WO2008125714A1 - Use of l-carnitine for treating arterial hypertension - Google Patents
Use of l-carnitine for treating arterial hypertension Download PDFInfo
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- WO2008125714A1 WO2008125714A1 PCT/ES2008/000249 ES2008000249W WO2008125714A1 WO 2008125714 A1 WO2008125714 A1 WO 2008125714A1 ES 2008000249 W ES2008000249 W ES 2008000249W WO 2008125714 A1 WO2008125714 A1 WO 2008125714A1
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- Prior art keywords
- carnitine
- arterial hypertension
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- hypertension
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Classifications
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/205—Amine addition salts of organic acids; Inner quaternary ammonium salts, e.g. betaine, carnitine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
Definitions
- the present invention relates to the use of L-carnitine for the preparation of a medicament or a nutritional supplement for the treatment or control of arterial hypertension.
- this invention also refers to pharmaceutical compositions for the treatment of said pathology that comprise a therapeutically effective amount of L-carnitine.
- L-Carnitine (L-3-hydroxy-4-N, N, N-trimethyllaminobutyrate) is an amino acid derivative present in most animal species and in many microorganisms and plants. It is widely distributed throughout the body, although it occurs in greater amounts in the heart and skeletal muscle (Panter RA and Mudd JB (1969). FEBS Lett. 5 (2): 169-170; Rebouche CJ (1992) FASEB J. 6 (15): 3379-3386.).
- this amino acid derivative consists in acting as a cofactor in the transport of fatty acids inside the mitochondria, where the ⁇ -oxidation of the same occurs, for the obtaining of metabolic energy (Bremer J. (1983). Physiol Rev. 63 (4): 1420-1480.), Playing a crucial role in the metabolism of fatty acids.
- Acute and chronic myocardial ischemia angina pectoris, sequelae of myocardial infarction, heart failure, senile heart, congestive heart disease, arrhythmias, etc.
- treatment with L-carnitine helps to alleviate the symptoms produced by the lack thereof.
- treatment with L-carnitine improves the recovery of patients, relieving symptoms, reducing the requirement of other drugs and reducing mortality.
- EBPOC chronic obstructive broncho-pulmonary disease
- emphysema DaI Negro R., et al (1988). Int. J. Clin. Pharmacol. Ther. Toxicol. 26 (5): 269-272; Montgomery SA, et al (2003). Int. Clin. Psychopharmacol. 18 (2): 61-71); in senile dementia (Bella R., et al (1990). Int. J. Clin. Pharmacol. Res. 10 (6): 355-360.); in some cases of patients with ataxia (Gallagher C, et al L. (2002). J. Child Neurol.
- L-Carnitine performs a control function on arterial hypertension, which may constitute a nutritional supplement that helps control said pathology, as well as being used together with others antihypertensives, as an adjuvant for greater control of arterial hypertension.
- L-carnitine could be used as a functional product, as a supplement in the diet or through the use of pharmaceutical forms, to help control arterial hypertension. It could be said that the consumption of L-carnitine could not be a substitute for those medications aimed at reducing blood pressure, as well as hygienic-dietary measures to improve blood pressure levels, however, its use either alone or in combination with other antihypertensive therapies, could perform an adjuvant effect to control blood pressure, given its hypotensive or anti-hypertensive effect. To all this should be added the low toxicity that L-carnitine has, as well as the lack of side effects, which makes it a perfect candidate as a supplement to apply in hypertensive people.
- a first aspect of the invention relates to the use of L-carnitine for the preparation of a medicament for the treatment of arterial hypertension.
- a second aspect of the invention relates to the use of L-camitin as an adjuvant in a pharmaceutical composition for the treatment of arterial hypertension.
- a third aspect of the invention relates to the use of L-carnitine for the preparation of a nutritional supplement for the treatment or control of arterial hypertension.
- a fourth aspect of the invention relates to a pharmaceutical composition for the treatment of arterial hypertension comprising L-carnitine in a therapeutically effective amount.
- the pharmaceutical composition also comprises other agents for the treatment of arterial hypertension or antihypertensives.
- Figure 1 shows the analysis of the diastolic pressure (mm Hg) for rats that have been treated with 300 mg / kg L-carnitine.
- Column A represents a group of normotensive rats not treated with L-carnitine
- column B a group of hypertensive rats not treated with L-carnitine
- column C a group of normotensive rats treated with L-carnitine
- column D a hypertensive rats treated with L-carnitine.
- Figure 2 shows the analysis of systolic pressure (mm Hg) for rats that have been treated with 300 mg / kg L-carnitine.
