Hypertrophic scarring is a difficult and debilitating condition where one develops excessive scarring after full thickness injury to the skin. This is very common in full thickness burn injury. Currently, there is no reliable treatment of these scars. One of the more effective treatments available is serial intralesional injection of a steroid.
Angiotensin II is an active peptide in the body that results in vasoconstriction of the blood vessels when activated. Medications used today like angiotensin II receptor blocks and angiotensin converting enzyme inhibitors work to prevent the activation of angiotensin II and are mainly used to help control blood pressure. Previous studies in rat models have shown that angiotensin II receptor blockers can effectively reduce scar hypertrophy.
In this study, the investigators will conduct a randomized control trial with a paired split-scar design. One arm receiving the standard therapy of serial intra-lesional injections of triamcinolone acetonide (TAC) and the second arm receiving an ACE-inhibitor. The outcome will be measured using the Patient and Observer Scar Assessment Scale (POSAS), a validated assessment tool.

开始日期2024-08-01

申办/合作机构

Nova Scotia Health Authority

NCT04640571

/ Completed临床4期IIT

Impact of Metformin and Polysorbate 80 on Drug Absorption and Disposition

The study employs two-sub-studies that share a common placebo arm.
The objective of one sub-study is to assess the impact of metformin on pravastatin and chenodeoxycholic acid pharmacokinetics. We hypothesize that metformin represses the bile salt export pump (BSEP) in the liver, which excretes pravastatin and chenodeoxycholic acid from the liver into the bile.
The objective of the other sub-study is to assess the impact of polysorbate 80 on valacyclovir, chenodeoxycholic acid, and enalaprilat pharmacokinetics. We hypothesize that polysorbate 80 inhibits uptake transporters in the intestine, which absorb valacyclovir and chenodeoxycholic acid in the gut via the peptide transporter 1 (PepT1) and apical sodium-bile acid transporter (ASBT), respectively. Enalaprilat is passively absorbed but with low permeability, and thus serves as a passive absorption reference.

开始日期2021-04-01

申办/合作机构

University of Maryland Baltimore

CTRI/2017/08/009230

/ Not yet recruitingN/AIIT

To compare the efficacy of pretreatment with intravenous enalaprilat or esmolol, in attenuating the pressor response to intubation in controlled hypertensive patients undergoing surgeries under general anesthesia requiring tracheal intubation

开始日期2017-08-15

申办/合作机构-

100 项与 Enalaprilat 相关的临床结果

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100 项与 Enalaprilat 相关的转化医学

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100 项与 Enalaprilat 相关的专利（医药）

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1,434

项与 Enalaprilat 相关的文献（医药）

2025-10-01·MICROBIAL PATHOGENESIS

MAMP - triggered immunity and in silico analysis elucidate the nematicidal properties of Bacillus velezensis VB7 against root-knot nematode Meloidogyne incognita infecting tomato

Article

作者: Sayyed, Riyaz ; Renukadevi, P ; Thiruvengadam, V ; Ashraf, Suhail ; Jothi, G ; Nakkeeran, S ; Alzahrani, Fares A ; Mohammed, Osama B ; Saranya, N ; Vinothini, K

Management of root-knot nematodes (RKN) remains as a major challenge in tomato cultivation, worldwide. In light of the harmful effects and environmental concerns associated with chemical pesticides, this study explored the use of bioagents and their bioactive compounds as a sustainable approach to manage Meloidogyne incognita infections in tomatoes. The nematicidal properties of metabolites from Bacillus velezensis VB7 against M. incognita have been assessed through molecular docking. Biomolecules extracted from the secondary metabolites of B. velezensis VB7 have been identified and validated through in silico approaches against the effector proteins of M. incognita. Molecular docking confirmed that the Enalaprilat biomolecule had the maximum binding energy ranges from -9.4 to -8.4 kcal/mol with all the five effector proteins of M. incognita. Further analysis revealed that applying of B. velezensis VB7 activated strong immune responses in tomato plants, significantly induced MAMP-triggered immunity via the expression of various transcription factors/defense genes by several folds to MAPK, NPR1, PAD1, MYC, and CAT in comparison to those RKN-inoculated and healthy control through qRT-PCR. Additionally, the protein-protein interaction confirmed the coordinated expression of various other genes associated with immune response. The present study confirmed the antinemic potential of B. velezensis VB7 against M. incognita and paved the way to explore the potential of bioagents against plant parasitic nematodes.

2025-09-01·ENVIRONMENTAL POLLUTION

Validation of a large volume-solid phase extraction methodology for biotoxicity assessment of pharmaceuticals in aquatic organisms

Article

作者: Gómez-Canela, Cristian ; Moragrega-Knol, Emma ; Barata, Carlos ; Romero-Alfano, Irene

The growing scarcity of freshwater has intensified the need for alternative water sources, which often require advanced treatments to eliminate contaminants. Among emerging pollutants, pharmaceuticals have become a significant concern due to their persistence and potential impact, making their detection essential. However, analysing these contaminants is challenging due to the extremely low concentrations at which they are present. For chemical analysis, minimal or no sample enrichment is often necessary, while bioanalysis typically requires larger sample volumes and an enrichment factor to conduct comprehensive bioassays across various endpoints. Consequently, sample preconcentration techniques for large water volumes are necessary to improve the sensitivity of subsequent toxicological experiments. In this study, a novel large volume solid-phase extraction (LV-SPE) procedure was validated and evaluated for monitoring multiple pharmaceutical compounds in water samples, while maintaining the traditional solid-phase extraction (SPE) methodology using cartridges. This method proved effective extraction and preconcentration of significant amounts of water, with recoveries between 19 % and 109 % in spiked wastewaters (except for fluvoxamine, remdesivir, tamoxifen and tetracycline, with recoveries <10 %). Furthermore, the optimization of this approach covers an expansive chemical space, enabling the capture of a diverse range of pharmaceutical compounds and enhancing the validity of toxicological studies. Bioassays conducted with Daphnia magna juveniles and Danio rerio embryos validated the method's applicability regarding optimized exposure conditions, the absence of adverse effects from SPE blanks or solvent controls and sensitivity in detecting effects across field samples. Overall, the LV-SPE approach enhances sensitivity and reliability for evaluating pharmaceutical mixtures' risks under realistic conditions.

