去氨普酶(Desmoteplase) - 药物靶点：PLG_专利_临床

概要

基本信息

药物类型

酶

别名

Bat-PA、Bat-tPA、Desmoteplase (USAN/INN)

+ [10]

靶点

PLG

作用方式

刺激剂

作用机制

PLG刺激剂(纤溶酶原刺激剂)

治疗领域

神经系统疾病心血管疾病

在研适应症-

非在研适应症

急性缺血性卒中

原研机构

Bayer AG

在研机构-

非在研机构

Forest Laboratories LLC

H. Lundbeck A/SLundbeck Japan KK

+ [1]

权益机构-

最高研发阶段终止临床3期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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结构/序列

Sequence Code 73158

来源: *****

关联

7

项与去氨普酶相关的临床试验

NCT01104467

/ Completed临床2期

Randomised, Double-blind, Placebo-controlled, Dose-escalation Study of Desmoteplase in Japanese Patients With Acute Ischemic Stroke

The purpose of the study is to evaluate whether desmoteplase is safe and tolerated when given to Japanese patients with acute ischemic stroke

开始日期2010-08-01

申办/合作机构

Lundbeck Japan KK

NCT00856661

/ Terminated临床3期

A Randomised, Double-Blind, Parallel-Group Placebo-Controlled Phase III Study to Evaluate the Efficacy and Safety of Desmoteplase in Subjects With Acute Ischemic Stroke

The purpose of the study is to determine whether desmoteplase is effective and safe in the treatment of patients with acute ischaemic stroke when given within 3 to 9 hours from onset of stroke symptoms.

开始日期2009-04-01

申办/合作机构

H. Lundbeck A/S

NCT00790920

/ Completed临床3期

A Randomised, Double-blind, Parallel-group Placebo-controlled Phase III Study to Evaluate the Efficacy and Safety of Desmoteplase in Subjects With Acute Ischemic Stroke

The purpose of the study is to determine whether desmoteplase is effective and safe in the treatment of patients with acute ischaemic stroke when given within 3-9 hours from onset of stroke symptoms.

开始日期2008-12-01

申办/合作机构

H. Lundbeck A/S

100 项与去氨普酶相关的临床结果

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100 项与去氨普酶相关的转化医学

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100 项与去氨普酶相关的专利（医药）

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124

项与去氨普酶相关的文献（医药）

2025-02-04·LANGMUIR

Effects of Lipid Headgroups on the Mechanical Properties and In Vitro Cellular Internalization of Liposomes

Article

作者: Abdelmessih, Rudolf G. ; Pandey, Simran ; Pérez Tetuán, Jimena ; Adepoju, Stephen ; Williams, Mary ; Hung, Francisco R. ; Auguste, Debra T. ; Xu, Jiaming

We performed all-atom and coarse-grained simulations of lipid bilayer mixtures of the unsaturated lipid DOPC, with saturated lipids having the same 18-carbon acyl tails and different headgroups, to understand their mechanical properties. The secondary lipids were DSPG, DSPA, DSPS, DSPC, and DSPE. The DOPC:DSPG system with 65:35 molar ratio was the softest, with area compressibility modulus K_A ∼ 22% smaller than the pure DOPC value. Raising the mole % of DOPC leads to increases in K_A, yet at any given composition the K_A trend is DSPG < DSPA < DSPS < DSPC < DSPE. Lipid-lipid interactions are weaker in DOPC:DSPG mixtures and stronger in DSPE systems. The head and phosphate groups of the secondary lipids DSPG, DSPA, and DSPS interact strongly with salt ions. Adding secondary lipids leads to DOPC having more ordered acyl tails relative to pure DOPC systems. No evidence of phase separation or inhomogeneities was observed in our simulations. We synthesized three liposomal formulations, L-DOPC (pure DOPC) and L-DOPC/DSPG and L-DOPC/DSPA, both with 15 mol % of secondary lipid. L-DOPC/DSPA had approximately 3- and 2-times higher in vitro internalization by normal epithelial (EpH4-Ev) and metastatic breast cancer (4T1) cells, compared with L-DOPC. The uptake of L-DOPC/DSPG by EpH4-Ev cells was almost 2-fold compared to L-DOPC, but both liposomes had similar uptakes by cancer cells. As L-DOPC/DSPG and L-DOPC/DSPA have similar K_A values, we presumed that the mechanical properties, possibly in combination with the higher negative surface charges in L-DOPC/DSPA and differences in effective liposome diameters and diffusivities, contributed to these observations.

