(12) Patent Application Publication (10) Pub. No.: US 2014/0350021 A1 Gonzalez-Cadavid Et Al

US 2014035 0021A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2014/0350021 A1 Gonzalez-Cadavid et al. (43) Pub. Date: Nov. 27, 2014

(54) METHODS OF USE OF INHIBITORS OF Publication Classification PHOSPHODESTERASES AND MODULATORS OF NITRICOXIDE, (51) Int. Cl. REACTIVE OXYGEN SPECIES, AND A613 L/4985 (2006.01) METALLOPROTEINASES IN THE A613 L/53 (2006.01) TREATMENT OF PEYRONIES DISEASE, A 6LX3/59 (2006.01) ARTEROSCLEROSIS AND OTHER (52) U.S. Cl. FBROTC DISEASES CPC ...... A6 IK3I/4985 (2013.01); A61 K3I/519 (2013.01); A61 K3I/53 (2013.01); A61 K (71) Applicant: Los Angeles Biomedical Research 220.1/094 (2013.01) Institute at Harbor-UCLA Medical USPC ...... 514/243; 514/252.16; 514/250 Center, Torrance, CA (US) (57) ABSTRACT (72) Inventors: Nestor F. Gonzalez-Cadavid, Pasadena, CA (US); Jacob Rajfer, San Pedro, CA The present methods and compositions are of use for treat (US) ment of conditions involving fibrosis, such as Peyronies disease plaque, penile corporal fibrosis, penile Veno-occlu (21) Appl. No.: 14/453,543 sive dysfunction, Dupuytren’s disease nodules, vaginal fibro sis, clitoral fibrosis, female sexual arousal disorder, abnormal (22) Filed: Aug. 6, 2014 wound healing, keloid formation, general fibrosis of the kid ney, bladder, prostate, skin, liver, lung, heart, intestines or any Related U.S. Application Data other localized or generalized fibrotic condition, vascular fibrosis, arterial intima hyperplasia, atherosclerosis, arterio (63) Continuation of application No. 13/372,094, filed on Sclerosis, restenosis, cardiac hypertrophy, hypertension or Feb. 13, 2012, which is a continuation of application any condition characterized by excessive fibroblast or smooth No. 10/779,069, filed on Feb. 13, 2004, now Pat. No. muscle cell proliferation or deposition of collagen and extra 8,133,903. cellular matrix in the blood vessels and/or heart. In certain (60) Provisional application No. 60/420,281, filed on Oct. embodiments, the compositions may comprise a PDE-4 22, 2002. inhibitor, a PDE-5 inhibitor, a compound that elevates cGMP and/or PKG, a stimulator of guanylyl cyclase and/or PKG, a (30) Foreign Application Priority Data combination of a compound that elevates cGMP PKG or NO with an antioxidant that decreases ROS, or a compound that Oct. 21, 2003 (WO) ...... USO3/33400 increases MMP activity.

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