A Randomised, Single Dose, 5-period, 5-treatment, Crossover Study to Assess the Relative Bioavailability of 4 Different Formulations of Verinurad and Allopurinol in Healthy Subjects

This study is a single centre, randomised, open-label, single-dose, 5-period, 5-treatment, crossover study in healthy male and female subjects. This study is intended to assess the relative bioavailability between the fixed dose combination (FDC, i.e. verinurad/allopurinol FDC capsule 12/300 mg) and free combination formulations of verinurad (i.e. verinurad prolonged release Hydroxypropyl methylcellulose [HPMC] capsule 12 mg) and allopurinol (i.e. allopurinol table 300 mg) in fasted and fed conditions. The study will also assess the relative bioavailability between a formulation only containing verinurad (i.e. verinurad prolonged release gelatin capsule 12 mg) and the FDC capsule.

开始日期2021-04-13

申办/合作机构

AstraZeneca PLC

[+1]

NCT04532918

/ Completed临床1期

An Open-label, 3-Treatment, 3-Period, Fixed Sequence Study in Healthy Subjects to Assess the Pharmacokinetics of Verinurad and Allopurinol When Administered Alone, and in Combination With Single Doses of Cyclosporine or Rifampicin

This Phase 1 study aims to quantify the effects of cyclosporine, a broad transporter inhibitor, and rifampicin, an OATP1B1/3 inhibitor, on verinurad pharmacokinetics (PK). The study is conducted in accordance with Food and Drug Administration guidance on Clinical Drug Interaction Studies, 2020. Verinurad will be developed as a fixed combination since it will always be administered together with allopurinol.

开始日期2020-09-10

申办/合作机构

AstraZeneca PLC

[+1]

NCT04327024

/ Completed临床2期

A Phase 2, Multicentre, Double-Blind, Placebo and Active Control Efficacy and Safety Study to Evaluate Verinurad Combined With Allopurinol in Heart Failure With Preserved Ejection Fraction

International, Multicenter, Double-Blind, Placebo and Active Control Efficacy and Safety Study to Evaluate Verinurad combined with Allopurinol in Heart Failure with Preserved Ejection Fraction

开始日期2020-05-19

申办/合作机构

AstraZeneca PLC

100 项与 Verinurad 相关的临床结果

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100 项与 Verinurad 相关的转化医学

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100 项与 Verinurad 相关的专利（医药）

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项与 Verinurad 相关的文献（医药）

2024-10-01·JAMA Cardiology

Verinurad Plus Allopurinol for Heart Failure With Preserved Ejection Fraction

Article

作者: Kitzman, Dalane W. ; Mentz, Robert J. ; Sjöström, C. David ; Voors, Adriaan A. ; Shah, Sanjiv J. ; Källgren, Christian ; Lewis, Gregory D. ; Myte, Robin ; Perl, Shira ; Kaguthi, Grace

Importance:

Elevated serum uric acid (SUA) level may contribute to endothelial dysfunction; therefore, SUA is an attractive target for heart failure with preserved ejection fraction (HFpEF). However, to the authors’ knowledge, no prior randomized clinical trials have evaluated SUA lowering in HFpEF.

Objective:

To investigate the efficacy and safety of the novel urate transporter–1 inhibitor, verinurad, in patients with HFpEF and elevated SUA level.

Design, Setting, and Participants:

This was a phase 2, double-blind, randomized clinical trial (32-week duration) conducted from May 2020 to April 2022. The study took place at 59 centers in 12 countries and included patients 40 years and older with HFpEF and SUA level greater than 6 mg/dL. Data were analyzed from August 2022 to May 2024.

Interventions:

Eligible patients were randomized 1:1:1 to once-daily, oral verinurad, 12 mg, plus allopurinol, 300 mg; allopurinol, 300 mg, monotherapy; or placebo for 24 weeks after an 8-week titration period. Allopurinol was combined with verinurad to prevent verinurad-induced urate nephropathy, and the allopurinol monotherapy group was included to account for allopurinol effects in the combination therapy group. All patients received oral colchicine, 0.5 to 0.6 mg, daily for the first 12 weeks after randomization.

Main Outcomes and Measures:

Key end points included changes from baseline to week 32 in peak oxygen uptake (VO2), Kansas City Cardiomyopathy Questionnaire total symptom score (KCCQ-TSS), and SUA level; and safety/tolerability (including adjudicated cardiovascular events).