2025-08-01·FOOD CHEMISTRY

Investigation into the effects of acute heat stress on stress level, meat quality, myofibrillar proteins properties and serum metabolites release of Muscovy ducks (Cairina moschata)

Article

作者: Huang, Tianran ; Xiao, Mengchao ; Huang, Jichao ; Li, Zimu ; Zhu, Zongshuai ; Huang, Ming

This study systematically investigated the effects of acute heat stress (AHS) on Muscovy ducks, focusing on plasma stress indicators, meat quality, myofibrillar proteins (MPs) properties, and serum metabolite profiles. AHS significantly elevated stress level, impairing meat quality, as evidenced by higher L* value, shear force, drip loss, and cooking loss (P < 0.05). It also induced MPs oxidation and aggregation, reflected by elevated carbonyl content, turbidity, zeta potential, and particle size. MPs structural alterations were confirmed by fluorescence quenching and increased exposure of hydrophobic groups. Correlation analysis revealed strong associations between physicochemical changes and MPs oxidation. Metabolomic analysis identified 161 and 105 differential metabolites in the CON vs. LS and CON vs. SS comparisons, respectively, involving 25 metabolic pathways related to energy, amino acids, and fatty acids. These findings provide novel insights into the molecular pathways of AHS-induced meat quality deterioration and reveal potential intervention timing for the poultry industry.

项与 Enalaprilat 相关的新闻（医药）

2024-08-01

·同写意

115亿美元收购的新秀，能否拯救“药王”？

本次以“突破瓶颈打造健康产业新引擎”为主题，设一场主论坛和五场主题论坛，从前沿创新突破、临床应用拓展、工艺技术优化、商业化开发等多个全新视角推动CGT技术开发与应用，成就健康产业未来。默沙东有些郁闷。2024年上半年业绩公布后，当天股价暴跌9.81%，创下2021年11月以来新纪录，次日仍未扭转。辛苦半年，股价涨幅尽数吐出——几乎等于白干。从财报整体数据看，默沙东表现似乎还不错。第二季度销售额161亿美元，超过去年同期的150亿美元，也高于分析师预计的159亿美元。而前两个季度的总营收，达到318.87亿美元，同比增长8%。 “药王”Keytruda依旧继续狂飙突进，Gardasil/Gardasil 9继续领跑疫苗板块，心血管领域迎来新的重磅产品。问题出在中国市场上。默沙东称，Gardasil的中国经销商智飞生物向疫苗接种点的发货量远低于预期，库存目前高于正常水平。默沙东CFO Caroline Litchfield回应道，如果该情况没有改观，默沙东今年向智飞生物运送的疫苗剂量可能会少于合同规定。中国一直是Gardasil的重要且不断增长的市场。第二季度，Gardasil销售额比去年同期只增长1%。但更大的麻烦，或许指向这家巨头的产品结构。在如今MNC的发展模式下，公司未来几乎可以与“重磅炸弹”划等号。默沙东所仰赖的现有产品矩阵，包括Keytruda在内，仍未能提供足够的支撑。 Winrevair是默沙东酝酿已久的额外筹码。然而，想要真实现“王车易位”，这款肺动脉高压（PAH）新药还需要更多的证明。 1 300亿的“药王”在路上癌症免疫疗法Keytruda，目前是全球最畅销的药物，它的上市之路却颇为周折。最初，这款PD-1抑制剂由Organon的科学家发现。2007年11月，Organon被先灵葆雅以144亿美元收购；2009年11月，先灵葆雅又被默沙东以411亿美元收购。然而，Keytruda仍处于临床前阶段。默沙东直到2011年才对Keytruda表现出一些兴趣，当时，该药被推进到转移性癌、黑色素瘤、非小细胞肺癌的I期临床。2014年被FDA批准后，Keytruda王朝正式拉开帷幕。今年第二季度，光是这一款产品，就贡献了73亿美元的营收，今年上半年累计的销售额142.17亿美元，可谓默沙东的半壁江山。治疗领域扩张，无疑对业绩增长提供了很大的帮助。 6月，Keytruda在美国获批第40个适应症，联合标准化疗治疗原发性晚期或复发性子宫内膜癌患者。并且，这不仅让Keytruda在子宫内膜癌领域拿到第3项批准，也是成就了其在子宫内膜癌领域首款无视错配修复状态的一线免疫疗法之名。 2023年，Keytruda首次以250亿美元的收入，从Humira那里接过“药王”的头衔，终结了这款自免疗法的霸榜记录。基于上半年两位数的同比增长，2024年，Keytruda销售额有望进一步爬升到300亿美元。而Evaluate Pharma数据显示，Keytruda销售额峰值的2027年，预计将产生312.8亿美元收入。