- Column A represents a group of normotensive rats not treated with L-carnitine
- column B a group of hypertensive rats not treated with L-carnitine
- column C a group of normotensive rats treated with L-carnitine
- column D a hypertensive rats treated with L-carnitine.
- the invention was carried out using hypertensive and normotensive rats aged between 20-22 weeks. At this age, hypertensive rats have continuous and sustained hypertension.
- Four experimental groups of animals were performed:
- Group A normotensive rats not treated with L-carnitine.
- Group C normotensive rats treated with L-carnitine.
- the treatment with L-carnitine consisted of administering 300 mg of L-carnitine / Kg of body weight in drinking water for a period of 12 weeks. Once this time has elapsed, we measure the systolic and diastolic blood pressure. The results obtained were:
Abstract
The present invention concerns the use of L-carnitine for producing a medicine or nutritional supplement for treatment or control of arterial hypertension. Likewise, this invention also concerns pharmaceutical compositions for treating said pathology and which include a therapeutically effective quantity of L-carnitine.
Description
Uso de la L-carnitina para el tratamiento de Ia hipertensión arterial Use of L-carnitine for the treatment of arterial hypertension
CAMPO DE LA INVENCIÓNFIELD OF THE INVENTION
La presente invención se refiere al uso de Ia L-carnitina para Ia elaboración de un medicamento o un suplemento nutricional para el tratamiento o control de Ia hipertensión arterial. Del mismo modo, esta invención también está referida a composiciones farmacéuticas para el tratamiento de Ia mencionada patología que comprendan una cantidad terapéuticamente efectiva de L-carnitina.The present invention relates to the use of L-carnitine for the preparation of a medicament or a nutritional supplement for the treatment or control of arterial hypertension. In the same way, this invention also refers to pharmaceutical compositions for the treatment of said pathology that comprise a therapeutically effective amount of L-carnitine.
ESTADO DE LA TÉCNICA ANTERIORSTATE OF THE PREVIOUS TECHNIQUE
La L-carnitina (L-3-h¡droxi-4-N,N,N-trimet¡laminobutirato) es un derivado aminoacídico presente en Ia mayoría de las especies animales y en muchos microorganismos y plantas. Se encuentra ampliamente distribuido por todo el organismo, aunque se presenta en mayores cantidades en el corazón y en el músculo esquelético (Panter R. A. y Mudd J. B. (1969). FEBS Lett. 5(2): 169-170; Rebouche C. J. (1992). FASEB J. 6(15): 3379- 3386.).L-Carnitine (L-3-hydroxy-4-N, N, N-trimethyllaminobutyrate) is an amino acid derivative present in most animal species and in many microorganisms and plants. It is widely distributed throughout the body, although it occurs in greater amounts in the heart and skeletal muscle (Panter RA and Mudd JB (1969). FEBS Lett. 5 (2): 169-170; Rebouche CJ (1992) FASEB J. 6 (15): 3379-3386.).
La función principal de este derivado aminoacídico consiste en actuar como cofactor en el transporte de ácidos grasos al interior de Ia mitocondria, donde se produce Ia β-oxidación de los mismos, para Ia obtención de energía metabólica (Bremer J. (1983). Physiol. Rev. 63(4): 1420-1480.), desempeñando un papel crucial en el metabolismo de los ácidos grasos.The main function of this amino acid derivative consists in acting as a cofactor in the transport of fatty acids inside the mitochondria, where the β-oxidation of the same occurs, for the obtaining of metabolic energy (Bremer J. (1983). Physiol Rev. 63 (4): 1420-1480.), Playing a crucial role in the metabolism of fatty acids.
El 75% de Ia cantidad de carnitina requerida por el organismo proviene de Ia dieta. El resto se sintetiza endógenamente en el hígado y en menor cantidad en el riñon y cerebro, a partir de los aminoácidos lisina y metionina (Tanphaichitr V. y Broquist H. P. (1973). Role of lysine and -N- trimethyllysine in carnitine biosynthesis. II. Studies in the rat. J. Biol. Chem. 248(6): 2176-2181.).
La carnitina no es considerada normalmente como un nutriente esencial, debido a que el organismo en condiciones normales es capaz de sintetizar las cantidades necesarias. Sin embargo, en Ia mayoría de las patologías producidas por una deficiencia de carnitina está justifica esta suplementación con L-camitina. Las deficiencias de carnitina afectan principalmente al músculo y al corazón, ya que su principal fuente de energía son los ácidos grasos. Por esta razón, el tratamiento con L- carnitina está especialmente indicado en enfermedades musculares y cardiovasculares.75% of the amount of carnitine required by the body comes from the diet. The rest is synthesized endogenously in the liver and to a lesser extent in the kidney and brain, from the amino acids lysine and methionine (Tanphaichitr V. and Broquist HP (1973). Role of lysine and -N-trimethyllysine in carnitine biosynthesis. II Studies in the rat J. Biol. Chem. 248 (6): 2176-2181.). Carnitine is not normally considered as an essential nutrient, because the organism in normal conditions is able to synthesize the necessary amounts. However, in most of the pathologies produced by a carnitine deficiency this supplementation with L-camitin is justified. Carnitine deficiencies mainly affect the muscle and heart, since its main source of energy is fatty acids. For this reason, treatment with L-carnitine is especially indicated in muscular and cardiovascular diseases.
