Nutraceutical compositions and their use in the prevention and / or treatment of erectile dysfunction and / or benign prostatic hyperplasia.

Abstract

The invention relates to a nutraceutical composition for use in the prevention or treatment of erectile dysfunction and / or benign prostatic hyperplasia in men, which nutraceutical composition is in a form suitable for oral administration and comprises as active agent, a combination consisting of: a) 33% to 53% w / p combination of a lipidosterolic extract of the fruit of saw palmetto, b) 33% to 53% w / p combination of a plant extract containing at least 30% w / p plant extract in oligo-proanthocyanidins (OPC), c) 3% to 23% w / p combination of an extract of saffron stigma, the sum of (a), (b) and (c) being equal to 100% w / p combination.

Description

Title of the invention: Nutraceutical compositions and their use in the prevention and / or treatment of erectile dysfunction and / or benign prostatic hyperplasia. Technical field.

[0001] The present invention relates to the technical field of erectile dysfunction and benign prostatic hyperplasia (BPH), more particularly to nutraceutical compositions and their use in the prevention and / or treatment of erectile dysfunction and / or BPH. State of the art.

[0002] Erectile dysfunction, also known as "sexual impotence" or "erectile dysfunction," refers to a persistent or recurring inability to achieve or maintain an erection suitable for sexual intercourse. Erectile dysfunction can cause significant emotional distress, negatively affecting intimate relationships, self-esteem, and overall quality of life. From a physiological perspective, erection is essentially a "vascular" phenomenon, requiring the proper functioning of the blood vessels that supply the penis. In fact, erection occurs when the corpora cavernosa, two spongy structures that run the length of the penis, become engorged with blood. Following sexual stimulation, nitric oxide (NO) is released into the endothelial cells of the arteries supplying the penis, increasing blood flow into these corpora cavernosa.At the same time, the pressure that builds up in the corpora cavernosa compresses the veins that normally drain blood, blocking its flow and maintaining the engorgement necessary for sexual intercourse. NO thus plays a key role in triggering and establishing erection by relaxing the smooth muscle fibers of the corpora cavernosa. The alteration of cavernous endothelial cells results in a decrease in the production of nitric oxide (NO), reducing vascular relaxation. Furthermore, an increase in oxidative stress, characterized by a relative increase in reactive oxygen species (ROS), can decrease the bioavailability of NO, leading to endothelial dysfunction. Various previous studies have shown a significant association between the production of reactive oxygen species (ROS) and erectile dysfunction.Thus, it would be desirable to have new active ingredients capable of stimulating the production of NO, and / or limiting its degradation and / or strengthening the body's antioxidant capacities, in order to prevent and / or treat erectile dysfunction.

[0003] Benign prostatic hyperplasia (BPH) is a benign condition characterized by an increase in the size of the prostate. As a reminder, the prostate is a male sex gland that secretes fluids that make up semen. This gland is located under the bladder and surrounds the upper part of the urethra (the urethral canal) where it joins the bladder. The urethral canal, which passes through the prostate, can be compressed or blocked when the prostate is large. On the other hand, the bladder, which rests on the prostate, can be irritated by the same changes in the prostate. Generally, the symptoms of BPH are: difficulty urinating, pain or burning during urination (the act of urinating), increased frequency of urination, loss of force of the urine stream. These symptoms can coexist and generally affect the quality of life of the men affected by them as well as their psychological well-being.As we age, the prostate naturally increases in size. From the age of 60, approximately 30% of men suffer from BPH. The precise causes of BPH are not yet clearly understood. In addition to age, it is believed that oxidative stress and hormones, particularly high testosterone levels, may play a role in the development of this condition.

[0004] Erectile dysfunction and BPH are distinct conditions. They are both induced by aging, affecting a large number of men over 50. Furthermore, BPH can lead to erectile dysfunction.

[0005] BPH is generally treated by taking medications aimed at limiting the growth of the prostate such as: - Alpha-blockers (alpha adrenergic receptor antagonists) such as tamsulosin, alfuzosin or silodosin. They act by relaxing the smooth muscle fibers of the prostate. Although their action is rapid and stable over several years, they have significant side effects such as dizziness and headaches, and - 5-alpha-reductase inhibitors (e.g., finasteride). They block the conversion of testosterone into dihydrotestosterone (DHT), which is the active metabolite in prostate growth. Their effectiveness has been demonstrated in reducing prostate volume and improving flow. However, they can cause sexual problems such as erectile and ejaculatory disorders or a decrease in libido.

[0006] Regarding erectile dysfunction, several drug treatments are available such as phosphodiesterase type 5 inhibitors (e.g. sildenafil Viagra® and tadalafil Cialis®), but these drugs only offer temporary benefits and can cause minor to serious side effects such as nausea, headache, dizziness and visual disturbances.

[0007] Plant extracts are also proposed for the treatment of BPH or erectile dysfunction, namely saw palmetto extract (Serenoa repens) marketed in France under the brand name Permixon® and which is recommended for the treatment of BPH and saffron extract (Crocus sativus) which is suggested for the treatment of certain symptoms of erectile dysfunction (notably mood, depression).

[0008] However, to the Applicant's knowledge and without disparaging current knowledge, there is currently no satisfactory treatment for treating erectile dysfunction as well as BPH.

[0009] It is known that treatment with tadalafil (Cialis®) is also indicated in patients with signs of BPH and erectile dysfunction. However, as noted above, this treatment is not without side effects.

