EP0010299A1
Expired / Lapsed
EP
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Pharmaceutical composition useful for the treatment of hypercholesteremia
Assignee: Merck and Co Inc
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Filing: 1979-10-18
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Granted: —
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Expires: 1999-10-18
Abstract
Abstract Pharmaceutical composition, useful for the treatment of hypercholesteremia in mammals, especially humans, comprising (a) a cholesterol synthesis inhibitor acting at the HMG-CoA reductase level with an EO,. less than 10-°, such as a 6-[2-(8-substituted- 2-methyl-1,2,6,7,8,8a -hexahydro-1-naphthyl) ethyl)-4-hydroxy-4, 5-dihydro-2-pyrone or a 4R trans-6-phenyi-E-4-hydroxytetrahydropyran-2-one in which E is a bond, a C 1-) alkylene or-CH =CH- and (b) a non-toxic anion exchange resin in the weight ratio of 1:0.08 to 1:15,000. The resin preferably is a styrene-divinylbenzene copolymer containing quaternary ammonium groups. When present in the indicated weight ratios, synergism exists between the cholesterol synthesis inhibitor and the anion exchange resin. The components can be present separately for separate dosages or, preferably, as a unitary combination. The effects of treatments with compound II (Compacun) and with cholestyramine, separately and in combination, are illustrated by figure 1.
Inventors
- 👤 Gunther W. Kuron
Bibliographic Details
Application Number
—
Jurisdiction
EP
Data Source
google_patents
Last Synchronized
2026-11-08 02:12
CPC Classifications
C; C12; C12P; C12P17/00; C12P17/02; C12P17/06; A; A61; A61K; A61K31/00; A61K31/185; A61K31/19; A61K31/21; A61K31/215; A61K31/22; A61K31/235; A61K31/33; A61K31/335; A61K31/365; A61K31/74; A61K31/785; C07; C07C; C07C45/00; C07C45/51; C07C45/516; C07C45/61; C07C45/67; C07C45/68; C07C45/70; C07C45/71; C07C45/72; C07C45/74; C07C47/00; C07C47/20; C07C47/277; C07D; C07D309/00; C07D309/16; C07D309/28; C07D309/30; C12N; C12N1/00; C12N1/14; C12N1/145; C12P7/00; C12P7/62; C12R; C12R2001/00; C12R2001/645; C12R2001/66
Claims Analysis
Total Claims: 19
Claim 1
Independent Claim
69 words
A pharmaceutical composition useful for the treatment of hypercholesteremia, comprising a) a cholesterol synthesis inhibitor acting at the HMG-CoA reductase level with a half level effective dose (ED 50 ) less than 10 -6 ; and b) a pharmaceutically acceptable nontoxic basic anion exchange resin capable of binding bile acids in a non-reabsorbable form in the gastrointestinal tract said respective components being present in ratio between 1:0.08 and 1:15,000.
Claim 2
Dependent Claim
69 words
A pharmaceutical composition useful for the treatment of hypercholesteremia, comprising a) a cholesterol synthesis inhibitor acting at the HMG-CoA reductase level with a half level effective dose (ED 50 ) less than 10 -6 ; and b) a pharmaceutically acceptable nontoxic basic anion exchange resin capable of binding bile acids in a non-reabsorbable form in the gastrointestinal tract said respective components being present in ratio between 1:0.08 and 1:15,000.
Claim 3
Dependent Claim
195 words
Compositions of claim 1 in which said cholesterol synthesis inhibitor is a) -compactin, b) MSD 803 or c) a (+) trans 6-E-4-hydroxy tetrahydropyran-2-one of the structure: wherein A is H or methyl; E is a direct bond, -CH 2 - , -CH 2 -CH 2 -' -CH 2 -CH 2 -CH 2 -or -CH=CH- 1 ; R 1 , R 2 , and R 3 are each selected from H, halogen, C 1-4 alkyl, C 1-4 haloalkyl, phenyl, phenyl substituted by halogen, C 1-4 alkoxy C 2-8 alkanoyloxy C 1-4 alkyl, OR 4 in which R 4 is H, C 2-8 alkanoyl, benzoyl, phenyl, phenyl C 1-3 alkyl, cinnamyl, C 1-4 haloalkyl, alkyl, preferably C 1-9 alkyl C 3-6 c y clo alkyl-C-alkyl, or adamantyl, substituted phenyl C 1-3 alkyl in each of which th substituents are selected from halogen, C 1-4 alkoxy, C 1-4 alkyl, or C 1-4 haloalkyl; d) The corresponding hydroxy acids of the compounds of a) b) or c) in which the lactone ring is hydrolytically opened; e) the pharmaceutically acceptable salts of said acids, and f) the lower alkyl and phenyl dimethylamino or acetamino lower alkyl esters of said acids.
