更新于：2024-12-07

Clemastine Fumarate

富马酸氯马斯汀

更新于：2024-12-07

概要

概要

基本信息

药物类型

小分子化药

别名

(+)-(2R)-2-(2-(((R)-p-chloro-α-methyl-α-phenylbenzyl)oxy)ethyl)-1-methylpyrrolidine、(+)-(2R)-2-[2-[[(R)-p-chloro-α-methyl-α-phenylbenzyl]oxy]ethyl]-1-methylpyrrolidine、Clemastine

+ [9]

靶点

H1 receptor

作用机制

H1 receptor拮抗剂(组胺H1受体拮抗剂)

治疗领域

在研适应症

非在研适应症

原研机构

在研机构

NISSIN Pharmaceutical Co., Ltd.

山东力诺制药有限公司

山东科源制药股份有限公司

非在研机构

Novartis Pharmaceuticals Corp.

NovaDel Pharma, Inc.

最高研发阶段批准上市

首次获批日期

日本 (1970-01-17),

普通感冒皮炎湿疹+ [3]

最高研发阶段(中国)批准上市

特殊审评-

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结构

分子式C25H30ClNO5

InChIKeyPMGQWSIVQFOFOQ-YKVZVUFRSA-N

CAS号14976-57-9

关联

项与富马酸氯马斯汀相关的临床试验

NCT06591091 / Not yet recruiting临床2期IIT

Clemastine for Improving White Matter and Boosting Antidepressant Response in Late-life Depression

The goal of this study is to find out if the antihistamine, clemastine, can make the white matter in the brain better in older adults with depression. The study will also determine whether this improvement can make antidepressant treatment work better, reduce depressive symptoms, and improve memory and thinking.

开始日期2024-10-01

申办/合作机构

University of Illinois

[+1]

NCT06065670 / Not yet recruiting临床1/2期IIT

A Randomized, Double-Blind, Delayed Treatment, Placebo-Controlled Trial to Assess the Changes in Multi-parametric MRI in Patients With Acute Demyelinating Lesions Taking Clemastine Fumarate as a Myelin Repair Therapy

The clinical trial is intended to assess for clinical evidence of Clemastine Fumarate as a myelin repair therapy in patients with acute inflammatory injury-causing demyelination as measured by multi-parametric MRI assessments.
No reparative therapies exist for the treatment of acute demyelinating lesions. Clemastine fumarate was identified along with a series of other antimuscarinic medications as a potential remyelinating agent using the micropillar screen (BIMA) developed at the University of California, San Francisco (UCSF). Following in vivo validation, an FDA IND exemption was granted to investigate clemastine for the treatment of multiple sclerosis in the context of chronic optic neuropathy. That pilot study was recently completed and is the first randomized control trial documenting efficacy for a putative remyelinating agent for the treatment of MS. The preselected primary efficacy endpoint (visual evoked potential) was met and a strong trend to benefit was seen for the principal secondary endpoint assessing function (low contrast visual acuity). That trial number was 13-11577.
This study seeks to follow up on that study and examine clemastine fumarate's protective and reparative effects in the context of acute demyelinating brain lesions as imaged by multi-parametric MRI assessments. The investigators will be assessing the effects of clemastine fumarate as a remyelinating therapy and assessing its effect on MRI metrics of lesions found in patients with a confirmed diagnosis of acute inflammatory injury-causing demyelination.
In addition to using conventional multi-parametric MRI assessments, this study will also evaluate a new MRI technique called Ultrashort Echo Time (UTE) MRI to assess the effects of clemastine fumarate as a remyelinating therapy of acute lesions found in patients with a confirmed diagnosis of acute inflammatory injury-causing demyelination and compare it to the other assessments.

开始日期2024-09-15

申办/合作机构

The University of California, San Francisco

NCT06087757 / Recruiting临床3期IIT

Clemastine Treatment in Individuals With Williams Syndrome- a Double-blind Placebo Control to Assess the Safety and Efficacy

This study explores the neurobiological etiology of Williams syndrome and potential therapeutic targets for associated social, motor, and cognitive abnormalities. The main translational objective will be to test the effectiveness of Clemasntine on neurocognitive and other associated abnormalities in individuals with Williams syndrome.