[0010] The main objective of the invention is to remedy this state of affairs. Also, one aim of the present invention is to provide nutraceutical compositions based on plant extracts and useful for the prevention and / or treatment of BPH and erectile dysfunction. Another aim of the present invention is to provide such nutraceutical compositions which are well tolerated by people showing signs of BPH and erectile dysfunction. Another aim of the present invention is to provide such nutraceutical compositions which make it possible to maintain and / or strengthen the antioxidant capacities of the body. Yet another aim of the present invention is to provide such nutraceutical compositions which are inexpensive and industrially easy to obtain. Presentation of the invention.

[0011] The solution proposed by the invention is a nutraceutical composition for use in the prevention and / or treatment of erectile dysfunction and / or benign prostatic hyperplasia (BPH). This nutraceutical composition is remarkable in that it is presented in a form suitable for oral administration and in that it comprises, as active agent, a combination consisting of: a) 33% to 53% w / w combination of a lipido-sterolic extract of the fruit of saw palmetto, b) 33% to 53% w / w combination of a plant extract containing at least 30% w / w plant extract in oligo-proanthocyanidins (OPC), c) 3% to 23% w / w combination of a saffron stigma extract, the sum of (a), (b) and (c) being equal to 100% w / w combination-

[0012] In this context, the Applicant has discovered, surprisingly and unexpectedly, that an oral nutraceutical composition comprising the combination of ingredients a) to c) presented above is effective on erectile dysfunction as well as on BPH.

[0013] Indeed, this nutraceutical composition is capable of alleviating the urination difficulties caused by BPH. In particular, it improves urinary flow and reduces the need to urinate frequently.

[0014] The nutraceutical composition according to the invention is also capable of preventing and treating the signs of erectile dysfunction, in particular the persistent inability to obtain or maintain an erection with a rigidity suitable for sexual intercourse. It helps to stimulate erection by increasing blood circulation and increasing the production of nitric oxide (NO). This is a compound that helps to dilate blood vessels, particularly in the penis, and to improve and / or support erection.

[0015] In addition, the nutraceutical composition according to the invention has good antioxidant power. It protects cells and blood vessels against oxidative stress by inhibiting free radicals (reactive oxygen species (ROS) produced by normal cellular metabolism). It is capable of inducing antioxidant enzymes such as glutathione peroxidase, catalase and superoxide dismutase, which decompose hydroperoxides, hydrogen peroxide and superoxide anions respectively.

[0016] Furthermore, the combination of active ingredients according to the invention and the nutraceutical composition containing it are remarkably well tolerated from a clinical point of view. They are also inexpensive, being based on products derived from plants, inexpensive and available on the market or simple to produce according to methods known to those skilled in the art.

[0017] To the Applicant's knowledge, there is currently no association containing an extract of Saffron stigma (Crocus sativus Lp), a lipido-sterolic extract of saw palmetto fruit (Serenoa repens) and a plant extract containing at least 30% in w / p plant extract in oligo-proanthocyanidins (OPC), in the proportions defined above, and even less its use for preventing and / or treating erectile dysfunction and / or BPH.

[0018] Other advantageous characteristics of the invention are listed below. Each of these characteristics can be considered alone or in combination with the remarkable characteristics defined above, and be the subject, where appropriate, of one or more divisional patent applications:

[0019] Preferably, the saffron stigma extract comprises, by weight relative to the total weight of said extract: - at least 0.2% safranal, and - at least 3% crocin.

[0020] The plant extract containing at least 30% in w / w plant extract in oligo-proanthocyanidin s OPC can be a plant extract chosen from the group consisting of an extract of apples, grape seed extract, black plum extract, pine bark extract, cinnamon extract, cocoa extract, blackcurrant extract, blueberry extract, cranberry extract, tea extract, aronia berry extract, strawberry extract, and mixtures thereof.

[0021] Preferably, the plant extract containing at least 30% w / w plant extract in oligo-proanthocyanidins OPC is an apple extract.

[0022] Advantageously, the apple extract contains at least 40% w / w Apple extract in polyphenols, of which at least 80%, and preferably more than 95%, are made up of oligo-proanthocyanidins (OPC).

[0023] In preferred embodiments, the nutraceutical composition according to the invention further comprises one or more additional components, including one or more components chosen from vitamins, carotenoids, mineral salts, antioxidants, amino acids, trace elements, antioxidants, plant extracts capable of promoting relaxation and / or reducing stress and / or anxiety, and amino acids.

[0024] In preferred embodiments, the nutraceutical composition according to the invention further comprises one or more suitable excipients.

[0025] In preferred embodiments, the nutraceutical composition according to the invention is in solid or liquid form, in particular, in the form of powders, chewable tablets, effervescent tablets, capsules, granules, hard, soft or gelled candies, chewing gums, or oral solutions or suspensions.

[0026] In preferred embodiments, the nutraceutical composition according to the invention can be used as a food supplement.

[0027] Preferably, the nutraceutical composition according to the present invention is formulated in daily doses, each daily dose providing: a) from 80 mg to 120 mg, preferably from 90 mg to 110 mg, of the lipidosterolic extract of saw palmetto fruit, b) from 80 mg to 120 mg, preferably from 90 mg to 110 mg, of the plant extract containing at least 30% w / w plant extract in oligoproanthocyanidins (OPC), c) from 10 mg to 50 mg, preferably from 20 mg to 40 mg, of saffron stigma extract.

