• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
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  • 优先权
    • 专利摘要:
    The encapsulated formulations comprise a capsule comprising tablets, microgranules, powder or granules of some, or all, of the following food components or supplements: plant extracts, vitamins, minerals, and amino acids. The capsule is used for the manufacture of a food supplement for the prevention and treatment of different types of disorders. (Machine-translation by Google Translate, not legally binding)
    公开号:ES2695503A1
    申请号:ES201730871
    申请日:2017-06-30
    公开日:2019-01-08
    发明作者:Aubareda Barbara Jane
    申请人:Pharmalink S L；
    IPC主号:
    专利说明:

    [0001]
    [0002]
    [0003]
    [0004] Field of the technique
    [0005]
    [0006] The present invention relates to food supplements in the form of capsules comprising different formulations of different components with different release forms, as well as their use to combat different disorders.
    [0007]
    [0008] Antecedents of the Invention
    [0009]
    [0010] A food supplement (or supplement) is a vitamin, mineral, plant extract or amino acid, which is taken to improve health or well-being.
    [0011]
    [0012] Although most of these supplements can be obtained with a varied diet, through food, there are many cases in which they are necessary, such as: vegetarians, pregnant women, lactating women, women with strong menstrual periods, women during and after of the menopause, people with gastrointestinal diseases, such as lactose intolerance or allergy to certain foods, people with diseases of the stomach, liver, pancreas or bile vesicle, and also to reduce the risk of cardiovascular diseases, cancer, etc.
    [0013]
    [0014] According to the US Department of Agriculture, most adults do not get enough of the following nutrients from the usual diet:
    [0015]
    [0016]
    [0017] The lack of some nutrients has been correlated with the higher incidence of certain diseases, as well as disorders of different severity such as sleep disorders, anxiety, joint pains, migraine.
    [0018]
    [0019] The human body takes advantage of these nutrients for many different functions, including the formation of bones, the production of hormones and the regulation of cardiac frequency. Many people with mild nutrient deficiencies have a predisposition to develop age-related diseases, such as cancer, heart disease, and loss of immune function or brain function.
    [0020]
    [0021] Different activities have been described for the different food supplements.
    [0022]
    [0023] Melatonin is produced in the body stimulated by the absence of light, which causes that the concentration of this hormone in the body increases at nightfall, with a maximum peak between 2 - 4 dawn. The external contribution of this hormone favors the conciliation of sleep. ( "Scientific Opinion on the substantiation of a health claim related to melatonin and reduction of sleep onset latency" ( ID 1698, 1780, 4080) pursuant to Article 13 of Regulation ( EC) No 1924/2006 and "Aging and Circadian Rhythms". Sleep Med Clin, 2015 December; 10 ( 4): 423-434, doi: 10.1016 / j.jsmc.2015.08.002).
    [0024]
    [0025] GABA is an inhibitory neurotransmitter in the mature brain. It is believed that GABA can influence the catabolism of serotonin to N-acetylserotonin and melatonin. Thus, the concomitant use of GABA and Melatonin has a synergistic action. ( "Neurotransmitters as food supplements: the effects of GABA on brain and behavior" Evert Boonstra, Roy de Kleijn, Lorenza S. Colzato, Anneke Alkemade, Birte U. Forstmann and Sander Nieuwenhuis, Cognitive Psychology Unit, Institute of Psychology, Leiden University, Leiden).
    [0026]
    [0027] The extract of Passiflora is widely used to treat cases of nervousness, insomnia or relief of anxiety. This is due to the sedative properties of the plant, research indicates that the compounds in the plant stimulate an increase in the production of gamma-aminobutyric acid, or cerebral GABA, which produces a mild sedative effect. ( "Efficacy and safety of a polyherbal sedative-hypnotic formulation NSF-3 in primary insomnia in comparison to zolpidem: A randomized controlled trial "Niteeka Maroo, Avijit Hazra, and Tapas Das)
    [0028] The Valerian extract, known since ancient times as valerian, is used as an anxiolytic. At present it is of demonstrated effectiveness in different clinical studies. ( "Efficacy and safety of a polyherbal sedative-hypnotic formulation NSF-3 in primary insomnia in comparison to zolpidem: A randomized controlled trial" Niteeka Maroo, Avijit Hazra, and Tapas Das).
    [0029]
    [0030] The kawa-kawa, kava kava or kava (Piper methysticum) is a plant of Polynesian origin. The roots of the plant are used to produce a beverage with sedative and anesthetic properties. Its active ingredients are called kavalactones. ( Kavain, the Major Constituent of the Anxiolytic Kava Extract, Potentiates GABAA Receptors: Functional Characteristics and Molecular Mechanism Han Chow Chua, Emilie TH Christensen, Kirsten Hoestgaard-Jensen, Leonny Y. Hartiadi, Iqbal Ramzan, Anders A. Jensen, Nathan L. Absalom, Mary Chebib).
    [0031]
    [0032] The mechanism of Kava's anxiolytic activity is postulated to be due to an improved binding to GABA type A receptors. ( Kavain, the Major Constituent of the Anxiolytic Kava Extract, Potentiates GABAA Receptors: Functional Characteristics and Molecular Mechanism Han Chow Chua, Emilie TH Christensen, Kirsten Hoestgaard-Jensen, Leonny Y. Hartiadi, Iqbal Ramzan, Anders A. Jensen, Nathan L. Absalom, Mary Chebib).
    [0033]
    [0034] Magnesium is a mineral that acts on the neurological system favoring sleep and relaxation, although the mechanism of action is little known. Situations of stress have been associated with a greater loss of magnesium in the body. ( The effects of magnesium supplementation on subjective anxiety Neil Bernard Boyle, Clare L. Lawton, Louise Dye School of Psychology, University of Leeds, Leeds, LS29JT, UK).
    [0035]
    [0036] Magnesium is present, typically, as Mg + 2 ion in all cells of the human body. Being the biologically active form of ATP, the main form of energy at the cellular level, that which is linked to magnesium. A recent metaanalysis concludes that the Mg + 2 deficit is strongly associated with migrainous crises.
    [0037]
    [0038] Vitamin B6 is involved in the metabolism of neurotransmitters that regulate mood, such as serotonin and in the synthesis of dopamine, adrenaline, norepinephrine and GABA (gamma-aminobutyric acid), which helps improve mood in cases of depression, stress and sleep disorders associated with lack of serotonin. There are studies which show that they improve the anxiolytic effect when it is administered together with magnesium. ( "The effects of magnesium supplementation on subjective anxiety") Neil Bernard Boyle, Clare L. Lawton, Louise Dye School of Psychology, University of Leeds, Leeds, LS2 9JT, UK, De Souza MC, Walker AF, Robinson PA, Bolland K "A synergistic effect of a daily supplement for 1 month of 200 mg magnesium plus 50 mg vitamin B6 for the relief of anxiety-related premenstrual symptoms: a randomized, double-blind, crossover study." J Womens Health Gend Based Med 2000; 9: 131-9; "Magnesium deficiency induces anxiety and HPA axis dysregulation: Modulation by therapeutic drug treatment" SB Sartori, N. Whittle, A. Hetzenauer, N. Singewald).
    [0039]
    [0040] 5-hydroxytryptophan (5-HTP), is a natural amino acid and chemical compound precursor and intermediary of the biosynthesis of the neurotransmitters serotonin and melatonin from tryptophan. ( "5-Hydroxytryptophan: A Clinically-effective Serotonin Precursor" by Timothy C. Birdsall, ND, Tryptophan overloading activates brain regions involved with cognition, mood and anxiety Luana CA Silva, Milena B. Viana, Jose S. Andrade, Melyssa A. Souza, Isabel C. Cespedes and Vania D'Almeida).
