ES2333842A1 - Pharmaceutical composition intended to improve sperm quality (Machine-translation by Google Translate, not legally binding) - Google Patents

Pharmaceutical composition intended to improve sperm quality (Machine-translation by Google Translate, not legally binding) Download PDF

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ES2333842A1
ES2333842A1 ES200931084A ES200931084A ES2333842A1 ES 2333842 A1 ES2333842 A1 ES 2333842A1 ES 200931084 A ES200931084 A ES 200931084A ES 200931084 A ES200931084 A ES 200931084A ES 2333842 A1 ES2333842 A1 ES 2333842A1
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sperm
vitamin
carnitine
pharmaceutical composition
sperm quality
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ES2333842B1 (en
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Cesar Quintanilla Ripoll
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LABORATORIOS Q PHARMA SL
Q PHARMA S L LAB
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Q PHARMA S L LAB
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/185Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/205Amine addition salts of organic acids; Inner quaternary ammonium salts, e.g. betaine, carnitine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/335Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A61K31/3533,4-Dihydrobenzopyrans, e.g. chroman, catechin
    • A61K31/355Tocopherols, e.g. vitamin E
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00Medicinal preparations containing inorganic active ingredients
    • A61K33/04Sulfur, selenium or tellurium; Compounds thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00Medicinal preparations containing inorganic active ingredients
    • A61K33/24Heavy metals; Compounds thereof
    • A61K33/30Zinc; Compounds thereof

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Inorganic Chemistry (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L-carnitine fumarate, acetyl-l-carnitine, coenzyme q10, zinc, folic acid, selenium, vitamin b12, vitamin c and vitamin e are involved in the composition, so that with them the maturation and functionality of sperm are improved. And protects the energy metabolism and protects the sperm from the attacks of free radicals. The composition is applicable to mammals, and in particular to man. (Machine-translation by Google Translate, not legally binding)

Description

Composición farmacéutica destinada a mejorar la calidad del esperma.Pharmaceutical composition aimed at improving sperm quality

Objeto de la invenciónObject of the invention

La presente invención se refiere a una composición farmacéutica o dietética, específicamente destinada a mejorar la calidad del esperma de los mamíferos, en particular del hombre.The present invention relates to a pharmaceutical or dietary composition, specifically intended for improve mammalian sperm quality, in particular of man.

De forma mas concreta, la composición farmacéutica o dietética que la invención propone es de aplicación en caso de bajo recuento de esperma, de presencia de aberraciones morfológicas en los espermatozoides, alta fragmentación del DNA, baja movilidad de los espermatozoides, e infertilidad asociada a una farmacoterapia.More specifically, the composition pharmaceutical or dietary that the invention proposes is applicable in case of low sperm count, presence of aberrations morphological in sperm, high DNA fragmentation, low sperm motility, and infertility associated with a pharmacotherapy

Consecuentemente, el objetivo de la invención es aumentar el recuento de espermatozoides, aumentar la concentración del esperma, aumentar la movilidad de los espermatozoides y mejorar la morfología de dichos espermatozoides.Consequently, the object of the invention is increase sperm count, increase concentration of sperm, increase sperm motility and improve the morphology of said sperm.

En resumen, la invención se refiere a un medicamento o complemento alimenticio, que gracias a su composición y después de su absorción, puede mejorar la calidad del esperma.In summary, the invention relates to a medication or food supplement, which thanks to its composition and after its absorption, it can improve the quality of sperm.

En un aspecto de particular interés, se puede utilizar la preparación de la invención para prevenir y/o tratar una condición conocida como infertilidad masculina, definida en general por la falta de concepción después de 1 año de relaciones sexuales no protegidas con una misma compañera; y en particular por una cantidad de esperma inferior a 20 millones de espermatozoides/ml, y/o donde menos del 30% de los espermatozoides tienen una morfología normal y/o menos del 50% de los espermatozoides tienen una movilidad normal.In an aspect of particular interest, you can use the preparation of the invention to prevent and / or treat a condition known as male infertility, defined in general due to lack of conception after 1 year of relationships unprotected sex with the same partner; and in particular by an amount of sperm less than 20 million sperm / ml, and / or where less than 30% of sperm have a normal morphology and / or less than 50% of Sperm have normal mobility.

