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Use of relaxin to treat diseases related to vasoconstriction

a technology of vasoconstriction and relaxin, which is applied in the direction of anti-noxious agents, drug compositions, peptide/protein ingredients, etc., can solve the problems of reducing cardiac output and other problems, and achieve the effect of safe relaxation profile and beneficial therapeutic

Inactive Publication Date: 2004-12-30
THE UNIVERSITY OF MEDICINE & DENTISTRY OF NEW JERSEY ROBERT WOOD JOHNSON MEDICAL SCHOOL +2
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0018] An advantage of the present invention lies in the fact that the safety profile of relaxin in humans is superior to other agents, such as VEGF and FGF.
[0019] A further advantage of the use of relaxin to treat hypertensive vascular diseases is that it is effective in both males and females.
[0020] Another object of the invention is a method whereby therapeutically effective amounts of relaxin are repeatedly administered to a patient over a period of time to obtain a beneficial therapeutic result.
[0021] Another aspect of the invention is to repeatedly or substantially continuously administer relaxin over a period of time in a manner so as to maintain therapeutic blood levels of relaxin over periods sufficient to obtain therapeutic results.
[0022] A feature of the invention is injectable and sustained-release formulations of relaxin which are useful in the method of the invention wherein the formulation comprises a pharmaceutically acceptable carrier and a therapeutically effective amount of relaxin.

Problems solved by technology

Vasoconstriction, or the reduction in the cross-sectional area of the lumen of small blood vessels, is a potentially lethal condition arising in a variety of pathologies, and is due either to vasospasm, inadequate vasodilation, thickening of the vessel wall, or the accumulation of flow-restricting materials on the internal wall surfaces or within the wall itself.
However, negative consequences, such as hypotension, tachycardia and reduced cardiac output have been observed when VEGF is given to patients.

Method used

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  • Use of relaxin to treat diseases related to vasoconstriction
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  • Use of relaxin to treat diseases related to vasoconstriction

Examples

Experimental program
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Effect test

example 1

Relaxin is a Potent Renal Vasodilator in Conscious Rats

[0090] Materials and Methods

[0091] Animal Preparation

[0092] Long-Evans female rats aged 10-14 weeks were purchased from Harlan Sprague-Dawley (Frederick, Md.). They were fed PROLAB RMH 2000 diet containing 0.48% sodium (PME Feeds Inc., St. Louis, Mo.) and provided water ad libitum. To prepare the rats for experimental procedures, they were trained for several hours in a Plexiglas restraining cage (Braintree Scientific Co., Braintree, Mass.) on at least five different occasions before surgical intervention. These cages afforded sufficient space for grooming of the face and front paws while preventing the rat from turning around. Thus, accurate timed-urine collections and blood samplings were made possible from the chronically implanted bladder and vascular catheters, respectively. Rats failing to habituate to the cage were eliminated from the study (<1%). All animal procedures were approved by the Institutional Animal Care and Us...

example 2

Impact of Gender and Endothelin on Renal Vasodilation and Hyperfiltration Induced by Relaxin in Conscious Rats

[0113] Methods

[0114] Animal preparation. Long Evans female and male rats of 10-14 weeks of age were used. Those animals studied at the University of New Mexico were purchased from Harlan Sprague-Dawley (Indianapolis, Ind.) and were fed PROLAB RMH 2500 diet containing 0.40% sodium (PME Feeds Inc., St. Louis, Mo.). The rats investigated at the Magee-Womens Research Institute were purchased from Harlan Sprague-Dawley (Frederick, Md.) and they were fed PROLAB RMH 2000 diet containing 0.48% sodium (PME Feeds Inc., St. Louis Mo.). The rats were maintained on a 12 hour light / dark cycle in fully accredited Animal Resource Facilities approved by the Association for Assessment and Accreditation of Laboratory Animal Care. All experiments were approved by the Institutional Animal Care and Use Committee of the University of New Mexico School of Medicine or the Magee-Womens Research Insti...

example 3

[0134] Example 3

Systemic Relaxin Administration Stimulates Angiogenic / Vasbdilatory Cytokine Expression and Vessel Formation in a Rat Myocardial Infarct Model

[0135] Female Sprague Dawley rats, approximately 12-weeks of age were used. Rats were anesthetized by intraperitoneal (i.p.) injection of up to 1 ml / kg ketamine / medetomidine (6:4). Following exteriorization of the heart, the left coronary artery was ligated near its origin with a silk suture. In sham surgery control animals, the suture was placed superficially into the muscle adjacent to the coronary artery. Post-closure EKG's were monitored for S-T segment elevation in LCAL animals to confirm the outcome of ligation. Immediately following cardiac surgery, a primed mini-osmotic pump containing relaxin or vehicle (20 mM acetate, pH 5.0) was aseptically implanted into a subcutaneous (s.c.) pocket on the dorsal interscapular region. Vehicle or relaxin (0.1 mg / kg / day) was delivered as a continuous s.c. infusion for 7 or 21 days to e...

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Abstract

The invention relates to methods of treating diseases related to vasodilation, generally comprising administering to an individual an effective amount of a pharmaceutically active relaxin. Relaxin functions to increase both vasodilation and angiogenesis in males as well as females, and is therefore useful in treating a wide variety of diseases relating to vasoconstriction.

Description

CROSS-REFERENCE[0001] This application claims the benefit of U.S. provisional patent application Nos. 60 / 181,408, filed Feb. 9, 2000; 60 / 200,284, filed Apr. 28, 2000; and 60 / 242,216, filed Oct. 20, 2000, each of which is incorporated herein by reference in their entirety.[0003] This invention is in the field of diseases related to vasoconstriction, and in particular to the use of relaxin to treat diseases related to vasoconstriction.[0004] Vasoconstriction, or the reduction in the cross-sectional area of the lumen of small blood vessels, is a potentially lethal condition arising in a variety of pathologies, and is due either to vasospasm, inadequate vasodilation, thickening of the vessel wall, or the accumulation of flow-restricting materials on the internal wall surfaces or within the wall itself. Vasoconstriction is a major factor in various hypertensive vascular diseases, as well as conditions which result from such diseases, including progressive generalized atherogenesis, myoca...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K38/22
CPCA61K38/2221A61P9/10A61P9/12
Inventor CONRAD, KIRK P.LEWIS, MARTYNUNEMORI, ELAINE N.HUANG, XINFANTOZZI, CAROL A.
Owner THE UNIVERSITY OF MEDICINE & DENTISTRY OF NEW JERSEY ROBERT WOOD JOHNSON MEDICAL SCHOOL
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