    [0041]
    [0042] Coenzyme Q10 is found mainly in the mitochondria, in the mitochondria energy is generated in the form of ATP through the cycle of krebs in the electron transport chain and participates in aerobic cell respiration. Ninety-five percent of the energy in the human body is generated in this way. Migraines are thought to be a mitochondrial disorder and mitochondrial dysfunction is improved with coenzyme Q10, so a supplement with CoQ10 may have a beneficial effect for the prophylaxis of migrainous crises. ( "Improvement of migraine symptoms with a proprietary supplement containing riboflavin, magnesium and Q10: a randomized, placebo-controlled, double-blind, multicenter trial" Charly Gaul, Hans-Christoph Diener, Ulrich Danesch and on behalf of the Migravent® Study Group ).
    [0043]
    [0044] Vitamin B2 (Riboflavin) is a vitamin B group involved in the synthesis of mitochondrial ATP. The recommended daily doses are 1.7 mg for adults. The assimilation of endogenous riboflavin is carried out mainly in the small intestine with a plasma half-life of 1 to 2 hours. Quantities greater than 30 - 50 mg of B2 are not assimilated by the organism, the excess being excreted in the urine. ( "Improvement of migraine symptoms with a proprietary supplement containing riboflavin, magnesium and Q10: a randomized, placebo-controlled, double-blind, multicenter trial" Charly Gaul, Hans-Christoph Diener, Ulrich Danesch and on behalf of the Migravent® Study Group ; "Effectiveness of Vitamin B2 versus Sodium Valproate in Migraine Prophylaxis: a randomized clinical trial" .Abolghasem Rahimdel, Ahmad Zeinali, Pouria Yazdian-anari, Rahele Hajizadeh, Ehsan Arefnia; "Intestinal absorption of water-soluble vitamins in health and disease" Hamid M. Said School of Medicine, University of California-Irvine, Irvine, CA 92697, USA, and Department of Medicine, VA Medical Center, Long Beach, CA 90822, USA ).
    [0045]
    [0046] Chondroitin sulfate (CS) is a major component of the extracellular matrix (ECM) of many tissues, including cartilage, bone, skin, ligaments and tendons. Osteoarthritis (OA) is characterized by a progressive change of structure and metabolism in joint tissues, mainly degradation, subchondral bone sclerosis and inflammation of the synovial membrane.
    [0047]
    [0048] CS is a sulfated glycosaminoglycan (GAG) composed of a long chain of unbranched polysaccharides with repetition of the disaccharide structure of N-acetylgalactosamine and glucuronic acid. The CS is responsible for many of the important properties of the cartilage, such as strength and elasticity. Its high aggrecan content plays an important role in allowing the cartilage to withstand pressure during various loading conditions. The sulfation profile of chondroitin has been described in the cartilage [Mourao, 1988]. Changes in CS structure have been described in tissues with OA [Caterson et al. 1990] and a decrease in CS-6: CS-4 has been found in synovial fl uid and cartilage in patients with OA [Shinmei et al. 1992]. More than three decades ago, it was proposed [Schwartz and Dorfman, 1975] that CS, as therapy for damaged cartilage, could provide the basic elements for the synthesis of the new component of the matrix (ECM), the administration of CS acts at please matrix regeneration.
    [0049]
    [0050] Glucosamine is one of the main macromolecules constituting the extracellular matrix (ECM) such as glycosaminoglycans. The relevant action mechanisms of glucosamine include the anti-inflammatory effect, the pro-anabolic effect, the promotion of osteoblast proliferation and the inhibition of catabolic intermediates. Chan and his colleagues reported that glucosamine plus chondroitin showed complementary anti-catabolic and anti-inflammatory effects compared to the use of glucosamine or chondroitin alone.
    [0051]
    [0052] Osteoarthrosis (OA) mainly affects the joints such as fingers, knees, hips, spine, wrist, elbows, shoulders and ankles. OA of the knee is the most frequent. Within the knee there is a substance called synovial fluid that acts as Body weight absorber when walking, jumping and running; at the same time that lubricates the articulations allowing a smooth and frictionless movement of the same. In a knee with OA the synovial fluid has undergone changes and has lost these qualities of cushioning and lubrication, leaving unprotected the cartilage and soft tissues, which produces pain and stiffness in the articulation, until reaching, in advanced stages, a destruction of the cartilage and damage to tendons and bones.
    [0053]
    [0054] Joint inflammation and pain are the main symptoms of this disease and can become incapacitating for those who suffer from it. Early treatment can help to delay the progression of the disease and reduce its symptoms.
    [0055]
    [0056] Curcuma longa (turmeric) has a long history of use in Ayurvedic Medicine as a treatment for inflammatory diseases. The turmeric is composed mainly of three curcuminoids: curcumin (diferuloylmethane, the primary constituent and responsible for its intense yellow color), demetoxicurcumin and bisdemetoxicurcumin. The turmeric interacts with different biomolecules involved in inflammatory processes, several studies have been published demonstrating the anti-inflammatory capacity of turmeric. However, due to the rapid metabolism of curcumin and its limited bioavailability, it has been necessary to associate the intake of this molecule with other compounds aimed at enhancing the bioavailability of this molecule, including the 10: 1 association with piperine to enhance its efficacy anti-inflammatory ( "Anti inflammatory Properties of Curcumin, a Major Constituent of Curcuma longa: A Review of Preclinical and Clinical Research." Julie S. Jurenka, MT (ASCP)).
    [0057]
    [0058] The association of curcumin with the alkaloid piperine, a constituent of black pepper and long pepper (Piper nigrum and Piper Longum, respectively) increases 20 times the bioavailability of curcumin by inhibition of hepatic and intestinal glucuronidation.
    [0059]
    [0060] The membrane of the egg shell is the material that separates from the shell typically after boiling or blanching an egg, they are the remains of the different membranes that protect the embryo during its development. The supplementation of the feed with membrane of the egg shell has shown good results in the disease of the joints. Its main composition is collagen, mostly type I, among other metabolites that have shown their action on joint problems such as glycosaminoglycans and proteins responsible for the mineralization of the egg shell. The membrane of the egg shell is also very rich in sulfur amino acids (SAA) that contribute to joint disinflammation, such as dermatan sulfate and chondroitin sulfate and sulphated glycoproteins including hexosamines, such as glucosamine. Other components identified in the eggshell membranes are hyaluronic acid, sialic acid, desmosin and isodesmosine, ovotransferrin, lysyl oxidase, lysozyme, and pN-acetylglucosaminidase. The discovery of the membrane of the egg shell as a source of collagen combined with glucosamine, chondroitin and hyaluronic acid associated with a multitude of other trace elements with synergistic anti-inflammatory action and repairing collagen make this compound an ideal candidate in diets for people with joint pains.
    [0061]
    [0062] Resveratrol is a polyphenol found naturally in grapes and red wine and has been shown to exert an important antioxidant effect. Since it was isolated for the first time in the mid-twentieth century, there are many studies and scientific articles that have worked with this molecule and highlight its antioxidant and anticancer properties and its relationship with the aging process.
    [0063]
    [0064] The rose hip or rosehip is the pomaceous fruit of the bushes of the genus Rosa. Rose hip is edible raw, being an excellent source of antioxidants among which include: vitamin C, vitamins A, D, E and antioxidant flavonoids.
    [0065]
    [0066] The Acai is the fleshy fruit of the Acai palm, common in the vegetation of the Amazon rainforest. At the moment its consumption has been popularized thanks to its great antioxidant power surpassing other fruits such as blueberries or raspberries.
    [0067]
    [0068] Quercetin is a flavonol that is present in fruits and vegetables especially in onions, apples, grapes, broccoli or tea, with a high antioxidant activity. In these foods quercetin is linked to polysaccharides, forming hydrophilic glucosides of low bioavailability. The organism assimilates them before hydrolysis in the small intestine. That is why our formula preserves the active in the stomach to be released quickly once the gastric emptying is done and reaches the upper part of the small intestine.