Antecedentes de la invenciónBackground of the invention

Se han realizado abundantes estudios orientados a aumentar la fertilidad entre los que cabe destacar los siguientes:There have been many studies oriented to increase fertility among which the following:

Zini A, et al, mediante un estudio observacional prospectivo publicado en Fertility and Sterility Vol. 75, Nº 4, 2001, buscaban evaluar la integridad del DNA espermático de pacientes fértiles frente al rango de desnaturalización y fragmentación del DNA en pacientes infértiles.Zini A, et al , through a prospective observational study published in Fertility and Sterility Vol. 75, No. 4, 2001, sought to assess the integrity of sperm DNA in fertile patients against the range of denaturation and fragmentation of DNA in infertile patients.

Agarwal A, et al, expusieron en Reproductive BioMedicine, Vol 8. Nº 4. 2004 376-384, de título "Carnitine and male infertility" que la L-Carnitina y la acetyl-L-carnitina son cruciales en el metabolismo y maduración del esperma, estando relacionadas a su vez con la motilidad del esperma y con sus propiedades antioxidantes. Indicaban a su vez que el aporte de 3 gr diarios llegaba a provocar un aumento de la concentración y el recuento total en hombres que padecían azospermia u oligospermia.Agarwal A, et al , reported in Reproductive BioMedicine, Vol 8. No. 4. 2004 376-384, entitled " Carnitine and male infertility " that L-Carnitine and acetyl-L-carnitine are crucial in the metabolism and maturation of sperm, being in turn related to sperm motility and its antioxidant properties. They indicated in turn that the contribution of 3 grams per day led to an increase in the concentration and total count in men suffering from azospermia or oligospermia.

Vicari E y Calogero AE, realizaron un ensayo clínico para evaluar el efecto de los tratamientos con antioxidantes en pacientes con prostato-vesículo-epididimitis (PVE). A los pacientes se les administró 1g de L-Carnitina y 0,5 g de acetil-carnitina 2 veces al día durante 3 meses. Los autores concluyen que las carnitinas son efectivas en pacientes con PVE no bacteriana.Vicari E and Calogero AE, conducted an essay clinical to assess the effect of treatments with antioxidants in patients with prostate-vesicle-epididymitis (PVE). Patients were given 1g of L-Carnitine and 0.5 g of acetyl-carnitine 2 times a day for 3 months. The authors conclude that carnitines are effective in patients with PVE not bacterial.

Costa M, et al, en Andrología Vol 26, 155-159, del año 1994 explican los resultados que obtuvieron en un estudio multicéntrico abierto realizado en 4 centros de infertilidad, realizado a 100 pacientes que sufrieran infertilidad a los que se les administró 3 gr diarios de L-carnitinas en tres tomas diarias de 1 gr. Los investigadores indican que tras la administración continuada de las L-carnitinas, la motilidad de los espermatozoides se incrementaba en un 30%.Costa M, et al , in Andrology Vol 26, 155-159, of the year 1994 explain the results they obtained in an open multicenter study conducted in 4 infertility centers, performed on 100 patients suffering from infertility who were administered 3 gr daily L-carnitines in three daily intakes of 1 gr. The researchers indicate that after continued administration of L-carnitines, sperm motility was increased by 30%.

