WO2012017128A1 - Composition à base d'extrait de romarin et de vitamine e et applications de celle-ci - Google Patents

Composition à base d'extrait de romarin et de vitamine e et applications de celle-ci

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WO2012017128A1
WO2012017128A1 PCT/ES2011/070586 ES2011070586W WO2012017128A1 WO 2012017128 A1 WO2012017128 A1 WO 2012017128A1 ES 2011070586 W ES2011070586 W ES 2011070586W WO 2012017128 A1 WO2012017128 A1 WO 2012017128A1
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vitamin
composition
rosemary
extract
weight
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WO2012017128A2 (fr
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  • the present invention relates to compositions comprising an extract of rosemary and vitamin E, and with its applications in both the food and pharmaceutical sectors.
  • said compositions can be used as nutritional supplements as well as in the preparation of pharmaceutical compositions for reducing inflammatory processes and lipid peroxidation in general, and, in particular those associated with menopause, as well as for prevention and / or treatment of the adverse effects of ionizing radiation.
  • Menopause corresponds to the transition from the reproductive state to the non-reproductive state in a woman's life and is characterized by the interruption of menstruation.
  • menopause has come to mean much more than simply the loss of reproductive capacity, as it is associated with a large number of acute and chronic conditions.
  • the menopausal syndrome consists of a variety of symptoms that are the result of hormonal imbalance and nutritional deficiency in women, such as sweating and vasomotor instability that affects approximately 75% of women. Also common are the psychological and emotional symptoms of fatigue, insomnia, irritability and nervousness. Other common symptoms include nausea, constipation, diarrhea and myalgia (The Merck Manual, 1793. 16th Ed. 1992).
  • the hormonal changes that occur during menopause cause various clinical manifestations that affect the health and well-being of women.
  • various clinical manifestations that affect the health and well-being of women.
  • it is of variable intensity it is convenient to treat these clinical manifestations, especially those that can evolve to chronic diseases of seriousness or significantly affect the quality of life of women.
  • Isoflavones are substances of plant origin that can act as estrogens. They are found mainly in soybeans and their therapeutic capacity is greater than that of other phytoestrogenic substances such as lignans. However, the effects of isoflavones are less than those of estrogen hormones. Isoflavones and phytoestrogens exert a stabilizing effect when the estrogen level is low, for example during menopause. Isoflavones can also reduce the effect of estrogen on cells and skin layers when hormone levels are high, and then, essentially, reduce the risk of cancers linked to estrogen.
  • the double activity of the isoflavones acting as estrogenic and antiestrogenic, confer isoflavones a series of qualities that allow to regulate the hormonal balance in women, being able to prevent osteoporosis and act as powerful antioxidants that protect against the development of breast cancer.
  • the use of isoflavones to treat the disorders associated with menopause requires their combination with vitamins and minerals to enhance their effect.
  • There are numerous publications on products for improving menopausal disorders based on the use of isoflavones for example, WO 2000/007566, WO 1993/023069, WO 1989/005655.
  • high diets ⁇ -carotene, a precursor of vitamin A reduce the incidence of respiratory and digestive tract cancer, while indicating the need for further clinical trials (Harrison Internal Medicine 16 Edition, 2005. 408 ).
  • Vitamin B9 also called folic acid, decreases hyperhomocysteinemia (one of the main cardiovascular risk factors). Although this protection is discussed, a recent study provides acceptable evidence of this (Yang, Circulation, March 2006;
  • the vitamin complex B l, B6 and B12 intervenes in numerous neurotropic, hematic, organic functions, etc.
  • the isolated properties of each of these vitamins are analyzed separately from the properties attributed to the group of the three.
  • vitamin B12 is given some protection against depression (Tolmunen et al, Psichother Psichosom 2004; 73: 334).
  • Vitamin B or Thiamin is a water soluble vitamin, whose phosphate derivatives are involved in many cellular processes. Adverse reactions have not been described by supplementation or with therapeutic doses that are much higher (up to 300 mg / day) (Martindale, 34 a ed 2005).
  • Vitamin B6 or Pyridoxine is a water soluble vitamin, whose severe deficiency is rare and manifested by neuropathies. Its mild deficiency produces alterations in the epithelia, hyperhomocysteinemia (with increased cardiovascular risk), microcytic anemia, depression etc. There are no adverse reactions to supplement said vitamin (Favier et al., J Ginecol Obstet Bio Repro 1997; 26: 102), although it must be borne in mind that the maximum tolerated dose is 100 mg / day (Martindale 34 to Ed 2005).
  • Vitamin B2 or Riboflavin is important for the metabolism of fats, carbohydrates and proteins. Its deficit is clinically similar to the B group vitamins: buccal and cutaneous ulcers, corneal vascularization, anemia and neurological and psychic alterations.
  • Vitamin B3 or Nicotinamide is a water soluble vitamin, whose severe deficiency (known as pellagra) is quite rare. Its mild deficiency is similar to that of other B group vitamins and can be seen as skin and mucosal alterations (mouth ulcers, etc). With the administration of nicotinamide the adverse effects of nicotinic acid are not observed.
  • Vitamin B5 or pantothenic acid is a water soluble vitamin required for life, that is, it is an essential nutrient, since it is critical for the metabolism and synthesis of carbohydrates, proteins and fats. Your deficit (which is exceptional), could lead to laxity, headaches, nausea, etc. Vitamin B7 or biotin is necessary for cell growth, the production of fatty acids and the metabolism of fats and amino acids. It is usually recommended to strengthen nails and hair. Its deficiency (which is very rare), includes dermatitis, seborrhea, muscle pain and alopecia. It is not known that there is toxicity or overdosage of said vitamin.
  • DHA docosahexaenoic acid
  • DHA is basic for optimal nervous communication. Some epidemiological studies have shown a relationship between depression and DHA, in the sense that this fatty acid contributes to reduce depression (Fernandes G et al., Prostaglandins, Leukotrienes and Essential Fatty Acids (2003) 68: 361-372; Simopoulos AP et al. Am Nutr Metab 1999, 43: 127-130).
  • DHA has been used for the preparation of some compositions for the treatment of menopause, such as in WO 2004/004638, where a composition for the improvement of certain inflammatory symptoms related to menopause, among other disorders is described.
  • Said composition comprises a tocopherol and an omega-3 (as DHA) or omega-9 polyunsaturated fatty acid.
  • compositions described for the reduction of inflammatory processes and lipid peroxidation associated with menopause there is still a need to have improved compositions for the effective reduction of such disorders, with which the effect is greater than those described.
