Description

Technical Field

The present invention relates to a functional food preparation based on dairy products, to which substances of vegetable origin containing various active ingredients are added and which is mainly intended to alleviate problems of the male population in advanced age (over 40 years).

The basic characteristic of the functional food preparation of the invention is a combination of phytocompounds, such as specific alkaloids, phytoestrogens, phytosterols and other substances, in a consumer food product belonging to the category of dairy products.

The functional food preparation of the invention has the object of alleviating, in particular, the problems tied to the male urogenital system. After forty years of age, men enter into a period known as "andropause", a clinical syndrome caused by a decrease in testosterone, the principally male hormone. In men, after forty years of age, this hormone decreases in a slow and gradual manner. It can be defined as a sort of male menopause, with an unclear, hazy profile. Even though they may not be directly associated with the phenomenon of andropause, after forty years of age problems of the urogenital system often arise in men, including bladder problems, urinary disorders, prostatic hypertrophy, prostate tumours and sexual disorders such as low libido or erectile dysfunctions.

Benign Prostatic Hypertrophy (BPH, also called prostatic adenomatosis) consists in an enlargement of the prostate. With increasing age, the central portion of the gland (disposed like a sleeve around the urinary canal) tends to develop in an excessive and disproportionate manner. As a result of the aforesaid enlargement, the urinary canal (urethra) can be compressed and squeezed, as can the peripheral part of the gland. After several years of development, BPH can also reach the dimensions of a grapefruit. Benign Prostatic Hypertrophy is characterized not only by an increase in the frequency of urination during the day and night (pollakiuria and nocturia), but also by a sensation of incomplete emptying and by an intermittent urine stream, eventually developing into acute urinary retention. The causes of BPH are still being studied. Some researchers believe that microtraumas occurring under the stimulus of continuous urination, ejaculations and inflammations release a substance from the prostatic tissues near the urethra which is capable of causing the enlargement of nearby glands. An essential role seems to be played by the hormonal situation that comes to be created with the passing of years. BPH can potentially begin to develop very early, already after 30 years of age, but does not develop in the same way or at the same rate in all subjects. The main symptoms associated with BPH are pollakiuria, nocturia, a sensation of incomplete emptying and an intermittent urine stream, eventually developing into acute urinary retention. The latter becomes a true urological urgency that requires the positioning of a vesical catether in order to empty the bladder. Rectal exploration, transrectal prostate ultrasonography and uroflowmetry are undoubtedly necessary for a correct study of the disease. Pharmacological treatments and therapies of a surgical type exist for BPH. Drugs that are extremely effective in reducing the disorders tied to BPH have been placed on the market in recent years. The therapy for treating Benign Prostatic Hypertrophy relies on the use of alpha-lytic agents and peripheral anti- androgens such as finasteride and dutasteride, which inhibit the growth in volume of the prostatic adenoma, also succeeding in reducing the volume in a good percentage of cases. Use is also made of phytotherapeutic products (vegetable extracts) whose action in some cases is still being studied, but which seem to act upon the inflammatory component.

Erectile dysfunction is the inability of a man to obtain and/or maintain a sufficient erection of the penis, both for his own needs and those of his partner when it comes to managing sexual intercourse. This fact may occur sporadically without inducing psychological or relationship problems, but when it repeats itself a number of times and the erectile defect becomes more significant in terms of quality and/or quantity, this triggers the problems connected to it. Erectile dysfunction frequently induces both emotional and relationship issues and often induces a reduction in self- esteem, which reinforces the dysfunctional processes. The causes are numerous and varied and not always clear or simple to demonstrate or therefore to treat. Moreover, erectile dysfunction is not an inevitable consequence of aging.

The incidence of erectile dysfunction is around 10% in the western population as a whole, but arrives at 50% in the age range between 40 and 70 years.

Numerous studies have demonstrated the effectiveness of substances of vegetable origin in preventing and treating many disorders of the male urogenital system which normally occur with advancing age, above all after forty years.

