DESCRIPTION

The present invention refers to products obtained from a plant belonging to the Origanum Majorana species for use in the treatment of decreased female libido. The present invention also refers to mixtu res and to pharmaceutical compositions comprising said obtained product for use i n the treatment of decreased female libido.

STATE OF THE PRIOR ART

Recent studies demonstrated that almost one-third of ad ult age women have lost interest in sex life. Decreased female libido, medically recognized and defined as Hypoactive Sexual Desi re Disorder, or H S D D, derives from a combination of various physical and mental factors.

Hypoactive Sexual Desire Disorder consists in the persistent and/or recurrent lack of sexual fantasies and desire for sexual activity, and is cause of anxiety and distress in the patient suffering from it, or of problems in her relations.

To date, in spite of the seriousness and diffusion of the problem, there are no treatments capable of re-establishing female sexual desire bringing about a standard frequency of sexual intercourse, or behaviors that could be defined as average.

It is known in the state of the art that the Origanum Majorana plant (Marjoram) has, like other plants belonging to the Lamiaceae (or Labiatae) family, digestive, carminative and antispasmodic properties; moreover, it has antineuralgic, diuretic, expectorant properties, and sedative properties on the nervous system.

Moreover, the female anaphrodisiac activity of Origanum Majorana at homeopathic doses is well-known. For this reason, products obtained from Origanum Majorana are marketed as remedy for pathological reduction of female sex drive or for sex manias (see www.abchomeopathy.com: Origanum Majorana), or the publication "Essential Herbal Wisdom : A Complete Exploration of 50 Remarkable Herbs", Nancy Arrowsmith, page 189.

Moreover, U.S. Pat. Application publ . N ° US20090215708 describes a method of treating male and female sexual dysfunctions by administering proton pump agonists.

SUMMARY OF THE INVENTION

The inventor has surprisingly found that by treating women exhibiting evident hypoactive sexual desire disorder (HSDD, hereinafter defined more simply as decreased female libido) with a product obtained from the plant belonging to Origanum Majorana species (also referred to as sweet marjoram and commonly known also under the name of marjoram), the patients showed, irrespective of age and the putative cause bringing about the decreased libido, a significant increase of sexual desire.

Therefore, an object of the present invention is a product obtained from a plant belonging to Origanum Majorana species for use in the treatment of decreased female libido.

A second object of the present invention is a pharmaceutical composition comprising said product and one or more excipients and/or vehicles and/or diluents for use in the treatment of decreased female libido.

A th i rd object of the i nvention is a composition containing, besides marjoram, other additional active principles, such as herb or plant extracts, and/or active substances, such as amino acids.

The invention at issue provides a new treatment, inexpensive and without side effects, for a problem highly felt and widespread in female population.

The advantages, features and the operation modes of the present invention wi l l be mad e a ppa rent from th e fol l owi n g deta i led d escri pti on of some embodiments thereof, given by way of example and not for limitative purposes.

DETAILED DESCRIPTION OF THE INVENTION

The present invention refers to a product obtained from a plant belonging to

Origanum Majorana species for use in the treatment of decreased female libido.

Origanum Majorana (or marjoram) is a species of the genus Origanum, native of Europe and of the central and southern regions of Asia , and it is a species commonly used in nutrition as an aromatic plant whose essential oil consists of terpenes, bitter principles, mucilage and natural substances.

The raw material used for preparing said product is both the whole plant belonging to said species and one or more parts thereof, like e.g. root, bark, leaf, fruit, seed or flower, both in a dried form and in a fresh form. The procedures for drying the plants or parts thereof are known to the technician in the field and require no further description herein.

The product could be prepared both in the form of whole plant, or parts thereof, dried and powdered, or i n the form of liquid extract, or of dry, soft, lyophilized, granulated, powdered extract.

Said extract is obtainable in liquid form by using a suitable solvent or solvent mixture selected from the group comprising ethanol, water, distilled water, esters, ethers, polyols or a hydroalcoholic mixture, e.g. of 80, 75, 70, 60% alcohol, e.g. ethyl alcohol, in water. The optionally concentrated hydroalcoholic extract is commonly referred to as mother tincture.

Marjoram mother tincture prepared according to the procedure reported in the pharmacopoeia contains a fixed ratio among fresh plant, dry residue and final tincture.

The procedure for preparing the mother tincture envisages maceration of the fresh vegetable material in a hydroalcoholic solution (with an ethanol/water ratio of about 60:40) for a period not shorter than 10 days. The amount of fresh vegetable material put to macerate in the hydroalcoholic solution is such as to result in a 1 : 10 ratio between the equivalent amount of the dried vegetable material and the final mother tincture. After 10 days of maceration at room temperature the supernatant is separated and filtered, while the solid residue is pressed and the liquid from the pressing (juice) filtered. Liquid fractions are then joined and, after 48 hours of rest, again filtered. The alcoholic titre of the vegetable mother tincture is of about 65° +/- 5°. The liquid can be stored in closed vessels, preferably not made of plastic, under cool and dark conditions.

