Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
2000-01-07
2002-01-08
Weddington, Kevin E. (Department: 1614)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
C514S247000, C514S259500, C514S367000, C514S409000, C514S431000, C514S451000, C514S474000, C514S518000
Reexamination Certificate
active
06337327
ABSTRACT:
The present invention relates to pharmaceutical compositions, and in particular to pharmaceutical compositions containing an aldose reductase inhibitor (ARI) and an angiotensin converting enzyme (ACE) inhibitor, which are useful in the prevention and treatment of the complications of diabetes mellitus.
Diabetes mellitus is a chronic disease characterised by hyperglycemia and by complications that include diabetic nephropathy, diabetic neuropathy, diabetic retinopathy, diabetic cataract and the like. While various investigators have studied the use of ACE inhibitors or aldose reductase inhibitors independently in such conditions, none have proposed the combination therapy provided by the present invention.
Prolonged administration of an ACE inhibitor at a therapeutically effective dose may be deleterious or give rise to side effects in certain patients, for example it may lead to significant deterioration of renal function, induce hyperkalemia, neutropenia, angioneurotic oedema, rash or diarrhoea or give rise to a dry cough. Administration of an ARI may also give rise to deleterious effects or side effects at the dose required to inhibit the enzyme aldose reductase sufficiently to produce a significant beneficial therapeutic effect. The present invention lessens the problems associated with administration of an ARI or an ACE inhibitor alone and/or provides a means for obtaining a therapeutic effect which is significantly greater than that otherwise obtainable with the single agents when administered alone. Furthermore, diabetic complications involve a complex mechanism or number of mechanisms, which initiate a cascade of biochemical alterations that in turn lead to structural changes. These may result in a diverse patient population. The present invention therefore provides the additional advantage that it allows tailoring of treatment to the needs of a particular patient population.
Accordingly the present invention provides a pharmaceutical composition which comprises an aldose reductase inhibitor and an ACE inhibitor, together with a pharmaceutically acceptable carrier and/or diluent.
Suitable aldose reductase inhibitors useful in the compositions of the present invention include, for example, epalrestat, tolrestat, ponolrestat, zopolrestat, AD-5467, SNK-860, ADN-138, AS-3201, zenarestat, sorbinil, methosorbinil, imirestat, minalrestat (WAY-121509) and ZD5522 (3′,5′-dimethyl-4′-nitromethylsulfonyl-2-(2-tolyl)acetanilide, prepared as described in European Patent Application, Publication No. 469887, Examples 3 and 60), or a pharmaceutically acceptable salt thereof. A preferred aldose reductase inhibitor includes, for example, ZD5522.
Suitable ACE inhibitors useful in the compositions of the present invention include, for example, benazepril, benazeprilat, captopril, delapril, fentiapril, fosinopril, libenzapril, moexipril, pentopril, perindopril, pivopril, quinapril, quinaprilat, ramipril, spirapril, spiraprilat, zofenopril, ceronapril, enalapril, indolapril, lisinopril, alacepril, and cilazapril, or a pharmaceutically acceptable salt thereof. A preferred ACE inhibitor includes, for example, lisinopril.