Alkaloids are organic substances formed from oxygen, hydrogen, carbon and nitrogen, i.e. quaternary. The chemical group of the alkaloids comprises a very ample number of substances that are heterogeneous from a structural viewpoint but have in common an alkaline reactivity and consequent ease of extraction from materials and separation from other constituents. The basic property is due to the presence of a nitrogen- containing functional group. Alkaloids thus represent a functional chemical alternative to numerous substances with acidic reactivity, such as carboxylic acids and phenolic compounds. Alkaloids are endowed with strong pharmacological effects in relation to the intake of small doses of the substance (e.g. caffeine, moφhine, strychnine). Among the plant constituents most studied and used in pharmacology, alkaloids are without a doubt the substances which induce the greatest effects in animal organisms. The known alkaloids amount to over 5,500, distributed in over 4000 plant species. It is estimated that around 20% of species contain alkaloids, where an alkaloid content above 0.1% is considered significant. Some alkaloids, principally indolic alkaloids, have marked aphrodisiac properties; these include yohimbine and muirapuamine, the alkaloids contained in Lepidium meyenii and the 5-methoxy-N,N- dimethyltryptamine contained in Mucuna pruriens. In particular, muirapuamine has the ability to stimulate peripheral vasodilation and increase the production of nitric oxide, as well as exerting an inhibitory action on the alpha-2 receptors which stimulate vascular smooth muscle contraction.

Plant sterols, or phytosterols, are molecules of a sterolic nature present in plants; they in fact make up part of plant cell membranes. About 40 phytosterols are known; the phytosterols most present in the diet are beta- sitosterol (50%), campesterol (33%) and stigmasterol (4%). As may be noted from the percentages, the other phytosterols are present in very modest amounts. Beta-sitosterol differs from cholesterol because of the ethyl group at position 24 of the side chain. In the diet, they are found especially in vegetable oils, nuts and some seeds and legumes. It is by now well-established that phytosterols are effective against high blood cholesterol. Their mechanism of action is very simple: phytosterols decrease the cholesterol levels in blood by reducing intestinal cholesterol absorption. This mechanism is based on the substitution of cholesterol inside micelles, which are veritable means of transport for cholesterol. Given that micelles have a limited ability to incorporate phytosterols, the concentration of cholesterol in the same is reduced and, accordingly, less is absorbed through the intestinal membrane. The cholesterol not incorporated into the micelles forms co-crystals with the phytosterols and together they are eliminated through faeces. Phytosterols, unlike cholesterol, are not capable of producing atherosclerotic plaques. Moreover, phytosterols, and beta-sitosterol in particular, are by now widely used to combat benign prostatic hyperplasia. The action of beta-sitosterol on prostate tissue is due to a number of synergistic mechanisms: inhibition of hepatic and prostatic 5-alpha-reductase (this is the enzyme which transforms testosterone into DHT, and DHT, through the expression of a variety of growth factors, represents one of the main factors in determining the proliferation and progression of BPH (benign prostatic hyperplasia)); inhibition of prostatic aromatase (which converts testosterone into estradiol, usually overexpressed in IBP); inhibition of prostatic Na, K-ATPasi; and antiinflammatory action. Among the most important and complete clinical studies carried out with beta-sitosterol on patients affected by BPH we shall mention: Berges RR, Kassen A, Senge T "Treatment of symptomatic benign prostatic hyperplasia with beta-sitosterol: an 18-month follow-up.". BJU Int. 2000 May;85(7):842-6; Klippel KF, Hiltl DM, Schipp B.German "A multicentric, placebo-controlled, double-blind clinical trial of beta- sitosterol for the treatment of benign prostatic hyperplasia." BPH-Phyto Study group. Br J Urol. 1997 Sep;80(3):427-32; Wilt TJ, MacDonald R, Ishani, A. "Beta-sitosterol for the treatment of benign prostatic hyperplasia: a systematic review.".BJU Int. 1999 Jun;83(9):976-83.