Las aplicaciones clínicas de Ia L-camitina según el Vademécum Médico Internacional (edición 43, 2002) son:The clinical applications of L-camitin according to the International Medical Vademecum (edition 43, 2002) are:
• Miopatías causadas por una deficiencia de L-carnitina. " Cardiomiopatías producidas por una deficiencia de L-carnitina.• Myopathies caused by a deficiency of L-carnitine. "Cardiomyopathies produced by a deficiency of L-carnitine.
• Pérdida secundaria de carnitina durante Ia hemodiálisis.• Secondary loss of carnitine during hemodialysis.
• Miocardiopatías producidas por adrimicina y antidepresivos tricíclicos.• Cardiomyopathies produced by adrimycin and tricyclic antidepressants.
• Isquemia miocárdica aguda y crónica: angina de pecho, secuelas de infarto de miocardio, insuficiencia cardiaca, corazón senil, cardiopatía congestiva, arritmias, etc.• Acute and chronic myocardial ischemia: angina pectoris, sequelae of myocardial infarction, heart failure, senile heart, congestive heart disease, arrhythmias, etc.
En las cuatro primeras indicaciones, el tratamiento con L-carnitina ayuda a paliar Ia sintomatología producida por Ia carencia de Ia misma. En el caso de las isquemias, el tratamiento con L-carnitina mejora Ia recuperación de los pacientes, aliviando los síntomas, reduciendo el requerimiento de otros fármacos y disminuyendo Ia mortalidad.In the first four indications, treatment with L-carnitine helps to alleviate the symptoms produced by the lack thereof. In the case of ischemia, treatment with L-carnitine improves the recovery of patients, relieving symptoms, reducing the requirement of other drugs and reducing mortality.
Además de las indicaciones terapéuticas mencionadas, existen muchos estudios que sugieren el uso de L-carnitina y algunos acil-derivados en otras patologías. Así, varios estudios sugieren que el tratamiento con L- carnitina o propionil-L-carnitina puede mejorar una condición llamada claudicación intermitente, que cursa con dolores en las piernas al caminar debido a un estrechamiento arterial (Brevetti G., et al (1988). Circulation. 77(4): 767-773.; Brevetti G., et al (1992). Eur. Heart J. 13(2): 251-255.; Dean S. M. (2002). Vasc. Med. 7(4): 301-309.).
De Ia misma forma, se ha demostrado su utilidad para mejorar Ia tolerancia al ejercicio en personas que sufren enfermedad bronco-pulmonar obstructiva crónica (EBPOC), mejor conocida como enfisema (DaI Negro R., et al (1988). Int. J. Clin. Pharmacol. Ther. Toxicol. 26(5): 269-272; Montgomery S. A., et al (2003). Int. Clin. Psychopharmacol. 18(2): 61-71); en Ia demencia senil (Bella R., et al (1990). Int. J. Clin. Pharmacol. Res. 10(6): 355-360.); en algunos casos de enfermos de ataxia (Gallagher C, et al L. (2002). J. Child Neurol. 17(6): 453-456.); en niños con beta talasemia mayor, donde demostraron que el tratamiento con L-camitina reducía Ia necesidad de transfusiones sanguíneas (Yesilipek M. A., et al (1998) Acta Haematol. 100(3): 162-163.); en Ia fatiga crónica (Kuratsune H., el al (2002) Neuroimage. 17(3): 1256-1265); en Ia terapéutica de Ia infertilidad (Lenzi A., et al (2003). Fértil. Steril. 79(2): 292-300); en el control de Ia glucemia en personas que padecen diabetes (Mingrone G., et al. J. Am. CoII. Nutr. 18(1): 77-82.), contribuyendo a prevenir las posibles complicaciones, principalmente las cardiovasculares.In addition to the therapeutic indications mentioned, there are many studies that suggest the use of L-carnitine and some acyl derivatives in other pathologies. Thus, several studies suggest that treatment with L-carnitine or propionyl-L-carnitine may improve a condition called intermittent claudication, which causes leg pain when walking due to arterial narrowing (Brevetti G., et al (1988) .Circulation. 77 (4): 767-773 .; Brevetti G., et al (1992). Eur. Heart J. 13 (2): 251-255 .; Dean SM (2002). Vasc. Med. 7 ( 4): 301-309.). Likewise, its usefulness has been demonstrated to improve exercise tolerance in people suffering from chronic obstructive broncho-pulmonary disease (EBPOC), better known as emphysema (DaI Negro R., et al (1988). Int. J. Clin. Pharmacol. Ther. Toxicol. 26 (5): 269-272; Montgomery SA, et al (2003). Int. Clin. Psychopharmacol. 