerberger, Robert ; Drescher, Dieter ; Rauch, Nicole

ABSTRACT:

Objectives:

This study aimed to assess the effect of the printing process itself and steam autoclaving on the geometrical stability of 3D‐printed guides for mini‐implant insertion.

Material and Methods:

Fifty guides (n = 10 per group) were printed with five printer/resin combinations (PRCs) from the same STL file using either digital light processing (DLP/EG, DLP/Next, DLP/Opti), desktop stereolithography (SLA/DSG) or liquid crystal display stereolithography printers (LCD/Amber). Half were sterilized by steam autoclaving with Cycle 1 (121°C, 1 bar, 20.5 min), half with Cycle 2 (134°C, 2 bars, 5.5 min). Before (T0) and after sterilization (T1) the guides were scanned with a structured light 3D scanner, and selected guides also with micro‐CT for validation. Linear measurements were performed in three axes on STL, and on T0 and T1 scans. Linear mixed‐effects models were used, followed by post‐hoc tests in case of significance.

Results:

Measurements at T0 and T1 differed significantly from STL in both x‐ and y‐axis (4 and 3 PRCs, respectively) (p < 0.05); in z‐axis only DLP/Next showed significant differences between T0 and STL (p < 0.001). The comparison between T0 and T1 revealed significant differences in x‐axis for DLP/Next and DLP/Opti after Cycle 1 and Cycle 2, respectively (p < 0.05), while in the y‐axis no intra‐group difference was recorded. In the z‐axis all PRCs except for SLA/DSG exhibited significant shrinkage (for Cycles 1 or 2). Differences between the two cycles at T1 were registered only in z‐axis (DLP/Next and LCD/Amber).

Conclusions:

Compared with the original, all PRCs except for SLA/DSG presented significant changes in their dimensional stability owing to the printing process itself and/or the sterilization. If these changes are of clinical significance, they remain to be verified.

Clinical Relevance:

With the utilized design, the guides fabricated with SLA provided lower dimensional changes as compared to the ones produced by the other printing techniques.