From a chemical viewpoint, estrogens of vegetable origin, or phytoestrogens, can be grouped into three main categories: lignans, coumestans and isoflavones. Of minor importance is another group represented by resorcylic acid lactones, whose principal constituent is zearalenone, present in mushrooms and defined as mycoestrogens.

Isoflavones are natural chemical compounds belonging to the phenolic compounds of vegetable origin which in turn belong to the broader class of flavonoids. Isoflavones are present in the Leguminosae and Iridaceae and in particular they are concentrated in the Papilionideae, subfamily of the Leguminosae, and are thus found in foods such as chick peas, whole grain cereals, beans, fava beans, fennel, lentils, soybean and red clover.

Several clinical studies (Zhuo X.G. et al., 2004; Mosca G., 2008; Zhan S. et al., 2005) have highlighted the effects of soy protein and the isoflavones contained in it on cholesterol and triglycerides and it was shown that soy protein containing isoflavones exerted a significant action in reducing total cholesterol, LDL (low-density lipoprotein) cholesterol and triglycerides, along with an action of increasing HDL (high-density lipoprotein) cholesterol (good cholesterol). The reduction effect demonstrated to be greater the higher the cholesterol level was prior to the therapy.

From a structural and functional viewpoint, isoflavones are similar to the estrogen produced by the body and have the property of binding to the same receptors. For this reason they are commonly called phytoestrogens; among them, one of the most important and studied, being considered to date the most biologically active one, is genistein and the respective b- glucoside of genistein. In soy-based foods, the glucosidic form can be found, even though the bio-active form is represented by the isoflavone devoid of glucose, namely, aglycone. Therefore, the natural isoflavones of soy must be activated by hydrolysis of the glucosidic group in order to acquire their biological functionality.

In the gastroenteric tract there are enzymes called b-glucosidases which intervene in the action of detaching glucose, transforming the glucose molecule into the active form called aglycone; in this form it can be absorbed at the intestinal level. The aglycone is structurally similar to estrogen and can thus bind to the same receptors. In humans, two different estrogen receptors have been identified, called ERa and ERb (Bitto A., 2010). Vis-a-vis these receptors a different and very interesting binding activity is exhibited by phytoestrogens, in particular genistein; in fact, genistein possesses a high affinity for ERb, similar to that of estrogen, and 20 times greater than the affinity for the receptors ERa. This differentiated action of genistein gives rise to an original profile of safety and effectiveness; the effectiveness can be explained with reference to genistein 's high affinity for b type estrogen receptors (ERb), which are abundant in the cardiovascular system.