18 (2): 61-71); in senile dementia (Bella R., et al (1990). Int. J. Clin. Pharmacol. Res. 10 (6): 355-360.); in some cases of patients with ataxia (Gallagher C, et al L. (2002). J. Child Neurol. 17 (6): 453-456.); in children with beta thalassemia major, where they demonstrated that treatment with L-camitin reduced the need for blood transfusions (Yesilipek MA, et al (1998) Acta Haematol. 100 (3): 162-163.); in chronic fatigue (Kuratsune H., al (2002) Neuroimage. 17 (3): 1256-1265); in the therapeutic of infertility (Lenzi A., et al (2003). Fertile. Steril. 79 (2): 292-300); in the control of blood glucose in people suffering from diabetes (Mingrone G., et al. J. Am. CoII. Nutr. 18 (1): 77-82.), contributing to prevent possible complications, mainly cardiovascular ones.
La utilidad del tratamiento con carnitina también se está abordando en el campo de las cirrosis, donde existen numerosas discrepancias (Selimoglu M. A., el al (2001). Plasma and liver carnitine status of children with chronic liver diseases and cirrhosis. Pediatr. Int. 43(4): 391-395.), y en las neuropatías periféricas, donde se están realizando estudios con Ia acetil-L- carnitina (Scarpini E., el al. Peripher. Nerv. Syst. 2(3): 250-252.). También se está estudiando el posible efecto beneficioso de Ia carnitina en enfermos de cáncer, ya que en muchos casos existe una deficiencia de Ia misma debida a los cambios metabólicos causados bien por Ia propia neoplasia o por Ia terapia antineoplásica (Graziano F., et al (2002). Br. J. Cáncer. 86(12): 1854-1857.).The usefulness of carnitine treatment is also being addressed in the field of cirrhosis, where there are numerous discrepancies (Selimoglu MA, al (2001). Plasma and liver carnitine status of children with chronic liver diseases and cirrhosis. Pediatr. Int. 43 (4): 391-395.), And in peripheral neuropathies, where studies are being carried out with acetyl-L-carnitine (Scarpini E., al. Peripher. Nerv. Syst. 2 (3): 250-252 .). The possible beneficial effect of carnitine in cancer patients is also being studied, since in many cases there is a deficiency due to metabolic changes caused either by the neoplasm itself or by the antineoplastic therapy (Graziano F., et al (2002) Br. J. Cancer. 86 (12): 1854-1857.).
Actualmente, existen en Ia industria farmacéutica multitud de medicamentos que actúan como antihipertensivos, citando entre otros diuréticos, betabloqueantes, IECA (inhibidores de Ia enzima convertidora de Ia angiotensina I) y ARA Il (antagonistas de los receptores de angiotensina II) ("Guía Española de Hipertensión Arterial 2005". Hipertensión, 22, Suplemento 2, 2005.19). La toma de decisión del tratamiento antihipertensivo está basada en el grado de Ia hipertensión
arterial (normal-alta, grado 1 , grado 2 y grado 3) y en Ia asociación con otros factores de riesgos como episodios cardiovasculares, diabetes ó insuficienecia renal ("Guía Española de Hipertensión Arterial 2005". Hipertensión, 22, Suplemento 2, 2005.19). Sin embargo, en todos los grados de hipertensión arterial, a excepción del grado 3, y según esté ó no asociado a factores de riesgos ("Guía Española de Hipertensión Arterial 2005". Hipertensión, 22, Suplemento 2, 2005.19), recomienda el uso de un tratamiento no farmacológico, o dicho de otra forma, adoptar cambios en el estilo de vida, complementado ó no con tratamiento farmacológico, para llegar a normalizar las cifras de tensión arterial y de esa forma prevenir el desarrollo de enfermedades cardiovasculares. Entre los cambios en el estilo de vida, Ia alimentación desempeña un papel fundamental en el tratamiento de Ia hipertensión arterial, como Io demuestran los estudios DASH y INTERSALT, sobre el beneficio del uso de verduras, pescado, frutas, grasas no saturadas y restricción de sal para el control de Ia presión arterial ("Guía Española de Hipertensión Arterial 2005". Hipertensión, 22, Suplemento 2, 2005.19).Currently, there are many drugs in the pharmaceutical industry that act as antihypertensives, citing among other diuretics, beta blockers, ACEI (inhibitors of the angiotensin I converting enzyme) and ARA Il (angiotensin II receptor antagonists) ("Spanish Guide of Hypertension 2005 ". Hypertension, 22, Supplement 2, 2005.19). The decision of the antihypertensive treatment is based on the degree of hypertension arterial (normal-high, grade 1, grade 2 and grade 3) and in association with other risk