WO2020100052A1

WO2020100052A1 - Composition comprising ginseng, moringa and rutin and the use thereof in the treatment of male sexual dysfunctions

Info

Publication number: WO2020100052A1
Application number: PCT/IB2019/059738
Authority: WO
Inventors: Sebastiano Maurizio CASTORINA; Arianna VANELLI; Alessandro Taddei; Stefania MURZILLI
Original assignee: Nutrilinea S.r.l.
Priority date: 2018-11-13
Filing date: 2019-11-13
Publication date: 2020-05-22
Also published as: WO2020100052A4; IT201800010301A1; EP3880222A1

Abstract

The present invention regards a composition based on Panax (ginseng) extract, Moringa extract and rutin, the innovative formulation thereof as a pharmaceutical or nutraceutical composition and the use thereof for the treatment of male sexual dysfunctions, in particular, the treatment of erectile dysfunction and damage of the endothelial microcirculation of the male genital organ.

Description

DESCRIPTION of the invention having the title:

“COMPOSITION COMPRISING GINSENG, MORINGA AND RUTIN AND THE USE THEREOF IN THE TREATMENT OF MALE SEXUAL DYSFUNCTIONS”.

Erectile dysfunction (ED or impotence or impotentia erigendi ) should be considered a disease which, in the organic component thereof (40-50% of cases), exhibits vascular physiopathogenesis. Furthermore, classic risk factors, such as age, cigarette smoking, hypertension, diabetes mellitus, obesity, dyslipidaemia, more generally metabolic syndrome, and poor physical activity, are associated with an increased risk of developing erectile dysfunction.

Current knowledge indicates that the relaxing of the smooth muscles of the cavernous body, or parts thereof, necessary for erection, is due to a non-adrenergic and non-cholinergic mechanism, mediated by nitric oxide (NO), a labile neurotransmitter. Originally called endothelium-derived relaxing factor, NO is synthesised by arginine and released by the neurones, by the endothelial cells and perhaps by the smooth muscle cells of the cavernous body of the penis, in response to sexual stimulation. After diffusion to the smooth muscle cells of the cavernous body, NO stimulates the cytosolic enzyme guanylate cyclase to produce a second messenger, cyclic guanosine monophosphate (cGMP). Cyclic nucleotides, such as cGMP, are hydrolysed by cyclic nucleotide phosphodiesterase (PDE) isoenzymes, located in various tissues. In human cavernous body, PDE-cGMP specific - Type 5 (PDE5) is the predominant isoenzyme. Various studies have shown that the NO/cGMP mechanism plays the main role in relaxing the cavernous body smooth muscle, or parts thereof, and in penile erection.

In addition, increasing the prevalence of erectile dysfunction and cardiovascular diseases with age and the many common risk factors between the two diseases have led to the assumption that these conditions may share common pathogenesis. Endothelial dysfunction is probably the link between erectile dysfunction and cardiovascular diseases. It manifests itself with a series of modifications of the function of the vascular endothelium, among which the reduction of the production of nitric oxide, the increase of the tone of the smooth muscle, the production of inflammatory cytokines and free radicals (with vasoconstrictor action). According to the arterial calibre hypothesis, the cavernous arteries of the penis, of small calibre, in pathological conditions reach critical stenosis levels, associated with relative blood hypoafflux, earlier than large calibre vessels, such as those of the coronary region, the epiaortic vessels (carotid) or those of the lower limbs (ileo-femoral). Therefore, several clinical evidence suggests that erectile dysfunction may be a possible tell-tale symptom of coronary artery disease, and in particular, it has been shown that the onset of erectile dysfunction precedes the occurrence of a cardiovascular event by 2-3 years. In this category of patients, oral pharmacotherapy with phosphodiesterase-5 (PDE-5) inhibitors achieves lower response rates than in the population of men suffering from erectile dysfunction without risk factors. The "rehabilitation” therapy for erectile dysfunction, which provides for the chronic use of oral drugs, with related adverse effects (e.g. headache, flushing, back pain, visual disorders, nasal congestion and tachycardia) has proved to be more effective than on-demand therapy. However, there is still a percentage of patients who do not respond to this therapy and there persists a high drop-out percentage (20-30%) from the therapy.

Persistent erectile dysfunction (ED) is an infrequent problem below 40 years of age whose incidence increases rapidly as years advance, to the point that 65% of 70-year-old men have problems with sexual dysfunction. This increase is mainly due to vascular disorders and it occurs approximately 10 years in advance in men suffering from diabetes or metabolic syndrome. Drugs currently available on the market for the treatment of male sexual dysfunctions, particularly erectile dysfunction, all belong to the phosphodiesterase-5 (PDE-5) inhibitor category , such as sildenafil (Viagra), vardenafil (Levitra or Vivanza), tadalafil (Cialis) and avanafil( Spedra). These drugs inhibit the enzymatic degradation of cGMP, an enzymatic messenger which leads, among other things, to a dilation of the arterioles of the penis, with consequent increase in the turgor and in the size of the organ. cGMP is released following increased nitric oxide (NO) production in response to nerve signals.

Furthermore, there are numerous nutraceutical compositions comprising natural substances that can be effective towards improving male sexual dysfunctions. Most of them are tonic and/or energising agents that act exclusively on erectile action by immediately improving sexual performance but they do not act on the various physiological mechanisms involved in erectile dysfunction as illustrated above.

The technical problem addressed and solved by the present invention lies in providing a valid solution for the effective therapeutic and non-therapeutic treatment of diseases, symptoms and/or disorders related with male sexual dysfunctions, in particular erectile dysfunction, problems to the endothelial microcirculation of the male genital organ (for example, microcirculatory endothelial trophism) and/or low or lack of male sexual drive (libido), capable of overcoming the drawbacks of the prior art yet to be solved, in particular as regards the resolution of problems in the long term and not only in the short term and/or the presence of adverse effects.

In order to overcome these problems, the present invention provides a composition comprising, as active ingredients, an extract of a plant of the Panax genus, an extract of a plant of the Moringa and rutin genus (in short, composition of the invention). This composition is capable of effectively and rapidly treating the diseases, symptoms or disorders caused by or related with an alteration of the physiological mechanisms of the male sexual sphere, in particular of erection, with antioxidant, ergogenic, cardioprotective, neuroprotective, vasoprotective and metabolic activities, vasodilators and stimulant of testosterone hormone.

Besides having tonic and energising effects, the present invention also acts on pathophysiological factors recognized as the causes of male sexual dysfunctions, in particular erectile dysfunction, protecting the endothelium from oxidative damage, improving the activity of the smooth muscle cells, reducing endothelial cell death and phlogosis in the vascular site and, lastly, adding-on the biological functionality of nitric oxide.

The composition of the present invention also revealed to be effective as an endothelial protector to prevent damage that could cause erectile dysfunction, particularly in subjects suffering from metabolic syndrome or, in general, in subjects with specific risk factors (for example, smoking, alcohol, dyslipidaemia, obesity, poor physical activity, hypertension, diabetes).