Moreover, genistein has demonstrated to be effective in reducing the growth of tumour-feeding blood vessels. This also seems to explain the protective effect that, according to several studies, soy has in the development of prostate cancer in men. In vitro studies with genistein on prostate tumour cell lines have demonstrated an antiproliferative effect on the cells, exerted both directly and via induction of apoptotic phenomena. Genistein is a potent inhibitor of protein-tyrosine kinases, with a consequent slowing in the growth of tumour cells. It has also recently been shown that genistein is capable of replenishing the reserves of endoglin, an important suppressor of prostate tumour cell growth. In particular, endoglin interacts with the motility of prostate tumour cells. Furthermore, it has been well demonstrated that genistein is a potent inhibitor of angiogenesis and of the development of metastasis. In particular, the progression of prostate cancer to the metastatic stage is prevented in experimental animals. It should be noted that genistein demonstrates to have significant effects on the androgen receptor of patients with high-grade prostatic intraepithelial neoplasia, atypical small acinar proliferation or a low-grade prostate tumour (Haseen F et al, 2009). The data supporting the chemopreventive quality of isoflavones in men are interesting. A study on about 13,000 men in California demonstrated that a frequent consumption of soy milk (containing isoflavones and genistein in particular) significantly reduced the incidence of prostate cancer. In a prospective study on about 46,000 Japanese men, it was moreover demonstrated that genistein supplementation in the diet significantly reduced the incidence of localized prostate cancer. This finding was further reinforced when the subgroup of men aged over 60 years was evaluated. The favourable chemopreventive action of the genistein against prostate cancer was confirmed in another two large prospective epidemiological studies conducted respectively in China and in North American west coast states (Goetzl MA et al, 2007). Cucurbitin is an amino acid or pyrrholizidine alkaloid contained in Cucurbita pepo (pumpkin seeds), which has a preventive action against benign prostatic disorders, as well as an antiparasitic action, especially against tapeworm, as it favours the latter' s detachment from the intestinal wall, thereby facilitating its elimination. Moreover, it seems to have an interesting preventive effect against prostate diseases, including tumours. In accordance with what has been illustrated above, in the market there are present food supplements in the form of capsules or spreadable creams containing the alkaloids yohimbine, muirapuamine or other alkaloids with an aphrodisiac action indicated for treating erectile dysfunctions or declines in libido, both among males and females. There also exist other supplements, mainly in the form of capsules or syrups, containing phytosterols, phytoestrogens or cucurbitin, indicated for the prevention and treatment of prostatic disorders, in particular benign prostatic hyperplasia. However, all of these food supplements make the aforesaid active ingredients available in the form of capsules, syrups and spreadable creams, very often without using the synergic action of the aforesaid active ingredients extracted from a number of plant species which contain them. The inventor guessed that an association of the above-mentioned active ingredients and still others, mixed and prepared in such a way as to be able to be added to dairy products, would be particularly synergistic and effective in the prevention and treatment of disorders of the male urogenital system. The principal object of the present invention is in fact to provide a food preparation based on dairy products supplemented with vegetable substances which combine the beneficial effects of alkaloids having an aphrodisiac action with phytosterols, phytoestrogens and other substances that have demonstrated effectiveness in the treatment of prostate disorders. A further object of the present invention is to provide a consumer product such as yogurt, or another consumer dairy product having high efficacy, without side effects, in the prevention and treatment of disorders of the male urogenital system which usually arise after forty years of age.

The dairy products used within the framework of the invention are milk or milk-derived products such as yogurt, butter, cream, fresh cheese or aged cheese and ice cream.

The milk used to produce the above-mentioned dairy products can be of varying origin, mainly milk of animal origin selected from among cow's, sheep's, goat's and buffalo's milk or mixtures thereof, but it can also be milk of vegetable origin, such as soy milk. The milk itself, when it is animal milk, has preferably undergone a pasteurization or sterilization process or another heat treatment.

Preferably, the functional food preparation of the present invention is based on yogurt obtained by fermentation of cow's milk. In this case, the yogurt is obtained through processes of homogenization, heat treatment, culture inoculation and fermentation with Lactobacillus bulgaricus and Streptococcus thermophilus, where said microorganisms are alive and viable up to the moment of consumption. Cell density must be equal to or greater than 100,000,000 cells per millilitre. The ferments can also be of a probiotic type, such as bifidobacteria and lactobacillus acidophilous.

The alkaloids having an aphrodisiac action which are used in the food preparation of the invention are preferably derived from extracts of Ptychopetalum olacoides (or Liriosma ovata). The phytosterols, and in particular beta-sitosterol, are advantageously derived from Ptychopetalum olacoides, Serenoa repens and/or Urtica dioica extracts.

The phytoestrogens, in particular isoflavones, are advantageously derived from Glycine max and/or Medicago sativa extracts.

Further substances which have beneficial effects against prostatic hypertrophy, in preventing cardiocirculatory disorders and against skin aging, etc. can also be advantageously added.

