SYNERGISTIC COMPOSITIONS COMPRISING ERYTHROPOIETIN AND SUCCINIC ACID (SALT)

The present invention provides a composition for achieving a synergistic therapeutic effect in a mammal, comprising an amount of erythropoietin, an amount of succinic acid(cas:110-15-6) or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable diluent or carrier.

Further, the present invention provides a method for achieving a synergistic therapeutic effect in a mammal, comprising co-administering to a mammal in need thereof an amount of erythropoietin and an amount of succinic acid(cas:110-15-6) or a pharmaceutically acceptable salt thereof.

Preferred therapeutic effects achieved according to this invention are stimulation of erythropoiesis, increasing hematocrit and blood hemoglobin levels.

Accordingly to this invention, it is now possible to achieve a synergistic therapeutic effect in a mammal with amounts of erythropoietin and succinic acid(cas:110-15-6) or a pharmaceutically acceptable salt thereof which, if administered in said amounts singly, are not capable of achieving said effect and which effect is greater than the sum of the effects achieved with erythropoietin and succinic acid(cas:110-15-6) or a pharmaceutically acceptable salt thereof administered separately.

Because of synergistic therapeutic effect, a particular advantage of the present invention is that the compositions hereof can comprise erythropoietin in amounts, which are less that those required for compositions containing erythropoietin without succinic acid(cas:110-15-6) or a pharmaceutically acceptable salt thereof. Therefore, in practicing this invention, it is possible to minimize potential adverse effects, which may be associated with larger, therapeutic doses of the erythropoietin and still achieve the therapeutic effect.

The term"erythropoietin"as used herein means the naturally occurring human erythropoietin, recombinant human erythropoietin, or synthetic erythropoietin analogs which stimulate erythropoiesis by the same mechanism as natural erythropoietin. The present invention is not limited in any way to specific erythropoietin but is applicable to all such erythropoietin or erythropoietin analogs now known or subsequently discovered or developed. Nonetheless, a preferred erythropoietin for use in the methods and compositions of this invention is human recombinant erythropoietin.

The term"co-administering"as used herein means that erythropoietin and succinic acid(cas:110-15-6) or a pharmaceutically acceptable salt thereof can be administered together as a composition if the route of administration for each component is the same and the individual components can be administered separately but as part of the same therapeutic treatment program or regimen, and it is contemplated that separate administration of each compound, at different times and by different routes, will sometimes be recommended. Thus, the two compounds need not necessarily be administered at essentially the same time. Preferably, the individual components are administered together as a composition.

The pharmaceutically acceptable salt of succinic acid is prepared by known methods from organic and inorganic bases. Such bases include, but are not limited to, nontoxic alkali metal and alkaline earth bases, for example, calcium, magnesium, sodium, and potassium hydroxide ; ammonium hydroxide and nontoxic organic bases, such as triethylamine, butylamine, diethanolamine, and triethanolamine base.

The amount of erythropoietin to achieve the desired therapeutic effect is within the skill of those who practice in the art having the benefit of the disclosure herein.

Succinic acid(cas:110-15-6) or a pharmaceutically acceptable salt thereof will be present in methods and compositions of the invention in amounts sufficient to achieve the desired therapeutic effect. The amount of succinic acid or a pharmaceutically acceptable salt thereof for use in the compositions and methods of the invention is from 0.1 to 250 mg per day per kg of body weight of the mammal.

In practicing the compositions and methods of this invention, erythropoietin and succinic acid(cas:110-15-6) or a pharmaceutically acceptable salt thereof can be administered in a variety of routes such as subcutaneous, intravenous, or intramuscular injections; or oromucosally through buccal or sublingual mucosa. Preferred route according to this invention is oromucosal route of administration.

Compositions of the invention can be administered in a wide variety of different dosage forms, i. e. , they may be formulated with various pharmaceutically acceptable inert carriers in the form of tablets, capsules, lozenges, troches, hard candies, powders, sprays, aqueous solutions, elixirs, syrups and the like.