  • Radiotherapy Radiotherapy is, at present, one of the most widespread mechanisms for the treatment of cancer. This technique has undergone a great development due, to a great extent, to its great effectiveness for the reduction or elimination of tumors. This effectiveness is based on the different sensitivity to radiation between tumor and non-tumor tissues. Tumor tissues, having affected the repair mechanisms of nucleic acids, are more sensitive to mutations. This means that when exposed to a harmful agent such as radiation, these tumor tissues can not repair all the damage, and therefore suffer a greater cell death than non-tumor tissues. In spite of this, in most cases, the radiation rate that must be applied for the elimination of a tumor can also affect, although to a lesser extent, the adjacent normal tissues, with the consequent pathological consequences that they generate.
  • Radiotherapy there are other situations in which a person can be exposed to radiation that involves tissue damage, such as exposure to radiation in nuclear power plants, the treatment of radioactive material from medical products, or even natural radiation .
  • Reactive oxygen species in physiological situations, are naturally neutralized by the existence of endogenous antioxidants.
  • endogenous antioxidants when a tissue is affected by radiation, the number of these reactive oxygen species increases significantly (Robbins et al., 2004. Int L Radiat Biol. 80: 251-259), so for its neutralization an exogenous contribution is necessary.
  • the non-neutralization of these reactive oxygen species leads to tissue damage and the consequent pathological state.
  • the exogenous contribution of these antioxidants is postulated as a recommendable solution to avoid cytotoxicity and increase the viability of the irradiated tissues, either by accident, or by radiotherapy treatments.
  • compositions including several of these compounds have already been formulated (JP60224629, SI22437).
  • vitamin E one of the best characterized is vitamin E.
  • This name naturally includes a set of 8 compounds, 4 tocopherols and 4 tocotrienols (Brigelius-Flohe et al., 1999. FASEB J. 13: 1145-1155). These present antioxidant functions, being the most powerful and the most studied a-tocopherol. Some of these compounds, both tocopherols and tocotrienols in various forms, have already been proposed as a radioprotective treatment (WO2004086412, WO2008065891). Despite its performance as an antioxidant, this molecule can also have pro-oxidative effects, so it is usually combined with ascorbic acid to avoid such effects (Kontush et al., 1996.
  • vitamin E has antiproliferative effects in a multitude of cell types such as glioma C6 cells (Betty et al., 2006 Free Radical Biology & Medicine, 41: 464-472), or smooth muscle cells ( Chatelain et al., 1993. Biochimica et Biophysica acta, 1176: 86-89).
  • Rosmarinus officinalis or rosemary is a species of the genus Rosmarinus whose natural habitat is the Mediterranean region, southern Europe, northern Africa and Asia Minor. In Spain it is located in most of Catalonia, up to the Pyrenees in Aragon and Navarre, Castilla-La Mancha, Castilla y León, La Rioja, Madrid, Murcia, Extremadura, in the mountainous areas of the Valencian Community, Andalusia and the Balearic Islands . It is very rare in points north or northwest of the peninsula. Rosemary is a evergreen woody shrub very branched, can reach 2 meters in height. It can be found green throughout the year, with blurred young stems and aged stems of reddish color and cracked bark.
  • the leaves small and very abundant, have a linear shape. They are opposite, sessile, entire, with the edges downwards and of a dark green color, while on the underside they present a whitish color and are covered with hairiness. In the area of union of the leaf with the stem are born the floriferous bouquets.
  • rosemary leaves also contain flavonoids with antioxidant activity (Okamura N. et al., 1994, Phytochem, 37, 1463).
  • the highest antioxidant activity corresponds to carnosic acid, followed by carnosol, rosmarinic acid, rosmanol and rosmadial (Cuvelier M.E. et al., 1996; JAOCS 73, 645).
  • Carnosol is the component that has generally been detected as the majority, often amounting to 90% of the extracts. In fact, it proceeds, along with other phenolic compounds found in rosemary, from the oxidation of carnosic acid during extraction operations.
  • the phytochemicals contained in the antioxidant extract of rosemary have important biological activities.
  • Supercritical rosemary extract is an extract enriched in different diterpenic polyphenols, such as carnosic acid, fleshy 1, romarinic acid obtained from the plant R. officinalis.
  • diterpenic polyphenols such as carnosic acid, fleshy 1, romarinic acid obtained from the plant R. officinalis.
  • the extraction by means of fluids in supercritical conditions is an advantageous alternative to extraction with solvents for obtaining antioxidants from natural sources.
  • the supercritical fluids behave like a liquid in the extraction process and therefore facilitates the dissolution of the solutes, at the same time, its behavior as gas allows an easy separation of the matrix. This involves a faster, more efficient and selective extraction process than in the case of liquid-liquid extraction.
  • "green solvents" such as C0 2 can be used, avoiding the use of the usual chlorinated solvents from liquid-liquid extractions. Extraction under mild and non-oxidizing conditions allows to obtain high quality products with their natural properties intact and free of solvent residues.
  • vitamin E It is found in many foods, mainly of plant origin, especially in green leafy (broccoli, spinach), seeds, including soy, wheat germ and brewer's yeast; It can also be found in foods of animal origin such as egg yolk.
  • the health benefits of vitamin E are many, for example in the circulatory system, it has antioxidant properties, eye properties and acts to prevent Parkinson's disease.
  • Human studies demonstrate the action of vitamin E as an important immunomodulator, potentiating the immune system (mononuclear peripheral cells) in healthy elderly individuals (Meydani, SN et al., 1990, Am. J. Clin. Nutr. 52 (3), 557-563).
  • compositions comprising a tocopherol and a polyunsaturated fatty acid omega-3 (as DHA) or omega-9 are described for the improvement of certain inflammatory symptoms related to menopause, among other disorders.
  • Smet et al. (Poultry Science 2008; 87: 1682-1688) describe a composition comprising rosemary and vitamin E, in addition to flaxseed oil as a supplement in the diet of chickens.
  • WO 10083206 discloses a composition containing at least one polyunsaturated fatty acid (PUF A) and additionally other antioxidants, such as vitamin E, ascorbyl palmitate, rosemary extract and grape seed oil. Also disclosed herein is a method for increasing the oxidative stability of concentrated fish oil.