Results:

Among 159 randomized patients (53 per treatment group; median [IQR] age, 71 [40-86] years; 103 male [65%]) with median (IQR) N-terminal pro–brain natriuretic peptide level of 527 (239-1044) pg/mL and SUA level of 7.5 (6.6-8.4) mg/dL, verinurad plus allopurinol (mean change, −59.6%; 95% CI, −64.4% to −54.2%) lowered SUA level to a greater extent than allopurinol (mean change, −37.6%; 95% CI, −45.3% to −28.9%) or placebo (mean change, 0.8%; 95% CI, −11.8% to 15.2%; P &lt; .001). Changes in peak VO2 (verinurad plus allopurinol, 0.27 mL/kg/min; 95% CI, −0.56 to 1.10 mL/kg/min; allopurinol, −0.17 mL/kg/min; 95% CI, −1.03 to 0.69 mL/kg/min; placebo, 0.37 mL/kg/min; 95% CI, −0.45 to 1.19 mL/kg/min) and KCCQ-TSS (verinurad plus allopurinol, 4.3; 95% CI, 0.3-8.3; allopurinol, 4.5; 95% CI, 0.3-8.6; placebo, 1.2; 95% CI, −3.0 to 5.3) were similar across groups. There were no adverse safety signals. Deaths or cardiovascular events occurred in 3 patients (5.7%) in the verinurad plus allopurinol group, 8 patients (15.1%) in the allopurinol monotherapy group, and 6 patients (11.3%) in the placebo group.

Conclusions and Relevance:

Results of this randomized clinical trial show that despite substantial SUA lowering, verinurad plus allopurinol did not result in a significant improvement in peak VO2 or symptoms compared with allopurinol monotherapy or placebo in HFpEF.

Trial Registration:

ClinicalTrials.gov Identifier: NCT04327024

2024-05-01·Journal of the American Society of Nephrology : JASN

Combination Treatment with Verinurad and Allopurinol in CKD

Article

作者: Perl, Shira ; Bjursell, Magnus ; Rikte, Tord ; Stack, Austin G. ; Perkovic, Vlado ; Inker, Lesley A. ; Maklad, Noha ; Heerspink, Hiddo J.L. ; Sjöström, C. David ; Jongs, Niels ; Terkeltaub, Robert ; Eklund, Olof

Key Points:

The SAPPHIRE trial was designed to assess albuminuria-lowering effects of the urate transporter 1 inhibitor verinurad combined with allopurinol in patients with CKD.Verinurad 3, 7.5, and 12 mg in combination with allopurinol 300 mg did not reduce albuminuria during 34 weeks treatment compared with allopurinol alone or placebo.Verinurad/allopurinol combination dose-dependently reduced serum urate concentrations compared with placebo.

Background:

Hyperuricemia is associated with elevated risks of cardiovascular and chronic kidney disease (CKD). Since inhibition of urate transporter 1 has been suggested to be potentially nephroprotective, we performed a phase 2b study to assess albuminuria-lowering effects of the urate transporter 1 inhibitor verinurad combined with the xanthine oxidase inhibitor allopurinol in patients with CKD and hyperuricemia.

Methods:

In this randomized placebo and active controlled trial, we enrolled participants with serum urate concentrations ≥6.0 mg/dl, eGFR ≥25 ml/min per 1.73 m2, and a urinary albumin-creatinine ratio (UACR) 30–5000 mg/g to one of five treatment arms: placebo, placebo+allopurinol 300 mg/day, verinurad 3 mg+allopurinol 300 mg/day, verinurad 7.5 mg+allopurinol 300 mg/day, or verinurad 12 mg+allopurinol 300 mg/day in a 1:1:1:1:1 ratio. The primary end point was the change in UACR from baseline to 34 weeks. Secondary end points were changes from baseline in UACR at week 60 and changes in serum urate and eGFR at weeks 34 and 60.

