Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1994-04-22
1995-03-07
Henley, III, Raymond J.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
514212, 514278, A61K 31405, A61K 3144, A61K 3155
Patent
active
053958489
DESCRIPTION:
BRIEF SUMMARY
This invention relates to a method of treatment of hyperlipidemia in a mammal, including a human, in need thereof which comprises administering to such mammal an effective therefor amount of a substituted azaspirane.
BACKGROUND OF THE INVENTION
Badger et al., U.S. Pat. No. 4,963,557 (Badger I) discloses compounds of the formula ##STR1## wherein: n is 3-7; m is 1 or 2; R.sup.1 and R.sup.2 are the same or different and are selected from hydrogen or straight or branched chain alkyl, provided that the total number of carbon atoms contained by R.sup.1 and R.sup.2 when taken together is 5-10; or R.sup.1 and R.sup.2 together form a cyclic alkyl group having 3-7 carbon atoms; R.sup.3 and R.sup.4 are the same or different and are selected from hydrogen or straight chain alkyl having 1-3 carbon atoms; or R.sup.3 and R.sup.4 are joined together with the nitrogen atom to form a heterocyclic group having 5-8 atoms; or a pharmaceutically acceptable salt or hydrate or solvate thereof.
Badger I does not disclose or claim the compounds of Formula I as antihyperlipidemic agents.
SUMMARY OF THE INVENTION
This invention relates to a a method of treatment of hyperlipidemia in a mammal, including a human, in need thereof which comprises administering to such mammal an effective therefor amount of a compound of the formula ##STR2## wherein: n is 3-7; hydrogen or straight or branched chain alkyl, provided that the total number of carbon atoms contained by R.sup.1 and R.sup.2 when taken together is 5-10; or R.sup.1 and R.sup.2 together form a cyclic alkyl group having 3-7 carbon atoms; hydrogen or straight chain alkyl having 1-3 carbon atoms; or R.sup.3 and R.sup.4 are joined together with the nitrogen atom to form a heterocyclic group having 5-8 atoms;
DETAILED DESCRIPTION OF THE INVENTION
The term "hyperlipidemia" as used in the specification and in the claims is meant the presence of an abnormally high level of lipids in the blood.
The term "antihyperlipidemic" as used herein is meant the lowering of excessive lipid concentrations to desired levels.
Preferred lipids, of which high levels thereof are treated by the presently invented methods, are; cholesterol, triglycerides and low-density lipoproteins.
The preparation of all compounds of Formula (I) and pharmaceutically acceptable salts, hydrates and solvates and formulations thereof is discolsed in U.S. Pat. No. 4,963,557, the entire disclosure of which is hereby incorporated by reference.
As used herein, the term "compound A" refers to the dihydrochloride salt of a compound of Formula (I) where R.sup.1 and R.sup.2 are propyl, R.sup.3 and R.sup.4 are methyl, m is 1 and n is 3 which is N,N-dimethyl-8,8-dipropyl-2-azaspiro[4,5]decane-2-propanamine dihydrochloride.
It has now been discovered that compounds of Formula (I) and pharmaceutically acceptable salts or hydrates or solvates thereof are useful for treatment of hyperlipidemia in a mammal, including humans, in need of such treatment.
Compound A was tested for its in vivo potency in lowering serum cholesterol in normal cholesterolemic dogs in two experiments. To perform experiment I a total of 6 pure bred normal cholesterolemic beagle dogs, 3 male and 3 female (Marshall Animal Farms, Inc., North Rose, N.Y.) were used. The dogs weighed between 10 and 15 kilograms at the start of the study. The dogs were maintained on tap water, which was available ad libitum from an automatic watering system, and standard laboratory chow (Pruina Laboratory Cainine Chow.RTM.). The 6 dogs were set up in 6 units as follows:
______________________________________ Unit 1 Male control, dosed orally once a day
with vehicle alone.
Unit 2 Male low dose, dosed orally once a day
with 3.0 mg/kg of compound A.
Unit 3 Male high dose, dosed orally once a
day with 6.0 mg/kg of compound A.
Unit 4 Female control, dosed orally once a
day with vehicle alone.
Unit 5 Female low dose, dosed orally once a
day with 3.0 mg/kg of compound A.
Unit 6 Female high dose, dosed orally once a
day with 6.0 mg/kg of compound A.
________________
REFERENCES:
patent: 4963557 (1990-10-01), Badger et al.
Bugelski Peter J.
Kerns Wiliam D.
Dustman Wayne J.
Henley III Raymond J.
Jarvis William R. A.
Lentz Edward T.
SmithKline Beecham Corporation
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