  • the invention relates to a composition
  • a composition comprising an extract of rosemary and vitamin E, wherein:
  • the weight ratio between rosemary extract and vitamin E is not 1: 1 (p: p), - if the percentage of rosemary extract in the composition is less than 0.2% by weight with respect to the total composition, then the percentage of Vitamin E in said composition is greater than 0.4% by weight with respect to the total composition, and
  • the percentage of vitamin E in the composition is less than 0.4% by weight with respect to the total composition, then the percentage of rosemary extract in said composition is greater than 0.2% by weight with respect to the total of the composition. composition.
  • said composition is administered in a suitable administration form for oral administration.
  • said composition further comprises a vehicle selected from a pharmaceutically acceptable carrier and a food grade carrier.
  • said composition comprises a compound of interest, such as a fatty acid, an isoflavone, a vitamin, an oligoelement, or combinations thereof.
  • the invention relates to a nutritional supplement comprising said composition and a food grade vehicle.
  • the invention relates to the use of a composition comprising an extract of rosemary and vitamin E for the preparation of a medicament.
  • the invention relates to the use of a composition comprising an extract of rosemary and vitamin E in the preparation of a medicament for the prevention and / or treatment of a disorder that occurs with an inflammatory process, or for the prevention and / or treatment of a disorder that occurs with an increase in lipid peroxidation, or for the prevention and / or treatment of an adverse effect of ionizing radiation.
  • the invention in another aspect, relates to a combined oral preparation for separate, simultaneous or sequential use, comprising at least one extract of rosemary and vitamin E, wherein the rosemary extract is between 10% and 90% in weight with respect to the total combined preparation, and vitamin E accounts for between 10% and 90% by weight with respect to the total combined preparation.
  • a composition comprising Rosmarinus officinalis and vitamin E can be used for the reduction of inflammatory processes or for the reduction of lipid peroxidation.
  • said composition can also be used for the prevention and / or treatment of at least one adverse effect of ionizing radiation.
  • said composition has an unexpected synergistic effect with respect to both ingredients administered separately, as shown in Examples 1 and 2.
  • said composition can be used as a dietary supplement.
  • composition of the invention comprising an extract of rosemary and vitamin E, wherein:
  • the weight ratio between rosemary extract and vitamin E is not 1: 1 (p: p), if the percentage of rosemary extract in the composition is less than 0.2% by weight with respect to the total composition, then the percentage of vitamin E in said composition is greater than 0.4% by weight with respect to the total composition, and
  • the percentage of vitamin E in the composition is less than 0.4% by weight with respect to the total composition, then the percentage of rosemary extract in said composition is greater than 0.2% by weight with respect to the total of the composition. composition.
  • rosemary extract refers to a compound or mixture of active compounds extracted from the Rosmarinus officinalis plant, or parts thereof.
  • the leaves of the plant are those that present the highest number of active compounds and in greater concentration.
  • the rosemary extract is obtained from the leaves of the plant, or from the inflorescences of the plant or from the leaves and inflorescences of the plant.
  • the extract of rosemary can be obtained by methods conventional classics known to the person skilled in the art including, but not limited to, distillation, maceration, percolation or leaching, soxhlet extraction, decoction, infusion, digestion, extraction by supercritical fluids, or any combination of the foregoing; however, in a particular embodiment, said rosemary extract is obtained by methods based on extraction with solvents, extraction by pressing or extraction with supercritical fluids.
  • the material In the case of extraction with solvents, the material must previously be ground, macerated or chopped, to allow a greater contact area between the solid and the solvent. To achieve better efficiency in the operation, it is convenient to carry out the process in continuous movement. It is preferably carried out at ambient temperature and pressure.
  • the process can be executed in batch (batch) or continuously (such as percolation, leaching and soxhlet type extraction).
  • the most commonly used solvents are ethanol, methane 1, isopropanol, hexane, cyclohexane, toluene, xylene, ligroin, ethyl ether, isopropyl ether, ethyl acetate, acetone, chloroform, etc.
  • the next step is to separate the solvent from the extract by evaporation, vacuum distillation, molecular distillation or by extraction by supercritical fluids.
  • the resulting extract generally green (although the hue may vary) and highly viscous, is usually subjected to concentration by molecular distillation.
  • the plant material is subjected to pressure, either in batch presses or continuously by, for example, the use of high or low pressure worm gear equipment, expeller extractors , centrifugal extractors, decanter extractors, press rollers, etc.
  • Extraction under supercritical conditions is based on the use of chemical compounds that, at room temperature, are in liquid or gaseous state and, under conditions of pressure and temperature above their critical point (point where the density of the liquid and gaseous state it is the same) they go to a supercritical state that is defined by the coexistence of the two states presenting the behavior and characteristics of both states.
  • ⁇ For the extraction by supercritical fluids are used compounds such as, without being limited to, carbon dioxide (C0 2 ), methane, methanol, ethane, ethylene, ethanol, propane, propylene, acetone, acetylene, trifluoromethane, chlorotrifluoro-methane, trichlorofluoromethane, dinitrogen monoxide, ammonium, water, cyclohexane, n-pentane, xenon, krypton, phenol, isopropanol, isobutanol, cyclohexanol, chloroform, toluene, or any combination thereof, which in this supercritical state have a great extraction capacity.
  • C0 2 carbon dioxide
  • methane methane
  • methanol methane
  • ethane ethylene
  • ethanol propane
  • propylene acetone
  • acetylene trifluoromethane
  • the use of this technique allows the resulting mixture or extract to present a lower quantity of solvents than with the extraction by liquid solvents, thus improving the ease of its elimination. In addition, it allows to obtain extracts with higher concentrations of the compounds of interest and reduce the generation of waste.
  • the extracted compounds undergo less alterations so their activity is not reduced by the extraction process as it occurs through the use of liquid solvents. Therefore, in a preferred embodiment of this aspect of the invention, the rosemary extract is obtained by extraction by supercritical fluids.
  • the critical point corresponds to the conditions of temperature and pressure, for a gas or a vapor, above which the substance can no longer be “liquefied” by increasing pressure .
  • the properties of the liquid and / or vapor phase are the same, ie there is no visible or measurable differentiation between gas and liquid.
  • the substance most used for extraction under supercritical conditions is C0 2 , which under these conditions has low viscosity, low surface tension, high diffusion coefficient (10 times more than a normal liquid), which leads to high contact with the surface of the material and can penetrate small pores and slits of it which ensures a good efficiency in the extraction in a short time.
  • rosemary extraction is carried out by extraction under supercritical conditions using C0 2 .
  • the plant extracts obtained by supercritical fluids maintain a more or less constant composition. Despite this, due to the plant variability, the chemical composition of the extracts may vary.