Por lo tanto, se demuestra que, aunque no está establecida la cantidad estándar de L-carnitinas (L-carnitina fumarato y Acetil L-carnitina) que se han de aportar de manera regular, si que se demuestra mediante estas publicaciones que la dosis recomendada para obtener los efectos beneficiosos citados anteriormente ronda en torno a los 1-3 gr diarios de L-carnitina y 0,5-1 gr de Acetil L-carnitina.Therefore, it is shown that, although it is not set the standard amount of L-carnitines (L-Carnitine fumarate and Acetyl L-carnitine) to be provided in a manner regular, if it is demonstrated by these publications that the recommended dose to obtain the aforementioned beneficial effects previously round around 1-3 gr daily of L-carnitine and 0.5-1 gr of Acetyl L-carnitine

Cabe destacar otros tipos de publicaciones no relacionadas con las L-carnitinas sino que se basan en el aporte de otras vitaminas y/o minerales que demuestran un efecto beneficioso sobre la calidad del esperma.Note other types of publications not related to L-carnitines but are based in the contribution of other vitamins and / or minerals that demonstrate a beneficial effect on sperm quality.

Dawson EB, et al, expusieron en el Annals New York Academy of Sciences, Nº 498, 312 - 328 con el título "Effect of ascorbic acid on male fertility" que tras un aporte de 1000 mg de ácido ascórbico durante una semana existió un aumento significativo de la viabilidad, motilidad, aglutinación y precursores inmaduros, consiguiéndose además un recuento total de espermatozoides del 140%. Por otro lado, la administración suplementaria de 200 mg de ácido ascórbico también provocaba una mejora de todas las características citadas anteriormente, a excepción de la viabilidad, y un recuento total de espermatozoides del 112%.Dawson EB, et al , presented at the Annals New York Academy of Sciences, No. 498, 312-328 with the title "Effect of ascorbic acid on male fertility" that after an increase of 1000 mg of ascorbic acid for a week there was an increase significant viability, motility, agglutination and immature precursors, also achieving a total sperm count of 140%. On the other hand, the supplementary administration of 200 mg of ascorbic acid also caused an improvement of all the aforementioned characteristics, except for the viability, and a total sperm count of 112%.

Teppa AD, et al, mediante un artículo de revisión repasa las terapias para la infertilidad y las distintas sustancias utilizadas para el tratamiento de dicha patología, repasando el papel de los antioxidantes como la Vitamina C y destacando la importancia en la mejora de la calidad espermática.Teppa AD, et al , through a review article reviews the therapies for infertility and the different substances used for the treatment of said pathology, reviewing the role of antioxidants such as Vitamin C and highlighting the importance in improving sperm quality .

En estos casos queda claramente demostrado el efecto beneficioso sobre el esperma del ácido ascórbico, debido a su papel como antioxidante.In these cases, the beneficial effect on ascorbic acid sperm, due to Its role as an antioxidant.

Suleiman SA, et al, publicaron un artículo en el Journal of Andrology, Vol 17, Nº 5, 530-537, de Sept./Oct. de 1996 de título "Lipid peroxidation and Human Sperm Motlity: Protective role of Vitamin E" en el que trataban la astenospermia de un grupo de 52 pacientes con un aporte de Vitamina E de manera oral. Esto provocó un aumento significativo de la motilidad de los espermatozoides.Suleiman SA, et al , published an article in the Journal of Andrology, Vol 17, No. 5, 530-537, of Sept./Oct. of 1996 of title "Lipid peroxidation and Human Sperm Motlity: Protective role of Vitamin E" in which they treated the astenospermia of a group of 52 patients with a contribution of Vitamin E orally. This caused a significant increase in sperm motility.