[0028] According to another aspect, the present invention relates to a combination which is constituted by: a) 33% to 53% w / w combination of a lipido-sterolic extract of the fruit of saw palmetto, b) 33% to 53% w / w combination of a plant extract containing at least 30% w / w plant extract in oligo-proanthocyanidins (OPC), c) 3% to 23% w / w combination of a saffron stigma extract, the sum of (a), (b) and (c) being equal to 100% p / pcombinaiSOn-

[0029] According to yet another aspect, the present invention aims at a use of said combination for preparing a food supplement or for enriching a food product or a drink. Description of the embodiments.

[0030] The present description is given without limitation, each characteristic exposed only in one embodiment being able to be generalized to the other embodiments. Similarly, one or more characteristics exposed only in one embodiment can be combined with one or more other characteristics exposed only in another embodiment.

[0031] Definitions

[0032] By the term "prevent" we mean reducing the risk of the onset of erectile dysfunction or symptoms of BPH.

[0033] The term "treat" also means preventing, reducing or slowing down the appearance of the signs of erectile dysfunction and / or the symptoms of BPH, and in particular, improving urinary flow and / or reducing the need to urinate frequently; and / or stimulating, improving or supporting erection, and / or increasing blood circulation, and / or stimulating or supporting the production of nitric oxide (NO); and, more generally, improving the well-being, mood and urinary comfort and / or sexual function of the subject presenting with the conditions of BPH and / or erectile dysfunction.

[0034] The term “nutritional product” designates all products having a nutritional and / or physiological effect, this includes in particular, food supplements, foods, dietetic products, etc.

[0035] The term "nutraceutical" refers to a substance or material, whether a whole food or a component of a food, designed to be consumed by a subject and capable of conferring health benefits. Dietary supplements and natural health products are examples of nutraceuticals.

[0036] The term "nutraceutical composition" refers to a composition whose purpose is to supplement the normal diet and to constitute a concentrated source of nutrients or other substances having a nutritional or physiological effect, alone or in a mixture.

[0037] The term "dietary supplement" means a product or composition which, when added to food or ingested alone, can provide nutrients or substances having a nutritional or physiological effect (e.g. vitamins, minerals, fatty acids or amino acids, dietary fiber, antioxidants) which are missing or in insufficient quantity in the normal diet of an individual. A dietary supplement may be added to a food before, during or after the preparation of said food. It can also be ingested alone, before, during or after a meal.

[0038] The expression “p / pcombinaiSOn” means that the percentage of the component or ingredient considered is calculated relative to the total weight of the combination according to the invention.

[0039] The expression “p / pcompositiOn” means that the percentage of the component or ingredient considered is calculated relative to the total weight of the composition according to the invention.

[0040] The expression “p / pplant extract” means that the percentage of the component or ingredient considered is calculated relative to the total weight of the plant extract used in the combination according to the invention.

[0041] Combination of active ingredients according to the invention:

[0042] The present invention relates firstly to a combination containing a lipidosterolic extract derived from the fruit of the saw palmetto, a saffron stigma extract and a plant extract rich in oligo-proanthocyanidins (OPC).

[0043] Lipido-sterolic extract:

[0044] The nutraceutical compositions according to the invention contain a lipido-sterolic extract derived from the fruit of the saw palmetto.

[0045] The saw palmetto (Serenoa repens or Sabal serrulata) also known as the saw palmetto is a shrubby palm native to the southeastern regions of North America and particularly abundant in Florida. It produces a hard green fruit (berry) the size of an olive with a large seed. The fruit ripens in summer and is harvested in late summer.

[0046] The fruit of the saw palmetto has long been used by Native Americans for its nutritional, diuretic, sedative, aphrodisiac and antitussive properties.

[0047] Currently, saw palmetto fruit is commonly used in dietary supplements (e.g., PERMIXON®) to improve BPH symptoms, balance hormone levels, and prevent hair loss in men. It acts as a 5-alpha reductase inhibitor. Its benefits are attributed to its phytosterols and fatty acids.

[0048] The lipidosterolic extract used in the context of the present invention is rich in fatty acids (in particular: oleic, lauric, myristic, linoleic, linolenic, palmitic, caprylic and capric acids) and contains phytosterols. It is preferably titrated to at least 35% in fatty acid, more preferably to 45% in fatty acid. It can be obtained by methods well known to those skilled in the art (see in particular patent document FR2480754).

[0049] Prevention and / or treatment of BPH and erectile dysfunction are promoted when lipid-steroid extract derived from saw palmetto fruit is present. in the combination according to the present invention at a content ranging from 33% to 53% w / w combination*

[0050] To the knowledge of the Applicant, the use of the lipidosterolic extract of saw palmetto fruit in combination with an extract of saffron stigma (Crocus sativus L.) and the plant extract containing at least 30% in w / p plant extract of oligo-proanthocyanidins (OPC), in the proportions indicated above, to obtain the beneficial effect of prevention and / or treatment of BPH and / or erectile dysfunction, has never been described in the state of the art.

[0051] In preferred embodiments, the amount of lipid-sterolic extract of saw palmetto fruit may range from 40 to 46% w / w combination-

[0052] The incorporation of said lipido-sterolic extract into the nutraceutical combination or composition of the present invention can be carried out by any usual method known in the nutraceutical field.

[0053] Saffron extract:

[0054] The combination according to the present invention advantageously contains an extract of saffron stigma (Crocus sativus L.).

[0055] Saffron is a bulbous plant belonging to the genus Crocus. Saffron (Crocus sativus L.) is native to southern Europe, Asia Minor and the Iranian plateau.

[0056] Since ancient times, saffron has been used as a spice. It is also used as a medicinal plant to improve mood, enhance memory, and increase libido and sexual function in both men and women.

