Purpose: Risk of severe psychopathology increases dramatically during adolescence, especially for females. Changes in ovarian steroids across the menstrual cycle produce windows of vulnerability to mood disturbances, particularly during the abrupt withdrawal of estradiol (E2) and progesterone (P4) prior to menses onset. Irrefutable evidence links stress with affective symptoms, potentially mediated by E2-related modifications of frontolimbic connectivity and prefrontal gamma-aminobutyric acid (GABA) inhibitory signaling. The primary objective of this project is to empirically test the impact of E2 and P4 change on vulnerable brain networks associated with irritability and other depressive symptoms in female adolescents at risk of suicide.
Participants: The investigators will enroll 50 female adolescents ages 12-16 who are at risk of suicide (i.e., moderate depressive symptoms), and are eligible to receive oral contraceptives and undergo MRI imaging.
Procedure: Using a randomized, placebo-controlled, cross-over design, participants will be studied under two conditions: 8 weeks of E2 and P4 stabilization (continuous combined oral contraceptive (COC) to prevent perimenstrual withdrawal) and 8 weeks of placebo, with a 1-month washout after each condition. Each condition will include: 1) daily samples of E2 and P4 urinary metabolites, 2) daily symptom ratings(e.g., irritability, negative affect and suicidal thoughts and behaviors (STBs)), and 3) a neuroimaging session with MRI and magnetic resonance spectroscopy (MRS).

开始日期2026-10-01

申办/合作机构

The University of North Carolina at Chapel Hill

NCT07792408

/ Recruiting临床1期

A Phase 1, Open-label Drug Interaction Study to Evaluate the Effect of VX-407 on the Pharmacokinetics of Combined Oral Contraceptives

The purpose of the study is to evaluate the pharmacokinetic effects and safety and tolerability of VX-407 when coadministered with oral contraceptives.

开始日期2026-09-01

申办/合作机构

Vertex Pharmaceuticals, Inc.

NCT07784894

/ Recruiting临床1期

A Phase 1, Open-Label, Fixed Sequence, 1-Way Drug-Drug Interaction Study to Investigate the Repeat-Dose Pharmacokinetics of Microgynon, an Oral Contraceptive Containing Ethinyl Estradiol and Levonorgestrel, When Administered Alone and in Combination With Ganfeborole in Healthy Female Participants of Non-Childbearing Potential Aged 18-65 Years Old

This study is designed to assess the pharmacokinetics (PK), safety, and tolerability of Ganfeborole and Microgynon, an oral contraceptive containing ethinylestradiol (EE) and levonorgestrel (LNG), when Microgynon is administered alone and in combination with Ganfeborole in healthy female participants of non-childbearing potential.

开始日期2026-08-20

申办/合作机构

GSK Plc

100 项与左炔诺孕酮/炔雌醇相关的临床结果

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100 项与左炔诺孕酮/炔雌醇相关的转化医学

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100 项与左炔诺孕酮/炔雌醇相关的专利（医药）

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705

项与左炔诺孕酮/炔雌醇相关的文献（医药）

2025-11-01·ATHEROSCLEROSIS

Targeting LDL aggregation decreases atherosclerotic lipid burden in a humanized mouse model of familial hypercholesterolemia: Crucial role of ApoB100 conformational stabilization

Article

作者: Caruana, P ; Tondo, M ; Pepe, A ; Céspedes, M V ; Martínez, A ; Borràs, C ; Escola-Gil, J C ; Prades, R ; Cenarro, A ; Llorente-Cortés, V ; Garcia, E ; Civeira, F ; Benitez-Amaro, A ; La Chica Lhoëst, M T ; Bochicchio, B

BACKGROUND AND AIMS:

Low-density lipoprotein (LDL) aggregation is nowadays considered a therapeutic target in atherosclerosis. DP3, the retro-enantio version of the sequence Gly¹¹²⁷-Cys¹¹⁴⁰ of LRP1, efficiently inhibits LDL aggregation and foam cell in vitro formation. Here, we investigate whether DP3 modulates atherosclerosis in a humanized ApoB100, LDL receptor (LDLR) knockout mice (Ldlr^-/-hApoB100 Tg) and determine the potential LDL-related underlying mechanisms.

METHODS:

Tg mice were fed an HFD for 21 days to induce atherosclerosis and then randomized into three groups that received a daily subcutaneous administration (10 mg/kg) of i) vehicle, ii) DP3 peptide, or iii) a non-active peptide (IP321). The in vivo biodistribution of a fluorescent-labeled peptide version (TAMRA-DP3), and its colocalization with ApoB100 in the arterial intima, was analyzed by imaging system (IVIS) and confocal microscopy. Heart aortic roots were used for atherosclerosis detection and quantification. LDL functionality was analyzed by biochemical, biophysical, molecular, and cellular studies.

RESULTS:

Intimal neutral lipid accumulation in the aortic root was reduced in the DP3-treated group as compared to control groups. ApoB100 in LDLs from the DP3 group exhibited an increased percentage of α-helix secondary structures and decreased immunoreactivity to anti-ApoB100 antibodies. LDL from DP3-treated mice were protected against passive and sphingomyelinase (SMase)-induced aggregation, although they still experienced SMase-induced sphingomyelin phospholysis. In patients with familial hypercholesterolemia (FH), DP3 efficiently inhibited both SMase-induced phospholysis and aggregation.

CONCLUSIONS:

DP3 peptide administration inhibits atherosclerosis by preserving the α-helix secondary structures of ApoB100 in a humanized ApoB100 murine model that mimicks the hallmark of human hypercholesterolemia.

2025-05-01·Acta Biomaterialia

A highly transparent dopamine-copolymerized hydrogel with enhanced ROS-scavenging and tissue-adhesive properties for chronic diabetic wounds

