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Compositions and methods for treating diseases

a technology applied in the field of compositions and methods for treating diseases, can solve the problems of affecting the survival of patients, and local l-arginine concentrations might become rate limiting, so as to prevent vascular conditions or local tissue no deficiencies, and increase metabolic or enzymatic production.

Inactive Publication Date: 2005-09-01
LUMEN THERAPEUTICS
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

It is also expected that the induced form of NOS produces a much greater amount of NO than cNOS, and may even result in toxicity when the L-arginine supply is limited.
However, under certain circumstances, local L-arginine concentrations might become rate limiting.
One of the greatest limitations in administering a NO donor is that in vivo administration of such compounds can induce severe systemic hypotension.

Method used

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Examples

Experimental program
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Effect test

example 1

[0154] An AV graft is contacted with in a solution containing 0.001 μM-100 mM NO enhancer(s), e.g., R9 or R10. The graft is contacted with the solution for a period preferably less than 60 minutes. The graft is contacted prior to, during, and / or post grafting. In some cases, the graft is infused intraluminally with the L-arginine solution and one or both ends of the graft are clamped such that only the intraluminal walls of the vessel are contacted.

example 2

[0155] An organ transplant solution (perfusate) preferably includes 0.001 μM-100 mM of a NO enhancer(s), e.g., R9 or R10. Furthermore, the solution may also include approximately 1-5% by weight hydroxyethyl starch. The solution can have a molecular weight ranging preferably between 150,000-350,000 Daltons. The solution can have an osmolality level ranging preferably between 100-500 mOsm / liter. Other agents that may be admixed into the solution include, but are not limited to, lactobionate salt, raffinose, electrolytes, glutathione, potassium phosphate, magnesium gluconate, adenosine, insulin, bactrim, dexamethasone, allopurinaol and other anti-inflammatory, antibiotic, anti-metabolic, and anti-neoplastic agents.

example 3

[0156] For the treatment of peripheral arterial disease, a drug eluting stent may be coated or immersed with a timed-release NO enhancer, e.g. an arginine homopolymer containing L-arginines, D-arginines, or a combination thereof. An additional slow release carrier or excipient may be admixed with the polyarginine. Alternatively, a stent or balloon can be inserted into the targeted area (an occlusion), and a Dispatch catheter can deliver locally and in vivo a composition of R9 (e.g., a solution of 0.001μ-100 mM R9) prior to, during, and / or post stenting or angioplasty.

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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.

Description

CROSS REFERENCE TO RELATED APPLICATION [0001] This application claims priority to U.S. Provisional Application No. 60 / 549,321, filed Mar. 1, 2004 and which is hereby incorporated by reference.BACKGROUND OF THE INVENTION [0002] Numerous vascular conditions afflict mammals. Such conditions include, but are not limited to, coronary and peripheral arterial diseases, chronic rejection, vasculopathy associated with diabetes, pulmonary vascular conditions (e.g., pulmonary arterial hypertension and chronic obstructive pulmonary disease), ocular vascular conditions (e.g., intraocular pressure and glaucoma), sexual dysfunction vascular conditions (e.g., erectile dysfunction and vulvodynia), and dermal vascular conditions (e.g., Raynaud's phenomenon, scleroderma and wound healing). [0003] A known compound that has a general dilatory effect on the vascular system is nitric oxide (NO). See Nathan et al., Cell (1994) 78:915-916. NO plays an essential role in mammalian physiology and is responsibl...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K31/137A61K31/4178A61K31/5377A61K38/00A61K38/08
CPCA61K31/137A61K31/4178A61K38/08A61K38/04A61K31/5377A61P1/00A61P11/00A61P11/06A61P15/08A61P15/10A61P15/12A61P17/00A61P17/02A61P17/14A61P25/02A61P25/28A61P27/02A61P27/06A61P27/12A61P29/00A61P3/12A61P31/04A61P7/02A61P9/00A61P9/10A61P9/12A61P9/14Y02A50/30
Inventor ROTHBARD, JONATHAN B.MCGRANE, PAUL L.ENGLEMAN, EDGAR G.FATHMAN, C. GARRISONKREIDER, ERIK
Owner LUMEN THERAPEUTICS
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