最大的挑战是专利。2028年，Keytruda开始逐渐失去专利保护，届时可能会遭受仿制药的冲击，营收跳水。 Evaluate Pharma预测，从2014年上市到2028年出现“专利悬崖”，Keytruda会创造制药行业单品累计收入之最（2510.9亿美元）。但默沙东需要一个指向未来的答案。考虑到Keytruda的地位，默沙东已在尝试减弱“专利悬崖”的影响，例如围绕开发新剂型。默沙东的想法，是开发一种含有特定酶的Keytruda皮下剂型，使每3周给药一次的频率，下降到每6周给药一次。按照时间表，该想法尚需要数年时间才能落地，I期临床数据预计在2026年公布。如果顺利，皮下剂型有望满足一半的Keytruda使用者需求，这是默沙东CEO Robert Davis在去年4月电话会上给出的说法。目前，默沙东还探索将Keytruda与TIGIT单抗Vibostolimab相加的复方。值得注意的是，这款代号为MK-7684A的疗法，并非一帆风顺。5月，因为在分析中达到无效性标准，默沙东宣布，将终止MK-7684A辅助治疗手术切除后的IIB-IV期高危黑色素瘤患者的III期KeyVibe-010研究。或许长久之计，还是另起炉灶，去讲一个全新的“重磅炸弹”故事。 2 Winrevair有多能打？ 3月，FDA批准了Winrevair（sotatercept）的上市申请，用于治疗PAH患者。这对于默沙东来说，是一个值得期待的节点。跟Keytruda的开发经过类似，Winrevair也来自外部创新。早在2021年，Davis出任默沙东CEO的4个月后，该公司就以115亿美元收购了Acceleron，从而获得sotatercept这款在研疗法。 Davis希望sotatercept能够对冲Keytruda销量下滑。接受采访时，他形容说：“我们最终将其视为一个价值数十亿美元的机会和收入潜力，而且重要的是，我们预计它将在未来十年内实现良好增长。” 这在当时有些过于乐观，毕竟Acceleron甚至还没有sotatercept的III期试验数据。然而一年后，当默沙东公布III期试验的积极结果，外界开始认为，该公司做出了正确的选择。 Winrevair获批上市的标签并没有携带黑框警告，FDA未要求默沙东制定风险评估和缓解策略，该适应症也没有限制患者的症状必须严重到何种程度才可以使用该药物——这些表现，都更令人对Winrevair的未来浮想联翩。至少在2024年以前，PAH一直是困恼业界、无法治愈的顽疾。它导致患者肺部血管变窄、阻塞或结构破坏，继而使肺动脉压持续升高，心脏负荷增加，心肌乏力，最终可能危及生命。另一方面，即使只是缓解症状，PAH市场照样催生出不少重磅商业化产品。像血管扩张剂，市场规模已达60亿美元。自1995年Flolan率先获得批准，用于PAH的血管扩张剂等药物数量不断增加。 MNC阵营里，强生一度凭借Uptravi和Opsumit占据PAH治疗领域的主导地位。其中，Uptravi属于前列环素受体激动剂，2023年销售额为16亿美元，同比增长20%；Opsumit则是一种内皮素受体激动剂，去年营收增长14%，达到20亿美元。今年3月，Opsumit还跟United Therapeutics开发的Adcirca组合，以Opsynvi的商品名获得FDA批准。一些Biotech的挑战尝试失败了，直到Winrevair的出现，PAH的治疗历史有望改写。第二季度，Winrevair销售额为7000万美元，高于5700万美元的普遍预期。FactSet在该药上市时的预测是，到2029年Winrevair销售额将达39亿美元，不过眼下它给出的数字更高，60亿美元。瑞穗医疗股票策略师Jared Holz表示，一些投资者可能还会觉得，Winrevair尽管取得超预期的成绩，还是有点“悄无声息”。他劝行业“不要太挑剔”，然而，二级市场的走势似乎表明，默沙东想要靠新产品说服投资者，尚需要一定的变现期。 3 心血管业务的扩张 Winrevair的商业化定价是每瓶1.4万美元。对于大多数患者（大约三分之二），他们将每三周使用一剂Winrenvair，全年治疗费用高达24.2万美元（剂量基于体重，费用会有所差异）。而根据美国肺脏协会的数据，PAH每年影响约500至1000名美国人。某种程度上，Winrevair是默沙东产品组合扩张战略的基石。与之对应，心血管疾病领域的扩张，也将成为默沙东未来的核心策略之一。长年被Keytruda光环笼罩，或许不少人都忽视了默沙东在心血管赛道的根基。这家MNC的第一款“重磅炸弹”Vasotec，就来自心血管疾病领域——1985年，Vasotec针对高血压的适应症获得FDA批准，并于三年后跻身“重磅炸弹”行列。1987年，默沙东又推出第一款针对高胆固醇的商业化他汀类药物Mevacor，并在此后开发了新一代他汀药物Zocor。换言之，默沙东是依靠心血管疾病疗法“登堂入室”的。如果再往前推，我们还可以追溯到1958年的高血压药物Diuril。如今，默沙东的一个重要战略目标，就是到2030年推出8种心血管疾病的适应症或新药，并实现100亿美元的收入。Winrevair的成功上市，标志着它朝向这个目标迈出坚实的一步。除了首发适应症，默沙东还计划把Winrevair的使用范围扩大到更多PAH患者，正在针对III类或IV类疾病的后期患者（ZENITH）和新诊断患者（HYPERION）进行III期试验，分别于2025年和2026年完成。默沙东管线里，仍然有多款心血管疾病候选药，包括多肽疗法MK-0616，可抑制PCSK9与LDL受体的相互作用，拟用于高胆固醇血症，现阶段处在III期临床。小分子MK-5475则针对PAH，单抗MK-2060适应症为血栓，二者都进入了II期临床。这些资产能在多大程度上取得成功，将决定默沙东在“后Keytruda”时代，是否会开辟出另一条业绩增长曲线。参考资料： 1.Merck Stock Had Its Worst Drop in Years After Earnings；Barron’s 2.Merck Scores Major Drug Approval, Easing Pain From Keytruda Patent Expiration；Barron’s 3.Merck CEO Rob Davis dubs Keytruda market exclusivity loss as 'more of a hill than a cliff'；Fierce Pharma 同写意媒体矩阵，欢迎关注↓↓↓

