Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Capsules
Reexamination Certificate
2001-08-28
2003-06-10
Page, Thurman K. (Department: 1615)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Capsules
C424S400000, C424S456000, C424S464000, C424S465000, C424S489000
Reexamination Certificate
active
06576256
ABSTRACT:
TECHNICAL FIELD
This invention relates generally to methods and pharmaceutical formulations for treating patients at elevated cardiovascular risk, and more particularly relates to treatment of such patients with a combination of a cholesterol-lowering agent, an inhibitor of the renin-angiotensin system, and aspirin.
BACKGROUND
Many individuals are at an elevated risk of suffering serious to life-threatening cardiovascular events, such as myocardial infarction (heart attack), cardiac arrest, congestive heart failure, stroke, peripheral vascular disease and/or claudication. The risk factors are numerous and widespread throughout the world population. They include cigarette smoking, diabetes, hypercholesterolemia (high serum cholesterol), hypertension, angina, systemic lupus erythematosus, prior heart attacks or strokes, hemodialysis, hyperhomocysteine levels, obesity, sedentary lifestyle, receiving an organ transplant, and others. Many of these risk factors are mediated through atherosclerosis. There is a need for a safe and convenient pharmaceutical formulation that would effectively reduce the risk of incurring a cardiovascular event in individuals who have these risk factors.
Olukotun et al., in U.S. Pat. No. 5,622,985, disclose that inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase (cholesterol-lowering drugs), particularly pravastatin, when used alone or with an angiotensin converting enzyme (ACE) inhibitor, decrease the risk of a second heart attack in a patient who has a substantially normal cholesterol level. The combination with an ACE inhibitor is optional, and no mention is made of combining HMG CoA reductase inhibitors with other inhibitors of the renin-angiotensin system or with aspirin. In addition, the prevention of cardiovascular events other than second heart attacks is not considered.
Similarly, McGovern et al., in U.S. Pat. No. 5,140,012, disclose the use of pravastatin alone, or in combination with an ACE inhibitor, to prevent the onset of restenosis following angioplasty. HMG CoA reductase inhibitors other than pravastatin are not considered, and no mention is made of combining HMG CoA reductase inhibitors with other inhibitors of the renin-angiotensin system or with aspirin. The prevention of cardiovascular disorders other than restenosis following angioplasty is not considered.
U.S. Pat. Nos. 5,461,039 and 5,593,971 to Tschollar et al. disclose the use of a cholesterol-lowering drug, alone or in combination with an ACE inhibitor, to inhibit hypertension in a normotensive individual who has insulin resistance. No mention is made of combining cholesterol-lowering drugs with inhibitors of the renin-angiotensin system other than ACE inhibitors or with aspirin. In addition, the disclosed methods are limited to normotensive individuals who are insulin resistant, and no mention is made of directly preventing cardiovascular events.
Eisman et al., in U.S. Statutory Invention Registration No. H1286, disclose a method for treating peripheral atherosclerotic disease and/or intermittent claudication by use of one or more cholesterol-lowering drugs by themselves or together with an ACE inhibitor, or by use of an ACE inhibitor alone. No mention is made of combining cholesterol-lowering drugs with inhibitors of the renin-angiotensin system other than ACE inhibitors or with aspirin. The treatment or prevention of cardiovascular disorders other than peripheral atherosclerotic disease and/or intermittent claudication is not considered.
Bergey et al., in European Patent Specification EP 0 457,514 B1, disclose the use of a cholesterol-lowering drug together with an ACE inhibitor to prevent, stabilize, or cause regression of atherosclerosis. No mention is made of combining cholesterol-lowering drugs with inhibitors of the renin-angiotensin system other than ACE inhibitors or with aspirin. The treatment or prevention of cardiovascular disorders other than atherosclerosis is not considered.