  • rosemary extracts obtained from R. officinalis are, for example, but without limitation, rosmanol, carnosol, carnosic acid, rosmarinic acid, methyl carnosate, caffeic acid, rosmaridiphenol, flavonoids such as genkwanina, escutellareina and other compounds such as verbenone, camphor, borneol and 1,8-cineol.
  • flavonoids such as genkwanina, escutellareina
  • other compounds such as verbenone, camphor, borneol and 1,8-cineol.
  • the antioxidant compounds that have shown the greatest potential are carnosic acid, carnosol and rosmarinic acid.
  • vitamin E includes any of the existing isoforms of said vitamin E, ie the 4 forms of tocopherols ( ⁇ , ⁇ , ⁇ and ⁇ forms) and the corresponding tocotrienols. It may also refer to a water-soluble form (tocopheryl acetate), water-soluble (tocopheryl phosphate). Other possible derivatives of vitamin E obtained synthetically are also included, such as ⁇ -tocopherol acetate and di- ⁇ -tocopherol and mixed tocopherols obtained by distillation of vegetable fatty fruits or tocotrienols. Vitamin E is commonly obtained from commercial suppliers, such as Calbiochem®, Sigma-Aldrich®, etc. The different isoforms of vitamin E present the following general formula:
  • the lipid-soluble form of vitamin E accounts for between 1% and 90% by weight of vitamin E, typically between 5% and 70%, generally between 10% and 50%.
  • the water-soluble form of vitamin E accounts for between 1% and 90% by weight of vitamin E, typically between 5% and 70%, generally between 10% and 50%.
  • the ⁇ -tocopherol and ⁇ -tocopherol forms each assume between 1% and 90%> by weight of vitamin E, typically between 5% and 70%>, usually between 10%> and 50%>.
  • the composition of the invention can be administered orally, so it will be presented in a form of administration suitable for administration orally, for example, liquid, solid or semi-solid.
  • the composition of the invention comprises only, is constituted or substantially constituted by, rosemary extract and vitamin E, wherein the rosemary extract is comprised between 0, 1% and 99, 9% by weight respect to the total of the composition and vitamin E is comprised between 99.9% and 0.1%) by weight with respect to the total composition.
  • the The composition of the invention may contain 0.5%, 1%, 5%, 10%>, 25%, 50%> or 75% by weight of rosemary extract and the corresponding amount of vitamin E, ie 99.5 %, 99%, 95%, 90%, 75%, 50% or 25%, respectively.
  • the weight ratio rosemary extract: vitamin E present in the composition of the invention can vary within a wide range, typically between 1: 10 and 10: 1, preferably between 1: 5 and 5: 1, preferably between about 1: 2 and 2: 1.
  • composition of the invention can be obtained by conventional methods, for example, by mixing the extract of rosemary and vitamin E in the appropriate amounts.
  • composition of the invention comprises, in addition to rosemary extract and vitamin E, a vehicle selected from a pharmaceutically acceptable carrier and a food grade vehicle.
  • vehicle refers, in general, to any product that serves to transport the composition based on rosemary extract and vitamin E.
  • said vehicle is a suitable vehicle for oral administration of the composition based on rosemary extract and vitamin E, that is, any product that can be used for oral administration that can be used to accompany these products and that can perform their function in a safe and effective way .
  • the composition of the invention comprises, in addition to rosemary extract and vitamin E, a pharmaceutically acceptable carrier, the resulting composition is a pharmaceutical composition.
  • the composition of the invention comprises a food grade vehicle, said composition would constitute, or be in the form of, a nutritional supplement.
  • compositions therefore, in another aspect, relates to a pharmaceutical composition
  • a pharmaceutical composition comprising a pharmaceutically effective amount of the active ingredients of the composition of the invention (rosemary extract and vitamin E) and at least one pharmaceutically acceptable excipient.
  • the active compounds are usually accompanied by pharmaceutically acceptable vehicles or excipients, ie, compounds that are capable of being administered to an animal or a human being, and that improve various characteristics of the active compounds.
  • excipients include, but are not limited to, coatings, dispersants, colorants, flavors, surfactants, flavoring agents, glidants, fillers, absorption improvers or binders.
  • the rosemary extract and vitamin E based composition can therefore be combined with one or more pharmaceutically acceptable carriers or inert excipients, including, but not limited to, binders such as micro crystalline cellulose, gum tragacanth, or gelatin; excipients such as starch or lactose; dispersing agents such as alginic acid or corn starch; lubricants such as magnesium stearate, glidants such as colloidal silicon dioxide; flavors such as sucrose or saccharin; or flavoring agents such as peppermint or methyl salicylate.
  • the composition further comprises rosemary extract and vitamin E at least one pharmaceutically acceptable excipient.
  • the person skilled in the art can select the excipients to be incorporated based on the chosen administration form.
  • Information on pharmaceutically acceptable carriers or excipients suitable for the practice of the present invention are described in any Galenica treatise, for example, in “Remington's Pharmaceutical Sciences” by EW Martin, 1995.
  • the vehicles of the invention are approved by Regulatory agencies (eg, FDA - Food and Drug Administration, etc.) or are listed in the Pharmacopoeias, for example, in the British, Spanish or United States Pharmacopoeia, or other pharmacopoeia generally recognized for use in animals, and more particularly in humans.
  • the composition of the invention including the pharmaceutical composition comprising rosemary extract, vitamin E and one or more pharmaceutically acceptable carriers or excipients, will be formulated into a suitable administration form for oral administration, for which the appropriate excipients for the chosen form of administration will be chosen.
  • Solid dosage forms for oral administration may include conventional capsules, sustained release capsules, conventional tablets, sustained release tablets, chewable tablets, sublingual tablets, effervescent tablets, pills, suspensions, powders, granules and gels.
  • the active compounds can be mixed with at least one inert diluent such as sucrose, lactose or starch.
  • Said dosage forms may also comprise, as in normal practice, additional substances other than inert diluents, for example, lubricating agents such as magnesium stearate.
  • additional substances other than inert diluents, for example, lubricating agents such as magnesium stearate.
  • the dosage forms may also comprise buffering agents.
  • the soft gelatin capsules can be prepared to contain a mixture of the active compounds or compositions of the invention and vegetable oil.
  • the hard gelatine capsules may contain granules of the active compound in combination with a solid, powdery carrier such as lactose, sucrose, sorbitol, mannitol, potato starch, corn starch, amylopectin, cellulose derivatives and gelatin. Tablets and pills can be prepared with enteric coatings.