[0057] Saffron has many beneficial biological properties for the body such as antioxidant, anti-inflammatory, antiatherogenic, antiapoptotic, and hypolipidemic properties. These benefits are attributed to its bioactive compounds including safranal, crocin, crocetin (carotenoid dicarboxylic acid and precursor of crocin) and picrocrocin, found mainly in the stigma of saffron.

[0058] The present invention exploits the synergy of the bioactive compounds present in the saffron stigma extract and in the other extracts of the combination according to the invention. By taking advantage of their respective biological properties, the present invention provides nutraceutical compositions offering an effective dual action against erectile dysfunction and BPH.

[0059] The saffron stigma extract used in the context of the present invention comprises safranal, crocin, crocetin and picrocrocin. Preferably, the saffron stigma extract used is titrated, by weight relative to the total weight of the stigma extract, to at least 0.2% safranal, and at least 3% crocin.

[0060] As a reminder, the pistil is the set of female reproductive organs of a flower, including the saffron flower. It includes the ovary, the style and the stigma. The stigma is the receptive end of a carpel, or of several fused carpels forming the pistil of a flower. Its main function is to capture pollen grains for fertilization.

[0061] The saffron stigma extract used can be extracted from saffron (stigma) by any method known to those skilled in the art (see in particular CN108542840A, the article by Nerome azuki et al.: “Extraction of phytochemicals from saffron by supercritical carbon dioxide with water and methanol as entrainer, The Journal of Supercritical Fluids”, January 2016, 107:377-383 - DOI: 10.1016 / j.supflu. 2015.10.007). It can also be analyzed by analytical methods such as HPLC (see in particular: the article by E. Masi et al.: PTR-TOF-MS and HPLC analysis in the characterization of saffron (Crocus sativus L) from Italy and Iran, 2016, Food Chemistry 192, 75-81).

[0062] The prevention and / or treatment of BPH and erectile dysfunction are promoted when the saffron stigma extract is present in the combination according to the present invention at a content ranging from 3% to 23% w / w combination-

[0063] To the knowledge of the Applicant, the use of saffron stigma extract in combination with the lipidosterolic extract from the fruit of the saw palmetto and the plant extract rich in oligoproanthocyanidins (OPC), in the proportions indicated above, to obtain the beneficial effect of prevention and / or treatment of BPH and / or erectile dysfunction, has never been described in the state of the art.

[0064] In preferred embodiments, the saffron extract is present in the combination according to the invention in a content ranging from 10 to 16% w / w.

[0065] The incorporation of the saffron stigma extract into the combination according to the invention or into the nutraceutical composition containing it in accordance with the invention can be carried out by any usual method known in the nutraceutical field.

[0066] Plant extract rich in oligo-proanthocyanidins:

[0067] The combination according to the invention and the nutraceutical compositions in accordance with the invention comprise a plant extract rich in oligoproanthocyanidins (OPC).

[0068] Proanthocyanidins, also known as condensed tannins, are compounds belonging to the large family of polyphenols and more precisely to the group of flavonoids. Oligoproanthocyanidins (OPCs) correspond within this group to the great structural diversity, to molecules composed of catechin or epicatechin monomeric units, which are linked either by 4-8 or 4-6 bonds, so that there are a large number of isomeric proanthocyanidins (OPCs). Typically, oligomers of proanthocyanidins have a chain length of 2 to 12 monomer units, for example from 2 to 6 monomers. They are present in many plants such as cinnamon, apple, grape seeds. They are of great interest in nutrition and medicine due to their numerous antioxidant, antibacterial, antiviral, anti-inflammatory, anti-allergic and vasodilatory properties. They help protect the body's cells and tissues against free radicals. They can also promote blood circulation and prevent cardiovascular disorders by inhibiting lipid peroxidation and platelet aggregation. Studies have reported that oligomeric proanthocyanidins (OPCs) can increase endogenous nitric oxide production (see especially the article by Xiaopei Cui et al., “Grape Seed Proanthocyanidin Extracts Enhance Enodthelial Nitric Oxide Synthase Expression,” Biological & Pharmaceutical Bulletin, 2012, 35(12):2192-2197. DOI: 10.1248 / bpb.b 12-00598).

[0069] The present invention takes advantage of the various effects, in particular antioxidant, anti-inflammatory, vasodilatory, anti-platelet aggregation actions, and stimulation of the production of NO, of oligo-proanthocyanidins on the body, and also of the effects of the other extracts present in the combination according to the invention to offer nutraceutical compositions effective on both erectile dysfunction and BPH.

[0070] In this context, the plant extract used contains at least 30% by weight of the plant extract of oligo-proanthocyanidins. It is advantageously titrated to more than 80% by weight of the plant extract, preferably to more than 95% by weight of the plant extract, in oligo-proanthocyanidins.

[0071] The plant extract rich in oligo-proanthocyanidins can be chosen from the group consisting of an apple extract, a grape seed extract, a black plum extract, a pine bark extract, a cinnamon extract, a cocoa extract, a blackcurrant extract, a blueberry extract, a cranberry extract, a tea extract, an aronia berry extract, a strawberry extract, and mixtures thereof. Apple extract is a preferred plant extract according to the present invention.

[0072] Advantageously, the apple extract contains at least 40% w / w apple extract in polyphenols, among which at least 80%, and preferably more than 95%, are made up of oligo-proanthocyanidins (OPC).