factors such as cardiovascular events, diabetes or renal insufficiency ("Spanish Guide to Arterial Hypertension 2005". Hypertension, 22, Supplement 2, 2005.19 ). However, in all degrees of arterial hypertension, with the exception of grade 3, and depending on whether or not it is associated with risk factors ("Spanish Guide to Arterial Hypertension 2005". Hypertension, 22, Supplement 2, 2005.19), recommends the use of a non-pharmacological treatment, or in other words, to adopt changes in lifestyle, complemented or not with pharmacological treatment, in order to normalize blood pressure figures and thereby prevent the development of cardiovascular diseases. Among the changes in lifestyle, food plays a fundamental role in the treatment of hypertension, as demonstrated by the DASH and INTERSALT studies, on the benefit of using vegetables, fish, fruits, unsaturated fats and restriction of salt for the control of blood pressure ("Spanish Guide to Arterial Hypertension 2005". Hypertension, 22, Supplement 2, 2005.19).
EXPLICACIÓN DE LA INVENCIÓNEXPLANATION OF THE INVENTION
Los autores de Ia presente invención han descubierto, sorprendentemente, que Ia L-Carnitina lleva a cabo una función de control sobre Ia hipertensión arterial, pudiendo constituir ésta un suplemento nutricional que ayude al control de Ia mencionada patología, así como usarse junto, a otros antihipertensivos, como coadyuvante para un mayor control de Ia hipertensión arterial.The authors of the present invention have discovered, surprisingly, that L-Carnitine performs a control function on arterial hypertension, which may constitute a nutritional supplement that helps control said pathology, as well as being used together with others antihypertensives, as an adjuvant for greater control of arterial hypertension.
La hipertensión arterial (HTA) constituye el principal factor de riesgo para las enfermedades cardiovasculares en los países occidentales, siendo uno de los principales problemas socio-sanitarios de las sociedades industrializadas. En España, los últimos datos de mortalidad analizados demuestran que Ia hipertensión arterial es responsable de una de cada cuatro muertes, de las cuales, una de cada 2,5 es debida a causa cardiovascular (Banegas J. R., y Rodríguez F. (2002). Rev. Clin. Esp. 202Arterial hypertension (hypertension) constitutes the main risk factor for cardiovascular diseases in Western countries, being one of the main socio-health problems of industrialized societies. In Spain, the latest mortality data analyzed show that arterial hypertension is responsible for one in four deaths, of which one in 2.5 is due to cardiovascular causes (Banegas JR, and Rodríguez F. (2002). Rev. Clin. Esp. 202
(1): 12-15.). Además, es importante señalar el hecho de que en los
pacientes hipertensos se produce una acumulación de otros factores de riesgo para las enfermedades cardiovasculares, como hipercolesterolemia, hipertrigliceridemia, diabetes mellitus e hiperinsulinemia basal o síndrome de insulinorresistencia (Almodóvar C. et al (1996) Asociación de los factores de riesgo metabólico y presiones arteriales en una población natural (Mora de Toledo). Atención Primaria 17: 458-462.)(1): 12-15.). In addition, it is important to point out the fact that in the Hypertensive patients produce an accumulation of other risk factors for cardiovascular diseases, such as hypercholesterolemia, hypertriglyceridemia, diabetes mellitus and basal hyperinsulinemia or insulin resistance syndrome (Almodóvar C. et al (1996) Association of metabolic risk factors and arterial pressures in a natural population (Mora de Toledo). Primary Care 17: 458-462.)
Según Io indicado previamente, existen medicamentos muy eficaces para el control de Ia presión arterial, sin embargo a pesar de ello, hay un alto porcentaje de Ia población cuyos niveles de presión arterial no llegan a controlarse, de forma que por una u otra causa, sólo se consigue controlar Ia HTA en menos de un 50% de los enfermos hipertensos.As previously indicated, there are very effective medications for the control of blood pressure, however, despite this, there is a high percentage of the population whose blood pressure levels are not controlled, so that for one reason or another, only HTA can be controlled in less than 50% of hypertensive patients.