开始日期2024-04-01

申办/合作机构

Sheba Medical Center

[+1]

100 项与富马酸氯马斯汀相关的临床结果

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100 项与富马酸氯马斯汀相关的转化医学

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100 项与富马酸氯马斯汀相关的专利（医药）

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482

项与富马酸氯马斯汀相关的文献（医药）

2025-01-01·BRAIN RESEARCH

Clemastine enhances exercise-induced motor improvement in hypoxic ischemic rats

Article

作者: Kunori, Nobuo ; Komaki, Yuji ; Goto, Taichi ; Tsurugizawa, Tomokazu ; Iwaki, Sunao ; Takashima, Ichiro

Neonatal hypoxic ischemia (HI) occurs owing to reduced cerebral oxygen levels and perfusion during the perinatal period. Brain injury after HI triggers neurological manifestations such as motor impairment, and the improvement of impaired brain function remains challenging. Recent studies suggest that cortical myelination plays a role in motor learning, but its involvement in motor improvement after HI injury is not well understood. This study aimed to investigate the impact of myelination on motor improvement following neonatal HI injury. We employed a modified Rice-Vannucci model; the right common carotid artery of postnatal day 7 (P7) Wistar rats was isolated and divided, and the rats were then exposed to hypoxic condition (90 min, 8 % O2). A total of 101 rats (66 males) were divided into four groups: trained-HI (n = 38), trained-Sham (n = 16), untrained-HI (n = 31), and untrained-Sham (n = 16). The trained groups underwent rotarod-based exercise training from P22 to P41 (3 days per week). Structural analysis using magnetic resonance imaging and immunohistochemistry (n = 6 per group) revealed increased fractional anisotropy and myelin density in the primary somatosensory cortex of the trained-HI group. We further evaluated the effect of myelination promotion on rotarod performance by administering clemastine, a myelination-promoting drug, via daily intraperitoneal injections. Clemastine did not enhance motor improvement in untrained-HI rats. However, clemastine-administered trained-HI rats (n = 7) exhibited significantly improved motor performance compared to both saline-administered trained-HI rats (n = 11) and clemastine-administered untrained-HI rats (n = 7). These findings suggest that myelination may be a key mechanism in motor improvement after HI injury and that combining exercise training with clemastine administration could be an effective therapeutic strategy for motor improvement following HI injury.

2024-12-31·Molecular & Cellular Oncology

Clemastine and hyperthermia enhance sensitization of osteosarcoma cells for apoptosis

Article

作者: Kumar, Deepak ; Hoang, Hieu ; He, Yiping ; Vandana ; Niture, Suryakant ; Gadi, Sashi ; Obu, Somtochukwu

Clemastine is an antagonist of histamine H1 receptor may provide benefits in the treatment of osteosarcoma (OS). In the current study, we used hyperthermia approach to sensitize OS cells to clemastine-mediated cell death. Osteosarcoma U-2 OS and Saos-2 cells were treated with clemastine at 37°C, followed by 42°C for 2 h, and released at 37°C for 6 h. The impact of clemastine and hyperthermia on OS cell survival and autophagy-mediated cell death was investigated. Exposure of U-2 OS and Saos-2 cells to clemastine and hyperthermia (42°C) inhibited dose-dependent clemastine-mediated cell survival by increasing cell apoptosis. Hyperthermia and clemastine exposure modulated inflammatory and unfolded protein response (UPR) signaling differentially in U-2 OS and Saos-2 cells. Exposure of U-2 OS and Saos-2 cells to hyperthermia and clemastine inhibited AKT/mTOR and induced expression of the autophagy biomarkers LC3B II and LC3-positive puncta formation. The inhibition of autophagy by 3-methyladenine blocked hyperthermia and clemastine-mediated induction of LC3B II, LC3-positive puncta formation, and OS cell apoptosis. These results indicate that clemastine and hyperthermia sensitize OS cell lines by inducing increased autophagic cell death. Collectively, our data suggest that hyperthermia along with antihistamine therapy may provide an improved approach for the treatment of OS.

2024-10-18·ANNALS OF NEUROLOGY

Clemastine Induces Oligodendrocyte Progenitor Pool Exhaustion and Senescence in the Context of Chronic Demyelination in a Rabbit Model.