Giancarlo Balercia MD, et al, expusieron en Fertility and Sterility, Vol 81, Nº 1 de Enero del 2004 un artículo de título "Coenzyme Q10 supplementation in infertile men with idiopathic asthenozoospermia an open, uncontrolled pilot study" los resultados que obtuvieron tras realizar un estudio piloto, abierto y no controlado con pacientes con infertilidad a los que se les administraba coenzima Q10. Con este ensayo buscaban demostrar el potencial terapéutico para el tratamiento de un tipo específico de infertilidad. A los pacientes se les administró durante seis meses una dosis de Coenzima Q10. Los resultados obtenidos concluyen que la Coenzima Q10 juega un rol positivo en el tratamiento de la astenozoospermia.Giancarlo Balercia MD, et al , presented in Fertility and Sterility, Vol 81, January 1, 2004 an article entitled "Coenzyme Q10 supplementation in infertile men with idiopathic asthenozoospermia an open, uncontrolled pilot study" the results obtained after performing a pilot study, open and uncontrolled with patients with infertility who were given coenzyme Q10. With this trial they sought to demonstrate the therapeutic potential for the treatment of a specific type of infertility. Patients were given a dose of Coenzyme Q10 for six months. The results obtained conclude that Coenzyme Q10 plays a positive role in the treatment of astenozoospermia.

Scott R, et al, mediante su publicación en el British Journal of Urology, 82, 76-80 de título "The effect of oral selenium supplementation on human sperm motility" explican los resultados obtenidos en un ensayo doble ciego controlado donde 69 pacientes que se dividieron en 3 grupos y a los que se les administró placebo, Selenio y Selenio/Vitamina A, C y E, respectivamente. Los resultados indican que el aporte de Selenio en pacientes con infertilidad y concentraciones bajas de Selenio, incrementa la motilidad de los espermatozoides y aumentan así el éxito en los intentos de concepción.Scott R, et al , by publication in the British Journal of Urology, 82, 76-80 entitled "The effect of oral selenium supplementation on human sperm motility" explain the results obtained in a double blind controlled trial where 69 patients who They divided into 3 groups and were given placebo, Selenium and Selenium / Vitamin A, C and E, respectively. The results indicate that the contribution of Selenium in patients with infertility and low concentrations of Selenium, increases sperm motility and thus increases success in conception attempts.

Wai Yee Wong, et al, realizaron un ensayo doble ciego, randomizado, placebo control, publicado en Fertility and Sterility, 77, Nº3, Marzo 2002, para estudiar los efectos del ácido fólico y el sulfato de zinc en la fertilidad y en el tratamiento de subfertilidad del hombre. El ensayo concluye indicando que tras la administración combinada de ambas sustancias existen incrementos significativos en la cantidad de esperma, tanto en voluntarios sanos como en pacientes con infertilidad.Wai Yee Wong, et al , conducted a double-blind, randomized, placebo-controlled trial, published in Fertility and Sterility, 77, No. 3, March 2002, to study the effects of folic acid and zinc sulfate on fertility and treatment. of subfertility of man. The trial concludes by indicating that after the combined administration of both substances there are significant increases in the amount of sperm, both in healthy volunteers and in patients with infertility.

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Descripción de la invenciónDescription of the invention

Tomando en consideración el número de las materias primas que se citan en el apartado anterior, la invención se centra en una formulación que incluye algunas de dichas sustancias y otras no, formulación con la que se consigue mejorar la calidad seminal de forma muy considerable, a nivel recuento, moviolidad, morfología y fragmentación del DNA.Taking into account the number of raw materials cited in the previous section, the invention it focuses on a formulation that includes some of those substances and others not, formulation with which it is possible to improve seminal quality in a very considerable way, at the count level, moviolity, morphology and DNA fragmentation.

En dicha formulación participan:In this formulation participate:

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Fuentes de L-CarnitinaSources of L-Carnitine

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Varias fuentes de antioxidantes.Several sources of antioxidants

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Sustancias que mejoran la maduración de los espermatozoides.Substances that improve the maturation of sperm