Policosanols are a mixture of phytomolecules consisting of high molecular weight aliphatic alcohols extracted prevalently from Saccharum officinarum, but also from other vegetable substances, such as Medicago sativa. The principal molecules are Octacosanol, Tetracosanol and Hexacosanol. Octacosanol is contained in the aforesaid plants, in cotton and in the waxy layer of the leaves of a variety of plants, and can also be found in significant quantities in wheat germ oil. Policosanols can also be produced synthetically, but not being accompanied by other phytocompounds normally present, they are less effective than natural ones. In nature, for example, octacosanol is always accompanied by and synergistic with vitamin E and B group vitamins, as well as minerals. The octacosanol extraction process is conducted by cold pressing, i.e. without the use of solvents; this makes it possible to obtain a product very rich in vitamin E, a potent factor with antioxidant action.

Policosanols, too, have medicinal properties, such as that of lowering "bad" cholesterol (LDL) by reducing an enzyme at the basis of the production thereof (Prat H. et al., 1999), and the percentage of triglycerides (Mas R. et al., 1999), as well as performing an anti-aggregating action in blood (Mas R. et al., 1998; Arruzazabala M.L. et al., 2002; Castano G., Mas R., Fernandez J.C. et al., 2001), thus reducing the risk of obstructions forming in blood vessels. Policosanols also have important antioxidant functions and are thus effective in combating free radicals and hindering LDL oxidation, which can represent the main cause of atherosclerotic manifestations.

Saponins, or saponin glycosides, are complex molecules characterized by an aglycone structure of a steroidic or triterpenic nature. They are responsible for a cholesterol lowering activity thanks to which total cholesterol and LDL cholesterol are significantly reduced.

Folic acid, or pteroyl(mono)glutamic acid or vitamin B9, exerts an action of limiting homocysteine, which is a sulphur-containing amino acid that forms following the enzymatic transformation of methionine, another sulphurated amino acid present in proteic foods (dairy products, meat, legumes, eggs) and which can prove even more harmful than cholesterol. Coenzyme Q10, also called ubiquinone, or vitamin Q, is an organic molecule, and more precisely a benzoquinone with very long isoprene side chain. This coenzyme, ubiquitous in biological systems, displays a structure similar to that of vitamin K and vitamin E. It is found in abundance in soybeans, cereals, walnuts and grapes. In organisms, it participates in redox reactions. It possesses a strong scavenger action and for this reason protects cellular structures against free radicals. It performs its action synergistically with vitamin E, protected in turn by coenzyme Q10, which assures the bond thereof with octacosanol; the latter, in turn, is also bonded to B group vitamins and minerals. This coenzyme is in fact a water-insoluble lipophilic compound with adjuvant action in the transport of electrons and in mitochondrial energy production.

The intake of coenzyme Q10 can exert cardioprotective, cytoprotective and neuroprotective effects; it also performs an action of inhibiting the oxidation of LDL cholesterol, which is believed to be the largest pathogenetic component of atherosclerosis. (Littaru G. P. & Tiano L., 2005; Linnane A.W. et al., 2002; Mizuno M. et al., 1997; Niklowitz P. et al., 2002).

The levels thereof in the human body decrease with advancing age, perhaps because of a decrease in its synthesis or because of the increase in lipid peroxidation which occurs with age.

Further substances of vegetable origin such as vitamins, vegetable globulins and minerals can be added to the food preparation of the invention, since supplementing a normal diet with the intake thereof is particularly indicated in the male population aged over forty and in the prevention and treatment of urogenital system disorders.

According to the present invention, the above-described objects are achieved thanks to the solution specifically referred to in the claims that follow.

In relation to the invention, the claims form an integral part of the technical teaching provided.