The extracts in liquid form, obtained as described above or according to other methods known to the technician in the field, could be filtered in order to separate the liquid extract from the residual vegetable material , and suitably concentrated or brought into the form of dry, soft, lyophilized extract or powder.

Dry extracts are prepared by concentrating the liquid extracts to complete evaporation of the extractive solvent at temperatures lower than 50°C and generally at a reduced pressure. Dry extracts generally have a dry residue not lower than 95% by mass.

Other methods for preparing dry extracts are nebulization, in which the liquid extract reduced to very fine droplets is dried by hot air, or lyophilization (freeze-drying). These methods entail the advantage of not subjecting the active principles contained in the extract to a thermal process that might degrade them.

Soft extracts are preparations of a texture intermediate between those of liquid extracts and of dry extracts, and are obtained by partial evaporation of extraction liquids at temperatures lower than 50°C, generally under reduced pressure. Evaporation of the extraction solution goes on until the residue does not wet glueless paper anymore.

Alternatively, extracts can be prepa red by steam d isti l lation of the herbaceous parts of the plant, preferably of leaves and desiccated flowers harvested at the flowering stage.

Marjoram extracts usually contain tannins, bitter substances a nd an essential oil consisting of terpineol, borneol, camphene, sabinene, and modest amounts of arbutin and/or hydroquinone.

Dosi ng of the prod uct orally administered to the patient could vary depending on age and general conditions, and on the nature and seriousness of the situation. Moreover, evidently the effective amount could, when required, be lowered or increased according to the responses of the patient treated and/or the assessment of the physician prescribing the extract of the present invention.

The product, preferably in the form of mother tincture, is administered in amounts comprised between 20 and 200 drops per day, preferably 20 to 80, e.g. 40 drops.

In another specific embodiment, the product is administered in dosages of

200 to 500 mg/die, preferably 250 mg/die, of dry extract obtained as described above.

Time of treatment is of at least one week and can last, e.g., 1 , 3, 5, 6 or 7 months.

Object of the present invention is also a mixture of products or extracts from herbs having the same purpose seen above, comprising the marjoram product according to the invention and at least one second plant extract selected from the group comprised of Tribulus terrestris, Lepidium mwyenei, Muira Puama, Salvia officinalis, Damiana. The mixture may further comprise other active substances such as amino acids, e.g. arginine, capable of modulating the activity of the composition.

The m ixtu res could be prepared both by mixing the various extracts obtained separately, and by performing the extraction process on a mixture of vegetable material obtained from different plants.

Object of the present invention are also pharmaceutical compositions comprising a marjoram product or a mixture as described above and one or more excipients and/or vehicles and/or diluents for use in the treatment of decreased female libido.

The pharmaceutical compositions according to the present invention can be formulated in various forms for oral or topic use, like, e.g., solution, suspension, emulsion, syrup, powder, granulate, capsule, tablet, pill, gel, cream, ointment, which could depend on the selected route of administration. The pharmaceutical composition in a form suitable for oral administration can include formulations such as capsules, tablets, pills, granules or powders. Normally, powders or granulates are prepared in single-dose bags or sachets, containing a unitary amount of dosage that may be administered in a solid form , or in a form suspended or dissolved in a suitable amount of water. In these solid forms, marjoram extract could be mixed with one or more inert and pharmaceutically acceptable excipients. Such excipients may be selected among those known in the state of the art, and include but are not limited to: a) carriers, such as sodium citrate and calcium phosphate, b) fillers, such as starch, lactose, microcrystalline cellulose, sucrose, glucose, mannitol and colloidal silica, c) humectants, such as glycerol, d) disintegrating agents, such as alginates, calcium carbonate, starches, derivatives of starch, of cellulose and of polyvinylpyrrolidone, silicates and sodium carbonate, e) b i n d e r s , s u c h a s carboxymethyl cellulose, alginates, gelatin, polyvinylpyrrolidone, sucrose, cellulose polymer derivatives, starch derivatives, f) retardants, such as paraffin, cellulose polymers, fatty acid esters, g) absorption accelerators, such as quaternary ammonium compounds, h) wetting agents and surfactants, such as cetyl alcohol and glycerol monostearate, i) adsorbents, such as bentonite clays and kaolin, k) lubricants, such as talc, calcium stearate, magnesium stearate, polyethylene glycol, sodium lauryl sulphate, sodium stearyl fumarate, j) glidants, such as talc, colloidal silica.

If the selected compositions constitute the filling of gelatin capsules, the excipients include, but are not limited to, compounds of the type: lactose, high molecular weight polyethylene glycol and the like.

Solid dosage forms may be coated with enteric, gastric coatings, or with coatings of other type well-known in the state of the art. Said forms may contain matting agents and may be of a type allowing release of active ingredients only or preferably in a certain tract of the intestine, optionally in a delayed manner. Substances that can allow such a delayed use include, but are not limited to polymers and waxes.