Los términos "Fuentes de L-carnitina" y "Varias fuentes de antioxidantes" indican la presencia, en la invención propuesta, de compuestos adecuados para ser administrados, en el caso que nos compete, de manera oral a un individuo macho de una especie mamífera; el cual mediante dicha administración proporciona y/o dispone L-carnitina y sustancias antioxidantes como Vitamina C, Zinc, Selenio o Coenzima Q10 para dicho individuo, con el fin de obtener niveles adecuados de dichas sustancias en el cuerpo de dicho mamífero o al menos en una parte del mismo, que incluye, aunque no únicamente, un fluido biológico como la sangre, el plasma y/o el semen (fluido).The terms "Sources of L-carnitine "and" Various sources of antioxidants "indicate the presence, in the proposed invention, of suitable compounds to be administered, in the case that we Orally competes a male individual of a species mammalian which through said administration provides and / or It has L-carnitine and antioxidant substances such as Vitamin C, Zinc, Selenium or Coenzyme Q10 for said individual, with in order to obtain adequate levels of said substances in the body of said mammal or at least in a part thereof, which It includes, but not only, a biological fluid such as blood, plasma and / or semen (fluid).

Las fuentes de L-carnitina propuestas en la invención son L-carnitina fumarato, Acetyl L-carnitina, cuyas propiedades beneficiosas se citaron anteriormente. Por otro lado, las sustancias con propiedades antioxidantes que se proponen en la invención son Selenio, CoQ 10, Vitamina C y Vitamina E.L-carnitine sources Proposals in the invention are L-carnitine fumarate, Acetyl L-carnitine, whose properties Beneficial cited above. On the other hand, the substances with antioxidant properties that are proposed in the invention are Selenium, CoQ 10, Vitamin C and Vitamin E.

Las sustancias propuestas en la invención y que irán dirigidas a mejorar la maduración de los espermatozoides son: Zinc, Vitamina B12, Acetyl L-carnitina, aunque alguna de ellas pueda estar presente en la invención debido a alguna otra propiedad que posea.The substances proposed in the invention and that They will be aimed at improving sperm maturation are: Zinc, Vitamin B12, Acetyl L-Carnitine, though some of them may be present in the invention due to Any other property you own.

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La dosificación prevista para las sustancias citadas es la siguiente:The planned dosage for substances cited is as follows:

1one

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Ejemplo de realización práctica de la invenciónExample of practical embodiment of the invention

De acuerdo con un ejemplo preferente de realización práctica de la invención, la composición farmacéutica que la invención propone, constituye un suplemento dietético de absorción oral, comercializado en sobres, correspondiendo cada sobre una dosis y habiéndose previsto la ingesta de dos sobres al día, para el tratamiento o prevención de los trastornos citados con anterioridad.According to a preferred example of practical embodiment of the invention, the pharmaceutical composition that the invention proposes, constitutes a dietary supplement of oral absorption, marketed in sachets, corresponding each on a dose and having planned the intake of two sachets at day, for the treatment or prevention of the disorders cited with anteriority.

La formula propuesta como procedente es la siguiente:The proposed formula as appropriate is the next:

33

La efectividad de esta composición viene determinada por lo siguiente:The effectiveness of this composition comes determined by the following:

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La carnitina está presente en dos formas en el esperma: L-carnitina y L-acetilcarnitina. Desempeña un papel en la adquisición de la movilidad progresiva, es un transportador de ácidos grasos. Es el marcador del cuerpo y la cola del epidídimo, pero no es secretada por las células de la cabeza. Existe una pequeña secreción extraepididimaria del orden del 15 al 20%.The Carnitine is present in two forms in sperm: L-carnitine and L-acetylcarnitine. It plays a role in the acquisition of progressive mobility, it is a fatty acid transporter. It is the marker of the body and the tail of the epididymis, but it is not secreted by the cells of the head. There is a small extraepididymal secretion of the order from 15 to 20%.

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La Coenzima Q10 evita la oxidación de la membrana lipídica de los espermatozoides y favorece su movilidad.The Coenzyme Q10 prevents oxidation of the lipid membrane of the sperm and promotes mobility.