Furthermore, the present invention provides a composition without the adverse effects present in the treatments of the prior art and, simultaneously, a composition that is easy to prepare, economically advantageous and quick to access even to patients who would tend not to request the pharmacological therapies currently available for psycho-social reasons.

In addition, the composition of the invention is well tolerated by all categories of subjects, including subjects with cardiovascular problems, preferably hypertension, and/or diabetes, preferably type 2 diabetes mellitus.

The composition according to the present invention can be used as monotherapy for the treatment of a male sexual dysfunction, preferably erectile dysfunction, or, alternatively, as an adjuvant therapy of a conventional pharmacological therapy of said dysfunctions (for example, PDE-5) to enhance the effect thereof, thus reducing the posology and/or adverse effects of said conventional pharmacological therapy. Furthermore, the composition according to the present invention can be used as a protector of the vascular endothelium, allowing to prolong the effect of the PDE-5i therapy. These and other objects, which will be clear from the detailed description that follows, are attained by the compositions and the mixtures of the present invention due to the technical characteristics claimed in the attached claims.

Following an intense research step, the Applicant discovered that the administration of a composition according to the present invention to a needy subject is capable of effectively and rapidly treating diseases, symptoms or disorders caused by or related with male sexual dysfunction, particularly erectile dysfunction.

Said therapeutic or non-therapeutic treatment activity is a result of the specific combination of the three active ingredients present in the composition, such as the extract of a plant of the Panax genus (Ginseng), extract of a plant of the Moringa and rutin genus, and synergistic effect thereof or increase of treatment activity with respect to the activity of the single components. As a matter of fact, the three active ingredients, administered orally, act in a synergistic fashion on the action mechanisms of NO, endothelial and oxidative stress for the treatment of erectile dysfunction.

The composition of the invention acts by stimulating the release of nitric oxide in the corpora cavernosa and supports the relaxing of the smooth muscle improving the endothelial microcirculation, thus allowing the flow of blood and alleviating the erectile dysfunction. Thus, thanks to the synergistic action of the aforementioned active components, the composition of the invention is an alternative to the pharmacological treatment currently known and used both for the prevention of erectile dysfunction by acting as endothelium protector in order to prevent tissue damage that could result in erectile dysfunction, as well as in the treatment as monotherapy for subjects suffering from mild erectile dysfunction.

According to a preferred aspect of the invention, the composition of the invention can be used as an adjuvant to a known treatment and in use for erectile dysfunction (for example, a PDE-5), in order to enhance the treatment effect thereof but acting on different physiological mechanisms though still directly related with erectile dysfunction.

Lastly, according to a further preferred aspect of the invention, the composition of the invention can be used as a post-therapy treatment with respect to a known and in use treatment, as a protector of the vascular endothelium, that allows to prolong the effect of a phosphodiesterase -5 (PDE-5) inhibitors pharmacological therapy that often has low adherence to a long-term treatment.

FIGURES: Figure 1 : clinical study outline

Figure 2: IIEF data from group A and group B of the clinical study

DETAILED DESCRIPTION OF THE INVENTION

The present invention regards a composition (in short composition of the invention) comprising (i) a mixture (in short mixture of the invention) comprising or, alternatively, consisting of (II), (I) and (III):

(I) an extract from at least one plant of the Panax genus ( Panax L, where L. is the abbreviation of C. N. Linnaeus) comprising ginsenosides (triterpene saponins), wherein said at least one plant of the Panax genus belongs to a species selected from among the group comprising or, alternatively, consisting of Panax ginseng ( Panax ginseng Meyer), Panax notoginseng ( Panax notoginseng Chen.), Panax pseudoginseng ( Panax pseudoginseng Wall.), Panax guinguefolium ( Panax guinguefolium L.) and the mixtures thereof;

(II) an extract from at least one plant of the Moringa genus comprising saponins, wherein said at least one plant of the Moringa genus belongs to the species selected from among the group comprising or, alternatively, consisting of Moringa oleifera ( Moringa olifera Lam), Moringa peregrina ( Moringa peregrina (Forssk.) Fiore) and mixtures thereof;

(III) rutin;

and said composition comprises, optionally,

(ii) at least one food grade or pharmaceutical additive and/or excipient.

Panax (ginseng) is a genus of plant belonging to the Araliacea family native to tropical Asia, comprising 11 species of slow-growing perennial plants with fleshy roots commonly known as ginseng. The two most common species are Panax ginseng Meyer (Asian or Chinese or Korean ginseng) and Panax guinguefolus L. (American or north American ginseng). The constituents thereof of therapeutic interest are ginsenosides, triterpene saponins with a steroid structure, of which about 60 types are known and which are detectable only in the plants of the Panax genus (ginseng).

Panax (ginseng) has always been considered a remedy for sexual dysfunctions in traditional Asian medicine, particularly for erectile function. Several mechanisms are considered to be the basis of the capacity of ginseng to improve sexual function. The primary one is represented by the stimulation of nitric oxide (NO) production at the level of corpora cavernosa, by activating NO-synthase (NOS). This results in vasodilation, amplified by two ancillary actions such as facilitating the effect of acetylcholine at the level of corpora cavernosa and converting arginine into citrulline. Furthermore, Panax (ginseng) appears to be capable of increasing the circulating levels of testosterone, but the pro-erectile mechanism at central level can also be explained by the ability to inhibit GABAergic receptors (A and B), to increase dopamine levels and reduce prolactin levels at pituitary level. Besides the energising action and the ability to reduce asthenia significantly, the anxiolytic and antidepressant action can further promote the relational and sexual function. Finally, sexual function can indirectly benefit from the Panax (ginseng) activity in reducing arterial atherosclerosis and blood glucose and lipid levels (LDL) and the ability thereof to act as a neuroprotector. A meta-analysis of 7 trials, published in 2008, and a subsequent update in 2013 showed a significant effect of Panax (ginseng) on erectile function in men (significant improvement in IIEF score in 60% of patients treated - RR: 2.40) as compared to placebo, already after 12 weeks of use. Flowever, it should be noted that the beneficial effect of ginseng occurs after days or months from the start of treatment. A review conducted by Khera and Goldstein gave ginseng a low degree of recommendation for the treatment of erectile dysfunction related with any cause.

In the composition according to the invention comprising (I), (II) and (III), said (I) extract from at least one plant of the Panax genus is an extract of leaves, fruits, roots or an extract obtained from two or more of said parts of the plant. Preferably, said (I) is an extract of roots or leaves, such as an extract of Panax ginseng roots, of Panax notoginseng roots or leaves, of Panax pseudoginseng roots or leaves, of Panax guinguefolium roots or leaves or a mixture of said extracts; preferably said (I) extracts are dry extracts.