Liquid forms suitable for oral administration are emulsions, solutions, prepared or extemporary suspensions, syrups, elixirs, tinctures. Excipients suitable to the formulations according to the present invention in liquid forms for oral use include, but are not limited to diluents commonly used in the art, such as water or other solvents, solubilizing and emulsifying agents selected from ethyl alcohol, polyalcohols, propylene glycol, glycerol, polyethylene glycol and sorbitan esters. These formulations can also contain sweeteners and aromas selected from those well-known in the state of the art.

Said compositions may also contain preservatives of antibacterial or antifungine type, selected, yet not exclusively, from: paraben, chlorbutanol, phenol, sorbic acid and the like. It may also be useful to include an isotonic agent, e.g. a sugar, sodium chloride or the l ike. Moreover, pharmaceutical forms having a delayed absorption may be obtained with agents such as, e.g., aluminum monostearate and gelatin.

Suspensions, beside marjoram extract, can contain suspending agents such as, e.g., isostearic alcohols, ethoxylates, polyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminium hydroxide, bentonite, alginates and cellulose derivatives in general, or the like. The right fluidity can be kept with coating material such as lecithin, with the keeping of the right particle size in the dispersions or with the use of surfactants.

Typically, compositions for oral use in solid form may contain an amount of marjoram extract in all of its forms described above, and preferably in the form of dry extract obtained by a drying of the mother tincture, in an amount comprised between 200 and 500 mg per dosage unit, e.g. 250 mg.

By the term "dosage unit" in the present description it is meant the unitary formulation for a single administration, e.g. a tablet, a capsule, a bag, etc.

The compositions in the form of emulsions may be O/W (Oil/Water) or W/O or W/O/W and 0/W/O, better if micro- o nanoemulsions, but can also be colloidal dispersions or solutions. Microemulsions can be proposed as gels, creams, or even in the form of foams. All known surfactants, like e.g. silicone, glucoside and phospholipid ones, can be used for preparing the emulsions.

The product of the present invention is used for the treatment of decreased female libido or hypoactive sexual desire disorder, even associated to other pathologies. I n fact, oft-times this disorder is accompanied by menopause disorders, depression, or occurs as a side effect of the intake of some drugs such as contraceptives.

The effect of increased female sexual desire following administration of a marjoram plant extract as described above is useful also in those women who do not suffer from decreased libido pathology, but anyway wish to increase their sexual desire.

Therefore, a further object of the present invention is the use of a marjoram product as described above for increasing female sexual desire and the use of said product in food supplements.

There are no particular limitations on the manufacturing of the supplement comprising the product of the present description; by way of example and not for limitative purposes, the supplement described herein could be manufactured in the form of sweets, gelatins, beverages (suspensions or emulsions) or in the form of more complex foods, nutraceuticals. A non-limiting example of said nutraceuticals could be represented by beverages such as shakes, juices, soft drinks, or foods like gums, biscuits, granulates, chocolate bars, crackers and crisp bread, etc. The extract could also be introduced at the most useful moment of the preparing, in a liquid or dried form, in liquid or solid foods, as the technician in the field for the manufacturing of food supplements could define in a simple way and without use of inventive activity. The food supplement could also contain other ingredients, like e.g. a combination of vitamins, salts and other substances aimed at supplementing a diet.

A further object of the invention is a method for the treatment of decreased female libido, comprising the administering, to a patient requiring such treatment, of a product obtained from a plant belonging to Origanum Majorana species, prepared according to all of the forms described herein. Preferably, the method envisages administering a dry extract in an amount comprised between 200 and 500 mg/die.

Hereinafter, the invention is described in detail in the following examples which are merely by way of example, without limiting the scope of the protection conferred.

EXAMPLES

Example 1. Method for preparing marjoram mother tincture.

Alcoholic extraction is carried out by maceration of the raw material in a hydroalcoholic solution (ethanol/water ratio: 60:40) for a time of 1 0 days. The amount of fresh plant will be such as to result in a 1 :10 ratio between the equivalent amount of dried plant and the final mother tincture. After the 10 days of maceration of room temperature supernatant is separated and filtered, whereas solid residue is pressed and liq uid from the pressing (juice) is filtered. Liquid fractions are then reunited and, after 48 hours of resting, filtered again.

The alcoholic titre of the vegetable mother tincture is of about 65° +/- 5°.

The liquid is stored in closed vessels, preferably not made of plastic, under cool and dark conditions.

Example 2. Testing of mother tincture as obtained in Example 1

Origanum Majorana mother tincture as obtained in exam ple 1 was administered to the extent of 20 drops, 2 times a day, for 2 months, to 13 women of ages ranging from 34 to 59 years who had disclosed evidently decreased libido, obtaining a stimulation and an increase of sexual desire in 10 of them.

The results of the testing are schematized in Table 1 reported hereinafter, with ratings ranging from a minimum value depicted by "-" to a maximum value depicted by "++++". Table 1.

Example 3. Powder formulation.

In a specific embodiment, the invention has the following powder formulation per dosage unit:

Ingredients Amount

Marjoram dry extract 250 mg

Sage dry extract 100 mg

Arginine 500 mg

Sorbitol, citric acid, lemon aroma, silica, 2.7 g

sucralose