[0073] The plant extract rich in oligo-proanthocyanidins (OPC) used contributes to the effectiveness of the nutraceutical compositions according to the invention on erectile dysfunction and also on BPH. It participates in the fight against cellular aging by protecting, for example, endothelial cells from oxidative stress. It contributes to reducing the risk of erectile problems by stimulating, facilitating and / or supporting the activity of endogenous nitric oxide (NO) leading to vasodilation. This vasodilation improves blood circulation and leads to an increase in blood flow. blood, particularly to the tissues of the genital tract. It also helps to inhibit the process of cell proliferation (hyperplasia) of the prostate.

[0074] The prevention and / or treatment of BPH and erectile dysfunction are promoted when the plant extract rich in oligoproanthocyanidins (OPC) is present in the combination according to the present invention at a content ranging from 33 to 53% w / wCOMBINAISON-

[0075] To the knowledge of the Applicant, the use of the plant extract rich in oligo-proanthocyanidins (OPC) in combination with an extract of saffron stigma (Crocus sativus L.) and a lipido-sterolic extract of the fruit of the saw palmetto, in the proportions indicated above, to obtain the beneficial effect of prevention and / or treatment of BPH and / or erectile dysfunction, has never been described in the state of the art.

[0076] In preferred embodiments, the plant extract rich in oligo-proanthocyanidins (OPC) may be present in the combination according to the invention at a rate of 40 to 46% w / w.

[0077] The incorporation of said plant extract rich in oligo-proanthocyanidins (OPC) into the nutraceutical combination or composition of the present invention can be carried out by any usual method known in the nutraceutical field.

[0078] A preferred combination according to the invention consists of: a) 33% to 53% w / w combination of a lipido-sterolic extract of saw palmetto fruit, b) 33% to 53% w / w combination of a plant extract containing at least 30% w / w plant extract in oligo-proanthocyanidins (OPC), c) 3% to 23% w / w combination of a saffron stigma extract, the sum of (a), (b) and (c) being equal to 100% w / w

[0079] Another example of a preferred combination according to the invention consists of: a') 40% to 46% w / w combination of a lipido-sterolic extract of the fruit of saw palmetto, b') 40% to 46% w / w combination of a plant extract containing at least 30% w / w plant extract in oligo-proanthocyanidins (OPC), c') 10% to 16% w / w combination of a saffron stigma extract, the sum of (a'), (b') and (c') being equal to 100% w / w combination-

[0080] Nutraceutical composition:

[0081] The combination according to the invention can be integrated into a nutraceutical composition or used as such as a nutraceutical composition. Hereinafter, the expressions "nutraceutical composition" and "combination" are sometimes used interchangeably.

[0082] Also, the present invention also relates to a nutraceutical composition comprising the components of the combination according to the invention, and optionally, one or more additional components and / or one or more suitable excipients.

[0083] Advantageously, the nutraceutical composition in accordance with the invention is presented in a form suitable for oral administration.

[0084] A preferred nutraceutical composition according to the invention, intended for oral administration, comprises a combination which consists of: a) 33 to 53% w / p combination of a lipidosterolic extract of the fruit of saw palmetto, b) 33 to 53% w / p combination of a plant extract containing at least 30% w / p plant extract in oligo-proanthocyanidins (OPC), c) 3 to 23% w / p combination of a saffron stigma extract, the sum of (a), (b) and (c) being equal to 100% w / p

[0085] Another example of a preferred nutraceutical composition according to the invention intended for oral administration comprises a combination which consists of: a') 40% to 46% w / pcombination of a lipidosterolic extract of the fruit of saw palmetto, b') 40% to 46% w / pcombination of a plant extract containing at least 30% w / p plant extract in oligo-proanthocyanidins (OPC), c') 10% to 16% w / pcombination of a saffron stigma extract, the sum of (a'), (b') and (c') being equal to 100% w / pcombination-

[0086] According to another preferred example according to the invention, the nutraceutical composition is formulated in daily doses, each daily dose providing: a) from 80 mg to 120 mg, preferably from 90 mg to 110 mg, of the lipidosterolic extract of saw palmetto fruit, b) from 80 mg to 120 mg, preferably from 90 mg to 110 mg, of the plant extract (from apples) containing at least 30% w / w plant extract oligo-proanthocyanidins (OPC), c) from 10 mg to 50 mg, preferably from 20 mg to 40 mg, of saffron stigma extract.

[0087] In the context of the present invention, the term "daily dose" represents the quantity of composition according to the invention administered per day. The daily dose may be taken in one or more unit doses. Advantageously, a unit dose according to the present invention may correspond, for example, to a capsule of conventional size, to a tablet of conventional weight (e.g.: approximately 500 mg) or to a yogurt of conventional volume (e.g.: 125 ml). Thus, whatever the weight of the nutraceutical composition, the quantity of ingredients of the combination per unit dose remains constant.

[0088] The amount of the combination according to the invention in the nutraceutical composition according to the invention can vary within wide limits, for example, from about 10% to about 95% or more, by weight relative to the total weight of the nutraceutical composition.

[0089] In addition to the lipidosterolic extract of the saw palmetto fruit, the plant extract rich in OPC and the saffron stigma extract, the nutraceutical composition according to the invention may also contain one or more excipients (or vehicles) suitable for oral administration.