项与盐酸胍立莫司相关的新闻（医药）

2022-07-14

·生物探索

“肿瘤克星”CAR-T疗法再升级！未来或能实现百病皆可CAR-T

摘要：2021年，120万一针的“天价”CAR-T由于价格高昂迅速成为业界的关注焦点，一时间成为话题之王。复星凯特的“奕凯达”、药明巨诺的“贝诺达”先后获批，传奇生物自主研发的“西达基奥伦赛”成为首个申请美国上市的中国CAR-T产品，驯鹿医疗的CT120获美国FDA孤儿药认定，成为全球首款全人源双靶点CAR-T产品。多个产品先后获批，2021年可谓是我国的CAR-T元年。既然CAR-T连医学难题“肿瘤”都可攻克，其治疗领域是否可以得到拓展？自2017年首款CAR-T细胞疗法上市以来，细胞治疗时代正式开启，在多种肿瘤治疗中取得了很好的临床效果，可用靶点数量也正迅速增加。CAR-T在肿瘤治疗领域取得的成功，助长了科学和临床对使用CAR-T作为其他类型疾病治疗方法的兴趣，他们试图从不同的角度去探讨CAR-T细胞疗法的未来发展趋势。近日，Biomedicines发表了一项题为“Application of CAR-T Cell Therapy beyond Oncology: Autoimmune Diseases and Viral Infections”的综述，在这篇综述中，研究人员通过关注CAR-T在肿瘤治疗领域之外的疾病，比如自身免疫性疾病和病毒感染，包括SARS-CoV-2，从全新的角度概述了CAR-T细胞疗法的现代趋势和最新发展[1]。图1 研究成果（图源：Biomedicines）CAR-T细胞疗法全称Chimeric antigen receotor T cell therapy，即嵌合抗原受体T细胞疗法。其原理是采集患者自身的T细胞，在体外通过基因技术对其进行改造，装载上具有识别肿瘤抗原的受体和共刺激分子，同时将其进行体外扩增之后再次输回患者体内，使其能够有效识别并更加精准地杀伤肿瘤细胞。尽管病因不同，但部分疾病的发病机制可能与肿瘤存在相似之处，这些共性可能使它们能够通过CAR-T疗法获得治疗。此外，在很多情况下，人类免疫系统会因疾病的发生而出现部分功能障碍，CAR-T则可以作为人类免疫系统的强大替代品，对人体起到一定保护作用。CAR-T细胞与自身免疫性疾病很多自身免疫性疾病（Autoimmune diseases，AIDs）的发病机制仍尚未得到确定，但可以确定的是，T细胞耐受失败在这类疾病的发病过程中起着重要作用。AID中免疫自我耐受性丧失的潜在机制包括激活自身反应性B细胞，从而产生促进组织损伤的自身抗体，以及抑制细胞毒性或调节性T细胞。嵌合自身抗体受体（Chimeric autoantibody receptor，CARR）T细胞靶向自身反应性B细胞表面的自身抗体蛋白，只针对携带特定自身抗体的免疫细胞有选择性细胞毒性，而不会导致免疫抑制。因此，这种细胞可直接消除表面免疫球蛋白记忆B细胞，间接消除产生致病性自身抗体的短暂浆细胞。此外，由于自身免疫性疾病中调节性T细胞（Tregs）在AID中通常受到抑制，研究人员通过将FOXP3转导到T细胞形成CAR-Tregs，以调节患者体内Tregs的功能和活力。图2 嵌合自身抗体受体和嵌合抗原受体活性机制（图源：Biomedicines）已经有研究使用CARR-T细胞治疗寻常型天疱疮（Pemphigus vulgaris，PV），这是一种自身免疫性疾病，由针对角质形成细胞粘附蛋白Dsg3的自身抗体引起。研究人员利用CARR-T细胞的原理设计出Dsg3-CARRT细胞，将其输入PV小鼠模型中，观察到该细胞疗法在PV小鼠模型体内显示出抗Dsg3 B细胞的特异性消除，同时未出现任何不良反应。表1 CAR-T细胞疗法在肿瘤学之外的临床试验列表表格来源：Biomedicines除此以外，CAR-T细胞疗法还被应用于研究血友病、1型糖尿病、多发性硬化症、全身性重症肌无力、系统性红斑狼疮、视神经脊髓炎谱系障碍等自身免疫性疾病的治疗中。CAR-T细胞疗法与传染性疾病慢性乙型肝炎病毒（Hepatitis B virus，HBV）患者通常免疫力低下，长期发展下去很有可能会导致肝癌的发生。基于CAR-T细胞疗法，研究人员设计了一种能特异性识别乙肝病毒表面抗原（Hepatitis B virus surface antigen，HBsAg）的CAR-T细胞，在体外评估了其识别HBV+细胞和HBsAg颗粒的能力，在人肝嵌合小鼠模型中检测其对HBV感染的肝细胞的功效。结果表明，抗HBsAg-CAR T细胞在体外可识别HBsAg颗粒和HBV+细胞，并且在小鼠体内可有效降低HBV-DNA和HBsAg水平。慢性丙型肝炎病毒（Hepatitis C virus，HCV）感染是对当前治疗无反应的终末期慢性感染患者进行肝移植的医学指征。对于很多HCV患者来说，治疗后再次感染的风险仍然很高，这意味着需要开发出有效的替代性疗法。为此，研究人员设计了可识别HCV E2糖蛋白（宿主免疫反应的主要靶标）的CAR-T细胞，结果表明抗HCV/E2 CAR-T细胞对HCV感染的细胞表现出显著的细胞毒性。此外，还有更多研究人员试图探索CAR-T细胞疗法在其他病毒传染性疾病中的作用。比如，人类巨细胞病毒感染以及甲型流感病毒感染。以上研究为进一步探索CAR-T细胞疗法在各种传染性疾病中的治疗提供了依据。CAR-T细胞疗法与其他难治性疾病艾滋病是一种获得性免疫缺陷综合征，由人免疫缺陷病毒引起，发病缓慢，潜伏期可长达15年，死亡率极高。至今，艾滋病仍然是世界性医疗难题，一旦感染病毒无法治愈，只能通过抗病毒治疗控制病情的发生及发展。由于CD8+ T细胞对HIV-1的细胞毒性在控制HIV-1感染中起着关键作用，也因此为将CAR-T细胞疗法用于HIV-1的治疗提供了有效途径。抗HIV-1 CAR-T细胞的治疗靶点为HIV感染细胞表面表达的HIV包膜糖蛋白的gp120区域。研究人员设计了CD4+ CAR-T细胞，经过体外试验，研究人员发现，CD4+ CAR-T细胞能够有效抑制HIV病毒的复制，同时破坏了HIV病毒感染的T细胞。此外，研究人员发现，接受CAR-T细胞疗法治疗的患者，其病毒反弹率较低，肠道HIV DNA显著减少，这表明CD4+ CAR-T细胞确实可以影响组织病毒库。图3 CAR-T细胞疗法在艾滋病治疗中的应用（图源：Biomedicines）除了艾滋病，CAR-T细胞疗法也被应用于COVID-19的治疗中。研究人员试图开发CAR-NK细胞以靶向具有CR3022 scFv结构域的SARS-CoV-2刺突蛋白，通过体外试验，他们发现CR3022 CAR-NK细胞能够消除SARS-CoV-2感染的细胞。除此之外，评估双特异性NKG2D-ACE2 CAR-NK细胞疗法的临床试验（图4）也正在进行中。图4 CAR-T细胞疗法在COVID-19治疗中的应用（图源：Biomedicines）从以上研究可以看出，随着对各种病理学及其分子机制的理解和认识不断发展，CAR-T细胞免疫疗法在医疗上的应用将远远超出肿瘤领域范畴。越来越多的分子被证实为多种疾病的治疗靶点，这使得CAR-T细胞疗法将成为一种有吸引力且极具前景的治疗选择。表2 可以通过CAR-T细胞疗法治疗的疾病列表和相应的靶点表格来源：Biomedicines从肿瘤到自身免疫性疾病，再到各种传染性疾病，CAR-T细胞疗法的应用范围正在不断拓展，相信随着疾病靶点的不断增加以及CAR-T细胞技术的不断升级，未来或许会有更多难治性疾病可以通过CAR-T细胞疗法得以治疗，实现百病且可CAR-T。题图来源：DONLIN LABORATORY，仅用于学术交流。撰文|木子久排版|文竞择 End 参考资料：[1]Zmievskaya E, Valiullina A, Ganeeva I, et al. Application of CAR-T Cell Therapy beyond Oncology: Autoimmune Diseases and Viral Infections. Biomedicines. 2021 Jan 9;9(1):59. doi: 10.3390/biomedicines9010059. PMID: 33435454; PMCID: PMC7827151. 本文系生物探索原创，欢迎个人转发分享。其他任何媒体、网站如需转载，须在正文前注明来源生物探索。往期精选围观“甜蜜的毒药”：这种常喝饮料致肝癌风险增加高达78%！热文『麦趣尔』牛奶中检出的『丙二醇』，是为何物？对身体有何影响？热文福奇：服用Paxlovid治疗新冠，转阴3天后复阳，症状却更严重！热文全球感染率最高的感染病，50%中国人中招，共餐、接吻更易感染？热文逆龄抗衰还可治疗抑郁！「粪便」入药真的有科学依据？点击“阅读原文”，了解更多~