2024-03-01·Biochimica et biophysica acta. Biomembranes

Magnetically controlled insertion of magnetic nanoparticles into membrane model

Article

作者: Juarez, Ana V ; Riva, Julieta S ; Moya Betancourt, Sara N ; Cámara, Candelaria I

Polysaccharide-coated magnetic nanoparticles (MNPs) have been reported to show potential applications in many biomedical fields. In this report, we have studied the interactions between magnetite (Fe₃O₄) MNPs functionalized with polysaccharides (diethylamino-ethyl dextran, DEAE-D or chitosan, CHI) with different membranes models by Langmuir isotherms, incorporation experiments, and brewster angle microscopy (BAM). In this report, zwitterionic 1,2-distearoyl-sn-glycerol-3-phosphoethanolamine (DSPE) and anionic 1,2-distearoyl-sn-glycerol-3-phosphate (DSPA) phospholipid, were used to form membrane models. Incorporation experiments (π-t) as well as the compression isotherms demonstrate positive interactions between MNPs and DSPE or DSPA monolayers. The study assessed the impact of varying initial surface pressure on a preformed phospholipid monolayer to determine the maximum insertion pressure (MIP) and synergy. Our findings indicate that the primary driving force of the coated MNPs incorporation into the monolayer predominantly stems from electrostatic interaction. The drop in the subphase pH from 6.0 to 4.0 led to an enhancement of the MIP value for DSPA phospholipid monolayer. On the other hand, for DSPE, the drop in the pH does not affect the MIP values. Besides, the presence of a magnetic field induces an enhancement of the insertion process of the MNPs into DSPA preformed monolayer, demonstrating that a previous interaction between MNPs and phospholipid preformed monolayer needs to take place to enhance the incorporation process. This work opens novel perspectives for the research of the influence of magnetic fields on the incorporation of MNPs into model membranes.

2023-09-01·Biotechnology advances

Identification, characterization, and engineering of glycosylation in thrombolytics

Review

作者: Toul, Martin ; Sedlak, Erik ; Hernychova, Lenka ; Tomkova, Maria ; Urminsky, Adam ; Slonkova, Veronika ; Prokop, Zbynek ; Bednar, David ; Damborsky, Jiri ; Mican, Jan

Cardiovascular diseases, such as myocardial infarction, ischemic stroke, and pulmonary embolism, are the most common causes of disability and death worldwide. Blood clot hydrolysis by thrombolytic enzymes and thrombectomy are key clinical interventions. The most widely used thrombolytic enzyme is alteplase, which has been used in clinical practice since 1986. Another clinically used thrombolytic protein is tenecteplase, which has modified epitopes and engineered glycosylation sites, suggesting that carbohydrate modification in thrombolytic enzymes is a viable strategy for their improvement. This comprehensive review summarizes current knowledge on computational and experimental identification of glycosylation sites and glycan identity, together with methods used for their reengineering. Practical examples from previous studies focus on modification of glycosylations in thrombolytics, e.g., alteplase, tenecteplase, reteplase, urokinase, saruplase, and desmoteplase. Collected clinical data on these glycoproteins demonstrate the great potential of this engineering strategy. Outstanding combinatorics originating from multiple glycosylation sites and the vast variety of covalently attached glycan species can be addressed by directed evolution or rational design. Directed evolution pipelines would benefit from more efficient cell-free expression and high-throughput screening assays, while rational design must employ structure prediction by machine learning and in silico characterization by supercomputing. Perspectives on challenges and opportunities for improvement of thrombolytic enzymes by engineering and evolution of protein glycosylation are provided.