[0090] By "excipient" is traditionally meant any compound or composition intended to act as a simple support or vehicle, that is to say which is not intended to have a physiological or biological activity. As examples of excipients or vehicles, mention may be made, but are not limited to, diluents, binders, lubricants, dispersants, antioxidants, disintegrants, anti-caking agents, colorants, preservatives, coating agents, humectants, flavoring agents (e.g. orange, cherry, vanilla, strawberry, lemon, mint, or other flavorings). Of course, a person skilled in the art will take care to choose the possible compounds or compositions of excipients as well as their proportions in such a way that the advantageous properties of the combination according to the invention or of the nutraceutical composition containing it in accordance with the invention are not or are not substantially altered by the envisaged addition.Excipients are well known in the nutraceutical field and are not described in detail here. Suitable excipients or vehicles are also described in the book "Handbook of Pharmaceutical Excipients," Second Edition, American Pharmaceutical Association, 1994.

[0091] For the purposes of the present invention, the term "suitable" means that the excipient(s) are compatible with nutraceutical or food use of the composition in accordance with the invention, i.e. they are not toxic to humans when used in a nutraceutical composition.

[0092] In preferred embodiments, the nutraceutical composition according to the invention may further comprise one or more additional components capable of promoting a complementary and / or synergistic action. The additional components may be selected from vitamins (e.g. one or more vitamins A, B, C, D, E and / or K), mineral salts and / or trace elements (e.g. selenium, zinc, magnesium), antioxidant agents (e.g. carotenoids and / or polyphenols other than the OPC-rich extract), one or more plant extracts capable of promoting relaxation and / or reducing stress and / or anxiety (e.g. passionflower, black horehound, hawthorn, lemon balm), amino acids (e.g. glutamine, aspartic acid, arginine, lysine), and mixtures thereof.

[0093] The concentration, in the nutraceutical composition according to the invention, of the possible additional component(s) may vary within wide limits. Of course, those skilled in the art will take care to choose the possible additional compounds and / or their quantities, in such a way that the advantageous properties of the nutraceutical composition are not, or not substantially, altered by the envisaged addition. For example, the additional component(s) may be used in a content of between 0.001% and 30% by weight relative to the total weight of the nutraceutical composition.

[0094] Process - galenic - applications:

[0095] The combination according to the invention and the nutraceutical composition containing it in accordance with the invention can be obtained by any usual formulation method known in the nutraceutical field. Their respective ingredients can be mixed, before shaping, in the order and under conditions easily determined by those skilled in the art.

[0096] In practice, before galenic formulation for oral administration, the combination according to the invention and the nutraceutical composition containing it in accordance with the invention, are in the form of anhydrous powder (particle size less than 1000 μm, preferably less than 500 μm, preferentially less than 250 μm) (water content less than 10%, preferentially less than 2.5% by weight relative to the weight of the powder). In certain preferred embodiments, the saffron stigma extract used is in the form coated or encapsulated in a coating or coating agent (e.g.: maltodextrin).

[0097] The nutraceutical composition (or combination) according to the invention makes it possible, by its oral administration, to prevent and / or treat erectile dysfunction as well as BPH in men. In particular, it makes it possible to improve urinary flow and / or reduce the need to urinate frequently; and also to stimulate and / or improve and / or support erection, and / or increase blood circulation and / or stimulate and / or support the production of nitric oxide (NO); and, more generally, to improve the well-being, mood and urinary comfort and sexual function of the subject presenting BPH and / or erectile dysfunction.

[0098] The combination, the nutraceutical composition and their use are thus of particular interest in the nutraceutical, nutritional and food fields.

[0099] The present invention does not relate to the therapeutic field.

[0100] The nutraceutical compositions (or the combination) according to the invention may be nutritional or food compositions. They are in particular suitable for oral administration (including buccal and sublingual) with or without suitable excipient(s). They may be formulated for administration to a subject (male human). In this context, different galenic forms are possible, such as in particular solid and liquid forms (e.g. syrups, gels, emulsions, drinkable ampoules).

[0101] In practice, the nutraceutical compositions (or the combination) according to the invention are presented in solid galenic forms, for example, but not limited to: tablets, lozenges, tablets, optionally coated, orodispersible, film-coated, gastro-resistant and / or modified-release, dragees; soft or hard capsules, gelatin capsules, possibly film-coated and / or gastro-resistant, chewing gums or pastes, confectionery or gummies, powders, in particular compressed powders or loose powders packaged in sachets or unit sticks.

[0102] Such galenic forms can be produced by any usual process known to those skilled in the art.

[0103] Advantageously, the nutraceutical composition (or the combination) according to the invention are in the form of capsules, preferably vegetable capsules. The vegetable capsules can be made simply, in particular with a cellulose-based shell (Hydroxypropylmethylcellulose, or “HPMC”, or even “Hypromellose”). The cellulose can be supplemented with natural colorants, so as to obtain the shell having the desired properties. In particular, said shell can also comprise opacifying agents such as titanium oxide.

[0104] The nutraceutical compositions (or the combination) according to the invention may be contained in a packaging, a wrapper or a dispensing device at the same time as instructions for use. Advantageously, the nutraceutical compositions in the form of tablets or capsules are presented in a sealed packaging, which may consist of a pillbox (e.g.: a pillbox made of polypropylene or high-density polyethylene), a plastic or aluminum bag, or a blister pack, in particular, a blister pack (cell) made of PVC / PVDC, covered with an aluminum film for optimal protection.

[0105] The nutraceutical compositions (or the combination) according to the present invention may be intended for use as a nutritional product.

[0106] A preferred nutraceutical composition (or combination) according to the invention is a food supplement.