Así Ia presente invención aporta un nuevo uso para Ia L-carnitina como producto para el control de Ia hipertensión. De este modo, Ia L-canitina podría emplearse como producto funcional, como suplemento en Ia dieta ó bien mediante Ia utilización de formas farmacéuticas, para ayudar al control de Ia hipertensión arterial. Cabría decir que el consumo de L-carnitina podría no ser un sustituto de aquellos medicamentos dirigidos a reducir Ia presión arterial, así como de las medidas higiénico-dietéticas para mejorar los niveles de presión arterial, sin embargo, su utilización bien sola ó combinación con otras terapias antihipertensiva, podría realizar un efecto coadyuvante al control de Ia tensión arterial, dado su efecto hipotensor o anti-hipertensivo. A todo ello habría que añadir Ia baja toxicidad que presenta Ia L-carnitina, así como Ia falta de efectos secundarios, Ia cual Ia hace candidata perfecta como suplemento a aplicar en las personas hipertensas.Thus, the present invention provides a new use for L-carnitine as a product for the control of hypertension. Thus, L-canitine could be used as a functional product, as a supplement in the diet or through the use of pharmaceutical forms, to help control arterial hypertension. It could be said that the consumption of L-carnitine could not be a substitute for those medications aimed at reducing blood pressure, as well as hygienic-dietary measures to improve blood pressure levels, however, its use either alone or in combination with other antihypertensive therapies, could perform an adjuvant effect to control blood pressure, given its hypotensive or anti-hypertensive effect. To all this should be added the low toxicity that L-carnitine has, as well as the lack of side effects, which makes it a perfect candidate as a supplement to apply in hypertensive people.
Así, un primer aspecto de Ia invención se relaciona con el uso de Ia L- carnitina para Ia elaboración de un medicamento para el tratamiento de Ia hipertensión arterial.Thus, a first aspect of the invention relates to the use of L-carnitine for the preparation of a medicament for the treatment of arterial hypertension.
Un segundo aspecto de Ia invención se relaciona con el uso de Ia L- camitina como coadyuvante en una composición farmacéutica para el tratamiento de Ia hipertensión arterial.
Un tercer aspecto de Ia invención se relaciona con el uso de Ia L-carnitina para Ia elaboración de un suplemento nutricional para el tratamiento o control de Ia hipertensión arterial.A second aspect of the invention relates to the use of L-camitin as an adjuvant in a pharmaceutical composition for the treatment of arterial hypertension. A third aspect of the invention relates to the use of L-carnitine for the preparation of a nutritional supplement for the treatment or control of arterial hypertension.
Un cuarto aspecto de Ia invención se relaciona con una composición farmacéutica para el tratamiento de Ia hipertensión arterial que comprende L-carnitina en una cantidad terapéuticamente efectiva. En una realización preferida de este aspecto de Ia invención Ia composición farmacéutica además comprende otros agentes para el tratamiento de Ia hipertensión arterial o antihipertensivos.A fourth aspect of the invention relates to a pharmaceutical composition for the treatment of arterial hypertension comprising L-carnitine in a therapeutically effective amount. In a preferred embodiment of this aspect of the invention, the pharmaceutical composition also comprises other agents for the treatment of arterial hypertension or antihypertensives.
BREVE DESCRIPCIÓN DE LAS FIGURASBRIEF DESCRIPTION OF THE FIGURES
La figura 1 muestra el análisis de Ia presión diastólica (mm de Hg) para ratas que han sido tratadas con 300 de L-carnitina mg/kg. La columna A representa un grupo de ratas normotensas no tratadas con L-carnitina, Ia columna B un grupo de ratas hipertensas no tratadas con L-carnitina, Ia columna C un grupo de ratas normotensas tratadas con L-carnitina, y Ia columna D grupo de un ratas hipertensas tratadas con L-carnitina.Figure 1 shows the analysis of the diastolic pressure (mm Hg) for rats that have been treated with 300 mg / kg L-carnitine. Column A represents a group of normotensive rats not treated with L-carnitine, column B a group of hypertensive rats not treated with L-carnitine, column C a group of normotensive rats treated with L-carnitine, and column D group of a hypertensive rats treated with L-carnitine.
