专利号:US-6469065-B1 优先权日:1996-02-02 标 题:Nitrosated and nitrosylated α-adrenergic receptor antagonist, compositions and methods of use 发明人:GARVEY DAVID S; SCHROEDER JOSEPH D; DE TEJADA INIGO SAENEZ; GASTON RICKY D; SHELEKHIN TATIANA E; WANG TIANSHENG 权利人:NITROMED INC 摘要:The present invention describes novel nitrosated and/or nitrosylated α-adrenergic receptor antagonists, and novel compositions containing at least one nitrosated and/or nitrosylated α-adrenergic receptor antagonist, and, optionally, one or more compounds that donate, transfer or release nitric oxide, elevate endogenous levels of endothelium-derived relaxing factor, stimulate endogenous synthesis of nitric oxide or are a substrate for nitric oxide synthase, and/or one or more vasoactive agents. The present invention also provides novel compositions containing at least one α-adrenergic receptor antagonist, and one or more compounds that donate, transfer or release nitric oxide, elevate endogenous levels of endothelium-derived relaxing factor, stimulate endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or one or more vasoactive agents. The present invention also provides methods for treating or preventing sexual dysfunctions in males and females, for enhancing sexual responses in males and females, and for treating or preventing benign prostatic hyperplasia, hypertension, congestive heart failure, variant (Printzmetal) angina, glaucoma, neurodegenerative disorders, vasospastic diseases, cognitive disorders, urge incontinence, or overactive bladder, and for reversing the state of anesthesia.
专利号:US-6436997-B1 优先权日:1998-06-01 标题 :Endogenous nitric oxide synthesis under conditions of low oxygen tension 发明人:DE TEJADA INIGO SAENZ 权利人:NITROMED INC 摘要:The present invention provides methods of promoting synthesis of nitric oxide or endothelium-derived relaxing factor (EDRF) in hypoxic mammalian tissues by administering at least one N-hydroxyguanidine compound that is a substrate of nitric oxide synthase, and, optionally, one or more vasoactive agents and/or thromboxane A2 receptor antagonists. The present invention also provides methods of promoting vasorelaxation and treating sexual dysfunctions in patients by administering at least one N-hydroxyguanidine compound that is a substrate for nitric oxide synthase, and, optionally, at least one vasoactive agent and/or thromboxane A2 receptor antagonist. The present invention also provides methods for treating clinical conditions resulting from hypoxic conditions such as pulmonary disease, cardiovascular disorders, circulatory hypoxia, specific organ hypoxia, localized hypoxia, edema, central nervous system disorders, memory loss, or arterial disease. The present invention also provides methods for treating clinical conditions resulting from an abnormally high level of arginase activity, such as, heart disease, systemic hypertension, pulmonary hypertension, sexual dysfunction, autoimmune disease, chronic renal failure and cerebral vasospasm. The present invention also provides methods for treating clinical conditions associated with a deficient nitric oxide pathway by administering at least one N-hydroxyguanidine compound and, optionally, one or more vasoactive agents and/or thromboxane A2 receptor antagonists. The present invention also provides pharmaceutical compositions comprising at least one N-hydroxyguanidine compound, and, optionally, one or more vasoactive agents and/or thromboxane A2 receptor antagonists.
专利号:US-10100028-B2 优先权日:2013-09-30 标 题:Synthesis routes for prostaglandins and prostaglandin intermediates using metathesis 发明人:YIANNIKOUROS GEORGE PETROS; KALARITIS PANOS; GAMAGE CHAMINDA PRIYAPUSHPA; AREFYEV DENIS VIKTOROVICH 权利人:IRIX PHARMACEUTICALS INC; PATHEON API SERVICES INC 摘要:Methods of synthesizing prostaglandins, prostaglandin analogs and their synthetic intermediates are described. The methods can comprise metal-catalyzed metathesis reactions. Also provided are synthetic intermediates that can be used in the synthesis of the prostaglandins and prostaglandin analogs.
专利号:US-6693122-B2 优先权日:1999-05-12 标题:Nitrosated and nitrosylated potassium channel activators, compositions and methods of use 发明人:GARVEY DAVID S; SAENZ DE TEJADA INIGO 权利人:NITROMED INC 摘要:The present invention describes novel nitrosated and/or nitrosylated potassium channel activators, and novel compositions comprising at least one nitrosated and/or nitrosylated potassium channel activator, and, optionally, at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or at least one vasoactive agent. The present invention also provides novel compositions comprising at least one potassium channel activator, and at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or at least one vasoactive agent. The present invention also provides methods for treating or preventing sexual dysfunctions in males and females, for enhancing sexual responses in males and females, and for treating or preventing cardiovascular disorders, cerebrovascular disorders, hypertension, asthma, baldness, urinary incontinence, epilepsy, sleep disorders, gastrointestinal disorders, migraines, irritable bowel syndrome and sensitive skin.