The invention is illustrated in detail below through an example of a non- restrictive embodiment of the functional food preparation of the invention. Example

A functional consumer food preparation which has properties of treating and preventing disorders of the male urogenital system that usually arise after forty years of age, including erectile dysfunctions and a decline in libido, prostatic hypertrophy, prostate inflammations and prostate tumours, is prepared by adding aphrodisiac alkaloids, phytosterols, phytoestrogens, minerals, vitamins and other substances extracted from various plant species to a dairy product, and precisely a yogurt, wherein, out of a total weight of 100 grams of the functional food preparation, there are present:

• Ptychopetalum olacoides bark extract

1.5 g

• Glycine max extract 180 mg

• Serenoa repens extract

320 mg

• Medicago Sativa extract

100 mg

• wheat germ extract

l g

• Cucurbita pepo L. (pumpkin seeds)

160 mg

• Urtica dioica extract

30 mg

• Semi-fluid dairy product (viscosity less than 10000 mPa.s at 10°C) - in particular yogurt-q.s. to a total of lOOg

wherein the Ptychopetalum olacoides, Glycine max and Serenoa repens extracts and pumpkin seeds are added to the milk after 20 minutes of refrigeration following the pasteurization process, whereas the Medicago Sativa and wheat germ are added to the milk after 30 minutes of refrigeration using what is called a "multipurpose" apparatus, commonly known in the dairy industry.

Some information and definitions regarding the plant species used in the above-described examples of composition are provided below.

Ptychopetalum olacoides (extract from the bark of branches and roots). Principal components:

mixture of esters (lupeol, behenic acid, beta-sitosterol);

bitter substances (alkaloid muirapuamin); and

traces of essential oil, resinous substances.

Glycine max x 100 g.

Contains isoflavones (genistein, daizein), coenzyme Q10.

Composition: protein 13.1 g

lipids 6.7 g

carbohydrates 9.6 g

fibre 1.1 g

water 69 g

ash 1.59 g

potassium 484 mg

phosphorous 174 mg

calcium 67 mg

sodium 14 mg

Serenoa repens (dried ripe fruit).

Contains:

essential oil (1-2%);

fixed oil with 75% free fatty acids and 25% neutral substances, including free or esterified sterols or fatty acid alcohol esters;

acids including caproic, caprylic (approx. 1.3%), caprinic (approx.

I.8%), lauric (approx. 24%), linoleic (approx. 3.6%), myristic (approx.

I I .6%), oleic (approx. 33.2%), palmitic (approx. 8.7%) and stearic acids; sterols including beta-sitosterol, beta-sitosterol-3-O-beta-D- glucoside, campesterol, stigmasterol, lupeol, 24- methylenecycloartenol, hexacosanol and 1-octacosanol;

alcohols including farnesol and phytol;

polysaccharides SI, S2, S3 and S4, with different percentages of glucose, galactose, mannose, fucose, arabinose, ramnose and glucuronic acid.

Medicago sativa x 100 g of dry product.

Contains isoflavones (genistein, daizein), policosanols, saponins, coumarins, folic acid.

Composition: protein 26 g lipids 0.2 g polysaccharides 61 g raw fibre 23.7 g starch 4.9 g lignin 12.3 g ash 9.3 g nitrogen-free extractives 37.9 g

CaO 2.56 g

P ₂ 0 ₅ 0.79 g Wheat germ x 100 g

Contains coenzyme Q10.

Composition:

protein 23.15 g lipids 9.72 g carbohydrates 51.8 g fibre 13.2 g water H-2 g ash 4.21 g minerals

potassium 892 mg phosphorous 842 mg magnesium 239 mg calcium 39 mg sodium 12 mg iron 6.26 mg vitamins

B l 1.882 mg

B2 0.449 mg B3 6.813 mg

B5 2.257 mg

B6 1.3 mg

Urtica dioica L. x 100 g

protein 5.9 g

lipids 0.7 g

carbohydrates 1.3 g

fibre 4.1 g

iron 4.4 mg

calcium 590 mg

vitamin C 175 mg

Cucurbita pepo L. x 100 g.

Contains cucurbitin, delta sterols, phytosterin, vegetable globulins, vitamins F and E

Composition:

protein 30.23 g

lipids 49.05 g

water 5.23

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