Article

作者: Zhang, Haiqi ; Wang, Jinze ; Ma, Lie ; Hu, Hongtao

Chronic diabetic wounds with complex symptoms represent a major challenge in clinical practice, causing a serious threat to human health and life. Excessive oxidative stress and persistent inflammatory responses are the important reasons for the long-term difficult healing of diabetic wounds. Designing wound dressing materials with intrinsic antioxidant performance, high transparency, adhesiveness, and favorable mechanical properties is of great significance for promoting wound healing, especially in movable parts. Here, a dopamine-copolymerized highly transparent antioxidant hydrogel was developed for the treatment of chronic diabetic wounds. The hydrogel was easily prepared via free radical polymerization using acrylated dopamine monomer (ADA), acrylamide (AM), and phenylboronic acid modified dextran (DP). The dynamic phenylborate ester bonds formed between the catechol of polydopamine and phenylboronic acid effectively mitigated the darkening of the hydrogel color caused by the auto-oxidation of catechol, resulting in the PAM/PDA/DP hydrogel (DP3) with durable transparency. In addition, this hydrogel had good adhesiveness and mechanical properties, as well as desirable reactive oxygen species (ROS)-scavenging performance. Furthermore, in vivo results demonstrated that DP3 hydrogel can stimulate the polarization of macrophages toward anti-inflammatory M2 phenotype, increase the secretion of anti-inflammatory factors, so as to smooth the transition of wound healing from the inflammatory phase to the proliferative phase, and accelerate the repair of diabetic wounds by promoting angiogenesis and collagen deposition. Therefore, the DP3 hydrogel holds great potential for remolding the tissue regeneration microenvironment and serving as a promising dressing for chronic diabetic wounds. STATEMENT OF SIGNIFICANCE: Polydopamine (PDA)-based hydrogels have been widely explored. However, existing PDA-based hydrogels suffer from low content of catechol groups and inferior transparency, and are prone to oxidation darkening during storage. In this study, a dopamine-copolymerized hydrogel with high catechol content was developed. The catechol groups are partially protected by phenylboronic acid-modified dextran, resulting in durable transparency and good adhesiveness of the hydrogel. The hydrogel exhibits desirable antioxidant performance and can effectively promote chronic diabetic wound healing by relieving oxidative stress and regulating immune function. This highly transparent hydrogel with intrinsic antioxidation and self-adhesiveness properties represents a potential and effective strategy for chronic wound management.

2025-05-01·Small

Inhibition of Insulin Amyloid Fibrillogenesis Using Antioxidant Copolymers with Dopamine Pendants

Article

作者: Tamanna Mallick ; Shubham Das ; Priyadarsi De ; Anushree Mondal

Abstract:

Amyloid aggregation, intricately related to various neurodegenerative and metabolic diseases, presents a significant growing health challenge. Dopamine, a potent antioxidant, plays a pivotal role in modulating protein misfolding by leveraging its potent anti‐amyloidogenic and neuroprotective properties. However, its biological applications are limited by poor aqueous solubility and suboptimal biocompatibility. To address these challenges, water‐soluble copolymers ( DP1 ‐ DP3 ) featuring dopamine and glucose side‐chain pendants are fabricated and investigated for their efficacy in inhibiting amyloid fibril formation from insulin and amyloid beta (A β42 ) peptide. The effects of DP1 ‐ DP3 copolymers on amyloid fibrillation are assessed using several biophysical techniques, which demonstrate excellent radical scavenging properties and the remarkable efficacy of DP3 copolymer in suppressing insulin amyloid fibrillation, achieving ≈97% inhibition. Isothermal titration calorimetry (ITC) and fluorescence binding experiments are carried out to quantify the insulin‐ DP3 complex formation. Molecular dynamics simulations validate the ability of DP3 to prevent amyloid fibrillogenesis of both insulin and A β42 . These studies demonstrate beneficial interactions between DP3 and amyloidogenic protein/peptide, facilitating the stability of the resulting complexes. Overall, the present findings suggest that dopamine‐based antioxidant polymers hold significant potential as advanced therapeutic agents for preventing amyloidogenic disorders.

项与左炔诺孕酮/炔雌醇相关的新闻（医药）

2026-10-06

·PRNewswire

Mint Pharmaceuticals Inc. and Bayer Inc. Expand Distribution Partnership in Canada

Expanded collaboration supports continued Canadian access to Bayer medicines across cardiovascular and women's health portfolios. MISSISSAUGA, ON, Oct. 6, 2026 /PRNewswire/ -- Mint Pharmaceuticals Inc. is pleased to announce the expansion of its distribution partnership with Bayer Inc. to include ANGELIQ® (drospirenone and estradiol-17β tablets), CLIMARA® 25, CLIMARA® 50 and CLIMARA® 75 (estradiol hemihydrate transdermal systems), TRIQUILAR® 21 and TRIQUILAR® 28 (levonorgestrel and ethinyl estradiol tablets), and XARELTO® (rivaroxaban granules for oral suspension) in Canada. The expanded collaboration builds on the companies' existing relationship and shared commitment to reliable access to medicines for Canadian patients and healthcare professionals. Continue Reading Olenka Crewe, VP of Business Development & Scientific Affairs, Mint Pharmaceuticals, Jaiveer Singh, CEO, Mint Pharmaceuticals, Viktoria Friedrich, President and CEO of Bayer Inc. in Canada. Jennifer Lloyd, Head of Finance, Pharmaceutical Division, Bayer Inc. (CNW Group/Mint Pharmaceuticals) The partnership was originally established to support the Canadian distribution of Bayer's ADALAT® XL® (nifedipine extended-release tablets), an antihypertensive / antianginal medicine. The addition of ANGELIQ®, CLIMARA®, TRIQUILAR®, and XARELTO® extends the collaboration across a broader range of therapeutic areas while maintaining the companies' focus on dependable supply and continuity of care. "Ensuring Canadian patients and healthcare professionals can rely on consistent access to established medicines is central to Mint's mission," said Jaiveer Singh, Chief Executive Officer of Mint Pharmaceuticals. "Expanding our work with Bayer allows us to apply Mint's resilient supply chain and nationwide distribution capabilities across a broader portfolio, while advancing our mutual focus on reliability, quality and patient care." "We are pleased to expand our partnership with Mint Pharmaceuticals Inc., building on a trusted collaboration rooted in quality, reliability and a shared commitment to patient care," said Viktoria Friedrich, President and CEO of Bayer Inc. in Canada. "By broadening this partnership across additional Bayer medicines, we can continue to leverage Mint's strong Canadian distribution network and market expertise to help ensure these treatments remain accessible to healthcare professionals and patients who rely on them." Through this expanded partnership, Mint Pharmaceuticals and Bayer Inc. aim to maintain high standards of distribution and supply continuity across the portfolio, helping ensure that healthcare professionals and patients across Canada have timely access to these medicines. About Mint Pharmaceuticals Mint Pharmaceuticals is a leading Canadian-owned and operated manufacturer of high-quality, affordable generic medicines. Mint has built one of the strongest and most resilient pharmaceutical supply chains in the country, helping safeguard patient access by averting 25 national drug shortages across 16 essential medicines in the last decade. The company has been recognized by Deloitte as one of Canada's Best Managed Companies for eight consecutive years, achieving Platinum Club status in 2025, and is a member company of the Canadian Generic Pharmaceutical Association (CGPA). About Bayer Bayer is a global enterprise with core competencies in the life science fields of health care and nutrition. In line with its mission, "Health for all, Hunger for none," the company's products and services are designed to help people and the planet thrive by supporting efforts to master the major challenges presented by a growing and aging global population. Bayer is committed to driving sustainable development and generating a positive impact with its businesses. At the same time, the Group aims to increase its earning power and create value through innovation and growth. The Bayer brand stands for trust, reliability and quality throughout the world. In fiscal 2025, the Group employed around 88,000 people and had sales of 45.6 billion euros. R&D expenses amounted to 5.8 billion euros. For more information, go to . Find more information at and at . SOURCE Mint Pharmaceuticals 21% more press release views with Request a Demo