Said (I) extracts from at least one plant of the Panax genus comprising ginsenosides are advantageously dry hydroalcoholic extracts obtained according to standard procedures known to the man skilled in the art and/or indicated in literature, with ginsenosides titration determined using spectrophotometric (UV) method according to standard procedures known to the man skilled in the art and/or indicated in the literature.

Preferably, in the composition according to the invention comprising (I), (II) and (III), said (I) extract from at least one plant of the Panax genus comprises ginsenosides in a range comprised between 1% and 30% by weight, preferably between 5% and 15%, more preferably about 10%, with respect to the total weight of said extract (I).

In a preferred embodiment, in the composition according to the invention, comprising (I), (II) and (III), said (I) extract from at least one plant of the Panax genus is an extract of Panax ginseng roots comprising ginsenosides in the above defined ranges (i.e. 1%-30%, 5%-15%, about 10% w/w); preferably a dry hydroalcoholic extract of Panax ginseng roots.

In an embodiment, the (i) mixture of the invention comprises or, alternatively, consists of:

(I) Panax ginseng root extract comprising ginsenosides at the concentrations described above (i.e. 1%- 30%, 5%-15%, about 10% w/w); more preferably hydroalcoholic dry extract; (II) an extract from at least one plant of the Moringa genus comprising saponins, wherein said at least one plant of the Moringa genus belongs to the species selected from among the group comprising or, alternatively, consisting of Moringa oleifera ( Moringa oleifera Lam), Moringa peregrina ( Moringa peregrina Fiore) and the mixtures thereof; and

(III) rutin.

Moringa is a genus of plant belonging to the Moringaceae family, widely used in the tropical and equatorial zones of the planet. Its leaves and seeds are a concentrate of proteins, iron, calcium, potassium, vitamins (especially C and E), beta-carotene but also flavonoids, alkaloids, tannins and saponins which are considered to have various properties. Currently known are 13 species of the Moringa genus, including Moringa oleifera and Moringa peregrina.

Moringa oleifera ( Moringa oleifera Lam, synonym: Hyperanthera moringa (L.) Vahl) was studied for its beneficial properties on metabolism and for its antioxidant action. In vivo and in vitro studies proved the ability of Moringa oleifera extracts to reduce glycaemic levels, blood lipids (cholesterol, LDL, triglycerides) and the formation of atheromatous plaques. Furthermore, they have a neuroprotective and cardiotonic effect, with significant improvement of cardiac function parameters and a reduction of blood pressure, mainly through inhibitory action on the angiotensin converting enzyme (ACE), which intervenes at the level of the cardiocirculatory system, leading to the variation of the blood pressure levels. Therefore, such extracts are active on all the components of the metabolic syndrome and they have a protective role as pertains to endothelial damage. The role of endothelial protector is linked to the very powerful antioxidant activity of the various components (quercetin, gallic acid, ascorbic acid, caffeoylquinic acid) and, in particular, a scavenging action on free radicals and a beneficial effect on erectile dysfunction induced by oxidative stress was observed. Furthermore, extracts of Moringa oleifera are able to inhibit arginase, and this allows an increase in the arginine bioavailability and therefore increasing its conversion into nitric oxide (NO) through the action of nitric oxide synthases. This mechanism can therefore oppose the reduction of nitric oxide synthases (NOS), caused by the endothelial and neuronal damage, thanks to the increased availability of arginine.

Moringa peregrina ( Moringa peregrina Fiore, synonym: Hyperanthera peregrina Forssk.) is a species of flowering plant of the Moringaceae family from the Arabian Peninsula, the Horn of Africa and South Sinai.

In the composition according to the invention comprising (I), (II) and (III), said (II) extract from at least one plant of the Moringa genus is an extract of leaves, fruits and oils, seeds or an extract obtained from two or more of said parts of the plant. Preferably said (II) is a seed extract, such as a Moringa oleifera seed extract, Moringa peregrin seed extract or a mixture of said extracts; preferably said extracts are dry extracts.

Said (II) extracts from at least one plant of the Moringa genus comprising saponins (terpene glycosides) are advantageously dry hydroalcoholic extracts obtained according to standard procedures known to the man skilled in the art and/or indicated in literature, with saponins titration determined using spectrophotometric (UV) method according to standard procedures known to the man skilled in the art and/or indicated in the literature.

Saponins are terpene glycosides of plant origin named after Saponaria officinalis. Structurally, saponins are formed by the union of sugar residues (such as glucose, fructose, galactose, arabinose or others) with a non-sugar molecule called aglycone (also sapogenin in this specific case). This particular structure is responsible for the detergent activity of saponins given that sugars form a water-soluble section while aglycone is liposoluble. On the contrary, sapogenins have a more complex structure, traceable to two groups: saponins with steroidal aglycone (C27) and saponins with triterpenoid aglycone (C30). However, the chemical-physical and biological properties of the two groups are similar. Both groups have a glucose binding at C3 position and have common biogenetic origin through mevalonic acid and isoprenoid units. Triterpene-nucleus saponins have a pentacyclic structure with 30 carbon atoms while those with steroid nucleus have a base structure with 27 carbons (often the aliphatic chain is transformed into two heterocyclic rings).

The steroid saponins present in Moringa oleifera Lam have active ingredients that increase the percentage of follicle-stimulating hormone (FSH) required for the proper functioning of the ovaries and testicles. Furthermore, saponins have a powerful toning effect and promote increased energy and dynamism, for a better physical strength. In therapy, at the moment, saponins present in the oleifera Moringaare are recognised as having anti-inflammatory, healing and anti-edemigenic activity.

Saponins are often used in the industry for the subsequent production of steroidal hormones (such as testosterone and cortisol, for example).

Preferably, in the composition according to the invention comprising (I), (II) and (III), said (II) extract from at least one plant of the Moringa genus comprises saponins in a range comprised between 1% and 50% by weight, preferably between 15% and 25%, more preferably about 20%, with respect to the total weight of said extract (II).

In a preferred embodiment, in the composition according to the invention, comprising (I), (II) and (III), said (II) extract from at least one plant of the Moringa genus is a Moringa oleifera seed extract comprising said in the above defined ranges (i.e. 1%-50%, 15%-25%, about 20% w/w); preferably a dry hydroalcoholic extract of Moringa oleifera seeds.

(I) Panax ginseng root extract comprising ginsenosides at the percentages described above (i.e. 1 %-30%, 5%-15%, about 10% w/w); more preferably a hydroalcoholic dry extract;

(II) an extract from a plant of the Moringa oleifera species comprising saponins at the percentages described above (i.e. 1 %-50%, 15%-25%, about 20% w/w); more preferably a hydroalcoholic dry extract; and

(III) rutin, preferably rutin from Styphnolobium japonicum (L.) Schott ( Leguminosae Sophora japonica L.) purified and identified through the U.V. method.