  • the composition of the invention can be administered in liquid dosage forms for oral administration.
  • the form of administration is through gelatin capsules, preferably soft gelatin capsules, which comprise, in addition to the composition of the invention, water, gelatin, glycerin and vegetable oil.
  • the vegetable oil is virgin olive oil.
  • the compounds having the anti-inflammatory, antioxidant and / or radioprotective effects in the pharmaceutical composition are rosemary extract and vitamin E, these must be advantageously in the highest possible amounts, allowing the addition of other components if necessary, such as, but not limited to, excipients. Therefore, in a particular embodiment, the rosemary extract supposes between 5% and 95% by weight with respect to the total weight of the pharmaceutical composition provided by this invention, comprising an extract of rosemary, vitamin E and, at least one pharmaceutically vehicle acceptable or excipient, generally between 10% and 90%, typically between 20% and 80%, preferably between 30% and 70%, more preferably, between 40% and 60% by weight with respect to the total of said pharmaceutical composition.
  • the rosemary extract accounts for between 5% and 25% by weight with respect to the total weight of the pharmaceutical composition provided by this invention.
  • vitamin E accounts for between 0.1% and 90%> by weight relative to the total weight of the pharmaceutical composition provided by this invention, comprising an extract of rosemary, vitamin E and, at least one pharmaceutically acceptable carrier or excipient, generally between 0.2% and 80%>, typically between 0.5%> and 70%>, preferably between 1% and 60%, more preferably, between 5% and 50% by weight with respect to the total of said pharmaceutical composition.
  • vitamin E accounts for between 0.2% and 5% by weight relative to the total weight of the pharmaceutical composition provided by this invention.
  • compositions of the invention comprising the composition of the invention and a pharmaceutically acceptable carrier can be obtained by conventional methods, for example, by mixing the rosemary extract, vitamin E and pharmaceutically acceptable carrier, in the appropriate amounts.
  • the components of the composition of the invention can be first mixed and the composition of the invention generated and mixed with the pharmaceutically acceptable carrier.
  • Nutritional supplement
  • the composition of the invention can be part of an enriched food product, for example, a dairy product or a derivative thereof such as a milkshake, cheese, milk, including flavored and fermented milk, yogurt, etc .; juice; a flour-based product or a derivative thereof, for example, bread, cake, a cookie, etc .; an oil; a candy, for example, a chewing gum, a candy, etc .; products based on fermented cereals; etc.
  • the composition of the invention can be used in the preparation of nutritional supplements for oral administration in liquid, solid or semi-solid form, for example, in the form of liquid suspensions, non-solid oral supplements, etc., or solids, for example, dry oral supplements (dehydrated), etc.
  • the composition of the invention is formed by elements that can be useful for nutritional or food purposes, since being formed by a component extracted from a plant species, as well as by a vitamin, it can be used to avoid nutritional deficiencies or to supplement the feeding. Therefore, due to its components the composition of the invention can be included in a food product or in a nutritional supplement, vitamin supplement, etc., it can be added to functional foods to try to improve its applicability or characteristics.
  • the invention relates to a nutritional supplement, hereinafter nutritional supplement of the invention, which comprises the composition of the invention and a food grade vehicle.
  • vitamin E has already been mentioned previously.
  • "nutritional supplement” is understood to be any dietary contribution that is consumed orally and that contains one or more nutrients intended to supplement the diet or to remedy a deficiency. Sayings Nutrients are often absent from the diet or are present at low concentrations.
  • nutritional supplements are distributed in the form of different presentations, such as tablets, capsules, soft capsules, liquids (syrups or beverages) and powders.
  • Said nutritional supplement may contain conventional excipients, such as binders, diluents, disintegrants, lubricants, humectants, etc., and may be prepared by conventional methods.
  • Examples of nutritional supplements may be, among others, liquid suspensions, dry oral supplements, non-dry oral supplements, etc.
  • food-grade vehicle means any product capable of being used in human or animal food. The choice of the suitable vehicle for oral administration for each case is made by an expert in the field from conventional vehicles existing in the state of the art.
  • the amount of rosemary extract and vitamin E in the nutritional supplement provided by this invention can vary within a wide range; nevertheless, in a particular embodiment, the rosemary extract supposes between 5% and 95% in weight with respect to the total weight of the nutritional supplement provided by this invention, which comprises an extract of rosemary, vitamin E and, at least one vehicle of degree food, generally between 10% and 90%, typically between 20% and 80%, preferably between 30% and 70%, more preferably, between 40% and 60% by weight with respect to the total of said nutritional supplement. In a specific embodiment, the rosemary extract supposes between 5% and 25% by weight with respect to the total weight of the nutritional supplement provided by this invention.
  • vitamin E accounts for between 0.1% and 90% by weight relative to the total weight of the nutritional supplement provided by this invention, which comprises an extract of rosemary, vitamin E and at least one food grade vehicle , generally between 0.2% and 80%, typically between 0.5%> and 70%>, preferably between 1% and 60%, more preferably, between 5% and 50% by weight with respect to the total of said supplement nutritional
  • vitamin E accounts for between 0.2% and 5% by weight with respect to the total weight of the nutritional supplement provided.
  • the nutritional supplement of the invention also comprises rosemary extract and vitamin E and a food grade vehicle, a compound of interest, ie, a compound that provides value, in particular nutritional value, to the composition of the invention, for example, a fatty acid (including polyunsaturated fatty acids or PUFAs), an isoflavone, a vitamin, a trace element, etc.
  • a compound of interest ie, a compound that provides value, in particular nutritional value, to the composition of the invention, for example, a fatty acid (including polyunsaturated fatty acids or PUFAs), an isoflavone, a vitamin, a trace element, etc.
  • a compound of interest ie, a compound that provides value, in particular nutritional value, to the composition of the invention, for example, a fatty acid (including polyunsaturated fatty acids or PUFAs), an isoflavone, a vitamin, a trace element, etc.
  • said compounds of interest include:
  • PUFAs eg, omega-3 acids (eg, alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), etc.), omega-6 (eg, linoleic acid, docosapentaenoic acid, etc.) , omega-9 (eg, oleic acid, eicosatrienoic acid, etc.), etc. and its combinations;
  • omega-3 acids eg, alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), etc.
  • omega-6 eg, linoleic acid, docosapentaenoic acid, etc.
  • omega-9 eg, oleic acid, eicosatrienoic acid, etc.
