Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form
Reexamination Certificate
2002-10-22
2004-11-09
Page, Thurman K. (Department: 1616)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
C424S439000, C424S451000, C424S464000
Reexamination Certificate
active
06814972
ABSTRACT:
The present invention relates to a combination composition suitable for the prevention and/or treatment of vasculopathic, cardiac, central and peripheral cerebral disturbances and of learning disorders or disorders related to ageing, and which comprises as its characterising ingredients propionyl L-carnitine or one of its pharmacologically acceptable salts and coenzyme Q
10
.
Correspondingly, the composition may take the form and perform the activities of a dietary supplement or of an actual medicine in its own right, depending on whether the action of the composition is meant to be supportive or preventive, or more strictly therapeutic according to the particular individuals for whom it is to be used.
U.S. Pat. No. 4,599,232 discloses a pharmaceutical composition containing L-carnitine or acetyl L-carnitine and coenzyme Q
10
suitable for the therapeutic treatment of atherosclerotic disorders, myocardial and coronary insufficiency and pathological conditions deriving from tissue anoxia. The composition according to the present invention is more effective than that disclosed in the aforementioned patent, as will be described in detail here below, on account of the potent, synergistic effect exerted by its components.
The action of the “carnitines” in general, and of propionyl L-carnitine in particular, on lipid metabolism is well known, as is their anti-atherosclerotic action and their action against lipid metabolism disorders Propionyl L-carnitine, however, differs from the other “carnitines” in its specific cardiovascular activity, though, like the other “carnitines”, it plays an important metabolic role contributing to the &bgr;-oxidation of fatty acids and ATP synthesis, particularly at the mitochondrial level.
Propionyl L-carnitine takes part in all the metabolic activities peculiar to the “carnitines”, but, unlike the others, it presents more pronounced activity at the vascular level, and particularly in the peripheral circulation, so much so indeed that its use is advocated as a therapeutic agent for the prevention and treatment of various peripheral vascular diseases.
Propionyl L-carnitine is superior to the other carnitines and is also active in conditions in which the other carnitines are unable to exert any activity, and this particular feature is related to a more direct metabolic intervention in processes of energy utilisation at the mitochondrial level and to the presence of the propionyl group which produces a different pharmacological effect compared to other similar molecules and which makes it a distinct chemical entity with properties which are different from and superior to those of the other carnitines.
The particular biochemical and pharmacological effect of propionyl L-carnitine is demonstrated by the numerous studies carried out on this molecule.
Propionyl L-carnitine is a natural component of the pool of carnitines and is synthesised by means of carnitine acetyltransferase starting from propionyl-Coenzyme A.
Its administration in human subjects leads to an increase in plasma concentrations of propionyl L-carnitine which in turn causes an increase in the plasma concentrations of L-carnitine which condition its content in the cells with an increase in their oxidative effect on fatty acids and glucose utilisation. Moreover, muscle carnitine transferase possesses a greater affinity for propionyl L-carnitine than for L-carnitine, and consequently propionyl L-carnitine possesses a greater degree of specificity for cardiac and skeletal muscle. Transporting the propionyl group, propionyl L-carnitine increases the uptake of this component by the muscle cells, particularly the myocardial ones. This may be of particular importance, since propionate can be used by the mitochondria as an anaplerotic substrate and can supply energy in anaerobic conditions.
It should be recalled that propionate cannot be used alone because of its toxic effects.
Apart from these metabolic effects, it should also be recalled that, because of its long alkanoyl chain, propionyl L-carnitine exerts a specific pharmacological action via peripheral vasodilatation and myocardial inotropism in conditions in which the other carnitines are inactive.
Coenzyme Q
10
is also known for its metabolic activity and for its important role in the transport and utilisation of mitochondrial oxygen necessary for energy transformation for the production of ATP. Beneficial activity in the treatment of various different forms of vascular disease has also been demonstrated for coenzyme Q
10
.
It has now been found that the combination of propionyl L-carnitine and coenzyme Q
10
powerfully favours cardiovascular and cerebral metabolic activity, enhances learning processes and prevents disorders related to ageing as a result of an unexpected synergistic effect exerted by its components. This synergistic effect is much more evident and more intense than the known effect exerted by the combination of L-carnitine or acetyl L-carnitine and coenzyme Q
10
, and is also manifested in conditions in which L-carnitine and acetyl L-carnitine prove ineffective. The synergistic effect is also evident when propionyl L-carnitine is part of a combination of “carnitines” containing L-carnitine, acetyl L-carnitine, butyryl L-carnitine, valeryl L-carnitine and isovaleryl L-carnitine or their pharmacological acceptable salts or mixtures thereof.
The subject matter of the present invention is therefore a combination composition containing as its characterising active ingredients.
(a) propionyl L-carnitine or one of its pharmacologically acceptable salts; and
(b) coenzyme Q
10
,
which is particularly useful, thanks to the unexpected, potent, synergistic effects of its components, in the prevention and/or treatment of vasculopathic, cardiac, central and peripheral cerebral disturbances, and for the prevention of learning disorders or disorders related to ageing as well as for coping with increased energy needs.
It has also been found that, advantageously, component (a) may further contains a “carnitine” selected from the group consisting of L-carnitine, acetyl L-carnitine, valeryl L-carnitine, isovaleryl L-carnitine and butyryl L-carnitine or their pharmacologically acceptable salts or mixtures thereof.
In the composition according to the invention, the weight-to-weight ratio of (a) to (b) may range from 1:0.05 to 1:0.5, and preferably from 1:0.05 to 1:0.1.
The composition according to the invention may further contain vitamins, coenzymes, mineral substances, amino acids and/or antioxidants.
The composition can be administered orally in the form of a dietary supplement, or can be administered parenterally, via the rectal, sublingual or transdermal routes in the form of a medication for the treatment of frank pathological states. It can therefore be packaged in solid, semisolid or liquid form, in the form, for example, of tablets, pills, capsules, granules, syrups, ampoules or drops.
The surprising synergistic effect which is produced by the combination of propionyl L-carnitine and coenzyme Q
10
has been demonstrated in various pharmacological tests (some of which are described here below) selected in such a way as to be strongly predictive for the practical use of this composition in both the preventive
utritional field and in the strictly therapeutic field.
Toxicology Tests
It is well known that both L-carnitine and coenzyme Q
10
are well tolerated and do not produce any particular toxic effects even when administered at high doses. Their use in combination also produces no damaging toxicological effects. Tests performed in a group of Sprague-Dawley male rats with a mean body weight of 250 g, to which high doses of proprionyl L-carnitine (2 g/kg) or coenzyme Q
10
(0.2 g/kg) or the same amounts of the two compounds in combination were given orally in a single administration, failed to reveal any toxic effects or signs of intolerance. Equally well tolerated appeared to be the prolonged administration of a dose of the two compounds in combination given with the diet in rats (propionyl L-carnitine 500 mg/kg/day and coenzyme Q
10
50 m
George Konata M.
Nixon & Vanderhye P.C.
Page Thurman K.
Sigma-Tau Industrie Farmaceutiche Riunite S.p.A.
LandOfFree
Composition for prevention and/or treatment of vascular... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Composition for prevention and/or treatment of vascular..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Composition for prevention and/or treatment of vascular... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3291709