Rutin (lUPAC name: (2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-3-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6- [(2R,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyl-oxan-2-yl]oximethyl]oxan-2-yl]oxy-chromen-4-one;CAS n° 153-18-4; common names: Rutoside, vitamin P, quercetin-3-rutinoside, soforin) is a flavonoic glycoside formed by quercetin bound to rutinose disaccharide. Rutin exerts its therapeutic effect mainly due to its antioxidant action. Rutin is capable of opposing the oxidative stress and endothelial damage that is generated during diabetic disease, resulting in a significant increase in sexual function. As a matter of fact, at tissue level, rutin seems to significantly reduce signs of inflammation, lipid peroxidation, oxidative stress and cell damage induced by hyperglycaemia. Moreover, rutin can reduce diabetes-induced hypotestosteronemia. In addition, plant extracts containing high concentrations of rutin have the ability to inhibit in vitro arginase, increasing the amount of arginine available for conversion into NO by nitric oxide synthetase (NOS), as well as a direct inhibiting effect of phosphodiesterase of type-5 (PDE-5) fully mimicking the mechanism of action of most of the already existing pharmaceutical formulations.

The rutin included in the (i) mixture of the present invention together with (I) and (II) has a purity comprised between 70% and 100%, preferably between 80% and 98%, more preferably about 95%, and it is advantageously obtained from Styphnolobium japonicum (L.) Schott ( Leguminosae Sophora japonica L.), purified and identified through the U.V. method.

In an embodiment, the composition according to the invention further comprises, besides said (i) mixture comprising (I), (II) and (III) as defined above, said (ii) at least one food or pharmaceutical grade additive and/or excipient comprising (ii-l) at least one anti-caking agent and/or (ii-ll) at least one bulking agent; preferably (ii-l) at least one anti-caking agent and (ii-ll) at least one bulking agent. Said (ii-l) at least one anti-caking agent and said (ii-ll) at least one bulking agent can be selected from among those known to the man skilled in the art.

Preferably, said (ii-l) at least one anti-caking agent is selected from silicon dioxide, magnesium salts of the C10-C20 fatty acids, preferably magnesium salts of the C16-C18 fatty acids, and the mixtures thereof. Preferably, said (ii-ll) at least one bulking agent is selected from calcium hydrogen phosphate (dicalcium phosphate), microcrystalline cellulose, hydroxypropyl methyl cellulose, cross-linked sodium carboxymethyl cellulose and the mixtures thereof.

The composition of the present invention comprising (I), (II) and (III) may be, by way of non-limiting example, in liquid form, such as solution, two-phase liquid system, suspension or syrup, semi-solid form, such as gel, cream or foam, or solid form, such as powder, granules, flakes, aggregates, tablets, capsules, pills, bars and equivalent forms.

Preferably, the composition of the invention comprising (I), (II) and (III) is formulated in a formulation for oral use, preferably in a formulation for oral use in solid form; even more preferably in a formulation for oral use in solid form of tablet or any other solid form similar to the tablet.

In a preferred embodiment, the composition of the invention is formulated in a formulation for oral use, wherein said formulation comprises:

- said (I) extract from at least one plant of the Panax genus comprising ginsenosides, preferably Panax ginseng, in a first immediate release formulation;

- said (II) extract from a plant of the Moringa genus comprising saponins, preferably Moringa oleifera, in a second delayed release formulation; and

- (Ill) rutin in a third intermediate release formulation.

In the context of the present invention, the expression "immediate release formulation” ( fast-release ) is used to indicate a release of the active ingredient (extract) into the gastric mucosa in a range comprised between 5 minutes and 20 minutes after swallowing the composition of the invention, preferably between 5 minutes and 15 minutes, more preferably between 5 minutes and 10 minutes.

In the context of the present invention, the expression "intermediate release formulation” ( normal-release ) is used to indicate a release of the active ingredient (extract) into the first intestinal tract in a time interval between 20 minutes and 90 minutes after swallowing the composition of the invention, preferably between 20 minutes and 60 minutes, more preferably between 20 minutes and 45 minutes. In the context of the present invention, the expression "delayed release formulation” (slow-release) is used to indicate a release of the active ingredient (extract) into the intestinal tract in a time interval between 1.5 hours and 8 hours after swallowing the composition of the invention, preferably between 2 hours and 7 hours, more preferably between 2 hours and 6 hours.

In a preferred embodiment, the composition of the present invention is formulated in a formulation for oral use in solid form, preferably a tablet, comprising:

- a first layer comprising said (I) extract from at least one plant of the Panax genus comprising ginsenosides, preferably Panax ginseng, in said first immediate release formulation;

- a second layer comprising said (II) extract from at least one plant of the Moringa genus comprising saponins, preferably Moringa oleifera in said second delayed release formulation; and

- a third layer comprising (III) rutin in said third intermediate release formulation.

Said formulation comprising said first, second and third layers may comprise further layers having or without specific release characteristics.

Furthermore, said first, second and third layers may be in any order of arrangement in the solid formulation form. Lastly, many of said first layer and/or many of said second layer and/or many of said third layer may be present in the solid formulation form, arranged in any order with respect to each other.

In a more preferred embodiment, the composition of the invention is a tablet comprising:

- a first layer comprising said (I) Panax ginseng extract comprising ginsenosides in said first immediate release formulation, preferably a dry extract of Panax ginseng roots;

- a second layer comprising said (II) Moringa oleifera extract comprising saponins in said second delayed- release formulation, preferably a dry extract of Moringa oleifera seeds;

The formulation for oral use of the composition of the invention in solid form of a tablet, or the like, subdivided into three layers (slow, normal and fast-release) promotes the release of the characterising components (I), (II) and (III) (or mixture of active ingredients) at different times depending on the type and percentage of excipients included per single layer. The formulation in several layers thus allows to optimise the efficacy of the various components (I), (II) and (III) by releasing them "at different times”.

In all the aforementioned forms of formulation, each component (I), (II) and (III) can be present at the amounts defined below. In an embodiment, said (I) at least one extract from a plant of the Panax genus, preferably a dry extract of Panax ginseng roots, more preferably a Panax ginseng extract comprising ginsenosides at 1 %-30% or 5%-15% or about 10% w/w, is present in said (i) mixture comprising (I), (II) and (III) at a by weight amount comprised in the range from 40% to 80%, with respect to the total weight of the mixture, preferably from 55% to 75%, more preferably from 60% to 70%; and it is present in the composition of the invention at a by weight amount comprised in the range from 15% to 65%, with respect to the total weight of the composition, preferably from 25% to 50%, more preferably from 30% to 40%.

In an embodiment, said (I) extract from at least one plant of the Panax genus, preferably a dry extract of Panax ginseng roots, comprises ginsenosides and said ginsenosides are present in said (i) mixture comprising (I), (II) and (III) at a by weight amount comprised in the range from 1% to 15%, with respect to the total weight of the mixture, preferably from 3% to 10%, more preferably from 5% to 8%; and wherein said ginsenosides are present in the composition of the invention at a by weight amount comprised in the range from 0.1% to 10%, with respect to the total weight of the composition, preferably from 1% to 8%, more preferably from 2% to 6%.