Article

作者: Ravichandar, Roopa ; Buck, Gregory T ; Raymond, Faye D ; Sim, Fraser J ; Frost, Jon R ; Gadelkarim, Farah ; Muthaiah, Rupadevi ; Cooper, James J M

OBJECTIVES:

Clemastine has emerged as a promising therapy for the restoration of neurologic function in patients with multiple sclerosis (MS). However, clemastine and other agents with prodifferentiative effects on oligodendrocyte progenitor cells (OPCs) in rodent models have underperformed in clinical trials. We hypothesized that the preclinical studies showed more robust effects because of the abundance of OPCs in rodent models. To better examine the therapeutic potential of clemastine, we examined its effect on demyelinated white matter lesions in rabbits, which exhibit progenitor densities and limited remyelination more closely matching those found in tissues from patients with MS.

METHODS:

We used lysolecithin to induce demyelination in white matter of New Zealand rabbits and then administered oral clemastine (10mg/kg/day) for various periods before assessing the OPC and oligodendrocyte (OL) populations in these lesions.

RESULTS:

Daily administration of clemastine for the full study period (56 days) increased oligodendrogenesis in white matter lesions. However, shorter durations of treatment failed to increase overall OL density despite enhancing OPC-to-OL differentiation. This effect was due to exhaustion of the OPC pool, as the differentiating progenitors were not replaced because of reduced OPC proliferation. Notably, delayed administration of clemastine led to an accumulation of activated OPCs expressing markers of senescence.

INTERPRETATION:

Although capable of driving OL differentiation, clemastine treatment in rabbits hampered progenitor pool replenishment, induced senescence, and promoted conversion of microglia/macrophages to a proinflammatory phenotype. Whether these effects would also occur in humans or with other prodifferentiative therapies should be studied further, but our data suggest the need to carefully consider progenitor dynamics in the treatment of MS. ANN NEUROL 2024.

