Drug – bio-affecting and body treating compositions – Radionuclide or intended radionuclide containing; adjuvant... – In an organic compound
Patent
1996-05-08
1998-05-26
Kight, John
Drug, bio-affecting and body treating compositions
Radionuclide or intended radionuclide containing; adjuvant...
In an organic compound
424 111, 424 165, A61K 5100, A61M 3614
Patent
active
057560676
DESCRIPTION:
BRIEF SUMMARY
This invention relates to formulations useful in the diagnosis of a patient's predisposition to the development of atherosclerosis and coronary artery disease. It also relates to a method of diagnosing a patient's tendency to develop such diseases.
The predisposition of a person to develop atherosclerosis is dependent on several factors including genetic inheritance and environment. Atherosclerosis is a progressive disease of the walls of blood vessels, beginning with the accumulation of lipid substances and over a period of years leading to pathological changes such as fibrosis, ulceration and thrombosis within the vessel wall. Serious diseases consequent upon atherosclerosis include myocardial infarction, aneurysm, stroke and failure of adequate blood supply to organs and limbs leading to organ failure and gangrene. The disease is very common in Western countries where a diet high in cholesterol, excessive fat ingestion, cigarette smoking, obesity and physical inactivity are all contributing factors. Genetic factors can also lead to onset of atherosclerosis.
Although methods such as angiography and measurements of blood flow currently exist for assessment of established atherosclerosis, there are no current, accurate tests available to determine the likelihood that a patient has a metabolic predisposition towards development of the disease. Since treatments are available and preventative behavioural changes possible, such a method of predetermining a propensity to develop atherosclerosis would be useful to both patient and physician.
Tests currently available to measure the risk of developing atherosclerosis include measuring the plasma contents of cholesterol, triglycerides and lipoproteins. However it is clear that these tests are not conclusive since approximately one-half of heart disease due to atherosclerosis occurs in patients with plasma triglycerides and cholesterol within the normal range of the population. Moreover, angiographic evidence of atherosclerosis has been documented in patients having normal lipid levels.
One such test is described in Australian Patent Application 66416/90 to LEHIGH UNIVERSITY. In this patent application a patients propensity for atherosclerosis is measured by the number of low density lipoprotein receptors in the blood sample. Specifically, the rate of low density lipoprotein and receptor internalisation, and the rate of synthesis of receptors is measured by fluorescent assay.
An alternative method is described in Australian Patent Application 71429/91 to THE BETH ISRAEL HOSPITAL FOUNDATION. This patent application discloses a method for predicting atherosclerotic risk by the NMR measurement of protein resonance of high density lipoproteins compared to that of healthy individuals.
One particle not measured in current tests is chylomicrons which transport fat in the form of triacylglycerols from the small intestine to fat depots. The triglycerides in these particles are subject to a hydrolysis action by lipoprotein lipases in the bloodstream resulting in formation of a secondary particle which still contains up to 30% triglycerides, and the whole of the particle cholesteryl ester. This secondary particle is known as a chylomicron remnant or chyloremnant. The chyloremnant, having been divested of much of its triglyceride content, then contains a much higher relative amount of cholesterol to phospholipid. The primary function of the chyloremnant is to transport cholesterol from the intestine to the liver.
There is now evidence to suggest that an individuals ability to metabolise chyloremnants may be directly related to their propensity to develop atherosclerosis, and thus measurement of chyloremnants, or their precursor particles, chylomicrons is desirable as a diagnostic tool for atherosclerosis and related diseases. A reduced tolerance for chyloremnant clearance would indicate increased risk of atherosclerosis, while repeated tolerance tests would be useful in judging the effectiveness of therapies and interventions aimed at reducing atherosclerosis risk.
Such measur
REFERENCES:
patent: 3894844 (1975-07-01), Pinto et al.
patent: 4039285 (1977-08-01), Teipel
patent: 4676974 (1987-06-01), Hofmann et al.
patent: 4753788 (1988-06-01), Gamble
patent: 4772549 (1988-09-01), Frossard
patent: 4933157 (1990-06-01), Counsell et al.
patent: 4938947 (1990-07-01), Nicolau
patent: 5135848 (1992-08-01), Abel et al.
patent: 5320968 (1994-06-01), Seman
patent: 5362649 (1994-11-01), Schwertner
patent: 5432058 (1995-07-01), Lange, III et al.
patent: 5496735 (1996-03-01), Schwertner
Mortimer et al (1995), Journal of Biological Chemistry, vol. 270 Nov. 48, pp. 28767-28776, Intracellular Localization and Metabolism of Chylomicron Remnants in the Livers of Low Density Lipoprotein Receptor-deficient Mice and ApoE-deficient Mice.
Redgrave et al (1995), Journal of Lipid Research, vol. 36, pp. 2670-2675, "Measurement of Expired Carbon Dioxide to Assess the Metabolism of Remnant Lipoproteins".
Oliveira et al (1988), Biochimica et Biophysica Acta, vol. 958, pp. 211-217, "Competition Between Chylomicrons and Their Remnants for Plasma Removal: A Study with Artificial Emulsion Models of Chylomicrons".
Lenzo et al (1988), Biochimica et Biophysica Acta, vol. 960, pp. 111-118, "Effects of Phospholipid Composition on the Metabolism of Triacylglycerol, Cholesteryl Ester and Phosphatidyl Choline from Lipid Emulsions Injected Intravenously in Rats".
Martins Ian J.
Redgrave Trevor G.
Jones Dameron
Kight John
Peptide Delivery Systems Pty Ltd
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