基因疗法抗体孤儿药细胞疗法免疫疗法突破性疗法

100 项与盐酸胍立莫司相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	盐酸胍立莫司	L04AA19	DB12991

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
肾移植排斥反应	日本	Nippon Kayaku Co., Ltd.	1994-01-19

未上市

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适应症	最高研发状态	国家/地区	公司	日期
多发性硬化症	申请上市	法国	Nippon Kayaku Co., Ltd.	-
多发性硬化症	申请上市	德国	Nippon Kayaku Co., Ltd.	-
肉芽肿伴多血管炎	临床3期	德国	Nordic Ltd.	-
肉芽肿伴多血管炎	临床3期	西班牙	Nordic Ltd.	-
肉芽肿伴多血管炎	临床3期	瑞典	Nordic Ltd.	-
肉芽肿伴多血管炎	临床3期	英国	Nordic Ltd.	-
韦格纳肉芽肿	临床2期	捷克	Nippon Kayaku Co., Ltd.	2003-12-01
韦格纳肉芽肿	临床2期	丹麦	Nippon Kayaku Co., Ltd.	2003-12-01
韦格纳肉芽肿	临床2期	德国	Nippon Kayaku Co., Ltd.	2003-12-01
韦格纳肉芽肿	临床2期	荷兰	Nippon Kayaku Co., Ltd.	2003-12-01

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临床结果

适应症

分期

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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


NCT00709722 (Pubmed \| Arthritis Res Ther)	临床1/2期	狼疮性肾炎	21	15-deoxyspergualin	遞襯鹹範遞齋艱鹹遞淵(窪繭鏇壓鬱艱鑰鑰廠餘) = Five patients dropped out due to adverse events or serious adverse events including fever, leukopenia, oral candidiasis, herpes zoster or pneumonia 鑰觸壓遞齋製鹹築衊鬱 (餘繭觸構願餘構觸簾鹽 ) 更多	-	2011-04-01
EULAR2004	临床1/2期	肾小球肾炎	3	15-Deoxyspergualin (15-DSG)	繭艱夢壓衊鹽窪獵顧願(鏇觸餘觸網襯壓憲築願) = No SAE were observed 選願範憲積範構積製廠 (鹹蓋範廠糧蓋鹹膚壓範 )	积极	2004-06-09