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Treatment for Cardiovascular Disease

a treatment and cardiovascular disease technology, applied in the field of treatment for cardiovascular disease, can solve the problems of increasing the risk of the development of hypertension, atherosclerosis, other cardiovascular diseases, and unresolved issues, and achieve the effects of reducing uric acid levels, and treating and preventing hypertension

Inactive Publication Date: 2007-10-04
KIVLIGHN SALAH +2
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0011] This invention relates to a method for treating and preventing hypertension by administering a therapeutically effective amount of an agent capable of reducing uric acid levels in a patient in need of such treatment. Additionally, the scope of the invention includes a method of treating coronary heart disease by administering a therapeutically effective amount of an agent capable of reducing uric acid levels in a patient in need of such treatment. The agent, or pharmaceutically acceptable salt thereof, capable of reducing uric acid levels is selected from the group consisting of gene therapy, a xanthine oxidase inhibitor, a uricosuric a

Problems solved by technology

In most subjects, the loss of uricase appears to be of no significance, but for the 10 to 15 percent of the general population with the highest uric acid levels (>6.0 mg / dl in women and >6.5 mg / dl in men), there is an increased risk for the development of hypertension, atherosclerosis, and other cardiovascular diseases.
The lack of a mechanistic pathway by which uric acid can cause cardiovascular disease, coupled with the inconclusive clinical and epidemiological data, have left this issue unresolved.
Controversy has existed, however, over whether hyperuricemia is the cause or consequence of renal vasoconstriction and tubulointerstitial lesions [Nickeleit, V., and Mihatsh, M. J., Uric acid nephropathy and end-stage renal disease.
The major risks classically attributed to hyperaricemia have been the risk of developing gout and / or uric acid renal stones.
However, investigators have challenged if ‘gouty nephropathy’ truly exists (Beck, L. H., Requiem for gouty nephropathy.
It is known that markedly elevated uric acid can crystallize in the tubules of the kidney and cause kidney failure.

Method used

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  • Treatment for Cardiovascular Disease
  • Treatment for Cardiovascular Disease
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Examples

Experimental program
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Effect test

example 1

[0051] Rats were placed on a normal salt (NaCl 0.26%) diet with or without 2% oxonic acid (Ziegler Bros, Gardners, Pa.) added to the diet and rats were sacrificed at week 7.

[0052] Systolic blood pressure was measured by tail cuff sphyngomanometer using an automated system with photoelectric sensor (IITC, Life Science) that has been shown to closely correlate with intra-arterial blood pressure measurements [Fischer E, Schnermann, J., Briggs, J. P, Kriz, W. Ronco, P. M., Bachmann, S. Ontogeny of NO synthase and renin in juxtaglomerular apparatus of rat kidneys. Am J Physiol 268:F1164-76, 1995].

example 2

[0053] Rats were placed on a low sodium diet (NaCl, 0.125%) with or without 2% oxonic acid for 7 weeks. A third group were administered allopurinol in the drinking water (150 mg / L) with weekly adjustments of the dose depending on the uric acid level.

[0054] Systolic blood pressure was measured by tail cuff sphyngomanometer using an automated system with photoelectric sensor (IITC, Life Science) that has been shown to closely correlate with intra-arterial blood pressure measurements [Fischer E, Schnermann, J., Briggs, J. P, Kriz, W. Ronco, P. M., and Bachmann, S., Ontogeny of NO synthase and renin in juxtaglomerular apparatus of rat kidneys. Am J Physiol 268:F1164-76, 1995].

example 3

[0055] Rats were placed on the low sodium diet with oxonic acid for 7 weeks, and then were matched based on uric acid level and blood pressure in various groups to either receive allopurinol, have the oxonic acid withdrawn from the diet, or continue the oxonic acid / low salt diet. A control group of six rats were placed on the low sodium diet alone for 11 weeks. All of these rats were sacrificed at week 11.

[0056] Systolic blood pressure was measured by tail cuff sphyngomanometer using an automated system with photoelectric sensor (IITC, Life Science) that has been shown to closely correlate with intra-arterial blood pressure measurements [Fischer, E., Schnermann, J., Briggs, J. P, Kriz, W., Ronco, P. M., and Bachmann, S., Ontogeny of NO synthase and renin in juxtaglomerular apparatus of rat kidneys. Am J Physiol 268:F1164-76, 1995].

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Abstract

This invention relates to a method for treating and preventing hypertension by administering a therapeutically effective amount of an agent capable of reducing uric acid levels in a patient in need of such treatment. Additionally, the scope of the invention includes a method of treating coronary heart disease by administering a therapeutically effective amount of an agent capable of reducing uric acid levels in a patient in need of such treatment.

Description

[0001] This application claims priority from co-pending provisional application Ser. No. 60 / 214,825 filed on Jun. 28, 2000.[0002] The U.S. Government has a paid-up license in this invention and a right in limited circumstances to require the patent owner to license others on reasonable terms as provided for by the terms of National Institute of Health Grant No. DK 47659.BACKGROUND OF THE INVENTION [0003] Uric acid is a purine metabolite that in most animals is degraded by the hepatic enzyme uricase to allantoin. However, several mutations of the gene for this enzyme occurred during early primate development with the consequence that man and other primates have relatively higher levels of serum uric acid [Wu, X., Muzny, D. M., Lee, C. C., and Caskey, C. T., Two independent mutational events resulted in the loss of urate oxidase during hominoid evolution. J Mol. Evol. 34:78-84 (1992)]. The adaptive benefit of this deletion is not known nor has the modern day consequences of these muta...

Claims

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Application Information

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IPC IPC(8): A61K31/495A61K31/54A61K38/00A61K45/00A61K31/19A61K31/195A61K31/343A61K31/381A61K31/401A61K31/403A61K31/405A61K31/4152A61K31/4178A61K31/423A61K31/505A61K31/513A61K31/519A61K38/13A61K45/06A61K47/48A61K48/00A61P9/10A61P9/12A61P19/06A61P25/08A61P43/00
CPCA61K31/195A61K31/343A61K47/48215A61K45/06A61K38/13A61K31/519A61K31/513A61K31/505A61K31/423A61K31/381A61K31/401A61K31/403A61K31/405A61K31/4152A61K31/4178A61K2300/00A61K47/60A61P19/06A61P25/08A61P43/00A61P9/10A61P9/12
Inventor KIVLIGHN, SALAHJOHNSON, RICHARDMAZZALI, MARILDA
Owner KIVLIGHN SALAH