Claims
- 1. A synergistic pharmaceutical composition containing:(a) a thienopyridine derivative of formula in which R is hydrogen or a (C1-C4)alkoxycarbonyl group, or one of its pharmaceutically acceptable salts; and (b) an HMG-CoA reductase inhibitor.
- 2. A composition according to claim 1, wherein Component (a) is present at a dose of between 10 and 250 mg of active principle and Component (b) is present at a dose of 2 to 50 mg of active principle.
- 3. A composition according to claim 1, wherein the thienopyridine derivative is ticlopidine hydrochloride.
- 4. A composition according to claim 3, wherein the amount of ticlopidine hydrochloride in the dosage unit is from 100 to 250 mg.
- 5. A composition according to claim 1, wherein the thienopyridine derivative is clopidogrel hydrogen sulphate.
- 6. A composition according to claim 5, wherein the amount of hydrogen sulphate in the dosage unit is from 10 to 75 mg (calculated as free base).
- 7. A composition according to claim 1, wherein the HMG-CoA reductase inhibitor is a compound selected from the group consisting of:(i) the naphthalene derivatives of formula (II) in which R1 and R2 are a hydroxyl group or alternatively together form an oxygen atom, R3 is a (C1-C10)alkyl, (C3-C10)cycloalkyl, (C2-C10)alkenyl, phenyl or phenyl(C1-C3)alkyl group and R4 is hydrogen or a methyl or hydroxyl group; (ii) the pharmaceutically acceptable salts of the compounds of formula (II) in which R1 and R2 are hydroxyl; (iii) the indole derivatives of formula (III) in which one of the substituents R° and R′ is a group of structure in which Q4 is a hydrogen, chlorine or fluorine atom or a (C1-C4)alkyl, (C1-C4)alkoxy (but other than t-butoxy), trifluoromethyl, phenoxy or benzyloxy group, Q5 is a hydrogen, chlorine or fluorine atom or a phenoxy or benzyloxy group and Q5a is a hydrogen, chlorine or fluorine atom or a methyl, ethyl, methoxy or ethoxy group; and the other substituent R° and R′ is a primary or secondary (C1-C6)alkyl, (C3-C6)cycloalkyl, benzyl, 2-phenylethyl or 3-phenylpropyl group; Q2 is a hydrogen, fluorine or chlorine atom or a (C1-C4)alkyl, (C3-C6)cycloalkyl, (C1-C4)alkoxy (but other than t-butoxy), trifluoromethyl, phenoxy or benzyloxy group; Q3 is a hydrogen, chlorine or fluorine atom or a (C1-C3)alkyl, (C1-C3)alkoxy, phenoxy or benzyloxy group; X is a methylene, ethylene or 1,3-propylene group; Q6 is a hydrogen atom or a (C1-C3)alkyl group; with the limitation that (1) Q5 and Q5a are hydrogen when R4 is hydrogen, (2) Q5a is hydrogen when Q5 is hydrogen, (3) Q4 and Q3 are not at the same time a trifluoromethyl, phenoxy or benzyloxy group, (4) Q3 is hydrogen when Q2 is hydrogen, (5) Q2 and Q3 are not at the same time a trifluoromethyl, phenoxy or benzyloxy group; (iv) the pharmaceutically acceptable esters of the compounds of formula (III), (v) the pharmaceutically acceptable salts of the compounds of formula (III), (vi) the δ-lactones of the compounds of formula (III), (vii) the tetrazole derivatives of formula (IV) in which Q1 and Q1′ are hydrogen, a halogen or a (C1-C4)alkyl, (C1-C4)alkoxy or trifluoromethyl group; Q7, Q7′, Q8, and Q8′ are hydrogen, a halogen or a (C1-C4)alkyl or (C1-C4)alkoxy group; Q9 is hydrogen or a (C1-C4)alkyl, (C1-C4)alkoxyalkyl or (2-methoxyethoxy)methyl group; (viii) the pharmaceutically acceptable salts of the compounds of formula (IV), (ix) the δ-lactones of the compounds of formula (IV), (x) the pyridine derivatives of formula (V) (xi) the pharmaceutically acceptable salts of the compounds of formula (V), (xii) the δ-lactones of the compounds of formula (V), (xiii) the pyrrole derivatives of formula (VI) (xiv) the pharmaceutically acceptable salts of the compounds of formula (VI), and (xv) the δ-lactones of the compounds of formula (VI).