[0107] Preferably, the food supplement is intended to be consumed or administered orally, to help a subject (male human) to prevent and / or treat erectile dysfunction and / or BPH in said subject, more particularly to improve urinary flow and / or reduce the need to urinate frequently; and / or to stimulate and / or improve and / or support erection, and / or to increase blood circulation, and / or to stimulate and / or support the production of nitric oxide (NO), and, more generally, to improve the well-being, mood and urinary comfort and sexual function of the subject suffering from BPH and / or erectile dysfunction. As a reminder, NO is a compound that helps to dilate blood vessels, particularly in the penis, and to improve and / or support erection.

[0108] The combination according to the invention or the nutraceutical composition containing it in accordance with the invention can also be used to supplement a diet intended to help a subject (male human) to prevent and / or treat erectile dysfunction and / or BPH in said subject, or to enrich drinks or food products: for example, but not limited to, dairy products such as yogurts; cereals; cereal bars; drinks (e.g. herbal teas) and salads.

[0109] Also, the present invention also relates to a non-therapeutic use, by oral route, of the combination according to the invention or of the composition containing it in accordance with the invention for preventing and / or treating erectile dysfunction and / or BPH in a subject (male human) who needs it.

[0110] It is recalled here that within the framework of the present invention the combination according to the invention or the nutraceutical composition containing it can be used (administered orally) in the form of a food supplement.

[0111] The present invention relates in particular to the use as defined above, in which the combination in accordance with the invention is implemented within a nutraceutical composition suitable for oral administration. The contents vary depending on the form of the nutraceutical composition in which the combination according to the invention is implemented.

[0112] The invention also relates to a method for preventing and / or treating erectile dysfunction and / or BPH. This method comprises the oral administration to a man of a combination according to the invention or of a nutraceutical composition containing it in accordance with the invention.

[0113] The methods according to the invention have the characteristics of non-therapeutic methods insofar as they make it possible to improve the well-being, urinary comfort and sexual function of the subject suffering from BPH and / or erectile dysfunction. In addition, a nutraceutical combination or composition such as, for example, a food supplement according to the invention can be used daily for several months, without a medical prescription. The present invention is therefore clearly outside the therapeutic field.

[0114] Advantageously, the application of a method of the invention confers the advantages indicated previously as being associated with the implementation of a combination according to the invention or of a composition containing it in accordance with the invention.

[0115] The method according to the invention can be implemented by the oral administration of a combination according to the invention or of a nutraceutical composition containing it.

[0116] A method of the invention can be implemented daily with a single administration per day (e.g. morning, midday or evening) or with an administration twice per day (e.g. once in the morning and once in the evening or twice in the morning or twice in the evening). evening), or three times a day (e.g. once in the morning, once at noon and once in the evening) or four times a day (e.g. twice in the morning and twice in the evening).

[0117] A method according to the invention can be implemented, for example by daily administration of a nutraceutical combination or composition formulated in solid form (e.g.: capsules, soft capsules, tablets, capsules, dragees, chewing gums or gummies) or liquid form (e.g.: gels, emulsions, syrups) in adequate quantity and number, depending on their form.

[0118] An effective amount of a combination according to the invention can be administered in a single dose per day or in divided doses over the day (e.g.: two to four times per day).

[0119] The quantity of the combination (active ingredient) according to the invention to be administered, per day, to a subject (male human) to prevent and / or treat erectile dysfunction and / or BPH is as defined above.

[0120] A method according to the invention may advantageously comprise a single administration.

[0121] The method according to the invention can be implemented over a period varying from one week to several weeks, or even several months, this period being able to be repeated after periods of non-treatment, for several months or even several years. By way of example, the administration of a combination in accordance with the invention or of a nutraceutical composition according to the invention can be carried out at a rate of, for example,! or 2 times per day, generally over a prolonged period of at least 4 weeks, or even 4 to 16 weeks, including or not including one or more periods of interruption or being repeated after a period of interruption.

[0122] The combination according to the invention and the compositions in accordance with the invention may in particular comprise all or only part of the daily dose.

[0123] The invention also relates to a kit or a combination product for simultaneous, separate or spread out use over time, preferably a food supplement, comprising a first composition containing a portion of the compounds forming the combination in accordance with the invention and a second composition comprising at least the other portion of the compounds forming the combination in accordance with the invention. This food supplement may be formulated in such a way that the two compositions are in the same forms or in different forms, for example chosen from those mentioned above. Such a kit may in particular be presented in a single package.

[0124] The ingredients are mixed, before being shaped, in the order and under conditions easily determined by those skilled in the art.

[0125] The content and nature of the ingredients used in the combination or nutraceutical compositions containing it in accordance with the invention are adjusted by those skilled in the art so as not to substantially affect the properties required for said combination or said nutraceutical compositions.

[0126] The chemical composition of the various plant and fruit extracts used in the present invention can be determined by any analytical method known in the state of the art (e.g. High Performance Liquid Chromatography coupled with a mass spectrometer (HPLC-MS).

[0127] The particle size of the nutraceutical composition (or its combination) and of each of its ingredients can be measured by any technique known per se, for example by using a laser particle sizer or a series of standardized sieves according to the requirements of the European Pharmacopoeia 2-1-4.

[0128] In the description and examples that follow, the ranges of values ​​labeled in the form "between ... and..." include the specified lower and upper limits.

[0129] Other characteristics and advantages of the invention will emerge more clearly from the following examples, given for illustrative and non-limiting purposes. The scope of the invention should not be limited in any way by these examples. Examples:

[0130] Example 1: Combinations according to the invention

[0131] A combination according to the present invention has been formulated in daily doses from the ingredients indicated in [Table 1] below.