  • isoflavones e.g., daidzein, glycitein, genistein, etc., and combinations thereof;
  • vitamin C ascorbic acid
  • vitamin D vitamin D
  • vitamin B also includes choline, carnitine, and alpha, beta, and gamma-carotenes; in a particular embodiment, vitamin A, vitamin D3, vitamin B9, vitamin B6, vitamin B12, vitamin C, vitamin Bl, vitamin B2, vitamin B3, vitamin B5, vitamin B7 and vitamin K, etc., or combinations thereof
  • Trace elements, or chemical elements required by organisms in small quantities, other than carbon, hydrogen, nitrogen and oxygen and obtained by diet for example, calcium, iron, zinc, magnesium, phosphorus, copper, iodine, selenium, chromium, potassium, chlorine, etc., and combinations thereof.
  • Table 1 are indicated the preferred amounts of some of said compounds of interest that can be incorporated into the composition of the invention:
  • the composition of the invention further comprises rosemary extract and vitamin E a compound of interest, such as a compound of those previously defined.
  • the percentage of the rosemary extract is between 1% and 50%, typically around 3% and 40%, preferably, between 5% and 25%, by weight, with respect to the total composition; and the percentage of vitamin E is present in a percentage comprised between 0.1% and 25%, typically between 0.15% and 10%, preferably between 0.2%) and 5% by weight with respect to to the total of the composition.
  • the nutritional supplement of the invention is administered orally to the subject, either by means of a solid, semi-solid or liquid administration form.
  • Solid forms of administration for oral administration include, but are not limited to, conventional capsules, sustained release capsules, conventional tablets, sustained release tablets, chewable tablets, sublingual tablets, effervescent tablets, pills, suspensions, powders, granules and gels. , etc., as previously mentioned in connection with the pharmaceutical compositions provided by this invention.
  • the active compounds (rosemary extract, E-triprin and, where appropriate, compound of interest) can be mixed with at least one inert diluent such as sucrose, lactose or starch.
  • Said administration forms may also comprise, as in normal practice, additional substances other than inert diluents, for example, lubricating agents such as magnesium stearate.
  • the administration forms may also comprise buffering agents.
  • the soft gelatin capsules can be prepared to contain a mixture of the active compounds or compositions of the invention and vegetable oil.
  • the hard gelatine capsules may contain granules of the active compound in combination with a solid, powdery carrier such as lactose, sucrose, sorbitol, mannitol, potato starch, corn starch, amylopectin, cellulose derivatives and gelatin. Tablets and pills can be prepared with enteric coatings.
  • the form of administration are gelatin capsules, preferably soft gelatin capsules, which comprise, in addition to the composition of the invention, water, gelatin, glycerin and a vegetable oil.
  • the vegetable oil is olive oil Virgin.
  • Said capsules contain between 25 and 3,000 mg of the composition of the invention which includes an extract of rosemary and vitamin E, and, additionally, among other ingredients, water, gelatin, glycerin and vegetable oil.
  • the total amount of the rosemary extract in said capsules is between 100 and 500 mg, while the total amount of vitamin E is between 5 and 15 mg.
  • the nutritional supplement provided by this invention comprising the composition of the invention and a food grade vehicle, and, optionally, compound of interest
  • the components of the composition of the invention can be first mixed and the composition of the invention generated and mixed with the food grade vehicle, and, optionally, with the compound of interest. Any order and appropriate form of mixing said components to obtain said nutritional supplement is contemplated within the scope of the present invention.
  • composition of the invention as well as the pharmaceutical composition provided by this invention, are useful for the treatment (including prevention) of disorders that occur with an increase in inflammatory processes and / or with an increase in lipid peroxidation, as well as with adverse effects of ionizing radiation. Therefore, in another aspect, the invention relates to the use of a composition comprising an extract of rosemary and vitamin E for the manufacture of a medicament. Expressed alternatively, the invention also relates to a composition comprising an extract of rosemary and vitamin E for use in medicine or as a medicine.
  • said composition is a composition formulated for oral administration.
  • compositions formulated for oral administration.
  • the characteristics of this type of compositions, including Pharmaceutical dosage and / or dosage forms suitable for oral administration have already been mentioned previously in connection with the pharmaceutical composition provided by this invention and are incorporated herein by reference.
  • said composition comprising an extract of rosemary and vitamin E is a composition of the invention, ie, a composition comprising an extract of rosemary and vitamin E, wherein:
  • the weight ratio between rosemary extract and vitamin E is not 1: 1 (p: p), - if the percentage of rosemary extract in the composition is less than 0.2% by weight with respect to the total composition, then the percentage of vitamin E in said composition is greater than 0.4% by weight with respect to the total composition, and
  • the percentage of vitamin E in the composition is less than 0.4% by weight with respect to the total composition, then the percentage of rosemary extract in said composition is greater than 0.2% by weight with respect to the total of the composition. composition.
  • composition of the invention is administered orally.
  • the invention relates to the use of a composition comprising an extract of rosemary and vitamin E for the preparation of a medicament for the prevention and / or treatment of a disorder that involves an inflammatory process, or for the prevention and / or treatment of a disorder that occurs with an increase in lipid peroxidation, or for the prevention and / or treatment of an adverse effect of ionizing radiation.
  • the invention also relates to a composition comprising an extract of rosemary and vitamin E for use in the prevention and / or treatment of a disorder that involves an inflammatory process, or for the prevention and / or treatment of a disorder that occurs with an increase in lipid peroxidation, or for the prevention and / or treatment of an adverse effect of ionizing radiation.
  • said composition is a composition formulated for oral administration.
  • said composition comprising an extract of rosemary and vitamin E is a composition of the invention.
  • said composition of the invention is administered orally.
  • inflammatory process refers to a nonspecific response to environmental insults, and is generated by inflammatory agents.
  • the inflammatory response occurs only in vascularized connective tissues and arises for the defensive purpose of isolating and destroying the harmful agent, as well as repairing the damaged tissue or organ. Therefore, a mechanism of innate, stereotyped immunity is considered, in contrast to the adaptive immune reaction, specific for each type of infectious agent.
  • the fundamental action of cytokines is the regulation of the mechanism of inflammation.
  • the main pro-inflammatory cytokines that act in the nonspecific response or inflammation are: Interleukin 1 (IL-1), Alpha Tumor Necrosis Factor (TNF- ⁇ ), Interleukin 8 (IL-8), Interleukin 12 (IL-12) , Interleukin 16 (IL-16) and Interferons.
  • IL-6 and IL-12 act on specific immunity: IL-6 is an autocrine factor of B7 lymphocytes while IL-12 stimulates cytotoxic cell immunity.
