KR20130062275A - 펩티드의 경피 투여 - Google Patents
펩티드의 경피 투여 Download PDFInfo
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- KR20130062275A KR20130062275A KR1020127027694A KR20127027694A KR20130062275A KR 20130062275 A KR20130062275 A KR 20130062275A KR 1020127027694 A KR1020127027694 A KR 1020127027694A KR 20127027694 A KR20127027694 A KR 20127027694A KR 20130062275 A KR20130062275 A KR 20130062275A
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| PCT/IE2011/000019 WO2011117851A1 (en) | 2010-03-25 | 2011-03-23 | Transdermal administration of peptides |
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Families Citing this family (45)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP5486690B2 (ja) | 2009-11-16 | 2014-05-07 | イプセン ファルマ ソシエテ パール アクシオン サンプリフィエ | メラノコルチン受容体リガンドの医薬組成物 |
| CN102821775B (zh) * | 2010-03-15 | 2014-10-22 | 益普生制药股份有限公司 | 生长激素促分泌素受体配体的药物组合物 |
| HUE030072T2 (en) | 2010-05-12 | 2017-04-28 | Radius Health Inc | Therapeutic prescriptions |
| US9133182B2 (en) | 2010-09-28 | 2015-09-15 | Radius Health, Inc. | Selective androgen receptor modulators |
| US9339457B2 (en) | 2013-03-13 | 2016-05-17 | Transdermal Biotechnology, Inc. | Cardiovascular disease treatment and prevention |
| US9314422B2 (en) | 2013-03-13 | 2016-04-19 | Transdermal Biotechnology, Inc. | Peptide systems and methods for metabolic conditions |
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| US20140271731A1 (en) | 2013-03-13 | 2014-09-18 | Transdermal Biotechnology, Inc. | Cardiovascular disease treatment and prevention |
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| US9724419B2 (en) | 2013-03-13 | 2017-08-08 | Transdermal Biotechnology, Inc. | Peptide systems and methods for metabolic conditions |
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| US20140271938A1 (en) | 2013-03-13 | 2014-09-18 | Transdermal Biotechnology, Inc. | Systems and methods for delivery of peptides |
| US9750787B2 (en) | 2013-03-13 | 2017-09-05 | Transdermal Biotechnology, Inc. | Memory or learning improvement using peptide and other compositions |
| US9241899B2 (en) | 2013-03-13 | 2016-01-26 | Transdermal Biotechnology, Inc. | Topical systems and methods for treating sexual dysfunction |
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| US9295636B2 (en) | 2013-03-13 | 2016-03-29 | Transdermal Biotechnology, Inc. | Wound healing using topical systems and methods |
| US9295637B2 (en) * | 2013-03-13 | 2016-03-29 | Transdermal Biotechnology, Inc. | Compositions and methods for affecting mood states |
| US9320706B2 (en) | 2013-03-13 | 2016-04-26 | Transdermal Biotechnology, Inc. | Immune modulation using peptides and other compositions |
| US9393264B2 (en) | 2013-03-13 | 2016-07-19 | Transdermal Biotechnology, Inc. | Immune modulation using peptides and other compositions |
| US9849160B2 (en) | 2013-03-13 | 2017-12-26 | Transdermal Biotechnology, Inc. | Methods and systems for treating or preventing cancer |
| US9320758B2 (en) | 2013-03-13 | 2016-04-26 | Transdermal Biotechnology, Inc. | Brain and neural treatments comprising peptides and other compositions |
| US9387159B2 (en) | 2013-03-13 | 2016-07-12 | Transdermal Biotechnology, Inc. | Treatment of skin, including aging skin, to improve appearance |
| US9687520B2 (en) | 2013-03-13 | 2017-06-27 | Transdermal Biotechnology, Inc. | Memory or learning improvement using peptide and other compositions |
| TWI662967B (zh) * | 2013-03-25 | 2019-06-21 | 日商志瑞亞新藥工業股份有限公司 | 食後期之胃運動亢進劑 |
| ES3055185T3 (en) | 2014-03-28 | 2026-02-10 | Univ Duke | Treatment of an estrogen receptor positive breast cancer using a selective estrogen receptor modulator |
| ES2942260T3 (es) | 2014-09-14 | 2023-05-31 | Tel Hashomer Medical Res Infrastructure & Services Ltd | Ligandos sintéticos de receptores de somatostatina |
| KR20250152679A (ko) | 2015-04-29 | 2025-10-23 | 래디어스 파마슈티컬스, 인코포레이티드 | 암을 치료하는 방법 |
| US12427121B2 (en) | 2016-05-05 | 2025-09-30 | Aquestive Therapeutics, Inc. | Enhanced delivery epinephrine compositions |
| US12433850B2 (en) | 2016-05-05 | 2025-10-07 | Aquestive Therapeutics, Inc. | Enhanced delivery epinephrine and prodrug compositions |
| US11273131B2 (en) | 2016-05-05 | 2022-03-15 | Aquestive Therapeutics, Inc. | Pharmaceutical compositions with enhanced permeation |
| WO2017192921A1 (en) | 2016-05-05 | 2017-11-09 | Monosol Rx, Llc | Enhanced delivery epinephrine compositions |
| MX389702B (es) | 2016-06-22 | 2025-03-20 | Ellipses Pharma Ltd | Compuestos para usarse en el tratamiento de cancer de mama que expresa el receptor de androgenos (ar+). |