    [0069]
    [0070] All these food supplements are added to the diets of people suffering from different types of disorders, such as sleep disorders, anxiety, joint pains or migraine, in different dosage forms, with different administration patterns.
    [0071] This presents the problem that the patient must be able to follow an organized pattern of dose taking, in different ways, at different times of the day, before, after or with meals, which means a difficult follow-up by the patient, ace! as a lower effectiveness of such supplements. The complexity of the dosage affects compliance with the prescription.
    [0072]
    [0073] Wald and Law (Br. Med. J. 326, No. 7404, 1419-23, 2003) defined the term "pollinator" referring to the combination of drugs such as statins, antihypertensives, aspirin and vitamins, such as folic acid, for use in a single daily intake. These authors recommend the use of polypill as a way to achieve an important effect in the prevention of cardiovascular disease with a few adverse effects. The strategy of the polypill that contains several effective components to reduce cardiovascular risk factors thus avoiding a high incidence of cardiac attacks and strokes. They concluded that the polypill's strategy would be safe and that its widespread use would have a greater impact on the prevention of cardiovascular diseases in the Western countries than any other intervention and estimated that the polypill could reduce the incidence of coronary heart disease and stroke in 88 and 80%, respectively.
    [0074]
    [0075] Patent EP 2273985 A1 of Ferrer International offers new compositions in the form of capsules comprising a variable number of acetylsalicylic acid tablets, a variable number of tablets of a HMN-CoA reductase inhibitor and a variable number of tablets of an ACE inhibitor. , so that the number of tablets of each active ingredient can be customized to the individual characteristics of each patient or subgroup of population to which they are destined.
    [0076]
    [0077] But to date has not been described the preparation of "polyphers" of food supplements for the treatment of different types of disorders, such as sleep disorders, anxiety, joint pain or migraine.
    [0078]
    [0079] Exposition of the Invention
    [0080]
    [0081] The present invention is aimed at solving the problems represented by the administration to the same patient of different food supplements that act on different points of the body, with different mechanisms and with different absorption rates, and that may present interaction problems between them, since it consists of a single dosage form, a capsule, which contains different dosage forms of the different food supplements to be administered (tablets, microgranules, powder, etc.). granulate), in different forms of liberation, so that in a single capsule the administration of each and every one of the food supplements necessary to treat a certain disorder is achieved, with the dose and the administration regime necessary to achieve the desired quantities of each of the supplements.
    [0082]
    [0083] In this sense, the object of the present invention is to provide new compositions in the form of capsules comprising a variable number of tablets, microgranules, powder or granules, of different food supplements, such as: plant extracts, vitamins, minerals and / or amino acids.
    [0084]
    [0085] The capsules of the present invention can be of vegetable or animal origin, being preferred the capsules of the n ° 0 of vegetal origin and in particular capsules of capsules of the n ° 0 of vegetable origin of transparent hypromellose (Vcaps® Plus natura).
    [0086]
    [0087] The food supplements used in the present invention are formulated in unit doses in the form of tablets, microgranules, powder or granules, which may or may not have modified release.
    [0088]
    [0089] The individual doses contained within the capsule can range from 0 to 6 tablets of one or more of the components a) to d) and microgranules, powder or granules of the rest of the components, preferably
    [0090] a) between 0 and 3 tablets of plant extracts,
    [0091] b) between 0 and 3 vitamin tablets,
    [0092] c) between 0 and 3 mineral tablets and
    [0093] d) between 0 and 3 tablets of amino acids
    [0094]
    [0095] The plant extracts used, according to the present invention, are preferably selected from: coenzyme Q10, Hypericum, valerian extract, passiflora extract, 5-HTP extract, Kava-Kava (amount of extract equivalent to 100 mg of Kawa lactones), preferably Griffonia simplicifolia, Tanacetum parthenium Passiflora incarnata and Valeriana officinalis.
    [0096] The vitamins used, according to the present invention, are selected from among Vitamins: A (retinol), B1 (thiamin), B2 (riboflavin), B3 (niacin), B5 (pantothenic acid), B6 (pyridoxine), B8 (biotin ), B9 (folic acid), B12 (cobalamin), C (ascorbic acid), D (calciferol), E (α-tocopherol), K (phylloquinone), preferably Vitamin B6 (pyridoxine), B2 (riboflavin) and C ( ascorbic acid) coated.
    [0097] The minerals used, according to the present invention, are selected from magnesium, calcium, phosphorus, sodium, potassium, chloride, iron, zinc, iodine, copper, manganese, fluorine, chromium, selenium, molybdenum, preferably magnesium oxide.
    [0098]
    [0099] The amino acids used, according to the present invention, are selected from tryptophan, valine, histidine, arginine, methionine, leucine, isoleucine, lysine, phenylalanine, threonine, glycine, proline, serine, asparagine preferably L-5-Hydroxytryptophan (5). -HTP).
    [0100]
    [0101] The individual dosage forms contained within the capsule, according to the present invention, are tablets, microgranules, powder or granules of any of components a) to d), which may also contain excipients of the type: diluent, binder, disintegrant, lubricant, surfactant, sweetener, colorant, preservative, stabilizer, flavoring, pH regulator, coatings.
    [0102]
    [0103] The diluents used in the individual dosage forms contained in the capsules, according to the present invention, comprise hydroxypropylmethyl cellulose, calcium phosphate, lactose, dextrose, sugar, starch, modified starch, starch of malt, mannitol, sorbitol, inorganic salts, microcrystalline cellulose, cellulose, calcium sulfate, calcium carbonate, xylitol, lactitol.
    [0104]
    [0105] The tablets and / or microgranules, according to the present invention, can be formed by a lipophilic or hydrophilic inert matrix that modifies the solubilization of the different ingredients that compose it to provide different release characteristics.
    [0106]
    [0107] The tablets and / or microgranules, according to the present invention, can be coated with a protective, enteric, dye and / or film coating to provide different release characteristics.
    [0108]
    [0109] A particular object of the present invention is the development of formulations in capsules, for the treatment of sleep disorders, containing melatonin tablets which allow their liberation in a precise way supplying the adequate quantity in the moments in which the organism needs it, thus enhancing! the effectiveness of the treatment for insomnia.
    [0110]
    [0111] So far sleep disorders have been treated with different nutritional supplements that act on different points of the body, with different mechanisms, with different rates of absorption and with different administration patterns.
    [0112]
    [0113] Therefore, an object of the present invention is the combined use of melatonin, GABA, valerian extract and passionflower extract, which has shown a useful synergistic effect to promote relaxation and sedation to facilitate sleep conciliation initial and subsequently maintain it thanks to the special formulation of controlled release of melatonin and GABA.
    [0114]
    [0115] It is also an object of the present invention a formulation in the form of a capsule containing a tablet of controlled release of vitamin B6 and a tablet of controlled release of 5_HTP which allows the body to gradually dispose of Vitamin B6 and 5_HTP facilitating the stimulation of serotonin prolonged. The same capsule contains two magnesium tablets that enhance the anxiolytic effect of vitamin B6.
    [0116]
    [0117] An object of the present invention is the use of a capsule containing a controlled release vitamin B6 tablet, a controlled release tablet of 5_HTP and two magnesium tablets for the treatment of anxiety.
    [0118]
    [0119] Another object of the invention is formulations twice a day (night and day) for the treatment of joint pain with mainly regenerative function at night and a formulation with anti-inflammatory action for the day.
    [0120]
    [0121] The capsule, to be administered at night, contains chondroitin sulfate and glucosamine to contribute in a beneficial way to the regeneration of damaged joint tissue. It also contains vitamin C, which is a cofactor for different enzymes involved in the biosynthesis of collagen, which is the structural component of numerous body tissues such as bones, cartilage, enamel, skin, tendons and blood vessels and curcumin with anti-inflammatory effect. The capsule to be administered per day contains two tablets of shell of egg shell: one of immediate release and another of controlled release to improve the absorption and reduce the saturation of transport systems and a controlled release tablet of curcumin with piperine: the controlled release over 12 hours allows to improve the assimilation of curcumin helping to reduce the inflammation produced during the day in the joints.