2

项与去氨普酶相关的新闻（医药）

2025-12-10

·百蓁生物

客户文章 | 百蓁生物HDX-MS技术助力中药显奇效——登革病毒抑制剂的发现及其抗病毒机制研究

文章解析研究成果展示 ▶ 发表时间：2025年11月29日 ▶ 期刊：《MedComm 》(IF=10.7) ▶ 发表团队：南方医科大学余林中课题组 ▶ 文章标题：Discovery ofa Novel Non-Nucleoside Inhibitor of RNA-Dependent RNA Polymerase Against Dengue Virus ▶ 核心内容：登革病毒（DENV）是全球分布最广的蚊媒病毒之一，每年导致数亿人感染，数万例死亡，目前尚无特异性抗病毒药物获批。病毒编码的RNA依赖性RNA聚合酶（RdRp）是病毒基因组复制的核心酶，因其在宿主细胞中无同源蛋白而成为理想的抗病毒靶点。近日，南方医科大学研究团队在《MedComm》发表论文，报道从中药三七中分离的天然化合物12β-hydroxydammar-3-one-20(S)-O-β-D-glucopyranoside（PN-1），可特异性靶向RdRp并有效抑制病毒复制，为抗登革病毒药物研发提供了新型先导化合物。 1 研究方法研究团队首先采用表面等离子共振技术，对14种三七来源的达玛烷型三萜皂苷进行筛选，发现PN-1与DENV-2 RdRp的结合亲和力最高，平衡解离常数KD 为1.42 nM。通过等温滴定量热法、细胞热转移实验及药物亲和反应靶点稳定性实验，进一步证实PN-1可直接与病毒非结构蛋白5（NS5）的RdRp结构域结合，且不影响其甲基转移酶结构域功能。 2 研究结果 1.PN-1通过共价修饰调控抑制RdRp活性液相色谱-串联质谱分析表明，PN-1通过其裂解片段共价修饰RdRp上的四个保守氨基酸残基：Glu255、Met387、Glu479和Ala507。定点突变实验证实，这些位点的突变显著减弱PN-1与RdRp的结合能力(图2.A-E)。图2. PN-1共价修饰到RdRp蛋白的LCMSMS谱图（A,C 体内非修饰肽段，B.PN-1修饰到Glu255肽段二级谱图, D. PN-1修饰到Ala507肽段二级谱图，E.对四个位点突变后显著减少PN-1与RdRp蛋白结合） 2.PN-1通过构象调控抑制RdRp活性 HDX-MS氢氘交换质谱分析显示，PN-1处理后，RdRp在多个结构区域的氢氘交换速率发生显著变化，尤其是在拇指结构域（肽段485–501与501–505）的交换率降低，提示该区域构象趋于稳定或封闭（图3）。色氨酸荧光光谱也观察到PN-1引起RdRp内源荧光猝灭，进一步支持其诱导蛋白质构象变化的结论（图2F）。这些构象改变最终导致RdRp酶活抑制，其半抑制浓度为6.10 μM。图3. PN-1结合并调控RdRp构象 3.PN-1在体外与体内模型中表现广谱抗病毒活性 PN-1在多种细胞系中均能显著抑制DENV-2复制，降低病毒RNA、蛋白表达及病毒斑块形成。作用阶段分析表明，PN-1主要作用于病毒复制早期，对病毒吸附与进入过程无影响。此外，PN-1对DENV-1和DENV-3同样具有抑制活性，提示其具备跨血清型抗病毒潜力。在ICR鼠和AG129小鼠模型中，PN-1治疗能显著缓解病毒感染引起的体重下降、临床症状及组织病理损伤，并提高存活率（图4）。在AG129小鼠中，PN-1还可降低血清病毒载量，减轻肝脏、小肠和结肠的病理损伤。图4. PN-1处理显著降低因病毒DENV-2引起的AG129小鼠生存危机 4.