2026-05-08

·药研

CDE老师文章｜FDA完整回复函药学缺陷对我国化学药药学审评的启示

美国食品药品监督管理局（FDA）为按时完成审评任务目标，制定了单轮审评期间灵活的资料发补方式，包括信息请求函和专业审评函；一轮审评结束后则采用完整回复函（Complete Response Letters，CRLs）发补[1]。CRLs是FDA在完成药品上市申请审评后，向申请人发出的正式书面通知，详细说明申请中存在的、阻碍批准的全部缺陷。这些缺陷可能涉及安全性、有效性和/或质量（药学）方面。CRLs发出意味着申请品种尚不能批准，申请人后续需在规定时间内采取措施，包括解决CRLs中所有问题并重新提交、撤回申请或者开会讨论[2]。历史上，CRLs仅发送给申请人，不为公众所知。为提升监管透明度，提高药品一轮审评通过率，2025年7月10日，FDA通过openFDA网站[3]首次公开了2020—2024年间已获批202个药物的CRLs。随后于2025年9月宣布将“实时发布”新签发的CRLs，并同时公布了89份涉及未决或撤回申请的历史CRLs[4]。 FDA法案505节描述了3种类型的药品申请：（1）包含安全性和有效性研究完整报告的申请[505（b）（1）节]；（2）包含安全性和有效性研究的完整报告，但其中批准所需的部分资料并非来自申请人进行的研究，且申请人未获得引用权的申请[505（b）（2）节]；（3）包含信息表明申报产品与之前已批准的产品具有相同的活性成分、剂型、规格、给药途径、标签、质量、性能特征、预期用途及其他申请[505（j）节][5]。FDA已公布215个化学药物CRLs，其中按照505（b）（1）申报的36个（占比16.7%），按照505（b）（2）申报的147个（占比68.4%），此外还有2个上市后补充申请的申报以及多个品种申报信息缺失，其中128个（占比59.5%）存在药学缺陷。由于所有公开的CRLs均经过脱敏处理，很多药学信息未能在CRLs中完全体现。本文通过梳理CRLs可获取公开信息中的药学缺陷共性问题，结合审评工作经验进行分析，为化学药的研发与监管提供借鉴，重点对处方工艺研究和工艺验证、质量标准、杂质研究、稳定性等代表性缺陷进行讨论。 1 处方工艺和工艺验证统计显示，约15个药物（占比7%）的CRLs明确指出了工艺研究和工艺验证方面的缺陷。主要问题包括：（1）处方工艺缺陷：处方工艺变更后研究不完善，桥接研究不满足要求。如注射用硼替佐米（Bortezomib for Injection）因批处方和生产工艺变更导致复溶时间延长，且缺乏与对照药（Velcade）理化性质的对比数据，FDA要求进行一致性对比研究，若存在差异需论证其不影响有效性和生物等效性。多奈哌齐贴剂（Adlarity）的商业化生产工艺与关键临床批次存在显著差异，且缺乏有效的体外桥接数据，FDA建议采用商业化产品与多奈哌齐片（Aricept）进行生物等效性桥接研究；同时，长期稳定性数据显示释放度和渗透量显著变化，需补充稳定性末期与初期样品的生物等效性研究。（2）工艺验证缺陷：工艺验证批量不符合要求，验证内容无法涵盖工艺，无菌验证不完善。如复方布洛芬片（Combogenic）因工艺验证批批量小于商业批，被要求参照FDA工艺验证指南[6]采用商业化规模进行验证。锝气体（Technegas Kit）被要求提供在高锝酸钠放射性负载最小和最大条件下至少3批的工艺验证数据。另外，无菌验证也提出多个缺陷，包括过滤器完整性测试、细菌截留研究、无菌工艺模拟验证缺失或不足等方面的缺陷。虽然CRLs中直接涉及处方工艺研究和工艺验证的缺陷比例看似不高，但这些往往是决定药物能否获批的关键，尤其对于复杂制剂（如缓释微球、透皮贴剂、复杂原料药等）。FDA重点关注处方变更以及稳定性期间质量变更的桥接研究，在体外研究难以充分表征其体内行为时，会提出开展体内桥接的要求。ICH Q8[7]对药物开发提出了基本要求。工艺验证的缺陷，反映了申请人对工艺控制的理解深度不足以及对相关指南要求掌握不全面。监管机构关注现行的处方工艺能够稳定持续生产出质量合格产品，因此在开发及验证中需提供尽可能多的数据支持。我国发布的《工艺验证检查指南》[8]可作为上市申报时工艺验证的重要参考。 2 质量标准约35个药物（占比16%）的CRLs明确指出质量标准存在缺陷，主要体现：（1）控制项目不全面。例如注射剂缺少装量控制；口溶膜缺少柔韧性和拉伸强度控制；鼻喷剂缺少液滴粒度分布控制；预充针缺少剂量准确性和滑动力控制；利培酮长效注射液（Risvan）缺少关键辅料乙交酯丙交酯共聚物的分子量控制；布洛芬长效注射液（Brixadi）缺少辅料乙醇含量及递送剂量检测项。（2）控制限度不严格。溶出度限度或关键取样点设置不当，如利培酮微球（Rykindo）被建议增加72小时溶出度取样点并收严56小时限度；杂质限度、含量（主成分/关键辅料）限度、崩解时限等不合理。（3）分析方法选择不合理。如硫酸羟氯喹片（Souvna）原料药是高溶解性药物，FDA建议采用其2018年指南[9]中的标准溶出方法，并要求说明自拟方法的理由及进行对比研究。硫代硫酸钠注射液（Pedmark）的含量测定方法与美国药典[10]方法不同，但未进行方法可比性研究，无法证明其优势。（4）方法验证不充分。例如多个CRLs指出浸出物检测等方法未经验证。与无菌药品相关的质量缺陷还包括微粒问题和密封性问题。3个注射剂存在不溶性微粒或颗粒污染问题，被要求进行原因调查。3个品种的容器密封性研究存在缺陷，如葡萄糖氯己定异丙醇溶液（SoluPrep）方法灵敏度低（仅能检出50μm以上泄漏）；呋塞米注射液（Furoscix）需提供完整的微生物和染料侵入测试结果；Risvan需验证在压力和真空条件下的密封性（可能因临床使用涉及注射器互推混合）。相较于传统剂型，特殊制剂更易出现控制项目缺失。ICHQ6A[11]为质量标准的制定提供了基本框架。药物的质量研究是质量标准制订的基础，质量研究的内容应尽可能全面，既要考虑一般性要求，又要有针对性。拟定质量标准的项目和限度需基于研发数据、药典标准、毒理/临床研究数据、稳定性结果、方法性能及生产波动进行充分论证，以使质量研究的内容能充分地反映产品的特性及质量变化的情况。若某项检测对质量控制至关重要，则应纳入标准。采用非药典方法时，需进行与药典方法的对比研究，择优使用，特别是涉及杂质检测方法时，需考虑采用富含杂质的样品对比方法的杂质分离和检出能力。无菌是注射液最基本的要求，应从物料、工艺、质控、包装全方面加强无菌控制，对于出现的与无菌相关的任何问题应引起足够重视，充分调查，守好安全底线。 