    [0122]
    [0123] Also formulated in capsules containing tablets with CoQ10, Vitamin B2 and Magnesium for the treatment of migraine is an object of the invention.
    [0124]
    [0125] The different formulations can have different release rates. A formulation of controlled release ensures its effect in a prolonged way without having to make several intakes per day.
    [0126]
    [0127] Detailed description of the Invention
    [0128]
    [0129] The capsules of the present invention comprise separate dosage forms of different food supplements. The preparation of different dosage unit forms of each of the food supplements allows to provide a different rate of release for each one of them while reducing the interaction between them and between the different pharmaceutically acceptable excipients of each of the forms.
    [0130]
    [0131] At the same time, the complicated processes combining different active principles known from the state of the art in a single dosage form are overcome using, for example, bilayer or trilayer tablets with or without intermediate barrier layers.
    [0132]
    [0133] In general, multiple dosage forms are more advantageous than single dosage forms in that they are dispersed in the gastrointestinal tract in a homogeneous manner and are transmitted from the stomach to the intestines. The effective dispersion of the active agents in the stomach is ensured and in this way the bioavailability is improved. The multiple dosage forms also have the advantage that they can be formulated in such a way as to allow different release characteristics of the different active agents and / or natural extracts.
    [0134]
    [0135] Thus, the capsules of the present invention comprise a variable number of tablets, microgranules, powder or granules, of different food supplements, such as: plant extracts, vitamins, minerals and / or amino acids.
    [0136] Unit dosage forms may be coated with a protective, enteric, film coat and / or coatings that can provide different release rates.
    [0137]
    [0138] The formulation of the vitamins object of the present invention, has been designed as a gastro-resistant coated tablet to ensure that the vitamin is released once the gastric emptying to the small intestine, also ensuring maximum bioavailability through a delayed formulation that releases gradually the vitamin. Said tablet also incorporates a certain amount of citric acid to improve the stability of riboflavin which is unstable at alkaline pH and protected from light by its opaque coating to avoid its photo degradation.
    [0139]
    [0140] The excipients preferably used in the present invention are: a) as carrier vehicle microcrystalline cellulose, bicalcic phosphate anhydrous or hydrated or a combination of both, b) as a slider colloidal silica and stearic acid lubricants, sodium stearyl fumarate, talc, magnesium stearate and / or glyceryl palmito-stearate, c) as release-modifying agents of the active substances present in the formulation, excipients such as: hydroxypropylmethylcellulose (HPMC), hydroxyethyl cellulose (HEC), hydroxypropyl cellulose (HPC) and sodium carboxymethylcellulose (Na CMC) and d) as gelling agents calcium alginate or xanthan gum or lipophilic substances such as hydrogenated vegetable oil preferably hydroxypropylmethylcellulose (HPMC) of a viscosity grade between 11,000 to 30,000 mPas preferably between 3000-5,600 mPas.
    [0141]
    [0142] The usual techniques used in pharmaceutical technology for the preparation of the different forms of individual doses were used: tablets, microgranules, powder or granules, which are described by way of examples below.
    [0143]
    [0144] Tablets
    [0145]
    [0146] The various tablets were manufactured according to standard procedures for tablets by direct compression mixture coated with pharmaceutically acceptable excipients, usually used in the industry.
    [0147]
    [0148] Thus, by way of example, the various components of the formulation of a tablet are mixed in a suitable mixer, for example a drum of biconical mixture which is rotated at a certain speed, for example 12 rpm, for the time necessary for get the mixture of the different components that are inside for example 30 minutes, the once homogeneous mixture is taken to a suitable equipment for its transformation into tablets using the appropriate tools for it, for example round punches of 6 mm in diameter, weight indicated in the composition of each tablet applying a sufficient force to achieve the cohesion of the particles at a suitable thickness for example 3 - 5 mm.
    [0149]
    [0150] These tablets, once obtained, are coated by applying in a suitable equipment, for example, a perforated coating drum, a coating agent that has previously been dissolved or dispersed in a suitable liquid vehicle, for example water or purified water, during the coating process the nuclei They keep in continuous rotation inside the coating equipment at the same time that the coating agent is sprayed on them by means of spray guns that atomize the coating suspension, getting the coating agent (solid part) to be deposited homogeneously on the surface of the tablet forming a continuous layer, at the same time that the liquid vehicle evaporates due to a current of hot air.
    [0151]
    [0152] At the end of the process, the tablets are wrapped in a thin film of coating material generally 3 - 15% by weight with respect to the total weight of the tablet.
    [0153] Depending on the chemical nature of the solid part of the coating agent, the coating film can confer different properties to the tablets, for example: solution of the tablet at a certain pH such as resistance to the acid medium (gastro resistant cover), protection to the oxidation of the components of the tablet by waterproofing gases such as oxygen or moisture protection and / or increased resistance to erosion or improvement of odor and taste organoleptic characteristics.
    [0154]
    [0155] Subsequently, the coated tablets were encapsulated using a specific encapsulating machine, such as, for example, one capsule containing one type A tablet, one type B tablet and two type C tablets.
    [0156]
    [0157] Microgranules
    [0158]
    [0159] The microgranules are multiparticulated systems that are characterized by their shape and size. The microgranules are spherical or semi-spherical agglomerates of free flow, with a very narrow particle size distribution generally between 0.5 to 1.5 mm and even smaller.
    [0160]
    [0161] The way of obtaining these microgranules or pellets can vary from compression (microtabiets), dry processes such as hot-melt or dryed spray techniques, although the most used is extrusion-spheronization.
    [0162]
    [0163] The spheronization extrusion technique consists of the agglomeration of the pulverized components by the addition of a vehicle (microcrystalline cellulose, starch, lactose, mannitol, hydroxypropylmethylcellulose or the like) and a binding agent and a humectant (such as HPMC, povidone and / or polysorbate 80) previously dispersed or dissolved in a liquid vehicle and its mixing in suitable equipment (High shear Mixers or planetary mixers or sigma). This mass is subsequently passed through a sinfln extrusion system through a multi-perforated plate of a given diameter, for example 1 mm, cutting the obtained cylinders to a certain size, for example 1-1.5 mm long.
    [0164]
    [0165] The thus obtained cylinders are rounded in a suitable equipment for example a spheronizer, with the suitable tooling for example conical plates with pyramidal relief of 1 mm rotating at high speed for example 900 - 1500 rpm during the necessary time for example 1- 2 minutes.
    [0166]
    [0167] These wet spheres are dried in a conventional dryer, for example an oven, drying tunnel or a fluid bed dryer, until the residual vehicle is removed from the mixture, for example water, and the desired consistency is obtained.
    [0168]
    [0169] The thus obtained spheres are screened to remove fines and agglomerates until the necessary particle size is obtained, for example 0.6 to 1.2 mm.
    [0170]
    [0171] These spheres can then be coated in suitable equipment, for example a smooth or perforated coating equipment, Wurster or the like in order to individually wrap them in a thin layer of coating material generally between 2 - 15% by weight with respect to total weight of the microgranule.
    [0172]
    [0173] Depending on the chemical nature of the solid part of the coating agent, the coating film can confer different properties to the microgranules by example: dissolution of the tablet at a certain pH such as resistance to the acid medium (gastroresistant coating), protection to the oxidation of the microgranule components by waterproofing gases such as oxygen or moisture protection and / or increased resistance to erosion or improvement of organoleptic characteristics, odor and taste or adding other active ingredients on the surface of the microgranule.
    [0174]
    [0175] The microgranules thus obtained are subsequently dosed at a certain weight that ensures the dose of the active ingredients to be administered inside capsules for subsequent oral administration.