| JP7481115B2 (ja) | 2017-01-05 | 2024-05-10 | ラジウス ファーマシューティカルズ,インコーポレイテッド | Rad1901-2hclの多形性形態 |
| KR101786914B1 (ko) * | 2017-01-31 | 2017-11-15 | 주식회사 삼양사 | 피부 리프팅 또는 탄력 개선을 위한 점착성 탄력 밴드 |
| CN107226840A (zh) * | 2017-05-04 | 2017-10-03 | 西安交通大学 | 一种细胞穿膜肽透皮吸收促进剂及其制备方法和应用 |
| EP3687508A1 (en) * | 2017-09-26 | 2020-08-05 | Aquestive Therapeutics, Inc. | Delivery pharmaceutical compositions including permeation enhancers |
| WO2019236603A1 (en) * | 2018-06-08 | 2019-12-12 | Saint Louis University | Methods and compositions for treating decreased cognitive ability |
| MX2020013713A (es) | 2018-07-04 | 2021-03-02 | Radius Pharmaceuticals Inc | Formas polimorficas de rad1901-2hcl. |
| IT201800009384A1 (it) * | 2018-10-11 | 2020-04-11 | Cosmo Srl | Peptide for cosmetic application |
| EP3924328A1 (en) | 2019-02-12 | 2021-12-22 | Radius Pharmaceuticals, Inc. | Processes and compounds |
| DE102020130492A1 (de) * | 2020-11-18 | 2022-05-19 | Lts Lohmann Therapie-Systeme Ag. | Temperiersystem für eine Diffusionszelle, Diffusionszelle, Diffusionszellensystem, sowie Verfahren zur Temperierung in einer Diffusionszelle |
| WO2023281447A1 (en) * | 2021-07-07 | 2023-01-12 | Radius Health, Inc. | Methods of treating a cardiovascular ischemic event |
| US12465564B2 (en) | 2021-10-25 | 2025-11-11 | Aquestive Therapeutics, Inc. | Oral and nasal compositions and methods of treatment |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3954975A (en) * | 1972-02-17 | 1976-05-04 | Ciba-Geigy Corporation | Salts of ACTH-peptides and processes for their manufacture |
| IL79134A (en) * | 1985-07-29 | 1991-06-10 | American Cyanamid Co | Continuous release peptide implants for parenteral administration |
| JPH08505367A (ja) * | 1992-10-16 | 1996-06-11 | スミスクライン・ビーチャム・コーポレイション | 医薬用エマルジョン組成物 |
| US6316414B1 (en) * | 2000-07-31 | 2001-11-13 | Dabur Research Foundation | Somatostatin analogs for the treatment of cancer |
| MXPA03012042A (es) * | 2001-06-25 | 2006-05-22 | Il Consorzio Ferrara Richerche | Composiciones farmaceuticas que inhiben la proliferacion de adenomas pituitarios y metodos de uso de las mismas. |
| US20030175329A1 (en) * | 2001-10-04 | 2003-09-18 | Cellegy Pharmaceuticals, Inc. | Semisolid topical hormonal compositions and methods for treatment |
| WO2006040447A1 (fr) * | 2004-10-07 | 2006-04-20 | L'oreal | Procédé de traitement cosmétique des fibres kératiniques et utilisation d'un inhibiteur de transglutaminase |
| US20060216242A1 (en) * | 2005-02-03 | 2006-09-28 | Rohloff Catherine M | Suspending vehicles and pharmaceutical suspensions for drug dosage forms |
| CA2647143A1 (en) * | 2006-03-30 | 2007-10-11 | Palatin Technologies, Inc. | Cyclic natriuretic peptide constructs |
| US8206735B2 (en) * | 2006-07-11 | 2012-06-26 | Foresee Pharmaceuticals, Llc | Pharmaceutical compositions for sustained release delivery of peptides |
| GB0705264D0 (en) * | 2007-03-20 | 2007-04-25 | Pliva Istrazivanje I Razvoj D | Gel forming compounds |
| WO2008143958A1 (en) * | 2007-05-18 | 2008-11-27 | The Brigham And Women's Hospital, Inc. | Use of somatostatin analogs in myocardial perfusion imaging |
| EP2244679A4 (en) * | 2008-02-08 | 2013-10-09 | Qps Llc | NON-POLYMERIC COMPOSITIONS FOR CONTROLLED MEDICINAL PRODUCTION |
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- 2011-03-23 RU RU2012145278/15A patent/RU2012145278A/ru not_active Application Discontinuation
- 2011-03-23 EP EP11712680A patent/EP2550005A1/en not_active Withdrawn
- 2011-03-23 JP JP2013500647A patent/JP2013523629A/ja not_active Ceased
- 2011-03-23 AU AU2011231173A patent/AU2011231173A1/en not_active Abandoned
- 2011-03-23 KR KR1020127027694A patent/KR20130062275A/ko not_active Withdrawn
- 2011-03-23 CA CA2792470A patent/CA2792470A1/en not_active Abandoned
- 2011-03-23 CN CN2011800157799A patent/CN102883735A/zh active Pending
- 2011-03-23 BR BR112012022377A patent/BR112012022377A2/pt not_active IP Right Cessation
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- 2011-03-23 WO PCT/IE2011/000019 patent/WO2011117851A1/en not_active Ceased
- 2011-03-23 MX MX2012010343A patent/MX2012010343A/es not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| JP2013523629A (ja) | 2013-06-17 |
| CA2792470A1 (en) | 2011-09-29 |
| IE20100174A1 (en) | 2012-02-29 |
| US20130085105A1 (en) | 2013-04-04 |
| AU2011231173A1 (en) | 2012-10-18 |
| EP2550005A1 (en) | 2013-01-30 |
| MX2012010343A (es) | 2013-01-29 |
| RU2012145278A (ru) | 2014-04-27 |
| BR112012022377A2 (pt) | 2017-01-10 |
| WO2011117851A1 (en) | 2011-09-29 |
| CN102883735A (zh) | 2013-01-16 |
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