3 杂质研究约37个药物（占比17%）的CRLs提示存在杂质缺陷，其中约27个涉及可提取物和浸出物（Extractables & Leachables，E&L）研究，是杂质缺陷的主要方面。E&L研究问题包括：（1）E&L试验设计缺陷，如斑蝥素溶液（Ycanth）提取条件不充分、注射用硼替佐米未进行稳定性倒置考察、纳洛酮注射液（Zimhi）和注射用对乙酰氨基酚的E&L研究缺乏相关性。（2）浸出物检测方法能力未经验证，如Brixadi要求方法需能检测出毒理学关注阈值（Threshold of Toxicological Concern，TTC，1.5μg/天）水平的杂质。（3）未对检出的浸出物进行结构表征。（4）浸出物毒理学风险评估不充分，如布洛芬长效注射液（Brixadi）被要求对超过界定限度（Qualification Threshold，QT，5μg/天）的杂质进行毒理评估。（5）缺乏长期或加速稳定性条件下的浸出物数据。除E&L外的杂质缺陷包括：（1）杂质研究不充分，如Zimhi的光照降解杂质未表征和评估、Combogenic的元素杂质未按ICH Q3D充分评估。（2）杂质限度宽泛缺乏依据，如注射用米卡芬净钠（Micafungin）超过0.2%的杂质未提供毒理学支持。（3）致突变杂质控制不完善。如对乙酰氨基酚（Acetaminophen）中某些潜在致突变杂质需更新标准或进行标准细菌回复突变（Ames）试验。（4）亚硝胺杂质风险评估和检测数据不足，如肾上腺素鼻喷剂（Neffy）被要求提交亚硝胺原料药相关杂质（NDSRIs）的风险评估和检测数据。杂质控制遵循“识别、评估与控制”原则，应参照ICH Q3[12]、ICH M7[13]等指南。E&L研究不全是高发问题，尤其见于注射剂、吸入剂等高风险包材的制剂。FDA有时允许上市后完善E&L研究，如要求Brixadi上市后提交24个月的浸出物数据并对未知杂质进行安全评估。我国E&L研究现状是申请人委托外部机构研究，对E&L研究的理解不足，缺乏重视。目前，ICH Q3E（可提取物与浸出物）正在国内征求意见[14]并提供系统指导。Neffy案例首次明确了NDSRIs缺陷，成为FDA近期关注点。我国对亚硝胺杂质的监管也非常重视，从临床早期阶段至上市申报都对亚硝胺杂质的评估以及控制方法提出了要求。亚硝胺杂质研究可参考国内外相关指导原则开展研究[15-16]。 4 稳定性约36个药物（占比17%）的CRLs提示稳定性存在缺陷，主要问题包括：（1）数据不足或批次缺乏代表性，如注册批稳定性数据不足，或关键指标在稳定性考察期内超出拟定质量标准，无法支持有效期。（2）试验设计不全面，如利扎曲普坦口溶膜（RizaFilm）缺少光稳定性研究；Brixadi缺少冻融和倒置研究；Risvan需额外开展热循环研究。（3）考察项目不全面，如氟维司琼注射液（Pulvestrant）长期稳定性缺乏浸出物考察（FDA允许用加速数据替代）。（4）溶液配伍研究缺陷，如磷苯妥英钠注射液（Sesquient）说明书提及可用5%葡萄糖和0.9%氯化钠配伍，但仅对后者进行了研究，需补充前者。（5）稳定性承诺需完善，如甘露醇（Bronchitol）因提交数据有问题，被建议在承诺中增加3个月时间点的含量考察。稳定性研究是药物在有效期内保持质量稳定可靠的支持依据。ICH Q1系列[17]提供了基本要求。试验设计需周全，涵盖项目、指标和方法。应结合产品特性开展专门研究，如Risvan因辅料乙交酯丙交酯共聚物对温度敏感，需进行热循环研究以确保短期冻融不影响质量。还需模拟临床使用条件进行稳定性考察，特别是配液后可能面临长期储藏要求的药物，可参照国内注射剂配伍指南[18]。对于新药，稳定性数据不足常见，申报时可提供支持性批次数据并附上可行的稳定性承诺。 5 辅料安全性约5个药物（占比2%）的CRLs明确提示辅料安全性缺陷，主要问题为安全性依据不足：（1）Combogenic中乳糖需提供牛海绵状脑病（Bovine Spongiform Encephalopathy，BSE）和传染性海绵状脑病（Transmissible Spongiform Encephalopathy，TSE）合规认证。（2）Pulvestrant中辅料中链甘油三酯安全性依据不足。（3）肾上腺素吸入剂（Primatene Mist）中百里香酚（Thymol）安全性依据不足。（4）布比卡因和美洛昔康缓释溶液（Zynrelef Kit）中二甲基亚砜和马来酸等辅料安全性依据不足。（5）利多卡因透皮贴剂（ZTlido）中异山梨酸等辅料安全性依据不足。辅料安全性评价是基于风险-获益评估过程，应该从适应证、给药途径、使用量、使用人群、用药周期等方面综合考虑。注射剂辅料风险高，FDA要求上市前完成安全性研究，如Pulvestrant在补充中链甘油三酯毒理研究后获批上市。外用制剂风险相对较低，FDA案例提示可能允许上市后完善，如ZTlido承诺上市后进行6个月啮齿动物研究。 6 药品生产质量管理规范（GMP）合规性约44个药物（占比20.5%）在上市前检查中发现GMP合规性缺陷，成为CRLs中非常显著的缺陷项。FDA通常要求申请人整改后再批准。我国《药品生产监督管理办法》[19]规定进行上市前的GMP符合性检查，拟生产药品需要进行药品注册现场核查的，同步开展药品注册现场核查和上市前的GMP符合性检查。其中，药品注册现场核查结果不符合规定的，按照《药品注册管理办法》[20]要求，不予批准。FDA大量的GMP合规性缺陷既是对我国生产企业GMP合规性的警示，同时也是学习的重要机会。 7 其他问题除上述共性问题外，还存在一些代表性缺陷：（1）说明书和标签，如Pedmark 规格表述需与美国药典（USP）统一、环磷酰胺（Cyclophosphamide）需标注辅料/乙醇用量、Twirla药品名称/规格信息缺失、丁苯诺啡和纳洛酮（Cassipa）需明确活性成分形态为游离碱、奥曲肽（Mycapssa）名称中需增加“迟释”字样等。（2）人因研究，约16个药物（占比7%）存在缺陷，主要涉及复杂给药装置（吸入剂、自动注射器、鼻喷剂等），如Bronchtol给药剂量不准确/不均一、设备设计/测试/验证不完善（如磷卡比多巴/磷左旋多巴（Vyalev）输注泵性能与耐久性测试不足；帕罗培特立帕肽（Yorvipath）含量和递送剂量变异性及不合格率高）、潜在安全风险（如Ycanth安瓿破碎力过大导致使用困难和伤害风险）。药械组合产品需在开发早期系统进行器械性能设计与验证。 8 讨论与建议 8.1 重视和加强药学研究的沟通交流 FDA发布的CRLs药学缺陷在上市申请中的高发性（59.5%）表明，这已成为系统性的行业挑战，而非个别案例。