并购疫苗财报免疫疗法

2024-07-14

·药精通Bio

行业研究 | 生物制药十巨头的多肽药物名录（附结构图）

深度聚焦多肽、多肽偶联药物研发、质控、工艺开发，展位咨询&免费入场券：联系电话181 1603 6798，扫码立即获取免费入场券：文章来源：多肽圈｜中肽生化内容团队编辑根据2024年4月15日的市值排行榜，全球前十名的生物制药公司所拥有的多肽/拟肽资产如下： 01 礼来（7146.3亿美元） Tirzepatide · Mounjaro (tirzepatide)：2型糖尿病，2022年5月13日获批 · Zepbound (tirzepatide)：肥胖症，2023年11月8日获批 · Forteo (Teriparatide)：骨质疏松症，2022年11月26日获批 Teriparatide 02 诺和诺德（5645.6亿美元） Semaglutide · Wegovy (semaglutide)：肥胖症，2021年6月4日获批 · Rybelsus (semaglutide)：2型糖尿病（口服），2019年9月20日获批 · Ozempic (semaglutide)：2型糖尿病，2017年12月5日获批 · Victoza (liraglutide)：2型糖尿病，2010年1月25日获批 · Saxenda (liraglutide)：肥胖症，2014年12月23日获批 Liraglutide 03 强生（3554.9亿美元）无上市多肽资产 04 默沙东（3185.0亿美元） · CANCIDAS® (caspofungin acetate，环肽): 棘白菌素类抗真菌药物，针对对其他抗真菌药物难治或不耐受的侵袭性曲霉菌病成人患者，2001年1月26日获批。 caspofungin · CUBICIN® (daptomycin for injection，环肽)：脂肽抗生素，用于治疗由革兰氏阳性菌引起的全身性和危及生命的感染，2023年9月12日获批。 Daptomycin · ZEPATIER（Grazoprevir环肽+ elbasvir）: 丙型肝炎，第二代丙型肝炎病毒蛋白酶抑制剂，2016年1月28日获批。 · ZERBAXA (ceftolozane环肽 and tazobactam)：复方抗生素药物，用于治疗成人复杂性尿路感染和复杂性腹腔内感染。Ceftolozane 是一种头孢菌素抗生素（β-内酰胺类），开发用于治疗对常规抗生素耐药的革兰氏阴性菌感染。2014年12月19日获批。 ceftolozane 05 艾伯维（2873.4亿美元）无上市多肽药物 06 阿斯利康（2137.1亿美元） · Zoladex (goserelin acetate implant)：用于抑制性激素（睾酮和雌激素）产生的药物，用于乳腺癌和前列腺癌的治疗。它是一种可注射的促性腺激素释放激素激动剂（GnRH 激动剂）。1989年12月29日获批。 Goserelin · Bydureon (exenatide)：2型糖尿病。2012年1月27日获批。 · Byetta (exenatide injection)：2型糖尿病。2005年4月28日获批。 exenatide · Symlin (pramlintide acetate)：用于治疗糖尿病（1 型和 2 型）的注射胰淀素类似物药物。2005年3月16日获批。 · Zestril (lisinopril dihydrate)：血管张力素转化酶抑制剂（ACE抑制剂）药物，用于治疗高血压、心脏衰竭和心肌梗塞。2003年1月7日获批。 Lisinopril · ARGATROBAN (argatroban injection, solution)：直接凝血酶抑制剂，用于预防或治疗肝素诱导的血小板减少症（HIT）患者的血栓形成。2000年6月30日获批。 Argatroban 07 罗氏（1986.6亿美元）无上市多肽药物 08 诺华（1934亿美元） · Cibacen® (benazepril hydrochloride)：治疗高血压、心力衰竭和糖尿病肾病，1999年6月16日获批。 Benazepril · Locametz (gallium Ga 68 gozetotide)：放射性药物，由与前列腺特异性膜抗原 (PSMA) 靶向配体 Glu-Urea-Lys(Ahx)-HBED-CC缀合的 68Ga 制成，用于通过正电子发射断层扫描 (PET) 对前列腺癌进行成像。2022年3月23日获批。 Gallium Ga 68 gozetotide（图片来源：Wikipedia） · Lutathera (lutetium Lu 177 dotatate, 环肽): 镥元素放射性同位素与 DOTA-TATE 的螯合复合物，用于肽受体放射性核素治疗 (PRRT)。用于治疗患有胃肠胰神经内分泌肿瘤 (GEP-NET) 的成人癌症，这些肿瘤对激素受体生长抑素呈阳性。2018年1月26日获批。 Lutetium Lu 177 dotatate（图片来源：Wikipedia） · Neoral/Sandimmune (cyclosporine环肽, USP Modified): 强效免疫抑制剂，用于治疗类风湿性关节炎、狼疮、牛皮癣和其他自身免疫性疾病。1995年7月获批。 Cyclosporine A · NETSPOT (gallium Ga 68 dotatate injection)：Ga 68 dotatate 注射液与 PET 扫描（正电子发射断层扫描）结合使用，可定位成人和儿童的生长抑素受体阳性神经内分泌肿瘤 (NET)。 · Pluvicto (lutetium Lu 177 vipivotide tetraxetan)：用于接受了雄激素受体 (AR) 途径抑制和紫杉醇类化疗治疗的成年患者，患有前列腺特异性膜抗原（PSMA）阳性的转移性去势抵抗性前列腺癌（mCRPC）。 lutetium Lu 177 vipivotide tetraxetan（图片来源：Wikipedia） · Sandostatin (octreotide acetate环肽): 用于治疗产生生长激素的肿瘤 (例如肢端肥大症和巨人症)。1998年11月25日获批。 Octreotide 09 辉瑞（1463.3亿美元） · ACCUPRIL (quinapril HCI) · ACCURETIC® (quinapril HCl/hydrochlorothiazide)：Quinapril用于治疗高血压、心力衰竭和糖尿病肾病。它是高血压的一线治疗方法。 