Antimicrobial peptide series(DermaGen)(Antimicrobial peptide series(DermaGen))

概要

基本信息

药物类型

合成多肽

别名

+ [2]

靶点-

作用机制

细胞膜通透性增强剂

治疗领域

免疫系统疾病遗传病与畸形耳鼻咽喉疾病+ [1]

在研适应症-

非在研适应症

急性外耳炎特应性皮炎

原研机构

DermaGen AB

在研机构-

非在研机构

Pergamum ABDermagen, Inc.

DermaGen AB

最高研发阶段无进展临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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关联

2

项与 Antimicrobial peptide series(DermaGen) 相关的临床试验

NCT01447017 / Completed临床2期

A Randomised, Parallel-group, Double-blind, Placebo-controlled Study of DPK-060 to Investigate Clinical Safety and Efficacy in Patients With Acute External Otitis

The primary objective of this study is to evaluate safety and tolerability of DPK-060 2% ear drops compared to placebo for DPK-060 ear drops in patients with acute external otitis. The secondary objectives are to evaluate clinical cure and microbiological growth following treatment with DPK-060 2% ear drops compared to placebo for DPK-060 ear drops.

开始日期2011-11-01

申办/合作机构

DermaGen AB

[+1]

NCT01522391 / Completed临床1/2期

A Randomized, Double-blinded Placebo-controlled Study to Investigate Antimicrobial Efficacy and Safety Following Topical Application of DPK-060

The primary objective of this study was to evaluate microbial density in eczematous lesions during two weeks of twice daily therapy with the investigational product, DPK-060 1% ointment, compared with placebo in patients with atopic dermatitis. This randomized, double-blind, placebo-controlled part of the study was preceded with an open-label investigation in a small group of patients (n=5) treated with two applications of DPK-060 1% ointment per day for four days to assess safety, local tolerability and systemic absorption of DPK-060.
The secondary objectives were to evaluate severity of eczema and pruritus, to assess the tolerability and safety of the treatment and to assess the degree of systemic absorption of DPK-060 in blood on Day 7 and Day 21 in a sub-set of 10 patients.

开始日期2008-03-01

申办/合作机构

DermaGen AB

100 项与 Antimicrobial peptide series(DermaGen) 相关的临床结果

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100 项与 Antimicrobial peptide series(DermaGen) 相关的转化医学

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100 项与 Antimicrobial peptide series(DermaGen) 相关的专利（医药）

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8

项与 Antimicrobial peptide series(DermaGen) 相关的文献（医药）

2023-04-01·Macromolecular Bioscience

Dendritic Nanogels Directed Dual‐Encapsulation Topical Delivery System of Antimicrobial Peptides Targeting Skin Infections

Article

作者: Hutchinson, Daniel J. ; Umerska, Anita ; Håkansson, Joakim ; Malkoch, Michael ; San Jacinto García, Jorge ; Mahlapuu, Margit ; Fan, Yanmiao ; Andrén, Oliver C. J. ; Lüchow, Mads ; Zhang, Yuning ; Qin, Liguo

AbstractAntimicrobial peptides (AMPs) are promising antibacterial agents in the fight against multidrug resistant pathogens. However, their application to skin infections is limited by the absence of a realizable topical delivery strategy. Herein, a hybrid hierarchical delivery system for topical delivery of AMPs is accomplished through the incorporation of AMPs into dendritic nanogels (DNGs) and their subsequent embedding into poloxamer gel. The high level of control over the crosslink density and the number of chosen functionalities makes DNGs ideal capsules with tunable loading capacity for DPK‐060, a human kininogen‐derived AMP. Once embedded into the poloxamer gel, DPK‐060 encapsulated in DNGs displays a slower release rate compared to those entrapped directly in the gels. In vitro EpiDerm Skin Irritation Tests show good biocompatibility, while MIC and time‐kill curves reveal the potency of the peptide toward Staphylococcus aureus. Anti‐infection tests on ex vivo pig skin and in vivo mouse infection models demonstrate that formulations with 0.5% and 1% AMPs significantly inhibit the growth of S. aureus. Similar outcomes are observed for an in vivo mouse surgical site infection model. Importantly, when normalizing the bacteria inhibition to released/free DPK‐060 at the wound site, all formulations display superior efficacy compared to DPK‐060 in solution.

2022-09-01·Colloids and Surfaces B: Biointerfaces

Design and pharmacodynamic evaluation of DPK-060 loaded Nanostructured lipid carrier embedded gel for dermal delivery: A novel approach in the treatment of atopic dermatitis