    [0176]
    [0177] Powder
    [0178]
    [0179] The various components of the formulation are screened, for example, through a mesh, for example of 1 mm of light, and are mixed in a suitable mixer, for example a biconical mezcal drum which is rotated at a certain speed, for example at 12 rpm during the time necessary to get the mixture of the different components that are inside, such as 30 minutes. The once homogenous mixture is taken to a suitable equipment for its filling inside capsules to the weight defined in the formulation.
    [0180]
    [0181] Granulated
    [0182]
    [0183] The granulation process consists of the agglomeration of the pulverized components by the addition of a vehicle (microcrystalline cellulose, starch, lactose, mannitol, hydroxypropylmethylcellulose or the like). An intragranular disintegrating agent may be included to improve the release of the components such as (croscarmellose sodium, modified starch or the like) and a binding agent (such as povidone, HPMC, sugar or the like) previously dispersed or dissolved in a liquid carrier. and its kneading in a suitable equipment (high speed shear mixers or planetary mixers or horizontal or vertical type sigma). This mass is wet granulated by passing it in a forced way by a suitable light passage mesh, for example 3-4 mm.
    [0184]
    [0185] The wet granulate obtained is dried in a conventional dryer, for example an oven, drying tunnel or a fluid bed dryer, until the residual vehicle is removed from the mixture, for example water, and the desired consistency is obtained.
    [0186] Once dry, this granulate is calibrated by passing it through mesh with suitable light passage, for example, 1 - 1.2 mm. This obtained granulate is mixed in a suitable mixer such as a rotating biconical at a suitable speed, for example 12 rpm, during the time necessary to homogenize the components of the mixture, for example 15 to 30 minutes, with extragranular excipients, for example lubricants ( magnesium stearate, stearic acid, talc or the like) and disintegrants (croscarmellose sodium, modified starch or the like).
    [0187]
    [0188] The obtained granulate is filled in capsules by means of equipment and tooling suitable to the necessary weight to guarantee the quantity of nutrients indicated in the formulation.
    [0189]
    [0190] The capsules of the present invention are useful for the treatment of different disorders, such as sleep disorders, anxiety, joint pain, migraine, etc.
    [0191]
    [0192] Examples of formulations
    [0193]
    [0194] The capsules of the present invention were filled with tablets, microgranules, powder and / or granules of the different food supplements, using a standard encapsulation machine of the market.
    [0195]
    [0196] The encapsulation system allows the addition within the same capsule of combinations of tablets as well as tablets with another type of product such as microgranules, or powder and / or granules.
    [0197]
    [0198] Types of tablets to be dosed in number 0 capsules with standard capsule:
    [0199]
    [0200]
    [0201] Combinations of tablets inside the capsule (compressed type A, B, C, D, E and F of identical dimensions but different composition)
    [0202]
    [0203]
    [0204]
    [0205]
    [0206] Preferably 4 coated round tablets of type 2 with 6 mm in diameter and a height comprised between 4.1 - 4.4 mm.
    [0207]
    [0208] Examples of capsules containing modified release tablets
    [0209]
    [0210] For the treatment of sleep:
    [0211] Controlled clinical trials were carried out in parallel groups, double blind, randomized, in patients diagnosed with primary insomnia with a total sleep time <6 hours treated with formulation for insomnia for 2 weeks. During this period They evaluated the total sleep time, the sleep latency and the number of awakenings per night. An improvement in the total sleep time, sleep latency, number of night awakenings was observed in the patients treated with the complement.
    [0212]
    [0213] Example 1:
    [0214] The capsule contains four tablets:
    [0215] i) one coated tablet A, containing
    [0216] • 0.30 mg melatonin
    [0217] • 50 mg GABA
    [0218] ii) a modified release coated tablet B, containing:
    [0219] • 1,65 mg melatonin
    [0220] • 50 mg GABA
    [0221] iii) two coated tablets C, containing:
    [0222] • 60 mg Valerian Extract
    [0223] • 60 mg Passiflora Extract
    [0224]
    [0225] Tablet A:
    [0226] Coated compressed composition containing 0.25 mg melatonin and 50 mg GABA
    [0227]
    [0228]
    [0229]
    [0230] total 0,155 100
    [0231] Tablet B:
    [0232] Compressed coated composition containing 1.65 mg melatonin and 50 mg GABA modified release:
    [0233]
    [0234]
    [0235] total 0,155 100
    [0236] Tablet C:
    [0237] Compressed coated composition containing 60 mg valerian extract and 60 mg passiflora extract with gastro-resistant coating:
    [0238]
    [0239]
    [0240]
    [0241] total 0,160 100
    [0242]
    [0243] Example 2:
    [0244] The capsule contains four tablets:
    [0245] i) one coated tablet A, containing
    [0246] • 0.25 mg melatonin
    [0247] • 25 mg GABA
    [0248] ii) a modified release coated tablet B, containing:
    [0249] • 0.75 mg melatonin
    [0250] • 25 mg GABA
    [0251] iii) two coated tablets C, containing:
    [0252] • 60 mg Valerian Extract
    [0253] • 60 mg of Passiflora Extract
    [0254] Tablet A:
    [0255] Coated compressed composition containing 0.25 mg melatonin and 25 mg GABA
    [0256]
    [0257]
    [0258]
    [0259] total 0,155 100
    [0260]
    [0261] Tablet B:
    [0262] Compressed coated composition containing 0.75 mg melatonin and 25 mg GABA modified release:
    [0263]
    [0264]
    [0265]
    [0266] total 0,155 100
    [0267]
    [0268] Tablet C:
    [0269] Compressed coated composition containing 60 mg valerian extract and 60 mg passiflora extract with gastro-resistant coating:
    [0270]
    [0271]
    [0272] total 0,160 100
    [0273]
    [0274] Example 3:
    [0275] The capsule contains four tablets:
    [0276] i) one coated tablet A, containing
    [0277] • 0.25 mg melatonin
    [0278] • 25 mg GABA
    [0279] ii) a modified release coated tablet B, containing:
    [0280] • 0.75 mg melatonin
    [0281] • 25 mg GABA
    [0282] iii) two coated tablets C, containing:
    [0283] • 60 mg Valerian Extract
    [0284] • 60 mg of Passiflora Extract
    [0285] Tablet A:
    [0286] Compressed coated composition containing 0.25 mg melatonin and 25 mg GABA
    [0287]
    [0288]
    [0289]
    [0290] total 0,155 100
    [0291]
    [0292] Tablet B:
    [0293] Compressed coated composition containing 0.75 mg melatonin and 25 mg GABA liberation modified:
    [0294]
    [0295]
    [0296]
    [0297] total 0,155 100
    [0298]
    [0299] Tablet C:
    [0300] Compressed coated composition containing 60 mg valerian extract and 60 mg passiflora extract with gastro-resistant coating:
    [0301]
    [0302]
    [0303]
    [0304] total 0,160 100
    [0305]
    [0306] Example 4:
    [0307] The capsule contains four tablets:
    [0308] i) one coated tablet A, containing
    [0309] • 0.25 mg melatonin
    [0310] • 25 mg GABA
    [0311] ii) a modified release coated tablet B, containing:
    [0312] • 0.75 mg melatonin
    [0313] • 25 mg GABA
    [0314] iii) two coated tablets C, containing:
    [0315] • 60 mg Valerian Extract
    [0316] • 60 mg of Passiflora Extract
    [0317]
    [0318] Tablet A:
    [0319] Coated compressed composition containing 0.25 mg melatonin and 25 mg GABA
    [0320]
    [0321]
    [0322]
    [0323] total 0,155 100
    [0324]
    [0325] Tablet B:
    [0326] Compressed coated composition containing 0.75 mg melatonin and 25 mg GABA modified release:
    [0327]
    [0328]
    [0329]
    [0330] total 0.155 100,000
    [0331]