项与富马酸氯马斯汀相关的新闻（医药）

2024-04-03

·生物制药小编

什么Biotech让强生和百济二股东看好？

昨日（4月1日），随着Contineum Therapeutics的FORM S-1文件更新披露，已经可以看到这家Biotech IPO过程的具体细节。此次IPO预计将会以16-18美元/每股发放880万股，最终募股规模有可能超过此前预计的1.5亿美元。股东方面，之前就是Contineum Therapeutics投资人的强生附属基金JJDC，知名资本Sectoral Asset Management，还吸引来了曾经的Seagen大股东和现在百济二股东Baker Brother。Contineum Therapeutics将是今年第八家申请上市的Biotech企业，但是与之前几家IPO的比如说：Alto Neuroscience、ArriVent Biopharma、CG Oncology、Kyverna Therapeutics和Metagenom较为不同的是，这家小分子药物公司的IPO募股金额相对较高，适应症上主要开发多发性硬化症（MS）这一红海市场，目前管线还都处于临床早期。按理来说，多发性硬化症是罕见病中竞争较为激烈的红海市场，从市场角度来看，曾经的霸主Biogen（渤健）这几年都因为仿制药和竞争对手罗氏的深度参与，销量大幅下滑了。竞争激烈程度可见一斑。而在这种情况下，这家公司能得到强生看重，肯定有其特殊的地方。管线概览虽然同样是MS，但是Contineum的管线机制与许多企业大相径庭。现有的MS治疗手段如富马酸二甲酯，Ocrelizumab等治疗手段都是通过抑制炎症的途径来进行治疗的。而Contineum Therapeutics已经明确适应症的管线采用的是两种与现有治疗药物机制完全不同的路线：一种是溶血磷脂酸1受体（LPA1R）抑制剂PIPE-791，另外一种是毒蕈碱1型M1受体（M1R）抑制剂PIPE-307。此外，这家公司还有一款不明适应症的管线：LPA1R抑制剂CTX-343。虽然这两款药物都有两种不同细分的MS适应症，但这家企业也没死磕MS，PIPE-791还能用于开发特发性肺纤维化（IPF），PIPE-307则被额外开发用于抑郁症。强生似乎很看重PIPE-307，Contineum Therapeutics（当时还叫Pipeline Therapeutics）在去年4月与强生授权交易中，不仅获得了5000万美元的预付款，有望获得10亿美元里程碑付款，还获得了2500万美元的股权投资和2500万美元的现有投资人投资。LPA1R抑制剂的开发溶血磷脂酸（LPA）是一种通过特异性G蛋白偶联受体（LPAR）发挥作用的生物活性介质，目前对其在纤维化病因中的作用有所了解。在许多器官中，纤维化与LPA产生增加以及某些LPAR亚型（主要是LPA1R）表达增加有关。所以PIPE-791的适应症是IPF似乎不难理解，而在MS中的应用主要起始于近几年Contineum Therapeutics的开发。MS是一种炎症性脱髓鞘疾病，导致神经元传递中断，最终导致神经变性。目前的治疗重点是抑制免疫系统，以限制炎症和髓鞘的进一步丧失。先前的几篇文献发现，在MS中，炎性脂质、溶血磷脂酸(LPA)水平升高，这种炎症脂质的升高对于MS病情进展是不利的。除了神经炎症，LPA还会抑制少突胶质前体细胞(OPC)分化。而少突胶质前体细胞是产生髓鞘化细胞的细胞，而MS常常伴随着慢性脱髓鞘，抑制LPA可能有助于MS中髓鞘化细胞的再生。而PIPE-791就是这一成果转化的产物。PIPE-791是首个口服生物可利用的脑渗透LPA1拮抗剂。毒蕈碱1型m1受体抑制剂大部分对毒蕈碱1型m1受体抑制剂的开发都集中在阿尔兹海默症和精神疾病如精神分裂症，但是Contineum Therapeutics竟然将其用于了MS上。机理机制和上述LPA用于MS的类似。以前MS的治疗药物主要通过抑制炎症途径来减少进展，而Contineum的注意力集中在调节髓鞘再生的分子上。MI毒蕈碱乙酰胆碱受体(MIR)已被证明是少突胶质前细胞(OPCs)成熟为少突胶质细胞(OLs)的关键调节剂，少突胶质细胞是制造髓磷脂的细胞。这一发现是基于非选择性抗毒蕈碱化合物，如Clemastine和Benzetropine，并随后通过细胞类型特异性MIR敲除研究验证。基于这一初步发现，Contineum就开始了一项药物化学研究，以发现一种新的MIR选择性拮抗剂。最初产生的拮抗剂是是PIPE-359，后续跟进迭代产生了PIPE-307。临床前研究表明，PIPE307可诱导功能性髓鞘再生。点评总的来看，PIPE307和PIPE-791在机制上其实和现有MS并不冲突，甚至能够互补，现有治疗手段大多着重于抑制炎症途径，而抑制炎症途径只能起到延缓作用，联合使用这两款药物可能改变现有MS的格局。这可能是强生对这家企业另眼先看的原因。不过也值得注意的是，虽然PPT讲得好是一回事，但是实际患者再生的有效性是另外一回事。PIPE307和PIPE-791是否能在疗效上展现出具有统计学意义上的临床改善或许才是关键。参考来源：Rancoule C, Pradère JP, Gonzalez J, Klein J, Valet P, Bascands JL, Schanstra JP, Saulnier-Blache JS. Lysophosphatidic acid-1-receptor targeting agents for fibrosis. Expert Opin Investig Drugs. 2011 May;20(5):657-67. doi: 10.1517/13543784.2011.566864. Epub 2011 Mar 24.https://www.contineum-tx.com/wp-content/uploads/2023/04/GRC-Glial-biology-conference-030123.pdf