Quinapril · ALTACE (ramipril)：Ramipril是一种 ACE 抑制剂类药物，用于治疗高血压、心力衰竭和糖尿病肾病。它还可以用作 55 岁以上患者的预防药物，以降低高危患者（例如一些糖尿病患者和血管疾病患者）心脏病发作、中风或心血管死亡的风险。 Ramipril · AMPICILLIN FOR INJECTION (Ampicillin Sodium)：Ampicillin是一种抗生素，属于青霉素家族的氨基青霉素类。用于预防和治疗多种细菌感染，如呼吸道感染、尿路感染、脑膜炎、沙门氏菌病和心内膜炎。它还可用于预防新生儿 B 族链球菌感染。它可以口服、肌肉注射或静脉注射。 Ampicillin · BIVALIRUDIN (bivalirudin)：比伐卢定（Bivalirudin）是一种特异性、可逆的直接凝血酶抑制剂 (DTI)。它是天然药物水蛭素的合成同系物，水蛭素存在于药用水蛭的唾液中。它是一种短肽，是一种有效且高度特异性的凝血酶抑制剂，可抑制循环凝血酶和凝块结合凝血酶，同时还抑制凝血酶介导的血小板活化和聚集。用于治疗肝素诱导的血小板减少症并预防经皮冠状动脉介入治疗期间的血栓形成。 · BLEOMYCIN：Bleomycin（博来霉素）是一种来自轮枝链霉菌的相关糖肽抗生素复合物。适应症包括霍奇金淋巴瘤、非霍奇金淋巴瘤、睾丸癌、卵巢癌和宫颈癌等。通常与其他癌症药物一起使用，通过肌肉注射、皮下注射或静脉注射。它抑制 DNA 代谢并用作抗肿瘤药物，尤其是实体瘤。 Bleomycin · CEFAZOLIN (cefazolin)：头孢唑林（Cefazolin）是一种用于治疗多种病原细菌的抗细菌药，尤其针对蜂窝组织炎、泌尿道感染、肺炎、心内膜炎、败血性关节炎及胆道发炎等疾病，也可用来预防手术前或手术中B群链球菌感染。 Cefazolin · CEFEPIME (Cefepime) · MAXIPIME (cefepime hydrochloride)：Cefepime（头孢吡肟）是第四代头孢菌素类抗生素。头孢吡肟对革兰氏阳性菌和革兰氏阴性菌具有更广泛的活性，比第三代药物对这两种类型的生物体的活性更强。 Cefepime · CEFOBID (cefoperazone sodium)：cefoperazone（头孢哌酮）是第三代头孢菌素抗生素。它是少数能有效治疗对这些抗生素耐药的假单胞菌感染的头孢菌素抗生素之一。 Cefoperazone · CEFTRIAXONE (ceftriaxone)：头孢曲松（ceftriaxone）是一种第三代头孢菌素抗生素，用于治疗多种细菌感染，包括中耳感染、心内膜炎、脑膜炎、肺炎、骨和关节感染、腹内感染、皮肤感染、尿路感染、淋病和盆腔炎。 ceftriaxone · CORTISPORIN (neomycin and polymyxin B sulfates, and hydrocortisone acetate)：新霉素/多粘菌素 B/氢化可的松以 Otosporin 品牌销售，是一种用于治疗外耳炎和某些眼部疾病的药物。 Polymyxin B (多粘菌素 B，环肽) 可以单独以Poly-Rx 等商品名出售，是一种用于治疗脑膜炎、肺炎、败血症和尿路感染的抗生素。虽然它对许多革兰氏阴性感染有用，但对革兰氏阳性感染没有用。Polymyxin B由Polymyxin B1和B2两种环肽组成。 Polymyxin B1（左）和Polymyxin B2（右） · NEOSPORIN G.U. Irrigant (neomycin sulfate – polymyxin B sulfate) · NEOSPORIN Ophthalmic Solution (neomycin and polymyxin B sulfates, and gramicidin)：新孢菌素滴眼液由新霉素/多粘菌素B/杆菌肽组成，适用于局部治疗敏感细菌引起的外眼及其附件的浅表感染。此类感染包括结膜炎、角膜炎和角结膜炎、睑缘炎和睑结膜炎。杆菌肽（gramicidin），也称为杆菌肽 D，是离子载体抗生素杆菌肽 A、B 和 C 的混合物，分别占混合物的 80%、5% 和 15%。每种都有 2 种isomer，因此混合物有 6 种不同类型的杆菌肽分子。它们可以从短芽孢杆菌土壤细菌中提取。杆菌肽是含有 15 个氨基酸的线性肽，不同于不相关的杆菌肽 S，后者是一种环肽。 · DAPTOMYCIN (daptomycin，环肽)：达托霉素（Daptomycin）是一种脂肽抗生素，用于治疗由革兰氏阳性菌引起的全身性和危及生命的感染。 Daptomycin · ENALAPRILAT (enalaprilat)：Enalaprilat (依那普利拉) 是enalapril (依那普利) 的活性代谢物。它是ACE 抑制剂，是一种抗高血压药，用于在口服治疗不可行时治疗高血压。 Enalapril和Enalaprilat · ERAXIS (anidulafungin，环肽)：Anidulafungin（阿尼芬净）是一种半合成棘白菌素，用作抗真菌药物。当与伏立康唑联合使用时，它还可能用于治疗侵袭性曲霉菌感染。它是棘白菌素类抗真菌药物的一员。其作用机制是抑制 (1→3)-β-D-葡聚糖合酶，后者是一种对真菌细胞壁合成很重要的酶。 Anidulafungin · PAXLOVID (nirmatrelvir and ritonavir)：Paxlovid是由nirmatrelvir和ritonavir两种成分组成的抗SARS-Cov-2病毒口服药，其中nirmatrelvir是活性成分，为拟肽分子，是3C 样蛋白酶抑制剂。 Nirmatrelvir · PIPERACILLIN AND TAZOBACTAM (piperacillin and tazobactam)：Piperacillin (哌拉西林)和tazobactam (他唑巴坦) 联合疗法用于治疗身体许多不同部位（例如胃或肠、肺、皮肤、女性生殖器官）的细菌感染。哌拉西林和他唑巴坦组合是抗生素，属于青霉素和 β-内酰胺酶抑制剂药物组。 Piperacillin · SYNAREL (nafarelin acetate)：Nafarelin是一种促性腺激素释放激素激动剂（GnRH 激动剂）药物，用于治疗子宫内膜异位症和青春期早期。它还用于治疗子宫肌瘤、控制体外受精 (IVF) 中的卵巢刺激，以及作为变性激素治疗的一部分。 Nafarelin · SYNERCID I.V. (quinupristin环肽/dalfopristin)：Synercid I.V.（奎奴普丁和达福普丁）是一种复方抗生素，用于治疗血液和其他身体系统的严重感染。 