RU2392962C2 - Противомикробные пептиды - Google Patents
Противомикробные пептиды Download PDFInfo
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- RU2392962C2 RU2392962C2 RU2007107390/15A RU2007107390A RU2392962C2 RU 2392962 C2 RU2392962 C2 RU 2392962C2 RU 2007107390/15 A RU2007107390/15 A RU 2007107390/15A RU 2007107390 A RU2007107390 A RU 2007107390A RU 2392962 C2 RU2392962 C2 RU 2392962C2
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- compounds
- bacterial
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- infection
- peptide
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| EP04077175.0 | 2004-07-28 |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2646102C2 (ru) * | 2012-05-09 | 2018-03-01 | Контрафект Корпорейшн | Предотвращение, разрушение и обработка биопленки лизином бактериофага |
| US10130677B2 (en) | 2013-12-12 | 2018-11-20 | Academisch Ziekenhuis Leiden H.O.D.N. Lumc | Antimicrobial peptide and uses thereof |
| RU2695455C2 (ru) * | 2013-05-10 | 2019-07-23 | Академиш Зикенхойс Лейден Х.О.Д.Н. Люмк | Противомикробный пептид |
| RU2707254C1 (ru) * | 2013-11-19 | 2019-11-25 | Проморе Фарма Аб | Водный фармацевтический препарат и способ лечения хронической язвы |
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| EP1621205A1 (en) * | 2004-07-28 | 2006-02-01 | OctoPlus Technologies B.V. | Antimicrobial peptides derived from CAP18 |
| EP2099466B1 (en) | 2006-12-01 | 2015-06-03 | Laclede, Inc. | Use of hydrolytic and oxidative enzymes to dissolve biofilm in ears |
| KR20100056479A (ko) | 2007-07-25 | 2010-05-27 | 바이오렉스 쎄라퓨틱스, 인코포레이티드 | 제어 방출 인터페론 약물 제품 및 이를 사용한 ｈｃｖ 감염의 치료 |
| US20100184684A1 (en) * | 2009-01-06 | 2010-07-22 | C3 Jian, Inc. | Antibacterial and antifungal peptides |
| EP3252068B1 (en) | 2009-10-12 | 2025-07-02 | Larry J. Smith | Methods and compositions for modulating gene expression using oligonucleotide based drugs administered in vivo or in vitro |
| RU2434880C1 (ru) * | 2010-07-21 | 2011-11-27 | Общество С Ограниченной Ответственностью "Биохарт" | Полипептид, имеющий антибактериальную активность и пригодный для получения лекарственных средств для лечения бактериальных инфекций человека |
| US9387189B2 (en) | 2013-05-22 | 2016-07-12 | Professional Compounding Centers Of America (Pcca) | Antibiotic composition comprising a chemotactic agent and a nutrient dispersion |
| WO2015164289A1 (en) * | 2014-04-21 | 2015-10-29 | Cidara Therapeutics, Inc. | Compositions and methods for the treatment of fungal infections |
| WO2023049162A1 (en) * | 2021-09-21 | 2023-03-30 | Biomedit, Llc | Antimicrobial peptides |
Family Cites Families (4)
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|---|---|---|---|---|
| JP4037525B2 (ja) * | 1998-03-25 | 2008-01-23 | 生化学工業株式会社 | 新規抗菌性ペプチド |
| EP1587830B1 (en) * | 2003-01-28 | 2009-07-08 | Academisch Ziekenhuis Leiden | Peptide inhibitors of toxins derived from ll-37 |
| US7718618B2 (en) * | 2003-10-21 | 2010-05-18 | The Regents Of The University Of California | Human cathelicidin antimicrobial peptides |
| EP1621205A1 (en) * | 2004-07-28 | 2006-02-01 | OctoPlus Technologies B.V. | Antimicrobial peptides derived from CAP18 |
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- 2005-07-26 CA CA002574959A patent/CA2574959A1/en not_active Abandoned
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Non-Patent Citations (1)
| Title |
|---|
| NAGAOKA ISAO ET L., Augmentation of the lipopolysaccharide-neutralizing activities of human cathelicidin CAP18/LL-37- derived antimicrobial peptides by replacement with hydrophobic and cationic amino acid residues, Clinical and Diagnostic laboratory Immunology, American Society for microbiology, US, 2002, v.9, № 5, p.972-982. TURNER J. ET AL., Activities of LL-37, a cathelin-associated antimicrobial peptide of human neutrophils, Antimicrobial agents and chemotherapy, American Society for microbiology, Washington, DC, US, 1998, v.42, № 9, p.2206-2214. KIRIKAE Т. et AL., Protective effects of a human 18-kilodalton cationic antimicrobial protein (CAP 18)-derived peptide against murine endotoxemia, Infection and Immunity, American Society for microbiology, Washington, US, 1998, v.66, № 5, p.1861-1868. * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2646102C2 (ru) * | 2012-05-09 | 2018-03-01 | Контрафект Корпорейшн | Предотвращение, разрушение и обработка биопленки лизином бактериофага |
| RU2695455C2 (ru) * | 2013-05-10 | 2019-07-23 | Академиш Зикенхойс Лейден Х.О.Д.Н. Люмк | Противомикробный пептид |
| RU2707254C1 (ru) * | 2013-11-19 | 2019-11-25 | Проморе Фарма Аб | Водный фармацевтический препарат и способ лечения хронической язвы |
| US10130677B2 (en) | 2013-12-12 | 2018-11-20 | Academisch Ziekenhuis Leiden H.O.D.N. Lumc | Antimicrobial peptide and uses thereof |
| RU2699712C1 (ru) * | 2013-12-12 | 2019-09-09 | Академиш Зикенхойс Лейден Х.О.Д.Н. Люмк | Антимикробный пептид и его применение |
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| EP1621205A1 (en) | 2006-02-01 |
| BRPI0513856A (pt) | 2008-05-20 |
| WO2006011792A3 (en) | 2006-09-14 |
| US20080249022A1 (en) | 2008-10-09 |
| RU2007107390A (ru) | 2008-09-10 |
| JP2008508265A (ja) | 2008-03-21 |
| KR20070050941A (ko) | 2007-05-16 |
| US20110053835A1 (en) | 2011-03-03 |
| US7803756B2 (en) | 2010-09-28 |
| AU2005267651A1 (en) | 2006-02-02 |
| AU2005267651B2 (en) | 2010-05-27 |
| CN101018563A (zh) | 2007-08-15 |
| NZ553175A (en) | 2009-10-30 |
| EP1784206A2 (en) | 2007-05-16 |
| EP2221061A1 (en) | 2010-08-25 |
| CA2574959A1 (en) | 2006-02-02 |
| WO2006011792A2 (en) | 2006-02-02 |
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