IPO引进/卖出临床1期

2023-09-13

·米内网

【获批】重磅罕见病药首仿，远大医药拿下

精彩内容9月12日，远大医药公告称，公司以仿制3类报产的卡谷氨酸分散片获批上市，为国内首仿+首家过评。该产品用于治疗高氨血症，是公司在心脑血管急救领域罕见病方向的重大研发进展。卡谷氨酸分散片有效成分卡谷氨酸是N-乙酰谷氨酸(NAG)结构类似物，用于治疗成人或儿童由N-乙酰谷氨酸合成酶(NAGS)缺乏症、异戊酸血症(IVA)、甲基丙二酸血症(MMA)或丙酸血症(PA)所引起的高氨血症。目前，卡谷氨酸分散片已经在欧美等多个国家和地区上市，并被纳入FDA的孤儿药品目录，是FDA批准的第一种也是唯一一种用于治疗由MMA和PA引发的高氨血症的药物。远大医药卡谷氨酸分散片卡谷氨酸分散片原研厂家为Recordati，于2023年6月27日在国内获批上市，已通过2023国谈药品初审。远大医药的卡谷氨酸分散片以仿制3类批产并视同过评，为国内首仿+首家过评。心脑血管急救板块是远大医药重点布局领域，公司已有近30个品种获批上市，在研产品超过20款，涉及多款罕见病药物，用于治疗韦斯特综合征的氨己烯酸口服溶液用散上市申请在审中。米内网数据显示，远大医药已有13个品种通过或视同通过一致性评价，5个品种重酒石酸去甲肾上腺素注射液、碳酸氢钠片、格列吡嗪片、富马酸氯马斯汀注射液、卡谷氨酸分散片为国内首家过评。资料来源：米内网数据库、公司公告本文为原创稿件，转载请注明来源和作者，否则将追究侵权责任。投稿及报料请发邮件到872470254@qq.com稿件要求详询米内微信首页菜单栏商务及内容合作可联系QQ：412539092【分享、点赞、在看】点一点不失联哦

上市批准一致性评价孤儿药

2023-02-05

·米内网

1月10个1类新药，3个生物类似药报产；7个首仿获批，4个品种获批新适应症

摘要abstract 2023年1月CDE共承办药品注册申请1337件 10个1类新药，3个生物类似药报产仿制申请有32个品种暂无国产获批 5个存量品种首次有企业申报一致性评价 2个1类新药获批，4个重磅品种获批新适应症 7个首仿品种获批，1个存量品种首家过评CDE总体承办情况据米内网中国申报进度（MED）数据库统计，2023年1月CDE共承办药品注册申请1337件。其中上市申请327件，临床申请263件，存量品种一致性评价111件。2023年1月CDE承办药品注册申请情况（按受理号计）创新药品种申报情况2023年1月，137个创新药品种（药品注册分类为1的品种）获CDE承办。其中有10个品种为上市申请。2023年1月创新药上市申请承办情况2023年1月创新药临床申请承办情况改良型新药品种申报情况2023年1月，37个改良型新药品种（药品注册分类为2的品种）获CDE承办。其中6个品种为上市申请，济川药业集团的小儿豉翘清热糖浆为新剂型上市申请，其他品种均为新适应症上市申请。2023年1月改良型新药上市申请承办情况2023年1月改良型新药临床申请承办情况仿制药品种申报情况（含中药同名同方）2023年1月，192个品种的仿制申请获CDE承办，其中氨磺必利注射液(南京恩泰医药)、比索洛尔氨氯地平片(成都硕德药业)、布立西坦口服溶液(江苏艾立康医药)、醋酸维持液(含葡萄糖)(南京赛瑞谱顿制药)、碘比醇注射液(重庆圣华曦药业)、恩格列净二甲双胍缓释片(乐普药业)、恩曲他滨利匹韦林丙酚替诺福韦片(齐鲁制药)......等32个品种目前暂无国产仿制药获批。2023年1月仿制药品种申报情况存量品种一致性评价申报情况2023年1月，56个品种的一致性评价补充申请获CDE承办。其中钆贝葡胺注射液、枸橼酸铋钾颗粒、氯氮平口腔崩解片、西洛他唑片、盐酸米托蒽醌注射液等5个品种为首次申报。2023年1月存量品种一致性评价申报情况其他类型申请情况2023年1月还有5个生物类似药，11个进口原研药以及1个按古代经典名方目录管理的中药复方制剂获CDE承办。其中齐鲁有2个生物类似药申请上市。2023年1月其他类型品种申请情况获批情况2023年1月有2个1类新药获批上市：江苏艾迪药业的艾诺米替片以及武田药品的琥珀酸莫博赛替尼胶囊。此外，正大天晴康方(上海)生物、上海复宏汉霖以及苏州盛迪亚生物各有1款重磅单抗获批新适应症。92个仿制药获批，艾司奥美拉唑镁肠溶干混悬剂(浙江尔婴药品)、低钙腹膜透析液(乳酸盐-G1.76%)(华仁药业)、低钙腹膜透析液(乳酸盐-G2.55%)(华仁药业)、复方电解质醋酸钠注射液(北京费森尤斯卡比医药)、环磷酰胺胶囊(江苏恒瑞医药)、钠钾镁钙注射用浓溶液(北京亿灵医药发展)、尼洛替尼胶囊(苏州特瑞药业)为国内首仿品种。41个存量品种有企业过评，远大医药(中国)的富马酸氯马斯汀注射液为首家过评。2023年1月主要注册类型品种获批情况数据来源：米内网中国申报进度数据库（MED）、CDE、NMPA；相关统计字段按药品名称统计，时间截至2023年1月31日；药物作用靶点以及适应症整理自公开资料。本文为原创稿件，转载请注明来源和作者，否则将追究侵权责任。投稿及报料请发邮件到872470254@qq.com稿件要求详询米内微信首页菜单栏商务及内容合作可联系QQ：412539092【分享、点赞、在看】点一点不失联哦