Quinupristin · TAZICEF (ceftazidime)：头孢他啶（ceftazidime）是第三代的头孢菌素抗生素。 ceftazidime · Vancomycin Hydrochloride：盐酸万古霉素是一种抗菌处方药，用于治疗某些细菌感染，例如由艰难梭菌和金黄色葡萄球菌引起的感染。艰难梭菌和金黄色葡萄球菌是可引起 HIV 机会性感染 (OIs) 的细菌。OIs是一种与免疫系统健康的人相比，拥有较弱免疫系统的人（例如艾滋病毒感染者）发生的频率更高或更严重的感染。 10 安进（1432.4亿美元） · Kyprolis (carfilzomib)：Carfilzomib是一种选择性蛋白酶体抑制剂的抗癌药物。 Carfilzomib · Parsabiv (Etelcalcetide)：Etelcalcetide是一种拟钙药物，用于治疗血液透析患者的继发性甲状旁腺功能亢进症。Etelcalcetide 通过结合并激活甲状旁腺中的钙敏感受体发挥作用。 Etelcalcetide END 免责声明：本文信息来源于网络，本文仅作知识交流与分享及科普目的，不涉及商业宣传，不作为相关医疗指导或用药建议。文章如有侵权请联系删除。深度聚焦多肽、多肽偶联药物研发、质控、工艺开发，7月相约苏州，联系电话18116036798上下滑动查看议程 7月25日上午：主会场多肽药物蓝海布局 9:00-9:30 李学臣，香港大学化学系理学院副院长多肽药物和蛋白偶联的新策略 9:00-9:30 王珠银，深圳肽盛生物科技有限公司董事长 3D结构多肽库的构建和靶向穿膜肽筛选 9:30-10:00 马亚平，深创生物董事长靶向核素药物研究与开发 10:30-10:50 茶歇&交流 10:50-11:20 徐寒梅，中国药科大学教授；南京安吉生物科技有限公司创始人新靶点多肽药物发现及PDC药物研究进展 11:20-11:50 钱海，中国药科大学理学院院长兼药物科学研究院新药研究中心主任话题确认中 11:50-12:20 圆桌讨论：多肽药物脱颖而出的关键、未来如何保持高热度、内卷何时到来？刘东舟，华东医药首席科学官/创新药全球研发中心总经理容明强，成都佩德生物医药有限公司董事长马亚平，深创生物董事长王珠银，深圳肽盛生物科技有限公司董事长邵军，同宜医药（苏州）有限公司首席技术官部分嘉宾确认中 12:20-14:00 午餐&休息 7月25日下午：论坛一多肽药物研发进展 14:00-14:30 周建伟，南京医科大学教授/南京明人医药科技有限公司创始人基于JWA基因的多肽创新药研究 14:30-15:00 容明强，成都佩德生物医药有限公司董事长基于生存策略的动物毒素多肽新药开发 15:00-15:30 江苏万略医药科技有限公司话题确认中 15:30-15:50 茶歇&交流 15:50-16:20 韩俊峰，上海贺普药业股份有限公司总裁贺普拉肽研究进展 16:20-16:50 方小翠,国家纳米科学中心,高级工程师肿瘤免疫治疗用靶向溶瘤多肽的药物转化 16:50-17:20 张晓君，石药集团北京研究院制剂四所所长多肽药物长效递送研发进展 7月25日下午：论坛二多肽药物质控与生产 14:00-14:30 邵军，同宜医药（苏州）有限公司首席技术官多肽类药物工艺与质量控制要点 14:30-15:00 姜建军，江苏诺泰澳赛诺生物制药有限公司，多肽事业部总经理/集团副总经理/研究院副院长多肽药物合成新工艺 15:00-15:30 大西弘晃，三菱化学株式会社 Purification of Cyclic Peptide and Its Analogues with Polymeric Separation Media 15:30-15:50 茶歇&交流 15:50-16:20 李子刚，北京大学深圳研究生院，化学生物学与生物技术学院执行院长/深圳湾实验室，坪山生物医药研发转化中心主任新颖稳定多肽方法学开发及其在多肽药物开发中的应用 16:20-16:50 苏贤斌，南京工业大学教授、博士生导师连续流动绿色多肽合成（拟定） 16:50-17:20 刁星星，中国科学院上海药物研究所研究员，课题组长/苏州锐迪欧医药科技有限公司创始人新类型药物PDC LN005体外、体内代谢研究策略 7月26日上午：论坛一多肽药物研发进展 9:00-9:30 陈小新，广东众生睿创生物科技有限公司联合创始人、董事、总裁基于GLP-1的单分子多重受体激动剂治疗肥胖和NASH的研究进展 9:30-10:00 谢天，甘李药业股份有限公司，医学事务部负责人 GLP-1研发的挑战与布局 10:00-10:30 温晓芳，浙江道尔生物科技有限公司副总裁 GLP-1/GCG/FGF-21三靶点激动剂在NASH中的临床前开发 10:30-10:50 茶歇&交流 10:50-11:20 景书谦，鸿运华宁（杭州）生物医药有限公司创始人、董事长兼首席执行官 GLP药物研发进展及商业化前景 11:20-11:50 夏帅，复旦大学基础医学院青年研究员广谱抗冠状病毒多肽类融合抑制剂的研究 11:50-14:00 午餐&休息 14:00-14:30 张传亮，青岛科技大学化工学院，副教授长效降糖减重药物的差异化开发：基于BH3模拟肽的PTP1B/TC-PTP抑制剂/降解剂的设计与研发 14:30-15:00 韩智豪，中国药科大学特聘副研究员，硕士生导师基于仿生多肽的放射性药物研究 15:00-15:30 杨浩哲，香港交易所，环球上市服务部助理副总裁香港交易所助力医药企业融资上市 7月26日上午：论坛二多肽药物质控与生产 9:00-9:30 丁伟，南京知和医药科技有限公司副总，多肽首席科学家多肽药物质量研究中的常见问题与解决方案 9:30-10:00 刘磊，江苏大学材料科学与工程学院副院长多肽基功能生物界面用于肿瘤细胞的捕获与分离 10:00-10:30 曹宇，重庆派金生物科技有限公司生产总监长效胰岛素结构相关杂质控制和表征 10:30-10:50 茶歇&交流 10:50-11:20 赵军锋，广州医科大学教授无保护氨基酸合成多肽 11:20-11:50 郭建，上海胜普泽泰医药科技有限公司副总裁多肽偶联药物CMC要点分享 11:50-14:00 午餐&休息 7月26日下午：论坛二 PDC药物研发 14:00-14:30 张普文，浙江汉鼎医药有限公司总经理多肽糖胺聚糖等新型PDC药物的研发 14:30-15:00 张富尧，上海弼领生物创始人、董事长&CEO 纳米PDC：用于药物高效递送的纳米列车 15:00-15:30 马步勇，上海交通大学药学院教授蛋白质动态结构的AI预测与应用 15:30-16:00 朱勍，浙江工业大学，生物制药与生物材料研究所所长 C-C键环肽及其偶联药物新进展戳“阅读原文”立即报名多肽药物论坛吧!