氢氘交换质谱HDXMS在机制阐释中的关键作用本研究通过HDX-MS技术，从蛋白质构象动力学层面揭示了PN-1的作用机制。该技术通过监测蛋白质肽键氢与氘的交换速率，反映蛋白质局部结构的动态性与溶剂可及性。实验结果显示：交换率降低的区域：主要位于拇指（thumb)结构域及部分指掌区，提示PN-1结合后这些区域构象更稳定或更封闭，可能与活性口袋变构调控有关；交换率升高的区域：分布于其他指(finger)掌(palm)区段，提示局部结构可能变得更动态或更暴露。这些数据不仅证实PN-1与RdRp发生物理结合，更重要的是阐明其通过变构调控机制改变酶的功能构象，从而抑制其催化活性。 HDX-MS所提供的动态结构信息，为理解PN-1作为非核苷类抑制剂的分子机制提供了直接证据。 PN-1作为首个被发现可通过共价修饰RdRp并变构调控其功能的天然来源非核苷类抑制剂，具有广谱应用潜力。由于RdRp在RNA病毒中相对保守，提示PN-1可能对黄病毒科其他成员（如寨卡病毒、丙肝病毒）也具有抑制活性。优品推荐 HDX-MS完整解决方案百蓁生物提供全套的 HDX-MS 服务体系，以发现各种类型样品，例如单克隆抗体(mAb)、抗体-药物偶联物(ADC)、病毒衣壳、生物仿制药等蛋白质构象、动力学、相互作用的信息，可用于生物仿制药评价、治疗性蛋白质QC、药理学研究等应用领域。服务优势：经验丰富：5年+专业团队经验，100+成功项目，助力发表10+高分文章。预实验保障：独家免费定制化预实验，确保正式实验高效推进。深度数据解析：自主PEAKS®软件平台精准分析，提升肽段覆盖率和数据准确性。全流程优化：一站式服务+人工谱图校正，保证结果高重现性、高准确性和高稳定性。可视化呈现：丰富图表结合pyMOL/Chimera蛋白结构渲染，提升结果直观性与可读性。图5. HDX-MS结果展示形式往期好文推荐【服务升级】氢氘交换质谱（HDX-MS）生物药高级结构分析【服务升级】百蓁生物HDX-MS技术，精准解析抗体/生物药高级结构与动态构象！【服务升级】HDX-MS抗原表位分析, 结构可视化+数据精准双突破! 【服务升级】高精度HDX-MS平台上线！优化分辨率与重现性，助力蛋白动态研究新突破关注我们了解更多在生物医药行业蓬勃发展的今天，医药企业百舸争流，力争上游。2020年，加拿大皇家科学院院士李明院士和单宝珍博士首创基于质谱的抗体和新抗原从头测序技术落地中国，百蓁生物应运而生，蓁蓁绿叶，助力医药研发桃花盛开。（注：百蓁取名源自《诗经·周南·桃夭》中“桃之夭夭，其叶蓁蓁”，寓意草木茂盛，欣欣向荣） 2021年12，百蓁上海研发中心成立，进一步加大研发投入，助力精准医疗。百蓁生物（Baizhen Biotechnologies）是一家以AI驱动质谱技术，聚焦精准医疗的生物科技公司，是Bioinformatics Solutions Inc的中国分公司，致力于构建免疫组学中心，推进抗体和新原在肿瘤和自身免疫治疗中的应用。百蓁生物通过抗体和新抗原的发现，设计，结构预测与表征，以服务医药研发为宗旨，为免疫治疗科研机构和生物医药企业研发生产提供精准、高效的个性化质谱解决方案。公司分别在武汉、上海和加拿大建有先进的质谱实验室，拥有经验丰富的技术团队和先进的Orbitrap Eclipse、timsTOF pro2等高分辨率质谱仪和全套的氢氘交换质谱系统，依托自主知识产权的PEAKS®数据分析系统，服务国内外超过4000多家客户单位，准确度和客户满意度遥遥领先，成为国内外制药企业、ivd企业和科研机构的首选。 BAIZHENBIO. 欢迎戳“阅读原文”进入官网了解更多！！!