多个药物仅因药学问题（如Zituvio因杂质含量高）未能获批，或需在上市前重新评估重大处方工艺缺陷，提示申请人必须在研发早期即重视药学的基础作用，并就重大变更与监管机构保持充分沟通。CRLs更多情况下涵盖临床、非临床、药学、GMP合规等多方面的缺陷，对于其中涉及的药学缺陷也需要理性看待。 8.2 强化药品质量体系建设 FDA发布CRLs的举措，体现其监管的透明性，也为我国制药行业提供了宝贵的借鉴。汇总的缺陷反映出部分企业在药品质量体系、风险管理能力和监管合规方面存在差距，突出表现在杂质研究、工艺验证、微生物控制和GMP符合性等方面。未来，上市许可持有人需持续完善药品质量风险管理体系，持续改进药品质量体系，加强从研发、技术转移、商业生产到临床应用终止全生命周期的合规性管理。 8.3 加速跟进先进监管理念与要求 CRLs不限于药学专业缺陷，还包括整个药品注册过程中临床、药理毒理等各专业的缺陷问题。CRLs对于我国的监管及研发都提供了重要参考。监管机构可借鉴审评缺陷案例掌握FDA审评要求和尺度，进一步提高审评审批质效。企业可将这些缺陷作为国际化申报的预审清单，提前在研发阶段排查高风险环节，提升申报成功率。 8.4 加强宣传与引导 2024年12月30日国务院办公厅发布的《关于全面深化药品医疗器械监管改革促进医药产业高质量发展的意见》（国办发〔2024〕53号）[21]明确提出提高审评审批质效。CRLs与我国药品注册过程中的发补有相似之处，均一次性告知目前申报存在的缺陷，为药物获批上市提出了明确要求。我国监管机构已经建立了相对完备的公开沟通渠道，包括药审云课堂、共性问题专栏、培训宣讲等，针对审评中的共性问题，可以有计划地进行公布或宣讲，引导企业完善药学研究，最终目标是提升药品研发生产能力与产品质量，提高审评效率，让更多安全有效的药品早日惠及患者。参考文献［1］吕旭峰，鞠梦琪，袁利佳，等. FDA 新药审评中补充资料的沟通交流机制研究及启示[J]. 中国新药杂志，2018，27（19）：2209-2213. [2] Code of Federal Regulations. Title 21, Chapter I,Subchapter D, Part 314—Applications for FDA Approvalto Market a New Drug[S/OL]. Washington, DC: Officeof the Federal Register, National Archives and RecordsAdministration. [2025-11-12]. https://www.ecfr.gov/current/title-21/chapter-I/subchapter-D/part-314. [3] FDA. Complete Response Letters[EB/OL]. [2025-1 1 - 1 2 ] . h t t p s : / / o p e n . f d a . g o v / a p i s / t r a n s p a r e n c y /completeresponseletters/. [4] FDA. FDA Announces Real-Time Release of Complete Response Letters, Posts Previously Unpublished Batch of 89[EB/OL]. [2025-11-12]. https://www.fda.gov/newsevents/ press-announcements/fda-announces-real-timerelease- complete-response-letters-posts-previouslyunpublished-batch-89. [5] U.S. Food and Drug Administration. Guidance for Industry: Applications Covered by Section 505(b)(2)[S/OL]. Silver Spring, MD: U.S. Food and Drug Administration. [2025-11-12]. https://www.hhs.gov/guidance/sites/default/files/ hhs-guidance-documents/FDA/Applications-Coveredby- Section-505%28b%29%282%29.pdf. [6] U.S. Food and Drug Administration. Guidance for Industry: Process Validation: General Principles and Practices[S/OL]. Silver Spring, MD: U.S. Food and Drug Administration.[2025-11-12]. https://www.fda.gov/media/71021/download. [7] International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). ICH Harmonised Guideline: Pharmaceutical Development Q8(R2)[S/OL]. Geneva: ICH. [2025-11-12]. https:// database.ich.org/sites/default/files/Q8%28R2%29%20Guideline.pdf. [8] 国家药品监督管理局食品药品审核查验中心. 