In an embodiment, said (II) at least one extract from a plant of the Moringa genus, preferably a dry extract of Moringa oleifera seeds, more preferably a Moringa oleifera extract comprising saponins at 1 %-50% or 15%-25% or about 20% w/w, is present in said (i) mixture comprising (I), (II) and (III) at a by weight amount comprised in the range from 5% to 50%, with respect to the total weight of the mixture, preferably from 15% to 35%, more preferably from 20% to 30%; and it is present in the composition of the invention at a by weight amount comprised in the range from 1% to 30%, with respect to the total weight of the composition, preferably from 5% to 25%, more preferably from 10% to 20%.

In an embodiment, said (II) extract from at least one plant of the Moringa genus, preferably a dry extract of Moringa oleifera seeds, comprises saponins and said saponins are present in said (i) mixture comprising (I), (II) and (III) at a by weight amount comprised in the range from 1% to 15%, with respect to the total weight of the mixture, preferably from 3% to 10%, more preferably from 5% to 8%; and wherein said saponins are present in the composition of the invention at a by weight amount comprised in the range from 0.1% to 10%, with respect to the total weight of the composition, preferably from 0.5% to 7%, more preferably from 1% to 5%.

In an embodiment, (III) rutin is present in said (i) mixture comprising (I), (II) and (III) at a by weight amount comprised in the range from 1% to 15%, with respect to the total weight of the mixture, preferably from 3% to 10%, more preferably from 5% to 8%; and it is present in the composition of the invention at an amount by weight comprised from 0.1% to 10%, with respect to the total weight of the composition, preferably from 1% to 8%, more preferably from 2% to 6%.

In a preferred embodiment, in the composition according to the invention comprises:

- ginsenosides from Panax ginseng at a by weight amount with respect to the total weight of the composition from 1% to 8%, more preferably from 2% to 6%;

- saponins from Moringa oleifera at a by weight amount with respect to the total weight of the composition from 0.5% to 7%, more preferably from 1% to 5%;

- rutin at a by weight amount with respect to the total weight of the composition from 1% to 8%, more preferably from 2% to 6%.

According to a preferred aspect of the invention, the composition of the present invention, preferably formulated in solid form for oral use, more preferably subdivided into at least three layers (slow, normal and fast-release), comprises in each single dose form, for example in each single tablet, the following amounts of components (I), (II) and (III):

• (I): from 200 mg to 700 mg, preferably from 300 mg to 600 mg, more preferably from 450 mg to 550 mg, preferably (I) is a dry extract of Panax ginseng roots;

• (II): from 50 mg to 350 mg, preferably from 100 mg to 300 mg, more preferably from 150 mg to 250 mg, preferably (II) is a dry extract of Moringa oleifera seeds; and

• (III): from 5 mg to 100 mg, preferably from 25 mg to 75 mg, more preferably from 45 mg to 55 mg. Advantageously, the composition of the present invention, preferably formulated in solid form for oral use, more preferably subdivided into at least three layers (slow, normal and fast-release), comprises in each single dose form, for example in each single tablet, the following amounts:

• ginsenosides contained in (I): from 5 mg to 100 mg, preferably from 25 mg to 75 mg, more preferably from 40 mg to 60 mg, preferably (I) is a dry extract of Panax ginseng roots;

• saponins contained in (II): from 5 mg to 80 mg, preferably from 25 mg to 55 mg, more preferably from 35 mg to 45 mg, preferably (II) is a dry extract of Moringa oleifera seeds; and

• rutin: from 5 mg to 100 mg, preferably from 25 mg to 75 mg, more preferably from 45 mg to 55 mg.

Forming an object of the present invention is the composition of the invention as described above, wherein said composition is for use as a medicament. In an embodiment, the composition according to the invention is for use in a method for the preventive and/or curative treatment of a disease, symptom and/or disorder related with male sexual dysfunctions in a needy subject.

In a preferred embodiment, the composition according to the invention is for use in a method for preventive and/or curative treatment of a disease, symptom and/or disorder related with erectile dysfunction, problems or dysfunctions to the endothelial microcirculation of the male genital organ (for example, microcirculatory endothelial trophism), low or lack of male sexual drive or libido.

In an embodiment, the composition according to the invention is for use as a vasodilator, testosterone hormone stimulant and/or antioxidant; preferably vasodilator, testosterone hormone stimulant and/or antioxidant for the treatment of erectile dysfunction or of a male sexual dysfunction.

Forming an object of the present invention is the non-therapeutic use of the composition of the invention as defined above for the non-therapeutic treatment of male sexual dysfunctions and disorders related therewith or for the improvement of male sexual performance in a needy subject; preferably for the non- therapeutic treatment of erectile dysfunction, problems with the endothelial microcirculation of the male genital organ, low or lack of male libido.

According to a preferred aspect of the invention, the composition of the invention comprises amounts of (I), (II) and (III) such to ensure administration, to said needy subjects, of daily doses of said components in the following ranges:

• (I): from 200 mg to 2000 mg, preferably from 300 mg to 1500 mg, more preferably from 400 mg to 1000 mg, preferably (I) is a dry extract of Panax ginseng roots;

• (II): from 50 mg to 800 mg, preferably from 100 mg to 600 mg, more preferably from 150 mg to 400 mg, preferably (II) is a dry extract of Moringa oleifera seeds; and

• (III): from 20 mg to 200 mg of (III), preferably from 30 mg to 150 mg, more preferably from 45 mg to 100 mg.

Advantageously, the composition of the invention comprises amounts of (I), (II) and (III) such to ensure administration, to said needy subjects, of daily doses of said components comprised in the following ranges:

• ginsenosides contained in (I): from 20 mg to 200 mg, preferably from 30 mg to 150 mg, more preferably from 40 mg to 100 mg, preferably (I) is a dry extract of Panax ginseng roots; • saponins contained in (II): from 5 mg to 160 mg, preferably from 15 mg to 120 mg, more preferably from 30 mg to 80 mg, preferably (II) is a dry extract of Moringa oleifera seeds; and

• rutin: from 20 mg to 200 mg, preferably from 30 mg to 150 mg, more preferably from 45 mg to 100 mg.

Said daily doses of components (I), (II) and (III) of the composition of the invention can be administered to subjects in need by administering a single dose form per day or by administering 2 to 4 single dose forms per day, depending on the type of dose form and on the needs of the subject.

Forming an object of the present invention is a method for the therapeutic or non-therapeutic, preventive and/or curative treatment of a disease, symptom and/or disorder related with male sexual dysfunctions, in particular erectile dysfunction, problems to the endothelial microcirculation (for example, microcirculatory endothelial trophism), low or lack of male sexual drive or libido, which provides for the use of the composition of the invention in a needy subject (administration of the composition of the invention at a therapeutically effective amount).