    [0332] Tablet C:
    [0333] Compressed coated composition containing 60 mg valerian extract and 60 mg passiflora extract with gastro-resistant coating:
    [0334]
    [0335]
    [0336] total 0,160 100
    [0337] Example 5:
    [0338] The capsule contains four tablets:
    [0339] i) one coated tablet A, containing
    [0340] • 0.25 mg melatonin
    [0341] • 25 mg GABA
    [0342] iv) a modified release coated tablet B, containing:
    [0343] • 0.75 mg melatonin
    [0344] • 25 mg GABA
    [0345] v) two coated tablets C, containing:
    [0346] • 60 mg Valerian Extract
    [0347] • 60 mg of Passiflora Extract
    [0348]
    [0349] Tablet A:
    [0350] Compressed coated composition containing 0.25 mg melatonin and 25 mg GABA
    [0351]
    [0352]
    [0353]
    [0354] total 0,155 100
    [0355]
    [0356] Tablet B:
    [0357] Compressed coated composition containing 0.75 mg melatonin and 25 mg GABA liberation modified:
    [0358]
    [0359]
    [0360]
    [0361] total 0,155 100
    [0362]
    [0363] Tablet C:
    [0364] Compressed coated composition containing 60 mg valerian extract and 60 mg passiflora extract with gastro-resistant coating:
    [0365]
    [0366]
    [0367]
    [0368] total 0,160 100
    [0369]
    [0370] Example 6:
    [0371]
    [0372] The capsule contains four tablets:
    [0373] i) one coated tablet A, containing
    [0374] • 0.25 mg melatonin
    [0375] • 25 mg GABA
    [0376] ii) a modified release coated tablet B, containing:
    [0377] • 0.75 mg melatonin
    [0378] • 25 mg GABA
    [0379] iii) two coated tablets C, containing:
    [0380] • 60 mg Valerian Extract
    [0381] • 60 mg of Passiflora Extract
    [0382]
    [0383] Tablet A:
    [0384] Coated compressed composition containing 0.25 mg melatonin and 25 mg GABA
    [0385]
    [0386]
    [0387]
    [0388] total 0,155 100
    [0389]
    [0390] Tablet B:
    [0391] Compressed coated composition containing 0.75 mg melatonin and 25 mg GABA modified release:
    [0392]
    [0393]
    [0394]
    [0395] total 0,155 100
    [0396] Tablet C:
    [0397] Compressed coated composition containing 60 mg valerian extract and 60 mg passiflora extract with gastro-resistant coating:
    [0398]
    [0399]
    [0400]
    [0401] total 0,160 100
    [0402]
    [0403] Example 7:
    [0404] The capsule contains four tablets:
    [0405] i) one coated tablet A, containing
    [0406] • 0.25 mg melatonin
    [0407] • 25 mg GABA
    [0408] vi) a modified release coated tablet B, containing:
    [0409] • 0.75 mg melatonin
    [0410] • 25 mg GABA
    [0411] vii) two coated tablets C, containing:
    [0412] • 60 mg Valerian Extract
    [0413] • 60 mg of Passiflora Extract
    [0414]
    [0415] Tablet A:
    [0416] Compressed coated composition containing 0.25 mg melatonin and 25 mg GABA
    [0417]
    [0418] total 0,155 100
    [0419]
    [0420] Tablet B:
    [0421] Compressed coated composition containing 0.75 mg melatonin and 25 mg GABA liberation modified:
    [0422]
    [0423]
    [0424]
    [0425] total 0,155 100
    [0426]
    [0427] Tablet C:
    [0428] Compressed coated composition containing 60 mg valerian extract and 60 mg passiflora extract with gastro-resistant coating:
    [0429]
    [0430]
    [0431] total 0,160 100 Example 8:
    [0432] The capsule contains four tablets:
    [0433] i) one coated tablet A, containing
    [0434] • 0.25 mg melatonin
    [0435] • 25 mg GABA
    [0436] ii) a modified release coated tablet B, containing:
    [0437] • 0.75 mg melatonin
    [0438] • 25 mg GABA
    [0439] iii) two coated tablets C, containing:
    [0440] • 60 mg Valerian Extract
    [0441] • 60 mg of Passiflora Extract
    [0442] Tablet A:
    [0443] Compressed coated composition containing 0.25 mg melatonin and 25 mg GABA
    [0444]
    [0445]
    [0446]
    [0447] total 0,155 100
    [0448]
    [0449] Tablet B:
    [0450] Compressed coated composition containing 0.75 mg melatonin and 25 mg GABA liberation modified:
    [0451]
    [0452]
    [0453]
    [0454] total 0,155 100
    [0455]
    [0456] Tablet C:
    [0457] Compressed coated composition containing 60 mg valerian extract and 60 mg passiflora extract with gastro-resistant coating:
    [0458]
    [0459]
    [0460]
    [0461] total 0,160 100
    [0462]
    [0463] Example 9:
    [0464] The gelatin capsule or HPMC contains:
    [0465] • 160 mg sustained release microgranules with gastroresistant coating
    [0466] • 1 type A tablet
    [0467] • 1 Tablet Type B
    [0468] Microqranules
    [0469] Composition microqranules per capsule containing 60 mq valerian extract and 60 mq passiflora extract with qastrorresistant coating:
    [0470]
    [0471]
    [0472]
    [0473] 0,160 100,000
    [0474] Tablet A:
    [0475] Compressed coated composition containing 0.25 mq melatonin and 25 mq GABA
    [0476]
    [0477]
    [0478]
    [0479] Totals 0.155 100 Compressed B:
    [0480] Compressed coated composition containing 0.75 mq melatonin and 25 mq GABA modified release:
    [0481]
    [0482]
    [0483] total 0.155 100 Example 10:
    [0484] The gelatin capsule or HPMC contains:
    [0485] • 160 mg of powder
    [0486] • 1 type A tablet
    [0487] • 1 Tablet Type B
    [0488] Powder:
    [0489] Powdered composition per capsule containing 60 mg valerian extract and 60 mg passiflora extract:
    [0490]
    [0491]
    [0492]
    [0493] total 0,160 100
    [0494] Tablet A:
    [0495] Coated compressed composition containing 0.25 mg melatonin and 25 mg GABA
    [0496]
    [0497]
    [0498]
    [0499] total 0,155 100 Tablet B:
    [0500] Compressed coated composition containing 0.75 mg melatonin and 25 mg GABA liberation modified:
    [0501]
    [0502]
    [0503]
    [0504] total 0,155 100
    [0505]
    [0506] Example 11:
    [0507] The gelatin capsule or HPMC contains:
    [0508] 160 mg of granules
    [0509] 1 Type A tablet
    [0510] 1 Type B Tablet
    [0511]
    [0512] Granulated:
    [0513] Composition granulated per capsule containing 60 mg valerian extract and 60 mg passiflora extract:
    [0514]
    [0515]
    [0516]
    [0517] total 0,155 100 Tablet A:
    [0518] Compressed coated composition containing 0.25 mg melatonin and 25 mg GABA
    [0519]
    [0520]
    [0521] total 0,155 100
    [0522] Tablet B:
    [0523] Compressed coated composition containing 0.75 mg melatonin and 25 mg GABA liberation modified:
    [0524]
    [0525]
    [0526] total 0,155 100 For the treatment of anxiety
    [0527] The patent-pending formulation for anxiety containing 5-HTP, Vitamin B6 and Magnesium was evaluated in comparison with a selective inhibitory serotonin reuptake inhibitor (SSRI) in a double-blind multicentric study design. A total of 36 subjects, all of whom were diagnosed with some form of depression, received the patent-pending formula for anxiety or an antidepressant medication three times a day. The subjects were evaluated at 0, 2, 4 and 6 weeks, using four evaluation tools: the Hamilton Rating Scale for Depression (HRSD), a standard scale of depression classification; A self-assessment performed by the patient; and the researcher's assessment of severity and a global clinical impression. Both treatment groups showed significant and almost equal reductions in depression from the second week and continued until the sixth week. After four weeks, 15 of the 36 patients treated with 5-HTP, and 18 of the 33 patients treated with the antidepressant medication had improved by at least 50 percent, according to the HRSD scores. In week six, the two groups had approximately the same number that showed the 50 percent improvement. When the numbers were totaled at the end of the study, the researchers found that the average percentage improvement from the baseline to the final evaluation was slightly higher (5%) for patients treated with the patent-subject formulation for anxiety.