La figura 2 muestra el análisis de Ia presión sistólica (mm de Hg) para ratas que han sido tratadas con 300 de L-carnitina mg/kg. La columna A representa un grupo de ratas normotensas no tratadas con L-carnitina, Ia columna B un grupo de ratas hipertensas no tratadas con L-carnitina, Ia columna C un grupo de ratas normotensas tratadas con L-carnitina, y Ia columna D grupo de un ratas hipertensas tratadas con L-carnitina.Figure 2 shows the analysis of systolic pressure (mm Hg) for rats that have been treated with 300 mg / kg L-carnitine. Column A represents a group of normotensive rats not treated with L-carnitine, column B a group of hypertensive rats not treated with L-carnitine, column C a group of normotensive rats treated with L-carnitine, and column D group of a hypertensive rats treated with L-carnitine.
EXPOSICIÓN DETALLADA DE MODOS DE REALIZACIÓNDETAILED EXHIBITION OF REALIZATION MODES
A continuación se detallan los ejemplos de realización de Ia invención, los cuales no limitan Ia invención, sino que su finalidad es ilustrarla, poniendo de manifiesto Ia capacidad de Ia L-carnitina para actuar como hipotensor.
EJEMPLOS DE REALIZACIÓN DE LA INVENCIÓNThe following are the examples of embodiment of the invention, which do not limit the invention, but its purpose is to illustrate it, demonstrating the ability of the L-carnitine to act as a hypotensive. EXAMPLES OF EMBODIMENT OF THE INVENTION
EJEMPLO 1EXAMPLE 1
La invención se llevó a cabo usando ratas hipertensas y normotensas de edades comprendidas entre 20-22 semanas. A esta edad las ratas hipertensas presentan una hipertensión continua y mantenida. Se realizaron cuatro grupos experimentales de animales:The invention was carried out using hypertensive and normotensive rats aged between 20-22 weeks. At this age, hypertensive rats have continuous and sustained hypertension. Four experimental groups of animals were performed:
• Grupo A: ratas normotensas no tratadas con L-carnitina.• Group A: normotensive rats not treated with L-carnitine.
" Grupo B: ratas hipertensas no tratadas con L-carnitina."Group B: hypertensive rats not treated with L-carnitine.
• Grupo C: ratas normotensas tratadas con L-carnitina.• Group C: normotensive rats treated with L-carnitine.
" Grupo D: ratas hipertensas tratadas con L-carnitina."Group D: hypertensive rats treated with L-carnitine.
El tratamiento con L-carnitina consistió en administrar en agua de bebida 300 mg de L-carnitina/Kg de peso corporal durante un periodo de 12 semanas. Una vez transcurrido este tiempo, realizamos medida de Ia presión arterial sistólica y diastólica. Los resultados obtenidos fueron:The treatment with L-carnitine consisted of administering 300 mg of L-carnitine / Kg of body weight in drinking water for a period of 12 weeks. Once this time has elapsed, we measure the systolic and diastolic blood pressure. The results obtained were:
Presión sistólica (Figura 2):Systolic pressure (Figure 2):
" grupo A: 166,6 ± 1 ,6 mm de Hg"group A: 166.6 ± 1.6 mm Hg
• grupo B: 238,5 ± 2,2 mm de Hg• group B: 238.5 ± 2.2 mm Hg
- grupo C: 167,3 ± 1 ,3 mm de Hg - grupo D: 191 ,5 ± 2,6 mm de Hg- group C: 167.3 ± 1.3 mm Hg - group D: 191, 5 ± 2.6 mm Hg
Una vez realizado el test de ANOVA se obtuvo una p<0.0001. Aplicando el análisis por test de Student-Newman-Keuls de comparación pareada se obtuvieron las siguientes significaciones:Once the ANOVA test was performed, a p <0.0001 was obtained. Applying the analysis by Student-Newman-Keuls paired comparison test, the following meanings were obtained:
• A-B: p<0.001• A-B: p <0.001
- A-D: p<0.001- A-D: p <0.001
- B-C: p< 0.001- B-C: p <0.001
- B-D: p< 0.001 - C-D: p< 0.001
Presión diastólica (Figura 1):- BD: p <0.001 - CD: p <0.001 Diastolic pressure (Figure 1):
- grupo A: 127,7 ± 0,7 mm de Hg- group A: 127.7 ± 0.7 mm Hg
- grupo B: 205,5 ± 1 ,0 mm de Hg - grupo C: 138,1 ± 0,4 mm de Hg- group B: 205.5 ± 1.0 mm Hg - group C: 138.1 ± 0.4 mm Hg
- grupo D: 167,7 ± 2,1 mm de Hg- group D: 167.7 ± 2.1 mm Hg
Una vez realizado el test de ANOVA se obtuvo una p<0.0001. Aplicando el análisis por test de Student-Newman-Keuls de comparación pareada se obtuvieron las siguientes significaciones:Once the ANOVA test was performed, a p <0.0001 was obtained. Applying the analysis by Student-Newman-Keuls paired comparison test, the following meanings were obtained:
- A-B: p<0.001- A-B: p <0.001
• A-D: p<0.001• A-D: p <0.001
- B-C: p< 0.001 - B-D: p< 0.001- B-C: p <0.001 - B-D: p <0.001
• C-D: p< 0.001• C-D: p <0.001
Estos resultados muestran que Ia administración diaria de 300mg / kg peso corporal de L-camitina durante 12 semanas, disminuye Ia presión arterial diastólica en un 56% y Ia sistólica en un 66%, Io que demuestra el efecto hipotensor de Ia L-carnitina.