U.S. Pat. No. 6,235,311 to Ullah et al. discloses pharmaceutical compositions containing a statin (HMG CoA reductase inhibitor) plus aspirin, optionally containing vitamins B
6
, B
12
, or folic acid, and methods of their use for: lowering serum cholesterol; preventing, inhibiting, or treating atherosclerosis; or reducing the risk of or treating a cardiovascular event or disease, coronary artery disease, or cerebrovascular disease. This reference makes no mention of, or considers in any way, inhibitors of the renin-angiotensin system.
Coniglio et al., in U.S. Pat. No. 6,248,729, disclose a method for preventing a cerebral infarction by administering to a patient a combination of an ADP-receptor blocking antiplatelet drug, an antihypertensive agent (such as an angiotensin II antagonist, an ACE inhibitor, or an ACE/NEP inhibitor), and optionally aspirin. Pharmaceutical compositions comprising combinations of these agents are also disclosed. The disclosed methods and compositions, however, require an ADP-receptor blocking antiplatelet drug (which does not include aspirin) and do not mention or consider cardiovascular events other than a cerebral infarction.
Schoelkens et al., in International Patent Publication No. WO 01/15674, disclose the use of an inhibitor of the renin-angiotensin system, optionally together with another antihypertensive drug, a cholesterol-lowering drug, a diuretic, or aspirin, in the prevention of cardiovascular events. Also disclosed is a combination product for this purpose containing an inhibitor of the renin-angiotensin system and a cholesterol-lowering agent. Further disclosed is the use of an inhibitor of the renin-angiotensin system together with another antihypertensive, or a cholesterol-lowering agent, or a diuretic, or aspirin in the manufacture of a medicament for the prevention of cardiovascular events. Never mentioned or considered is the possibility of combining three or more active agents, either in a method for the treatment of a patient or in the manufacture of a pharmaceutical product. Even though certain inhibitors of the renin-angiotensin system, cholesterol-lowering agents, and aspirin are mentioned, and combination therapies involving inhibitors of the renin-angiotensin system together with a cholesterol-lowering agent or aspirin are disclosed, no consideration is made of combining all three.
SUMMARY OF THE INVENTION
Accordingly, it is a primary object of the invention to provide a pharmaceutical composition that overcomes the limitations of the above-described formulations and dosage forms.
One object of the invention is to provide a method for treating a patient at elevated cardiovascular risk, such method involving the daily oral administration of a pharmaceutical composition, preferably a single pharmaceutical composition, containing therapeutically effective unit dosages of a cholesterol-lowering agent, an inhibitor of the renin-angiotensin system, aspirin, and optionally one or more B vitamins.
Another object of the invention is to provide such a method wherein the elevated cardiovascular risk as is an elevated risk of cardiac arrest, myocardial infarction (including acute or chronic myocardial infarction), coronary heart disease, ischemia, stroke, claudication, peripheral vascular disease, restenosis, and/or atherosclerosis.
Still another object of the invention is to provide such a method wherein the patient at elevated cardiovascular risk has systemic lupus erythematosus, is or has been a cigarette smoker, is diabetic, is on hemodialysis, or has received an organ transplant.
Still another object of the invention is to provide such a method wherein the cholesterol-lowering agent is an HMG CoA reductase inhibitor, the inhibitor of the renin-angiotensin system is an ACE inhibitor or an angiotensin II antagonist, and the composition contains vitamin B
6
, vitamin B
12
, and folic acid.
Yet another object of the invention is to provide a method for increasing the likelihood that a patient suffering an acute myocardial infarction (MI) will survive, the method comprising administering the pharmaceutical composition to the patie
Liang Matthew H.
Manson JoAnn E.
Canaan Karen
Oh Simon J.
Page Thurman K.
Reed Dianne E.
Reed & Eberle LLP
LandOfFree
Treatment of patients at elevated cardiovascular risk with a... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Treatment of patients at elevated cardiovascular risk with a..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Treatment of patients at elevated cardiovascular risk with a... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3119430