  • CRP C-reactive protein
  • Illustrative examples, not limiting, of disorders that occur with an inflammatory process include allergies, myopathies, different types of cancer, acne, asthma, chronic prostatitis, glomerolonephritis, hypersensitivity, interstitial cystitis, atherosclerosis, osteoarthritis, multiple sclerosis, Guillain-Barre syndrome , Crohn's disease, ulcerative colitis, psoriasis, graft rejection disease, systemic lupus erythematosus, obesity and insulin-dependent diabetes mellitus.
  • composition based on rosemary extract and vitamin for example, the composition of the invention, could be used to treat other disorders associated with high levels of proinflammatory cytokines, such as in response to infectious agents and in a large number of autoimmune diseases, for example, rheumatoid arthritis, toxic shock syndrome, diabetes, etc.
  • said inflammatory processes are related to menopause.
  • the composition of the invention is capable of decreasing inflammation, specifically decreasing the pro-inflammatory cytokines, in particular, the cytokines TNF-alpha and IL-6.
  • the expression of some / s of the aforementioned compounds is measured.
  • the proinflammatory cytokines are measured; for this, conventional methods such as, for example, those mentioned in Example 1 can be followed. Therefore, a person skilled in the art knows that if a decrease in the expression of pro-inflammatory cytokines is detected, it implies an anti-inflammatory effect. and therefore, a positive effect of the composition of the invention.
  • lipid peroxidation refers to the oxidative degradation of lipids. It is the process through which free radicals capture electrons from lipids in cell membranes. This process is initiated by a chain reaction mechanism of a free radical. In most cases it affects polyunsaturated fatty acids, because they contain multiple double bonds among which are the methylene groups (-CH 2 -) that have particularly reactive hydrogens. Lipid peroxidation is a well-known mechanism of cell damage in animals, and is therefore sometimes used as an indicator of oxidative stress and biomarker of environmental contamination.
  • malonyl aldehyde (MDA) and 4-hydroxyalkene (4-HNE) are generated as final products of the reaction, among others. Thanks to its determination, it is possible to quantify the lipid peroxidation and, therefore, oxidative stress in organisms.
  • Disorders associated with an increase in lipid peroxidation include, but are not limited to, liver diseases (such as hepatitis, cirrhosis, liver cancer), Alzheimer's, different types of cancer, AIDS, intestinal ischemia, Crohn's disease, ulcerative colitis, etc. .
  • the determination of the levels of lipid peroxidation in the invention is carried out by conventional methods known to a person skilled in the art (see, for example, Example 1).
  • menopause refers to the transition from the reproductive stage of a woman to the non-reproductive stage.
  • Such symptoms include but are not limited to one or more symptoms commonly experienced by women during periods associated with hormonal fluctuations, such as menopause, such as dysmenorrhea, fluid retention in the body, fatigue, dizziness, headaches, sweating sudden, insomnia, nausea, diarrhea, constipation, heart palpitations, abdominal cramps, mood swings, irascibility, violent tendencies, anxiety, nervousness, tension, difficulty concentrating, depression, forgetfulness, appetite increases, back pain, osteoporosis and increased emotional sensitivity.
  • hormonal fluctuations such as menopause, such as dysmenorrhea, fluid retention in the body, fatigue, dizziness, headaches, sweating sudden, insomnia, nausea, diarrhea, constipation, heart palpitations, abdominal cramps, mood swings, irascibility, violent tendencies, anxiety, nervousness, tension, difficulty concentrating, depression, forgetfulness, appetite increases, back pain, osteoporosis and increased emotional sensitivity.
  • ionizing radiation is understood to mean that radiation capable of producing electrically charged atoms or molecules due to the gain or loss of electrons, and therefore capable of altering their structures and functions, as, for example, although without limitation, electromagnetic waves (X rays or ⁇ rays) or particles (particles, ⁇ particles, protons, neutrons, muons or pions).
  • An individual may be exposed to radiation in multiple situations, such as, but not limited to, nuclear power plants, the use or treatment of radioactive material from medical devices, the treatment of radioactive waste, radiation therapy, manipulation or exposure to ionic detectors. smoke, natural radiation or cosmic radiation.
  • adverse effect of ionizing radiation in the present invention is understood to mean that undesirable or toxic effect produced by said radiation that implies an alteration of the physiological situation in a tissue or cell, such as, but not limited to, an increase in the membrane permeability, inflammation, generation of free radicals, chromosome rupture, mutations, reduction of ciliary motility, vacuolization or apoptosis.
  • Adverse effect is also understood as any effect derived from the foregoing, such as, but not limited to, hair loss, headache, nausea, dizziness, fainting, delirium, coma, radiation enteritis, throat irritation, epistaxis, burns in skin, vomiting, anorexia, weight loss, fever, intestinal bleeding, temporary or permanent sterility, abnormal tissue reproduction, cataracts, plastic anemia, leukemia or cancer.
  • Radiotherapy is understood in the present description, that medical treatment based on the use of ionizing radiation that seeks to obtain a benefit in the organism. Normally this treatment is used, although not limited, for the removal of a tumor or a cancer.
  • the nervous system, as well as the digestive system, are two of the most sensitive systems to the indirect effects of radiotherapy treatments. These two systems, in patients treated with radiotherapy, can present complications. Digestive problems are one of the most widespread complications in those patients who have to undergo radiotherapy treatment in which it must inevitably reach the digestive system. An example is radiation enteritis, where the inner wall of the intestine is inflamed by radiotherapy.
  • an even more preferred embodiment of this aspect of the invention relates to the use of a composition comprising rosemary extract and vitamin E, for example, a composition of the invention, for the preparation of a medicament for prevention and / or the treatment of at least one adverse effect of ionizing radiation where the tissue exposed to radiotherapy is a tissue of the digestive system or the nervous system.
  • the adverse effect related to the digestive system is for example, but without limitation, enteritis, nausea, vomiting, anorexia, intestinal bleeding or cancer.
  • the adverse effect related to the nervous system is for example, but not limited to, headache, dizziness, fainting, delirium, fever, coma or cancer.
  • the composition comprising rosemary extract and vitamin E e.g., a composition of the invention
  • the composition will be formulated with the pharmaceutically acceptable excipients suitable for the form of chosen administration, as previously mentioned in connection with the pharmaceutical composition provided by this invention.
  • said pharmaceutical composition is administered orally so it will include the excipients suitable for the desired solid or liquid oral administration form.