In an embodiment, the composition of the present invention, comprising (I), (II) and (III) according to any one of the embodiments of the invention, can be administered combined/associated with a drug for the treatment of erectile dysfunctions, preferably a drug belonging to the category of phosphodiesterase-5 (PDE-5) inhibitors, more preferably a drug selected from among sildenafil (Viagra), vardenafil (Levitra o Vivanza), tadalafil (Cialis) and avanafil (Spedra). In other words, the composition of the invention serves as an adjuvant in the treatment of erectile dysfunction by means of a PDE-5.

Advantageously, the composition of the invention can be taken daily for a time interval (for example as defined below) and said drug for the treatment of erectile dysfunctions can be taken on demand, or, both the composition of the invention and said drug can be taken daily for a time interval.

The composition of the invention, combined/associated with said drug or not combined/associated with said drug, can be taken daily for cycles lasting from 10 days to 120 days repeatable from 2 to 4 times a year, preferably cycles from 30 days to 120 days, for example two annual cycles lasting about 2-3 months each.

The daily use of the composition of the invention proved to be advantageous in that it has a triple energising tonic action, endothelial protection action and smooth muscle protection action. The inventors surprisingly found that the composition according to the present invention, administered combined/associated with a medicament for the treatment of erectile dysfunctions, allows to obtain a “sexual training, to be understood as a beneficial action on the disease that adds on to the effect of said drug taken daily or on demand.

The add-on use of the composition of the invention with a drug for the treatment of erectile dysfunctions (for example, a PDE-5) allows to lower the posology of said drug, taken daily or on demand; for example, the dose of said drug taken daily and/or on demand can be comprised in the range of from 0.5 mg to 10 mg, preferably from 1 mg to 8 mg, for example it can be about 5 mg. This is particularly advantageous for subjects suffering from cardiovascular disorders (e.g. hypertension) and/or diabetes.

The composition of the present invention may comprise, additionally or replacing (ii-l) and (ii-ll), further food grade or pharmaceutical additives and/or excipients, i.e. a substance without therapeutic activity suitable for pharmaceutical or food use. In the context of the present invention the acceptable ingredients for pharmaceutical or food use comprise all auxiliary substances known to the man skilled in the art such as, by way of non-limiting example, diluents, solvents (including water, glycerine, ethyl alcohol), solubilisers, thickeners, sweeteners, flavourings, dyes, lubricants, surfactants, antimicrobials, antioxidants, preservatives, pH stabilisation buffers and the mixtures thereof. Non-limiting examples of such substances are maltodextrins, phosphate buffers, bases such as sodium hydroxide, xanthan gum, guar gum, fructose, natural or artificial flavours.

Besides the components (I), (II) and (III) of the (i) mixture as defined above and, optionally, besides (ii) additives and/or excipients, the composition according to the present invention may further comprise other active ingredients such as, by way of non-limiting example, extracts of terrestrial Tribulus rich in saponins, Ginko Biloba, anti-inflammatory agents, antioxidants, probiotics, in particular with antioxidant effects, antihypertensives, antacids, products for the treatment of the urological system, vitamins and mineral salts.

Lastly, forming an object of the present invention is a pharmaceutical composition, nutraceutical composition, dietary supplement product or a food product for special medical purpose or a medical device composition comprising or, alternatively, consisting of the composition of the present invention.

The expression "medical device” in the context of the present invention is used according to the meaning laid down by the Italian Legislative Decree n° 46, dated 24 February 1997, i.e. it indicates a substance or another product, used alone or in combination, designated by the manufacturer to be used in humans for diagnosis, prevention, control, therapy or disease attenuation purposes, the product not exercising the main action, in or on the human body, for which it is designated, neither with pharmacological or immunology means nor by means of a metabolic process but the function thereof can be added-onto by such means.

For the sake of clarity, with the aim of achieving the object of the present invention, the active ingredients of the mixture of the present invention (I), (II) and (III) may also be administered separately (preferably at a time interval ranging from 30 minutes to 1 hour) and in any order, preferably, (I), (II) and (III) are administered to a subject simultaneously, even more preferably in a single composition so as to obtain a more rapid effect and for ease of administration.

When the active ingredients (I), (II) and (III) are administered in a single composition, said single composition corresponds to the composition of the present invention.

The expression "treatment method” in the context of the present invention is used to indicate an action, comprising the administration of a substance, or mixture of substances or combination thereof, with the aim of eliminating, reducing/decreasing or preventing a pathology or disease and its symptoms or disorders.

Unless specified otherwise, the indication that a composition "comprises” one or more components or substances means that other components or substances can be present besides the one, or the ones, indicated specifically.

Unless specified otherwise, the expression composition comprises a component at an amount "comprised in a range from x to y” is used to indicate that said component can be present in the composition at all the amounts present in said range, even though not specified, extremes of the range comprised.

The compositions of the present invention allow the effective therapeutic and non-therapeutic treatment of diseases, symptoms and/or disorders related with male sexual dysfunctions, in particular erectile dysfunction, problems or dysfunctions to the endothelial microcirculation (for example, microcirculatory endothelial trophism), low or lack of male sexual drive or libido, in particular in the absence of relevant adverse effects.

Embodiments (FRnr) of the present invention are indicated below: FR1. A composition comprising

(i) a mixture comprising, or alternatively, consisting of:

(I) an extract from at least one plant of the Panax genus comprising ginsenosides, wherein said at least one plant of the Panax genus belongs to a species selected from among the group comprising or, alternatively, consisting of Panax ginseng Meyer, Panax notoginseng Chen., Panax pseudoginseng Wall., Panax guinguefolium L. and mixtures thereof;

(II) an extract from at least one plant of the Moringa genus comprising saponins, wherein said at least one plant of the Moringa genus belongs to the species selected in the group comprising or, alternatively, consisting of Moringa oieifera Lam, Moringa peregrina Fiore and the mixtures thereof;

(III) rutin; and, optionally,

(ii) at least one food grade or pharmaceutical additive and/or excipient.

FR2. A composition according to FR1 , wherein said (I) extract from at least one plant of the Panax genus is an extract of Panax ginseng Meyer; preferably an extract of Panax ginseng Meyer roots comprising ginsenoside in a range comprised between 1% and 30% by weight, preferably between 5% and 15%, with respect to the total weight of said extract (I).

FR3. A composition according to any one of FR 1-2, wherein said (II) extract from at least one plant of the Moringa genus is an extract of Moringa oieifera Lam; preferably an extract of Moringa oieifera Lam seeds comprising saponins in a range comprised between 10% and 50% by weight, preferably between 15% and 25%, with respect to the total weight of said extract (II).

FR4. A composition according to any one of FR 1-3, wherein said composition comprises:

- ginsenoside from said (I) extract from a plant of the Panax genus, preferably Panax ginseng Meyer, at an amount comprised between 5 mg and 100 mg, preferably between 25 mg and 75 mg;

- saponins from said (II) extract from a plant of the Moringa genus, preferably Moringa oieifera Lam, at an amount comprised between 5 mg and 80 mg, preferably between 25 mg and 55 mg; and

- rutin at an amount comprised between 5 mg and 100 mg, preferably between 25 mg and 75 mg.