Article

作者: Thakkar, Hetal ; Misra, Ambikanandan ; Javia, Ankit

DPK-060 is a synthetic, 17 amino acid peptide, structurally derived from the human protein kininogen. DPK-060 mainly acts by membrane disruption mechanism, thus demonstrating strong broad-spectrum antimicrobial activity against both gram-positive and gram-negative microbes, including methicillin-resistant S. aureus (MRSA) in-vitro and in-vivo. Apart from its antimicrobial effect, DPK-060 also possesses anti-inflammatory activity. In addition, DPK-060 has demonstrated positive results in phase II clinical trials in atopic dermatitis (AD) patients; but was not statistically conclusive due to the instability of DPK-060 as a drug substance in the formulation. Thus, the present investigation was aimed to assess and compare the efficacy of DPK-060 nanostructured lipid (NLC) based gel with conventional formulations (free DPK-060 gel and lotion) in AD mice animal models. DPK-060 loaded NLCs were formulated by meltemulsification technique and loaded into Carbopol 934 P gel and characterized for various physicochemical parameters such as particle size, zeta-potential, shape and surface morphology, rheological parameters, in-vitro drug release, cytotoxicity, cellular uptake, ex-vivo skin permeation/deposition, in-vitro antimicrobial activity, and proteolytic stability studies. NLCs exhibited 85 % encapsulation with 6.7 % loading efficacy, a size, and zeta potential of 128.6 nm and -22.5 mv, respectively. Additionally, DPK-060 NLC gel demonstrated controlled release and a better permeation profile in comparison to free DPK-060 gel and lotion. A substantial reduction in pro-inflammatory cytokines levels and improvement in AD lesions was achieved by DPK-060 NLC gel compared to free DPK-060 gel and lotion-based formulations. The present study confirms that DPK-060 NLC gel-based formulation can be an effective, safe, and novel alternative for the treatment of AD.

2019-10-01·Journal of Colloid and Interface Science2区 · 化学

Degradable dendritic nanogels as carriers for antimicrobial peptides

2区 · 化学

Article

作者: Singh, Shalini ; Malmsten, Martin ; Davoudi, Mina ; Malkoch, Michael ; Schmidtchen, Artur ; Nordström, Randi ; Andrén, Oliver C J

In the present study, we investigate degradable anionic dendritic nanogels (DNG) as carriers for antimicrobial peptides (AMPs). In such systems, the dendritic part contains carboxylic acid-based anionic binding sites for cationic AMPs, whereas linear poly(ethylene glycol) (PEG) chains form a shell for promotion of biological stealth. In order to clarify factors influencing membrane interactions of such systems, we here address effects of nanogel charge, cross-linking, and degradation on peptide loading/release, as well as consequences of these factors for lipid membrane interactions and antimicrobial effects. The DNGs were found to bind the AMPs LL-37 (LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES) and DPK-060 (GKHKNKGKKNGKHNGWKWWW). For the smaller DPK-060 peptide, loading was found to increase with increasing nanogel charge density. For the larger LL-37, on the other hand, peptide loading was largely insensitive to nanogel charge density. In line with this, results on the secondary structure, as well as on the absence of stabilization from proteolytic degradation by the nanogels, show that the larger LL-37 is unable to enter into the interior of the nanogels. While 40-60% nanogel degradation occurred over 10 days, promoted at high ionic strength and lower cross-linking density/higher anionic charge content, peptide release at physiological ionic strength was substantially faster, and membrane destabilization not relying on nanogel degradation. Ellipsometry and liposome leakage experiments showed both free peptide and peptide/DNG complexes to cause membrane destabilization, indicated also by antimicrobial activities being comparable for nanogel-bound and free peptide. Finally, the DNGs were demonstrated to display low toxicity towards erythrocytes even at peptide concentrations of 100 µM.

100 项与 Antimicrobial peptide series(DermaGen) 相关的药物交易

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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
急性外耳炎	临床2期	瑞典	Pergamum AB	2011-11-01
特应性皮炎	临床2期	瑞典	DermaGen AB	-
特应性皮炎	临床2期	瑞典	Dermagen, 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


NCT01522391 (CTgov)	临床1/2期	特应性皮炎	41	Placebo for DPK-060 ointment (Placebo for DPK-060 Ointment)	(夢鏇製衊簾製鹹鑰願網) = 醖獵襯艱淵壓鏇餘膚膚餘鹽選繭蓋繭淵醖繭觸 (窪觸選齋範製積築觸壓, 蓋構積顧窪鹹廠網鬱獵 ~ 憲鏇繭廠鹹廠餘餘鑰獵) 更多	-	2018-12-05
				DPK-060 1% ointment (DPK-060 1% Ointment)	(夢鏇製衊簾製鹹鑰願網) = 範膚鑰願築艱鹹選糧鬱餘鹽選繭蓋繭淵醖繭觸 (窪觸選齋範製積築觸壓, 齋鏇製網鹹繭鹹淵夢衊 ~ 鏇獵蓋糧築淵築窪觸製) 更多
NCT01447017 (CTgov)	临床2期	急性外耳炎	69	DPK-060 (DPK-060 2% Ear Drops)	齋鹽願齋膚築選鹹網鏇(製觸鏇鹹觸鹹艱襯膚淵) = 鏇淵鬱糧築窪餘糧獵艱範鏇鬱壓積鬱齋繭醖網 (鑰糧餘艱糧願鏇鹹構顧, 蓋構壓壓醖鏇築製築鹽 ~ 築鑰窪鏇築糧繭艱壓窪) 更多	-	2013-12-10
				Placebo for DPK-060 ear drops (Placebo for DPK-060 Ear Drops)	齋鹽願齋膚築選鹹網鏇(製觸鏇鹹觸鹹艱襯膚淵) = 鏇願網鹽壓壓糧襯鹽簾範鏇鬱壓積鬱齋繭醖網 (鑰糧餘艱糧願鏇鹹構顧, 積壓壓構襯憲製壓構餘 ~ 鹹鏇積廠膚簾鏇觸製選) 更多