Results:

Between August 2019 and November 2021, 861 adults with CKD (mean age 65 years, 33.0% female, mean eGFR 48 ml/min per 1.73 m2, median UACR 217 mg/g) were enrolled. At 34 weeks, the geometric mean percentage change in UACR from baseline did not differ among treatment groups (16.7%, 95% confidence interval [CI], −0.6 to 37.1 in the 3 mg group, 15.0% [95% CI, −1.85 to 34.6] in the 7.5 mg group, 14.0% [95% CI, −3.4 to 34.4] in the 12 mg group versus 9.9% [95% CI, −6.6 to 29.4] in the allopurinol group, and 37.3% [95% CI, 16.6 to 61.8] in the placebo group). UACR and eGFR change from baseline did not differ among treatment groups after 60 weeks. Verinurad/allopurinol combination dose-dependently reduced serum urate concentrations compared with placebo. The proportion of patients with adverse events and serious adverse events was balanced among treatment groups.

Conclusions:

Verinurad in combination with allopurinol did not decrease UACR or eGFR decline, but further reduced serum urate compared with allopurinol alone or placebo.

Clinical Trial registry name and registration number::

SAPPHIRE Trial registration number, NCT03990363.

2024-04-01·European journal of medicinal chemistry

Proline-derived quinoline formamide compounds as human urate transporter 1 inhibitors with potent uric acid-lowering activities

Article

作者: Zheng, Fengxin ; Luo, Lijun ; Zhao, Kunlu ; Sheng, Li ; Zhai, Jiayu ; Pang, Jianxin ; Liao, Hui ; Wu, Ting ; Li, Gang ; Huan, Yi ; Meng, Bingxu ; Huang, Haihong ; Zhao, Hongyi ; Tian, Jinhong ; Li, Shengnan ; Lei, Lei

We report the design and synthesis of a series of proline-derived quinoline formamide compounds as human urate transporter 1 (URAT1) inhibitors via a ligand-based pharmacophore approach. Structure-activity relationship studies reveal that the replacement of the carboxyl group on the polar fragment with trifluoromethanesulfonamide and substituent modification at the 6-position of the quinoline ring greatly improve URAT1 inhibitory activity compared with lesinurad. Compounds 21c, 21e, 24b, 24c, and 23a exhibit potent activities against URAT1 with IC₅₀ values ranging from 0.052 to 0.56 μM. Furthermore, compound 23a displays improved selectivity towards organic anion transporter 1 (OAT1), good microsomal stability, low potential for genotoxicity and no inhibition of the hERG K⁺ channel. Compounds 21c and 23a, which have superior pharmacokinetic properties, also demonstrate significant uric acid-lowering activities in a mouse model of hyperuricemia. Notably, 21c also exhibits moderate anti-inflammatory activity related to the gout inflammatory pathway. Compounds 21c and 23a with superior druggability are potential candidates for the treatment of hyperuricemia and gout.

项与 Verinurad 相关的新闻（医药）

2021-11-12

·Endpoints

AstraZeneca expects 'modest profitability' for next round of Covid-19 vaccine supply deals — and prunes pipeline in Q3 update

Having sent 1.5 billion Covid-19 vaccines around the world on a not-for-profit basis, AstraZeneca says it’s time to move into “modest profitability.” While the priority is to deliver all the “pandemic doses” — a total of 3 billion are set to be delivered by the end of the year — AstraZeneca expects to be taking new orders in Q4, leading to a blend in sales. “Don’t expect massive profitability, which is sometimes the case for other vaccine makers,” Ruud Dobber, head of the biopharmaceuticals business unit, told Endpoints News . Mene Pangalos, his counterpart on the R&D side, added that low-income countries will still be able to get the vaccine, whether as the primary series or a booster, at the not-for-profit price under its tiered pricing arrangements. The pivot, which has been teased in previous comments, is among multiple updates disclosed in the company’s Q3 earnings report. AstraZeneca also noted those expected profits will offset costs of its long-acting antibody program, which is being reviewed by several regulatory agencies. Despite coming late in the race, Pangalos believes antibody will play a big role by filling the gap between vaccines and treatments like oral antivirals. “Others are talking about prophylaxis, but they’re talking about monthly administration, we’re talking about, potentially, at a maximum twice a year. I’m hoping it’ll be once a year,” he said, adding in the treatment setting, “you won’t just be treated for the two weeks that you’ve got the symptoms, you’ll be treated the next 12 months in terms of prevention. I know what I would take.” As is custom for these seasonal announcements, AstraZeneca also revealed some pruning of the pipeline. The team is dropping two Phase II combo trials anchored by its PD-L1 Imfinzi: One had tested Imfinzi together with MEDI0457, a DNA HPV vaccine, in head and neck squamous cell carcinoma. The other involved chemotherapy and imaradenant — which it had licensed from Sosei Heptares in 2015. Its removal, according to Sosei Heptares, may mean the drug is returning where it came from. Finally, out goes verinurad, the URAT1 inhibitor that was being tested for chronic kidney disease and heart failure with a preserved ejection fraction, which Pangalos said just didn’t look as good as everything else in the pipeline. “Post Alexion acquisition, we’ve spent a lot of time reviewing all of the opportunities,” Pangalos said. “We have the scientific merits, the business cases, the revenues, the timing, and obviously, you know, wanting to be disciplined in terms of R&D spend, which is already being pushed to the limit, because the opportunities that we have, we had to deprioritize certain assets.” Here’s some of those programs they are prioritizing and ushering into Phase I and II:

疫苗抗体并购

2021-04-23

·BioSpace

Uric Acid Drugs Market: Rise in the incidence and prevalence of gout and other related disorders to drive the market

Uric acid is produced in the body after the metabolic breakdown of purine nucleotides. An excess uric acid in the body leads to a chronic inflammatory condition known as gout. An excess of uric acid leads to the formation of crystals in the body, which eventually leads to the deposition of uric acid crystals in joints, resulting in inflammation and pain. Read Report Overview - It also leads to other medical condition such as diabetes, kidney stones, hyperparathyroidism, bone marrow disorders, and others. Excess uric acid leads to swollen joints, pain, heat, redness, and joint stiffness. Symptoms start with the inflammation of the big toe. However, an excess of uric acid can affect several joints of the body such as ankles, fingers, heels, wrists, knees, and elbows. Symptoms are more prevalent in men compared to women. Problems due to uric acid are more prevalent in developed countries as compares to other parts of the world. In 2013, uric acid problems affected around 5.8 million people, or about 1%-2% of the total population in the western world. Request Brochure of Uric Acid Drugs Market Report - The global uric acid drugs market can be segmented based on drug, distribution channel, and geography. Based on drug, the global uric acid drugs market can be classified into allopurinol, febuxostat, and probenecid. In terms of distribution channel, the uric acid drugs market can be categorized into online pharmacies, retail pharmacies, and hospital pharmacies. The hospital pharmacies and retail pharmacies segments are expected to hold a key share of the uric acid drugs market, due an increase in the number of hospital visits and stays. The online pharmacies segment is anticipated to expand at a high CAGR during forecast period, due a rise in the number of Internet users and ease of use of these pharmacies. Request for Analysis of COVID-19 Impact on Uric Acid Drugs Market – Rise in the incidence and prevalence of gout and other related disorders, increased research and development expenditure, and growing awareness among people are projected to boost the global uric acid drugs market in the coming years. Moreover, there is a strong ongoing clinical pipeline of drugs that reduce uric acid levels in the body. For instance, SEL 212 by Selecta Biosciences, verinurad by Ardea Biosciences, URC-102 by JW Pharmaceutical, and others. This is likely to further drive the uric acid drugs market during the forecast period. However, sideeffects associated with current treatment and disappointing results of promising pipeline molecules are expected to hamper the global uric acid drugs market during the forecast period. Pre-book Uric Acid Drugs Market Report -

100 项与 Verinurad 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D11129	-	-	DB11873

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
射血分数保留型心力衰竭	临床2期	美国	AstraZeneca PLC	2020-05-19
射血分数保留型心力衰竭	临床2期	阿根廷	AstraZeneca PLC	2020-05-19
射血分数保留型心力衰竭	临床2期	澳大利亚	AstraZeneca PLC	2020-05-19
射血分数保留型心力衰竭	临床2期	奥地利	AstraZeneca PLC	2020-05-19
射血分数保留型心力衰竭	临床2期	保加利亚	AstraZeneca PLC	2020-05-19
射血分数保留型心力衰竭	临床2期	加拿大	AstraZeneca PLC	2020-05-19
射血分数保留型心力衰竭	临床2期	德国	AstraZeneca PLC	2020-05-19
射血分数保留型心力衰竭	临床2期	墨西哥	AstraZeneca PLC	2020-05-19
射血分数保留型心力衰竭	临床2期	波兰	AstraZeneca PLC	2020-05-19
射血分数保留型心力衰竭	临床2期	俄罗斯	AstraZeneca PLC	2020-05-19