Independent aspects of the present invention include a pharmaceutical composition which comprises any one of the named aldose reductase inhibitors identified above and any one of the named ACE inhibitors identified above, together with a pharmaceutically acceptable carrier and/or diluent. Accordingly, further independent aspects of the present invention include the following:
(1) A pharmaceutical composition which comprises epalrestat and lisinopril, together with a pharmaceutically acceptable carrier and/or diluent;
(2) A pharmaceutical composition which comprises tolrestat and lisinopril, together with a pharmaceutically acceptable carrier and/or diluent;
(3) A pharmaceutical composition which comprises ponolrestat and lisinopril, together with a pharmaceutically acceptable carrier and/or diluent;
(4) A pharmaceutical composition which comprises zopolrestat and lisinopril, together with a pharmaceutically acceptable carrier and/or diluent;
(5) A pharmaceutical composition which comprises AD-5467 and lisinopril, together with a pharmaceutically acceptable carrier and/or diluent;
(6) A pharmaceutical composition which comprises SNK-860 and lisinopril, together with a pharmaceutically acceptable carrier and/or diluent;
(7) A pharmaceutical composition which comprises ADN-138 and lisinopril, together with a pharmaceutically acceptable carrier and/or diluent;
(8) A pharmaceutical composition which comprises AS-3201 and lisinopril, together with a pharmaceutically acceptable carrier and/or diluent;
(9) A pharmaceutical composition which comprises zenarestat and lisinopril, together with a pharmaceutically acceptable carrier and/or diluent;
(10) A pharmaceutical composition which comprises sorbinil and lisinopril, together with a pharmaceutically acceptable carrier and/or diluent;
(11) A pharmaceutical composition which comprises methosorbinil and lisinopril, together with a pharmaceutically acceptable carrier and/or diluent;
(12) A pharmaceutical composition which comprises imirestat and lisinopril, together with a pharmaceutically acceptable carrier and/or diluent; and
(13) A pharmaceutical composition which comprises minalrestat and lisinopril, together with a pharmaceutically acceptable carrier and/or diluent.
A preferred pharmaceutical composition of the invention comprises the aldose reductase inhibitor ZD5522, or a pharmaceutically acceptable salt thereof, and an ACE inhibitor (including any of the ACE inhibitors specifically named above), together with a pharmaceutically acceptable carrier and/or diluent.
An especially preferred pharmaceutical composition of the invention comprises the aldose reductase inhibitor ZD5522, or a pharmaceutically acceptable salt thereof, and the ACE inhibitor lisinopril, or a pharmaceutically acceptable salt thereof, together with a pharmaceutically acceptable diluent and/or carrier.
Pharmaceutically acceptable salts of the aldose reductase inhibitors and of the ACE inhibitors, in accordance with the present invention, are the salts with physiologically acceptable bases and/or acids well known to those skilled in the art of pharmaceutical technique. Suitable salts with physiologically acceptable bases include, for example, alkali metal and alkaline earth metal salts, such as sodium, potassium, calcium and magnesium salts, and ammonium salts and salts with suitable organic bases, such as methylamine, dimethylamine, trimethylamine, piperidine, morpholine and triethanolamine. Suitable salts with physiologically acceptable acids include, for example, salts with inorganic acids such as hydrohalides (especially hydrochlorides or hydrobromides), sulphates and phosphates, and salts with organic acids.
The pharmaceutical compositions of the present invention may be administered in standard manner for example by oral or parenteral administration, using conventional systemic dosage forms, such as a tablets, capsules, pills, powders, aqueous or oily solutions or suspensions, emulsions, sterile injectable aqueous or oily solutions or suspensions. These dosage forms will include the necessary carrier material, excipient, lubricant, buffer, bulking agent, anti-oxidant, dispersant or the like.
In particular, compositions for oral administration are preferred.
The doses of an aldose reductase inhibitor and an ACE inhibitor which can be administered in accordance with the present invention depends on several factors, for example the age, weight and the severity of the condition under treatment, as well as the route of administration, dosage form and regimen and the desired result, and additionally the potency of the particular aldose reductase inhibitor and ACE inhibitor employed in the composition. In addition, account should be taken of the recommended maximum daily dosages for the ACE inhibitors.
A unit dosage formulation such as a tablet or capsule will usually contain, for example, from 0.1 mg to 500 mg of an aldose reductase inhibitor and
Cameron Norman Eugene
Carey Frank
Cotter Mary Anne
Tuffin David Patrick
Pillsbury & Winthrop LLP
Weddington Kevin E.
Zeneca Limited
LandOfFree
Pharmaceutical compositions comprising an aldose reductase... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Pharmaceutical compositions comprising an aldose reductase..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Pharmaceutical compositions comprising an aldose reductase... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2845294