Compositions and methods for treating diseases

• US 20050192210A1
• Filed: 03/01/2005
• Published: 09/01/2005
• Est. Priority Date: 03/01/2004
• Status: Abandoned Application

• Current Assignee: Lumen Therapeutics LLC
• Original Assignee: Lumen Therapeutics LLC
• Inventors: Fathman, C. Garrison, Kreider, Erik, Rothbard, Jonathan B., McGrane, Paul L., Engleman, Edgar G.
• Application Number:
  US11/070,528
• Publication Number:
  US 20050192210A1
• Time in Patent Office: Days
• US Class Current: 514/1.5
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 31/4178 not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
• CPC Class Codes: A61K 31/5377 not condensed and containing further heterocyclic rings, e.g. timolol
• CPC Class Codes: A61K 38/04 Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof enzyme inhibitors A61K38/005; gastrins A61K38/2207, somatostatins A61K38/31, melanotropins A61K38/34 ; protease inhibitors A61K38/55
• CPC Class Codes: A61K 38/08 Peptides having 5 to 11 amino acids A61K38/043 - A61K38/046 take precedence
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 15/08 for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
• CPC Class Codes: A61P 15/10 for impotence
• CPC Class Codes: A61P 15/12 for climacteric disorders
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 17/14 for baldness or alopecia
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/06 Antiglaucoma agents or miotics
• CPC Class Codes: A61P 27/12 for cataracts
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/12 : for electrolyte homeostasis
• CPC Class Codes: A61P 31/04 : Antibacterial agents
• CPC Class Codes: A61P 7/02 : Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/12 : Antihypertensives
• CPC Class Codes: A61P 9/14 : Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
• CPC Class Codes: Y02A 50/30 : Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

This invention relates to compositions and methods for treatment of vascular conditions. The invention provides arginine polymers and arginine homopolymers for the treatment and/or prevention of glaucoma, pulmonary hypertension, asthma, chronic obstructive pulmonary disease, erectile dysfunction, Raynaud'"'"'s syndrome, heparin overdose, vulvodynia, and wound healing. The invention also provides arginine polymers and arginine homopolymers for use in organ perfusate and preservation solutions.

Claims

1. A method for treating or preventing a vascular condition in a patient comprising administering locally to said patient a therapeutically effective amount of a composition that increases the metabolic production of NO.

2. The method of claim 1 wherein said metabolic production is by NOS.

3. The method of claim 2 wherein said NOS is inducible NOS.

4. The method of claim 1 wherein said composition is an arginine polymer comprising of at least 8 consecutive arginine residues.

5. The method of claim 1 wherein said composition is an arginine homopolymer

6. The method of claim 5 wherein said arginine homopolymer comprises essentially of L-arginine residues.

7. The method of claim 1 wherein said composition is administered subcutaneously, topically, via inhalation, vaginally, rectally, ocularly, or parenterally.

8. The method of claim 1 wherein said condition is selected from the group consisting of aneurysm, anastomatic intimal hyperplasia, atherosclerosis, Behcet'"'"'s Syndrome, carotid artery disease, chronic obstructive pulmonary disease, chronic rejection, coronary artery disease, degos, dementia, headaches, hemorrhoids, heparin overdose, hereditary angioedema, pulmonary arterial hypertension, ischemia, lymphedema, myoamoya, peripheral arterial disease, pseudoxanthoma elasticum, thoracic outlet syndrome, thromboangiitis obliterans, thrombosis, varicose veins, and Wegener'"'"'s granulomatosis, atelectasis, acidosis, acute bronchitis, acute mountain sickness, acute pulmonary edema, acute pulmonary thrombolism, adult respiratory distress syndrome, bronchial asthma, early embolic stroke, emphysema, fat embolism in the lung, hypertension, hypoxia, hyaline membrane disease, inflammation of the lung, Kartaagener'"'"'s syndrome, Legionnaire'"'"'s disease, myocardial infraction, panacinar emphysema, persistent pulmonary hypertension of newborn, post cardiac surgery acute pulmonary pneumonia, prenatal aspiration syndrome, erectile dysfunction, Peyronie'"'"'s syndrome, priapism, premature ejaculation, female sexual dysfunctions, vaginal lubrication, vaginal engorgement, pain during intercourse (e.g., dyspareunia or vulvadynia), urologenital infections, estrogen depletion conditions, menopause and post-menopause, hot flashes, preeclampsia, vulvodynia, cataract, intraocular pressure, dry eye, and diabetic retinopathy, aging, necrotizing fascitis, decubitus ulcers, anal fissures, scleroderma, Raynaud'"'"'s phenomenon, sclerosis, malignant nephroangioscelerosis, infraction from occlusion of major renal vessels, atheromatoous embolization, renal cortical necrosis, and renal vein thrombosis.

27. A method for treating peripheral arterial disease comprising administering to a patient suffering from said disease a drug eluting stent of claim 2.

28. The stent of claim 2 wherein said metabolic production NO is by NOS

29. The method of claim 2 wherein said NOS is inducible NOS

30. The method of claim 3 wherein said composition is an arginine polymer comprising of at least 8 consecutive arginine residues.

31. The method of claim 3 wherein said composition is an arginine homopolymer.

32. The method of claim 3 wherein said arginine homopolymer comprises essentially of L-arginine residues.

9. A method for treating or preventing glaucoma in a patient comprising administering to said patient a therapeutically effective amount of a composition that increases the metabolic production of NO.

10. The method of claim 9 wherein said metabolic production is by NOS.

11. The method of claim 10 wherein said NOS is inducible NOS.

12. The method of claim 9 wherein said composition is administered topically, parenterally, subcutaneously, or ocularly.

13. The method of claim 9 wherein said composition is administered locally to a trabecular meshwork or a Schlemm'"'"'s canal.

14. The method of claim 9 wherein said composition is an arginine polymer comprising of at least 8 consecutive arginine residues.

15. The method of claim 9 wherein said composition is an arginine homopolymer.

16. The method of claim 15 wherein said arginine homopolymer comprises essentially of L-arginine residues.

17. The method of claim 9 further comprising administering to said patient an agent selected from the group consisting of pilocarpine, timolol maleate, betataxolol HCl, epinephrine, dipivefrin, demecarium bromide, echothiophate iodide, A3 subtype adenosine receptor antagonist, antiestrogen, and calmodulin antagonist.

18. A composition for the preservation and reperfusion having an osmolality level of about 150-350 mOsm/liter comprising an agent that increases the metabolic production of NO.

19. The method of claim 18 wherein said metabolic production is by NOS.

20. The method of claim 19 wherein said NOS is inducible NOS.

21. The composition of claim 18 further comprising hydroxyethyl starch, lactobionate salt, or raffinose.

22. The composition of claim 18 wherein said agent is an arginine polymer comprising of at least 9 consecutive arginine residues.

23. The composition of claim 18 wherein said agent is an arginine homopolymer.

24. The composition of claim 23 wherein said arginine homopolymer comprises essentially of L-arginine residues.

25. The composition of claim 18 further comprising one or more agents selects from the group consisting of:

insulin, dexamethasone, phenol red, penicillin, sodium gluconate, calcium chloride, magnesium gluconate, HEPES buffer, glucose, adenosine, glutathione, and potassium phosphate.

26. A drug eluting stent comprising a composition that increases the metabolic production of NO in a cell, tissue, or organ.