    [0528]
    [0529] Example 11:
    [0530] The gelatin capsule or HPMC contains four tablets inside a capsule:
    [0531] • 1 tablet of modified release containing Kava-Kava (amount of extract equivalent to 100 mg of Kava lactones)
    [0532] • 2 coated tablets containing: 100 mg of Magnesium
    [0533] • 1 tablet of modified release containing: 26 mg Vitamin B6
    [0534]
    [0535] Tablet A:
    [0536] Compressed coated tablet containing 100 mg of Kava-Kava:
    [0537]
    [0538]
    [0539] Totals 0.209 100
    [0540] Tablet B:
    [0541] Coated compressed composition containing 100 mg of Magnesium:
    [0542]
    [0543]
    [0544]
    [0545] Totals 0.209 100
    [0546]
    [0547] Tablet C:
    [0548] Compressed composition with modified release containing 26 mg of Vitamin B6:
    [0549]
    [0550]
    [0551]
    [0552] to ta le s 0, 209 100 Example 12:
    [0553] The gelatin capsule or HPMC contains four tablets inside a capsule:
    [0554] • 1 modified release coated tablet containing 100 mg 5-Hydroxytryptophan (5-HTP)
    [0555] • I modified release coated tablet containing 10 mg Vitamin B6
    [0556] • 2 coated tablets containing 100 mg of Magnesium
    [0557]
    [0558] Tablet A:
    [0559] Modified release coated compressed composition containing 100 mg of 5-HTP:
    [0560]
    [0561]
    [0562]
    [0563] total 0.209 100
    [0564] Tablet B:
    [0565] Compressed composition with modified release containing 10 mg of Vitamin B6:
    [0566]
    [0567]
    [0568]
    [0569] total 0.209 100 Tablet C:
    [0570] Coated compressed composition containing 100 mg of Magnesium:
    [0571]
    [0572]
    [0573]
    [0574] Totals 0.209 100
    [0575]
    [0576] MIGRANA Liberation modified:
    [0577] A simple blind clinical trial performed in randomly assigned migraine patients in two parallel groups determined the efficacy of a treatment based on the food supplement object of the patent versus placebo. The first group was treated with the supplement based on Vitamin B2, CoQ10 and magnesium object of the patent and the second group was treated with placebo. The patients were examined at the beginning of the study and 4, 8 and 12 weeks later. After the administration of the products in both groups, the frequency of the migraine episodes and the severity of the headaches were recorded, as well as a self-evaluation of the efficacy performed by the patient.
    [0578]
    [0579] Summary results:
    [0580]
    [0581] Days with migraine per month were reduced from 6.2 days during the initial period to 4.4 days after 12 weeks of treatment with the dietary supplement and from 6.2 to 5.2 days in the placebo group (p = 0.23).
    [0582]
    [0583] The intensity of the Headaches was significantly reduced in the group treated with the food supplement compared to the group treated with placebo (p = 0.03).
    [0584]
    [0585] The evaluation of efficacy by the patient was better in the group treated with the supplement compared to placebo (p = 0.01).
    [0586] The hypromellose capsule of No. 0 contains four tablets:
    [0587] • 1 coated tablet containing 100 mg Coenzyme Q-10
    [0588] • 1 coated tablet with modified release enteric coating containing:
    [0589] - 100 mg Vitamin B2
    [0590] - 25 mg Cl Acrid
    [0591] • 2 coated tablets containing 100 mg magnesium
    [0592]
    [0593] Tablet A:
    [0594] Coated compressed composition containing 100 mg of Coenzyme Q10:
    [0595]
    [0596]
    [0597]
    [0598] total 0.209 100
    [0599]
    [0600] Tablet B:
    [0601] Compressed composition coated with modified release gastro-resistant coating containing 100 mg of Vitamin B2 and 25 mg of citric acid:
    [0602]
    [0603]
    [0604]
    [0605] to ta le s 0, 212 100 Tablet C:
    [0606] Coated compressed composition containing 100 mg of Magnesium:
    [0607]
    [0608]
    [0609]
    [0610] Totals 0.209 100
    [0611]
    [0612] ANTIOXIDANT Modified Liberation:
    [0613] Example 14:
    [0614] The hypromellose capsule No. 0 contains four tablets:
    [0615] - 1 coated tablet containing 100 mg resveratrol
    [0616] - 1 coated tablet containing 100 mg Rosehip Extract - 1 coated tablet containing 100 mg of acal
    [0617] - 1 tablet with enteric coating containing 100 mg of quercetin.
    [0618]
    [0619] This formulation combines natural ingredients with high antioxidant power with a modified release to ensure the duration of the effect.
    [0620]
    [0621] Tablet A:
    [0622] Coated compressed composition containing 100 mg Resveratrol:
    [0623]
    [0624]
    [0625]
    [0626] total 0.209 100
    [0627] Tablet B:
    [0628] Compressed coated composition containing 100 mg of Rosehip Extract:
    [0629]
    [0630]
    [0631]
    [0632] total 0.209 100
    [0633] Tablet C:
    [0634] Coated compressed composition containing 100 mg of Acal:
    [0635]
    [0636]
    [0637]
    [0638] total 0.209 100
    [0639] Tablet D:
    [0640] Compressed composition coated with gastro-resistant coating containing 100 mg of quercetin:
    [0641]
    [0642]
    [0643] total 0.209 100
    [0644]
    [0645] Modified Liberation Joints:
    [0646] The formulation with turmeric, piperine, egg shell membrane, chondroitin sulfate, glucosamine and vitamin C was evaluated for its efficacy 50 individuals affected by OA (confirmation of diagnosis of X-rays). The symptoms were evaluated by the WOMAC score; Mobility was studied by the performance of walking on the treadmill and the Global of the inflammatory response function was assessed by measurements of the plasma concentration of C-reactive protein. The trial was carried out during a period of three months, the individuals were divided at random into two groups that received respectively the complement object of the patent (in two separate administrations per day) and the "best treatment available", or the " Better Treatment "by itself, as defined by professionals or specialists. The performance on the treadmill (10% Inclination, speed 3 Km / h) showed an improvement of 201% of the initial distance walked after two months, and an improvement (+ 44%) three months after the beginning of the study. These positive results were complemented by secondary observations, that is, the reduction of the rescue rate with additional medication (63% in the complement group compared to 12% in the group with pharmacological treatment) and the decrease in gastrointestinal complications (38 % in the complement group vs 15% in controls (p <0.05).
    [0647]
    [0648] The following table summarizes the results obtained:
    [0649]
    [0650]
    [0651]
    [0652] This shows a remarkable improvement of the group treated with the complement object of the patent with respect to the control group.