专利号:US-6930113-B2 优先权日:1996-11-01 标题 :Nitrosated and nitrosylated phosphodiesterase inhibitors, compositions and methods of use 发明人:GARVEY DAVID S; DE TEJADA INIGO SAENZ; EARL RICHARD A; KHANAPURE SUBHASH P 权利人:NITROMED INC 摘要:The present invention describes novel nitrosated and/or nitrosylated phosphodiesterase inhibitors, and novel compositions containing at least one nitrosated and/or nitrosylated phosphodiesterase inhibitor, and, optionally, one or more compounds that donate, transfer or release nitric oxide, elevate endogenous levels of endothelium-derived relaxing factor, stimulate endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or one or more vasoactive agents. The present invention also provides novel compositions containing at least one phosphodiesterase inhibitor, and one or more compounds that donate, transfer or release nitric oxide, elevate endogenous levels of endothelium-derived relaxing factor, stimulate endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or one or more vasoactive agents. The present invention also provides methods for treating or preventing sexual dysfunctions in males and females, for enhancing sexual responses in males and females, and for treating or preventing diseases induced by the increased metabolism of cyclic guanosine 3′,5′-monophosphate (cGMP), such as hypertension, pulmonary hypertension, congestive heart failure, renal failure, myocardial infraction, stable, unstable and variant (Prinzmetal) angina, atherosclerosis, cardiac edema, renal insufficiency, nephrotic edema, hepatic edema, stroke, asthma, bronchitis, chronic obstructive pulmonary disease (COPD), cystic fibrosis, dementia, immunodeficiency, premature labor, dysmenorrhoea, benign prostatic hyperplasis (BPH), bladder outlet obstruction, incontinence, conditions of reduced blood vessel patency, e.g., postpercutaneous transluminal coronary angioplasty (post-PTCA), peripheral vascular disease, allergic rhinitis, glucoma, and diseases characterized by disorders of gut motility, e.g., irritable bowel syndrome (IBS).
专利号:US-5905091-A 优先权日:1996-07-03 标 题 :Enhancement of skin pigmentation by prostaglandins 发明人:FULLER BRYAN B 权利人:UNIV OKLAHOMA 摘要:A composition comprising a carrier and prostaglandin effective in stimulating synthesis of melanin in a human melanocyte thereby enhancing pigmentation of the human skin and optionally comprising a lysosomotropic agent, a phosphodiesterase inhibitor, and/or methylxanthines, and a method of use of the composition. Use of this composition promotes tanning of the human skin and increases photoprotection from ultraviolet radiation.
1: Zhuo Z, Yu H, Jiang X. A systematic review and meta-analysis of randomized controlled trials on the effectiveness of cervical ripening with misoprostol administration before hysteroscopy. Int J Gynaecol Obstet. 2016 Mar;132(3):272-7. doi: 10.1016/j.ijgo.2015.07.039. Epub 2015 Dec 11. Review. doi: 10.1111/1471-0528.13456. Epub 2015 Nov 5. Review. doi: 10.1093/heapol/czv012. Epub 2015 Mar 21. Review. doi: 10.1007/s00404-015-3779-x. Epub 2015 Jun 4. Review. Review. 6: Stephenson ML, Wing DA. Misoprostol for induction of labor. Semin Perinatol. 2015 Oct;39(6):459-62. doi: 10.1053/j.semperi.2015.07.008. Review. doi: 10.1016/j.ijgo.2015.04.031. Epub 2015 Jun 10. Review. doi: 10.1097/AOG.0000000000000897. Review. doi: 10.1016/j.ijgo.2015.01.005. Epub 2015 Mar 10. Review. Review. Overview and expert assessment of off-label use of misoprostol in obstetrics and gynaecology: review and report by the Collège national des gynécologues obstétriciens français. Eur J Obstet Gynecol Reprod Biol. 2015 Apr;187:80-4. doi: 10.1016/j.ejogrb.2015.01.018. Epub 2015 Jan 31. Review. doi: 10.1111/1471-0528.12935. Epub 2014 Jul 3. Review. doi: 10.2147/DDDT.S64227. eCollection 2015. Review. 14: Patte C, Deruelle P. A critical appraisal of the misoprostol removable, controlled-release vaginal delivery system of labor induction. Int J Womens Health. 2015 Nov 12;7:889-99. doi: 10.2147/IJWH.S62372. eCollection 2015. Review.
合成参考文献
参考文献:10.1056/nejmoa051620 摘要:Fischer M, Bhatnagar J, Guarner J, Reagan S, Hacker JK, Van Meter SH, Poukens V, Whiteman DB, Iton A, Cheung M, Dassey DE, Shieh WJ, Zaki SR. Fatal toxic shock syndrome associated with Clostridium sordellii after medical abortion. N Engl J Med. 2005 Dec 01;353(22):2352–60. doi: 10.1056/nejmoa051620. 参考文献:10.1056/nejm200512013532216 摘要:Shukunami K, Nishijima K, Kotsuji F. Medical vs. surgical management of early pregnancy failure. N Engl J Med. 2005 Dec 01;353(22):2403–4; author reply 2403. doi: 10.1056/nejm200512013532216. 参考文献:10.1007/s00101-009-1673-2 摘要:Wallenborn J; German Society for Anesthesiology and Intensive Care Medicine; Professional Association of German Anesthetists; German Society for Gynecology and Obstetrics. [Execution of analgesia and anesthesia procedures in obstetrics : Second revised recommendations of the German Society for Anesthesiology and Intensive Care Medicine and the Professional Association of German Anesthetists in cooperation with the German Society for Gynecology and Obstetrics]. Anaesthesist. 2010 Mar;59(3):250–4. doi: 10.1007/s00101-009-1673-2. 参考文献:10.1007/s00228-010-0789-2 摘要:Gudbjornsson B, Thorsteinsson SB, Sigvaldason H, Einarsdottir R, Johannsson M, Zoega H, Halldorsson M, Thorgeirsson G. Rofecoxib, but not celecoxib, increases the risk of thromboembolic cardiovascular events in young adults—a nationwide registry-based study. European Journal of Clinical Pharmacology. 2010 Feb 16;66(6):619–25. doi: 10.1007/s00228-010-0789-2. 参考文献:10.1016/j.contraception.2009.10.008 摘要:Lohr PA, Reeves MF, Creinin MD. A comparison of transabdominal and transvaginal ultrasonography for determination of gestational age and clinical outcomes in women undergoing early medical abortion. Contraception. 2010 Mar;81(3):240–4. doi: 10.1016/j.contraception.2009.10.008.