临床研究临床终止临床1期临床结果

2007-06-04

·Pharma Times

Lundbeck shares sink as stroke drug desmoteplase falters

Shares in Denmark’s Lundbeck have taken a battering after the company, along with partners Paion of Germany and the USA’s Forest Laboratories announced disappointing late-stage data for the new stroke drug desmoteplase. Data presented at the European Stroke Conference in Glasgow, Scotland revealed that the Phase III DIAS-2 study of desmoteplase in acute ischemic stroke failed to indicate any difference versus placebo. The primary efficacy endpoint of the 186-patient study was clinical improvement at day 90 but while 47.4% treated with 90mcg desmoteplase and 36.4% on 125mcg of the drug responded well, so did a lofty 46% in the placebo group. Four deaths were reported in the placebo group compared with 17 among those taking desmoteplase, three receiving the lower dose of the drug and 14 receiving the 125mcg dose within the 90-day follow-up period. However, ten of those 14 “were considered by the investigators as not related to the drug, nine of which occurred 14 or more days after stroke and were from non-neurological causes," the companies said. The firms stated that “these data are surprising and are not consistent with previously observed patterns” in other stroke trials, adding that “the absence of consistency with previous findings is not easy to explain, but in-depth analyses are planned to better understand the data”. In a conference call afterwards, Paion's chief executive Wolfgang Soehngen said he was disappointed but claimed that “desmoteplase didn't fail, placebo was just by chance better than usual". Lundbeck said it will await the outcome of the detailed analysis before deciding if it will proceed with a second Phase III trial of desmoteplase. Investors seem to think that further development may not happen and the stock ended down 8% on Friday night on the Copenhagen Stock Exchange. The news represents yet another clinical setback for Lundbeck which announced in March that it was discontinuing development of its insomnia drug gaboxadol, which was partnered with Merck & Co. The desmoteplase disappointment prompted Dresdner Kleinwort to reiterate its ‘reduce’ rating on the firm in a research note and the analysts said Lundbeck’s late-stage pipeline is looking far too slim. They added that the company remains greatly exposed to the weak US dollar and the patent expiry of the antidepressant Lexapro (escitalopram) in 2012, and suggested that the firm’s management should start to seek merger partners.