- 8. A composition according to claim 7, wherein the HMG-CoA reductase inhibitor is selected from the group consisting of simvastatin, pravastatin sodium, mevastatin, lovastatin, cerivastatin, atorvastatin, an indole derivative of formula (III) in which R° is 4-fluorophenyl, R′ is isopropyl, X is ethylene and Q2, Q3 and Q6 are hydrogen, in its racemic or optically active (E) form, the pharmaceutically acceptable salts of the said indole derivative, a tetrazole derivative of formula (IV) in which Q1 and Q1′ are each a fluorine atom and Q7, Q7′, Q8 and Q8′ are hydrogen, in its (E) form of (βR,δS) configuration, and the pharmaceutically acceptable salts of the said tetrazole derivative.
- 9. A composition according to claim 2, wherein Component (a) is ticlopidine hydrochloride and Component (b) is selected from the group consisting of simvastatin and pravastatin sodium.
- 10. A composition according to claim 9, which contains from 100 to 250 mg of ticlopidine hydrochloride and from 10 to 40 mg of simvastatin or of pravastatin sodium.
- 11. A composition according to claim 2, wherein Component (a) is clopidogrel hydrogen sulphate and Component (b) is selected from the group consisting of simvastatin and pravastatin sodium.
- 12. A composition according to claim 11, which contains from 10 to 75 mg (calculated as free base) of clopidogrel hydrogen sulphate and from 10 to 40 mg of simvastatin or of pravastatin sodium.
- 13. A method for the treatment of a thromboembolic disorder which comprises administering to a patient in need of such treatment an effective amount of a synergistic composition containing:(a) a thienopyridine derivative of formula in which R is hydrogen or a (C1-C4)alkoxycarbonyl group, or one of its pharmaceutically acceptable salts; and (b) an HMG-CoA reductase inhibitor.
- 14. A method for the treatment of an atherosclerosis disorder which comprises administering to a patient in need of such treatment a synergistic composition containing:(a) a thienopyridine derivative of formula in which R is hydrogen or a (C1-C4)alkoxycarbonyl group, or one of its pharmaceutically acceptable salts; and (b) an HMG-CoA reductase inhibitor.
- 15. A method according to claim 13 wherein component (a) is ticlopidine hydrochloride and component (b) is selected from the group consisting of simvastatin and pravastatin sodium.
- 16. A method according to claim 13 wherein component (a) is clopidogrel hydrogen sulfate and component (b) is selected from the group consisting of simvastatin and pravastatin sodium.
- 17. A method according to claim 14 wherein component (a) is ticlopidine hydrochloride and component (b) is selected from the group consisting of simvastatin and pravastatin sodium.
- 18. A method according to claim 14 wherein component (a) is clopidogrel hydrogen sulfate and component (b) is selected from the group consisting of simvastatin and pravastatin sodium.
Priority Claims (1)
Number |
Date |
Country |
Kind |
96 09474 |
Jul 1996 |
FR |
|
Parent Case Info
This application is a 371 of PCT/FR97/01353, filed Jul. 21, 1997.
PCT Information
Filing Document |
Filing Date |
Country |
Kind |
102e Date |
371c Date |
PCT/FR97/01353 |
|
WO |
00 |
1/22/1999 |
1/22/1999 |
Publishing Document |
Publishing Date |
Country |
Kind |
WO98/04259 |
2/5/1998 |
WO |
A |
US Referenced Citations (1)
Number |
Name |
Date |
Kind |
5945432 |
Bednar et al. |
Aug 1999 |
|
Foreign Referenced Citations (4)
Number |
Date |
Country |
0 373 507 |
Dec 1989 |
EP |
0 472 449 |
Jul 1991 |
WO |
WO9511898 |
Oct 1993 |
WO |
WO9513063 |
May 1995 |
WO |
Non-Patent Literature Citations (3)
Entry |
International Journal of Tissue Reactions, vol. 13, No. 3, pp. 124-129, 1991. |
Fibrinolysis, vol. 7, No. 1, pp. 23-30, 1993. |
Diabete & Metabolisme, vol. 21, pp. 139-146, 1995. |