FR5. A composition according to any one of FR 1-4, wherein the composition is in a formulation for oral use, wherein said formulation comprises: - said (I) extract from at least one plant of the Panax genus comprising ginsenosides formulated according to a first immediate release formulation;

- said (II) extract from a plant of the Moringa genus comprising saponins formulated according to a second delayed release formulation; and/or

- (Ill) rutin formulated according to a third intermediate release formulation.

FR6. A composition according to FR5, wherein the composition is in solid form comprising:

- a first layer comprising or, alternatively, consisting of said (I) extract from at least one plant of the Panax genus comprising ginsenosides formulated according to said first immediate release formulation, preferably said (I) extract is a dry extract of Panax ginseng Meyer roots;

- a second layer comprising or, alternatively, consisting of said (II) extract from a plant of the Moringa genus comprising saponins formulated according to said second delayed release formulation, preferably said (II) extract is a dry extract of Moringa oleifera Lam seeds; and

- a third layer comprising or, alternatively, consisting of (III) rutin formulated according to said third intermediate release formulation.

FR7. A composition according to FR6, wherein the composition in solid form is a tablet.

FR8. The composition according to any one of FR 1-7, wherein said composition is for use in a method for the preventive and/or curative treatment of a disease, symptom and/or disorder related with a male sexual dysfunction in a needy subject.

FR9. The composition according to FR8, wherein said male sexual dysfunction is selected from among erectile dysfunction, a problem to the endothelial microcirculation of the male genital organ, and low or lack of male sexual drive or libido.

FR10. Non-therapeutic use of the composition according to any one of FR1 to FR7, wherein said use is for non-therapeutic treatment of a male sexual dysfunction and/or a disorder related therewith or for the improvement of male sexual functions, in a needy subject; preferably said male sexual dysfunction is selected from among an erectile dysfunction, a problem to the endothelial microcirculation of the male genital organ and low or lack of male sexual drive or libido.

EXPERIMENTAL PART MATERIAL - Composition 1 (according to the invention) is a composition for oral use in solid form of a tablet (abbreviated as tab) comprising three layers as indicated in Table 1.

Table 1

METHODOLOGY

The clinical study (Figure 1):

- multicentre, randomised, double-blind, placebo-controlled study.

- Recruitment: 78 subjects aged between 18 and 69 years diagnosed with mild to moderate erectile dysfunction (in short, ED).

- Evaluated Parameters: the efficacy of the treatment will be evaluated based on questionnaires aimed at investigating sexual function before and after the therapy and by means of a marker found in the blood, platelet cGMP, measured before and after the therapy.

- Duration of the trial: 3 months.

The composition 1 (indicated in Table 1) was evaluated in said clinical study, with the primary objective of evaluating the efficacy of the composition of the invention combined with a drug for male-related sexual dysfunctions, in particular a drug belonging to the category of phosphodiesterase-5 (PDE-5) inhibitors. Tadalafil 5 mg was used in this study. The drug (Tadafil) was taken daily with a dose of 5 mg once a day (OAD).

Patients were divided into two groups. The first group (Group A) took Tadafil (5 mg) OAD and the nutraceutical composition according to the present invention (Composition 1), the second group (Group B) took Tadalafil 5 mg OAD, associated with placebo.

Treatment:

Group A: Tadalafil 5 mg 1 tab / day + Composition 1 (according to Table 1) 1 tab / day, before bedtime for 3 months.

Group B: Tadalafil 5 mg 1 tab / day + Placebo 1 tab / day, before bedtime for 3 months. The evaluation was conducted in patients suffering from organic aetiology Erectile Dysfunction, through the IIEF-EF questionnaire (questionnaire consisting of 6 questions with score varying from 0 to 30, used to evaluate the erectile function - see Annex) at baseline and after 12 weeks of treatment. The treatment lasted three months.

Platelet cGMP values were also evaluated at baseline and at 12 weeks. Platelet cGMP represents an indirect and objective measure of phosphodiesterase inhibition activity and it is not affected by placebo (Mirone V. et al, Platelet cyclic guanosine monophophosphate as a biomarker of phosphodiesterase type 5 inhibitor efficiency in the treatment of erectile dysfunction: A randomized placebo-controlled study. Eur Urol. 2009 Dec;56(6):1067-73).

The multicentre, randomised, double-blind, placebo-controlled clinical study was conducted at the Urology Department of University of Naples Federico II and the Urology Department of University of Campania Luigi Vanvitelli. 78 sexually active patients aged between 18 and 69 with stable relationship since at least 3 months were recruited to general Urology and Andrology clinics, diagnosed with mild to moderate ED (IIEF-EF > 10 < 26) since at least 6 months and suffering from essential arterial hypertension under pharmacological treatment with ACE inhibitors, beta-blockers or calcium channel blockers and/or suffering from type 2 diabetes mellitus on oral blood glucose lowering therapy. All patients included in the study suffered from hypertension and/or diabetes (patients difficult to treat).

All patients suffering from ED secondary to endocrine disorders, premature ejaculation, pelvic surgery, anatomical anomalies of the penis, moderate or severe renal and/or hepatic impairment, history of cardiovascular diseases, myocardial infarction, stroke, unstable angina and heart failure in the previous 6 months, intake of nitroderivatives, hypertension treated with drugs that do not meet the inclusion criteria, diabetes mellitus under insulin therapy, dyslipidaemia under pharmacological treatment and medullary lesions were excluded.

All patients were shown the study protocol and required to sign an informed consent form in order to be admitted to the study protocol at the baseline visit. Prior to initiation of treatment, all patients filled out the IIEF questionnaire and had their blood collected (conducted by a nurse at the respective centre) with evaluation of blood count, biochemistry, total and free testosterone, prolactin and platelet cGMP collection. Patient diaries were delivered for evaluation of possible adverse events. A number of supplement and/or placebo boxes sufficient to cover the demand of the three subsequent months were delivered and Tadalafil 5 mg to be taken daily was prescribed. All patients were contacted by phone at 4 and 8 weeks after initiation of treatment. Out of the 78 recruited patients, 2 subsequently withdrew from the study. Patients were divided into 2 groups: treatment group 45 patients (GROUP A), placebo group 33 patients (GROUP B).

The entire study had a duration of 12 weeks of treatment at the end of which patients returned to the clinics at their centres where the same nurse from the baseline visit repeated blood collection for clinical chemistry with the aim of evaluating: blood count, biochemistry, total and free testosterone, prolactin, platelet cGMP collection, handing back the patient diary, adverse event recording, filling out the IIEF questionnaire.

The primary analysis was the evaluation of the primary endpoint, i.e. the difference in the IIEF-EF score at baseline visit and after 12 weeks. The statistical analysis was conducted using an analysis of covariance (ANCOVA) with treatment and centre as independent factors, the IIEF-EF baseline score as covariate and the variation with respect to the baseline as a dependent variable. The final analysis used the Pampallona- Tsiatis sequential design with allocation of O'Brien-Fleming of the type I and II error level.

