PHARMACEUTICAL COMPOSITION COMPRISING AN ALGAE ADAPTED TO INCREASE THE EFFICACY OF AN ENZYMATIC INHIBITOR

A pharmaceutical composition comprising at least one algae, wherein said algae is adapted to increase the efficacy of an enzymatic inhibitor.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

In the following description, various aspects of the invention will be described. For the purposes of explanation, specific details are set forth in order to provide a thorough understanding of the invention. It will be apparent to one skilled in the art that there are other embodiments of the invention that differ in details without affecting the essential nature thereof. Therefore the invention is not limited by that which is illustrated in the FIGURE and described in the specification, but only as indicated in the accompanying claims, with the proper scope determined only by the broadest interpretation of said claims.

As used herein, the term “enzyme inhibitor” refers to any compound or composition that has the effect of inhibiting the action of an enzyme.

As used herein, the term “PDE5 inhibitor” refers to any compound or composition that has the effect of inhibiting the degradative action of phosphodiesterase type 5 on cyclic guanosine monophosphate (cGMP).

As used herein, the term “Tadalafil” refers to the compound depicted, (6R,12aR)-6-(1,3-benzodioxol-5-yl)-2,3,6,7,12,12a-hexahydro-2-methylpyrazino[1′,2′:1,6]pyrido[3,4-b]indole-1,4-dione.

As used herein, the term “pharmaceutical composition” refers to any composition comprising at least one pharmaceutically active ingredient and at least one other ingredient, as well as any product which results, directly or indirectly, from combination, complexation, or aggregation of any two or more of the ingredients, from dissociation of one or more of the ingredients, or from other types of reactions or interactions of one or more of the ingredients. Accordingly, the term “pharmaceutical composition” as used herein may encompass, inter alia, any composition made by admixing a pharmaceutically active ingredient and one or more pharmaceutically acceptable carriers.

As used herein, the term “MAFA” refers to modified Aphanizomenon flos aquae.

As used herein, the term “MAFATIL” refers to a biocomplex that comprises a PDE5 inhibitor and MAFA.

It is another object of the present invention to disclose a pharmaceutical composition comprising at least one algae, wherein said algae is adapted to increase the efficacy of an enzymatic inhibitor.

It is another object of the present invention to disclose the pharmaceutical composition as defined above, wherein said Algae is modified.

It is another object of the present invention to disclose the pharmaceutical composition as defined above, wherein said modified Algae is modified Aphanizomenon flos-aquae (MAFA).

It is another object of the present invention to disclose the pharmaceutical composition as defined above, wherein said enzyme inhibitor is a Statin or HMG-CoA reductase inhibitors adapted to lower cholesterol levels.

It is another object of the present invention to disclose the pharmaceutical composition as defined above, wherein said enzyme inhibitor is a phosphodiesterase type 5 (PDE5) inhibitor.

It is another object of the present invention to disclose the pharmaceutical composition as defined above, wherein said PDE5 inhibitor is Taladafil.

The present invention provides a pharmaceutical composition comprising a therapeutically amount of an algae, wherein said algae is adapted to increase the efficacy of an Active Ingredient adapted to delay enzymatic inhibitor.

The present invention provides a pharmaceutical composition, comprising a complex comprising (a) an enzyme inhibitor or a pharmaceutically acceptable salt, derivative or solvate of said substance; and (b) modified algae, wherein said complex decomposes within the body of a patient to provide a therapeutically effective concentration of said enzyme inhibitor.

According to one specific embodiment, said modified Algae is modified Aphanizomenon flos-aquae (MAFA).

According to another embodiment of the present invention, the enzyme inhibitor is a Statin or HMG-CoA reductase inhibitors adapted to lower cholesterol levels.

According to another embodiment of the present invention, said enzyme inhibitor is a phosphodiesterase type 5 (PDE5) inhibitor (e.g., Taladafil).

In a preferred embodiment of the present invention, the MAFA is grown artificially in fresh water under controlled conditions. It is then harvested and dried so as to preserve all of its phytonutrient properties.

In one embodiment of the present invention, an enzyme inhibitor is incorporated into the modified algae cells to produce a stable biocomplex. In a preferred embodiment, the enzyme inhibitor is a PDE5 inhibitor. In a most preferred embodiment, the PDE5 inhibitor is Tadalafil.

A solution or suspension of the enzyme inhibitor (in a preferred embodiment, a PDE5 inhibitor; in a most preferred embodiment, Tadalafil) in water is prepared. An excess of MAFA is then added, and the resulting complex removed from the liquid, whereupon it is then dried according to any method known in the art.

In preferred embodiments, the biocomplex is then further treated according to conventional pharmaceutical practices well-known in the art to produce a form suitable for oral administration to a patient. In a most preferred embodiment in which the biocomplex incorporates tadalafil, the composition is prepared in the form of hard-gelatin capsules, each of which contains 180 mg of the biocomplex, formed from 20 mg of Tadalafil and 160 mg of MAFA. In alternative embodiments, the capsules are prepared from an amount of complex containing a different amount of active ingredient (as non-limiting examples, 5 mg or 10 mg).

As demonstrated in the example given below, administration of the composition disclosed herein does not lead to any of the side effects known side effects of Tadalafil use, including headache, dyspepsia, back pain, myalgia, rhinitis (nasal congestion), and vasodilatation (flushing).

MAFATIL as produced by the above method is nearly insoluble in water or in a buffer solution over the pH range of 1 to 10. MAFATIL is freely soluble in solvents such as DMSO and dimethylformamide.

The stability of several batches of MAFATIL manufactured by the process disclosed above and stored in containers identical to those intended for commercial distribution, was tested. The biocomplex was stored at a temperature of 30±2° C. and a relative humidity of 75±5%. The results of the stability studies are summarized in Table 1.

Example

Reference is now made toFIG. 1, which illustrates the pharmacokinetics of MAFATIL according to the present invention in comparison to those of commercially available tadalafil. In both cases, a single dose of a pharmaceutical composition equivalent to 20 mg of tadalafil was administered to a test population of otherwise healthy subjects suffering from ED and the plasma concentration of Tadalafil was measured at intervals following the administration. The difference in the peak concentrations of Tadalafil administered via the composition disclosed in the present invention (279 μg/L) and that administered according to the composition known in the art (320±70 μg/L) is not statistically significant. The time to the maximum plasma concentration was similar in both cases, approximately 4 hours after administration. In contrast to the formulation known in the art, however, rather than an exponential decay from the peak concentration with a half-life of 17.5 hours, the serum concentration of Tadalafil administered according to the present invention remained elevated and nearly a plateau for some 60 hours after administration, at which point the concentration had declined only to about 85% of its peak value. The plasma Tadalafil concentration begins to drop rapidly after about 90 hours, but the concentration remains at a therapeutically effective level (i.e. the patient is free of symptoms of ED) for at least 96 hours following the administration of a single dose. Also in contrast to the Tadalafil compositions known in the art, no side effects were reported from the use of MAFATIL.