并购合作

100 项与去氨普酶相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D03695	去氨普酶	-	DB04925

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
急性缺血性卒中	临床3期	美国	Forest Laboratories LLC	2005-04-01
急性缺血性卒中	临床3期	澳大利亚	Forest Laboratories LLC	2005-04-01
急性缺血性卒中	临床3期	奥地利	Forest Laboratories LLC	2005-04-01
急性缺血性卒中	临床3期	加拿大	Forest Laboratories LLC	2005-04-01
急性缺血性卒中	临床3期	芬兰	Forest Laboratories LLC	2005-04-01
急性缺血性卒中	临床3期	德国	Forest Laboratories LLC	2005-04-01
急性缺血性卒中	临床3期	荷兰	Forest Laboratories LLC	2005-04-01
急性缺血性卒中	临床3期	西班牙	Forest Laboratories LLC	2005-04-01

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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


NCT00856661 (CTgov)	临床3期	急性缺血性卒中	270	Desmoteplase (Desmoteplase)	觸選醖鑰窪願鹽繭廠鏇 = 窪範憲糧夢鬱糧蓋鑰網鏇鹽壓鬱獵衊廠艱簾願 (廠夢鑰壓鹽獵鏇齋構窪, 繭襯廠壓壓鏇鏇顧鹽壓 ~ 網鏇遞醖願醖淵淵衊膚) 更多	-	2015-12-22
				Placebo (Placebo)	觸選醖鑰窪願鹽繭廠鏇 = 淵壓餘壓淵觸獵廠鹹淵鏇鹽壓鬱獵衊廠艱簾願 (廠夢鑰壓鹽獵鏇齋構窪, 鹹襯鑰餘簾衊鬱鬱構繭 ~ 鬱選醖願鹽願積壓遞願) 更多
NCT01104467 (Pubmed \| Cochrane Database Syst Rev \| Stroke) 人工标引	临床2期	缺血性卒中	-	Desmoteplase	醖醖選衊窪構選憲顧顧(網餘衊憲醖夢憲鬱構繭) = 願範蓋衊鹹顧範顧窪憲選願築遞憲糧夢齋鹽夢 (襯襯遞餘鬱餘膚願獵範 ) 更多	积极	2015-09-01
				Placebo	醖醖選衊窪構選憲顧顧(網餘衊憲醖夢憲鬱構繭) = 遞壓襯鬱窪蓋簾鏇膚鬱選願築遞憲糧夢齋鹽夢 (襯襯遞餘鬱餘膚願獵範 ) 更多
NCT00790920 (DIAS-3, Pubmed \| Lancet Neurol) 人工标引	临床3期	缺血性卒中	492	desmoteplase	淵鹹齋積憲艱鏇窪艱構(網顧選範夢憲憲膚膚積) = 膚衊願餘鬱築廠鬱廠簾積鹹選築廠齋選鬱憲廠 (構鹹顧鹹廠觸構範糧簾 ) 更多	不佳	2015-06-01
				Placebo	淵鹹齋積憲艱鏇窪艱構(網顧選範夢憲憲膚膚積) = 膚夢獵鑰夢鬱窪製鏇膚積鹹選築廠齋選鬱憲廠 (構鹹顧鹹廠觸構範糧簾 ) 更多
NCT00111852 \| NCT00638248 \| NCT00638781 (Pubmed \| Stroke)	N/A	-	-	Desmoteplase	鏇積鑰鏇顧網憲醖膚鑰(遞構構鏇蓋網觸衊鬱夢) = 願齋築淵製構餘繭願選醖齋鏇鏇網鑰製夢憲襯 (簾製膚簾繭顧構選簾鬱 )	-	2012-09-01
				Placebo	鏇積鑰鏇顧網憲醖膚鑰(遞構構鏇蓋網觸衊鬱夢) = 鏇蓋構網夢膚繭鹹獵繭醖齋鏇鏇網鑰製夢憲襯 (簾製膚簾繭顧構選簾鬱 )
NCT00111852 \| NCT00638248 \| NCT00638781 (Pubmed \| Stroke)	临床3期	急性缺血性卒中	-	Desmoteplase	餘網積顧鑰夢衊網壓鑰(齋網醖顧蓋齋網築積鹹) = 獵窪夢繭積鑰網壓艱繭壓願簾築醖淵觸製獵選 (憲構衊蓋鑰鏇夢齋願艱 )	-	2012-06-01
				Placebo	餘網積顧鑰夢衊網壓鑰(齋網醖顧蓋齋網築積鹹) = 廠淵齋艱製衊膚選繭壓壓願簾築醖淵觸製獵選 (憲構衊蓋鑰鏇夢齋願艱 )
ISC2012	临床3期	急性缺血性卒中	-	Desmoteplase	廠獵蓋餘鹹餘積壓築繭(選築鏇選獵鹽簾鏇蓋壓) = 鏇窪衊網觸膚繭膚構壓齋膚範壓憲鬱顧鹽夢鏇 (夢鹹積壓製鬱繭鬱醖遞 )	-	2012-02-01
				Placebo	廠獵蓋餘鹹餘積壓築繭(選築鏇選獵鹽簾鏇蓋壓) = 衊獵衊簾鏇鹹顧憲構顧齋膚範壓憲鬱顧鹽夢鏇 (夢鹹積壓製鬱繭鬱醖遞 )
NCT00111852 (DIAS-2, Pubmed \| Lancet Neurol)	临床3期	急性缺血性卒中	193	90 microg/kg desmoteplase	網齋鬱製憲夢糧齋鏇糧(夢鑰糧繭淵築簾鏇糧糧) = 獵簾壓獵廠蓋襯鏇繭醖遞壓繭鹽遞簾糧鏇遞窪 (選憲餘鏇憲構選獵膚鹹 ) 更多	不佳	2009-02-01
				125 microg/kg desmoteplase	網齋鬱製憲夢糧齋鏇糧(夢鑰糧繭淵築簾鏇糧糧) = 獵衊膚鬱憲廠醖願艱窪遞壓繭鹽遞簾糧鏇遞窪 (選憲餘鏇憲構選獵膚鹹 ) 更多
DEDAS (Pubmed \| Stroke)	临床1/2期	急性缺血性卒中	37	Placebo	遞遞繭鏇範糧憲襯鏇遞(艱鏇鏇鬱願鏇築築廠窪) = 糧糧餘願夢積廠蓋窪繭鏇鏇築襯鑰獵積艱廠糧 (襯蓋鏇壓遞艱憲鑰壓選, [8.5 ~ 75.5]) 更多	-	2006-05-01
				Desmoteplase 90 microg/kg	遞遞繭鏇範糧憲襯鏇遞(艱鏇鏇鬱願鏇築築廠窪) = 願網鹹鹹糧齋鹽廠廠膚鏇鏇築襯鑰獵積艱廠糧 (襯蓋鏇壓遞艱憲鑰壓選, [2.3 ~ 51.8]) 更多
DIAS (Pubmed \| Stroke)	临床2期	急性缺血性卒中	104	Desmoteplase	糧壓醖醖憲衊鹹鏇鹽蓋(衊襯繭鬱網鑰夢選壓廠) = 膚鬱鑰鹹衊憲糧餘網窪簾衊齋獵鹽選艱築淵糧 (築製憲願膚壓願遞衊觸 ) 更多	积极	2005-01-01
				Placebo	糧壓醖醖憲衊鹹鏇鹽蓋(衊襯繭鬱網鑰夢選壓廠) = 衊鹽顧壓餘窪淵範襯齋簾衊齋獵鹽選艱築淵糧 (築製憲願膚壓願遞衊觸 )