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El zinc es un catión específico del plasma seminal dotado de poder bactericida. Su papel sería estabilizar la condensación de la cromatina. Es transportado por el citrato y las proteínas. Eleva los niveles de testosterona, aumenta el número y la movilidad de los espermatozoides, pero no se debe tomar cantidades muy elevadas de zinc durante mucho tiempo, ya que puede agotar las reservas de cobre.He zinc is a specific cation of the seminal plasma endowed with power bactericide. Its role would be to stabilize the condensation of the chromatin It is transported by citrate and proteins. Raise testosterone levels, increases the number and mobility of sperm, but you should not take very high amounts of zinc for a long time, since it can deplete the reserves of copper.

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Se han detectado altas concentraciones de ácido fólico en el esperma, y su disminución provoca alteraciones en la movilidad y recuento espermático.They have detected high concentrations of folic acid in sperm, and its decrease causes alterations in mobility and counting spermatic.

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El selenio aumenta la movilidad y la calidad del esperma cuando se toma en conjunto con la vitamina E. También aumenta la progesterona. En un estudio de doble ciego de 64 hombres infértiles con motilidad espermática reducida, un suplemento de selenio incrementó en forma importante la movilidad, pero no afectó al recuento de espermatozoides.He Selenium increases mobility and sperm quality when taken in conjunction with vitamin E. It also increases progesterone.  In a double-blind study of 64 infertile men with motility  reduced sperm, a selenium supplement increased in shape important mobility, but did not affect the count of sperm

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La Vitamina B12 está implicada en la maduración celular y en la síntesis del DNA. Una deficiencia en Vitamina B12 está asociada al descenso en el recuento espermático y a su movilidad. Por lo tanto es una vitamina esencial en la calidad del esperma.The Vitamin B12 is involved in cell maturation and in the DNA synthesis A deficiency in Vitamin B12 is associated with decrease in sperm count and mobility. Thus It is an essential vitamin in sperm quality.

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La vitamina C protege a los espermatozoides del daño provocado por la oxidación, aumenta el número de espermatozoides y su motilidad, además reduce el número de anomalías del esperma y evita que se aglutine. Regenera la forma oxidada de vitamina E.The Vitamin C protects sperm from damage caused by oxidation, increases the number of sperm and their motility, It also reduces the number of sperm abnormalities and prevents agglutinate Regenerates the oxidized form of vitamin E.

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Finalmente, la vitamina E es importante para la función gonadal, mejora la movilidad de los espermatozoides y evita la peroxidación lipídica del esperma.Finally, vitamin E is important for gonadal function, improves sperm mobility and prevents lipid peroxidation of sperm.

En conclusión, los ingredientes de la invención propuesta tienen distintas funciones específicas:In conclusion, the ingredients of the invention Proposals have different specific functions:

44

Claims (3)

1. Composición farmacéutica destinada a mejorar la calidad del esperma, caracterizada porque en la misma participan como componentes L-carnitina fumarato, Acetil-L-Carnitina, Coenzima Q10, Zinc, Ácido Fólico, Selenio, Vitamina B12, Vitamina C y Vitamina E.1. Pharmaceutical composition aimed at improving sperm quality, characterized in that L-carnitine fumarate, Acetyl-L-Carnitine, Coenzyme Q10, Zinc, Folic Acid, Selenium, Vitamin B12, Vitamin C and Vitamin E participate as components. 2. Composición farmacéutica destinada a mejorar la calidad del esperma, según reivindicación 1, caracterizada porque en cada dosis participan los componentes citados en las siguientes cantidades:2. Pharmaceutical composition intended to improve sperm quality, according to claim 1, characterized in that in each dose the components mentioned in the following quantities participate: 55 3. Composición farmacéutica destinada a mejorar la calidad del esperma, según reivindicaciones anteriores, caracterizada porque la ingesta diaria es de dos monodosis.3. Pharmaceutical composition intended to improve sperm quality, according to previous claims, characterized in that the daily intake is two doses.
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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IT201600115036A1 (en) * 2016-11-15 2018-05-15 Lta Biotech S R L Method for in vitro diagnosis of male infertility.

Citations (6)

* Cited by examiner, † Cited by third party
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