上市批准生物类似药一致性评价

100 项与富马酸氯马斯汀相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D00666	富马酸氯马斯汀	R06AA04 D04AA14	DB00283

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
变应性结膜炎	美国	Novartis Pharmaceuticals Corp.	1977-02-25
普通感冒	日本	NISSIN Pharmaceutical Co., Ltd.	1970-01-17
皮炎	日本	NISSIN Pharmaceutical Co., Ltd.	1970-01-17
湿疹	日本	NISSIN Pharmaceutical Co., Ltd.	1970-01-17
瘙痒	日本	NISSIN Pharmaceutical Co., Ltd.	1970-01-17
过敏性鼻炎	日本	NISSIN Pharmaceutical Co., Ltd.	1970-01-17
荨麻疹	日本	NISSIN Pharmaceutical Co., Ltd.	1970-01-17

未上市

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
季节性过敏性鼻炎	临床2期	美国	NovaDel Pharma, Inc.	-

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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


NCT06039137 (H1-Switch Study, Pubmed \| JCO Oncol Pract)	N/A	-	-	Intravenous Clemastine	廠遞獵繭鏇製鑰範膚窪(淵鹽觸製醖艱網鑰蓋構) = 廠餘鬱窪窪蓋鬱觸鏇齋廠襯簾獵簾夢壓襯艱遞 (鑰網構糧鹽襯願積構觸, -3.4 ~ 1.1)	积极	2024-06-07
				Oral Cetirizine	廠遞獵繭鏇製鑰範膚窪(淵鹽觸製醖艱網鑰蓋構) = 鏇鹹衊蓋憲鹽夢餘襯獵廠襯簾獵簾夢壓襯艱遞 (鑰網構糧鹽襯願積構觸, -3.4 ~ 1.1)
TRAP-MS (ACTRIMS2024)	N/A	慢性进行性多发性硬化	9	Clemastine Fumarate	窪蓋觸製艱鏇糧觸鬱繭(蓋網觸鹽襯構鏇衊選鹽) = 築艱衊選製蓋餘餘廠衊襯選積繭艱獵鑰壓憲襯 (範壓膚鑰餘膚淵繭網襯 )	不佳	2024-02-29
NCT02040298 (ReBUILD, CTgov)	临床2期	复发-缓解型多发性硬化	50	Clemastine (Clemastine)	繭網構糧構構壓衊餘餘(齋蓋範鬱築築鏇鹹艱壓) = 糧齋膚獵窪襯膚齋繭憲積觸簾構廠衊襯壓獵製 (鬱廠築壓鑰築廠憲觸顧, 製獵網窪積艱選憲簾廠 ~ 繭壓願願鹽獵製餘廠鬱) 更多	-	2021-07-15
				Placebo+clemastine (Placebo)	繭網構糧構構壓衊餘餘(齋蓋範鬱築築鏇鹹艱壓) = 鑰選壓襯鬱繭餘鑰繭廠積觸簾構廠衊襯壓獵製 (鬱廠築壓鑰築廠憲觸顧, 餘窪範積衊艱網廠窪鹹 ~ 製鬱壓選獵鏇鏇範網願) 更多