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临床结果

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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


NCT04327024 (AMETHYST, Pubmed \| JAMA Cardiol) 人工标引	临床2期	射血分数保留型心力衰竭	159	Verinurad plus Allopurinol	艱顧餘範壓艱範鹽襯鹽(淵蓋衊淵築鑰範淵網構) = 簾醖憲鏇艱壓艱構顧觸蓋廠鹽膚範簾夢膚網選 (壓獵醖積積餘網鑰鹽網, -0.56 ~ 1.10) 更多	不佳	2024-08-14
				Allopurinol	艱顧餘範壓艱範鹽襯鹽(淵蓋衊淵築鑰範淵網構) = 窪艱壓簾壓選簾餘齋壓蓋廠鹽膚範簾夢膚網選 (壓獵醖積積餘網鑰鹽網, -1.03 ~ 0.69) 更多
NCT04327024 (AMETHYST, CTgov)	临床2期	射血分数保留型心力衰竭	159	Placebo for verinurad	顧糧選艱衊獵餘觸糧醖(願願蓋齋壓夢糧製鏇蓋) = 醖鹽蓋鹽廠鹽襯構襯選蓋糧廠鹹願餘鑰蓋齋廠 (憲醖鏇膚廠衊觸遞獵淵, 範鏇餘壓憲醖夢淵顧願 ~ 鏇夢膚憲蓋範製鹽夢膚) 更多	-	2023-06-29
NCT04550234 (CTgov)	临床1期	慢性肾病	25	Verinurad prolonged release HPMC capsule+Allopurinol Tablet (Treatment 1)	鏇襯願構遞衊糧齋鑰顧(簾衊獵淵鏇蓋範艱選製) = 積網淵鑰選鏇鏇繭廠餘艱夢淵製窪選獵憲齋鬱 (選襯鬱膚構齋齋鏇壓衊, 48.87) 更多	-	2023-05-10
				Verinurad/Allopurinol FDC Capsule (Treatment 2)	鏇襯願構遞衊糧齋鑰顧(簾衊獵淵鏇蓋範艱選製) = 餘網繭遞蓋衊餘衊獵餘艱夢淵製窪選獵憲齋鬱 (選襯鬱膚構齋齋鏇壓衊, 48.63) 更多
NCT04532918 (CTgov)	临床1期	慢性肾病	14	Verinurad+Allopurinol (Period 1: Verinurad + Allopurinol)	構製憲襯製觸遞範簾觸(壓鬱鑰構觸簾網蓋蓋網) = 鹽構觸壓廠顧醖衊醖壓願鏇願夢鏇積獵鬱餘構 (觸齋繭獵衊齋艱構鹽艱, 53.48) 更多	-	2023-03-27
				Verinurad+Cyclosporine+Allopurinol (Period 2: Verinurad + Allopurinol + Cyclosporine)	構製憲襯製觸遞範簾觸(壓鬱鑰構觸簾網蓋蓋網) = 鑰壓願衊築醖製醖蓋壓願鏇願夢鏇積獵鬱餘構 (觸齋繭獵衊齋艱構鹽艱, 29.39) 更多
NCT04256629 (Pubmed \| Br J Clin Pharmacol)	临床1期	慢性肾病	24	Verinurad 24 mg extended release + allopurinol 300 mg	醖壓製蓋壓顧襯構壓鑰(衊衊顧網艱衊鏇膚選齋) = 憲膚鑰鹽齋選繭鹽憲鏇醖蓋夢餘積鏇構衊繭選 (顧願憲構願範範繭觸糧, -4.6, ~ 0.8)	-	2022-12-12