上市批准生物类似药

2023-02-02

·GlobeNewswire-Health Care

Amarin Mails Letter to Shareholders Highlighting New Board and Superior Leadership

Significantly Refreshed Board Overseeing Successful Execution of Amarin’s Transformation Plan to Drive Short- and Long-Term Value; Outmatches Sarissa’s Slate in Every Critical Area Chairman Per Wold-Olsen Brings Critical Experience and Leadership Releases Additional Board Videos Available at www.voteamarin.com Urges Shareholders to Vote “AGAINST” Sarissa’s Proposals on the WHITE Proxy Card DUBLIN, Ireland and BRIDGEWATER, N.J., Feb. 02, 2023 (GLOBE NEWSWIRE) -- Amarin Corporation plc (NASDAQ: AMRN) (“Amarin” or the “Company”) today announced that it has mailed a letter to shareholders in connection with the General Meeting of Shareholders urging shareholders to vote “AGAINST” all proposals on the WHITE proxy card. The General Meeting of Shareholders is scheduled to be held on February 28, 2023, and shareholders of record as of January 23, 2023, will be entitled to vote at the meeting. The Company also released additional videos featuring its Board of Directors, which can be viewed at www.voteamarin.com. The full text of the letter being mailed to shareholders follows: Dear Shareholder, At the upcoming General Meeting on February 28, 2023, Sarissa Capital Management is attempting to remove our newly appointed Board Chair, Per Wold-Olsen, and nearly double the size of the Amarin Board with an underqualified slate of seven nominees. This change would dramatically impede momentum that is underway and significantly risk the short- and long-term value of your investment. Your Board and management team are actively executing a thoughtful and practical strategic plan designed to create value now. This is a NEW Amarin with a NEW Board, a NEW leadership team and a NEW strategy. We urge you to vote “AGAINST” Sarissa’s harmful proposals on the WHITE proxy card. Please follow the instructions on the enclosed WHITE proxy card and vote by telephone, internet or mail. For ADS holders, the deadline to submit your vote is 3 PM GMT (10 AM ET) February 22, 2023, and for holders of ordinary shares, the deadline is 3 PM GMT (10 AM ET) February 24, 2023. Scan this QR code to hear directly from our Board of Directors about the opportunity we see for Amarin and why you should vote AGAINST Sarissa’s proposals. We also encourage you to submit your questions and we will answer the most frequently asked questions in the coming weeks. The Change Agents Amarin Needs Are Already Here When we embarked on our Board refreshment process in October 2021, we did so with one goal: recruit individuals with a specific set of skills to shape Amarin’s new strategy and support its execution – and we have done it. The Amarin Board now consists of nine directors – six of whom were appointed in the last year. We have also completely refreshed our Board leadership structure – appointing Mr. Wold-Olsen as Chairman of the Board and Chair of Amarin’s Renumeration Committee, Erin Enright as Chair of Amarin’s Audit Committee and Adam Berger as Chair of Amarin’s Nominating and Corporate Governance Committee. We will continue to take proactive, decisive actions to transform Amarin and better position the Company to succeed and drive value. The refreshed Board, alongside the new management team, has contributed to substantial progress in a short period of time across all facets of the business – strategic, operational and financial. These efforts are reflected in Amarin’s performance in 2022 and early 2023, including: Secured six international regulatory approvals in 2022 and regulatory approval in New Zealand in January 2023Obtained attractive reimbursement and pricing in five European countries and advanced five additional European markets to pricing negotiationDelivered four consecutive quarters of U.S. revenue stabilizationImplemented $100 million annual cost savings plan in mid-2022, which has delivered actual savings of $50 million in the second half of 2022 and on track to achieve $100 million by mid-2023Initiated and progressed initial fixed-dose combination program for icosapent ethyl, which will improve the future value, penetration and durability of our VASCEPA®/VAZKEPA® franchise in Europe Per Wold-Olsen’s Experience and Leadership are Critical to Amarin’s Transformation Since Mr. Wold-Olsen’s appointment to the Board in January 2022 and subsequently his appointment as Chairman in May 2022, he has demonstrated steadfast leadership and his contributions to Amarin have been far-reaching: Providing critical oversight and assistance in navigating European pricing negotiations, which has led to five favorable pricing outcomesRecognizing the need for cost containment, which led to a comprehensive cost savings plan that is well on-trackEmphasizing the importance of a new and purpose-built Board for Amarin’s transformation, which has resulted in a nearly 70% refreshed Board in the past yearWorking closely with President and CEO Karim Mikhail and the rest of the Board to advance and refine our new strategy Mr. Wold-Olsen is one of the most well-respected international healthcare executives in the world with a demonstrated ability to transform companies, and his track record of successful product launches is undisputed. During Mr. Wold-Olsen’s 30-year tenure at Merck, he: Oversaw multiple global launches of multi-billion-dollar products, including ZOCOR, FOSAMAX, VASOTEC, COZAAR AND VIOXXInitiated critical regulatory filing strategies for new products in Europe that resulted in accelerated launches and significant strategic benefitsDoubled the European business’ revenueMaintained profitability during a time of extensive patent cliffsRestructured the EMEA Eastern Europe business and grew sales six-timesBuilt several landmark studies that served as key drivers of the company’s strategy to demonstrate clinical endpoint in large-scale outcomes trials He has extensive governance experience from a number of prestigious pharmaceutical companies: Chairman of H. Lundbeck – transformed the Company’s go-forward strategy, implemented Board and CEO transitions and restructured executive compensation programDirector of Gilead Sciences – oversaw asset acquisitions and global launch strategies of numerous Hepatitis C products resulting in an industry all-time revenue generation record and helped oversee the continued evolution of the Company’s HIV combination and commercial success of a multi-billion franchiseChairman of Oncopeptides – built and downsized the Company’s U.S. organization over 12 months, following the loss of continued commercialization opportunityChairman of the Great Nordic Company – led the transformation of the Company from near bankruptcy in 2008 to being a global innovation leader todayChairman of the Advisory Committee of Novo Holdings, one of the world’s largest healthcare investors Our Board Has the Expertise Amarin Needs; Sarissa’s Slate Does Not Offer the Skills Amarin Needs Amarin is at a critical inflection point. Now, more than ever, we must remain focused on driving positive pricing and reimbursement decisions in Europe, continuing to stabilize the U.S. business, advancing our international strategy and progressing on our FDC program. As we continue our work, our Board refreshment process remains active. We are open to all qualified candidates and have offered to interview two of Sarissa’s new nominees with backgrounds in specific areas we are evaluating as part of our ongoing Board refreshment process. The newly refreshed Amarin Board has put the Company on a solid path on which management is executing. Amarin's new strategy is taking root and deserves another year to prove the value it is creating. Sarissa and its candidates have not put forth any plan to deliver value. The Board continues to look to augment its skillset with strong experience in cardiology and commercial execution. As we evaluate candidates who have those skills, we offered to interview two of Sarissa’s nominees, Paul Cohen, MD and cardiologist, and Diane Sullivan, who has some experience with commercial launches. Sarissa has indicated that any engagement is predicated on shareholder representation. We are here to build the best Board possible to generate value for all shareholders – shouldn’t that be Sarissa’s goal too? Sarissa’s other candidates do not provide incremental industry or public company expertise beyond the Board’s current makeup to help oversee Amarin’s execution. This is why we recommend that Amarin shareholders vote against adding Sarissa’s slate to the Board. Your Vote is Important – Help Ensure Amarin’s Continued Momentum Our refreshed Board is best equipped to guide the NEW Amarin. Our highly relevant experience in international, and in particular European, cardiovascular and related product launches has been vital to Amarin’s early success. Do not let Sarissa derail Amarin’s positive trajectory by replacing your Chairman and appointing its hand-picked, underqualified nominees. We do not believe the changes to the Board proposed by Sarissa are warranted or in the best interests of all shareholders at this time. Protect the value of your investment and vote the WHITE proxy card today “AGAINST” all of Sarissa’s resolutions. Thank you for your support,The Amarin Board of Directors YOUR VOTE IS IMPORTANT! If you have any questions, or need assistance in voting your ADS or shares on the WHITE proxy card, please call our proxy solicitor: Morrow Sodali LLC Okapi Partners LLC509 Madison Avenue, 12th Floor1212 Avenue of the Americas, 17th FloorNew York, NY 10022 New York, NY 10036 Toll-free: 1 (800) 662-5200 Toll-free: 1 (844) 343-2625Collect: 1 (203) 658-9400 International: 1 (212) 297-0720Email: AMRN@info.morrowsodali.com Email: info@okapipartners.com Advisors J.P. Morgan is acting as financial advisor. Ropes & Gray LLP and Goodwin Procter LLP are acting as legal advisors to the Company. About Amarin Amarin is an innovative pharmaceutical company leading a new paradigm in cardiovascular disease management. From our foundation in scientific research to our focus on clinical trials, and now our commercial expansion, we are evolving and growing rapidly. Amarin has offices in Bridgewater, New Jersey in the United States, Dublin in Ireland, Zug in Switzerland, and other countries in Europe as well as commercial partners and suppliers around the world. We are committed to increasing the scientific understanding of the cardiovascular risk that persists beyond traditional therapies and advancing the treatment of that risk. Forward-Looking Statements This press release contains forward-looking statements which are made pursuant to U.S. federal securities law. These forward-looking statements are not promises or guarantees and involve substantial risks and uncertainties. A further list and description of these risks, uncertainties and other risks associated with an investment in Amarin can be found in Amarin’s filings with the U.S. Securities and Exchange Commission, including Amarin’s annual report on Form 10-K for the full year ended 2021, and Amarin’s quarterly reports on Form 10-Q for the quarters ended March 31, 2022, June 30, 2022, and September 30, 2022, and its other filings. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date they are made. Amarin undertakes no obligation to update or revise the information contained in its forward-looking statements, whether as a result of new information, future events or circumstances or otherwise. Amarin’s forward-looking statements do not reflect the potential impact of significant transactions the company may enter into, such as mergers, acquisitions, dispositions, joint ventures or any material agreements that Amarin may enter into, amend or terminate. Amarin Contact Information Investor Inquiries:Lisa DeFrancescoInvestor Relations Amarin Corporation plcinvestor.relations@amarincorp.com (investor inquiries) Media Inquiries:Mark MarmurCorporate Communications, Amarin Corporation plcPR@amarincorp.com (media inquiries) Or Steve Frankel / Andi Rose / Tali EpsteinJoele Frank, Wilkinson Brimmer Katcher212-355-4449