  • the invention relates to a method of treatment and / or prevention of:
  • the effective amount of the composition of the invention to be administered will depend, among other factors, on the individual to be treated, the severity of the disorder suffered by said subject, etc. For this reason, the doses mentioned in this invention should only be considered as guidelines for the person skilled in the art, and he should adjust the doses according to the variables mentioned above.
  • the invention also contemplates the administration of the extract of rosemary and vitamin E to a subject separately, jointly or sequentially, depending on which is the most appropriate administration regimen in each case. Therefore, it would be useful to carry out a combined preparation that includes both components and allows the administration of the compounds jointly, separately or sequentially. Therefore, in another aspect, a combined oral preparation (hereinafter “combined preparation of the invention") is described for its separate, simultaneous or sequential use, comprising at least one extract of rosemary and vitamin E, wherein rosemary extract is between 10% and 90% by weight with respect to the total combined preparation, and vitamin E accounts for between 10% and 90% by weight with respect to the total combined preparation.
  • the ratio of rosemary extract and vitamin E is from 1: 5 to 5: 1, preferably 1: 2 to 2: 1.
  • each of the components may be accompanied by pharmaceutically acceptable excipients. that provide them with suitable characteristics for their administration. Therefore, in one embodiment Preferred, the combined preparation of the invention further includes at least one pharmaceutically acceptable excipient.
  • the rosemary extract is between 5% and 95% by weight with respect to the total weight of the combined preparation of the invention, generally between 10%) and 90%), typically between 20%> and 80%>, preferably between 30%> and 70%>, more preferably, between 40% and 60% by weight with respect to the total of said combined preparation of the invention.
  • the rosemary extract accounts for between 5% and 25% by weight with respect to the total weight of the combined preparation of the invention.
  • vitamin E accounts for between 0.1% and 90% by weight relative to the total weight of the combined preparation of the invention, generally between 0.2%> and 80%>, typically between 0.5%> and 70%>, preferably between 1% and 60%>, more preferably, between 5% and 50% by weight with respect to the total of said combined preparation of the invention. In a specific embodiment, vitamin E accounts for between 0.2% and 5% by weight relative to the total weight of the combined preparation of the invention.
  • the characteristics of rosemary extract and vitamin E have already been mentioned previously, so they are incorporated herein by reference.
  • Said combined preparation of the invention can be used as a medicine. Therefore, in another aspect, the invention relates to the use of the combined preparation of the invention for the preparation of a medicament. Expressed alternatively, the invention relates to a combined preparation of the invention for use in medicine or as a medicament.
  • the invention relates to the use of said combined preparation of the invention for the preparation of a medicament for the prevention and / or treatment of a disorder that occurs with an inflammatory process, or for the prevention and / or treatment of a disorder that occurs with an increase in lipid peroxidation, or for the prevention and / or treatment of an adverse effect of ionizing radiation.
  • the invention also relates to a combined preparation of the invention for its use in the prevention and / or treatment of a disorder that occurs with an inflammatory process, or for the prevention and / or treatment of a disorder occurring with an increase in lipid peroxidation, or for the prevention and / or treatment of an adverse effect of ionizing radiation.
  • the adverse effect occurs in a tissue exposed to radiotherapy; in particular, said tissue is tissue of the digestive or nervous system.
  • the term “combined preparation” or also referred to as “juxtaposition”, in this specification, means that the components of the combined preparation do not need to be present as a unit, for example, in a composition, in order to be available for its separate or sequential application.
  • the expression “juxtaposed” implies that it is not necessarily a true combination, in view of the physical separation of the components.
  • the dosage of this combined preparation to obtain a therapeutically effective amount depends on factors such as, but not limited to, the age, weight, sex or tolerance of the mammal.
  • another preferred embodiment refers to the use of the combined preparation for the preparation of a medicament characterized in that the medicament is administered at a daily dose of 25 mg to 3,000 mg of the combined preparation.
  • the combined preparation of the invention is suitable for oral administration.
  • This administration of oral form is preferably carried out, but without limitation, in the form of capsules or tablets. Therefore, a preferred embodiment of this aspect of the invention refers to the use of the combined preparation for the preparation of a medicament in solid form.
  • the combined preparation of the invention may also contain, if desired, one or more compounds of interest, as previously defined.
  • the extract of rosemary is obtained in an extractor for supercritical fluids using C0 2 as an extractant agent.
  • Rosemary leaves dried in darkness and subjected to cryogenic grinding are extracted by percolation of C0 2 at a pressure comprised between 100 bar (100 x 10 5 Pa) and 300 bar (300 x 10 5 Pa) and at a temperature between 40 ° C and 60 ° C.
  • the amount of C0 2 used is between 10 kg and 40 kg for each kg of rosemary (Rosmarinus officinalis) dried and ground.
  • the obtained extract is divided in line into 2 different separators mounted in series with independent control of temperature and pressure.
  • the first separator works at 30 ° C and at a pressure between 30% and 60% of the extraction
  • the second separator works at 30 ° C and at a pressure between 30% and 60% of the first separator.
  • This model also served to evaluate the anti-inflammatory and antioxidant effect of the composition comprising vitamin E and rosemary extract in the nervous system.
  • lipid peroxidation [expressed as MDA / mg of total protein, in nervous tissue samples (hippocampus) obtained at 2 hours post-radiation and at 72 hours post-radiation with the expression of said chemokines, pro-inflammatory cytokine and lipid peroxidation in a control group subjected to the same gamma radiation but without having been administered the treatment with rosemary extract and vitamin E.

Abstract

La présente invention concerne une composition comprenant un extrait de romarin et de la vitamine E, laquelle composition peut être utilisée comme complément alimentaire et pour préparer des compositions pharmaceutiques destinées à réduire les processus inflammatoires et la peroxydation lipidique de manière générale, en particulier les processus associés à la ménopause, et à prévenir et/ou traiter les effets secondaires des rayonnements ionisants.
PCT/ES2011/070586 2011-08-05 Composition à base d'extrait de romarin et de vitamine e et applications de celle-ci Ceased WO2012017128A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
ES201031225A ES2374482B1 (es) 2010-08-05 2010-08-05 Composición para la reducción de síntomas asociados a la menopausia.
ESP201031225 2010-08-05

Publications (3)

Publication Number Publication Date
WO2012017128A2 WO2012017128A2 (fr) 2012-02-09
WO2012017128A1 true WO2012017128A1 (fr) 2012-02-09
WO2012017128A3 WO2012017128A3 (fr) 2012-03-08

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