[0132] [Tables 1] Ingredients Quantity (for one daily serving) Lipido-sterolic extract of saw palmetto fruit1 80 mg to 120 mg Plant extract containing oligo-proanthocyanidins (OPC)2 80 mg to 120 mg Saffron stigma extract3 10 mg and 50 mg 1 Extract standardized to at least 45% in fatty acids. 2 Apple extract standardized to 95% in oligo-proanthocyanidins (OPC). 3 In the form coated with maltodextrin.

[0133] The lipidosterolic extract of the fruit of the saw palmetto, the plant extract containing oligo-proanthocyanidins (OPC) and the extract of saffron stigma, are in the form of powders (< 500 pm). They are independently weighed and then mixed in the presence of nitrogen.

[0134] After being mixed in a suitable volume of water, for example 150 ml, the combination according to the invention is administered orally on a daily basis for the prevention and / or treatment of erectile dysfunction and BPH. It is capable of significantly improving sexual function in men showing signs of erectile dysfunction and / or BPH. It is also capable of increasing and / or strengthening antioxidant capacities in men.

[0135] Example 2: Compositions of food supplements presented in the form of capsules

[0136] A vegetable capsule (HPMC) “hereinafter capsule G1” is prepared according to the usual techniques, containing 115 mg of the combination consisting of the lipidosterolic extract from the fruit of the saw palmetto, the plant extract containing oligo-proanthocyanidins (OPC) and the saffron stigma extract, the respective quantities of which are presented in [Table 2] below.

[0137] [Tables2] Ingredients Quantity (mg) per capsule Lipido-sterolic extract of saw palmetto fruit1 50.00 Plant extract containing oligo-proanthocyanidins (OPC)2 50.00 Saffron stigma extract3 15.00 Magnesium carbonate 81.80 Talc 15.00 Magnesium stearate 18.00 1) Extract standardized to at least 45% in fatty acids. 2) Apple extract standardized to 95% in oligo-proanthocyanidins (OPC). 3) In the form coated with maltodextrin

[0138] The G1 capsule can be prepared as follows: the lipidosterolic extract of the saw palmetto fruit, the plant extract containing oligo-proanthocyanidins (OPC) and the saffron stigma extract, and the excipients are in the form of powders (< 500 pm). They are independently weighed and then mixed in the presence of nitrogen. The mixture is then homogenized and then encapsulated in the vegetable capsule (HPMC).

[0139] The G1 capsules can then be packaged in pill boxes and are used (Dosage: 2 capsules / day swallowed with water) as food supplements to prevent and / or treat erectile dysfunction and / or benign prostatic hyperplasia (BPH) in men in accordance with the invention.

Claims

Claims

1. A nutraceutical composition for use in the prevention and / or treatment of erectile dysfunction and / or benign prostatic hyperplasia in men, which nutraceutical composition is in a form suitable for oral administration and comprises as active agent, a combination consisting of: a) 33 to 53% w / w combination of a lipidosterolic extract of saw palmetto fruit, b) 33 to 53% w / w combination of a plant extract containing at least 30% w / w plant extract in oligo-proanthocyanidins (OPC), c) 3 to 23% w / w combination of a saffron stigma extract, the sum of (a), (b) and (c) being equal to 100% w / w Combination-

2. Nutraceutical composition for use according to claim 1, characterized in that the saffron stigma extract comprises, by weight relative to the total weight of said extract: - at least 0.2% of safranal, and - at least 3% of crocin.

3. Nutraceutical composition for use according to claim 1 or 2, characterized in that the plant extract containing at least 30% w / w plant extract in oligo-proanthocyanidins (OPC) is a plant extract selected from the group consisting of an apple extract, a grape seed extract, a black plum extract, a pine bark extract, a cinnamon extract, a cocoa extract, a blackcurrant extract, a blueberry extract, a cranberry extract, a tea extract, an aronia berry extract, a strawberry extract, and mixtures thereof.

4. Nutraceutical composition for use according to any one of claims 1 to 3, characterized in that the plant extract containing at least 30% w / p plant extract oligo-proanthocyanidins (OPC) is an apple extract.

5. Nutraceutical composition for use according to claim 4, characterized in that the apple extract contains at least 40% w / w apple extract in polyphenols, of which at least 80%, and preferably more than 95%, consist of oligo-proanthocyanidins (OPC).

6. Nutraceutical composition for use according to any one of claims 1 to 5, characterized in that it further comprises one or more additional components, including one or more components chosen from vitamins, carotenoids, mineral salts and / or trace elements, antioxidants, plant extracts capable of promoting relaxation and / or reducing stress and / or anxiety, amino acids.

7. Nutraceutical composition for use according to any one of claims 1 to 6 characterized in that it further comprises one or more suitable excipients.

8. Nutraceutical composition for use according to any one of claims 1 to 7, characterized in that it is in solid or liquid form, in particular, in the form of powders, chewable tablets, effervescent tablets, capsules, granules, hard, soft or gelled candies, chewing gums, or oral solutions or suspensions.

9. A nutraceutical composition for use according to any one of claims 1 to 8, which is a dietary supplement.

10. Combination consisting of: a) 33 to 53% w / p combination of a lipidosterolic extract of saw palmetto fruit, b) 33 to 53% w / p combination of a plant extract containing at least 30% w / p plant extract of oligo-proanthocyanidins (OPC), c) 3 to 23% w / p combination of a saffron stigma extract, the sum of (a), (b) and (c) being equal to 100% w / p combination-

11. Use of the combination according to claim 10 for preparing a food supplement or for enriching a food product or a beverage