关于发布《工艺验证检查指南》的通告[EB/OL]. [2025-11-12]. https://www.cfdi.org.cn/cfdi/resource/news/16532.html. [9] U.S. Food and Drug Administration. Guidance for Industry:Dissolution Testing and Acceptance Criteria for Immediate-Release Solid Oral Dosage Form Drug Products Containing High Solubility Drug Substances[S/OL]. Silver Spring, MD:U.S. Food and Drug Administration. [2025-11-12]. https://www.fda.gov/media/70936/download. [10] United States Pharmacopeia and National Formulary. Sodium Thiosulfate Injection[S/OL]. USPNF 2025 Issue 2. Rockville, MD: United States Pharmacopeial Convention, （2025-02-03）[2025-11-12].https://online.uspnf.com/uspnf/document/1_GUID-0DD3909A-71A4-498B- 8953-C5E7F55EB3DC_4_en-US?source=Search%20 Results&highlight=sodium%20thiosulfate. [11] International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). ICH Harmonised Guideline: Specifications: Test Procedures and Acceptance Criteria for New Drug Substances and New Drug Products: Chemical Substances Q6A[S/OL]. Geneva: ICH. [2025-11-12]. https://database.ich.org/sites/default/ files/Q6A%20Guideline.pdf. [12] International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). ICH Harmonised Guideline: Impurities in NewDrug Substances Q3A(R2)[S/OL]. Geneva: ICH. [2025-11-12]. https://database.ich.org/sites/default/files/ Q3A%28R2%29%20Guideline.pdf. [13] International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). ICH Harmonised Guideline: Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk M7(R1)[S/OL]. Geneva: ICH. [2025-11-12]. https://database.ich.org/sites/ default/files/M7_R1_Guideline.pdf. [14] 国家药品监督管理局药品审评中心. 关于公开征求ICH《Q3E：可提取物与浸出物指导原则》指导原则草案及其支持性文件意见的通知[EB/OL]. [2025-11-12]. https://www.cde.org.cn/main/news/viewInfoCommon/8073cfc1c0a300972e391d4a613d44ec. [15] 王胜鹏，赵晓婷，刘刚，等. 药品中亚硝胺类杂质监管与检验技术研究进展[J]. 药物评价研究，2024，47（7）：1631-1637. [16] Burns MJ，Ponting DJ，Foster RS，et al. Revisiting the Landscape of Potential Small and Drug Substance Related Nitrosamines in Pharmaceuticals[J]. Journal of Pharmaceutical Sciences，2023，112(12)：3005-3011. [17] International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). ICH Harmonised Guideline: Stability Testing of New Drug Substances and Products Q1A(R2)[S/OL]. Geneva: ICH. [2025-11-12]. https://database.ich.org/sites/default/files/ Q1A%28R2%29%20Guideline.pdf. [18] 国家药品监督管理局药品审评中心. 关于发布《化学药品注射剂配伍稳定性药学研究技术指导原则（试行）》的通告（2024 年第26 号）[EB/OL]. [2025-11-12].https://www.cde.org.cn/main/news/viewInfoCommon/3c1ae40ec75850f8bff5a24bc4394bd7. [19] 国家市场监督管理总局. 药品生产监督管理办法[EB/ OL].（2020-01-22）[2025-11-17]. https://www.samr.gov. cn/zw/zfxxgk/fdzdgknr/fgs/art/2023/art_65070d0ee03a4109 ac831ee7b3cee51c.html. [20] 国家市场监督管理总局. 药品注册管理办法[EB/OL]. （2020-01-22）[2025-11-17]. https://www.samr.gov.cn/ zw/zfxxgk/fdzdgknr/fgs/art/2023/art_3275cb2a929d4c34ac 8c0421b2a9c257.html. [21] 国务院办公厅. 国办发〔2024〕53 号国务院办公厅关于全面深化药品医疗器械监管改革促进医药产业高质量发展的意见[EB/OL].（2025-01-06）[2025-11-12].http://www.scio.gov.cn/zdgz/jj/202501/t20250106_880144.html. （收稿日期　2025 年11 月20 日　编辑　李亚徽） ------------THE END------------ 内容来源：中国药事 2026年 4 月本文仅作交流学习使用，版权归原作者所有，如有侵权请联系删除，微信：yaoyanluntan