NCT04256629 (CTgov)	临床1期	慢性肾病	24	ER8+verinurad+allopurinol (Treatment A)	糧糧齋觸範選廠齋鏇鹹(網衊醖繭顧獵鹽選簾繭) = 繭鏇襯衊醖淵蓋選範艱壓製餘齋鹹蓋衊網簾醖 (餘積襯夢憲衊憲糧壓鏇, 襯壓願窪餘窪遞艱範觸 ~ 廠鑰艱壓鬱衊膚鏇餘夢) 更多	-	2022-01-31
				verinurad+allopurinol (Treatment B)	糧糧齋觸範選廠齋鏇鹹(網衊醖繭顧獵鹽選簾繭) = 窪網鬱觸鹽願願觸餘醖壓製餘齋鹹蓋衊網簾醖 (餘積襯夢憲衊憲糧壓鏇, 夢範簾遞範構廠壓齋選 ~ 遞構顧網襯網蓋鹹齋夢) 更多
NCT03316131 (Pubmed \| J Clin Endocrinol Metab) 人工标引	临床2期	高尿酸血症	36	verinurad+febuxostat+dapagliflozin	膚鬱遞蓋窪構鹹積餘夢(艱獵製鬱構構構壓廠構) = 襯艱鹹鑰壓構網顧壓蓋衊獵鬱餘製艱觸顧壓艱 (淵鹹廠鏇醖鑰餘製憲淵, -21.0 ~ -4.7) 更多	积极	2021-04-23
				Placebo+verinurad+febuxostat	膚鬱遞蓋窪構鹹積餘夢(艱獵製鬱構構構壓廠構) = 繭遞廠遞蓋襯遞衊簾鹽衊獵鬱餘製艱觸顧壓艱 (淵鹹廠鏇醖鑰餘製憲淵, -21.3 ~ -5.0) 更多
NCT04024501 (CTgov)	临床1期	慢性肾病	25	ER8 (Treatment 1: 1 x 12 mg ER8 Capsule Fasted)	鹹鏇齋鏇築壓選鬱餘繭(選膚窪淵觸繭廠壓蓋襯) = 顧鬱範選顧構齋衊憲鏇淵醖鬱衊齋鏇鬱鑰窪築 (鬱壓醖夢鹹選繭網鑰繭, 47.60) 更多	-	2020-08-21
				verinurad A (Treatment 2: 2 x 6 mg A-capsule Fasted)	鹹鏇齋鏇築壓選鬱餘繭(選膚窪淵觸繭廠壓蓋襯) = 餘觸製憲鏇觸憲蓋廠鏇淵醖鬱衊齋鏇鬱鑰窪築 (鬱壓醖夢鹹選繭網鑰繭, 33.72) 更多
NCT03118739 (SP262 \| URATE-LOWERING THERAPY WITH VERINURAD AND FEBUXOSTAT, CTgov)	临床2期	高尿酸血症 \| 2型糖尿病 \| 白蛋白尿	60	Verinurad+Febuxostat (Verinurad 9 mg+Febuxostat 80 mg)	夢鑰蓋簾衊淵壓鹹顧鹽(簾鏇淵觸膚壓網範簾鹽) = 醖廠淵鹽遞鏇醖鹹構選醖繭襯鏇夢膚築膚蓋廠 (選獵蓋壓衊糧選艱範願, 艱襯醖蓋膚醖範顧憲襯 ~ 願網鑰夢簾選繭淵膚願) 更多	-	2020-01-10
				Placebo (Placebo)	夢鑰蓋簾衊淵壓鹹顧鹽(簾鏇淵觸膚壓網範簾鹽) = 繭觸製鬱憲鏇鹽鹽觸築醖繭襯鏇夢膚築膚蓋廠 (選獵蓋壓衊糧選艱範願, 繭鏇鏇鏇觸壓獵鏇醖蓋 ~ 遞鑰繭鹹齋壓糧獵築鏇) 更多
NCT02078219 (CTgov)	临床2期	高尿酸血症 \| 痛风	204	RDEA3170 (RDEA3170 Treatment Group 1)	繭構糧選鹹範鏇範壓簾(齋襯簾襯簾構網遞淵構) = 壓遞衊觸製積窪顧膚獵艱鑰製糧積築糧衊繭範 (鑰觸夢鬱鬱網範醖築網, 17.80) 更多	-	2019-09-24
				RDEA3170 (RDEA3170 Treatment Group 2)	繭構糧選鹹範鏇範壓簾(齋襯簾襯簾構網遞淵構) = 廠觸構積構構鏇網淵積艱鑰製糧積築糧衊繭範 (鑰觸夢鬱鬱網範醖築網, 18.38) 更多