Claim 4
Dependent Claim
13 words
A composition of claim 2 in which said anionic exchange resin is cholestyramine.
Claim 5
Dependent Claim
13 words
A composition of claim 2 in which said anion exchange resin is colestipol.
Claim 6
Dependent Claim
14 words
The compostion of claim 3 in which the cholesterol synthesis inhibitor is MSD 803.
Claim 7
Dependent Claim
13 words
The composition of claim 3 in which the cholesterol synthesis inhibitor is compactin.
Claim 8
Dependent Claim
15 words
The composition of claim 2 in which said anion exchange resin is poly[methyl-(3-trimethylammonio- propyl)imino-trimethylene dihalide].
Claim 9
Dependent Claim
13 words
The composition of claim 7 in which the cholesterol-synthesis inhibitor is MSD 803.
Claim 10
Dependent Claim
3 words
Claims for Austria
Claim 11
Dependent Claim
75 words
Process for preparing a pharmaceutical composition, which is useful for the treatment of hypercholesteremia,by admixing a) a cholesterol synthesis inhibitor acting at the HMG-CoA reductase level with a half level effective dose (ED 50 ) less than 10 -6 ; and b) a pharmaceutically acceptable nontoxic basic anion exchange resin capable of binding bile acids in a non-reabsorbable form in the gastrointestinal tract said respective components being admixed in a ratio between 1:0.08 and 1:15,000.
Claim 12
Dependent Claim
75 words
Process for preparing a pharmaceutical composition, which is useful for the treatment of hypercholesteremia,by admixing a) a cholesterol synthesis inhibitor acting at the HMG-CoA reductase level with a half level effective dose (ED 50 ) less than 10 -6 ; and b) a pharmaceutically acceptable nontoxic basic anion exchange resin capable of binding bile acids in a non-reabsorbable form in the gastrointestinal tract said respective components being admixed in a ratio between 1:0.08 and 1:15,000.
Claim 13
Dependent Claim
193 words
Process of claim i in which said cholesterol synthesis inhibitor is a) compactin, b) MSD 803 or c) a (+) trans 6-E-4-hydroxy tetrahydropyran-2-one of the structure: wherein A is H or methyl; E is a direct bond, -CH 2 - , -CH 2 -CH 2 -, -CH 2 -CH 2 -CH 2 -or -CH=CH- 1 ; R 1 , R 2 , and R 3 are each selected from H, halogen, C 1-4 alkyl, C 1-4 haloalkyl, phenyl, phenyl substituted by halogen, C 1-4 alkoxy C 2-8 alkanoyloxy C 1-4 alkyl, OR 4 in which R 4 is H, C 2-8 alkanoyl, benzoyl, phenyl, phenyl C 1-3 alkyl, cinnamyl, C 1-4 haloalkyl, alkyl, preferably C 1-9 alkyl, C 3-6 cyclo alkyl-C-alkyl, or adamantyl, substituted phenyl C 1-3 alkyl in each of which the substituents are selected from halogen, C 1-4 alkoxy, C 1-4 alkyl, or C 1-4 haloalkyl; d) the corresponding hydroxy acids of the compounds of a), b) or c) in which the lactone ring is hydrolytically opened; e) the pharmaceutically acceptable salts of said acids, and f) the lower alkyl and phenyl dimethylamino or acetamino lower alkyl esters of said acids.
Claim 14
Dependent Claim
12 words
Process of claim 2 in which said anionic exchange resin is cholestyramine.
Claim 15
Dependent Claim
12 words
Process of claim 2 in which said anion exchange resin is colestipol.
Claim 16
Dependent Claim
13 words
Process of claim 3 in which the cholesterol synthesis inhibitor is MSD 803.
Claim 17
Dependent Claim
12 words
Process of claim 3 in which the cholesterol synthesis inhibitor is compactin.
Claim 18
Dependent Claim
13 words
Process of claim 2 in which said anion exchange resin is poly[methyl-(3-trimethylammonio-propyl)-imino-trimethylene- dihalideJ.
Claim 19
Dependent Claim
13 words
Process of claim 7 in which the cholesterol synthesis inhibitor is MSD 803.
References Cited (Backward Citations)
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