2026-01-15

·同写意

药明合联的“生态野心”

100+全球先锋领袖现场开讲、50+顶尖新基建机构抢先入驻、1000+产业精英面对面链接，中国ADC和核药产业界规格最高、影响力最大、汇聚创新力量最全的年度品牌盛会！ 1月15日，香港股市开盘，东曜药业在停牌两周后恢复股票交易，瞬间成为焦点。这背后不仅因为复牌，更因为一份刚刚公告的收购要约。前一天，ADC研发生产外包领域的龙头药明合联，在发布2025年亮眼盈喜预告的同时，掷出一份收购方案：以每股4港元的价格，现金收购东曜药业全部已发行股份。这个价格，比东曜药业过去30个交易日的平均收盘价高出约114.67%。药明合联在公告中直言，收购旨在快速获取在中国的额外营运产能，强化整体实力，并丰富客户群。几乎在同一时间，药明合联的盈喜公告显示，其2025年营收同比增长超过45%，毛利增长更是超过70%。一边是远超行业平均增速的业绩爆发，一边是溢价超过一倍的果断收购。一增一收之间，是药明合联围绕ADC构建全产业链生态的战略落子，其正在用资本换取最稀缺的资源——时间。 TONACEA 01 “甜蜜烦恼” 药明合联的故事，始于2013年中国ADC行业的“蛮荒时代”。彼时全球仅3款ADC获批，国内尚无自主研发产品，药明生物敏锐捕捉到这一赛道的潜力，在内部成立生物偶联药物业务部（BCD），签下首份ADC CMC合约，成为药明合联的起点。 2020年，药明合联正式注册成立，从药明生物的业务部门独立为法人实体；2023年11月，药明合联在香港联交所上市；同年，无锡新ADC设施XBCM2和XDP2正式投运，上海外高桥基地启动运营，全球布局初见雏形。上市首年，药明合联便交出营收21.2亿元（+114%）、净利润2.8亿元（+82%）的答卷，服务客户达345家，其中包括6家全球Top10药企。随后，药明合联进入“全球份额冲刺期”。2024年，药明合联全年新签iCMC项目53个；新加坡基地破土动工。2025年披露的业绩保持高增长态势，该公司营收增长超45%，毛利增长超70%。经调整净利润（不含利息收入和支出）同比增长超45%，扣除汇率变动影响后，该增长率预期将超过65%。这些数字背后，是客户与项目数量的激增。截至2025年底，药明合联的全球合作客户已超过630家，其一体化项目总数达到252个，全球市场份额从2022年的9.9%飙升超过24%。图源：药明合联公告然而，这份亮眼的成绩单也暴露了药明合联的“甜蜜烦恼”：订单增速远超产能扩张速度。从数据看，其2025年新签70个iCMC项目，PPQ（工艺验证）项目从2024年的8个增至18个，还有1个已落地的商业化项目。按照ADC研发周期，18个PPQ项目中，预计2026-2027年将有至少5个推进至BLA阶段，商业化订单规模将大幅增长。但产能却已逼近极限。目前，药明合联的核心产能集中在无锡基地：偶联制剂年产能1500万瓶，2025年7月新增的DP3生产线投产后，凭借充足订单储备迅速满负荷运行。苏州基地以研发为主，缺乏商业化规模的DP产能。新加坡基地虽计划于2026年年中实现GMP放行，但从投产到满产还需6-8个月，远赶不上PPQ项目的推进节奏。这些项目如同一批整装待发的船只，即将驶入商业化的海洋。它们既是未来收入的保障，也对后端的大规模生产能力提出了即时且苛刻的要求。可以说，这也是全球ADC行业共同面临的“甜蜜的烦恼”。截至2025年底，全球获批的ADC药物已达21款，而处于临床后期的管线正日益丰富，包括AOC、RDC等在内的新型生物偶联药物也在快速崛起。根据弗若斯特沙利文的数据，2025年全球ADC药物市场规模已达172亿美元，预计2032年将突破1151亿美元，年复合增长率超过30%。市场的爆发性增长，使得“高质量、一体化”的商业化产能成为最稀缺的资源。对于药明合联而言，解决产能瓶颈有两条路：自建或并购。自建新生产基地，从选址、建设到通过国际GMP认证，周期通常长达3-5年。这显然无法匹配其手中十多个PPQ项目和潜在客户需求的爆炸性增长节奏。时间，成为比金钱更宝贵的成本。于是，收购东曜药业成为高效的选择。作为国内少数具备“抗体、ADC、制剂”全链条产能的企业，东曜苏州基地拥有2条抗体原液生产线，总产能已突破20000L；2条ADC偶联生产线，ADC原液年产能为960公斤，单次偶联最大规模达500L；2条抗体制剂灌装线（含1条冻干线、1条水针线）、2条ADC制剂灌装线（均为冻干线），且已通过中国、巴西、阿根廷等多国GMP认证。更关键的是，东曜已有成功的商业化交付经验。2025年10月，其支持乐普生物的美佑恒（全球首个EGFR ADC）顺利上市，完成了从技术转移到BLA申报的全流程验证。对于药明合联而言，收购东曜相当于直接“跳过”3年建设期和认证期，获得现成的商业化产能，避免因产能不足错失市场份额。 TONACEA 02 “不可替代” 收购东曜药业，是药明合联全球化产能网络拼图中的关键一块。在此之前，药明合联的产能基地主要分布在中国的无锡、上海、常州，以及正在建设中的合肥和江阴基地。而海外方面，其位于新加坡大士生物医药园的生产基地已于2025年6月机械完工，预计将在2026年开始GMP生产。这张初步的网络，旨在践行其“全球双厂生产”策略，为客户提供地域多元化的供应链保障。此次收购后，东曜的产能可以与药明合联现有的无锡等基地形成协同，在应对国内庞大市场需求的同时，优化生产资源的内部调配。更重要的是，这使其在为客户设计供应链方案时，拥有了更灵活、更可靠的国内支点。可以预期，药明合联的产能扩张脚步不会停止。比如，资金准备上，药明合联在2025年9月完成了3.5亿美元的再融资，拥有充裕的资金储备用于全球拓展。其长期目标明确：到2029年，实现DP产能翻倍，并将多肽类偶联药的年产能提升至40公斤。药明合联预计，2025年至2030年，其营收年复合增长率将保持在30%-35%之间。到2030年，目标是让来自商业化阶段项目的收入贡献占比达到20%，并累计完成12-15个生物制品许可申请的申报。要实现这些目标，稳定且强大的商业化生产能力是根本前提。从更广阔的视角看，药明合联通过自建和并购构建的全球化产能网络，最终是为了夯实一种更深层次的竞争力，即确定性。在创新药研发九死一生的高风险世界里，跨国药企和生物科技公司选择合作伙伴时，考量的不再仅仅是研发能力或生产成本，更是能否提供一条从靶点发现到药品上市、全程可控且可靠的“高速公路”。当一家公司能够确保客户的分子，无论其临床试验成功于世界何地，都能被准时、合规、高质量地生产出来并送达市场，它就从一个技术服务商，蜕变为客户研发管线中不可或缺的基础设施。药明合联的这步棋，关乎的不仅是当下的项目交付，更是未来十年在全球生物制药产业链中，定义行业标准与游戏规则的能力。参考资料：公司公告

抗体药物偶联物财报并购

100 项与左炔诺孕酮/炔雌醇相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	G03AB03 G03AA07	-

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
痛经	日本	Nobelpharma Co., Ltd.	2018-07-02
避孕	美国	Teva Branded Pharmaceutical Products R&D LLC	1982-05-10

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
无先兆偏头痛	临床2期	美国	Teva Branded Pharmaceutical Products R&D LLC	2009-01-01
出血	临床2期	美国	Teva Branded Pharmaceutical Products R&D LLC	2006-10-01
子宫不规则出血	临床2期	美国	Teva Branded Pharmaceutical Products R&D LLC	2006-10-01
丙型肝炎	临床1期	比利时	Pfizer Inc.	2010-06-01

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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