The analyses were conducted both on the intention to treat (ITT) and protocol (PP) populations. ITT results were considered to be the main ones, while the protocol population was analysed with the aim of ensuring that protocol violations/deviations and drop-outs did not affect the results. All calculations were conducted using SAS version 9.4 procedures.

The secondary efficacy variables were analysed applying the same statistical approach used for the primary endpoint analysis (ANCOVA) when the statistical analysis regarded continuous variables (differences from baseline at week 12) and using the Cochran-Mantel-Haenszel (CMH) test when the statistical analysis concerned response proportions.

Results

- Table 2 shows the epidemiological characteristics of the two groups; all values indicated in table 2 are intended prior to the study. The two populations are homogeneous. The mean age of group A is: 60.15 (+/- 7.11); group B: 60.64 (+/- 8.16).

The prevalence of diabetes and hypertension is similar in the two groups and matches the prevalence data known in the general population of the same mean age.

The IIEF baseline (IIEF-pre) of the two groups was 13.18 (+/- 3.75) and 14.15 (+/- 4.09), respectively.

i Total testosterone ! 526.04 ± 128.49 ! 481.97 ± 139.1 1 i

I FSH I 6.48 ± 1.96 | 6.16 ± 2.09 |

I LH I 6.13 ± 2.72 | 4.93 ± 2.72 |

I PRL I 1 1.43± 8.32 | 12.1 1 ± 4.90 |

Table 2: FHS: follicle stimulating hormone; LH plasma luteinizing hormone; PRL prolactin

The efficacy of treatment was evaluated based on the questionnaires which will examine sexual function before and after therapy.

The results of the I IEF questionnaire of Group A and of Group B are shown in Figure 2 and Table 3.

Table 3

The combination of Tadanafil 5 mg with Composition 1 according to the invention resulted in a statistically significant increase in II EF-posi with respect to the IIEF- pre evaluation thereof (+7.3 points, pO.0001 ) as shown in Figure 2 and Table 3.

As observable from the data indicated in Table 3 and Figure 2, the Composition 1 according to the invention based on rutin, ginseng and moringa proved a significant efficacy in increasing and supporting the scores regarding ED domains of IIEF. In addition, no significant adverse events were observed in group A with respect to group B; no significant change in testosterone, FSH, LH or prolactin after treatment was observed in group A; no impairment of blood glucose, cholesterol, GOT, GPT and GGT after treatment was observed in group A.

Claims

1. A composition comprising

(i) a mixture comprising, or alternatively, consisting of:

(II) an extract from at least one plant of the Moringa genus comprising saponins, wherein said at least one plant of the Moringa genus belongs to the species selected from among the group comprising or, alternatively, consisting of Moringa oleifera Lam, Moringa peregrina Fiore and the mixtures thereof; and

(III) rutin; and, optionally,

(ii) at least one food grade or pharmaceutical additive and/or excipient.

2. A composition according to composition 1, wherein said composition comprises

(i) a mixture comprising, or alternatively, consisting of:

(I) an extract from at least one plant of the Panax genus comprising ginsenosides at a by weight % comprised in a range from 1% to 30% with respect to the total weight of said extract (I), wherein said at least one plant of the Panax genus belongs to a species selected from among the group comprising or, alternatively, consisting of Panax ginseng Meyer, Panax notoginseng Chen., Panax pseudoginseng Wall., Panax guinguefolium L. and the mixtures thereof;

(II) an extract from at least one plant of the Moringa genus comprising saponins at a by weight % comprised in the range from 10% to 50% with respect to the total weight of said extract (I), wherein said at least one plant of the Moringa genus belongs to the species selected from among the group comprising or, alternatively, consisting of Moringa oleifera Lam, Moringa peregrina Fiore and the mixtures thereof;

(III) rutin; and, optionally,

(ii) at least one food grade or pharmaceutical additive and/or excipient.

3. The composition according to composition 1, wherein said composition comprises

(i) a mixture comprising, or alternatively, consisting of:

(I) an extract from a plant of the Panax ginseng Meyer species comprising ginsenosides;

(II) an extract from a plant of the Moringa oleifera Lam species comprising saponins; and (III) rutin; and, optionally,

(ii) at least one food grade or pharmaceutical additive and/or excipient.

4. A composition according to any one of compositions 1 to 3, wherein said composition comprises

(i) a mixture comprising, or alternatively, consisting of:

(I) an extract from a plant of the Panax ginseng Meyer species comprising ginsenosides at a by weight % comprised in a range from 1 % to 30% with respect to the total weight of said extract (I), preferably from 5% to 15%, more preferably 10%;

(II) an extract from a plant of the Moringa oleifera Lam species comprising saponins at a by weight % comprised in a range from 10% to 50% with respect to the total weight of said extract

(II), preferably from 15% to 25%, more preferably 20%;

and

(III) rutin; and, optionally,

(ii) at least one food grade or pharmaceutical additive and/or excipient.

5. A composition according to any one of the preceding claims, wherein said composition is in solid form.

6. A composition according to any one of the preceding claims, wherein said composition comprises:

- saponins from said (II) extract from a plant of the Moringa genus, preferably Moringa oleifera Lam, at an amount comprised between 5 mg and 80 mg, preferably between 25 mg and 55 mg; and

7. A composition according to any one of the preceding claims, wherein the composition is in a formulation for oral use, wherein said formulation comprises:

- said (I) extract from at least one plant of the Panax genus comprising ginsenosides formulated according to a first immediate release formulation;

- (Ill) rutin formulated according to a third intermediate release formulation.

8. A composition according to claim 7, wherein the composition is in solid form comprising: - a first layer comprising or, alternatively, consisting of said (I) extract from at least one plant of the Panax genus comprising ginsenosides formulated according to said first immediate release formulation, preferably said (I) extract is a dry extract of Panax ginseng Meyer roots;

9. The composition according to any one of claims 1 to 8 for use as a medicament.

10. The composition for use according to claim 9, wherein said composition is for use in a method for the preventive and/or curative treatment of a male sexual dysfunction in a needy subject.

11. The composition for use according to claim 9, wherein said male sexual dysfunction is selected from among an erectile dysfunction and a microcirculatory endothelial dysfunction of the male genital organ, preferably microcirculatory endothelial trophism of the male genital organ.

12. The composition for use according to any one of claims 9 to 11, said composition being for use as a vasodilator and/or stimulant of testosterone hormone.

13. A composition for use according to any one of claims 9 to 12, said composition being for use as an adjuvant to a drug for the treatment of erectile dysfunctions.

14. A composition for use according to claim 13, said drug for the treatment of erectile dysfunctions being an inhibitor of phosphodiesterase-5 (PDE-5).

15. Non-therapeutic use of the composition according to any one of claims 1 to 8, wherein said use is for a non-therapeutic treatment of a low or lack of male sexual drive or libido.