高管变更

100 项与 Enalaprilat 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D03769	Enalaprilat	C09AA02	DB09477

研发状态

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
高血压	美国	Biovail Laboratories International SRL	1988-02-09

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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


NCT04640571 (CTgov)	临床4期	-	18	Metformin (Metformin)	憲鏇積遞餘淵遞衊觸遞(艱積衊蓋蓋襯齋齋窪憲) = 壓艱夢遞鹹鹽淵艱獵鏇範襯鏇顧膚獵壓繭餘窪 (獵製壓獵淵鹽鹽鑰願鹹, 34.1) 更多	-	2024-07-16
				placebo+enalaprilat+pravastatin+valacyclovir+CDCA (Placebo)	憲鏇積遞餘淵遞衊觸遞(艱積衊蓋蓋襯齋齋窪憲) = 網廠衊蓋遞憲窪醖鹹鹹範襯鏇顧膚獵壓繭餘窪 (獵製壓獵淵鹽鹽鑰願鹹, 24.7) 更多
NCT01669434 (CTgov)	临床4期	低血压	291	LISINOPRIL+Captopril+ENALAPRILAT+BENAZEPRIL HYDROCHLORIDE+PERINDOPRIL ERBUMINE+RAMIPRIL+QUINAPRIL HYDROCHLORIDE+Enalapril Maleate+Perindopril Arginine+FOSINOPRIL SODIUM+TRANDOLAPRIL+MOEXIPRIL HYDROCHLORIDE (ACEI Omission)	衊衊遞鏇餘鬱觸夢獵網 = 網餘壓憲積醖構憲網鬱鹹範繭選窪齋遞襯繭繭 (壓製觸衊齋艱鏇糧範壓, 鑰構襯簾艱構簾窪鹽鬱 ~ 製窪廠鹹願衊遞衊鹹積) 更多	-	2017-12-11
				ACEI continuation (ACEI Continuation)	衊衊遞鏇餘鬱觸夢獵網 = 蓋選鏇觸構觸壓糧願鏇鹹範繭選窪齋遞襯繭繭 (壓製觸衊齋艱鏇糧範壓, 醖壓網夢鬱築膚積艱艱 ~ 糧簾衊繭窪夢積淵鏇鹽) 更多
NCT00248807 (CTgov)	N/A	脊髓损伤 \| 直立性低血压 \| 四肢麻痹	30	Head up tilt (HUT) (ARM 1)	網鹹淵餘蓋網夢繭選衊(願製淵壓選壓築餘選製) = 顧獵鏇壓觸艱範鹹鹹製夢壓鑰製衊糧觸鏇膚繭 (鬱鬱襯鬱網淵製鑰築憲, 37) 更多	-	2014-06-23
				Head up tilt (HUT)+1.25 mg enalaprilat IV (ARM 2)	網鹹淵餘蓋網夢繭選衊(願製淵壓選壓築餘選製) = 艱簾鹹齋淵築積顧鹹艱夢壓鑰製衊糧觸鏇膚繭 (鬱鬱襯鬱網淵製鑰築憲, 15) 更多