These results show that the daily administration of 300mg / kg body weight of L-camitin for 12 weeks decreases the diastolic blood pressure by 56% and the systolic blood pressure by 66%, which demonstrates the hypotensive effect of L-carnitine.
Claims
1. Uso de Ia L-carnitina para Ia elaboración de un medicamento para el tratamiento de Ia hipertensión arterial.1. Use of L-carnitine for the preparation of a medicament for the treatment of arterial hypertension.
2. Uso de Ia L-carnitina como coadyuvante en Ia preparación de composiciones farmacéuticas para el tratamiento de Ia hipertensión arterial.2. Use of L-carnitine as an adjuvant in the preparation of pharmaceutical compositions for the treatment of arterial hypertension.
3. Uso de Ia L-carnitina para Ia elaboración de un suplemento nutricional para el tratamiento de Ia hipertensión arterial.3. Use of L-carnitine for the elaboration of a nutritional supplement for the treatment of arterial hypertension.
4. Composición farmacéutica para el tratamiento de Ia hipertensión arterial que comprende L-carnitina en una cantidad terapéuticamente efectiva.4. Pharmaceutical composition for the treatment of arterial hypertension comprising L-carnitine in a therapeutically effective amount.
5. Composición farmacéutica según Ia reivindicación anterior que además comprende otros agentes para el tratamiento de Ia hipertensión arterial. 5. Pharmaceutical composition according to the preceding claim which further comprises other agents for the treatment of arterial hypertension.
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| ES200701091A ES2306610B1 (en) | 2007-04-16 | 2007-04-16 | USE OF L-CARNITINE FOR THE TREATMENT OF ARTERIAL HYPERTENSION. |
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| RU2632619C1 (en) * | 2016-04-20 | 2017-10-06 | Владимир Павлович Лобко | Method for treatment of patients with arterial hypertension |
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| ES2351753B1 (en) * | 2009-07-07 | 2011-09-29 | Universidad De Sevilla | USE OF L-CARNITINE FOR THE PREVENTION AND TREATMENT OF INFLAMMATORY CARDIAC DAMAGE ASSOCIATED WITH ARTERIAL HYPERTENSION. |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4599232A (en) * | 1983-02-16 | 1986-07-08 | Sigma Tau Industrie Faramaceutiche Riunite S.P.A. | Pharmaceutical composition with metabolic and energetic activity for the use in cardiac and vascular therapy |
| WO2000027386A1 (en) * | 1998-11-11 | 2000-05-18 | Sigma-Tau Industrie Farmaceutiche Riunite S.P.A. | Use of propionylcarnitine for the manufacture of a medicament for inhibiting smooth muscle cell proliferation |
| US20070072927A1 (en) * | 1999-09-23 | 2007-03-29 | Vita Joseph A | Nutritional supplement for increased energy and stamina |
-
2007
- 2007-04-16 ES ES200701091A patent/ES2306610B1/en active Active
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4599232A (en) * | 1983-02-16 | 1986-07-08 | Sigma Tau Industrie Faramaceutiche Riunite S.P.A. | Pharmaceutical composition with metabolic and energetic activity for the use in cardiac and vascular therapy |
| WO2000027386A1 (en) * | 1998-11-11 | 2000-05-18 | Sigma-Tau Industrie Farmaceutiche Riunite S.P.A. | Use of propionylcarnitine for the manufacture of a medicament for inhibiting smooth muscle cell proliferation |
| US20070072927A1 (en) * | 1999-09-23 | 2007-03-29 | Vita Joseph A | Nutritional supplement for increased energy and stamina |
Non-Patent Citations (1)
| Title |
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| ALVAREZ DE SOTOMAYOR M. ET AL.: "L-Carnitine and its propionate: Improvements of endothelial function in SHR through superoxide dismutase-dependent mechanisms", FREE RADICAL RESEARCH, vol. 41, no. 8, August 2007 (2007-08-01), pages 884 - 891 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2632619C1 (en) * | 2016-04-20 | 2017-10-06 | Владимир Павлович Лобко | Method for treatment of patients with arterial hypertension |
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