    [0653]
    [0654] Example 15:
    [0655] Night capsule (Regenerative effect)
    [0656] The capsule contains 4 tablets:
    [0657] - 2 comp A x 50 mg chondroitin Sulphate
    [0658] - 1 comp B x 30.6 mg glucosamine
    [0659] - 1 comp C x 41 mg vitamin C sustained release
    [0660] Capsula dia (Anti-inflammatory effect):
    [0661] The capsule contains 4 tablets:
    [0662] - 1 comp A x 100 mg Ovomet® Egg Shell Membrane (it is pure egg membrane that is obtained through a production process patented by Eggnovo)
    [0663] - 2 comp B x 100 mg Ovomet® Egg Shell Membrane sustained release 12 h - 1comp C x 105 mg 95% turmeric + 1 mg piperine sustained release 12 h and gastroresistant coating
    [0664]
    [0665] Night capsule (Regenerative effect)
    [0666]
    [0667] Tablet A:
    [0668] Compressed coated tablet containing 50 mg chondroitin sulfate
    [0669]
    [0670]
    [0671]
    [0672] total 0,155 100
    [0673] Compressed coated tablet containing 30.6 mg Glucosamine:
    [0674]
    [0675]
    [0676]
    [0677] total 0,155 100
    [0678] Tablet C:
    [0679] Compressed coated composition containing 41 mg of sustained release vitamin C:
    [0680]
    [0681]
    [0682]
    [0683] total 0.155 100 Capsule day (Anti-inflammatory effect):
    [0684] Tablet A:
    [0685] Compressed coated tablet containing 100 mg 100 mg of Egg Membrane (OVOMED ®)
    [0686]
    [0687]
    [0688]
    [0689] to ta le s 0, 215 100, 00 Tablet B:
    [0690] Compressed coated composition containing 100 mg of egg membrane (OVOMED ®) sustained release:
    [0691]
    [0692]
    [0693]
    [0694] total 0.215 100.00
    [0695] Tablet C:
    [0696] Compressed composition coated with modified release gastro-resistant coating containing 105 mg 95% turmeric + 1 mg piperine:
    [0697]
    [0698]
    [0699]
    [0700] total 0,222 100.00
    权利要求:
    Claims (18)
    [1]
    Encapsulated formulations comprising a capsule comprising tablets, microgranules, powder or granules of some, or all, of the following components or food supplements:
    a) Plant extracts,
    b) Vitamins,
    c) Minerals
    d) Amino acids
    [2]
    2. Encapsulated formulations according to claim 1, characterized in that the capsule can be of vegetable or animal origin.
    [3]
    Encapsulated formulations according to any of claims 1 and 2, characterized in that the tablets, microgranules, powder or granules of a), b), c) and d) may or may not have modified release.
    [4]
    Encapsulated formulations according to any of claims 1 to 3, comprising between 0 and 6 tablets of one or more of the components a) to d) and microgranules, powder or granules of the rest of the components.
    [5]
    5. Encapsulated formulations according to any of claims 1 to 3, comprising:
    e) Between 0 and 3 tablets of plant extracts,
    f) Between 0 and 3 vitamin tablets,
    g) Between 0 and 3 tablets of minerals and
    h) Between 0 and 3 tablets of amino acids
    [6]
    Encapsulated formulations according to any of claims 1 to 5, characterized in that the plant extracts are selected from Hypericum, Curcuma Kwangsiensis, Curcuma Phaeocaulis, Curcuma Zedoary, Curcuma Wenyujin, Curcuma aromatica, Harpagophytum procumbens, Harpagophytum zeyheri, Mimosaceae (Piptadeniastrum) africanum), Passiflora caerulea, Passiflora edulis, Passiflora decaisneana, Passiflora manicata, Valeriana collina, Valeriana pratensis, Valeriana repens, Valeriana sambucifolia, Griffonia physocarpa, Griffonia speciosa, Griffonia tessmannii, Matricaria perforata, Matricaria recutita, Matricaria discoidea, Matricaria aurea, Tanacetum corymbosum , Tanacetum microphyllum, Chamaemelum nobile, Helichrysum italicum, Santolina chamaecyparissus preferably L-5-Hydroxytryptophan (5-HTP) dry extract of griffonia simplicifolia seeds, Tanacetum parthenium Passiflora incarnata and Valeriana officinalis.
    [7]
    Encapsulated formulations according to any of claims 1 to 6, characterized in that the vitamins are selected from Vitamin A (retinol), B1 (thiamine), B2 (riboflavin), B3 (niacin), B5 (pantothenic acid), B6 ( pyridoxine), B8 (biotin), B9 (folic acid), B12 (cobalamin), Coenzyme Q10 (ubiquinone), C (ascorbic acid), D (calciferol), E (α-tocopherol), K (phylloquinone), preferably acid ascorbic coated with ethylcellulose, pyridoxine hydrochloride, riboflavin and ubiquinone.
    4
    [8]
    Encapsulated formulations according to any of claims 1 to 7 characterized in that the minerals are selected from magnesium, calcium, phosphorus, sodium, potassium, chloride, iron, zinc, iodine, copper, manganese, fluorine, chromium, selenium, molybdenum preferably magnesium oxide and magnesium chloride.
    [9]
    Encapsulated formulations according to any of claims 1 to 8 characterized in that the amino acids or peptides are selected from tryptophan, valine, histidine, arginine, methionine, leucine, isoleucine, lysine, phenylalanine, threonine, glycine, proline, serine, asparagine preferably Egg shell membrane (OVOMET ®), 90% marine chondroitin sulfate, D-glucosamine sulfate sodium (2NaCL) Vegetable, Melatonin and GABA (Gamma-AminoButyric Acid).
    [10]
    Encapsulated formulations according to any one of claims 1 to 9, characterized in that the tablets, microgranules, powder or granules of any of components a) to d) may also contain excipients of the type: diluent, binder, disintegrant, lubricant, surfactant , sweetener, colorant, preservative, stabilizer, flavoring, pH regulator, coatings.
    [11]
    Encapsulated formulations according to any of claims 1 to 10, characterized in that the diluent comprises hydroxypropylmethylcellulose, HPMC, calcium phosphate, lactose, dextrose, sugar, starch, modified starch, malt starch, mannitol, sorbitol, inorganic salts, microcrystalline cellulose , cellulose, calcium sulfate, xylitol and / or lactitol.
    [12]
    12. Encapsulated formulations according to any of claims 1 to 11, characterized in that the tablets and / or microgranules can be formed by an inert lipophilic or hydrophilic matrix that modifies the solubilization of the different ingredients that compose it to provide different release characteristics.
    [13]
    Encapsulated formulations according to any of claims 1 to 12 characterized in that the tablets and / or microgranules can be coated with a protective, enteric, dye and / or film coating to provide different release characteristics.
    [14]
    14. Use of a capsule according to any of claims 1 to 13 for the manufacture of a food supplement for the prevention and treatment of different types of disorders.
    [15]
    15. Use of a capsule according to any of claims 1 to 14 for the manufacture of a food supplement for the prevention and treatment of sleep disorders.
    [16]
    16. Use of a capsule according to any of claims 1 to 14 for the manufacture of a food supplement for the prevention and treatment of anxiety.
    4
    [17]
    17. Use of a capsule according to any of claims 1 to 14 for the manufacture of a food supplement for the prevention and treatment of joint pain.
    [18]
    18. Use of a capsule according to any of claims 1 to 14 for the manufacture of a food supplement for the prevention and treatment of migraine.
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    同族专利:
    公开号 | 公开日
    EP3646858A4|2020-05-27|
    ES2695503B2|2020-05-08|
    WO2019002657A1|2019-01-03|
    EP3646858A1|2020-05-06|
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    AU2015237909B2|2014-03-28|2019-11-07|Hortus Novus Srl|Compositions based on saffron for the prevention and/or treatment of degenerative eye disorders.|
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    法律状态:
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    优先权:
    申请号 | 申请日 | 专利标题
    ES201730871A|ES2695503B2|2017-06-30|2017-06-30|ENCAPSULATED FORMULATIONS|ES201730871A| ES2695503B2|2017-06-30|2017-06-30|ENCAPSULATED FORMULATIONS|
    PCT/ES2018/070465| WO2019002657A1|2017-06-30|2018-06-28|Encapsulated formulations|
    EP18822991.8A| EP3646858A4|2017-06-30|2018-06-28|Encapsulated formulations|
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