NCT02158572 (Pubmed \| Contraception) 人工标引	临床2期	避孕	2,032	Ethinylestradiol/Levonorgestrel	製顧鬱網壓壓淵觸築憲(構蓋鏇鑰齋觸願夢餘鹹) = 窪艱製夢鹹網壓廠鹹築鹹襯淵齋窪艱簾積鬱艱 (遞餘遞艱積衊範簾積衊 ) 更多	积极	2021-03-01
NCT02493712 (CTgov)	临床2期	溃疡性结肠炎	51	IBD98-M (High Dose Group)	製顧選構廠顧鹹範衊憲 = 築夢遞膚壓築糧蓋夢膚窪醖齋憲膚鹽顧艱齋範 (醖網製網鏇夢醖壓淵淵, 鏇鏇鏇築製餘簾構構鏇 ~ 窪積膚製餘構糧廠廠繭) 更多	-	2020-08-14
				IBD98-M (Low Dose Group)	製顧選構廠顧鹹範衊憲 = 鬱憲醖範窪選襯繭膚膚窪醖齋憲膚鹽顧艱齋範 (醖網製網鏇夢醖壓淵淵, 獵築窪膚積觸壓鹹糧齋 ~ 築繭廠醖鏇餘網鏇鬱餘) 更多
NCT02531321 (CTgov)	临床4期	HIV感染 \| 避孕	17	Levonorgestrel and Ethinyl Estradiol (Ritonavir)	繭簾顧膚簾鏇夢窪獵淵(夢窪齋衊獵夢遞獵遞夢) = 製膚網廠鹽膚鹹簾襯鬱製鏇襯顧蓋糧艱齋齋選 (鹹遞糧獵襯積壓壓餘夢, 61) 更多	-	2019-05-31
				Levonorgestrel and Ethinyl Estradiol (Control)	繭簾顧膚簾鏇夢窪獵淵(夢窪齋衊獵夢遞獵遞夢) = 獵鏇壓衊廠願網築膚淵製鏇襯顧蓋糧艱齋齋選 (鹹遞糧獵襯積壓壓餘夢, 83) 更多
NCT01422135 (CTgov)	临床1期	-	24	EE+LNG (AG200-15)	艱鑰遞顧鑰壓夢築壓顧(願襯獵鏇顧鹹膚鑰顧鹽) = 鑰襯鬱壓艱選廠遞廠製鏇蓋選選觸醖鏇艱鑰醖 (鬱窪構淵鏇餘遞齋網壓, 998) 更多	-	2018-12-31
				EE+LNG (AG200-15 on Lower Abdomen)	糧繭獵鑰鏇範築簾積繭(膚憲網顧鏇繭願構構顧) = 淵網鏇夢獵範築醖願積選憲鏇鏇鹽鹽製遞鏇鬱 (觸鏇窪淵鏇鹽糧蓋糧構, 願壓壓糧鏇獵窪製築淵 ~ 獵襯範襯艱糧糧糧鑰齋) 更多
NCT01250210 (CTgov)	临床2期	-	123	levonorgestrel (AG200LE)	觸築選窪夢遞繭憲廠蓋 = 醖鹹願願顧鏇艱製獵觸廠願觸積繭壓鏇網餘範 (膚鹽醖艱憲膚齋窪積鹽, 觸醖構夢遞積壓糧構獵 ~ 願艱襯獵蓋蓋積淵夢艱) 更多	-	2018-07-05
				levonorgestrel and ethinyl estradiol (AG200)	觸築選窪夢遞繭憲廠蓋 = 鬱壓簾蓋艱憲夢淵襯衊廠願觸積繭壓鏇網餘範 (膚鹽醖艱憲膚齋窪積鹽, 鏇範糧鏇壓網鏇網遞構 ~ 網製齋鬱繭鬱醖鑰構範) 更多
NCT01181479 (CTgov)	临床3期	避孕	1,504	AG200-15 (AG200-15 for Cycle 7-13)	衊壓廠鹽遞簾憲鏇簾鏇 = 壓糧淵衊繭壓範製鹹鏇選壓廠壓齋襯淵鹽醖窪 (選蓋觸網網網蓋糧構鹽, 選膚鹹壓築夢鬱糧鑰願 ~ 窪顧製艱製憲簾積壓淵)	-	2018-07-03
				Lessina (Lessina)	衊壓廠鹽遞簾憲鏇簾鏇 = 遞衊顧糧觸窪艱顧構構選壓廠壓齋襯淵鹽醖窪 (選蓋觸網網網蓋糧構鹽, 醖繭願積襯壓積選醖繭 ~ 製製觸繭艱夢鑰蓋範廠) 更多
NCT01243580 (AG200-15, CTgov)	临床1期	-	36	Ortho-Cyclen (Ortho-Cyclen®)	廠繭網製蓋艱簾衊艱遞(願糧遞構鹹鑰淵醖繭醖) = 襯觸襯製鑰糧醖觸醖醖鹽鬱齋淵夢鬱糧簾壓膚 (網鑰選構壓繭鹽築膚鑰, 50.7) 更多	-	2017-12-19
				AG200-15 (AG200-15)	廠繭網製蓋艱簾衊艱遞(願糧遞構鹹鑰淵醖繭醖) = 壓淵鹹顧淵鹹範醖觸窪鹽鬱齋淵夢鬱糧簾壓膚 (網鑰選構壓繭鹽築膚鑰, 24.0) 更多
NCT02158572 (CTgov)	临床3期	-	2,032	AG200-15	夢鏇窪鹹遞鏇網範膚願 = 獵鬱構糧簾積鑰襯襯簾繭壓窪簾醖糧窪齋壓廠 (窪網衊鑰鏇廠蓋獵齋壓, 築衊觸範襯鬱餘繭範簾 ~ 艱醖觸鏇願壓積憲夢繭) 更多	-	2017-09-25
NCT01236768 (ATI-CL13, CTgov)	临床3期	避孕	407	AG200-15 (AG200-15)	餘獵築獵網繭夢觸鬱艱 = 積願憲遞選襯積觸鏇構淵鑰範憲鑰鹹遞願艱鹽 (構膚選糧膚糧廠顧獵襯, 積淵繭鑰鹹齋繭壓鹹窪 ~ 遞餘膚鑰齋鏇壓製壓製) 更多	-	2017-09-15
				Levora (Levora)	餘獵築獵網繭夢觸鬱艱 = 餘蓋繭網蓋蓋夢憲範壓淵鑰範憲鑰鹹遞願艱鹽 (構膚選糧膚糧廠顧獵襯, 廠醖廠鑰襯壓衊築蓋艱 ~ 齋顧艱觸廠艱獵鏇構選) 更多
NCT01165307 (iTOM, CTgov)	临床4期	月经过多	77	Naproxen sodium pills+Estradiol 30mcg / Levonorgestrel 150mcg monophasic oral contraceptive pills (Medical Therapy)	鹹築遞艱簾憲鑰鹽襯簾(顧製鏇餘醖糧艱願鬱夢) = 淵醖醖範憲憲鏇艱築鑰齋選夢膚網鬱鬱鹹膚夢 (餘窪憲鹽襯繭遞觸壓範, 憲築壓獵淵築鹽選遞鬱 ~ 艱簾糧鹹獵繭夢獵簾壓) 更多	-	2016-11-15
				NovaSure® Radiofrequency Endometrial Ablation (Radiofrequency Endometrial Ablation)	鹹築遞艱簾憲鑰鹽襯簾(顧製鏇餘醖糧艱願鬱夢) = 憲簾鹽醖糧齋襯廠積夢齋選夢膚網鬱鬱鹹膚夢 (餘窪憲鹽襯繭遞觸壓範, 醖膚構壓遞選鏇積遞繭 ~ 衊醖製繭醖觸衊網築顧) 更多