Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Liposomes
Reexamination Certificate
1994-06-10
2001-05-22
Travers, Russell (Department: 1617)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Liposomes
C514S078000
Reexamination Certificate
active
06235308
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to a method for treating hypertension.
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Barenholz, Y., et al.,
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BACKGROUND OF THE INVENTION
Hypertension, which refers to elevated arterial pressure, is a widespread health problem in developed countries. Diagnosis of hypertension depends on measurement of blood pressure, which is typically reported as a ratio of systolic pressure (arterial pressure during contraction of the heart muscle) to diastolic pressure (residual arterial pressure during relaxation of the heart muscle), reported in units of mmHg. A normal diastolic blood pressure is between about 60-85 mmHg. Diastolic pressures above 85 mmHg are generally diagnostic of hypertension. By some estimates, the arterial blood pressure of fifteen percent of American adults is in a hypertension range that requires medical treatment.
A number of factors have been implicated in the development of hypertension. These include heredity and a number of environmental factors such as salt intake, obesity, occupation, family size, and crowding. Additional factors which may modify the course of hypertension include age, race, sex, stress, diet, smoking, serum cholesterol, and glucose intolerance.
The effects of hypertension are numerous, with the most severe being premature death, commonly caused by heart disease related to hypertension. Hypertension imposes an increased work load on the heart; related effects on the heart include angina pectoris, increased myocardial mass or hypertrophy (enlarged heart), and, late in the disease, evidence of ischemia or infarction.
Neurologic effects of hypertension are commonly divided into retinal and central nervous system changes. With respect to retinal impact, increasing severity of hypertension is associated with focal spasm as well as hemorrhages, exudates and papilledema, which often produce scotomata, blurred vision and even blindness. Central nervous system dysfunction may cause occipital headaches, dizziness, lightheadedness, vertigo, tinnitus and dimmed vision.
Drug therapy is a common approach to treatment of hypertension. In general, antihypertensive drugs belong to one of five classes of compounds: diuretics, antiadrenergic agents, vasodilators, calcium entry blockers, and angiotensin-converting enzyme (ACE) inhibitors (e.g., Harrison, Katzung). Each of the types of drugs, though generally effective in reducing hypertension, has side effects, such as potassium depletion, hyperglycemia, hypokalemia, depression, carbohydrate intolerance, tachycardia, and/or allergic skin rashes, and in more severe cases, vomiting, fever, diarrhea, angina, and cardiac failure.
SUMMARY OF THE INVENTION
The present invention is based on the discovery that treatment of human subjects with intravenously administered liposomes of the type described herein results in a significant lowering of blood pressure without apparent side effects. The treatment also leads to a reversal of myocardial hypertrophy, a common side effect of elevated arterial pressure.
In one aspect, the invention includes a method for treating hypertension in a subject having elevated blood pressure. The method includes intravenously administering to the subject a suspension of small unilamellar liposomes composed primarily of phosphatidylcholine phospholipids having phase transition temperatures in the range between about −10 and 37° C. Administration is repeated over a period of at least several days and in an amount effective to produce a significant reduction in blood pressure.
Preferably, the liposomes in the suspension have sizes ranging predominantly between 0.02 and 0.08 microns and are composed of egg phosphatidylcholine.
Preferably, the liposomal suspension is administered 1-3 times per week, at a dose of between about 0.05 and 1 &mgr;g lipid/kg body weight. Administration of the liposomes is continued until a drop in blood pressure of at least about 10% is observed.
The features and details of the invention will become more apparent and appreciated by one skilled in the art to which this invention pertains from the following detailed description of the invention.
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Barenholz Yechezkel
Shmeeda Hilary
Foley & Lardner
Travers Russell
Wang S.
Yissum Research Development Company of the Hebrew University of
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