Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1997-12-22
1999-11-02
Rose, Shep K.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
A61K 31415, A01N 4350
Patent
active
059771216
DESCRIPTION:
BRIEF SUMMARY
This invention relates to the use of moxonidine in the treatment of atherosclerosis.
Moxonidine is a well known compound described in, for example, U.S. Pat. No. 4,323,570, for its properties as an agent for lowering blood pressure. The compound has the chemical formula 4-chloro-6-methoxy-2-methyl-5-(2-imidazolin-2-yl)aminopyrimidine.
Atherosclerosis is a major cause of death from ischaemia (ischaemic heart disease) in industrialised countries. It is now accepted that atherosclerosis begins with local injury to the arterial endothelium which results in proliferation of arterial smooth muscle cells with deposition of lipid and accumulation of macrophages. As the atherosclerotic plaque develops it progressively obstructs more and more of the blood vessel and can thus lead to ischaemia or infarction.
It has now been found that moxonidine is useful in the treatment of atherosclerosis.
Thus the invention comprises the use of moxonidine, or a pharmaceutically-acceptable acid addition salt thereof, in the treatment of atherosclerosis. More particularly, the invention comprises the use of moxonidine, or a pharmaceutically-acceptable acid addition salt thereof, in the preparation of a medicament for treating atherosclerosis.
It has been found in test models that moxonidine significantly decreases cholesterol accumulation induced by atherogenic serum, and also that it inhibits proliferation in cells cultured from an atherosclerotic plaque.
As mentioned above, moxonidine is the compound 4-chloro-6-methoxy-2-methyl-5(2-imidazolin-2-yl)aminopyrimidine, and can also be utilised in pharmaceutically-acceptable acid addition salt form. Suitable acid addition salts are the pharmaceutically acceptable, non-toxic addition salts with suitable acids, such as those with inorganic acids, for example hydrochloric, hydrobromic, nitric, sulphuric or phosphoric acids, or with organic acids, such as organic carboxylic acids, for example, glycollic, maleic, hydroxymaleic, fumaric, malic, tartaric, citric, salicyclic, o-acetoxybenzoic, or organic sulphonic, 2-hydroxyethane sulphonic, toluene-p-sulphonic, or naphthalene-2-sulphonic acid.
The identification of those patients who are in need of treatment for atherosclerosis is well within the ability and knowledge of one skilled in the art. For example, individuals who are either suffering from clinically significant atherosclerosis or who are at risk of developing clinically significnat atheroslcerosis are patients in need of treatment for atherosclerosis. A clinician skilled in the art can readily determine, by the use of clinical tests, physical examination and medical/family history, if an individual is a patient in need of treatment for atherosclerosis.
An effective antiatherosclerotic amount of a compound of formula (1) is an amount which is effective in inhibiting development or growth of atherosclerosis in a patient in need thereof. As such, successful treatment of a patient for atherosclerosis is understood to include effectively slowing, interrupting, arresting, or stopping atherosclerotic lesion or plaque development or growth and does not necessarily indicate a total elimination of the atherosclerosis. It is further understood and appreciated by those skilled in the art that successful treatment for atherosclerosis can include prophylaxis in preventing atherosclerotic lesion or plaque formation, and inhibition of atherogenesis.
For the purpose of the invention, moxonidine may be administered by various routes, for example by the oral or rectal route, topically or parenterally, for example by injection or infusion, being usually employed in the form of a pharmaceutical composition. Such compositions are prepared in a manner well known in the pharmaceutical art. In making the composition the active ingredient will usually be mixed with a carrier, or diluted by a carrier, and/or enclosed within a carrier which may, for example, be in the form of a capsule, sachet, paper or other container. When the carrier serves as a diluent, it may be a solid, semi-solid, or liquid material whic
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Eli Lilly and Company
Rose Shep K.
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